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COVER PIC:
Post corneal neurotsation: resolved neurotrophic keratopathy with pooling demonstrated in an area of corneal scarring.
Spring 2024
Vol 19 • No 4
4 FROM THE EDITOR
From print to digital: OSSA enters a new digital chapter
N du Toit
6 REVIEW ARTICLE
Understanding the impact of climate change on ocular health
SD Mathebula
11
ORIGINAL STUDY
Correlation between corneal endothelial cell density and pterygium size in patients with a unilateral pterygium at St John Eye Hospital in Soweto
A Hajee
17
30 ORIGINAL STUDY
An educational intervention to improve topical treatment technique success in glaucoma patients in central South Africa
A Jansen van Rensburg
38
41
46
ORIGINAL STUDY
A survey of Ocular Trauma at Groote Schuur Hospital in Cape Town, South Africa
Z Logday
24
50
ORIGINAL STUDY
Preclinical chloroquine maculopathy detection in a South African multiracial population by spectraldomain optical coherence tomography (OCT)
P Mncube
56
CASE REPORT
Corneal neurotisation
S Swaminathan
CASE REPORT
Treatment of a conjunctival papilloma using topical Mitomycin C
S Gaibie
CASE REPORT
Disseminated hydatid cyst disease presenting with unilateral orbital proptosis and vision loss: a rare orbital presentation of systemic echinococcosis in a young child
N Narainswami
CASE REPORT
Keratoglobus: An Overview of the Surgical Management Options for this Rare Corneal Ectasia
N van der Merwe
CASE REPORT
A case of tuberculous panophthalmitis with orbital abscess
S Swaminathan
From print to pixels: OSSA enters a new digital chapter
Welcome to our final issue of 2024 and I am sad to say, our last issue of the SAOJ in its current format!
This is a bumper edition with double the number of articles of a standard issue. We actually stopped accepting submissions as 01 July this year, so we have included all articles that were submitted, reviewed and accepted up to that point, in this, our final publication of the SAOJ as a peerreviewed, DHET-accredited, and Google Scholar-listed journal. In this issue, we have a review article, four original studies and five case reports.
After being unable to resolve some differences despite several meetings, the OSSA EXCO and New Media (the publishers of the SAOJ) decided to part ways. Although the SAOJ is the “official mouthpiece of OSSA”, it belongs to New Media. The first prize for OSSA would have been to negotiate the purchase of the SAOJ from New Media, so that all the hard work (since mid-2017) that was put into transforming the SAOJ from a magazine into a proper academic journal could have been preserved and perpetuated. Peer-review was achieved early in 2018; DHET-accreditation in December 2019, with assistance from Pat Botes and Johan Gerber; Google Scholar listing in early 2020; while Chris Tinley and Naseer Ally were appointed as assistant editors in late 2021. OSSA will now be embarking on the road to establishing a new academic journal.
After seven and a half years as editor-inchief, I decided to step down from this position, as I could not envisage myself slogging through the entire application process to gain accreditation for a second time. It also seemed like an opportune moment to hand over the reins and bring in new energy.
The SAOJ as a platform for MMed by publication, as well as publishing our local research, is now temporarily lost, but hopefully OSSA’s new journal will receive accreditation fairly soon. Naseer Ally will be the editor of the new journal –congratulations on this appointment! I wish him and OSSA all the best with this endeavour. Naseer will be establishing an online submission platform (via AOSIS); hopefully expand the journal’s footprint on our continent; and, once accredited, push for Pubmed indexing. With new open access online platforms, it is possible to achieve DHET-accreditation within one year. Chris Tinley and I have moved on to the positions of Deputy Assistant Editor and Assistant Editor (for Ophthalmology) of the Journal of the CMSA, which is an open access journal and now fully accredited by the DHET. We will thus still have a platform for the accredited publication of local research in the immediate future.
New Media will continue with the SAOJ in a different format and will be taking an alternate path. The SAOJ will still be spearheaded by Johan Gerber and assisted
by Gill Abrahams. Johan would like to bring the latest information, research and other content to the SAOJ. With this in mind, he wants to try to include content (whether academic or just interesting material that will benefit the industry) from the ophthalmology community, should we want to use the platform.
New Media remains open to consider any ophthalmology-related material for publication.
I would like to end by thanking all of you for your amazing support over these seven years – New Media and staff, OSSA EXCO, Expert Board members, reviewers, authors, and readers. Without you this wonderful journey at the helm of the SAOJ would not have been possible. Au revoir!
Editor-in-Chief: South African Ophthalmology Journal
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Understanding the impact of climate change on ocular health
SD Mathebula B Optom, M Optom, DPhil, Department of Optometry, Faculty of Health Sciences, University of Limpopo, South Africa. ORCID: https://orcid.org/0001-8196-2567
L Masiwa B Optom, M Optom, PhD, Optometry Unit, Department of Primary Care, Parirenyatwa Hospital, Faculty of Medicine, University of Zimbabwe, Harare, Zimbabwe. ORCID: https://orcid.org/0000-0001-7898-7675
MD Ntsoane B Optom, MPH, PhD, Department of Optometry, Faculty of Health Sciences, University of Limpopo, South Africa. ORCID: https://orcid.org/0009-0003-9543-613X
Background : The eye is a unique organ and is uniquely susceptible to environmental factors such as air, ultraviolet radiation (UVR) and to the external environment. Climate change can affect the eye in varying degrees.
Method : Terms related to climate change and eye disease outcomes were used to search for relevant publications. Our comprehensive review delineates a spectrum of eye conditions associated with climate change-related variables.
Results : We identified 33 peer-reviewed articles which included cross sectional, case-control, and longitudinal studies. Most research was done in global regions with climate variability. This review has outlined the influence of climate change on a diverse array of eye conditions. Extremes in temperatures and weather events have been observed to affect the ocular surface, resulting in conjunctivitis, keratitis, dry eye disease and pterygium. Furthermore, climate change is linked to a rising occurrence of cataract, uveitis, glaucoma, and retinal disease.
Conclusion : Despite the global rate of cataract surgery
Introduction
Climate change is the significant variation of average weather conditions becoming warmer, wetter or drier over seasons, years, decades or even longer due to direct or indirect human activities that alters the global atmosphere.1-3 The Australian Academy of Science 4 defines weather as “the state of the atmosphere which include its temperature, humidity, wind, rainfall and so on over a period of time. It is influenced by the oceans, land surface and ice sheets which together with the atmosphere form the climate system.” Global warming is the rise in global temperature due to the increasing concentration of greenhouse gases in the atmosphere. 5 Global warming
increasing with population growth, the number of people with vision loss associated with cataract has also increased due to the change in the overall age composition of populations, especially among women. This is exacerbated by the effect of climate change. Climate change may be the next major risk to eye health.
Acknowledgement: The authors would like to thank Professor Alan Rubin of the University of Johannesburg for his assistance in proofreading the manuscript.
Competing interests: The authors declare that they have no financial or personal interests that may have inappropriately influenced them in authoring this article.
Funding information: This work did not receive any specific grant from funding agencies in the public, commercial, or notfor-profit sectors.
is largely man-made due to burning of fossil fuels and widespread deforestation. The Intergovernmental Panel on Climate Change in 2022 suggested a climate crisis and risk in climate change hazards which include vector-borne diseases, drought, elevated temperatures, increased ultraviolet radiation (UVR) exposure, increased levels of precipitation, loss of biodiversity in land, lack of freshwater and degradation of ecosystems leading to nutrition deprivation. 5 Climate change is the cause and reason for the increased frequency of El Nino, which results in the warming of sea temperatures in the Pacific Ocean.6-9 Global rising temperatures are associated with the increasing prevalence
of several diseases, smoke from wildfires and increased particulate matter and atmospheric dust that has been linked to cardiovascular risk, respiratory system damage, kidney disorders and cancers. In addition, the loss of wildlife habitats is causing an increase in zoonotic diseases.7-14 Climate change is a significant threat to global health, especially in low- and middle-income countries where there are disproportionate health inequalities. 7-11 As local and global average temperatures continue to rise, the risk level associated with health consequences will rise and ocular diseases will not be spared. Higher temperatures and increased levels of rainfall favour an increase in the incidence
of vector-borne diseases and a possible appearance of disease-carrying vectors in areas where they did not exist before.10 Some diseases, such as malaria and trachoma could reappear where infection is most prevalent due to extreme heat and low precipitation.12-15 Countries mostly affected by heatwaves are at risk of microbial keratitis due to fungal infections that can also result in ocular infection, especially among immunocompromised persons due to mould contamination from major flooding.12
Climate change can cause higher levels of rainfall in certain areas while causing severe drought in other areas. Drought can affect the hydration status of individuals living in that area or region resulting in malnutrition and/or workrelated health problems. Malnutrition or undernourishment can be a direct effect of changes in harvest because of temperature changes. Malnutrition is the consumption of food without crucial active principles of proper nourishment 16-18 and malnutrition is a feature in xerophthalmia, a disease caused by a deficiency of vitamin A.16 Incidences of night blindness and ocular surface diseases are expected to rise parallel to food insecurity. Malnutrition is also responsible for certain ocular diseases such as dry eye, glaucoma, cataract, and age-related macular degeneration.7
Emerging literature is increasingly showing the effects and influences that rising global temperature rises will have on our communities and on systemic and ocular health. Thus, the purpose of this paper is to discuss the effect of climate change primarily on ocular health. The eyes (and parts of skin) are possibly the first anatomical structures to be affected by climate change since the skin and the external surface of the eye are often directly exposed to the environment every day.
Methods
The authors performed a review of the literature using a combination of subject heading and keywords for bibliographic databases including PubMed, Medline, Google Scholar and Science Direct. The inclusion criterion for this paper was sources on climate change and eye health from January 1990 to March 2024. The keywords used to search the databases were: climate change, global warming, air pollution, El Nino, heavy rainfall, ocular health, vision, eye, rising temperatures. We included studies written in English, original articles (experimental research, case-control, cross-sectional) and reviews.
We excluded conference abstracts, letters to the editor and articles that did not have specified wording related to climate change and ocular health.
Results
A total of 623 records was found from the initial search with 18 additional records from the references, yielding an overall total of 641 records. After removal of duplicates, articles without full-text and non-English studies 97 records met the inclusion criteria. From there, a total of 64 studies whose topics were irrelevant to the topic of this review, namely those that related to climate change but with no ocular or eye association were deemed ineligible. After the exclusion process, a final total of 33 records were included in the study (see Figure 1).
Records identified through databases searching (n = 641)
PubMed (n = 221)
Medline (n = 194)
Google Scholar (n = 105)
ScienceDirect (n = 121)
Records after duplication removed (n = 325)
Records screened (n = 316)
Records excluded (n = 219)
Full-text articles assessed for eligibility (n = 97 )
Studies included (n = 33)
Studies not eligible (n = 64)
Figure 1. Flow diagram for this review with duplicates removed prior to the screening of the articles.
Discussion
According to the WHO, the impacts of climate change on the environment are wide ranging and diverse as accelerating climate change continues to be the single greatest short- and long-term threat to human health globally. Climate change is predicted by many authorities to increase death rate by a quarter of a million per year from malnutrition, malaria, diarrhoea, and heat stress alone. With such detrimental effects on general health predicted, it is plausible to expect ocular health effects too. 2 Climate change has been implicated in the increased frequency and severity of extreme heat,
floods, and droughts. The main causes of climate change include burning fossil fuels and plastic and other waste and cutting down forests that together are increasingly adding enormous amounts of greenhouse effect and global warming. Carbon dioxide, methane and water vapour are the primary greenhouse gases emitted through human activities. While middle- and high-income countries are among the highest greenhouse gas emitters, the low-income countries, disadvantaged and vulnerable communities and populations contribute the least to the cause but nevertheless are the most affected. Several studies 8-11 have shed light on the impact of climate change, climaterelated hazards (such as floods, storms, and heat wave) on global health.
Open eyes, and protective tear layers, are almost constantly exposed to desiccating stress but are generally protected from damage by homeostatic mechanisms. Physiologically, homeostasis is the state of equilibrium in the body with respect to its various functions, and to the chemical composition of the various fluids and tissues.19 Maintaining homeostasis is essential for maintaining the optimum function of the eye, however, any external factor (such as climate change) can influence or affect its performance. Change in the eye can serve as an early indicator before systemic signs and symptoms of a disease become apparent. This is because certain chronic medical and vascular conditions frequently manifest themselves through ocular symptoms. 20
Multiple studies 21-32 have explored the association between climate change and ocular health. These studies found that an increase in global temperature rise is associated with the increased prevalence of various ocular diseases as we shall detail in this report.
Ultraviolet radiation exposure
Ultraviolet radiation (UVR) is a form of non-ionizing radiation emitted by the sun and artificial sources used in industry, commerce, and recreation. 21-26 The benefit of UVR is the production of a vital nutrient, vitamin D. 27 The ozone particles in the stratosphere are responsible for dispensing harmful amounts of UVR. Reduction or thinning in the ozone layer increases the amount of UVR and results in less protection from the sun’s rays. When UVR reaches the eye, the structures affected are determined by the wavelength of the radiation. The shorter wavelengths
are more biologically active and most damaging, and these wavelengths are mostly absorbed by the cornea. This may result in an increase in corneal ectasias such as keratoconus that are associated with increased UVR exposure. There is a notable impact of sunlight and ultraviolet exposure on the ocular surface as higher levels of ultraviolet appears to alter the biomechanical properties of the cornea and crystalline lens. The longer wavelengths can, however, reach the crystalline lens and cause cataract. 24-26
Elevated temperatures
Studies have revealed a positive correlation between rising temperatures to several ocular pathologies, dry eye diseases, pterygium, conjunctivitis (acute haemorrhagic and microsporidia), allergic eye diseases, photokeratitis and keratoconus. 24 and a nationwide study done in Taiwan by Lin et al 28 found a significant increase in retinal pathology and rhegmatogenous retinal detachment due to increasing environmental heat. Another study in Quebec also found a significant increase in tractional retinal detachment following a heat wave. 29 However, the association between ambient temperature and rhegmatogenous retinal detachment is not always obvious but the rising ambient temperatures are linked epidemiologically to several forms of cataract formation. One study pointed to the prevalence of nuclear subtype cataract in tropical and subtropical regions due to high ambient temperatures of that region 34 , while a case-controlled study found a link between heat waves and the incidence of pre-senile cataract. 35 Nonetheless, current understanding of the link between rising ambient temperature and cataract formation is still poorly understood since the link to cataract involves multifactorial complex events.
Increased levels of rainfall and vector-borne diseases
Higher temperatures and increased levels of rainfall are also linked to an increase in vector-borne diseases and this produces favourable condition for biting insects, such as mosquitoes. 36-38 Trachoma is prevalent in sub-Saharan Africa where hot climate, minimal precipitation and infrastructural concerns lead to poor hygiene conditions and expose individuals vulnerable to infection. 36 One study found an association between rising temperature associated with climate change and the prevalence of fungal keratitis. 39 The
continued process of human-induced warmer climates could lead to an extended diseases transmission seasons and thereby expand distribution of the fly vector and the disease.
Due to continued global warming, increased levels of heavy precipitation may become more frequent resulting in flash flooding which could lead to water contamination.40 Developing, and even developed, countries are at risk to contamination if the frequency of floods exceeds the capacity of drainage systems. This can predispose communities to pathogens with ocular significance, such as toxoplasmosis and acanthamoeba. Toxoplasmosis 41 can cause retinochoroiditis while the acanthamoeba cause corneal disorders such as acanthamoeba keratitis.42 Conjunctivitis also may become more frequent due to changes in atmospheric circulation and biota, storm dynamics, regional warming, and regional increased rainfall and floods.
Air quality
Climate change and air quality are intricately connected, and air pollution is the contamination of the indoor or outdoor environment by airborne suspension of extreme small solid or liquid particles (called particulates) that modifies the natural characteristics of the atmosphere.43-49 The pollutants in the atmosphere are harmful to the health of humans and other living beings. Major airborne pollutants include ozone, nitrogen dioxide, nitric oxide, sulphur dioxide and carbon monoxide. They are the primary drivers of climate change due to combustion of fossil fuels and this is responsible for the reduction of air quality. Airborne pollutants have been shown to cause risks of conjunctivitis and exacerbate dry eye disease, and have a negative impact on ocular surface healthy tear film quality and increased risk of keratitis.48 Air pollutants can affect the immune system and lead to an increase in cases of uveitis.49 Additionally, air pollutants may increase the rate of agerelated macular degeneration. 30 However, the pathophysiology of ocular diseases due to air pollution is unknown but could be caused by the combination of inflammatory responses and oxidative stress triggered by the particulate matter and the greenhouse gas emissions in the presence of nutritional deficiencies. Several studies explored the relationship between air pollutants and glaucoma. 50-52 One study found that
higher exposure of ambient pollutants was associated with the thinning of ganglion cell inner plexiform layer and with an increased odds ratio for glaucoma. 51 The mechanism of glaucoma development is not clear but could be due to pollutant-induced oxidative stress and neuroinflammation causing retinal ganglion cell death, which is a possible cause of glaucoma, without necessarily an associated increase in intraocular pressure (IOP). Alternatively, an increase in IOP and glaucoma could be due to trabecular meshwork cell damage with oxidative stress and/or some type of particulate matter-induced process.
Conclusion
Climate change is not only a global environmental issue of concern. It has an important and growing impact on global health but seems to be underappreciated within the eye and vision professional communities. Literature has shown that climate change can exacerbate a range of ocular conditions that can dramatically impact upon quality of life through vision impairment and other dysfunctionality. Several studies have revealed a positive correlation between ultraviolet light exposure and the occurrence of pterygium, dry eye disease, keratitis, and development of cataract. Increasing temperatures, air pollution and heat waves are risk factors for the development and rise in the prevalence of cataract, allergic, bacterial, viral, or fungal eye diseases, glaucoma, age-related macular degeneration, ocular inflammations, or infections such as trachoma and vitamin A deficiency. Although numerous studies have reported a positive correlation between climate change and systemic or ocular diseases, further research is needed to increase awareness of how climate change affects particularly ocular health. This may provide guidelines for prevention and therapeutic strategies in dealing with climate variability and ocular disease and vision impairment in the future while attempts are made to reduce the impact of global warming.
References
1. Chen M, Caldeira K. Climate change as an incentive for future human migration. Earth Syst Dynam. 2020; 11:875-883.
2. Watts N, Adger WN, Agnolucci P. Health and climate change: policy responses to protect public health. Lancet. 2015; 386:1861-1914.
3. O’Neill B, Carter T, Ebi K. Achievements and needs for the climate change scenario
4. Australian Academy of Science. What is climate change? https://www.science.org.au accessed 22 March 2024.
5. Intergovernmental Panel on Climate Change. Climate change: impact, adaptation and vulnerability. 2023; https://www.ipcc.ch/ report/ar6 Accessed 30 March 2024.
6. World Meteorological Organisation. World Meteorological Organisation declares onset of El Nino conditions. www.wmo.int/news/ media-centre/el-nino-la-nina.
7. Kim KH, Kabir E, Ara Jahan S. A review of the consequences of global climate change on human health. J Environ Sci Health Environ Carcino Ecotoxicol. 2014;32(3):299-318.
8. Ray C, Ming X. Climate change and human health: A review of allergies, autoimmunity and the microbiome. Int J Environ Res Public Health. 2020;17(3): a17134814.
9. Haines A, Lam HCY. El Nino and health in an era of unprecedented climate change. Lancet 2023; 402:1811-1813.
11. Chang AY, Tan AX, Nadeau KC, Odden MC. Aging hearts in a hotter, more turbulent world: The impact of climate change on the cardiovascular health of older adults. Curr Cardiol Rep. 2022;24(6):749-760.
12. Wilhelmus KR. Climatology of dematiaceous fungal keratitis. Am J Ophthalmol. 2005;140(6):1156-1157.
13. Walkden A, Fullwood C, Tan SZ. Association between season, temperature and causative organism in microbial keratitis in the UK. Cornea. 2018;37(12):1555-1560.
14. Waisberg E, Ong J, Lee AG. El Nino and eye health: ophthalmic manifestation of changes in climate. Eye (London). 2024; doi. org/10.10.38/s41433-023-02907-z.
15. Smith JR, Ashander LM, Arruda SL. Pathogenesis of ocular toxoplasmosis. Prog Retinal Eye Res. 2021;81: a100882.
16. Muller O, Krawinkel M. Malnutrition and health in developing countries. Can Med Assoc J. 2005; 173:279-286.
17. Chandran R, Consultant N, Gedam DS. Ocular manifestation of childhood malnutrition-an overview. Int J Med Res Rev. 2017; 5:925-926.
18. Shubhrica D. Effect of environment on eyes: A review. Indian J Clin Pract . 2013; 24:381-384.
19. Billman GE. Homeostais: The underappreciated and far too often ignored central organizing principle of physiology. Fron Physiol. 2020;11: a200.
20. Nowinska AK, Machalinska A, Modis L. Ocular manifestation of systemic disease. J Ophthalmol. 2018;2018: a7851691.
22. Nishigori C, Yamano N, Kunisada M. Biological impact of shorter wavelength ultraviolet radiation-C. Photochem Photobiol 2023;99(92):335-343.
23. Bornman JF, Burnes PW, Robson TM. Linkages between stratospheric ozone, ultraviolet radiation and climate change and their implication for terrestrial ecosystem. Photochem Photobiol. 2019;18(30):681-716.
24. Coroneo M. Ultraviolet radiation and the anterior eye. Eye Contact Lens 2011;37(40):214-224.
25. Delic NC, Lyons JG, Di Girolamo N. Damaging effects of ultraviolet radiation on the cornea. Photochem Photobiol. 2017;93(4):920-929.
26. Yam JCS, Kwok AKH. Ultraviolet light and ocular diseases. Int Ophthalmol. 2014; 34:383-400.
27. Mathebula SD. Vitamin D in ocular and systemic health. African Vision Eye Health. 2015;74(1): a35.
28. Lin HC, Chen CS, Keller JJ. Seasonality of retinal detachment incidence and its association with climate: a 11-year nationwide population-based study. Chronobiol Int . 2011; 28:942-948.
29. Auger N, Rheaume MA, Bilodeau-Bertrand M. Climate and the eye: cae-crossover analysis of retinal detachment after exposure to ambient heat. Environ Res. 2017; 157:103-109.
30. Al Sammarrai AR. Seasonal variations of retinal detachment among Arabs in Kuwait. Ophthalmic Res. 1990; 22940:220-223.
31. Kim DY, Hwang H, Kim JH. The association between the frequency of rhegmatogenous retinal detachment and atmospheric temperature. J Ophthalmol. 2020;2020: a2103743.
32. Sharon N, Bar-Yoseph PZ, Bormusov E. Simulation of heat exposure and damage to the eye lens in a neighbourhood bakery. Exp Eye Res. 2008;87(1):49-55.
33. Al-Ghadyana AA, Cotlier E. Rise in lens temperature on exposure to sunlight or high ambient temperature. Br J Ophthalmol 1986;70(6):421-426.
34. Sliney DA. Physical factors in cataractogenesis: ambient ultraviolet radiation and temperature. Invest Ophthalmol Vis Sci. 1986;27(50):781-790.
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36. Minassion DC, Mehra V, Verrey JD. Dehydration crises: a major risk factor in blinding cataract. Br J Ophthalmol 1989;73(2):100-105.
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38. El-Sayed A, Kmel M. Climate change and their role in emergence and re-emergence of diseases. Environ Sci Pollut Res Int. 2020;27(18):22336-22352.
39. Saad-Hussein A, El-Mofty HM, Hassanien MA. Climate change and predicted trend of fungal keratitis in Egypt. East Mediterr Health J. 2011;17(6):468-473.
40. Talbot CJ, Bennett EM, Cassell K. The impact of flooding on aquatic ecosystem services. Biogeochemistry. 2018; 141930:439-461.
41. Smith JR, Ashander LM, Arruda SL. Pathogenesis of ocular toxoplasmosis. Prog Retin Eye Res. 2021;81: a100882.
42. Meier PA, Mathers WD, Sutphin JC. An epidemic of acanthamoeba keratitis that followed regional flooding: result of a casecontrol investigation. Arch Ophthalmol 1998;116(8):1090-1094.
43. Manisalidis I, Stravropoulou E, Stravropoulos A. Environmental and health impact of air pollution: A review. Front Public Health. 2020;8: a00014.
44. Orru H, Ebi KL, Forsberg B. The interplay of climate change and air pollution on health. Curr Environ Health Rep. 2017;4(4):504-513.
45. Mandell JT, Idarraga M, Kumar N. Impact of air pollution and weather on dry eye. J Clin Med 2020;99110: a9113740.
46. Lin CC, Chiu CC, Lee PY. The adverse effects of air pollution on the eye: a review. Int J Environ Res Public Health. 2022;1993): a19031186.
47. Chen R, Yang J, Chen D. Air pollution and hospital outpatient visits for conjunctivitis: a time-series analysis in Tdi’an, China. Environ Sci Pollut Res Int. 2021;28(12):15453-15461.
48. Ju MJ, Kim J, Park SK. Long-term exposure to ambient air pollutants and age-related macular degeneration in middle-aged and older adults. Environ Res. 2022;204:a111953.
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51. Luo CW, Chiang YW, Sun HY. Fine particulate matter exposure levels in patients with normal-tension glaucoma and primary openangle glaucoma: a population-based study from Taiwan. Int J Environ Res Public Health. 2022;19(7):a4224.
52. Bourne R, Steinmetz JD, Flaxman S. Trends in prevalence of blindness and distance and near vision impairment over 30 years: an analysis for the global burden of diseases study. Lancet Glob Health. 2021;9(2):e130-e143.
Correlation between corneal endothelial cell density and pterygium size in patients with a unilateral pterygium at St John Eye Hospital in Soweto
A Hajee MBBCH (Wits), FC Ophth (SA), Division of Ophthalmology, Neurosciences Department, University of Witwatersrand, Johannesburg, South Africa.
ORCID: https://orchid.org/000-0001-8617-6856
N D Welsh MBChB (UCT), MMed (Wits) (Ophth), FCS (SA) (Ophth).
ORCID: https:// orchid.org/0000-0001-7258-2730
T Seobi MBChB (UCT), FC Ophth (SA), MMed (Wits) Department of Surgery, Division of Ophthalmology, University of Cape Town.
ORCID ID: https://orchid/0000-0001-7125-4217
Corresponding author: Dr A Hajee, email : docamy786@gmail.com
Abstract
Background: A pterygium is a triangular wing-shaped degenerative growth from the conjunctiva to the cornea. Studies have shown that pterygium is linked to a decrease in endothelial cell density (ECD). The aim of this study is to assess the correlation between ECD and pterygium size in patients with a unilateral pterygium at St John Eye Hospital, Soweto. This is to assist in better planning for ocular surgical procedures and to address endothelial protection prior to the use of endothelial toxic agents.
