EuroTimes December 2021/January 2022, Volume 26, Issue 11

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Dec 2021/Jan 2022 | Vol 26 Issue 11

What Does the

FUTURE Hold for Global



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OZURDEX® (dexamethasone intravitreal implant) acts fast1,2 and lasts3–5 with less treatment visits compared with anti-VEGFs.5 Effective DME treatment doesn’t have to be a burden.6

The most commonly reported adverse events reported following treatment with OZURDEX® are those frequently observed with ophthalmic steroid treatment or intravitreal injections (elevated IOP, cataract formation and conjunctival or vitreal haemorrhage respectively). Less frequently reported, but more serious, adverse reactions include endophthalmitis, necrotizing retinitis, retinal detachment and retinal tear. This advert is consistent with the UK marketing authorisation. Licences may vary by country, please refer to your local country SmPC. DME, diabetic macular edema; IOP, intraocular pressure; VEGF, vascular endothelial growth factor. 1. Lo Giudice G et al. Eur J Ophthalmol 2018;28(1):74–79. 2. Veritti D et al. Ophthalmologica 2017;238(1–2): 100–105. 3. Escobar-Barranco JJ et al. Ophthalmologica 2015;233(3–4):176–185. 4. Allergan. OZURDEX® Summary of Product Characteristics. 5. Kodjikian L et al. Biomed Res Int 2018:8289253. 6. Boyer DS et al. Ophthalmology 2014;121:(10):1904–1914.

OZURDEX® (Dexamethasone 700 micrograms intravitreal implant in applicator) Abbreviated Prescribing Information Presentation: Intravitreal implant in applicator. One implant contains 700 micrograms of dexamethasone. Disposable injection device, containing a rod-shaped implant which is not visible. The implant is approximately 0.46 mm in diameter and 6 mm in length. Indications: Treatment of adult patients: with macular oedema following either Branch Retinal Vein Occlusion (BRVO) or Central Retinal Vein Occlusion (CRVO), inflammation of the posterior segment of the eye presenting as non-infectious uveitis and visual impairment due to diabetic macular oedema (DME) who are pseudophakic or who are considered insufficiently responsive to, or unsuitable for non-corticosteroid therapy. Dosage and Administration: Please refer to the Summary of Product Characteristics before prescribing for full information. OZURDEX must be administered by a qualified ophthalmologist experienced in intravitreal injections. The recommended dose is one OZURDEX implant to be administered intra-vitreally to the affected eye. Administration to both eyes concurrently is not recommended. Repeat doses should be considered when a patient experiences a response to treatment followed subsequently by a loss in visual acuity and in the physician’s opinion may benefit from retreatment without being exposed to significant risk. Patients who experience and retain improved vision should not be retreated. Patients who experience a deterioration in vision, which is not slowed by OZURDEX, should not be retreated. In RVO and uveitis there is only very limited information on repeat dosing intervals less than 6 months. There is currently no experience of repeat administrations in posterior segment non-infectious uveitis or beyond 2 implants in Retinal Vein Occlusion. In DME there is no experience of repeat administration beyond 7 implants. Patients should be monitored following the injection to permit early treatment if an infection or increased intraocular pressure occurs. Singleuse intravitreal implant in applicator for intravitreal use only. The intravitreal injection procedure should be carried out under controlled aseptic conditions as described in the Summary of Product Characteristics. The patient should be instructed to selfadminister broad spectrum antimicrobial drops daily for 3 days before and after each injection. Contraindications: Hypersensitivity to the active substance or to any of the excipients. Active or suspected ocular or periocular infection including most viral diseases of the cornea and conjunctiva, including active epithelial herpes simplex keratitis (dendritic keratitis), vaccinia, varicella, mycobacterial infections, and fungal diseases. Advanced glaucoma which cannot be adequately controlled by medicinal products alone. Aphakic eyes with ruptured posterior lens capsule. Eyes with Anterior Chamber Intraocular Lens (ACIOL), iris or transscleral fixated intraocular lens and ruptured posterior lens capsule. Warnings/Precautions: Intravitreous injections, including OZURDEX can be associated with endophthalmitis, intraocular inflammation,