Methods: A prospective cross-sectional comparative study was conducted on 100 patients between 18 and 60 years old with a unilateral primary pterygium attending St John Eye Hospital in Soweto, Johannesburg, between August 2021 and August 2022. Corneal endothelial cell parameters using a noncontact specular microscope (Tomey EM-4000) were assessed. The healthy contralateral eye was considered as a control.
Results: There was a statistically significant reduction in the mean corneal ECD (cells/mm) ECD:(P) M-2335.67, SD = 267.45 compared to the control eye ECD:(C): M-2536.78, SD = 206.02; p = <0.001, CI [-238.34, -163.88]) as well as a negative correlation
Introduction
The worldwide prevalence of pterygium is said to be 10.2%, but depending on the age and racial groups examined, reaching up to 33% in some populations.1,2
A pterygium is a triangular wingshaped degenerative hyperplastic growth of tissue from the conjunctiva to the cornea. 3 A pterygium arises in response to mechanical or chemical injury resulting in changes of the eye’s defense mechanisms, increasing its growth.4 Pterygium causes symptoms of irritation which can compromise visual acuity by causing irregular astigmatism. 5 Some studies
between ECD and % pterygium size; p = <0.001, R = -0.44.
Conclusion: Eyes with a pterygium were associated with a significant reduction in corneal endothelial cell parameters. This study has demonstrated the adverse effects that pterygia have on corneal endothelial cell parameters in our patient population.
Funding: This study received no financial contributions from private individuals, government, commercial or non-profit organisations.
Conflict of interest: The authors hereby declare that they have no conflict of interest.
Submission forms part of an MMED dissertation by publication.
Acknowledgements: The author wishes to acknowledge the management of St John Eye Hospital, which provided a conducive environment for work and the study.
have shown that pterygium is linked to a decrease in endothelial cell density.
Unilateral pterygium is more common than bilateral pterygia, and its development is often asymmetric. The hypotheses for this include ocular dominance, single eye closure in sunlight, driving where solar radiation is concentrated to one side of the face, corneal curvature, and anterior chamber depth. 3,6
The pathogenesis for pterygium formation is multifactorial. Ultraviolet (UV) radiation is the single most accepted risk factor for pterygium formation.6
Ocular factors such as a protruding eye is more likely to be affected by UV radiation than an eye that is recessed and protected by the superior orbital bone.4 The preference for the nasal limbus is explained by incidental light passing through the cornea. 7 Genetic factors may also play a role. 8 People residing within the “pterygium belt” have an increased UV radiation exposure and thus a higher risk for the development of ophthalmohelioses including pterygium. 7 Reactive Oxygen Species has also been found in pterygium tissue.9
Corneal endothelial cells are derived
from neural crest cells composed of a single layer of interdigitated cells arranged in a mosaic pattern of hexagonal cells.10 The mean corneal endothelial cell density (ECD) is usually highest at birth, at approximately 6000cells/mm2 . It declines to roughly 3500 cells/mm2 in young adult years and stabilises at the age of 50.11 The function of the corneal endothelium is to maintain the optical transparency of the cornea.
Measuring the corneal endothelial cell density is a salient clinical feature in the evaluation of the corneal stress response.12 Corneal oedema occurs when the endothelial cell count has declined to 500-1000 cells/mm2 11
Specular Microscopy is the most commonly used diagnostic modality to obtain endothelial cell images. The images produce an automated or manual ECD measured as cells per mm2 11 There are three parameters that assess endothelial cell health. The endothelial cell count (ECC), Coefficient of variation (CV) and Index of hexagonality.10,11 The Coefficient of variation is the standard deviation of the mean cell area. Index of hexagonality is a measure of the hexagonal morphology of the cells.10,11
With regards to pterygia, studies have confirmed that there is an association between pterygium and endothelial cell loss.13,14,15,16,17,18,19 Patients undergoing pterygium excision have a high rate of recurrence unless adjuvant therapy isused. 2 Unfortunately, adjuvant treatments such as Mitomycin C (even used topically), to prevent recurrence have deleterious effects on the corneal endothelium. This may potentially cause further damage in an already compromised corneal endothelium. 2 This is important as patients with pterygium may have other ocular pathology that require surgery that may further compromise their endothelial cell counts. These include but are not restricted to cataract and refractive surgery, as well as corneal transplant surgery. Examination of the ECD prior to commencing surgery and before the use of topical adjunctive therapy may prove beneficial.
The endothelial cell density in the South African population with pterygium has not yet been analysed. This study aims to determine the ECD in an African context, and whether there is a negative correlation between pterygium, pterygium size and ECD in the South African population.
Methods Ethical considerations and approval
Ethics approval was granted by the Human Research Ethics Committee of the University of Witwatersrand in July 2021. (Ethics approval number M210255).
Permission to conduct research at St John Eye Hospital in Soweto was granted by Professor I Mayet (Head of Department at St John Eye Hospital), as well as from the hospital management.
Informed consent was obtained from all participants prior to data collection.
Participant confidentiality was ensured by not including any identifiers on data sheets. Each participant was assigned a unique reference number to maintain anonymity. Data was stored in a password protected computer.
Study design
This was a prospective cross-sectional comparative analysis of corneal endothelial cell density in patients aged between 18 and 60 years with a unilateral pterygium and control eyes. It included patients seen in the Outpatients’ Clinic from the 1 August 2021 to the 31 August 2022 at St John Eye Hospital in Johannesburg, South Africa. All eligible patients who met the inclusion criteria were identified and included in the study.
Patients who had other corneal disorders affecting endothelial density such as corneal scars, dystrophies and ectasias were not included. Patients with a previous history of chemical injury or ocular burns, previous ocular trauma or intraocular surgery were also excluded.
Patients with previous pterygium surgery, recurrence or a pseudopterygium and those patients who gave a history of long-term contact lens wear (PMMA contact lens use for more than three consecutive years), uveitis, glaucoma or diabetes mellitus were also excluded due to their potential for affecting endothelial cell parameters.
Pterygium size was measured from the limbus to the apex of the pterygium overlying the cornea using slit lamp
biomicroscopy. Pterygium size was expressed as a percentage (%):ratio of size of pterygium overlyingcornea in millimetres (mm) / corneal diameter in millimetres (mm).
To compare the difference in the corneal ECD between eyes, the fellow eyes were considered as controls. To measure the corneal ECD, endothelial images were acquired at the centre of the cornea using a non-contact specular microscope (Tomey EM-4000). When the pterygium involved the central cornea such that the measurement of the ECD could not be made, that patient was then excluded. All measures were performed by the principal investigator.
Statistical analysis
Data was analysed using The Statistical Package for Social Sciences (SPSS) software (IBM Corp. Released 201. IBM SPSS Statistics for Windows, Version 25.0 Armonk, NY: IBM Corp).
Descriptive statistics including frequencies and percentages were calculated to summarise the categorical data.
The paired t-test was used to measure the parametric data, and the Pearson correlation test was used to test the association between the percentage of the pterygium and the endothelial cell density in the affected eye (ECDP). A p-value of <0.05 was considered statistically significant.
Results
One hundred patients with unilateral primary pterygium were included in this study. The contralateral eye was used as the control. Only patients between the ages of 18 and 60 were included, to ensure that no age-related endothelial cell loss bias was made.
Table I shows the age and gender distribution of patients affected by pterygium expressed asa percentage The ages ranged from 26 to 60 years, with a mean age of 45.59 and a standard deviation of 8.72. Of these subjects, 62 patients were female, and 38 patients were male.
Table I: Gender and age distribution of patients affected by pterygium.
Table II shows the laterality of eyes affected by pterygium. The right eye was affected in 55% (n = 55) and the left eye wasaffected in 45% (n = 45) of the patients.
Table II: Laterality of eyes affected by pterygium.
Laterality
Right
Left
In the eyes with pterygium, the right eye was affected in 55% (n = 55) and the left eye was affected in 45% (n = 45) of the patients.
Table III shows the comparison between ECD:(P) and the control eye ECD: (C). The ECD:(P) group had lower values (M = 2335.67, SD = 267.45) than the ECD:(C) group (M = 2536.78, SD = 206.02). A t-test for dependent samples showed that this difference was statistically significant, t (99) = -10.72, p = <0.001, and a 95% confidence interval (CI) [- 238.34,-163.88]. This results in a P-value of <0.001, which is below the specified significance level of 0.05. The t-test result therefore shows that there is a decrease in ECD-P when compared to the ECD-C eyes, and these values are statistically significant.
Table III: Comparison between Endothelial Cell Density (ECD) between pterygium (ECD-P) and control eye (ECD-C).
for dependent samples showed that this difference was not statistically significant,
Table IV: Comparison between Coefficient of variation (CV) between pterygium (CV-P) and control eye (CV-C).
The ECD:(P) group had lower values (M = 2335.67, SD = 267.45) than the ECD:(C) group (M = 2536.78, SD = 206.02). The t-test for dependent samples showed that this difference was statistically significant, t (99) = -10.72, p = <.001, 95% confidence interval (CI) [- 238.34, -163.88]. This results in a p-value of <.001, which is below the specified significance level of 0.05. The t-test result is therefore significant for the present data and the null hypothesis is rejected.
Table IV shows the comparison between CV:(P) and the control eye CV: (C). The CV:(P) group had higher values (M = 41.14, SD = 5.04) than the CV:(C) group (M = 40.24, SD = 4.45). A t-test for dependent samples showed that this difference was statistically significant, t (99) = 2, p = 0.049, 95% CI [0.01, 1.79]. This results in a p-value of 0.049, which is below the specified significance level of 0.05. The t-test result is therefore statistically significant.
Table V shows the Index of hexagonality (6A). It showed that the 6A:(P) group had lower values (M = 41.76, SD = 5.81) than the 6A:(C) group (M = 42.41, SD = 5.99). At – test
The CV:(P) group had higher values (M = 41.14, SD = 5.04) than the CV:(C) group (M = 40.24, SD = 4.45). A t-test for dependent samples showed that this difference was statistically significant, t (99) = 2, p = 0.049, 95% CI [0.01, 1.79]. This results in a p-value of 0.049, which is below the specified significance level of 0.05. The t-test result is therefore significant for the present data and the null hypothesis is rejected.
Table V: Comparison between index of Hexagonality(6A) between the pterygium (6A-P) and the control (6A-C) eye.
Table VI: Comparison between the central corneal thickness (CCT) of the rygium (CCT-P) and the control (CCT-C) eye.
The 6A:(P) group had lower values (M = 41.76, SD = 5.81) than the 6A:(C) group (M = 42.41, SD = 5.99). A t-test for dependent samples showed that this difference was not statistically significant, t (99) = -1.26, p = 0.21, 95% CI [-1.67, 0.37]. This results in a p-value of 0.21, which is above the specified significance level of 0.05. The t-test result is therefore not significant for the present data and the null hypothesis is retained.
The CCT:(P) group had higher values (M = 492.04, SD = 30.03) than the CCT:(C) group (M = 479.58, SD = 26.76). A t-test for dependent samples showed that this difference was statistically significant, t (99) = 6.51, p = <0.001, 95% CI [8.66, 16.26]. This results in a p-value of <0.001, which is below the specified significance level of 0.05. The t-test result is therefore significant for the present data and the null hypothesis is rejected.
t(99) = -1.26, p = 0.21, 95% CI [-1.67, 0.37]. This results in a p-value of 0.21, which is above the specified significance level of 0.05. The t-test result is therefore not statistically significant.
Table VI shows the comparison between the central corneal thickness (CCT) in the affected and control eyes. The CCT:(P) group had higher values (M = 492.04, SD = 30.03) than the CCT:(C) group (M = 479.58, SD = 26.76). A t-test for dependent samples showed that this difference was statistically significant, t (99) = 6.51, p = <.001, 95% CI [8.66, 16.26]. This results in a p-value of <0.001, which is below the specified significance level of 0.05. The t- test result is therefore statistically significant.
Figure 1 shows the comparison between the ECD-P and percentage (%) pterygium.
Scatter diagram
Figure 1: Comparison between the ECD-P and percentage (%) pterygium. A Pearson correlation was performed to test whether there was an association between % pterygium: and ECD:(P). The result of the Pearson correlation showed that there was a significant association between % pterygium: and ECD:(P), r (98) = -0.44, p = <0.001. There is a medium, negative correlation between the variables % pterygium: and ECD:(P) with r = -0.44. Thus, there is a medium, negative association between % pterygium: and ECD:(P) in this sample.
Scatter diagram
Figure 2. Comparision between ECD (P) and Age.
A Pearson correlation was performed to test whether there was an association between Age: and ECD: (P). The result of the Pearson correlation showed that there was no significant association between Age: and ECD:(P), r (98) = -0.19, p = 0.057.
A Pearson correlation was performed to test whether there was an association between the percentage (%) pterygium overlying the cornea and ECD:(P). The result of the Pearson correlation showed that there was a significant association between % pterygium and ECD:(P):
r (98) = -0.44, p = <0.001. There is a medium, negative correlation between the variables % pterygium: and ECD:(P) with r = -0.44. Thus, there is a medium, negative association between %pterygium:and ECD:(P) in this sample.
Figure 2 shows a comparision between ECD (P) and Age A Pearson correlation test was performed to test whether there was an association between Age: and ECD:(P). The result of the Pearson correlation showed that there was no significant association between Age: and ECD:(P), r (98) = -0.19, p = 0.057.
Discussion
To the best of our knowledge, this is the first study in South Africa as well as subSaharan Africa to document an association between pterygium growth, pterygium size and the corneal ECD.
There are a multitude of theories behind corneal endothelial cell damage in patients with pterygium. Elevation of local angiogenesis and inflammatory mediators by invasion of cornea by pterygium tissue, the direct effect of UV radiation on the cornea, mechanical trauma caused by impeded ocular movements
in larger pterygia and distortion of the deeper layers of the cornea by induced astigmatism caused by pterygium are all potential causes of endothelial cell damage. 2,8,13
A pterygium generally emerges in the superficial layers of the nasal cornea. When it invades the anterior elastic layer of the cornea, it is associated with Bowman’s layer dissolution and scarring of the stomal layer. This causes an upregulation in local inflammatory and angiogenesis mediators and can activate elevation of matrix metalloproteinase (such as MMP-1, MMP2, and MMP-9) expression. This in turn causes degradation of hemidesmosome attachments and leads to damage of corneal endothelial cells. 5,13 Mootha et al. first described deep corneal changes at the level of the endothelium and Descemet membrane. Their study found deep corneal marks in chronic nasal pterygium in older patients. This theory proposes that pterygium invasion exerts deeper layer damage in the cornea.13 Ultraviolet radiation which generates reactive oxygen species (ROS) is mutagenic for the suppressor gene p53 in limbal cells, leading to loss of collagenase and deregulation of apoptosis. 2
Our study not only showed that there was a statistically significant decrease in ECD-P when compared to the ECD-C (P = <0.001), but there was also a statistically significant decrease in CV-P
(P = <0.049) and CCT-P (P = <0.001). Notably, there was also a negative correlation between cornea ECD and % pterygium size which was statistically significant. (P = <0.001) (R = -0.44).
The study also showed a mild decrease in 6A-P group; however, this was not statistically significant. There was also no correlation between ECD-P and patient’s age.
Regarding the association between pterygia and the corneal ECD, studies from around the world have largely been inconclusive.
Hsu et al. conducted a retrospective study over a 30-month period in a Taiwanese population. The study included 90 patients. Corneal endothelial cell density was measured in both eyes, with the fellow eye being the control. Their reported mean ECD value in the affected eyes was 2232 cells/mm 2 , which was lower than their control value mean ECD:(C) of 2462.5 cells/mm 2 . Their results illustrated a significant decrease in endothelial cell density (p<0.0001) in eyes of patients with a pterygium. 5 Sousa et al. conducted a cross-sectional study in a hospital in Brazil. Sixty-one patients were enrolled into the study over a oneyear period. Their study was very similar to our South African study. Patients in their study group with pterygium showed a mean ECD:(P) of 2451.83 cells/ mm 2 compared to our affected patients, who had an ECD:(P) of 2536.78 cells/mm 2 They also demonstrated a statistically significant negative correlation between corneal endothelial cell density and the percentage of pterygium invasion of the cornea (p<0.001).13 Similar to our study, Kereem et al. in Iraq looked at the relationship between pterygium size and corneal ECD and found a negative correlation between these two variables. They also looked at the duration of being affected with pterygium and found that patients who had been affected for a longer duration had a lower corneal ECD.14 Another study which showed a significant decrease in ECD in patients with larger pterygia was conducted by Songur et al. in the Turkish population.15 Zaidi et al. who conducted a study in Pakistan showed a highly statistically significant decrease in ECD in eyes affected by pterygium. Their study also looked at other confounding variables such as smoking and sun exposure, both of which did not affect ECD measured.16 This is an important finding as it is a commonly understood fact that sun exposure could
be the reason for the ECD loss in patients with pterygia but is not always the case. Interestingly, Ragab et al. conducted a prospective cross-sectional comparative study in an Egyptian population that included 20 adult patients, where the contralateral eye of each patient served as a control. They demonstrated a numerically lower endothelial cell count in patients with pterygium (1271 cells/mm2) compared to our affected patients’ group with a measurement of 2335.67 cells/mm2 However, in their study the difference in the mean of the ECC was statistically insignificant.17 Other Egyptian studies including Ahmed et al. and Bagalaty et al. also demonstrated a negative correlation between pterygium and endothelial cell density and both studies showed statistically significant results.18,19 Since these studies were conducted in Egypt, it is more reflective of an African population.
Other studies such as Midgely et al. and Hu et al. both showed no difference in corneal ECD parameters in patients with pterygia. 20,21 Midgely et al. conducted the largest study analysing the effect of pterygium on corneal ECD which included 152 patients. They also assessed the correlation between astigmatism and corneal ECD. This report found that there was no correlation between pterygium and a loss of corneal ECD. They also noted that when astigmatism was used as a measure for pterygium severity, there was still no difference in corneal ECD loss. 20
Another study conducted in China by Hu et al. which included a retrospective as well as a prospective arm, showed no decrease in corneal ECD in eyes with a pterygium. The retrospective study reviewed patient medical records of 1 565 patients with primary pterygium and 3 448 patients without a pterygium and even though eyes with a primary pterygium did show a lower corneal endothelial cell density, this was not statistically significant. 21 Ninety-five patients were included in their prospective study, and no statistically significant decrease in endothelial cell parameters were noted. 21 There can be a multitude of factors contributing to this result which also demonstrates the importance of considering variables such as ethnicity, genetic factors and social behaviours such as diet and smoking in affected individuals to accurately assess its effect on the corneal parameters. Neither of these studies measured the size of the pterygium and patients may have had
smaller sized pterygia, possibly having a less profound effect on ECD.
Conclusion
This South African study conducted in Johannesburg demonstrates that patients with aprimary pterygium have an associated decrease in their endothelial cell density when compared to their unaffected contralateral eye. Patients with a primary pterygium also have a decrease in their Co-efficient of variation (CV) as well as a statistically significant lower central corneal thickness (CCT) compared to the control eyes. There is also a negative correlation between pterygium size and ECD.
Recommendations
In our Black South African population with pterygia, a recommendation can be given for the measurement of corneal endothelial cell parameters prior to any ocular surgical intervention (cataract surgery, corneal transplantation, and refractive procedures) or prior to the use of endothelial toxic agents such a Mitomycin C, which are often used in the management of pterygium recurrence. This is necessary for better surgical planning and patient counselling in this group of patients.
Limitations
This study did not measure the amount of UV exposure each patient received to correlate if this was directly proportional to a loss of endothelial cell parameters or (%) pterygium. The study also did not measure astigmatism produced by the pterygium to see if this correlated with loss in endothelial cell parameters.
References
1. Lui L, Wu J, Geng J, et al. Geographical prevalence, and risk factors for pterygium: a systematic review and meta-analysis. BMJ Open. 2013; 3:003787.
2. Radwan TM, Abdelghany AA, Ali AAF, et al. Assessment of corneal endothelial cell changes caused by Mitomycin-C application during pterygium surgery. J Egypt Ophthalmol Soc. 2019; 113:67-77.
3. Sudhalkar A. Pterygium fixation in amblyopes and non-amblyopes: a comparative evaluation. Eye. 2012; 26:438-443.
4. Anduze L.A. Pterygium – A Practical Guide to Management. Ed 1, Jaypee Brothers Medical Publishers, New Delhi, 2009; 7-9, 12-14, 24, 38-43.
5. Hsu M-Y, Lea H-N, Liang C-Y, et al. Pterygium is Related to a Decrease in Corneal Endothelial Cell Density. Cornea. 2014; 33:712-715.
6. Bahuva A, Rao KS. Current Concepts in Management of Pterygium. Delhi J Ophthalmol 2014; 25(2):78-84.
7. CoroneoM.Ultraviolet Radiation and the Anterior Eye. Eye Contact Lens. 2011; 37(4):214-224.
8. Anguria P, Kitinya J, Ntuli S, et al. The role of heredity in pterygium development. Int J Ophthalmol. 2014; 7(3):563-573.
9. Li X, Dai Y, Xu W, et al. Essential role of ultraviolet radiation in the decrease of corneal endothelial cell density caused by pterygium. Eye. 2018; 32:1886-1892.
10. Phathai S, Lawn SD, Shiels PG, et al. Corneal Endothelial Cells Provide Evidence of Accelerated Cellular Senescence Associated with HIV Infection: A Case-Control Study. PLoS ONE. 2013; 8:(2) e57422.
11. Gupta PK, Berdahl JP, Chan CC. The corneal endothelium: clinical review of endothelial cell health and function. J Cataract Refract Surg 2021; 47(9):1218-1226.
12. Ewete T, Ani EU, Alabi AS. Normal corneal endothelial cell density in Nigerians. Clin Ophthalmol. 2016; 10:497-501.
13. Sousa HCC, Silva LNP, Tzelikis PF. Corneal endothelial cell density and pterygium: a cross-sectional study. Arq Bras Oftalmol. 2017; 80(5):317-320.
14. Kereem AA, Mehdy IS, Al-Rubaye HS. The effects of Primary Pterygium on corneal Endothelial Cell Density in Iraqi Eyes. J Ophthalmol Adv Res. 2021; 2(2):1-11
15. Songur MS, Erkan E, Bayhan SA, et al. Evaluation of changes in corneal endothelial morphology during the progression of pterygium by specular microscopy. J Surg Med. 2021; 5(7):679-682.
16. Zaidi SBH, Ali Khan W. Is Pterygium Morphology Related to Loss of Corneal Endothelial Cells? A Cross-Sectional Study. Clin Ophthalmol. 2021; 15:1259-1266.
17. Ragab M, Saif M, Gouda AT. Assessment of Endothelial cell Density in Pterygium: A Crosssectional Study. Geriatric Ophthalmol. 2020; 3(5):34-39.
18. Ahmed ES, El Shayeb AA, Uosry RM. Evaluation of Effect of Pterygium on the Endothelial Cell Density of the Cornea by Specular Microscopy. BJAS 2020; 5:211- 217.
19. El Bagalaty DS, Farag RK, El-Khouly SE, et al. Effect of Primary Pterygium on Corneal Endothelial cell density. EJO (MOC) 2021; 4:223-230.
20. Midgley K, Ha J, Korchak M. Largest Report of the Effect of Primary Pterygium on Corneal Endothelial Cell Density. Invest. Ophthalmol. Vis. Sci. 2016; 57(12):5262.
21. Hu Y, Atik A, Qi W, et al. The association between primary pterygium and corneal endothelial cell density. Clin Exp Optom 2020; 103:778-781.
A survey of Ocular Trauma at Groote Schuur Hospital in Cape Town, South Africa
Z Logday MBChB (UCT), MSc Med (UCT), Global Surgery Division, University of Cape Town, Cape Town, South Africa. ORCID: https://orchid.org/0009-0002-9738-0830
S Maswime MBChB (UKZN), FCOG, MMed (Wits), PhD (Wits), Global Surgery Division, Department of Surgery, University of Cape Town, Cape Town, South Africa.
ORCID: https://orchid.org/0000-0003-4013-5164
D Minnies NHDMedTech (PenTech), MPH (UCT), PhD (UCT), Community Eye Health Institute UCT, Division of Opthalmology, Department of Surgery, University of Cape Town, Cape Town, South Africa.
This paper was submitted as a dissertation for MSc Med Global Surgery at the University of Cape Town.
Abstract
Background: Ocular trauma is an important cause of unilateral blindness around the world. There have been a few studies around Southern Africa that demonstrate the causality and outcomes. However, there is a dearth of evidence on the contribution of ocular trauma, despite the high prevalence of trauma that exists.
Objectives: To investigate the prevalence of ocular trauma cases that presented to Groote Schuur Hospital in Cape Town, South Africa from 1 December 2019 to 31 May 2020.
Methods: This was a retrospective cohort study of all ocular trauma cases seen at the Groote Schuur Hospital Trauma Unit over a six-month period.
Results: There was a total of 1301 trauma cases and a total of 47 ocular trauma cases, representing 3.6% of total trauma cases.
Introduction
Trauma affects tens of millions of people every year worldwide.1 Low- and middleincome countries (LMICs) have the highest prevalence of trauma, contributing 90% of trauma cases globally. 2,3 Approximately 4.4 million people die from trauma every year4; deaths that could be largely preventable by implementing policies that enforce safety, for example reducing availability of illicit substances that contribute to interpersonal violence.4 Millions more suffer from nonfatal injuries, as well as temporary and permanent disabilities such as blindness.1,4 In addition to the prevailing burden of trauma, the world was faced with a devastating lockdown as a result of the COVID-19 pandemic. During this time, it was documented that the number of trauma
Assault was the most common manner of trauma. Most cases involved males and those aged 18-30 years. Most cases were referred from primary healthcare facilities and 47% of cases required medical management only.
Conclusion: In this study, ocular trauma was found in 3.6% of cases that presented to the Emergency Unit. Ocular trauma predominantly occurred in males. Importantly, the majority of ocular trauma that occurred is as a result of assault; and a third of patients required a surgical intervention. During COVID19, there was a significant decline in the number of ocular trauma cases.