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increased intraocular pressure and retinal detachment. Proper aseptic injection techniques must always be used. Patients should be monitored following the injection to permit early treatment if an infection or increased intraocular pressure occurs. Monitoring may consist of a check for perfusion of the optic nerve head immediately after the injection, tonometry within 30 minutes following the injection, and biomicroscopy between two and seven days following the injection. Patients must be instructed to report any symptoms suggestive of endophthalmitis or any of the above mentioned events without delay. All patients with posterior capsule tear, such as those with a posterior lens (e.g. due to cataract surgery), and/or those who have an iris opening to the vitreous cavity (e.g. due to iridectomy) with or without a history of vitrectomy, are at risk of implant migration into the anterior chamber. Implant migration to the anterior chamber may lead to corneal oedema. Persistent severe corneal oedema could progress to the need for corneal transplantation. Other than those patients contraindicated where OZURDEX should not be used, OZURDEX should be used with caution and only following a careful risk benefit assessment. These patients should be closely monitored to allow for early diagnosis and management of device migration. Use of corticosteroids, including OZURDEX, may induce cataracts (including posterior subcapsular cataracts), increased IOP, steroid induced glaucoma and may result in secondary ocular infections. The rise in IOP is normally manageable with IOP lowering medication. Corticosteroids should be used cautiously in patients with a history of ocular herpes simplex and not be used in active ocular herpes simplex. OZURDEX is not recommended in patients with macular oedema secondary to RVO with significant retinal ischemia. OZURDEX should be used with caution in patients taking anticoagulant or anti-platelet medicinal products. OZURDEX administration to both eyes concurrently is not recommended. Visual disturbance may be reported with systemic and topical corticosteroid use. If a patient presents with symptoms such as blurred vision or other visual disturbances, consider evaluating for possible causes which may include cataract, glaucoma or rare diseases such as central serous chorioretinopathy (CSCR) which have been reported after use of systemic and topical corticosteroids. Interactions: No interaction studies have been performed. Systemic absorption is minimal and no interactions are anticipated. Pregnancy: There are no adequate data from the use of intravitreally administered dexamethasone in pregnant women. OZURDEX is not recommended during pregnancy unless the potential benefit justifies the potential risk to the foetus. Lactation: Dexamethasone is excreted in breast milk. No effects on the child are anticipated due to the route of administration and the resulting systemic levels. However OZURDEX is not recommended during breast-feeding unless clearly necessary. Driving/Use of Machines: Patients may experience temporarily reduced vision after receiving OZURDEX by intravitreal injection. They should not drive or use machines until this has resolved. Adverse Effects: In clinical trials the

most frequently reported adverse events were increased intraocular pressure (IOP), cataract and conjunctival haemorrhage*. Increased IOP with OZURDEX peaked at day 60 and returned to baseline levels by day 180. The majority of elevations of IOP either did not require treatment or were managed with the temporary use of topical IOP-lowering medicinal products. 1% of patients (4/347 in DME and 3/421 in RVO) had surgical procedures in the study eye for the treatment of IOP elevation. The following adverse events were reported: Very Common (≥ 1/10): IOP increased, cataract, conjunctival haemorrhage*. Common (≥1/100 to <1/10): headache, ocular hypertension, cataract subcapsular, vitreous haemorrhage*, visual acuity reduced*, visual impairment/ disturbance, vitreous detachment*, vitreous floaters*, vitreous opacities*, blepharitis, eye pain*, photopsia*, conjunctival oedema*, conjunctival hyperaemia. Uncommon (≥1/1,000 to <1/100): migraine, necrotizing retinitis, endophthalmitis*, glaucoma, retinal detachment*, retinal tear*, hypotony of the eye*, anterior chamber inflammation*, anterior chamber cells/flares*, abnormal sensation in eye*, eyelids pruritus, scleral hyperaemia*, device dislocation* (migration of implant) with or without corneal oedema , complication of device insertion resulting in ocular tissue injury* (implant misplacement). (*Adverse reactions considered to be related to the intravitreous injection procedure rather than the dexamethasone implant). Please refer to Summary of Product Characteristics for full information on side effects. Basic NHS Price: £870 (ex VAT) per pack containing 1 implant. Marketing Authorisation Number: EU/1/10/638/001. Marketing Authorisation Holder: Allergan Pharmaceuticals Ireland, Castlebar Road, Westport, Co. Mayo, Ireland. Legal Category: POM. Date of Preparation: May 2019. UK/0288/2019