Key words: Ocular trauma, assault, blindness, low-middle income countries, COVID-19
cases had reduced significantly around the world. 5,6 Reasons for this reduction have been hypothesised, which include the alcohol sale restrictions and fear of contracting COVID-19, where people would avoid hospitals in fear of contracting the virus.7 South Africa’s trauma-related mortality rate is 4.5 times the global average.8 Interpersonal violence is one of the top ten causes of death and trauma resulting from it a significant contributor to the prevalence of disability.9 Morbidity from trauma, in this case ocular trauma, generates a major impact on the individual, healthcare system, and the economy.10
Over 90% of trauma-related mortality and morbidity occurs in LMICs with road traffic injuries and interpersonal violence predominating as causes. 3 Within
a country, trauma is more prevalent in low socioeconomic settings than high socioeconomic settings, in part because people from low socioeconomic settings live and work in unsafe environments, have inequitable access to healthcare, and less preventative measures are implemented and enforced in poorer areas.4 Furthermore, the economic impact of trauma is two-fold; it may preclude individuals from working, resulting in loss of income and it contributes to increased expenditure of medical care and recovery.4
Ocular trauma is a global concern with 90% of vision loss due to ocular trauma being preventable.11 According to Négrel and Thylefors, the World Health Organisation Program for the Prevention of Blindness captured that, some fifteen
years ago, trauma accounted for 1.6 million cases of blindness, 2.3 million cases of bilateral low vision, and 19 million cases of unilateral blindness worldwide.12 This data was captured In 2021, with increasing rates of global trauma, 2,4 it is possible that prevalence of ocular trauma has been on a steady rise, however there is no recent study to verify this. Most ocular trauma is accidental in high income countries; in contrast, in LMICs, interpersonal violence is a leading cause.12-14 In South Africa, interpersonal violence is the leading cause of ocular trauma.15 However, only four studies in South Africa have reported on ocular trauma:16 one study in Cape Town15, two in Kwa-Zulu Natal province,16,17 and one in East London.18 The studies described similar risk factors related to increased incidence of ocular trauma in South Africa, such as young males, drug and alcohol consumption, recreational settings, and low socioeconomic settings.15-18 These results reflect those found in other countries.12-14
In 2013, a study at Groote Schuur Hospital in Cape Town focused on the causes and effects of open globe injuries and found that ocular trauma accounted for 12.6% of all ophthalmology admission with 66% being open globe injuries as a result of interpersonal violence.15 The study focused on open globe injuries, excluding closed globe injuries, which accounted for 34% of the ocular trauma admissions.15 This finding provides a solid foundation and rationale to investigate all ocular trauma cases, especially considering that 12 000 general trauma cases present to Groote Schuur Hospital emergency unit every year.8 In 2016, a study done in East London focusing on epidemiology of ocular trauma found that 41% of ocular trauma admissions were closed globe injuries.15,18 Other studies have shown that open globe injuries are more severe, often requiring admission but closed globed injuries are more common, therefore it is important to include and investigate, and can require medical and/or surgical intervention.10,19
During the COVID-19 pandemic, countries around the world continued to treat ocular trauma.7,20,21 In the United Kingdom, two studies investigated the impact of COVID-19 lockdown on eye emergencies, one found a 43% reduction in ocular trauma during March 2020 to April 2020 when compared to March 2019 to April 2019, 22 and the other described a 3-fold increase in ocular trauma during the lockdown attributed to increase in falls and accidental domestic injuries. 23 Pellegrini et al. (2020) observed the changing trends of ocular trauma in the time of
COVID-19 and found a 68.4% reduction in ocular trauma however, concerned that patients with serious ocular injury avoided care in fear of contracting COVID-19. 24 A study in India found that 88% of patients missed their follow-up appointment due to lockdown restrictions and fear of COVID19. 25 Regular follow-up is necessary to delay ocular disease progression. 25 In South Africa, the impact of COVID-19 lockdown on ophthalmology follow-up for ocular trauma has not been investigated at the time of this study.
Overall, incidence of trauma and ocular trauma during immediate COVID-19 hard lockdown from March 2020 to April 2020 was reduced in countries around the world compared to March to April 2019, however the impact on ocular trauma before and during COVID-19 lockdown in South Africa has yet to be described.
Several studies have been conducted worldwide; however, research on ocular trauma is limited in South Africa.17 In Cape Town, no singular study that researches epidemiology of all ocular trauma cases that present to emergency centres has been published to our knowledge despite the high prevalence of trauma that exists.8 The primary aim of this study was to investigate the epidemiology of ocular trauma that presented to Groote Schuur Hospital in Cape Town, South Africa from 1 December 2019 to 31 May 2020. The secondary aim is to determine whether COVID-19 had a major influence on the prevalence and incidence of ocular trauma. The objectives were to identify the demographics of all patients with ocular trauma, to determine the prevalence, causes and severity of ocular
trauma cases, to identify the types of ocular trauma that was managed at Groote Schuur Hospital, whether it required medical or surgical management or specialist care and to investigate how many cases had isolated ocular trauma versus polytrauma. Additional objectives were to determine whether the COVID-19 pandemic affected prevalence of ocular trauma, ophthalmology services in terms of accessibility to care and outpatient follow up for ocular trauma.
Method
This was a retrospective cohort study that was conducted using patient case records from the hospital’s trauma unit. All patients with ocular trauma that present to the trauma unit were filtered based on the inclusion criteria during the six-month period. The inclusion criteria included all patients who presented to Groote Schuur Hospital, a large tertiary level academic public hospital in Cape Town, South Africa, with ocular trauma, including polytrauma cases with direct ocular trauma from 1 December 2019 to 31 May 2020. The exclusion criteria are participants under the age of 18 years, participants who sustained indirect ocular trauma i.e. ophthalmoplegia from a traumatic brain injury and patients who had a recurrent complication of a pre-existing ocular injury before 1 December 2019. The study sample comprised of all ocular trauma cases that were seen in the trauma unit during the study period. It excluded patients younger than 18-years-old. Patient information was captured from patient files and captured into an Excel (Microsoft Corporation, 2018) worksheet. Statistical analysis was performed on the data using
Table I. Age and sex of patients pre-COVID-19, during COVID-19 and overall (percentages of cases pre-COVID 19, during COVID 19 and the total, affecting different age ranges and sexes).
R-Studio (RStudio Team, 2020). The data was separated into pre-COVID, COVID and total cases and descriptive statistics was calculated for all variables in each category, which included central tendencies i.e. mean, median and range. Univariate analysis was done for each data set and predominantly observed frequency distributions.
Approval was granted for the study from the University of Cape Town Surgical Department Research Committee and Human Research Ethics Committee. Access to patient records was granted by Groote Schuur Hospital.
Results
There were 1301 trauma cases in Groote Schuur Hospital between December 2019 and May 2020. A total of 47 ocular trauma cases that met the inclusion criteria for this study during this time, which translates to approximately 3.6% of cases. The mean age was 33.9 years. The most common age range was 18-30 years, with 20/47 (42.6%) of cases followed by 31 to 40 years, which accounted for 14/47 (29.8%) of cases. The age range was 18 to 63 years. Males accounted for 46/47 (97.9%) of all cases. Patients in this study were predominantly unemployed, accounting for 28/47 (59.6%) of cases. Most of the patients were single, making up 34/47 (72.3%) of cases, followed by those married, which was 7/47 (14.9%) cases, 1/47 (2.1%) of cases were divorce then 5/47 (10.7%) cases were unknown marital status. Most patients were referred from a primary healthcare facility, accounting for 37/47 (78.7%) of cases. Most cases occurred in lower socioeconomic areas of Cape Town, most notably Mitchells Plain (31.9%) and Gugulethu (14.9%), this is also in keeping with the referral facilities that transferred patients from Mitchells Plain (32%) and Gugulethu (22%) to Groote Schuur Trauma Unit.
Ocular injury was most commonly due to blunt trauma, accounting for 29/47 (61.7%) cases, followed by sharp/penetrating trauma with 14/47 (29.7%), then by chemical trauma with 2/47 (4.3%) and foreign body with 2/47 (4.3%).
The most common manner of trauma was assault, accounting for 36/47 (77%) of cases. A detailed list of the objects used in assault cases can be found in Table II. Of the total cases, only 11/47 cases (23%) accounted for accidental trauma, most commonly due to road traffic accidents in 5/11 (45%) of accidental cases. Of note, community assault accounted for 9/36 (25%) of assault cases alone.
The most common injury sustained was a ruptured globe in 13/47 cases (27%)
followed by lid laceration in 9/47 cases (19%). A detailed list of all injuries can be found in Table III. Alcohol was implicated in 8/47 (17%) of cases, followed by 2/47 (4.3%) for illicit substances, 25/47 (53.2%) cases it was unknown cases whether alcohol/ substances were used, and 12/47 (25.5%) no alcohol/illicit substances were implicated. Unilateral injury was found in 40/47 (85%) of cases, with the left and right eye being equally affected. Most patients presented to a facility within six hours of injury, accounting for 33/47 (70%), 6/47 (12.8%) presented within 6-12 hours, 4/47 (8.5%) within 12-24 hours and 4/47 (8.5%) after 48 hours. Approximately 31/47 (66%) of patients received a consultation within six hours of
presentation to a facility, 9/47 (19.1%) within 6-12 hours, 3/47 (6.4%) within 12-24 hours and 4/47 (8.5%) within 24-48 hours. Isolated ocular injury account for 16/47 (34%) of total cases, the remaining 31/47 (66%) of cases sustained other injuries, most commonly facial fractures.
Medical management alone was needed in 22/47 (47%) of cases, followed by surgical management in 13/47 (28%) of cases.
Ophthalmology services were required in 38/47 (81%) of cases, with 25/47 (53%) of total cases also required additional care from other specialties, most commonly Neurosurgery and Maxillo-Facial. Most patients were discharged from the trauma unit (38%), followed by ophthalmology
Table II. Causes of accidental trauma and objects used in assault cases (percentages of cases pre-COVID 19, during COVID 19 and the total regarding accidental causes and objects used in assault cases). Pre-COVID 19 COVID 19
Table III. Types of ocular injuries (percentages of cases pre-COVID
admissions to the ward in 14/47 (30%) of cases. Most patients required followup, accounting for 34/47 (72%), of which 22/34 (65%) attended the follow-up. Of the 47 cases, 33 (70%) presented as unilateral blindness with a visual acuity of <3/60 (including counting fingers, hand movements, light perception and no light perception) and six (12%) cases as bilateral blindness, with a visual acuity of <3/60 on the first presentation comparative to final presentation, with 23 (48%) cases of unilateral blindness with a visual acuity of <3/60 of which, 10 (21%) cases resulted in unilateral evisceration and two (4%) cases of bilateral blindness with a visual acuity of <3/60.
During the COVID-19 pandemic period, only 11 of the total (47) were cases of ocular trauma, accounting for 23% of total cases. The mean age was 33.9 years. The most common age category was 18-30 years, with 36% of cases followed by 31-40 years, which also accounted for 36% of cases. The age
range was 23-43 years, with demographics similar to the pre-COVID -19 cases. Mitchells Plain and Gugulethu, two areas inhabited by people belonging to with mostly low to medium socio-economic strata of society, remained the most common areas where injuries occurred. Assault remained the most common manner of trauma, accounting for 7/11 (63%) of cases and accidental trauma accounted for 4/11 (37%). Workrelated injuries accounted for ¾ (75%) of total accidental trauma, with home-related accounting for ¼ (25%). Most common injuries remained as ruptured globe and lid laceration, account for almost 4/11 (37%) of all cases. Medical management was sufficient in 7/11 (63%) of cases, with the remaining needing surgical intervention, in keeping with the most common injuries. Ophthalmology services were required in 7/11 (63%) of cases. Of the total cases, 4/11 (36%) were discharged from the trauma unit and 4/11 (36%) needed outpatient management. Approximately, 5/11 (45%) of
Table IV. Type of management and types of other specialities required (percentages of cases pre-COVID 19, during COVID 19 and the management required, as well as other surgical specialist services that were needed for ocular trauma).
patients required follow-up, of which only 1/5 (20%) attended the follow-up.
Discussion
This study revealed that ocular trauma accounted for 3.6% of total trauma cases for the study period. A key finding is that assault was the leading cause of ocular trauma with a much higher proportion of young males being affected. Most ocular trauma cases were polytrauma cases involving the head, neck and face, which required multidisciplinary management. These injuries were also more likely to result in worse visual outcomes requiring surgical intervention. A significant proportion (48%) of cases resulted in unilateral blindness despite presenting to a facility and being treated timeously. COVID-19 lockdown observed an overall reduction in trauma cases however those that occurred were most commonly due to assault and the outpatient follow-up during this period was worse.
According to our knowledge, no similar study has been conducted in recent years. This study revealed that roughly 36 per 1000 individuals that sustain injuries from trauma are likely to sustain ocular trauma. The cause of the majority of ocular trauma was assault, accounting for 77% of cases and regarded as preventable.11,13 Some studies have documented that prevention strategies to reduce assault and interpersonal violence are difficult to develop.1,4 Some mention reducing drug and alcohol intake with stricter laws, prohibiting access to weapons and community education.1 In this study, assault remained the leading cause of trauma even during lockdowns.
Many studies have shown that men have a greater tendency to suffer from injury compared to females.1,8,10-13,16,28 Ocular trauma is no different and it is well documented that men are more likely to sustain ocular injuries compared to females. A study in New Zealand quoted a ratio of 3:1, a study in Malaysia was 6:1, in India it was 2.7:1 and in the United Stated it was 3.5:1.10,27,29,30 Two studies in South Africa, quoted a ratio of approximately 4:1.16,18 A study showed that women who are victims of intimate partner violence are likely to sustain facial injuries and ocular trauma, this is not reflected in this study. 31 This could be masked by the low occurrence of ocular trauma in women.
Most ocular injuries do not occur in isolation, they are often associated with other injuries, most commonly affecting the head, neck and face. As a result, neurosurgery, maxillofacial surgery and ENT surgery are involved in the co-management
of these patients. 29,30 In this study, a larger proportion of patients needed multidisciplinary intervention, approximately 25/47 (53%) of cases sustained other injuries, most notably facial fractures and traumatic brain injury and needed other specialist services such as maxillofacial surgery and neurosurgery. The remaining 22/47 (47%) of cases sustained isolated ocular injuries. These polytrauma cases were accompanied by severe ocular injuries, most notably ruptured globe injuries, accounting for eight out of 25 (32%) cases. Unilateral blindness resulted in 10/25 (40%) of the polytrauma cases and the only two bilateral blindness cases of the study were also as a result of polytrauma. A study in Malaysia documented 7% of cases having other injuries compared to India, which had 55% of cases involving other injuries, which is in keeping with this study. 29,30 The need for multidisciplinary services is key to improving trauma outcomes.
Most of the cases required surgical intervention accounting for 25/47 (53%) of cases. Surgery was either indicated for a ruptured globe or for a lid laceration. Unfortunately, surgery for the ruptured globes, 13/25 cases (52%) resulted in evisceration therefore not a vision-saving operation and consequently, resulted in the use of limited and valuable state resources without the reward of restoring vision.15,32 This is relevant as most of the polytrauma cases in this study resulted in other life-threatening injuries, such as a traumatic brain injury that required immediate attention and often the ocular injury is given less attention. However, this appropriate delay can result in worse visual outcomes as vision-threatening injury will not take preference over a life-threatening injury. 33 The impact of both bilateral and unilateral blindness on an individual’s life is two-fold, there are personal implications as well as economic.12,26 It may affect quality of life and independence, less involvement in the workforce and has been associated with mental health disorders. Those with bilateral blindness experience more severe consequences of daily life compared to those with unilateral blindness. 34 There is also a macro – and micro – economic cost implication, as mentioned individuals are less likely to be involved in the workforce, which may lead to unemployment and poverty. It has also been shown to affect global productivity, with a loss of $411 billion, according to WHO. 26
As previously mentioned, ocular trauma is a public health concern that can lead to vision loss.11-13 It has been noted that 90%
of ocular trauma is preventable with simple interventions, however this statement may be incomplete and should state that 90% of ocular trauma as a result of accidental injury is easily preventable. Accidental injuries in the workplace, sports field and due to road traffic accidents have clear prevention strategies in places, such as use of protective eyewear. Most of the studies, which have quoted this proportion of preventable blindness have been conducted in high income countries where more ocular trauma is as a result of accidental injuries. In LMIC, ocular trauma is most commonly due to assault and interpersonal violence, which is evident in this study with 36/47 (77%) of cases being assault-related and 11/47 (23%) of cases due to accidents. The World Health Organisation has stated that assault is preventable and strategies such as identifying risk factors for assault are targeted in order to mitigate violence. This is challenging and easily implemented interventions for interpersonal violence are difficult to develop. The WHO specifically targets reducing access and availability of alcohol and illicit substances, reducing access to weapons, promoting gender equality and deconstructing ideas that support violent behaviour. The effect of these interventions is not immediate.
Most cases were referred appropriately from primary healthcare facilities, as 81% of cases required ophthalmology services. Most patients presented and were treated timeously by a healthcare facility, which has been found to result in improved outcomes.15,18 This may indicate that there is a functional tertiary level service and efficient referral systems that exist. A study in Tanzania found that most patients presented after 24 hours, but in developed countries the timeous presentation and treatment reflects what was found in this study.14,15,19,33 Other parts of the African continent may not be as well-equipped or have enough resources, and it may result in delayed care and worse outcomes.
During COVID-19, there was an overall reduction in the number of ocular trauma cases, resulting in only 11/47 (23%) during COVID-19 compared to 36/47 (77%) preCOVID-19, roughly translates to 5.5 cases per month vs 9 cases per month, respectively; however, there were more assault cases (7 out of 11) compared to accidental cases (4 out of 11), which is a conflicting finding to most studies but supported by Navsaria, demonstrating that there was an overall reduction of trauma however, assault cases predominated over accidental ones. 35-39 The characteristics of individuals affected
remained consistent between pre-COVID-19 and COVID-19 periods, such as young males, who are unemployed and live in LMIC areas. These factors are the social determinants of trauma and ocular trauma. It has been theorised that young males are more likely to participate in risky behaviour that result in unintentional injuries.40 This could explain why these cases continued to occur during COVID-19 as these factors remain unchanged in a densely populated area. Another reason for the relative disproportion is that accidental injuries due to road traffic accidents were unlikely to occur as there were strict enforcements made on freedom of movement of people thereby restricting use of vehicles. The healthcare system continued to treat vision-threatening pathology throughout the pandemic, although access to follow-up was adversely affected. Patients were not seen due to COVID-19 and patients did not follow up, possibly due to fear of contracting COVID-19. The effect of the pandemic was detrimental to ocular health and trauma as loss to follow-up resulted in worse outcomes that may have been preventable. 25 As this was a retrospective study, it is difficult to determine the reason for the lack of attendance, however inference may be made that there was 2-fold reasons: there may have been difficulty in accessing transport to attend the follow-up and during this time people were afraid of contracting COVID-19 and avoided hospitals.7,25 This behaviour may be mimicked in future pandemics and likely to have negative outcomes on ocular health. There were outlying findings in this study that have not been documented in other studies, such as the consequence of community assault. Community assault resulted in 25% of ocular trauma cases, of which 30% resulted in severe injury and unilateral blindness. It is described as a form of vigilante justice in South Africa that is commonly seen in low-income areas and is a result of community retribution for criminals not tried or convicted by law enforcement.41 In order to correct and solve this societal disruption in the community requires improved law enforcement possibly with patrol units, community outreach centres that focus on holistic betterment of the community or the involvement of community health forums or street committees.
The strengths of this study
The strength of this study is that it involved a large cohort of cases with adequate documentation that could be reviewed to reveal incidence of ocular trauma in a
general trauma unit. It was relatively easy to conduct and cost efficient. This study provides novel data regarding contribution of ocular trauma to the general trauma burden, which has not been recently described in any other study according to our knowledge.
The limitations of this study
This was a retrospective cohort study and by its nature occasionally resulted in missing data. It was also difficult to establish cause and effect of ocular trauma, given it was retrospective.
Recommendations
A recommendation would be to conduct more clinically relevant studies in order to single out modifiable risk factors for ocular trauma, which can be targeted for prevention strategies. A further recommendation would be to reinforce and support current surgical services to improve the current standard of care for ocular trauma. The current service may benefit from an outreach programme that will upskill healthcare workers in the primary healthcare facilities to manage ocular trauma that is appropriate for their level of care prior to referring to a tertiary level of service. In order to reduce the level of ocular trauma, assault and interpersonal violence needs to be addressed and intervention needs to implemented accordingly, such as reducing access and availability of alcohol and illicit substances, reducing access to weapons, promoting gender equality and deconstructing ideas that support violent behaviour.
Conclusion
The study revealed demographic findings in keeping with current literature. It also provided incidence of ocular trauma and its burden on a trauma centre. Ocular trauma is more likely to occur in polytrauma and as a result of assault, which are both associated with worse visual outcomes and require multidisciplinary teams. Trauma due to assault is difficult to prevent compared to accidental injuries and developing prevention strategies may be challenging. COVID-19 lockdown resulted in less ocular trauma cases overall however assault continued to predominate. It was found that follow-up was worse possibly due to fear of contracting COVID-19 and difficulty in accessing transport. It will be important to maintain and improve current allocation of resources that treat ocular trauma in the context of polytrauma to preserve the current response level. Public
health interventions are required to prevent trauma and the long-term consequences of ocular trauma.
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An anti-infective and corticosteroid combination to treat a wide range of ocular infl ammation with infection or a risk of infection 1
0,5 % Loteprednol Etabonate with site-specific, high anti-inflammatory e cacy 2-4 0,3 % Tobramycin with broad spectrum activity 5 Reduced propensity for elevation in intraocular pressure 6 When inflammation and infection hits, strike back with our double-agent 1
Compared With Olopatadine Solution 0.1% Administered BID in the Treatment of Seasonal Allergic Conjunctivitis: A Multicenter, Randomized, Investigator Masked, Parallel Group Study in Chinese Patients. Clin Ther. 2012;34:1259–1272.
Preclinical chloroquine maculopathy detection in a South African multiracial population by spectral-domain optical coherence tomography (OCT)
P Mncube MBChB (UKZN), FC Ophth (SA), Consultant, Ophthalmology Department Greys Hospital, Nelson R Mandela School of Medicine, University of KwaZulu-Natal, Durban, KwaZulu-Natal, South Africa.
ORCID ID: https://orcid.org/0009-0005-0462-1626
P Mthethwa MBChB (Wits), MMEd Orth (UKZN), H.dip Orth (SA), FC Orth (SA), Head of Department of Orthopaedic Surgery, Nelson R Mandela School of Medicine, University of KwaZulu-Natal, Durban, KwaZulu-Natal, South Africa.
ORCID ID: https://orcid.org/0000-0001-6432-1899
CH Kruse MBChB (UP), FCOphth (SA) MMed (Ophth) (UKZN), Ophthalmologist and lecturer at the University of KwaZulu-Natal, Durban, KwaZulu-Natal, South Africa.
ORCID ID: https://orcid.org/0000-0002- 8805-8383
Corresponding author: P Mncube; email: pdmncube@webmail.co.za
Abstract
Aim: We aimed to determine preclinical chloroquine maculopathy detection by spectral-domain optical coherence tomography (OCT).
Materials and methods : This case-control study included 91 patients (chloroquine vs control group). We employed descriptive and linear regression statistical analysis and correlation between OCT measurements in relation to clinical-related factors and the assessment of cumulative chloroquine dosages.
Results: The mean age was 44.7 years (SD 14.0; range 16-81). There were significant differences in means of the three parameters (p < 0.001) in the chloroquine group compared to controls: chloroquine-treated nerve fibre layer (NFL) thickness of 298.04 µm (SD 16.303) vs. 308.16 µm (SD 9.788), ganglion cell layer (GCL) volume 1.03 mm³ (SD 0.112) vs. 1.11 mm³ (SD 0.109)
Introduction
Chloroquine (CQ) and hydroxychloroquine (HCQ) are antimalarial drugs that are also used to treat many inflammatory conditions, such as rheumatoid arthritis and dermatological conditions, because of their immunosuppressive capabilities.1 Like all drugs, chloroquine can have adverse effects, including ocular side effects, the most detrimental being retinal toxicity. Previous studies on symptomatic patients receiving CQ or HCQ therapy reported retinal thinning and loss of outer retinal layers with early retinal toxicity.1-2 For early detection of retinal drug toxicity, the American Academy of Ophthalmology (AAO) published a revised
and retinal volume (RV) 8.30 mm³ (SD 0.47) vs. 8.62 mm³ (SD of 0.317), respectively. However, the total cumulative dose did not correlate with decreasing NFL thickness, GCL, or RV.
Conclusion: Rheumatological patients treated with chloroquine in South Africa exhibited significant thinning of NFL, GCL, and retinal volume on spectral-domain OCT images. The total cumulative dose, however, did not correlate with decreasing NFL thickness, GCL, or RV suggesting that the inflammatory disease itself, rather than the medication, is the cause of the retinal volume loss.
2016 recommendation for surveillance in these patients. 3-4 The AAO recommended baseline exploration during the first year of treatment to discard any maculopathy which would contraindicate their administration and as a benchmark for comparing subsequent findings. Annual examinations should be performed before the fifth year of treatment or earlier in the presence of risk factors. The final objective of these examinations was to identify any paracentral retinal damage or visual field (VF) defects at an early stage. The ophthalmological examination recommended by the AAO consists of a standard examination including visual acuity [VA], IOP, and anterior pole
biomicroscopy and two tests that have proven useful for detecting retinal toxicity caused by antimalarial drugs. 34 The 2020 revised guidelines from the UK Royal College of Ophthalmology grossly mirror its recommendations with the AAO guidelines for monitoring retinal toxicity in patients taking HQC and CQ. 5 Monitoring for patients on HCQ begins after five years if there are no additional risk factors. Monitoring for CQ begins after one year of drug therapy, baseline testing for new initiators of HCQ or CQ is no longer recommended. Screening employs the use of spectral domain optical coherence tomography (SD-OCT) and fundus autofluorescence (FAF), ideally
using widefield imaging where possible. If imaging reveals any abnormalities, it is recommended that patients undergo automated visual field testing. 5 The location of the observed structural abnormality should determine the choice of a 10-2 or 30-2 protocol. In instances where dilating eye drops are used for imaging or when assessments are conducted within virtual clinic settings, visual field tests may need to be scheduled in a separate visit following the image review. For patients who present with confirmed structural abnormalities on SD-OCT or FAF but do not show corresponding visual field defects upon repeat testing, multifocal electroretinography is advised to further assess retinal function. 5
SD-OCT was introduced approximately two decades ago and has revolutionised ophthalmic practice.6-7 It is a non-invasive, non-contact imaging modality that provides high-resolution cross-sectional images of the cornea, retina, choroid, and optic nerve head, analogous to that of histological sections.6-7 Advances in OCT technology in signal detection techniques, from time-domain (TD) to spectral-domain (SD) detection, have given us the potential to study various retinal layers more precisely and in less time. SD-OCT delineates structural changes and fine lesions in the individual retinal layers. Thus, we have gained substantial information about the pathologic and structural changes in ocular conditions with primary or secondary retinal involvement.6-7
The ability to detect these changes during the preclinical stages of chloroquine maculopathy is of utmost importance. These changes include loss of retinal thickness and loss of the outer retinal layers. 3-7 Thinning of the photoreceptors in the parafovea is highly specific evidence of chloroquine toxicity, assuming no other retinal condition is present. Initial changes are recognised on SD-OCT as distinct focal interruptions of photoreceptors’ outer segment structural lines. 3-7
The “bull’s-eye maculopathy,” which is classically described in textbooks as chloroquine-induced retinopathy, corresponds to a ring scotoma. 8 This is a very late and severe stage of parafoveal damage. 8 With modern imaging like SD-OCT, this late stage should be seen much less frequently as the imaging can recognise toxicity much earlier, prior to the onset of bull’s maculopathy and even before visual symptoms occur. 8-9 HCQ has lesser retinal toxicity than CQ.10 However, in our context, HCQ is only available on a motivational
Preclinical chloroquine maculopathy detection
basis, making it mostly inaccessible to physicians to prescribe.11 Pressure from rheumatologists, dermatologists, and ophthalmologists to acquire HCQ registered in South Africa (RSA) is critical.11
We aimed: 1) To determine preclinical chloroquine maculopathy detection in a South African multiracial population using spectral-domain optical coherence tomography (OCT) with specific reference to central foveal thickness (CFT), parafoveal and perifoveal thickness in all quadrants, ellipsoid layer integrity, average retinal nerve fibre layer (NFL) thickness, ganglion cell layer (GCL) thickness, and 2) to determine the association between OCT parameters and cumulative dose and duration of treatment.