Adverse events should be reported. Reporting forms and information can be found at Adverse events should also be reported to Allergan Ltd. or 01628 494026 JOB CODE: INT-OZU-2050217 DATE OF PREPARATION: DECEMBER 2020

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Publishers Therese Dolan Operations Director ESCRS Barbara Calderwood Mark Wheeler Executive Editor Stuart Hales email: Editor-in-Chief Sean Henahan Senior Content Editor Kelsey Ingram Design Director Kelsy McCarthy Designer Jen Basel Circulation Manager Vanessa McCourt Contributing Editors Cheryl Guttman Krader Howard Larkin Dermot McGrath Roibeárd O’hÉineacháin Contributors Leigh Spielberg Gearóid Tuohy Priscilla Lynch Soosan Jacob Colour and Print W&G Baird Printers Advertising Sales Roo Khan MCI UK Tel: +44 203 530 0100 email:

Published by the European Society of Cataract and Refractive Surgeons, Temple House, Temple Road, Blackrock, Co Dublin, Ireland. No part of this publication may be reproduced without the permission of the executive editor. Letters to the editor and other unsolicited contributions are assumed intended for this publication and are subject to editorial review and acceptance. ESCRS EuroTimes is not responsible for statements made by any contributor. These contributions are presented for review and comment and not as a statement on the standard of care. Although all advertising material is expected to conform to ethical medical standards, acceptance does not imply endorsement by ESCRS EuroTimes. ISSN 1393-8983




Global Vision Care

06 Best of the Best in Amsterdam

08 Two Centuries of Progress

09 No Free Lunch in Optics 10 Light-Adjustable Lens

Yields Positive Outcomes

11 Game Changer

RETINA 24 Vitreomacular Traction 25 Studying Progression in


Early Geographic Atrophy

26 Designer Optogenetics to Restore Vision

GLAUCOMA 28 Choosing Combined

Surgery for Cataract and Glaucoma

for Presbyopia?

12 Enhancements After Refractive Surgery

CORNEA 14 Cataract Surgery


15 Keratoconus and Cross-linking

16 Unregulated Anterior

Segment Devices Show Their True Colours

19 Dry Eye Therapies 21 Ocular Surface Rehab 22 Healing Treatment—

OCULAR UPDATE 30 My Aching Back!


31 JCRS Highlights 32 Resident Diary 33 Industry News 34 Everything You Always

Wanted to Know About...

36 2021 John Henahan Prize 38 Vox Dox 40 Calendar

Refractory Neurotrophic Keratopathy

As certified by ABC, the EuroTimes average net circulation for the 10 issues distributed between February and December 2019 was 47,863

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Oliver Findl


Thomas Kohnen Chief Medical Editor

José Güell

Progress is impossible without change, and those who cannot change their minds cannot change anything.

Paul Rosen

INTERNATIONAL EDITORIAL BOARD Noel Alpins (Australia), Bekir Aslan (Turkey), Roberto Bellucci (Italy), Hiroko Bissen-Miyajima (Japan), John Chang (China), Béatrice Cochener-Lamard (France), Oliver Findl (Austria), Nino Hirnschall (Austria), Soosan Jacob (India), Vikentia Katsanevaki (Greece), Daniel Kook (Germany), Boris Malyugin (Russia), Marguerite McDonald (USA), Cyres Mehta (India), Sorcha Ní Dhubhghaill (Ireland), Rudy Nuijts (The Netherlands), Leigh Spielberg (The Netherlands), Sathish Srinivasan (UK), Robert Stegmann (South Africa), Ulf Stenevi (Sweden), Marie-José Tassignon (Belgium), Manfred Tetz (Germany), Carlo Enrico Traverso (Italy)