Materials and methods
Study subjects
This was a prospective, cross-sectional, observational, case-matched cohort study on the eyes of subjects recruited from the Ophthalmology and Rheumatology outpatient clinics at Greys Hospital, a tertiary-level state hospital in the province of KwaZulu-Natal, South Africa. This study examined whether microscopic retinal changes might be evident in patients receiving chloroquine therapy before the clinical signs of toxicity. The study followed the principles of the Declaration of Helsinki, and ethical approval was obtained from the Biomedical Research Ethics Committee of the University of KwaZuluNatal (BREC REF: BE659/18), the provincial ethics committee, and the health facility.
Arbitrarily, the left eye of each patient was used unless the patient had a condition that prohibited the inclusion of that eye from being included. The study population consisted of two groups: Group A (chloroquine group) and patients on chloroquine therapy for at least one year with clinically normal eyes. Group B (control group), Chloroquine-naïve patients with a clinically normal ophthalmological examination. Patients with a history of renal and hepatic disease, previous intraocular surgery, previous or current chorioretinitis, previous or current retinopathy, optic neuropathy, glaucoma, or any eye condition precluded good vision were excluded from the study. In this study, we included all adults, irrespective of racial group, sex, or systemic diagnosis.
Patient evaluation
After obtaining informed consent, all patients underwent full history taking, with special attention to the daily dose
of chloroquine, treatment duration, and disease details. The lifetime cumulative dose was calculated for each patient. Daily and cumulative dose data were collected from the patient’s history and verified by comparing them to their health records and medication prescriptions.
Clinical assessment
Complete ophthalmologic examination was performed, including pupillary reaction, best corrected visual acuity (BCVA) in logMAR units, anterior segment assessment by slit lamp examination, intraocular pressure measurement with an applanation tonometer, and fundus examination with a +90D lens to assess the posterior pole and mid-peripheral fundus.
Structural assessment
Spectral domain ocular coherence tomography (SD-OCT) scans were performed using Heidelberg Spectralis®, and analyses were performed according to the manufacturer’s standard software protocols (version 1.10.4.0). Data collected included central foveal thickness (CFT), parafoveal and perifoveal thicknesses in all four quadrants (ETDRS grid), and the average thicknesses of the retinal nerve fibre layer (NFL) and ganglion cell layer (GCL). The examiner evaluated the integrity of the ellipsoid layer (IS/OS junction) by using scans passing through the fovea. Integrity breaches were defined by any horizontal discontinuity in the ellipsoid layer of 5µm or more.
Outcome measures
Primary outcome measures included NFL thickness, GCL, and retinal volume (RV), which were compared between the study groups (chloroquine versus nonchloroquine). Correlations between OCT parameters, cumulative dose, and duration of treatment were determined.
Statistical analysis
To detect a clinically significant difference of 7 µm in retinal thickness (the minimum resolution of our OCT), with a mean retinal thickness of 230 µm (SD 15 µm), a minimum of 40 participants per group is required. Continuous variables, such as patient age, were summarised as mean (± standard deviation) or median (with interquartile range) as appropriate and compared using the Student’s T-test or Wilcoxon test, respectively. Categorised variables, such as the presence or absence of early maculopathy, were described as percentages or proportions and compared
using the chi-square test or Fisher’s exact test, as appropriate. Linear regression was used to describe the impact of chloroquine dose on the retinal metrics. All statistical analyses were performed using the SPSS® v25 software. A power of 0.80 was used and statistical significance was maintained at a p-value < 0.05.
Sampling and data collection
The first 40+ eligible patients on chloroquine who were present at the rheumatology clinic formed Group A. The first 40+ patients at the eye clinic who were not exposed to chloroquine, formed Group B and were matched to Group A patients with regard to sex and age (within 10 years). Controls that could not be matched to Group A cases were excluded.
Raw data were collected using two methods
Demographic data, treatment history, and clinical examination data were captured by the primary investigator (or designated trained staff) from the original hospital health records on data entry sheets. SD-OCT data were captured electronically on the available Heidelberg Spectralis OCT system in the Department of Ophthalmology. The final data entry was entered into a Microsoft Table I: Demographics and rheumatological disease descriptive statistics. Overall (N = 91)
Group
Office Excel® spreadsheet, optimised for statistical analysis.
Results
Demographics and rheumatological disease descriptive statistics of the cohort. Table I summarises the demographics of this observational case-control study of 91 patients. The mean age was 44.7 years (SD\ 14.0. years; range, 16-81 years), and 75.8% were female. The greatest proportion of patients were of African descent (78.0%) compared to Indians (17.6%) and whites (4.4%). The mean weight
was 75.9 kg (SD, 14.8; range, 47.0-124.0 kg). In terms of the diagnosis proportional distribution, the majority of patients in Group A were being treated for rheumatoid arthritis (RA) (52.2%) and systemic lupus erythematosus (SLE) (43.5%).
The effect of demographic and clinical factors on retinal volume
None of the demographic factors (Table II), including age, normalised lean weight, sex, race, or clinical diagnosis, were associated with retinal volume or any other retinal layer metrics measured. (p 0.195-0.903)
Table II: Model Coefficients – Effects on
Table III: Retinal measurements in
OCT: Retinal measurements of experimental and control groups
Table III and Figure 1 show the differences in NFL thickness, GCL volume, and retinal volume between the case and control groups. Their retinal volume (RV) was significantly lower in cases with a mean of 8.30 mm³ (SD of 0.470) compared to 8.62 mm³ (SD of 0.317) for controls (p < 0.001). (Fig 1A) In addition, ganglion cell layer (GCL) volume was also significantly lower in the chloroquine-treated cases, with a mean of 1.03 mm³ (SD 0.112) compared to 1.11 mm³ (SD 0.109) in the controls (p < 0.001). (Fig 1B) Furthermore, there was a significant difference in means (p < 0.001) between the chloroquine-treated NFL thickness of 298.04 µm (SD 16.303) compared to the control mean NFL thickness of 308.16 µm (SD 9.788).
The effect of total cumulative dose on retinal measurements
All Group A patients used 200 mg of chloroquine tablets once daily, as per the protocol at the Greys Hospital Rheumatology Clinic. This means they all shared the same daily dose but differed in the cumulative dose due to their different treatment durations only. Cumulative dosage was thus the only metric of the three that was analysed.
Despite the difference between group A and B for all retinal measurements (p < 0.001) (Table IV ), the total cumulative dose was not a predictor of either NFL thickness, GCL volume or retinal volume.
Figure 2 shows that although there was a difference in retinal volume between groups A and B, there was no change in volume as the cumulative chloroquine amount increased. NFL thickness and GCL volume were also indifferent to the cumulative dosage of chloroquine (p = 0.255-0.286).
No differences were found in any of the metrics when comparing the different ETDRS grid quadrants to each other. No ellipsoid layer defects were noted in any patient in either group.
Discussion
We aimed to determine preclinical chloroquine maculopathy detection in a South African multiracial population using spectral-domain OCT with specific reference to NFL thickness, GCL, and retinal volume. The clinical characteristics of our cohort grossly mirror those found globally, where racial differences had no effect on OCT findings and factors associated with chloroquine retinal toxicity. 2-9 Increasing age was not an independent factor in retinal thickness (p = 0.195). This is
inconsistent with global reports, where the general population is mostly Caucasians. 2-8, 11 For instance, in 2003, Alamouti et al., in the UK, found that total retinal thickness and the nerve fibre layer thickness significantly decreased with age.11 Their explanation was that approximately 80% of the changes in retinal thickness over time are caused by NFL shrinkage.11
To the best of our knowledge, this is the largest series in the African region, comprising 77.3% (n = 144) of Africans, compared to Asians (18.2%, n = 33) and Caucasians (4.4%, n = 8). In 2015, Allam et al., in Egypt, recorded the largest series in Africa (n = 88) when they assessed chloroquine OCT preclinical findings associated with retinal toxicities in left-eye females with rheumatoid arthritis (RA), which found that chloroquine toxicity can lead to thinning of the central fovea and parafoveal regions.12 This aligns with the findings that clinically asymptomatic patients receiving chloroquine for inflammatory diseases exhibited significant mean NFL thickness, with reduced GCL and retinal volumes
compared to the experimental groups (p < 0.001). Furthermore, previous studies on symptomatic patients treated with chloroquine or hydroxychloroquine showed retinal thinning and loss of the outer retinal layers with early retinal toxicity.6-10 However, while there is a general consensus about retinal toxicity for both drugs, 6-10 hydroxychloroquine confers much lesser adverse effects than chloroquine.10 This may have serious clinical implications in South Africa because hydroxychloroquine is essentially unavailable. 10 Chloroquine is a core element of treatment protocols for various systemic conditions,1-2 and its toxicity requires healthcare resources in terms of screening and management of visual complications in a resourceconstrained setting like ours. However, in our series, the absence of a larger sample size, lack of a national database, and standardised national guidelines for carefully using the drug and screening tools underscores the need for further research in this area.
Traditionally, in previous studies, the
Linear regression – model coefficients
Table IV: The effect of total cumulative dose on retinal measurements.
Figure 2: The total cumulative chloroquine dose did not influence retinal volume in a South African population when examined on spectral-domain OCT images.
total cumulative chloroquine dosage was associated with retinal volume loss. 3-9,14-16 However, current evidence suggests that the cumulative dosage and duration of therapy are relatively unimportant and that the crucial index is daily dosage normalised by lean body weight.14-16 Current recommendations suggest that a daily chloroquine dose not exceeding 4 mg/kg/ day is safe for most patients. 3-4 In our study, although there was a significant effect on the difference between the two groups for retinal measurements (p < 0.001) (Table III), the total cumulative dose was not a predictor of NFL thickness, GCL volume, or retinal volume. Our rheumatological patients shared the same daily dose of 200 mg but differed in the cumulative dose due to their different treatment durations. The effects of cumulative dose can therefore be directly correlated to treatment duration in this study.
Despite reduced retinal metrics in chloroquine patients, the length of treatment and the cumulative chloroquine dose had no effect. This suggests that retinal differences can likely not be attributed to chloroquine therapy itself. Multiple studies have shown that systemic inflammatory disease processes can independently affect the thickness of various retinal layers.17-22 Macular OCT measurements were correlated with the severity and duration of the disease itself, including in patients with SLE and rheumatoid arthritis.17, 22 Systemic disease severity was not evaluated in our study, but the reduction in thickness and volume of the retinal layers in the chloroquine group, while independent of total chloroquine dosage, seems to support this finding. This is the largest series among the African population; the cross-sectional design of the prospectively collected data of patients in the chloroquine and control groups is one of the strengths of this study. The relatively small sample size is a limitation, and our findings should be interpreted cautiously. The lack of a national registry and standardised national guidelines for drug usage and screening tools underscores the need for further research in this area, especially in the areas of larger studies on racial differences and whether specific diseases cause retinal thinning.
Conclusion
Rheumatological patients receiving chloroquine therapy in South Africa exhibited significant decreases in NFL thickness, GCL volume, and retinal volume
on spectral-domain OCT images. These changes were, however, independent of the cumulative chloroquine dosage and treatment duration and are more likely to indicate the effects of the underlying systemic inflammatory condition itself. Therefore, in our preclinical population, decreases in retinal layer OCT metrics cannot be used as indicators of the progressive ocular effects of chloroquine.
References
1. Tanenbaum L, Tuffanelli DL. Antimalarial Agents: Chloroquine, Hydroxychloroquine, and Quinacrine. Archives of Dermatology. 1980;116(5):587-91.
2. Ding HJ, Denniston AK, Rao VK, Gordon C. Hydroxychloroquine-related retinal toxicity. Rheumatology. 2015;55(6):957-67.
3. Cramarossa G, Liu HY, Turk MA, Pope JE. Guidelines on prescribing and monitoring antimalarials in rheumatic diseases: a systematic review. Clin Exp Rheumatol. 2021;39(2):407-12.
4. Marmor MF, Kellner U, Lai TY, Melles RB, Mieler WF. Recommendations on Screening for Chloroquine and Hydroxychloroquine Retinopathy (2016 Revision). Ophthalmology 2016;123(6):1386-94.
5. Yusuf IH, Foot B, Lotery AJ. The Royal College of Ophthalmologists recommendations on monitoring for hydroxychloroquine and chloroquine users in the United Kingdom (2020 revision): executive summary. Eye. 2021;35(6):1532-7.
6. Kahn JB, Haberman ID, Reddy S. Spectraldomain optical coherence tomography as a screening technique for chloroquine and hydroxychloroquine retinal toxicity. Ophthalmic Surgery, Lasers and Imaging Retina. 2011;42(6):493-7.
6. Chen E, Brown DM, Benz MS, Fish RH, Wong TP, Kim RY, et al. Spectral-domain optical coherence tomography as an effective screening test for hydroxychloroquine retinopathy (the “flying saucer” sign). Clin. Ophthalmol 2010:1151-8.
7. Shinjo SK, Maia Júnior OO, Tizziani VAP, Morita C, Kochen JAL, Takahashi WY, et al. Chloroquine-induced bull’s eye maculopathy in rheumatoid arthritis: related to disease duration? Clinical Rheumatology. 2007;26(8):1248-53.
8. Scherbel Arthur L, Mackenzie Allen H, Nousek James E, Atdjian M. Ocular Lesions in Rheumatoid Arthritis and Related Disorders with Particular Reference to Retinopathy. N Engl J Med. 1965;273(7):360-6.
9. Yusuf IH, Charbel Issa P, Ahn SJ. Hydroxychloroquine-induced Retinal Toxicity. Front. Pharmacol. 2023; 14:1196783.
10. Whitelaw D, Jessop S. Chloroquine-induced
retinal toxicity 2008.
11. Alamouti B, Funk J. Retinal thickness decreases with age: an OCT study. Br. J. Ophthalmol. 2003;87(7):899.
12. Allam RS, Abd-Elmohsen MN, Khafagy MM, Raafat KA, Sheta SM. Spectral-Domain Optical Coherence Tomography of Preclinical Chloroquine Maculopathy in Egyptian Rheumatoid Arthritis Patients. J Ophthalmol. 2015; 2015:292357.
14. Lenfant T, Salah S, Leroux G, Bousquet E, Le Guern V, Chasset F, et al. Risk factors for hydroxychloroquine retinopathy in systemic lupus erythematosus: a case-control study with hydroxychloroquine blood-level analysis. Rheumatology (Oxford). 2020;59(12):3807-16.
15. Wolfe F, Marmor MF. Rates and predictors of hydroxychloroquine retinal toxicity in patients with rheumatoid arthritis and systemic lupus erythematosus. Arthritis Care & Research 2010;62(6):775-84.
16. Levy G, Munz S, Paschal J, Cohen H, Pince K, Peterson T. Incidence of hydroxychloroquine retinopathy in 1,207 patients in a large multicenter outpatient practice. Arthritis & Rheumatism: Official Journal of the American College of Rheumatology. 1997;40(8):1482-6.
17. Fekrazad S, Shahrabi Farahani M, Salehi MA, Hassanzadeh G, Arevalo JF. Choroidal thickness in eyes of rheumatoid arthritis patients measured using optical coherence tomography: A systematic review and meta-analysis. Survey of Ophthalmology. 2024;69(3):435-40.
18. Pelegrín L, Morató M, Araújo O, FiguerasRoca M, Zarranz-Ventura J, Adán A, et al. Preclinical ocular changes in systemic lupus erythematosus patients by optical coherence tomography. Rheumatology. 2023;62(7):2475-82.
19. Mimier-Janczak MK, Kaczmarek D, Proc K, Misiuk-Hojło M, Kaczmarek R. Subclinical retinopathy in systemic lupus erythematosus patients-optical coherence tomography study. Reumatologia. 2023;61(3):161.
20. Altinkaynak H, Duru N, Uysal BS, Erten Ş, Kürkcüoğlu PZ, Yüksel N, et al. Choroidal Thickness in Patients with Systemic Lupus Erythematosus Analyzed by Spectraldomain Optical Coherence Tomography. Ocular Immunology and Inflammation. 2016;24(3):254-60.
21. Valenzuela MEV, Díaz VG, Martinez-Bonilla G, Medina AGB, Martinez JFU, Arteaga CAR, et al. AB0679 ophthalmological findings by structural, spectral domain optical coherence tomography in patients with systemic lupus erythematosus. Annals of the Rheumatic Diseases. 2023;82(Suppl 1):1542-3.
22. Rashidifard C, Vercollone C, Martin S, Liu B, Brezinski ME. The Application of Optical Coherence Tomography in Musculoskeletal Disease. Arthritis. 2013; 2013:563268.
CONFIDENCE FIRST
Globally over 10-million patients’ years 1
Globally Over 70-million doses admissted 2
In Routine practice, IOI with EYLEA® Remains Rare
0.0095% (0.95 cases per 10,000 vials/PFS sold globally)3 a
An educational intervention to improve topical treatment technique success in glaucoma patients in central South Africa
A Jansen van Rensburg MBChB (UFS), MMed (Ophth) UFS, Dip Ophth (SA), FCOphth (SA), Registrar, Department of Ophthalmology, University of the Free State.
ORCID: https://orcid.org/0000-0001-7971-4556
W Marais MBChB (UFS), MMed (Ophth) UFS, FCOphth (SA), Head of Department, Department of Ophthalmology, University of the Free State.
ORCID: https://orcid.org/0000-0003-1704-3659
C van Rooyen Department of Biostatistics, Faculty of Health Sciences, University of the Free State
ORCID: https://orcid.org/0000-0002-5092-2957
Corresponding author: Arno Jansen van Rensburg; email address: arno.eyes@gmail.com
Abstract
Background: Glaucoma is a leading cause of blindness globally. The deterioration of glaucoma can be avoided by decreasing the intraocular pressure (IOP) with topical eye drops, which should be done correctly to gain the greatest benefit.
Objectives: To determine whether patients’ eye drop instillation technique and self-efficacy improved immediately after watching a short educational video or reading an instruction pamphlet.
Methods: A prospective interventional study was conducted. We enrolled 100 patients with primary open-angle glaucoma (POAG) administering their own eye drops into a simple randomised sampling method, who either received an instruction pamphlet or watched a short educational video on the correct eye drop instillation technique. We assessed the patients with an objective direct observational method at baseline and immediately after the interventions, using a tenstep scoring system.
Results: Compared to the baseline assessment, the final scores improved with both interventions. The video intervention averaged 3.74 steps better compared to the 1.8 average steps improvement
Introduction
Glaucoma is one of the leading causes of blindness in South Africa, with a total of approximately two million patients currently affected in the country.1-3 Intraocular pressure- (IOP-) reducing eye drops are still being used worldwide as part of the standard treatment to prevent the progression of glaucoma.4 To instil these eye drops correctly requires the patient to use a proper technique to ensure that the optimal results are achieved while minimising side effects. 5,6
Previous studies demonstrated suboptimal eye drop instillation technique with patients failing to perform critical steps, such as applying a single drop effectively
with the instruction pamphlet (p = 0.0008). With both interventions, the patients’ self-efficacy increased similarly (p = 0.6757).
Conclusion: Both interventions yielded improved proficiency of eye drop instillation technique and self-efficacy of patients with glaucoma. The educational video had superior results that may provide an easy-to-distribute and cost-effective method of substantial educational value to all patients who administer their own eye drops.
Conflict of interest: The authors do not have any conflict of interest to declare.
Funding: The research was supported by an educational grant from Gen-eye®
Acknowledgements: Dr. Daleen Struwig, medical writer/editor, for technical and editorial preparation of the article.
Declaration: This research was conducted by Arno Jansen van Rensburg in partial fulfilment of the degree Master of Medicine (MMed) in Ophthalmology (MMed dissertation by publication).
in the eye without contamination. 7,8
Patients with glaucoma that are not adequately controlled, on maximal topical eye drop treatment, often tend to require additional surgical interventions that can cause further strain to the healthcare sector.9,10 The current need to successfully treat patients using eye drop medication is important to address and can be achieved by using innovative educational methods. 8 Healthcare staff often lack time to train patients on the suitable technique when prescribing their medication.11 Providing the necessary education can show great benefit in managing patients with glaucoma but often influences patient contact time.12 Studies that have used educational
materials as part of their intervention, reported an improvement in patients’ eye drop instillation technique. 8,13 Only one previous study conducted a randomised controlled trial that showed significant improvement in glaucoma patients’ eye drop instillation technique after using an appropriate educational video.13 The aim of this prospective study was to determine whether a short educational video or instruction pamphlet intervention on eye drop administration technique would improve the proficiency and selfefficacy in patients with glaucoma instilling their own eye drops at the Department of Ophthalmology of the Universitas Academic Hospital (UAH) in Bloemfontein, South Africa.
Methods Study design
A prospective interventional study was conducted to determine whether glaucoma patients’ eye drop instillation technique improved after reading an instruction pamphlet or watching an educational video instructing them on the accurate technique.
Setting
In this single centre study, data were collected at the Ophthalmology Department at UAH, which is the tertiary referral centre for ophthalmology patients of the Free State Province. Patients were enrolled with a simple random sampling method at the department’s weekly glaucoma clinic, from 1 September 2022 to 1 December 2022.
Participants
All adult patients with primary open-angle glaucoma (POAG), who self-administered their eye drops and met the inclusion criteria, were recruited by the researcher. A sample size of 100 patients were obtained.
The inclusion criteria were the following:
(i) Age of 18 years and older.
(ii) Diagnosed with documented POAG.
(iii) Administering a minimum of one eye drop medication daily.
(iv) Eye drop medication use of at least six months.
(v) Patient self-instilling their eye drops.
(vi) Not legally documented blind on their record.
(vii) Patients not receiving mydriatic eye drops on the day of the study.
Ethical considerations
Our study obtained approval from the Health Sciences Research Ethics Committee (HSREC) of the University of the Free State (reference number UFSHSD2022/0897/3008) and complied to the principles of the declaration of Helsinki.
Data collection method
All the participating patients were required to complete the initial questionnaire to obtain their demographic information and evaluate the characteristics in relation to their eye drop instillation technique.
The baseline self-efficacy confidence score was obtained in all patients prior to the interventions. This was achieved by completing the self-efficacy scale consisting of five questions on their confidence levels with regard to performing particular steps in the eye drop instillation process. The scale was used and validated in a previous study.14 Patients were asked
how confident they were to correctly hold and squeeze the bottle, keep their head in the appropriate position, administer the drop into their eye, deliver the required amount of medication and not touch their face or eye with the bottle tip. These questions related to the steps that were covered in the instruction pamphlet and the educational video. Each of the five questions was scored as follows: 1 – not at all confident, 2 – somewhat confident, 3 –confident, or 4 – very confident. The scores were summed to give a total score ranging from five to 20.
All patients were then evaluated by the researcher with direct observation of their baseline eye drop instillation technique using a 2 mL artificial tear bottle before any interventions were implemented. To determine their eligibility to continue with the study, patients had to incorrectly perform at least one of the ten steps of the eye drop administration technique. The researcher used a printed checklist with a score out of ten to determine whether the patient missed any steps. The steps in the proper eye drop technique are outlined in Table I. It was conducted using evidence-based guidelines and previous studies that assessed the correct technique in eye drop administration.12,15-20 All the enrolled patients qualified to continue in this study.
The sample of patients were equally divided numbered 1-100 using a simple alternated 1:1 randomised method, into two groups of 50 patients, with one group receiving the instruction pamphlet and the other group watching the educational video on the correct eye drop instillation technique. Language options were available in English, Afrikaans, and Sesotho for both the educational interventions.
1. Wash hands with soap and water.
2. Shake the eye drop bottle gently, then remove the cap without touching the tip.
3. Tilt the head backwards with the eyes open gazing upward to the ceiling.
4. Hold the lower eyelid open by using a finger to create a pocket.
5. Deliver a single drop by squeezing the bottle above the eye.
6. The drop has to be placed in the eye correctly into the pocket.
7. Avoid touching of the bottle tip with the eye or face.
8. Close the eye after the drop has been instilled.
9. Perform punctal occlusion for one minute.
10. Gently remove excess fluid from face with a clean tissue.
A two-minute animated video created by the researcher was to instruct one group of patients in a comprehensible manner on the important steps in appropriate eye drop instillation. The video demonstrated the ten steps in an attempt to make it understandable for patients of all literacy backgrounds. Figure 1 represents an image from the video.
The other group received the printed instruction pamphlet for the patient to read about the correct eye drop instillation technique. The text of the ten steps was of an appropriate size and easily legible. All patients in the group were able to read the pamphlet. Patients were provided sufficient time to read the
Table I: Steps in the eye drop instillation technique21
Figure 1. An illustration of the instructions on the eye drop installation technique in the educational video.
Enrolment Before Intervention After
Glaucoma patients included who instil their own eye-drops (n = 100)
Obtain consent
Obtain demographic information and patient characteristics
Measure baseline selfefficacy
Observe and score
baseline eye drop instillation technique
Determine eligibility
steps multiple times, like they would have done at home.