—George Bernard Shaw

nprecedented. We have been hearing this word a lot in recent years. The spread of the coronavirus pandemic with its near-incomprehensible mortality and morbidity; hurricanes, flooding, firestorms, and other extreme weather events around the world; the growing lack of civility in political discourse; mass migrations of desperate populations; the rising baseline temperaOur profession exists ture of our oceans—all within the larger unprecedented. What does this have to medical sphere, do with ophthalmology? which in turn exists Our profession exists within the context of within the larger medithe global community cal sphere, which in turn exists within the context of the global community. We are facing these crises together and need to develop rational and effective responses together. In this issue, our cover story takes a look at the state of ophthalmology in the world. This article discusses the long-overdue resolution from the United Nations on dealing with vision care issues on a global level. The resolution calls for adding eye health targets to the Sustainable Development Goals, the UN’s ambitious roadmap for transitioning to greener, more inclusive economies across the globe by 2030. Closer to home, there are many aspects of our daily clinical practice that can be made more sustainable and less polluting. This could include reducing our dependence on single-use eye drops, phaco tips, tubing, sleeves, and other accessories such as surgical markers. We could also evaluate our current ophthalmic instrument cleaning and sterilisation practices. Industry could play an important role in reducing wasteful packaging. We can learn much from the Aravind Eye Hospital in Pondicherry, India. Surgeons at that institution regularly reuse gowns, gloves, irrigation/aspiration tubing, phaco tips, cannulae, irrigating solution, and medications. They have done this while keeping endophthalmitis rates low. Because of COVID, we have had to rethink how we handle patient flow. This has helped us streamline our operations, from intake to discharge, handling more actions with telemedicine or even a simple phone call rather than having patients come in. It looks like some of these changes will remain after the pandemic recedes. High tech can also play a role. Our cover story highlights the use of remote training—simulators and digital dry labs as a way to extend education opportunities globally. Even before the pandemic, artificial intelligence and telemedicine were already improving screening of diabetic eye disease. Implantable devices that allow medication release over a period of months also appear to be promising alternatives to eye drops for many conditions. Finally, we have a duty to our patients and the larger community to encourage practices that will help turn back the pandemic. We mustn’t shy away from educating patients on the value of vaccination and dispelling any confused ideas they might have picked up from unreliable sources. We can and must do our part to meet these challenges. The urgency is, yes, unprecedented. Oliver Findl MD, FEBO Incoming President of the ESCRS Chief of the Department of Ophthalmology, Hanusch Hospital, and the Vienna Institute for Research in Ocular Surgery (VIROS), Vienna, Austria.


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Sustainable Global Vision Care


UN adds eye care to development goals; remote training helps meet need. Howard Larkin reports

nternational policy development and remote training technology are converging to help eliminate preventable blindness. For the first time, the United Nations General Assembly has affirmed the need for vision care to eradicate poverty and promote worldwide development. Sponsored by Bangladesh, Antigua, and Ireland, and co-sponsored by more than 100 countries, the “Vision for Everyone” resolution was adopted in July by unanimous consent of the organization’s 193 members. The resolution calls for adding eye health targets to the Sustainable Development Goals (SDGs), the UN’s ambitious roadmap for transitioning to greener, more inclusive economies across the globe by 2030. The SDGs are 17 general goals ranging from eliminating poverty and hunger to promoting gender equality and quality education to developing economies and infrastructure in sustainable ways. The new eye care resolution mostly falls under the universal health coverage provisions of SDG 3, ensuring good health and well-being for all while also contributing to all the others. Explicitly adding eye care not only raises its visibility as a global good but encourages support from the many governments and private donors around the world that embrace SDGs in their development and funding strategies, said ESCRS President Rudy MMA Nuijts MD, PhD. ESCRS plans to play a role. “The resolution asks for international financial institutions and donors to provide targeted finances, especially to support

Photo credit: UN Photo/Olivier Chassot | A Nepalese doctor with the African Union-United Nations Hybrid Operation in Darfur (UNAMID) checks a young boy’s eyes, as part of a seven-day, free medical campaign provided by UNAMID to the population of Shangil Tobaya, North Darfur. More than 2,000 individuals, including women and children, received medical treatment from UNAMID’s Nepalese Special Forces, Mongolian Level II hospital personnel and Rwandan protection force and medical personnel.

developing countries, in tackling preventable sight loss. This is a significant milestone, and the ESCRS, not least through its Charitable Committee, is ready to support the aim of making eye care services more widely available [and] an integral part of universal healthcare,” Dr Nuijts said.


Adding two eye health indicators—rate of effective cataract surgical coverage and rate of effective refractive error coverage—to outcomes reported for SDG 3 is especially

important, said Matthew J Burton PhD, FRCOphth, director of the International Centre for Eye Health (ICEH) at the London School of Hygiene & Tropical Medicine, London, UK. “It means that countries will have to measure and report what they are doing in these areas.” This creates an incentive to allocate state resources to eye care, Prof Burton added, who is also co-chair of the Lancet Global Health Commission on Global Eye Care and lead author of its February 2021 report.i

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The two eye health indicators are also important because they address about 80% of avoidable blindness and moderate to severe visual impairment (MSVI), Prof Burton said. According to the Commission report, about 157 million people suffer MSVI due to uncorrected refractive error and about 83 million from cataract. There are a further 17.1 million who are blind from cataract and 3.7 blind from uncorrected refractive error.

BUILDING CAPACITY About 90% of people with vision impairment live in low- to middle-income countries—with many in remote rural areas, Prof Burton said. More research to find where the need is greatest and how to address it in rural areas is critical to development, he added. These solutions need to integrate eye care with general primary care in national health plans and delivery systems. “Eye care has been on the fringe of healthcare, often looked after by NGOs rather than by national health systems. It has tended to be neglected.” Building local capacity and ensuring access for vulnerable populations are major goals for Orbis programmes, according to Doris Macharia MD, senior vice president, Global Programs, Orbis International, London, UK. For example, working with the Rohingya population and local people in Bangladesh, “Our focus is on strengthening the integration of eye care services into the primary healthcare system, improving the capacity of partner hospitals, deployment of mHealth platforms for diagnosis and data management, and establishing emergency referral systems.” Similarly, Orbis has integrated a trachoma elimination programme with the national health system in Ethiopia and integrated eye care services into existing Universal Child Immunization programmes in Zambia. Other programmes are underway in Africa, Latin America, Asia, and the Caribbean. With low- and middle-income countries still reeling from COVID-19, and its damage to eye care and health systems generally, Dr Macharia also welcomes the UN action. “Adding eye care to the SDG framework is a major step forward and affirms the importance of including eye health as part of Universal Health Coverage.”

SIMULATION TRAINING New training practices, including extensive use of simulations and remote learning, are essential to building the necessary capacity to surgically treat cataract, glaucoma, and other causes of blindness in LMICs, according to presenters at the Orbis Symposium at the 39th Congress of the ESCRS in Amsterdam. While factors such as cost and backlogs from the COVID-19 pandemic are significant, patient safety is the most important reason to train using simulations, said John Ferris MB, ChB, FRCOphth, head of the School of Ophthalmology–Severn Deanery,

Photo credit: UN Photo/Stuart Price | An elderly man undergoes an eye examination from a Ugandan ophthalmic clinical officer, serving with the African Union Mission in Somalia (AMISOM). Free medical services are being provided by AMISOM personnel at the Qatar Camp for Internally Displaced Persons (IDPs) in Mogadishu as part of a week-long programme called Tarehe Sita — Kiswahili for “6 February” — the date which commemorates the establishment of the Ugandan People’s Defence Force (UPDF).

and consultant surgeon at Gloucestershire Eye Unit, Cheltenham, UK. “In the twenty-first century, it is frankly unacceptable for any surgeon anywhere in the world to be undertaking a surgical manoeuvre for the first time on an actual patient.” The goal of the simulation is for trainees to develop competence in basic manoeuvres such as instrument handling and suturing skills, Dr Ferris said. Course material is available for many ocular surgical procedures, including trabeculectomy, small-incision manual cataract surgery, and strabismus, through Orbis.ii The process starts with pre-course learning, watching videos, and instructional courses, which can be done online. Then trainees move to develop basic skills, such as cutting a trabecular flap on apples or simulating releasable sutures on plastic foam before moving to model eye simulations. Sustained, deliberate practice on these inexpensive materials between lessons is critical, Dr Ferris added. Equally critical is evaluating skills using the “ophthalmic simulates surgical competency assessment rubric” (OSSCARS) to help trainees advance from novice to competent in each surgical step before going on to treating live patients. Recording simulations and having trainees score their own performance is very helpful, Dr Ferris said. “This scoring tool can easily differentiate between novice and expert surgeons.” Digital dry labs enable one instructor to monitor as many as eight trainees practicing at once, Dr Ferris said. Such labs can be conducted remotely, allowing one expert to help trainees in many parts of the world. With one camera showing the surgical field and another showing the trainees’ hands, Dr Ferris can provide real-time coaching on hand positioning and suturing techniques remotely. Similar remote sessions have been conducted for everything from capsulorhexis and small-incision cataract surgery to strabismus muscle repair, and many can