Following the interventions, the next step was to determine whether the patients’ eye drop instillation technique and self-efficacy improved immediately on the same day of visit, after receiving the pamphlet or watching the video. The same scoring system was used to reassess the patients’ instillation technique and selfefficacy on administering their eye drops. The final eye drop instillation technique score was assessed through direct observation by the same researcher and the research assistant. The two observers decided on a score out of ten by using the checklist score sheet, as the patient was guided to the waiting room.
Lastly, after both interventions, the researcher interviewed the patients once more to complete the final questionnaire and self-efficacy confidence scale. The data collection procedure is illustrated in Figure 2
Measurements
The eye drop instillation technique was the primary outcome measure in this study. Our central hypothesis was that the eye drop instillation technique and self-efficacy would improve immediately after receiving an educational video or instruction pamphlet intervention.
Variables
Patients’ demographic variables and characteristics of the study population were documented. Eligible patients were evaluated on their current eye drop instillation technique and self-efficacy before any intervention. The effectiveness of the eye drop instillation technique and self-efficacy were determined after the implementation of an educational video or instruction pamphlet. A comparison between the effectiveness of the educational video and the instruction
Randomise patients into two groups of n = 50 each One group studies a printed information pamphlet on the eye drop installation technique The other group watches an educatlonal video on the eye drop instillation technique
pamphlet on the eye drop instillation technique and self-efficacy was obtained.
Data management and analysis
Reassess the eye drop instillation technique and self-efficacy after intervention in both groups
Compare the effectiveness of the eye drop instillation technique and selfefficacy between the two intervention groups
All data were captured electronically on a secure password-protected Microsoft Excel (version 2016) spreadsheet and sent to the Department of Biostatistics, University of the Free State, for analysis. The data was de-identified as each patient
Variables
Table II: Baseline demographics and patient characteristics of both intervention groups (n = 50 per group, unless indicated otherwise).
Figure 2 . Flow diagram outlining the data collection process.
was given a number that was used on the data form to ensure confidentiality. Numerical variables were summarised by means, standard deviations, minimum and maximum values. Categorical variables were summarised by frequencies and percentages. Differences between groups, categorical variables, was evaluated using appropriate statistical tests (chi-square or Fisher’s exact test) for unpaired data. The analysis was done by the Department of Biostatistics, using Statistical Analyses Software (SAS 9.4).
Results
Demographic information
Patients with glaucoma who administered their own eye drops were enrolled from the UAH Department of Ophthalmology. A comparison between the demographic variables and patient characteristics in the pamphlet-instructed and educational video intervention groups is shown in Table II. The gender distribution of the study population was almost similar between the patients, with 47.0% (n = 47) being male. The mean age was 57.9 (standard deviation [SD] 14.4) years in the pamphlet intervention group and 57.1 (SD 13.4) years in the educational video intervention group. The highest level of education among eligible patients was a diploma or university degree, which was obtained by eight (8.0%) of the participants. Forty-eight (48.0%) participants completed primary school, while 41 (41.0%) finished secondary school.
Patient characteristics
As shown in Table II, most of the patients enrolled in the study had used their eye drops between one and 10 years (n = 60; 66.0%), with some who had 10 years and more experience (n = 17; 17.0%). Both intervention groups had similar experience of using eye drops. A total of 35 patients (35%) indicated that during the last six months, they finished their eye drop medication before the prescription renewal time. Fortytwo (42.0%) patients were without their medication for a few days, while two (2.0%) mentioned that they remained without medication for a month or more. When questioned on the difficulty to administer their eye drops, 18 participants (18.0%) mentioned that they often did not administer their medication due to the fact that it was too difficult to instil the drops into the eye. The majority of eligible patients never used the internet to educate themselves on the correct way of administering eye drop medication. Only 33 (33.0%)
of patients had previous exposure to guidance in eye drop instillation technique. Most of the study population (n = 90; 90.0%) had never received any printed instructions or watched a video on the correct eye drop instillation technique.
Self-efficacy confidence scale before intervention
Patients were asked how confident they are to perform various steps in the eye drop instillation technique. The options ranged from “1 – no confidence” to “4 –very confident”. Overall, the mean self-efficacy score was 17.24, which reflected a high level of confidence among the patients before any intervention was implemented. The most confidence was reported in the step that involved getting the drops into the eye (n = 66; 66.0%). More than half of the study population demonstrated confidence that they only applied one drop at a time, while 57 (57.0%) were sure the bottle tip never touched the eye.
Eye drop instillation technique score before intervention
A mean score of 3.88 out of 10 for the eye drop instillation technique was achieved by the total group of participants before the interventions. The step missed most frequently was performing punctal occlusion (n = 91; 91.0%) after the drop was instilled. The second most frequently missed step was handwashing (n = 90; 90.0%) before commencing the eye drop instillation technique. Forty-nine percent (49%) of the patients failed to deliver a single drop into the eye, while 50.0% (n = 50) missed the eye while instilling their eye drops. More than half of the patients (n = 51; 51.0%) made
contact with the bottle tip to their eye or face in their baseline assessment. The minimum score obtained was zero out of 10, which was observed in two patients.
Eye drop instillation technique score after intervention of the educational video
The overall score for patients included in the educational video intervention improved from a mean score 3.68 before to 7.42 out of 10 steps after the intervention. Handwashing showed a remarkable increase of 68%. Only eight (8.0%) patients washed their hands before the intervention compared to 76% (n = 76) after watching the educational video. An improvement was observed in delivering only a single drop into the eye in 12.0% (n = 12) of patients, with a notably increased effort in 40.0% (n = 40) to place the drop correctly into the eye pocket. Not touching the eye or face with the bottle tip was observed in 80.0% (n = 80) of the patients after the intervention, compared to 38.0% (n = 38) before. Eye closing after drop instillation improved in 54.0% (n = 54) of patient’s post-intervention. More patients (n = 42; 42.0%) applied punctal occlusion on their second attempt administering their drops. There were no steps in the correct eye drop instillation technique that showed a decline in performance after the video intervention.
Eye drop instillation technique score after intervention with the printed instruction pamphlet
The overall average score for patients included in the pamphlet intervention, improved from a mean score of 4.08 before to 5.88 out of 10 steps after the intervention. Handwashing was the most
Figure 3: Eye drop technique score before and after intervention.
Pamphlet (n = 50) Video (n = 50)
Steps assessed in the eye drop instillation technique
Wash hands with soap and water.
Shake the eye drop bottle gently, then remove the cap without touching the tip.
Tilt the head backwards with the eyes open gazing upward to the ceiling.
Hold the lower eyelid open by using a finger to create a pocket. 29
Deliver a single drop by squeezing the bottle above the eye. 31
Drop to be placed into eye correctly into the pocket.
Avoid touching of the bottle tip with the eye or face. 30
Close the eye after the drop is instilled. 25 (30.0)
Perform punctal occlusion for one minute.
Gently remove excess fluid from face with a clean tissue. 15 (30.0)
improved step in this group with an increase of 46.0% (n = 46) of patients.
One step performed poorer after the intervention compared to the baseline assessment on their eye drop instillation technique. The step to deliver only a single drop by squeezing the bottle showed a decline in 6.0% (n = 6) of patients.
Improvement in the steps to place the drop into the eye (n = 6; 6.0%), contamination avoidance (n = 12; 12.0%), closing the eye (n = 30; 30.0%) and performing punctal occlusion (n = 10; 10.0%) were noticed.
Comparison between the educational video and instruction pamphlet intervention results
As shown in Table III, the educational video showed superior results overall compared to the instruction pamphlet. Of the patients in the video group, 37.4% improved their end score results, compared to 18.0% of the pamphlet group (p = 0.0008). The educational video intervention demonstrated better results in improving the eye drop instillation technique in almost all the steps.
Self-efficacy confidence scale after intervention
The total self-efficacy score for all patients included in the study improved to 18.25. The group that watched the educational video had a mean score of 17.76 before the intervention and improved to 18.94 afterwards. In both interventions, patients showed improved confidence in placing the eye drops into the eye, applying only a single drop at a time and not touching the eye with the bottle tip. On these steps, the
educational video intervention patients had more improved confidence after watching the video (although not statistically significant, with p = 0.6757), compared to the patients who received the pamphlet intervention.
Patients’ feedback after the interventions
Table IV summarises the results of the patients’ feedback following the intervention. The glaucoma patients used in this study indicated that they found the interventions to be useful to improve their eye drop instillation technique. When comparing the two interventions, 96.0% (n = 48) of the patients in the educational video group indicated that it was very useful. Although patients in the pamphlet group also indicated they found it useful, only 48.0% (n = 24) found it to be very useful. All (100%) the patients in the respective intervention groups indicated that they would recommend the intervention they experienced to other patients to improve their eye drop instillation technique.
Seventy-two percent of patients in the pamphlet intervention group recommended that they would prefer to receive a copy which would allow them to read it again at home. Of the patients included in the educational video intervention, the majority (n = 31; 62.0%) would prefer to watch the video again in future in the waiting room of the clinic or doctor’s office, while the remainder opted for to watch it at home on social media or via a multimedia link.
Discussion
The glaucoma population in South Africa
is at considerable risk of developing blindness. 2 The majority of patients in our setting are currently using antiglaucoma eye drops as part of the first line treatment to help fight the disease progression. The results of this study demonstrate that educational interventions can successfully enhance the eye drop instillation technique and lead to a significant immediate improvement in patients’ self-efficacy.
The findings provide essential information to promote understanding of the ophthalmological challenges confronting care providers low- to middle income countries. Furthermore, recommendations are provided as to which interventions would improve glaucoma patient care in our setting. To our knowledge, this was the first prospective trial documented in South Africa on improving eye drop instillation technique.
Demographics and characteristics
Our study included patients from different educational backgrounds with male and female participants practically equal in the two intervention groups. On average, glaucoma patients enrolled in the study had a basic educational background. This characteristic is consistent with previous studies showing that low literacy is associated with an inferior eye drop instillation technique. 7
The majority of patients had several years of experience in administering their own eye drops. It has been demonstrated that the length of time glaucoma patients are using their eye drop medication is
Table III: Comparison of scores obtained before and after intervention on assessment of the eye drop instillation technique.
associated with better self-efficacy. 22,23 Although the patients included had been using their eye drops for an extended period of time, they still showed a suboptimal eye drop instilling technique.
Eye drop instillation is challenging for our patients to administer correctly. Eighteen percent of patients indicated that they did not use their eye drop medications because it was too difficult, showing the need for more educational efforts to help improve our patients’ understanding of appropriate administration techniques.
Thirty-five percent (35.0%) indicated that they occasionally finished all their eye drop medication before it was time for their prescription renewal. Using more than a single drop at each attempt can contribute to unnecessary medication loss. The concern was that twenty (20.0%) of these patients were without eye drops for a month or more, which can lead to serious negative effects and eventually blindness due to suboptimal IOP control. This in turn could result in an increased burden on the healthcare sector as patients collect more medication than required, and experience disease progression due to vision loss.10,25
With the current fast-paced outpatient clinic setting, it was noticed that 67.0% (n = 67) of glaucoma patients never received any instructions on the correct eye drop instillation technique before initiating their medication. Four patients mentioned that a family member or friend assisted with their eye drop technique which could have been incorrect and contributed to a poor instillation technique. In the few previous studies that addressed the eye drop instillation technique with an educational intervention, patients showed positive outcomes.10,21,26 In our study, patients improved substantially with both interventions, although significantly better with the educational video compared to the pamphlet.
Self-efficacy confidence scale
Eye drop technique self-efficacy and confidence was determined before and after the interventions as was done in previous studies on eye drop instillation technique.7,13 The mean score for all patients included in this study was 17.24 before any intervention. This result reflected a study population being very confident in the self-assessment of their ability to perform the technique correctly. When the self-efficacy was assessed for a second time after scoring the patient’s eye drop technique and providing an educational intervention, the outcomes
showed a median improvement of 1.00 in both groups’ results. Overconfidence in the patients’ perceived ability to perform the correct eye drop steps could indicate that our patients were unaware of their suboptimal technique. 27,28 In previous studies, a higher self-efficacy score was associated with a better technique, contrary to our study. 29 The poor increase in confidence in the second assessment after the educational interventions, could display that the patients realised their shortcomings in the correct technique. To educate patients adequately on the proper instillation technique could lead to better self-efficacy and improved performance when instilling their eye drops.
Eye drop instillation technique
The eye drop instillation technique scores prior to any intervention were in keeping with findings in similar studies.8,13,21 The majority of patients (n = 90; 90.0%) did not wash their hands prior to using their eye drops. This step improved significantly in both groups after the intervention, with patients realising the importance of a hygienic start to their eye drop medication usage. The patients touched their eye or face in 51.0% (n = 51) of the cases, which was a higher result compared to the findings of Davis et al.13 Besides the risk of ocular trauma, contamination by unintentionally touching of the bottle tip in improper technique, is a matter of concern. The steps to close the eye and perform punctal occlusion to prevent systemic absorption were frequently missed, as reported in other studies. 33,34
The results of the patients in the pamphlet group improved from an average of 4.08 to 5.88 steps out of 10. All steps gained a better performance after reading the pamphlet, except the step that required only a single drop to be delivered to the eye. The inability to instil only one drop to the eye could result from several contributing factors in this group. It is important to avoid delivering multiple drops as it can lead to better patient compliance, is more cost effective and side-effects are reduced. 26,32,35
The educational video intervention showed a better improvement in the groups’ overall score with the second assessment compared to the paper instructed group. The mean score increased from 3.68 to 7.42 steps out of 10. None of the steps showed lower mean score compared to their baseline assessment. The video intervention group outperformed the paper group in the steps required for the correct eye drop instillation technique. Interestingly, the steps to avoid touching
the bottle tip with the eye, placing the drop into the eye, and closing the eye after the drop was installed, had the most significant improvement compared to the pamphlet intervention. The educational video had the benefit of demonstrating the steps in a timely fashion to the patients and could have led to a better understanding of using the correct technique. Since the majority of patients indicated that they had never used the internet to educate themselves on the correct technique to instil eye drops, and the fact that 28% of South Africans did not have internet access in 2023, 37 it would be ideal to use the video as an educational tool to teach patients the necessary skills when they visit the outpatient clinic.
Limitations
This study evaluated the patients’ response to the interventions immediately. By assessing the long-term effects of the interventions on future follow-up visits could provide further detail on the success of the interventions. Furthermore, the patients were required to remember past encounters, such as whether they received previous instructions on the eye drop technique, which could contribute to recall bias. The eye drop bottle used in the intervention groups could have been different compared to their regular glaucoma medication bottle. Researcher bias was a concern in this prospective analysis, as the researcher formed part of the assessment of patients’ eye drop technique before and after the intervention was implemented. By including a research assistant to independently score the final eye drop technique resulted in a more valid outcome. At the time of the assessment, the research assistant was unaware of the patient’s initial baseline score and incorrect steps taken before the intervention, which minimised the risk of bias.
Recommendations
This short, educational animated video can easily and cost-effectively be distributed to ophthalmology clinic waiting rooms across South Africa in multiple languages, enabling all patients from different educational backgrounds to gain knowledge without requiring additional time from healthcare staff.
Conclusion
This study emphasises the need to improve our glaucoma patients’ ability to correctly perform the necessary steps when instilling their eye drops. Patients should be adequately informed on the
correct eye drop instillation technique and continuously assessed regardless of their previous experience. The improvement in eye drop instillation technique ultimately improves adherence, which may lead to better glaucoma management. The success of the educational video can have significant benefits in our patients’ self-efficacy and preserve their vision, which in turn will benefit the healthcare system. Further studies may evaluate the long-term effects resulting from the impact of the video. The eye drop instillation technique video link and QR code: https:// www.youtube.com/ watch?app=desktop& v=1UxC2zMxvhw
References
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Corneal neurotisation
S Swaminathan (MBChB UCT), Registrar Ophthalmology, Groote Schuur Hospital, Cape Town, South Africa. ORCID: https://orcid.org/0009-0004-3463-3970
Corresponding author: S Swaminathan, email: hari.swam@gmail.com
Introduction
Neurotrophic keratopathy is defined as a dysfunction of corneal innervation that results in the dysregulation of corneal and cellular function. The tear film is regulated by a densely innervated cornea, and it acts as the interface between the eye and the environment. Corneal nerves have multiple functions which include: the detection of pain, sensation, temperature, mechanoreception and the blink response as well as tear production. The cornea is kept healthy by trophic factors such as nerve growth factor (NGF) which is produced by corneal nerves.1
Neurotrophic keratopathy occurs because of the partial or complete impairment of the trigeminal nerve which can be due to several different reasons, and these include:
Impaired corneal sensation can be sight threatening because of persistent epithelial defects, ulcers, and perforations and this occurs because of an imbalance in trophic factors; changes to the lacrimal functional unit and impaired wound healing.1
Neurotrophic keratopathy can be clinically staged into three different categories, and this is known as the Mackie classification. Stage 1 has features such as superficial punctate keratopathy, stromal scarring, and corneal neovascularization. Stage 2 is characterised by persistent epithelial defects with a smooth rolled up margin. There may also be stromal edema and Descemet’s membrane folds with anterior chamber inflammation. Stage 3 is the worst stage as it involves corneal ulcers, melts, and perforation. 2
Case
A 41-year-old female was referred
to the eye clinic with a history of a persistently painful, red eye ever since she was diagnosed with lateral medullary syndrome, also known as Wallenberg syndrome. As a result of this, there was trigeminal nerve fallout over the right side of her face. She has presented several times complaining about this problem. In addition to this, she was known for systemic hypertension and idiopathic intracranial hypertension for which she was receiving acetazolamide. The examination revealed:
In addition to the above findings, the patient was found to have reduced sensation over the Ophthalmic (V1), Maxillary (V2) and Mandibular (V3) distribution of the trigeminal nerve ipsilaterally. The patient was assessed as having neurotrophic keratopathy classified as Mackie stage 1 and occasionally Mackie stage 2. The pre-operative corneal aesthesiometry using a Cochet Bonnet Aesthesiometer was found to be zero in all the areas checked.
The patient then underwent indirect contralateral corneal neurotisation performed at Groote Schuur Hospital in May 2022. Ten centimeters of the patient’s own Sural nerve was harvested and utilised as an interpositional nerve graft. Lid skin crease incisions were made in both upper eyelids.
The left orbital margin was accessed through this incision and the left supra-orbital nerve was identified. A tunnel was created through the lid skin crease incisions medial to the levator aponeurosis. The tunnel was subcutaneous and above the nasal bridge. One end of the harvested autologous sural nerve was sutured to the left supraorbital nerve using 10-0 nylon. This donor nerve was then taken across from the left side, through the tunnel that was created, through the right skin crease incision, through the superior fornix and then the endings of the sural nerve were dissected into four fascicles. These fascicles were sutured at the limbus using 10-0 nylon and two of these fascicles were embedded deeper into the cornea with the aid of tunnels.
One year later, the patient had improved subjectively. The clinical exam revealed Mackie Stage 1 with a significant improvement in the state of the ocular surface.
Corneal aesthesiometry using the Cochet Bonnet aesthestiometer also improved in all areas. The measurements one year after surgery were 50 mm superiorly, 35 mm nasally, 20 mm temporally, 20 mm inferiorly and 15 mm centrally.
Discussion
The main goal of treating neurotrophic
keratopathy is to promote epithelial healing and prevent new episodes of corneal damage. 2 The traditional management of neurotrophic keratopathy has followed a step-wise treatment algorithm. 3 The medical management includes: determining the aetiology, dealing with eyelid abnormalities, stopping drugs with known corneal toxicity, lubricating eyes and the use of punctal plugs, metalloprotease inhibitors and autologous serum. 3 Stage 1 neurotrophic keratopathy typically responds well to just lubricants. 2 Mackie stage 2 is typically treated with a combination of medical and surgical options. Including the treatments used in stage 1. Some of the additional medical options include insulin drops, bandage contact lenses, chemically induced ptosis with botulinum toxin, nerve growth factor drops and matrix regeneration therapy. 2 Matrix regeneration therapy uses analogous of heparin sulphate which binds to extracellular matrix proteins and growth factors. This protects the extracellular matrix from proteolysis and aids in wound healing by reconstructing the micro-medium.4 Recombinant human nerve growth factor drops have been shown to regenerate corneal nerves and improve corneal sensation. 5 The Surgical options for stage 2 involve: tarsorrhaphy and overlay amniotic membrane transplants. 3 Mackie stage 3 generally requires surgical treatment options such as: amniotic membrane transplants, corneal patch grafts, glue patches, keratoplasty and conjunctival flaps. 3
Surgical corneal neurotisation is a treatment that can be used in all stages of neurotrophic keratopathy. 2 This technique is a permanent and definitive surgical solution to a unilateral anaesthetic cornea.6 The procedure results in the reinnervation of diseased cornea using healthy, donor graft nerve tissue. 2 The first person to describe corneal neurotisation was the German neurosurgeon, Samii in 1972, where the sural nerve was used as an interpositional graft between the greater occipital nerve and transected ophthalmic nerve.7 In 2009 an American plastic surgeon, Terzis, described the direct transfer of supratrochlear and supraorbital nerves to the corneoscleral limbus.7 Broadly, corneal neurotisation can be performed in a direct or an indirect manner and this can be done as an open or an endoscopic procedure. Endoscopic nerve transfers have been successfully attempted and have proven to be minimally invasive as the incisions are smaller and this allows faster recovery. Ipsilateral or contralateral
nerves can be used.
Terzis was pioneer in her efforts of corneal neurotisation. Her technique has fallen out of favour due to the large skin incisions associated with poor cosmetic outcomes and long procedure times.
Ipsilateral nerves can be used for direct corneal neurotisation if the cause of neurotrophic keratopathy is due to localised eye pathology. 7 For instance, ipsilateral supraorbital and supratrochlear nerves can be used so long as preoperative sensation testing shows intact sensation in the V1 distribution. 7 Central causes of corneal anaesthesia require contralateral nerve transfers. There are documented cases of ipsilateral supraorbital nerve and ipsilateral infraorbital nerve transfers. These techniques provide greater access and allow easier placement of nerves. 2
The indirect approach utilises an interpositional graft and this can be an autograft where the most commonly used autografts include: sural nerve, greater auricular nerve and lateral antebrachial cutaneous nerve. 7 It can also be an allograft, where cryopreserved, processed cadaveric nerves are used as a substitute for an autograft. 7 These allografts have been shown to be as effective as autografts and studies have shown that the time to the first gain in sensation is similar in both allografts and autografts. 7 The benefits of using this approach is that the length of the sural nerve allows one to acquire a well sized graft with relative ease as the sural nerve is also a superficial one. This technique, however, requires two surgical teams, takes longer and the risk of graft failure and coaptation complications is higher since the interpositional graft has to heal on two ends. 8
The coaptation of nerves is done in an end to end or end to side manner using a 10.0 nylon monofilament suture, some surgeons complement this with fibrin glue and amniotic membrane wraps around the coaptation sites. 2
In our case, the sural nerve was used as an interpositional graft, the benefit to this is that it did not require a scalp incision and was thus cosmetically superior. 8 This technique also reduces the risk of alopecia and injury to the facial nerve. 8
Post operative recovery
Patients who have had corneal neurotisation should keep using lubricating eye drops both during the recovery period and after corneal sensation returns. As the
corneal sensation begins to improve, the ocular discomfort may increase because of the damaged epithelium. A strange phenomenon experienced is referred sensation to the donor nerve site when the cornea is stimulated. Numbness of the donor site, hyperaesthesia, neuropathic pain, and scarring are late complications of the procedure.7
Outcomes
The procedure has been shown to be effective in recovering corneal sensation and improving the ocular surface. 2 A systematic review published in 2020 found that corneal aesthesiometry improved when compared to the preoperative corneal sensitivity. In this review the pre-operative sensation was 2.18 mm on Cochet Bonnet aesthesiometry; postoperatively this improved to about 40 mm. 2
Pre-operative anterior segment photograph of the patients neurotrophic keratoapathy-Mackie grade 1. Images courtesy of Professor Mustak
Post corneal neurotsation: resolved neurotrophic keratopathy with pooling demonstrated in an area of corneal scarring. Images courtesy of Professor Mustak
Corneal neurotisation showed a marked increase in corneal nerve density after surgery.7 The recovery of corneal sensitivity is similar in both the direct and the indirect corneal neurotisation approaches. 2 In vivo confocal microscopy is a non-invasive imaging modality that offers high resolution images of the cornea and this has been used to prove corneal nerve regeneration by direct visualisation of nerves.8 The regeneration of nerves post operatively is hypothesised to be a result of the release of neurotrophic factors and not direct nerve sprouting. 2 The time to corneal recovery has been shown to be between six and nine months post operatively.7 Corneal neurotisation can even be performed in cases of herpetic neurotrophic keratopathy.7 A number of patients have had neurotisation and there have not been any reported cases of reactivation. These patients were put onto therapeutic antivirals prior to and after surgery and then switched to life-long prophylactic dosing.7 Both ipsilateral and contralateral donor nerves have been used with similar success rates.7
Conclusion
Corneal neurotisation is a technique
that provides a definitive solution to neurotrophic keratopathy. The improvement in the patient’s symptoms and clinical examination is attributed to the release of growth factors from the new nerve endings which have been transferred to the insensate cornea. Various studies have proven the effectiveness of the procedure in regenerating corneal nerves and improving the quality of life in patients. It is a technique that can be used at any stage of the disease process, however, it requires a multi-disciplinary team and significant theatre time.
I have no financial interests to declare.
References
1. Cheung AY, Holland EJ, Lee WB, Beckman KA, Tu E, Farid M, et al. Neurotrophic keratopathy: An updated understanding. Ocul Surf. 2023 Oct;30:129-38.
2. Rathi A, Bothra N, Priyadarshini S, Achanta DR, Fernandes M, Murthy S, et al. Neurotization of the human cornea – A comprehensive review and an interim report. Indian J Ophthalmol. 2022;70(6):1905.
3. Saad S, Abdelmassih Y, Saad R, Guindolet D, Khoury S el, Doan S, et al. Neurotrophic keratitis: Frequency, etiologies, clinical management and outcomes. Ocul Surf. 2020 Apr;18(2):231-6.
4. Solmaz N. Regenerating Agent (RGTA) based matrix therapy for treatment-resistant persistent epithelial defects. New Front Ophthalmol [Internet]. 2017 [cited 2024 Feb 11];3(4). Available from: http://www.oatext. com/regenerating-agent-rgta-based-matrixtherapy-for-treatment-resistant-persistentepithelial-defects.php
5. Balbuena-Pareja A, Bogen CS, Cox SM, Hamrah P. Effect of recombinant human nerve growth factor treatment on corneal nerve regeneration in patients with neurotrophic keratopathy. Front Neurosci. 2023 Oct 30;17:1210179.
6. Terzis JK, Dryer MM, Bodner BI. Corneal Neurotization: A Novel Solution to Neurotrophic Keratopathy. Plast Reconstr Surg. 2009 Jan;123(1):112-20.
7. Liu CY, Arteaga AC, Fung SE, Cortina MS, Leyngold IM, Aakalu VK. Corneal neurotization for neurotrophic keratopathy: Review of surgical techniques and outcomes. Ocul Surf. 2021 Apr; 20:163-72.
8. Zhang J, Barmettler A. Corneal neurotization: a narrative review of techniques, outcomes, and surgical considerations. Ann Eye Sci. 2023 Jun; 8:7-7.
Treatment of a conjunctival papilloma using topical Mitomycin C
S Gaibie MBBCH (Wits), DipOphth (SA), Ophthalmology Registrar, University of the Witwatersrand, Johannesburg, South Africa.
ORCID: https:// 0009-0005-1002-3489
A Asvat FCOphth (SA), MBBCH (Wits), Consultant Ophthalmologist, St John Eye Hospital, Johannesburg (Soweto), Gauteng, South Africa.
ORCID: https:// 0000-0002-4622-120X
Corresponding author: email: S Gaibie, saajidahg@gmail.com
Abstract
Background : Conjunctival papilloma is a benign lesion of epithelial origin with minimal tendency towards malignancy. Treatment includes surgical excision, cryotherapy, cimetidine and topical agents such as MMC and Interferon alpha-2b. These could result in extensive ocular surface injury and have a high recurrence rate.
Objectives : Describe the response of bilateral conjunctival papilloma to topical Mitomycin C in an 11-year-old patient at St Johns Eye Hospital.
Introduction
Conjunctival papilloma is an acquired benign epithelial tumour of the conjunctiva.1 There have been multiple causative factors identified, the most common factor is Human papilloma virus type 6 and type 11. 2
Other risk factors include ultraviolet light exposure, smoking and immunodeficiency. 3 Management of conjunctival papilloma is diverse and both medical and surgical approaches have been described. Surgical excision has been the most favoured method to treat this lesion, however frequent recurrences are not uncommon.4 Other interventions described in the literature include perilesional cryotherapy, intralesional or
Results : An 11-year-old male presented to St Johns Eye Hospital with bilateral conjunctival masses. Bilateral conjunctival papilloma was diagnosed clinically. Topical Mitomycin C 0.02% was initiated bilaterally, and treatment response monitored with each cycle. Complete regression of lesions was achieved.
Conclusion: Treatment of a conjunctival papilloma with topical Mitomycin C led to complete regression of the lesion with no recurrent lesions noted on follow up.
topical interferon-alpha-2b, carbon dioxide (CO2) laser, topical Mitomycin- C (MMC), and oral cimetidine.
These may be used in isolation or as an adjunctive treatment to surgical excision to prevent recurrence.4
Case
An 11-year-old male presented to the eye clinic with bilateral conjunctival lesions. On clinical examination there was a small red fleshy lesion located near the superonasal fornix of the right eye. A similar lesion was found in the superonasal fornix of the left eye. The left inferior fornix displayed a greyish red, fleshy mass that spanned the entire length of the fornix. The masses were
raised and had an irregular surface. Clinical diagnosis of a conjunctival squamous papilloma was made. Both eyes had 6/6 vision, and the papilloma did not obstruct the visual axis. Due to the extensive nature of the left lower lid papilloma, medical management was opted for instead of surgical excision. Mitomycin C was unavailable at our facility at the time of initiation, hence we opted to start 5-Flourourail. Topical 5-Flourouracil (5-FU) 1% was initiated and prescribed four times a day. The patient used 5-FU for a total of 12 weeks. The patient was reviewed every four weeks for response to treatment. The papilloma reduced in size but the response to 5-FU was inadequate. The patient was then changed to
Mitomycin C which had become available at that point.
Topical Mitomycin C (MMC) 0.02mg/ ml was prescribed for the right eye daily and the for the left eye four times a day. The treatment was administered on every alternate week (one week on, one week off). Eight weeks post initiation of MMC, the lesion on the right caruncle had completely resolved, and both lesions on left showed significant decrease in size. MMC 0.02mg/ml was then continued only on the left eye four times a day for a week, every alternate week. The patient completed a further 20 weeks of treatment in the left eye until clinical resolution of the lesion was achieved. Review of the patient was conducted once every two weeks for the first eight weeks and then monthly for the remainder of his treatment. He was assessed for clinical response as well side effects of the MMC. The only side effect experienced by the patient was foreign body sensation which was controlled with topical lubricants.
MMC was stopped upon resolution of the papilloma and the patient was monitored every two months for recurrences. Nine months post cessation of treatment the patient showed no signs of recurrence.
Discussion
Conjunctival papilloma is an acquired benign tumour that arises from the stratified squamous epithelium of the conjunctiva.4 It may occur in adults and children, with a higher incidence in adults.1 In adolescence and children the papilloma appears to present with a larger mass which is commonly multicentric when compared to adults.1 Recurrence is also more common in children when compared to adults.1 The most commonly affected site in adults is debated. Ash et al. described the most common site as the bulbar conjunctiva while Sjo et al. described the most common site as the palpebral conjunctiva. In children and adolescence, the most common locations include the inferior fornix and the caruncle. 2
Human papilloma virus (HPV) has demonstrated a strong correlation with conjunctival papilloma with the most common subtypes implicated being HPV 6 and HPV 11. 2 Other risk factors described include Ultraviolet (UV) exposure, smoking and immunodeficiency, however a clear link has not been demonstrated in the literature. 3 A study by Mlakar et al. demonstrated different morphological
features of HPV – negative and HPV –positive papillomas. This supports the theory that conjunctival papilloma could be caused by additional factors and not just HPV. Furthermore, HPV negative papilloma displayed features of elastosis, which is indicative of UV damage. 2
The management of conjunctival papilloma is diverse with both medical and surgical approaches being described. Surgical excision and cryotherapy are still widely favoured as the treatment of choice; however, post-surgical recurrence is common and may be more aggressive than the original lesion.1,3 The management has since evolved to include non-surgical treatment modalities to provide less invasive, effective and sustained therapies. The introduction of chemotherapy and immunotherapy drugs have improved the treatment options for conjunctival papilloma providing a suitable primary non-invasive treatment option as well an effective adjunct to surgical management.4
Interferon alpha-2b is a recombinant form of the glycoprotein released by various immune cells. It has antiangiogenic effects, antiproliferative effects and antiviral properties.4 Interferonalpha2b may be administered topically or as an intralesional injection. Topical Interferon alpha-2b has been described by Schechter et al., Falco et al. and Bolek et al. to cause lesion regression when used as a primary topical therapy. 5-7 All three case studies used a concentration of 1MIU/ml four times a day until clinical resolution. Intralesional Interferon alpha-2b is considered in patients who report poor compliance to topical treatment, however case studies report complete regression only when used in conjunction with topical treatment.4 Interferon alpha-2b may be used alone or in conjunction with surgical excision.4,7 Unfortunately Interferon alpha-2b is costly and supply needed for the duration of treatment required was unavailable at our facility and therefore was not our first option for treatment in this case.
Mitomycin C is an alkylating agent that demonstrates anti-neoplastic effects. 8 Yuen et al. first reported the use of topical MMC in a patient with diffuse tumour reoccurrence after four surgical excisions with the aim to prevent further recurrence. No recurrence was noted on 24 month follow up.9 It has subsequently been used as a primary treatment modality noting successful lesion regression and resolution by Ganapathy et al. and Parozzini et al.
Treatment process after four months of Mitomycin C (Picture C and Picture D). The eye showed significant improvement, no signs of papilloma was noted at nine month follow up post cessation of treatment (Picture E and Picture F).
Figure 1. Treatment outcome of conjunctival papilloma. Top right and left show the squamous papilloma prior to initiation of Mitomycin C (Picture A and Picture B).
A dosing regimen of MMC 0.04% applied topically four times a day and cycle of one week on and one week off was used.10,11 MMC has a higher rate of ocular side effects with the most common being ocular discomfort and conjunctival hyperaemia. Less common side effects include recurrent corneal erosion, punctal stenosis, iritis, cataract formation and glaucoma. 8 The chance of toxicity increases with duration of treatment; however, our patient maintained a normal cornea and conjunctiva throughout the duration of treatment, with only mild ocular discomfort being reported and managed successfully with topical lubricants.
5-Flourouracil is a pyrimidine analogue that blocks DNA and RNA synthesis. It is affordable and readily available. There is a paucity of literature on the effects of 5-FU on squamous papilloma with only one published report where 5-FU was used postoperatively to decrease recurrence.4 A dose of 5-FU 1% was used four times a day for one month however recurrence was noted.4
Cimetidine has been described in one publication by Shields et al. as a safe primary treatment for conjunctival papilloma. The case report describes dramatic regression of a conjunctival papilloma in an 11-year-old child initiated on oral cimetidine prescribed at 30mg/kg/day.12 Cimetidine is an oral H2-receptor agonist that is commonly used in the management of peptic ulcer disease. It also demonstrates immunomodulatory effects which is postulated to play a role in papilloma regression.4
Conclusion
Despite the benign nature of a conjunctival papilloma, management can be challenging. The course of disease can be complicated by multiple recurrences. This case report demonstrates the effective use of MMC in the regression of an extensive squamous papilloma. MMC proved superior to 5-FU. Majority of the evidence is from case reports and case series making comparison of treatment approaches challenging.4 It is important to be aware of advancements in available medical and surgical therapeutic options of conjunctival papilloma.
References
1. Kaliki S, Arepalli S, Shields CL, Klein K, Sun H, Hysenj E, et al Conjunctival papilloma: Features and outcomes based on age at initial examination. JAMA Ophthalmology 2013.131(5):585-93.
2. Mlakar J, Kocjan BJ, Hošnjak L, Em JP, Beltram M, Gale N, et al Morphological characteristics of conjunctival squamous papilloma in relation to human papillomavirus infection. Br J Ophthalmol 2015.99(3):431-6.
3. Huang YM, Huang YY, Yang HY, Tsai CC, Yu WK, Kao SC, et al. Conjunctival papilloma: Clinical features, outcome, and factors related to recurrence. Taiwan J Ophthalmol 2018.8(1):15-8.
4. Theotoka D, Morkin MI, Galor A, Karp CL. Update on Diagnosis and Management of Conjunctival Papilloma. Eye and Vision 2019. 6;18.
5. Falco LA, Gruosso PJ, Skolnick K, Bejar L. Topical interferon alpha 2 beta therapy in the management of conjunctival papilloma. Optometry – Journal of the American Optometric Association 2007.78(4):162-6.
6. Schechter BA, Rand WJ, Velazquez GE, Williams WD, Starasoler L. Treatment of conjunctival papillomata with topical interferon Alfa-2b. Am J Ophthalmol 2002.134(2):268-70.
7. Bolek B, Wylęgała A, Teper S, Kokot J, Wylęgała E. Treatment of conjunctival papilloma with topical interferon alpha-2b – Case report. Medicine 2020;99(7).
8. Russell HC, Chadha V, Lockington D, Kemp EG. Topical mitomycin C chemotherapy in the management of ocular surface neoplasia:
2. Prior to initiation of Mitomycin C (Picture G). Nine months post cessation of treatment, no recurrence noted (Picture H).
A 10-year review of treatment outcomes and complications. Br J Ophthalmol 2010.94(10):1316-21.
9. Yuen HK, Yeung EF, Chan NR, Chi SC, Lam DS. The Use of Postoperative Topical Mitomycin C in the Treatment of Recurrent Conjunctival Papilloma. Cornea 2002. 21;8.
10. Parrozzani R, Frizziero L, Midena E, Author C. Giant Ocular Surface Squamous Cell Papilloma Treated with Topical Mitomycin C. Ophthalmic Images 2017. 135.
11. Hawkins AS, Yu J, Hamming NA, Rubenstein JB. Treatment of Recurrent Conjunctival Papillomatosis with Mitomycin C. J Refract Surg 1998.14.
12. Shields CL, Lally MR, Singh AD, Shields JA, Nowinski T. Oral cimetidine (Tagamet) for recalcitrant, diffuse conjunctival papillomatosis. Am J
Figure
NO ONE DREAMS OF SILVER
Disseminated hydatid cyst disease presenting with unilateral orbital proptosis and vision loss: a rare orbital presentation of systemic echinococcosis in a young child
N Narainswami MBBCH(Wits), Dip (Ophth)SA, Dip (HIV Man) SA, FCOphth(SA), MMed(UKZN), Consultant ophthalmologist Grey’s Hospital Pietermaritzburg, Fellow in Paediatric Ophthalmology and Strabismus, Red Cross War Memorial Children’s Hospital, Cape Town, South Africa.
ORCID ID: https://orcid.org/0000-0002-5495-7153
N Freeman MB ChB (Stell), FCOphth (SA), MMed (Ophth) (Stell); Head of Clinical Unit, Paediatric Ophthalmology, Red Cross War Memorial Children’s Hospital, Cape Town, South Africa.
ORCID ID: https://orcid.org/0000-0002-1110-9795
T Seobi MBBCH (Wits), MMed(Wits), FCOphth(SA); Consultant, Paediatric Ophthalmology, Red Cross War Memorial Children’s Hospital, Cape Town, South Africa.
ORCID: https://orcid.org/0000-0001-7125-4217
H Mustak MBChB (UCT), Dip (Ophth) SA, FCOphth(SA); Professor Division of Ophthalmology, Oculoplastics and Oncology, University of Cape Town and Groote Schuur Hospital, Cape Town, South Africa.
ORCID: https://orcid.org/0000-0002-8538-7296
Corresponding author: N Narainswami: neerannarainswami@gmail.com
Abstract
Orbital hydatid disease is a rare manifestation of zoonotic larval infection by the tapeworm Echinococcus granulosus.
Humans act as accidental intermediate hosts. This is a report of an inferior orbital hydatid cyst presenting with acute on chronic unilateral non-pulsatile proptosis in a young otherwiseasymptomatic child evolving to a diagnosis of disseminated systemic echinococcosis.
Conclusion: Orbital hydatid cyst is an important differential to bear in mind in young children presenting with unilateral non-pulsatile proptosis. Meticulous surgical excision of the
Background and introduction
Hydatid disease is a zoonotic infection caused by the tapeworm Echinococcus granulosus which is endemic to South Africa.1 Globally the incidence is on the rise as population migration patterns mean that more cases are being diagnosed in better resourced non-endemic areas.1,2 The liver is the commonest site of involvement followed by the lung and various other sites such as brain, bones, kidney and heart have been sporadically described in the
cyst using the puncture-aspiration-irrigation-re-aspiration (PAIR) technique with perioperative albendazole, and steroid therapy can lead to excellent outcomes even in eyes with poor presenting vision.
literature. 3 Orbital involvement forms less than 1% of cases and typically affects the superolateral or superomedial aspect of the orbit. 3
A three-year-old girl presented to Red Cross War Memorial Children’s Hospital eye clinic with a two-month history of painless gradual proptosis of her right eye. Her mother reported a fall while playing with sudden increase in proptosis and loss of vision two weeks prior. She was an otherwise well child systemically with no comorbidities nor complaints.
Ocular examination revealed gross non-pulsatile proptosis and superior dystopia of her right globe with lid oedema, chemosis and conjunctivitis with severely limited ocular movements especially on infraduction. Vision had no perception of light (NPL) with a brisk relative afferent pupillary defect (RAPD). Her cornea was clear and anterior segment exam otherwise normal. There was severe hyperaemic optic disc swelling with posterior choroidal folds on right fundoscopy. The left eye examination
was normal. There was no associated lymphadenopathy of the head or neck.
An MRI of the orbits revealed a large uniformly-walled, cystic intraconal lesion, measuring 23 mm x 17.5 mm, in the inferior orbit, without any associated daughter cysts. At this point, the diagnosis of probable orbital hydatid cyst was made and definitive surgical diagnostic and therapeutic intervention planned with oculoplastic surgery.
An inferior conjunctival orbital approach, employing the PAIR (puncture, aspirate, irrigate, re-aspirate) technique using a three-way tap attached to a syringe and 27-gauge needle, was used. Clear fluid was aspirated from the cyst in keeping with the diagnosis of hydatid disease and hypertonic saline injected into the sac as a scolicidal agent.
Following re-aspiration of the hypertonic saline, the cyst collapsed and removal in its entirety was facilitated gently and carefully with forceps. Clinically the diagnosis of hydatid cyst disease was evident and a postoperative course of oral albendazole for 28 days and prednisolone taper over a week was commenced. She was also given a stat dose of intravenous steroid intraoperatively to assist with post-operative swelling. Day one post operatively there was a notable marked reduction in proptosis, improvement in ocular motility, and the vision had improved to PL. Systemic workup, including chest X-ray and abdominal ultrasound, revealed the presence of multiple small cystic lesions in her right lung, with a large solitary cyst of her left upper lobe,
and multiple splenic cysts, respectively. Histology confirmed the diagnosis of echinococcus granulosus and referrals to paediatric cardiothoracic and general surgery were made to further manage her extraocular disseminated systemic echinococcosis. One week postoperatively, the vision in her right eye had improved to 6/24 with a residual RAPD still evident. At the last ophthalmology review two months post-op, VA was at least 6/12 with marked improvement in ocular motility and proptosis.
Discussion
Echinococcosis in humans presents in one of two important clinical forms; cystic hydatosis (E. granulosus) or alveolar echinococcosis (E. multilocularis).1
There are over 1.2 million cases of echinococcosis at any one time globally, so familiarity with diagnosis and treatment is important for clinicians. 2 Hydatid disease has been described on every continent except Antartica and is endemic to Africa, the Middle East, South America, New Zealand and Australia.1,2 The definitive hosts of this genus of tapeworm include carnivores (dogs and cats) while herbivores (sheep and goat) and omnivores act as intermediate hosts.1,2 The classic dog-sheep-dog cycle found in pastoral areas allows for survival of the parasite. 2 Humans become accidental intermediate hosts through ingestion of parasite eggs in contaminated food, water, soil or faeces of definitive hosts. 2,3
The eggs hatch in the small intestine releasing oncospheres which penetrate
Figure 1: Preoperative unilateral proptosis right eye with chemosis.
Figure 2: Preoperative sagittal CT scan with simple cyst in right intraconal space with associated proptosis.
Figure 3: Intraoperative PAIR technique with three way tap.
Figure 4: Extirpation of hydatid cyst.
Figure 5: Postoperative result with dramatic reduction in proptosis.
through the intestinal wall into the circulation to migrate most often to the liver and lungs. 2,3 The oncospheres then develop into cysts in their destination organ gradually enlarging and producing protoscolices and daughter cysts within the main cyst. 2-4 Patients may remain asymptomatic for years until either a mass effect or rupture of the cyst occurs, eliciting a severe inflammatory response causing symptoms. 2-4 An antecedent history of minor trauma during play at creche in our patient was probably what led to leakage of cystic fluid into her surrounding orbital tissue and the subsequent sudden history of acute on chronic worsening proptosis and painful vision loss.
It is important to consider the diagnosis of hydatid cyst in the differential of unilateral proptosis presenting in a child (orbital cellulitis, vascular malformations, malignancies, metastasis), especially from an endemic area. MRI is usually preferred to CT scan to better delineate the cystic structure and distinguish compressive effects on contiguous tissue pre-operatively. 5 However, neither are confirmatory of the diagnosis. Serology for organ-specific or systemic echinococcosis is variable and a negative test does not rule out disease. Laboratory work-up in our patient was non-contributory. Ultrasound has been gaining popularity in recent years for assessing abdominal and most other sites of hydatosis. The classic
“double wall” sign aids differentiation from other cysts including neoplasms. 5 Importantly there is no risk of radiation as with CT and unlike MRI it is portable allowing ease of use, particularly for screening in endemic and often resourceconstrained settings. 5,6
Surgical excision of the cyst, either in totality (extirpation) without rupture of its fluid contents, or by using the PAIR technique, remains the cornerstone of diagnosis and definitive treatment. 7 Other scolicidal agents in use include absolute alcohol, chlorhexidine, formalin and cetrimide. 7,8 Hypertonic saline was used in our patient as it is associated with the least risk of injury to the vulnerable optic nerve and orbital tissues. Two weeks postoperatively there was marked improvement with almost complete subsiding of inflammation and return to near-normal ocular movements and sustained visual gains. Albendazole was repeated for two cycles, equaling 28 days as per case reports in the published literature. Albendazole has also been described to be given at least two weeks pre-operatively in an attempt to sterilise the cysts and strengthen the cyst wall.9 This is to mitigate the risks of rupture with extravasation of inciting cystic fluid, which carries with it not only the risks of severe post-operative inflammation, but also the risk, in some instances, of precipitating a life-threatening anaphylactic reaction.9,11
Surgical treatment of paediatric orbital hydatid disease is an elegant and expensive undertaking and best done at a tertiary paediatric centre, or by the most experienced available surgeon.9-11 Following completion of her 28-day course of albendazole, our patient will be reassessed with consideration for repeat MRI scan of the orbits if necessary, to assess for any local recurrence, as has been described in the literature.10,11 Education of the family unit at home is critical to decrease spread of the parasite. This not only includes deworming and vaccination of domesticated dogs, but also the role of hand washing and hygienic food preparation which are vital and cannot be underestimated in the prevention of transmission.12
Conclusion
Disseminated systemic hydatid cyst disease may present initially as unilateral proptosis in a child. It is important for the ophthalmologist to screen for extraocular features in these children, especially in endemic areas. Surgical extirpation of the
orbital cyst in totality without spillage of its contents is the gold standard treatment of care.
2. World Health Organization, World Organisation for Animal Health and Food Agriculture Organization of the United Nations, Foodborne parasitic infections: Cystic and alveolar echinococcosis, 22 June 2021, Brochure and flyer, WHO/UCN/NTD/ VVE/2021.3.
3. Al-Muala HD, Sami SM, Shukri MA, Hasson HK, Alaboudy AT. Orbital hydatid cyst. Ann Maxillofac Surg. 2012 Jul;2(2):197-9. doi: 10.4103/2231-0746.101365. PMID: 23483684; PMCID: PMC3591069.
4. Primary Orbital Hydatid Cyst, Anna M. Lentzsch, MD, Heike Göbel, MD, Ludwig M. Heindl, MD, DOI: https://doi.org/10.1016/j. ophtha.2016.02.042.
5. Brunetti E, Tamarozzi F, Macpherson C, Filice C, Piontek MS, Kabaalioglu A, Dong Y, Atkinson N, Richter J, Schreiber-Dietrich D, Dietrich CF. Ultrasound and Cystic Echinococcosis. Ultrasound Int Open. 2018 Sep;4(3). E70-E78. doi: 10.1055/a-0650-3807. Epub 2018 Oct 23. PMID: 30364890; PMCID: PMC6199172.
6. Rezaee A, Bell D, Knipe H, et al. Orbital cystic lesions. Reference article, Radiopaedia. org (Accessed on 06 Nov 2023) https://doi. org/10.53347/rID-39904.
7. Cooney RM, Flanagan KP, Zehyle E. Review of surgical management of cystic hydatid disease in a resource limited setting: Turkana, Kenya. Eur J Gastroenterol Hepatol 2004; 16:1233-36.
8. Kamal Chtira et al. The surgery of intra-orbital hydatid cyst: a case report and literature review Pan Afr Med J. 2019;33: 167.doi: 10.11604/ pamj.2019.33.167.18277
9. Majd Abouassi, Mohammad Aloulou, Nouran Hawa, Tayf Toutounji, Safwan Alyousef, Successful eradication of a large orbital hydatid cyst without rupture using frontoorbitozygomatic approach, the first case reported from Syria, J. Surg. Case Rep, Volume 2020, Issue 10, October 2020, rjaa357, https:// doi.org/10.1093/jscr/rjaa357
10. Gokcek C, Gokcek A, Bayar M, Tanrikulu S, Buharali Z. Orbital hydatid cyst: CT and MRI; Neuroradiology 1997;39:512.
11. Sihota R, Sharma T. Albendazole therapy for a recurrent orbital hydatid cyst. Indian J Ophthalmol 2000; 48:142-43.
12. Zhang W, Li J, McManus DP. Concepts in immunology and diagnosis of hydatid disease. Clin Microbiol Rev. 2003 Jan;16(1):18-36. doi: 10.1128/CMR.16.1.18-36.2003. PMID: 12525423; PMCID: PMC145297.
Figure 7: Multiple splenic cysts on ultrasound.
Figure 6: CXR showing large cyst in left lung and multiple smaller cysts in right lung.
Keratoglobus: An Overview of the Surgical Management Options for this Rare Corneal Ectasia
N van der Merwe MBChB (Stell), Dip Ophth (SA), Medical Officer, Division of Ophthalmology, St John Eye Hospital, Chris Hani Baragwanath Academic Hospital, South Africa.
ORCID: https://orcid.org/0009-0005-4959-4588
A Asvat MBChB (Wits), FC Ophth (SA), Consultant, Ophthalmology Department St John Eye Hospital, Chris Hani Baragwanath Academic Hospital, South Africa.
ORCID: https://orcid.org/0000-0002-4622-120X
Corresponding author : N van der Merwe; email: dreyernina@gmail.com
Funding and conflict of interest: The authors declare no conflict of interest, financial or otherwise.
Introduction Presentation
A 49-year-old, healthy male presented to St John’s Eye Hospital in early 2023 after being referred from a district hospital for suspected bilateral Pellucid Marginal Degeneration. On systemic history, the patient reported that he had sober habits and had no prior medical or surgical history. On ophthalmic history, the patient reported no previous surgical ocular interventions and was not using either contact lenses or spectacles. He had been prescribed topical lubricants by the referring hospital.
The patient reported no history of extreme joint or skin elasticity, musculoskeletal deformities, history of vernal keratoconjunctivitis (VKC), atopy or excessive eye rubbing. He provided a history of poor vision since childhood, the onset was during school-going age. He noted that his eyes began to protrude and became progressive globular, together with worsening visual acuity at all distances. He had been prescribed spectacles previously but had not used contact lenses. His greatest concern was that his vision did not improve with spectacle wear, which was interfering with his occupation.
His family history revealed that both his father and sister had poor distance vision since childhood, but notably they did not
Ethics: Ethical approval was obtained from the University of the Witwatersrand Human Research Ethics Committee and written informed consent was obtained from the patient to use his information and the images taken during examination.
seem to have the same extreme globular protrusion of their eyes.
The findings of his ocular examination
are tabulated in Table I and special investigations performed are noted in the figures below.
Figure 1: Colour photograph of the left eye from above.
Figure 2: Colour photograph of the left eye from the front.
Figure 3: Colour photograph of the right eye from the temporal view.
Figure 4: Colour photograph of the right eye from above showing the anterior chamber angle structures readily visible without gonioscopy.
Management plan
The patient was advised to wear protective eyewear to minimise the risk of corneal perforation and was cautioned against eye rubbing. He was prescribed topical, preservative free lubricant gels and eye drops, as well as a topical mast cell stabiliser. The patient was referred for rigid scleral contact lenses, failing which he was counselled on potentially requiring surgery to improve his vision.
Discussion Background
Keratoglobus is an extremely rare, bilateral, non-inflammatory corneoscleral ectasia, characterised by diffuse, peripheral corneal thinning, resulting in the characteristic globular protrusion of the entire cornea.1-6 It may be congenital or acquired, the former being associated with connective tissue disorders such as Ehlers-Danlos syndrome type VI, Leber’s congenital amaurosis and Marfan syndrome. The latter is associated with vernal keratoconjunctivitis (VKC), idiopathic orbital inflammation, blepharitis, thyroid eye disease and extreme eye rubbing.1-3,5 The true prevalence of keratoglobus is not known, but it is estimated that 2.6% of the Indian population suffer from this rare ectasia. 7
Keratoglobus results in visual impairment due to extreme myopia, irregular astigmatism, corneal scarring from previous hydrops, limbal stem cell deficiency and occasionally, even spontaneous globe rupture may occur.4 The corneoscleral limbus is known to have a niche of adult stem cells, which provide a constant, unlimited supply of corneal epithelial cells, ensuring a stable and uniformly refractive corneal surface is maintained. Disruption of this reservoir results in ineffective corneal epithelial healing, persistent epithelial defects, progressive superficial corneal vascularization, and scarring.6,8
The first step towards visual rehabilitation in these patients usually involves spectacle correction, which may provide protection from trauma, but often leave patients wanting.4 It is technically challenging to obtain a good contact lens fit, with rigid gas permeable (RGP) scleral contact lenses, small diameter RGP lenses or hydrogel lenses providing a more favourable result.4,5 The repeated insertion and removal of rigid lenses may however increase the risk of corneal perforation. Research has also shown that it is possible to use corneal cross-linking (CXL) on thin, keratoconic corneas,
Anterior chamber angle clearly visible on retroillumination
Round, regular, reactive No RAPD
thereby possibly slowing the progression to keratoglobus. 5
When the above measures fail and functional vision cannot be obtained, surgery may be undertaken. The exaggerated, global thinning of the cornea, together with the resultant LSCD, does however create exceptional difficulties when the surgeon is faced with anterior segment surgery in these patients.
This case report aims to discuss the various risks, complications, and considerations in performing anterior segment surgeries for patients with keratoglobus. To date, no clear consensus exists as to the optimal surgical management of these patients.
Surgical considerations
The surgical techniques can broadly be divided into full thickness or lamellar procedures.
Full thickness procedures include conventional penetrating keratoplasty, corneoscleroplasty and a two-step tectonic lamellar keratoplasty combined with secondary penetrating keratoplasty.
Lamellar procedures include epikeratoplasty, central lamellar keratoplasty with peripheral tuck-in, limbal stem cell sparing lamellar keratoplasty and corneoscleral rim procedures.
The overall surgical outcome aims to restore corneal and scleral anatomical integrity whilst ensuring that central corneal clarity is maintained.10
Full thickness procedures
Penetrating Keratoplasty (PKP)
Conventional PKP is not possible in keratoglobus, due to the extreme thinness of the entire cornea and limbus, resulting in a technically challenging surgery requiring a very large donor graft with poor tectonic support. This large graft is technically challenging to manoeuvre, with a risk of cheese-wiring of the thin corneal periphery during suture placement, not to mention peripheral graft-host thickness disparity that prevents adequate wound closure.4,6 A larger limbus to limbus graft (>9.0 mm) has been attempted to avoid the grafthost junction disparity, and although more stability was achieved, it resulted in
increased endothelial rejection due to loss of immune privilege, as well as limbal stem cell disruption. These patients ultimately require long term immunosuppression to prevent graft rejection and may require multiple staged procedures, leading to an overall delay in visual rehabilitation.1,4-6 As a result, modifications of the standard PKP have been attempted in patients with keratoglobus.
Corneoscleroplasty
Traditionally a corneoscleroplasty involves performing a central full-thickness PKP, with a lamellar peripheral corneoscleral dissection extending up to 14 mm from the edge of the PKP. The deeper tissues of the graft are fashioned to fit seamlessly over
the peripheral lamellar host sclera and limbus, whilst maintaining the integrity of the anterior chamber angle structures and avoiding complications relating to secondary glaucoma.4,10
Wallang et al. performed this technique with satisfactory visual outcomes and structural integrity of the anterior segments, whilst also avoiding secondary glaucoma. The patients did however develop complications related to LSCD and immunological graft reactions did occur.4
Esquenazi et al. describes the use of a large 14 mm donor corneoscleral tectonic allograft, superimposed upon the de-epithelialised host cornea after decompressing the anterior chamber. The onlay graft, devoid of endothelium
and Descemet’s membrane, was secured with compressive sutures to create a more favourable corneal contour. The host limbal stem cells were retained, and the host conjunctiva was sutured over the graft in the periphery, to promote re-epithelialisation. The overall recovery was uneventful with acceptable visual outcomes.6
Jarade et al. performed a single staged full-thickness central PKP with a peripheral lamellar corneoscleral tucking procedure.10 A 360-degree limbal stem cell sparing dissection was performed into the sclera, followed by a limbus-tolimbus lamellar keratectomy from the periphery towards the centre. The donor corneoscleral button was trimmed to ensure tapered ends and the peripheral donor endothelium was removed. A full thickness central trephination was performed in the host cornea and the donor button was positioned over the defect. The dissected host limbus was replaced over the donor graft and the graft secured into the peripheral pocket with 10-0 nylon interrupted buried sutures. An air bubble was left in the anterior chamber to enhance tissue adherence. The authors report satisfactory visual outcomes, with no features of epithelial breakdown or limbal stem cell deficiency.10
A case report by Kanellopoulos and Lawrence discusses the novel use of a perilimbal allograft corneoscleral ring to stabilise the peripheral cornea in an attempt to reinforce and stabilise the thinned mid-peripheral cornea, without disturbing the clear central visual axis. 2 A 360-degree conjunctival peritomy and epithelial dissection was performed on the host eye. A donor corneoscleral button was prepared by removing the central 7 mm of tissue and trimming the periphery to size. 2 The graft was sutured to the host sclera in the periphery and the dissected conjunctiva was repositioned and secured over the corneoscleral ring. Post-operative findings determined that this extraocular procedure halts the progressive thinning and expansion of the mid-peripheral cornea, provides tectonic support and maintains central corneal clarity. 2
Tectonic lamellar keratoplasty with secondary PKP
This two-staged technique by Jones and Kirkness utilises a partial thickness onlay lamellar corneoscleral graft, void of endothelium, which is draped over the de-epithelialised host cornea beyond the limbus.1 A 360-degree trephine of the
Figure 5: Four Maps Pentacam images of the right eye.
Figure 6: Four Maps Pentacam images of the left eye
peripheral, perilimbal cornea, deep to and beyond the limbus and into the host sclera was created, whilst leaving the overlying conjunctiva, limbal stem cells and peripheral corneal stroma intact. The anterior chamber was decompressed via a paracentesis, allowing the overlay graft to both alter the shape of the cornea and add substance to its thickness. The graft was sutured to the host sclera in the periphery.1 The surgery improved corneal contour and overall tectonic stability of the anterior segment, however there were significant interface opacities created by the remaining host corneal tissue, which prompted a further PKP to restore the patient’s vision. This procedure may serve as a limbal stem cell sparing anterior segment stabilising surgery but requires two donor grafts per eye and multiple surgeries, which is costly and delays visual rehabilitation. Despite this, the patient attained good visual acuity with no reports of delayed epithelialisation or rejection.1
Lamellar procedures
Anterior lamellar keratoplasty (ALK)
Lamellar keratoplasty involves removing and replacing only a thin layer of diseased cornea. The advantages of ALK include less endothelial cell loss, lower rates of graft rejection, prolonged graft survival, as well as less intra- and postoperative complications, including a lower incidence of steroid induced lens opacities and glaucoma.11
An epikeratoplasty (EKP) is a type of onlay lamellar keratoplasty in which a lenticule of human donor corneal tissue, devoid of endothelium and Descemet’s membrane, is sutured onto the anterior surface of the host cornea, following posterior dissection of the conjunctiva and removal of host epithelium. It is essentially an extraocular procedure aimed at treating keratoconus and myopia, but which has been found to aid in stabilising thin, fragile corneas.12 ALK is considered superior to PKP in thinned corneas, as there is less manipulation of an already compromised host cornea. The downside is that the very large onlay lenticule that is required may envelop and disrupt the host limbal stem cells. This in turn exposes the patient to an increased risk of graft infection and rejection. These complications may be minimised by performing a modified technique. By creating a 360-degree peripheral lamellar intrastromal pocket in the host cornea, into which the donor lenticule is inserted peripherally, the
compromised limbal stem cell niche is avoided. Issues relating to lamellar keratoplasty surgeries such as micro- or macro-perforations, lenticule interface opacities and intraepithelial cysts may impair initial visual outcomes, but the potential for future secondary PKP does exist, if it were to become necessary.4,5
Vajpayee et al. describe a central lamellar keratoplasty with peripheral ‘tuckin’ flange, which serves as a combination of both an inlay and overlay lamellar keratoplasty. It entails lamellar dissection of a central 8.5 mm button of host cornea to prevent central corneal thickening, whilst simultaneously providing space for the creation of a 360-degree peripheral intrastromal pocket in the periphery of the host cornea. By doing this, the surgeon avoids manipulation of the host limbal stem cells. A full-thickness donor graft measuring 12.0 mm in diameter is prepared by removing both the epithelium and endothelium. The periphery of the donor
graft is thinned from the stromal aspect to create a complementary bevel-shaped flange for the host intrastromal pocket and is secured with nylon interrupted sutures, providing structural support at the point of maximum corneal thinning.4,13 This singlestage technique has been successful in reducing corneal-induced myopia and astigmatism, providing tectonic support to the globe, whilst simultaneously avoiding the host limbus and anterior segment structures. As an extraocular procedure, it avoids issues of graft rejection, endophthalmitis and it does not preclude future central penetrating corneal grafts if they were to become necessary.4,13
This technique is technically challenging, has a high risk of corneal perforation intraoperatively and may result in interface opacities associated with the lamellar graft. As in the case of epikeratoplasty, the initial surgery may serve to stabilise the host bed for a future PKP, should it be necessary.4,13
Figure 7: Scheimpflug images of the anterior segment of the right eye.
Figure 8: Scheimpflug images of the anterior segment of the left eye.
Javadi et al. analysed the visual and anatomical outcomes of six patients with keratoglobus who underwent epikeratoplasties during an interventional case series in Iran.12 The surgical technique performed was similar to techniques previously described by Jones, Kirkness and Vajpayee et al. A 360-degree conjunctival peritomy was performed, whereafter the host corneal epithelium was mechanically and chemically debrided with alcohol until no cells remained. A limbal stem cell sparing circumferential lamellar dissection was performed 2 mm posterior to the limbus, to create a pocket in the host sclera for the donor graft. The donor corneoscleral button, devoid of endothelium and Descemet’s membrane, was cut 1 mm larger than the recipient’s cornea. The host’s anterior chamber was decompressed via a paracentesis and the onlay button was buried beneath the scleral rim and sutured into place with 10-0 nylon adjustable sutures. The sutures were adjusted under guidance of a manual keratoscope to reduce astigmatism. The results of this study concluded that there was an overall increase in corneal thickness, a reduction in irregular myopic astigmatism, improved corneal curvature and improved tectonic stability, paving the way for future penetrating keratoplasties.12
Karimian et al. evaluated eight eyes with advanced keratoglobus who all underwent limbal stem cell sparing lamellar keratoplasties, where the surgeon created a 360-degree peripheral corneoscleral pocket 2 mm beyond the limbus, into which the donor cornea was positioned and fixed with nylon sutures. The results showed significant improvements in visual acuity without any significant interface haziness, limbal stem cell deficiency, delayed epithelial healing or recurrence of ectasia within the two-year followup period. The procedure ultimately provides tectonic support and restores the structural integrity of the cornea without compromising the limbal stem cell niche or postoperative visual acuity. 3
Lockington and Ramaesh published a case report in 2014 where they described a novel procedure to address many of the aforementioned surgical issues.9 The procedure involved performing a modified anterior lamellar keratoplasty with peripheral pleating technique, to normalise the corneal contour and simultaneously stabilise the thinned peripheral cornea.9 The analogy of turning a muffin into a cupcake was described in their publication and provides a visual representation of
the result when 360-degree pleating of the host cornea was performed. A baseline measurement of the white-to-white (WTW) diameter was taken and found to be 15 mm. The host corneal epithelium was debrided, and a marking pen was used to delineate a circle with an internal diameter of 9-mm on the anterior surface of the cornea. The anterior chamber was decompressed via a paracentesis and 10-0 nylon interrupted compression sutures were placed in the four cardinal positions.
The host corneal stroma was hydrated with a balanced salt solution to aid dissection down to Descemet’s membrane. The peripheral cornea was then gathered into a folded shape to form a circumferential pleat, which was then sutured with 10-0 nylon modified mattress sutures at 90% depth under a high degree of tension. This ensured that there was no interface gap left in the pleats, adding to the tectonic stability of the future grafthost junction. The 9.5 mm donor corneal button, devoid of Descemet’s membrane and endothelium, was then placed onto the host cornea and secured with 10-0 nylon interrupted sutures. The surgeons aimed to pass the suture material through the donor graft, as well as the host pleats at a depth of 90%, whilst taking care to avoid the limbus. This step was aimed at ensuring further compression of the pleats and enhanced stabilisation of the grafthost junction, whilst minimising injury to the limbal niche. During this procedure, the limbus was reduced from the vertical meridian to its normal horizontal position, thereby restoring the normal anatomical relationship of the tissues and reducing the angle between the limbus and iris.9
Following this procedure, the WTW diameter had been reduced to 12 mm and the patient had an overall improvement in visual acuity up to three years following surgery. The corneal epithelium healed within two weeks and no reports of epithelial defects were documented in the follow-up period. Anterior segment imaging revealed an overall increase in central corneal thickness and examination revealed no clinically significant interface opacities. It is however important to note that the patient was kept on both topical and systemic immunosuppression following her surgery, which could ultimately cause unwanted systemic and local side-effects.9
Summary
The surgical management of a patient with keratoglobus is inherently complicated and although various authors have
reported varying degrees of success with essentially experimental procedures, there is no clear consensus as to the optimal surgical approach for these patients. As a result, when confronted with such a patient, the surgeon should rather take their own surgical expertise, available resources, individual patient factors and desire for rapid visual rehabilitation into consideration prior to embarking on any surgical interventions.
References
1. Jones DH, Kirkness CM. A New Surgical Technique for Keratoglobus-Tectonic Lamellar Keratoplasty Followed by Secondary Penetrating Keratoplasty. Cornea 2001;20(8):885-87.
2. Kanellopoulos AJ, Pe LH. An Alternative Surgical Procedure for the Management of Keratoglobus. Cornea 2005;24(8):1024-26.
3. Karimian F, Baradaran-Rafii A, Faramarzi A, et al. Limbal Stem Cell-Sparing Lamellar Keratoplasty for the Management of Advanced Keratoglobus. Cornea 2014;33(1):105-8.
4. Wallang BS, Das S. Keratoglobus. Eye 2013; 27:1004-12.
5. Hafezi F, Torres-Netto EA, Randleman JB, et al. Corneal Cross-linking for Keratoglobus Using Individualized Fluence . J.Refract. Surg 2021;1(1):10-14.
6. Esquenazi S, Shihadeh WA, Abderkader A, et al. Ophthalmic Surgery, Lasers and Imaging 2006;37(5):434-36.
7. Tidke PK, Bajpayee N. Keratoglobus after Long Standing Keratoconus – A Rare Case. J. Evol. Med. Dent. Sci. 2021;10(6):394-8.
8. Sangwan VS, Jain R, Basu S, et al. Transforming ocular surface stem cell research into successful clinical practice. Indian J Ophthalmol 2014;62(1):29-40.
9. Lockington D, Ramaesh K. Use of a Novel Lamellar Keratoplasty with Pleat Technique to Address the Abnormal White-to-White Diameter in Keratoglobus. Cornea 2015; 34:239-42.
10. Jarade E, Antonios R, El-Khoury S. Limbal Stem Cell-Sparing Corneoscleroplasty with Peripheral Intralamellar Tuck: A New Surgical Technique for Keratoglobus. Case Reports in Ophthalmology 2017;8(1):279-87.
11. Patil M, Mehta JS. Lamellar keratoplasty for advanced keratoconus. Asia Pac J Ophthalmol 2020;9(6):580-8.
12. Javadi MA, Kanavi MR, Ahmadi M, et al. Outcomes of Epikeratoplasty for Advanced Keratoglobus. Cornea 2007; 26:154-57.
12. Vajpayee RB, Bhartiya P, Sharma N. Central Lamellar Keratoplasty with Peripheral Intralamellar Tuck- A New Surgical Technique for Keratoglobus. Cornea 2002;21(7):657-60.
TREAT to keep more light than TUNNEL
1,2
An efficacious and comfortable treatment for glaucoma and ocular hypertension 3,4
When monotherapy provides insufficient IOP reduction 5
IOP = Intra Ocular Pressure
TEST • TREAT • PRESERVE
References: 1. Weinreb RN, Khaw PT. Primary open-angle glaucoma. Lancet 2004; 363:1711-20. 2. Weinreb RN, Aung T, Medeiros FA. The pathophysiology and treatment of glaucoma: a review. JAMA. 2014; 311(18):1901-1911. 3. Manni G, Denis P, Chew P, Sharpe ED, Orengo-Nania S, Coote JMA, et al. The safety and efficacy of brinzolamide 1%/timolol 0.5% fixed combination versus dorzolamide 2%/timolol 0.5% in Patients with open-angle glaucoma or ocular hypertension. J Glaucoma 2009;18:293–300. 4. Vold SD, Evans RM, Stewart RH, Walters T, Mallick S, et al. A one-week comfort study of BID-dosed brinzolamide 1%/ timolol 0.5% ophthalmic suspension fixed combination compared to BID-dosed dorzolamide 2%/timolol 0.5% ophthalmic solution in patients with open-angle glaucoma or ocular hypertension. J Ocul Pharmacol Ther. 2008; 24(6):601-605. 5. Azarga® professional information dated 20 March 2018.
For full prescribing information, please refer to the SAPHRA approved Professional Information. S4 AZARGA® eye drops, suspension. Reg no.: 44/15.4/0046. Each 1 ml of suspension contains 10 mg brinzolamide and 5 mg timolol (as timolol maleate). Preservative: benzalkonium chloride 0,01 % (w/v).
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A case of tuberculous panophthalmitis with orbital abscess
S Swaminathan (MBChB UCT), Registrar Ophthalmology, Groote Schuur Hospital, Cape Town, South Africa.
ORCID: https://orcid.org/0009-0004-3463-3970
N Mc Donald MBChB University of Pretoria, Dip Ophth (SA), Medical officer, Department of Ophthalmology, George Regional Hospital, South Africa
ORCID: https://orcid.org/0009-0001-7079-6142
Corresponding author: N McDonald, email: neelsmcd@gmail.com
Abstract
The purpose of this report is to describe a rare clinical case of orbital Tuberculosis (TB) with subsequent Tuberculous panophthalmitis. In this report an orbital abscess, formed in an immunocompromised patient became continuous with the globe. The patient had delayed presentation and prior to being diagnosed with an orbital abscess, was found to have both Human Immunodeficiency Virus (HIV) and Rifampicin-sensitive pulmonary tuberculosis. She presented with a painful, proptotic and blind left eye with complete ophthalmoplegia, features of granulomatous uveitis and retinal detachment. Further investigations revealed a large retrobulbar mass. Anti-tuberculous drug treatment
Introduction
The WHO Global Tuberculosis Report of 2022 identified TB as the leading infectious cause of mortality in 2019. Globally, 17% of new episodes of TB that were diagnosed and notified in 2021 were cases of extrapulmonary TB.1 An immunocompromised state places an individual at higher risk for extra-pulmonary TB infection. 2 Extra-ocular TB may manifest in five different forms: classic periostitis, orbital cold abscess (tuberculoma) without any bony involvement, tuberculoma with bone involvement, dacryoadenitis, and contiguous spread from paranasal sinuses. 2 The ophthalmic presentation of TB is very rarely in the form of endophthalmitis or panophthalmitis. 3 Definitive diagnosis of ocular TB relies on obtaining a tissue specimen for histopathological diagnosis, which is often challenging. 2,4 The presence of pulmonary TB, or a response to anti-tuberculous treatment, should raise suspicion for TB being the cause of intra-ocular or orbital infection. 2,3 The mainstay of treatment for TB, including extra-pulmonary TB, is a regimen of anti-tuberculous drugs. The extent of infection, structures involved, and visual prognosis must all be considered if the clinician decides on a more invasive diagnostic and therapeutic approach. 2 This article describes the case of TB
for pulmonary TB had been initiated four weeks prior to the ophthalmic presentation. After consultation with physicians, a treatment duration of 12 months was advised. In addition to this, the patient was offered an evisceration without silicone ball insertion. She recovered well. The proptosis improved and the patient was more comfortable. Orbital TB should be considered when patients with a diagnosis of TB elsewhere in the body present with proptosis. A comprehensive workup to determine the cause of proptosis is essential in all cases.
Funding and conflict of interest: None.
panophthalmitis with orbital tuberculoma in an 18-year-old female with HIV.
Case presentation
An 18-year-old female was newly diagnosed with HIV and Rifampicin sensitive pulmonary TB. She reported a history of constitutional symptoms. She was started on anti-tuberculosis treatment and after the completion of four weeks of treatment she was initiated on antiretroviral treatment. She was then referred to Ophthalmology with progressively worsening proptosis of the left eye over the last few months and poor vision.
On examination the patient, was a young female with a slender build.
Investigations revealed a positive HIV ELISA result, CD4 count of 109 cells/µL and HIV viral load of 10951 copies/ml. Cryptococcal antigen testing, and syphilis serology (Rapid Plasma Reagin) were negative. Serum Toxoplasma IgG and IgM were also negative. Inflammatory markers were raised; C-Reactive protein was 93mg/L, erythrocyte sedimentation rate was 111mm/hr. White cell count was elevated at 16.69 H x 109L and the platelet count was also increased. Thyroid functions were within normal limits. Sputum PCR testing from the referring hospital was positive for Mycobacterium Tuberculosis which was Rifampicin sensitive.
B-Scan of the left eye showed a total retinal detachment with a hyperechoic mass which extended from the orbit and was continuous with the globe. Contrasted computed tomography (CT) of the brain
Figures 1 and 2: Contrast enhanced axial and sagittal CT of the brain and orbits showing a thick walled intraconal mass in the left orbit that extends into the globe.
and orbit revealed a left thick walled intraconal abscess measuring 20 x 27 x 24 mm (transverse x anteroposterior x craniocaudal). The abscess encased the optic nerve and invaded the posterior wall of the globe with extension of pus into the vitreous. The rectus muscles and extraconal space were normal and no periostitis was noted. The lacrimal gland, sinuses, muscles, superior ophthalmic vein, and cavernous sinuses were all normal. A ring enhancing lesion suggestive of a tuberculoma was noted in the left cerebellar hemisphere. Right sided cervical necrotic adenitis was noted.
Management
The suspicion for a TB abscess was very high and to confirm the diagnosis needle aspiration was performed under general anaesthesia. The aspirate revealed fragments of lesional tissue which consisted of suppurative inflammation and necrotising granulomatous inflammation. The PCR result was positive for Mycobacterium Tuberculosis with sensitivity to Rifampicin. There was no evidence of malignancy. Ziehl Neelsen stain was positive for acid fast bacilli. PAS and Grocott staining were negative for fungal organisms. Following the aspiration, an improvement in proptosis was noted, but a subsequent CT scan did not show any change in the size of the abscess. Incision and drainage of the abscess was then performed through a sub-brow incision, and this significantly improved the proptosis.
The patient then agreed to an evisceration in light of persistent pain. The evisceration was performed, and the orbital collection was evacuated through the defect in the posterior sclera. During admission, the patient was also evaluated by physicians who advised 12 months of anti-tuberculous treatment. The patient was discharged with analgesia, systemic anti-inflammatories, topical steroids, and antibiotics. She maintained good adherence to treatment but follow up was inconsistent due to transportation issues. The proptosis resolved and her level of comfort improved.
Discussion
The incidence of Tuberculous orbital abscess is rare throughout the world, even in countries with a high prevalence of Tuberculosis. 5 There have been fewer than 44 documented cases of endogenous endophthalmitis and/or panophthalmitis secondary to Tuberculosis.6 There are 18 reported cases of patients with endogenous endophthalmitis and 25
with panophthalmitis secondary to Tuberculosis.6 Only three of the patients with panophthalmitis had orbital involvement.6 In this particular case, the presentation was unique as there was both panophthalmitis and an intra-orbital abscess which was continuous with the globe. The panophthalmitis likely occurred because of the abscess eroding through the globe. This has never been reported before. Diagnosing orbital Tuberculosis or Tuberculous panophthalmitis is challenging.6 In this particular case however, it was suspected from presentation, as the patient had pulmonary Tuberculosis and was immunocompromised.
Mycobacterium Tuberculosis (mTB) is the organism that causes Tuberculosis, and it is an obligate, aerobic acid-fast bacillus.7 Transmission of the organism is via airborne/ droplet spread.7 Normally, the inhaled bacillus forms an asymptomatic, self-limiting pulmonary granuloma that remains dormant and reactivates at a later stage.8 Intra-orbital Tuberculosis manifests in two forms. The first is Tuberculous periostitis and the second is an orbital space occupying lesion.8 Intraorbital Tuberculosis may occur secondary to a focus in the lungs or the gastrointestinal system through haematogenous spread.8 Alternatively, intra-orbital Tuberculosis may spread from adjacent structures like the sinuses.8 An immune response to the bacilli can result in hypersensitivity reactions in various parts of the eye.9
Extra-ocular manifestations of Tuberculosis
Orbital Tuberculosis and extra-ocular Tuberculosis may manifest in various ways.7 The ocular manifestation of TB affecting the eyelid margin has been noted to appear as
Figure 3: Contrast enhanced coronal CT of the orbits showing an intraconal mass in the left orbit surrounding the optic nerve.
chronic blepharitis and recurrent chalazia.7 Cutaneous TB involvement may appear as nodules, ulcers or even as a cellulitis when diffuse skin involvement is present.7 Conjunctival TB presents as conjunctivitis, conjunctival nodules, polyps, tuberculomas and ulcers.7 Scleral involvement with TB may manifest as scleritis which could be necrotising, non-necrotising, anterior or posterior, diffuse or nodular.7 Corneal involvement may appear as interstitial keratitis, disciform keratitis or as corneal erosions.7 If the lacrimal gland is involved, it may present as dacryoadenitis – typically one that fails to respond to antibiotics.7 When the orbit is involved it may manifest as proptosis secondary to a space occupying orbital lesion, or it may present with diplopia from cranial nerve or extra-ocular muscle involvement.7 The peri-orbital bone may be affected and appear as periostitis which can affect the outer margin of the orbit or cortical irregularities that evolve into thickening and sclerosis of the bone.7
TB panophthalmitis and abscesses
The majority of documented cases of TB
Table summarising ocular examination findings
Deep and formed Anterior chamber
Very deep, formed, 4+ cells, sliver of hypopyon Round
No lens opacity
No vitritis; pink, healthy disc, cup to disc ratio of 0.3 and normal macular reflex
Vitreous and retina
Grade 4 RAPD
No lens opacity; pigment on lens
Pronounced vitritis; poor view of retina
Figure 4: Contrast enhanced axial CT of the brain showing a ring enhancing lesion in the left cerebellar hemisphere suggestive of a tuberculoma.
endophthalmitis and panophthalmitis have been unilateral and associated with a poor prognosis often requiring enucleation or evisceration.9 Panophthalmitis is an infectious process caused by a pyogenic organism that encompasses all structures of the globe along with surrounding orbital and periorbital structures.10 Inflammation of intra-ocular fluids and structures due to TB can present with a granulomatous uveitis, vitritis and painful glaucoma.11 Orbital abscesses can act as orbital space occupying lesions that cause proptosis. This can cause exposure keratopathy, optic nerve dysfunction resulting in reduced visual acuity, colour vision, an afferent pupillary defect and visual field deficits.12 In most cases orbital TB may manifest as tuberculomas or cold abscesses. 5 A cold abscess is a space occupying purulent collection that does not exhibit features of acute inflammation. 5 There have been two documented cases of sphenoidal extension but no documented cases of intracranial extension of TB orbital abscesses. 5 Often the diagnosis of endogenous TB endophthalmitis can be difficult to make especially if the differential is not considered. One should have a high index of suspicion for the diagnosis if patients are immunocompromised and from TB endemic areas.
The treatment of an orbital TB abscess requires the initiation of antituberculosis treatment with a four-drug treatment regimen which includes Isoniazid, Rifampicin, Pyrazinamide and Ethambutol for two months; followed by a further four-seven months of treatment with Rifampicin and Isoniazid.7 Eighteen months of treatment is recommended in patients with TB involving the central
nervous system, bones, and joints. Orbital TB has been reported more frequently than panophthalmitis, and the treatment regimens are not always documented.7 Documented cases have had a range of treatment durations and regimens that have been successful. Duration for antituberculosis treatment for orbital TB ranges between six and 18 months.7 There is no consensus on the optimum duration of treatment. In general, a six to nine month period of treatment is recommended.7 Treatment regimens need to be adjusted according to drug sensitivity of organisms.11 In addition to the use of anti-tuberculosis medications, the orbital abscess needs to be drained. This process also allows for the confirmation of the diagnosis as specimens may be sent for testing.
The optimal surgical management of TB endophthalmitis and panophthalmitis is yet to be determined as only 44 cases have been reported worldwide. About half the documented cases had eviscerations and the other half enucleations.9 In this case, evisceration of the globe and drainage of the abscess aided in the relief of the patient’s symptoms and fast tracked her recovery. The benefits to performing evisceration over enucleation is that it is a simpler procedure which is less time consuming. Expedited drainage of an orbital abscess can prevent communication with the globe and mass effect resulting in exposure keratopathy or optic neuropathy. A concern in this case was the potential extra-orbital spread of the abscess. A review of the literature revealed two documented cases of orbital Tuberculosis with sphenoidal extension however, direct intra-cranial extension has never been noted. 5 There have been a few documented cases that have received steroids prior to their surgery, the benefit of which is yet to be determined. Mortality outcomes are favourable as 97.7% of the patients with TB endophthalmitis/ panophthalmitis survived or their outcome was not specified by authors; only 2.3% of patients were reported to have demised.6 Ocular outcomes for these patients are poor with 83.7% requiring an evisceration, enucleation or exenteration.6 Only 2.3% of reported cases had a documented visual acuity better than 20/200.6
Conclusion
Tuberculosis is a significant infectious contributor to global morbidity and mortality. TB as the causative aetiology for an orbital process or intra-ocular inflammation must be considered, especially in immunocompromised patients. Imaging
and tissue biopsy play an important role in diagnosis of orbital TB. Extended medical treatment with anti-TB drugs must be undertaken and surgery is often required for the diagnosis and the treatment of orbital TB. Evisceration and enucleation have been performed for orbital TB involving the globe. Orbital TB should be considered when patients with a diagnosis of TB elsewhere in the body present with proptosis. A comprehensive workup to determine the cause of proptosis is essential in all cases.
References
1. Global tuberculosis report 2022. Geneva: World Health Organization; 2022. Licence: CC BY-NC-SA 3.0 IGO.
2. Madge SN, Prabhakaran VC, Shome D, Kim U, Honavar S, Selva D. Orbital tuberculosis: a review of the literature. Orbit. 2008;27(4):267-77.
3. Dalvin LA, Smith WM. Intraocular manifestations of mycobacterium tuberculosis: A review of the literature. J Clin Tuberc Other Mycobact Dis. 2017 Feb 17; 7:13-21.
4. Diyora B, Giri SA, Bhende B, Giri D, Kukreja S, Sharma A. Orbital tuberculosis with intracranial extension. J Neurosci Rural Pract 2018; 9:636-8.
5. Aggarwal D, Suri A, Mahapatra AK. Orbital Tuberculosis with Abscess: J Neuroophthalmol. 2002 Sep;22(3):208-10.
6. Antaki F, Javidi S, Touma S, Aubin MJ. Endogenous Tuberculous Endophthalmitis and Panophthalmitis: A Systematic Review of Case Reports and Case Series. Clin Ophthalmol. 2020 Oct; Volume 14:3075-96.
7. Dalvin LA, Smith WM. Orbital and external ocular manifestations of Mycobacterium tuberculosis: A review of the literature. J Clin Tuberc Mycobact Dis. 2016 Aug; 4:50-7.
8. Kaur A, Agrawal A. Orbital Tuberculosis – an Interesting Case Report. Int Ophthalmol. 2006 Nov 17;26(3):107-9.
9. Srichatrapimuk S, Wattanatranon D, Sungkanuparph S. Tuberculous Panophthalmitis with Lymphadenitis and Central Nervous System Tuberculoma. Case Rep Infect Dis. 2016; 2016:1-7.
10. Ahmad Fauzi N, Rosli AH, Jabbari AJ. A Rare Occurrence of Isolated Endogenous Escherichia coli Panophthalmitis: A Case Report. Cureus [Internet]. 2023 Oct 15 [cited 2024 Mar 17]; Available from: https://www. cureus.com/articles/174421-a-rare-occurrenceof-isolated-endogenous-escherichia-colipanophthalmitis-a-case-report
11. Chuka-Okosa CM. Tuberculosis and the eye. Niger J Clin Pract. 2006 Jun;9(1):68-76.
12. Jain J, Parihar P, Karwassara V, Banait S. Orbital tuberculosis manifesting as proptosis in an immunocompromised host. Indian J Sex Transm Dis AIDS. 2012;33(2):128.
Four
NEW BEGINNINGS await the South African Ophthalmology Journal
Dear Colleagues,
As we prepare to bid farewell to this final edition of the South African Ophthalmology Journal under the Ophthalmological Society of South Africa’s (OSSA’s) involvement, I am filled with a mix of gratitude and sadness. Over the years, the journal has been an integral platform for sharing knowledge, advancing eye care, and uniting our profession. It has served as a vital link between practitioners, researchers, and advocates in the field of ophthalmology, and for this, we are deeply appreciative to all involved. While OSSA parts ways with New Media , we do so with immense respect and thanks for their invaluable contribution to the success of this publication.
OSSA, as the custodian of eye care in South Africa, stands committed to advocating for the best possible outcomes for our patients. It is our responsibility not only to advance the field of ophthalmology but also to ensure that our profession maintains the highest
standards of practice and ethics. Throughout OSSA’s history, we have taken pride in championing patient advocacy, ensuring equitable access to eye care, and working to improve the quality of care available to all South Africans.
Through the Journal, we have been able to contribute to the education of professionals and the dissemination of high-quality academic research articles, ensuring that our patients are receiving the best care our industry can provide. We hope that in the years to come, OSSA will continue to inspire future generations of ophthalmologists to keep striving for excellence, grounded in patient-centric care.
The end of OSSA’s involvement with the Journal is not the end of our journey. We will continue to uphold our mission of education, patient advocacy, and promoting access to quality eye care services. Our focus remains on collaboration to foster innovation and share knowledge, ensuring that ophthalmology in South Africa stays
Let us take this moment to reflect on the achievements we have made together through the Journal and let us move forward with renewed dedication to our patients, our profession, and to OSSA’s enduring mission.
Society, South Africa steven.lapere@gmail.com
at the forefront of healthcare research and excellence.
Dr Steven Lapere MMed (Ophth) Cape Town, FC Ophth (SA) (MB ChB Free State President Ophthalmology
Study links diabetes drug Ozempic to serious eye condition
A recent study by Mass Eye and Ear researchers found a link between semaglutide, a drug used for diabetes and weight loss, and an increased risk of a serious eye condition called NAION (nonarteritic anterior ischemic optic neuropathy). Semaglutide is sold under the brand names Ozempic and Wegovy, developed by Novo Nordisk.
The study, led by Dr Joseph Rizzo and published in JAMA Ophthalmology, showed that diabetic patients taking semaglutide were four times more likely to develop NAION compared to those not using the drug. Overweight or obese patients on semaglutide had an even higher risk, with a sevenfold increase in NAION cases.
Dr Rizzo emphasised the need for careful discussion of this risk, as NAION, though rare, can cause permanent vision loss. The research was prompted by a rise in NAION cases among semaglutide users in 2023, leading to a review of over 17 000 patients treated since Ozempic’s release in 2017.
Ferdinand Monoyer: The ophthalmologist who left his name in eye charts
Ferdinand Monoyer is best known for inventing the dioptre, the unit for measuring lens power, and designing a famous eye chart for testing visual acuity, which cleverly hides his name within the letters. Monoyer studied medicine in Strasbourg, later becoming a professor at the University of Nancy, and finishing his career at the University of Lyon (1877-1909). His eye chart inspired the Dutch ophthalmologist Herman Snellen, who created a similar chart in 1862, originally
using abstract symbols before switching to letters. Today, the most accurate eye chart is the LogMAR chart, developed by Australian researchers in 1976.
Challenges ahead for Musk’s vision implant
Elon Musk recently claimed that Neuralink’s Blindsight, a brain implant designed to restore vision, could eventually surpass normal human eyesight, though it would initially offer low-resolution vision. However, University of Washington researchers, led by Ione Fine, disagree. Their study in Scientific Reports suggests that even with 45 000 electrodes, vision would remain blurry and far from the clear images Musk envisions. Fine explains that the brain’s complex processing of visual signals makes it difficult to replicate clear vision with electrodes alone. She warns that Musk’s claims might create false hope, especially for older adults losing their sight.
Reference: Ione Fine et al, A virtual patient simulation modeling the neural and perceptual effects of human visual cortical stimulation, from pulse trains to percepts, Scientific Reports (2024). DOI: 10.1038/ s41598-024-65
Scientists identify RNF114 Protein that may reverse cataracts without surgery
Researchers at the National Institutes of Health (NIH) and collaborators have identified a protein called RNF114 that may reverse cataracts, potentially offering a surgery-free treatment for cataracts, a leading cause of vision loss. The study, published in the Journal of Clinical Investigation , involved experiments with 13-lined ground squirrels and rats. While ground squirrels naturally reverse cataracts formed during hibernation at low temperatures, rats and non-hibernating animals do not.
The researchers developed a model using stem cells from the ground squirrels and
discovered that RNF114 plays a key role in breaking down old proteins that contribute to cataract formation. In their experiments, pre-treating rat lenses with RNF114 enabled cataract reversal upon warming, showing promise for future therapeutic strategies.
This research could help develop new treatments by targeting protein degradation, an important factor in both cataract formation and other diseases like neurodegeneration. The study emphasises the role of RNF114 in maintaining protein balance under stress conditions.
Artificial Intelligence (AI) in disease detection
By combining advanced imaging tools with AI’s ability to analyse complex data, healthcare professionals can now identify ocular diseases with unprecedented speed, accuracy, and precision. This powerful combination not only enhances early detection of conditions such as glaucoma, diabetic retinopathy, and age-related macular degeneration but also offers the potential for personalised treatment plans, ultimately improving patient outcomes and reducing the burden of blindness worldwide. Diagnostic tools empowered by artificial intelligence offer a promising future, potentially improving patient outcomes and reducing the burden on healthcare systems by enabling earlier intervention.
The use of robotics in ophthalmic surgery has revolutionised the precision and accuracy of procedures. Robotic systems allow surgeons to perform delicate maneuvers with enhanced control and visualisation, leading to improved outcomes for patients undergoing eye surgeries.
It is remarkable to see how robotics technology has seamlessly integrated into the field of ophthalmology, providing new possibilities for surgeons and better treatment options for patients.
Reference: Mayo Clinic
CATARACT SURGERY may reduce dementia risk
Individuals who undergo cataract surgery could experience about a 25% lower risk of long-term cognitive decline to those who do not have the surgery. However, the short-term effects of the surgery on cognitive function remain uncertain. These findings are drawn from a systematic review and meta-analysis, reinforcing previous research that suggests addressing sensory impairments may help slow cognitive decline. This underlines the importance of discussing cataract surgery as a potential cognitive health benefit with patients.
Visual impairment is known to contribute to faster cognitive decline and an increased risk of dementia, possibly due to the reduction in visual stimuli accelerating neurodegenerative processes. The potential for cataract surgery to mitigate this risk, however, has not been definitively established.
While some studies indicate short-term cognitive benefits, others suggest long-term advantages, with mixed and sometimes conflicting results.
To better understand these impacts, a research team from Singapore conducted an extensive review and meta-analysis of data from studies published up to September 2022. The selected studies examined adults who underwent cataract surgery, comparing their cognitive outcomes with control groups (either those without cataract or with untreated cataract).
Clear evidence of long-term benefits
The review included 24 studies encompassing 558,276 participants (average age 66 years, 46% male). This comprised 16 prospective cohort studies and one randomized controlled trial, with an overall low to moderate risk of bias. In eight of the 11 studies that specified laterality, the cataracts were bilateral. Six of the 11 studies detailed phacoemulsification as the surgical method used.
For short-term outcomes (3-12 months), pooled data from eight studies (662 patients) indicated a modest 4% improvement in cognitive scores post- surgery among patients
O er Neuroprotection1
This is reprinted courtesy of Medical Chronicle
with normal cognitive function compared to controls (mean ratio 0.96 [0.94-0.99]). However, there was significant variability across studies (I² = 75%). Despite differences in cognitive tests used, the benefit was consistent.
Conversely, for patients with preexisting cognitive impairment (358 patients across four studies), no significant change in cognitive scores was observed after surgery. For longterm outcomes, data from six studies with 246 640 parti icipants and a follow-up of 7-10 years showed a 25% reduction in the risk of cognitive decline or dementia in those who had undergone cataract surgery compared to those who had not (hazard ratio 0.75 [0.72-0.78], I² = 9%).
This benefit was consistent for both cognitive decline and dementia risk. However, when comparing patients who had surgery to those without cataracts, long-term cognitive decline risk was similar (pooled analysis of 308,795 participants, follow-up of 24-101 months, hazard ratio 0.84 [0.66-1.06]).
Source: MedScape UK .
South African & Africa congresses and meetings 2024
OPTICAL tr.
2024
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NOVEMBER
International Conference on Retinoblastoma and Retinal Disorders
Date: 04-05 November 2024
Venue: Cape Town, South Africa
Website: https://waset.org/
2025
FEBRUARY
Ophthalmological Society of South Africa (OSSA) Conference
Date: 12-15 February 2025
Venue: Sandton Convention Centre
Website: https://2025.ossacongress.co.za
APRIL
International Conference on Ophthalmology and Optometry (ICOO)
American Glaucoma Society Annual Meeting 2025 (AGS)
Date: 26 February-2 March 2025
Venue: Omni Shoreham Hotel Washington, DC, USA
Website: https://www. americanglaucomasociety
The European Society of Cataract & Refractive Surgeons 2025 (ESCRS)
Date: 28 February-2 March 2025
Venue: Megaron Athens, Athens, Greece
Website: https://wintermeeting.escrs.org
APRIL
ASCRS 2025 American Society of Cataract and Refractive Surgery
Date: 25-28 April 2025
Venue: Los Angeles, CA, USA
Website: https://annualmeeting.ascrs.org
JUNE
World Glaucoma Congress (WGC 2025)
Date: 25 June – 28 June 2025
Venue: Honolulu, Hawaii, USA
Website: https://worldglaucomacongress.org
SEPTEMBER
25th European Society of Retina Specialists Congress 2025 (EURETINA)
Date: 4-7 September 2025
Venue: Paris, France
Website: https://euretina.org
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4 BOOK REVIEWS FOR 2024
Title: Clinical Atlas of Anterior Segment OCT: Ocular Coherence Tomography
Most eye care providers know how useful optical coherence tomography (OCT) is for diagnosing and treating glaucoma and retinal diseases. However, many are less familiar with its benefits for diagnosing corneal and front-of-the-eye (anterior segment) conditions. Anterior segment OCT (AS-OCT) can help identify different corneal issues, show the structure of the eye’s angles, give details about the lens and capsule, and even assist with contact lens fittings. Clinical Atlas of Anterior Segment OCT provides clear guidance for clinicians, with hundreds of high-quality images demonstrating how AS-OCT can be used to diagnose and treat a variety of anterior segment diseases.
For price visit: https://books. google.co.za/books/about/Clinical_ Atlas_of_Anterior_Segment_OCT_O. html?id=poH1EAAAQBAJ&redir_esc=y
Title: The Neuro-Ophthalmology Survival Guide E-Book
Authors: Anthony Pane, Neil R. Miller, Michael Burdon
This book is a practical guide for both trainees and practicing ophthalmologists and optometrists, focusing on neuroophthalmology, and acquired strabismus. It’s organised by symptoms, making it easy
to follow. Each chapter covers a different symptom and includes an introduction on how to assess it, an exam checklist, a flowchart for managing the issue, and diagnostic criteria. There’s also extra information on the diseases that can cause the symptom, along with a short discussion on how to manage them. It’s a helpful, stepby-step resource for eye care professionals.
For price visit: https://www. amazon.com/Neuro-OphthalmologySurvival-Anthony-MMedSc-FRANZCO/ dp/0702072672
Title: Fixing My Gaze: A Scientist’s Journey into Seeing in Three Dimensions
Author : Susan R. Barry
In her fifties, neuroscientist Susan Barry experienced something extraordinary during a trip to Manhattan. Stepping out of the subway, she saw the city in a completely new way. This revelatory account of the brain’s capacity for change, Fixing My Gaze describes Barry’s remarkable journey and celebrates the joyous pleasure of our senses.
Barry had been cross-eyed and stereoblind since infancy, seeing the world as flat and compressed. At fifty, she saw Manhattan in 3D for the first time, a life-changing moment. As a neuroscientist, she knew how remarkable this transformation was, defying the belief that the brain can only change during early childhood.
Despite this, Barry found an optometrist
who introduced her to vision therapy. After intensive training, she achieved what was once thought impossible, challenging the limits of brain plasticity.
For price visit: https://www.amazon.com/ Fixing-My-Gaze-Scientists-Dimensions/ dp/0465020739#:~:text=Book%20 overview&text=When%20neuroscientist%20 Susan%20Barry%20was,the%20bows%20 of%20giant%20ships.
Title: Chinese Ophthalmology: Acupuncture, Herbal Therapy, Dietary Therapy, Tuina and Qigong
Authors: Agnes Fatrai, Stefan Uhrig , Ute Engelhardt
Foundations and basic concepts of Chinese ophthalmology, Eye physiology in Chinese Medicine (CM), Theories of the Five Wheels and Eight Boundaries
Pathophysiology and treatment of eye diseases in CM, Acupuncture, moxa, Chinese materia medica, dietary therapy, tuina, and Eye Qigong.
It provides treatment options for various conditions, from common issues like blepharitis and dry eye syndrome to more serious conditions such as diabetic retinopathy and macular degeneration, along with preventive recommendations for maintaining eye health.
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When inflammation hits, strike back with Loteprednol
Etabonate
Site-specific, high-anti-inflammatory e cacy 1-3
Improved safety profile 1, 2, 4
Modulates and inhibits early-and late-phase inflammatory mediators for multi-symptom relief 1, 5 Lower risk for IOP elevation in short and long-term use 5
Engineered to adhere to the ocular surface, for post-operative inflammation 6-8
Uniform dose delivery, in every drop 7, 9
References: 1. Pavesio CE, et al. Treatment of ocular inflammatory conditions with loteprednol etabonate. Br J Ophthalmol 2008;92:455– 459. 2. Dell SJ, et al. A randomized, double-masked, placebo-controlled parallel study of 0.2% loteprednol etabonate in patients with seasonal allergic conjunctivitis. J Allergy Clin Immunol 1998;102:251-5. 3. Gong L, et al. Loteprednol Etabonate Suspension 0.2% Administered QID Compared With Olopatadine Solution 0.1% Administered BID in the Treatment of Seasonal Allergic Conjunctivitis: A Multicenter, Randomized, Investigator Masked, Parallel Group Study in Chinese Patients. Clin Ther. 2012;34:1259–1272. 4. Comstock TL, et al. Advances in Corticosteroid Therapy for Ocular Inflammation:Loteprednol Etabonate. Int J Inflam 2012; 789623:1-11. 5. Ilyas H, et al. Long-term safety of loteprednol etabonate 0.2% in the treatment of seasonal and perennial allergic conjunctivitis. Eye Contact Lens 2004;30(1):10-13. 6. Lotemax® Ophthalmic Gel package insert, August 2022. 7. Fong R., et al. Loteprednol etabonate gel 0.5% for postoperative pain and inflammation after cataract surgery: results of a multicentre trial. Clin Ophthalmol. 2012;6:1113-1124. 8. Shaikh R et al. Mucoadhesive drug delivery systems. J Pharm Bioallied Sci. 2011;3:89-100. 9. Co ey MJ and Davio SR. Presented at: ARVO 2012; May 2012; Ft. Lauderdale, FL. Poster D1143. S4 Proprietary name and dosage form: Lotemax ophthalmic suspension, eye drops. Composition: Each 1 ml contains: Loteprednol Etabonate 5,00 mg (0,5 % m/v) and Benzalkonium chloride (preservative) 0,01 % m/v Pharmacological classification: A 15.2 Ophthalmic preparations with corticosteroids. Registration number: 37/15.2/0588. S4 Proprietary name and dosage form: Alrex Ophthalmic Suspension. Composition: Each 1 ml contains: Loteprednol etabonate 2,00 mg (0,2 % m/v) and Benzalkonium chloride (preservative) 0,01 % m/v Pharmacological classification: A 15.2 Ophthalmic preparations with corticosteroids. Registration number: 38/15.2/0203. S4 Proprietary name and dosage form: Lotemax Ophthalmic Gel. Composition: Loteprednol etabonate 5,00 mg (0,5 % m/v) and Benzalkonium chloride (preservative) 0,003 %
Target multiple pro-inflammatory mediators to help treat oedema in DME and RVO with OZURDEX®1-7
OZURDEX® contains dexamethasone.1 Dexamethasone has been shown to help treat oedema by targeting and suppressing VEGF,* MCP-1, IL-6, IL-8 and ICAM-1 pro-inflammatory mediators involved in, and significant to, the pathophysiology of DME and RVO.1-7
OZURDEX® is indicated for the treatment of adult patients with visual impairment due to diabetic macular oedema (DME) who are pseudophakic or who are considered insufficiently responsive to, or unsuitable for non-corticosteroid therapy and for adult patients with macular oedema following either branch retinal vein occlusion (BRVO) or central retinal vein occlusion (CRVO).1
*Corticosteroids have been shown to have some inhibitive effect on the expression of VEGF , to a lesser extent than anti-VEGFs. Supporting evidence contains data from animal models and in vitro studies which cannot necessarily be extrapolated to clinical situations. BRVO: Branch retinal vein occlusion; CRVO: Central retinal vein occlusion; DME: Diabetic macular oedema; ICAM: Intercellular adhesion molecule; IL: Interleukin; MCP:Monocyte chemoattractant protein; RVO: Retinal vein occlusion; VEGF: Vascular endothelial growth factor. OZURDEX intravitreal implant. Contains dexamethasone 700 μg in a polymer matrix. Registration numbers: South Africa: 44/15.2/0045; Mauritius: PB12805/11/2016. AbbVie (Pty) Ltd, Reg. 2012/068113/07. Address: Building 7, Waterfall Corporate Campus, 74 Waterfall Drive, Midrand, 1685, South Africa. Tel: 011 031 1600. Date of Publication of this material: March 2024. Promo. No. ZA-OZU-240004. For full prescribing information refer to the professional information approved by the medicines regulatory authority, accessible by e-mailing medicalinfo.za@abbvie.com. For adverse events, report to MEAPV@abbvie.com.
REFERENCES: 1. Ozurdex® professional information, April 2023. 2. Garcia-Layana A et al. Ophthalmologica 2018; doi: 10.1159/000486800 (accessed February 2024). 3. Wang K et al. Biol Pharm Bull 2008; 31(8): 1541-6. 4. RezarDreindl S et al. Acta Ophthalmol 2017; 95(2): e119-27. http://dx.doi.org/10.1155/2013/438412 (accessed February 2024). 5. Edelman JL et al. Exp Eye Res 2005; 80: 249-58. 6. Tamura H et al. Invest Ophthalmol Vis Sci 2005; 46(4): 1440-4. 7. Nehme A and Edelman J. Invest Ophthalmol Vis Sci 2008; 49(5): 2030-8.