be seen online.iii It can even be conducted with a cell phone camera and a homemade model eye, Dr Ferris said. Studies show simulation improves patient safety and outcomes, he added. One randomised trial compared 25 trainees who received simulation training early in their study with 25 who received conventional training with simulation added after one year. The early simulation group improved their skills three-fold over the conventional group in the first three months of training and had higher confidence scores. In their first year operating on patients, the early simulation group had 2.5 times more cataract cases, with complication rates 72% lower than the conventional group and a posterior capsule tear rate of 7.4% versus 26.2% in the control group.iv Results were similar in a study of glaucoma surgical skills.v Remote mentoring can help democratise surgical training, Dr Ferris said. “It doesn’t have to be high tech nor expensive. Trainees can teach themselves the basics of many surgical techniques.” Rudy Nuijts Matthew Burton matthew.burton@lshtm. Doris Macharia via Anna Kharbanda John Ferris i ii iii iv Dean WH et al. JAMA Ophthalmol 2021; 139(1) 9–15. v Dean WH et al. BJO published online 25 January 2021.

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Best of the Best in Amsterdam Advances in cataract surgery, keratoconus treatment, and preoperative assessment for advanced IOLs highlighted at final session of ESCRS Congress. Roibeárd O’hÉineacháin reports from the 39th Congress of the ESCRS in Amsterdam


resentations concerning advanced fluidics for phacoemulsification, customised corneal cross-linking (CXL), and innovations in preoperative assessment for patients considering multifocal and extended depth of focus (EDOF) intraocular lenses were among the “best of the best”, according to a panel of experts at the meeting’s final session. Professor Oliver Findl MD, Austria, and Professor Boris Malyugin MD, Russia, were the session chairs. The panel included Professor Ehud Assia MD, Israel; Professor Sri Ganesh, India; Professor Thomas Kohnen MD, PhD, Germany; Professor Rudy Nuijts, the Netherlands; and Professor Filomena Ribeiro MD, Portugal.

ADVANCES IN FLUIDICS Starting with the notable videos, Prof Malyugin reviewed the 2021 Michael Blumenthal prize winner—Hisaharu Suzuki, Japan, for “Evolution of fluid system in cataract surgery”. The presentation described the use of a pressure sensor within a phaco handpiece with active pressurised fluidics to reduce the oscillations in anterior chamber depth (ACD) during phacoemulsification. EUROTIMES | DECEMBER 2021/JANUARY 2022 Dec-Jan_EuroTimes.indd 6

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The video showed how, in a laboratory study using pigs’ eyes, the variation in the ACD was only 10% in eyes with the pressure sensor handpiece, 20% with a pressurised peristaltic pump and a conventional handpiece, 50% with a non-pressurised peristaltic pump and a conventional phaco handpiece, and 80% with a pressurised venturi pump and a conventional phaco handpiece. Prof Nuijts noted better control of the pressure fluctuations with the active infusion and the pressure sensor could be particularly beneficial in glaucoma surgery. Prof Malyugin suggested it could also prevent anterior vitreous detachment by reducing the flow of aqueous through the zonule.

CATARACT SURGERY DURING THE PANDEMIC Another winning entry the panel highlighted was Lucio Buratto’s “Safety and prevention and protection in cataract surgery during the COVID-19 pandemic”, which took the first prize in the new “Pandemic” category. It outlined the many new safety measures adopted to prevent transmission of COVID-19 in the cataract clinic, such as daily PCR tests of surgeons and their staff and the use of masks by patients during surgery. In his comments on the video, Prof Assia emphasised the most important precaution now is vaccination for the surgeon, staff, and patients. He added the danger of infection from aerosols during surgery may have been exaggerated in the early months of the pandemic. He pointed out that, as yet, there have been no reports of surgeons or their staff becoming infected with the COVID-19 virus from performing cataract surgery. Prof Kohnen noted continuing with some of the precautions adopted for safety during the pandemic runs contrary to the current trend towards the reduced one-time use of plastics. On the other hand, he noted the attention which the pandemic has brought to potential infection in a clinical setting will be of benefit once the pandemic is over.

CUSTOMISED CXL Another video highlighted at the session was “Topography guided removal of the epithelium in keratoconus (TREK)” by Sneha Gupta, India. The presentation describes a technique of reshaping the keratoconic cornea by CXL. The video showed that when patients underwent CXL in this way, they had improvements in their visual acuity. “I think this is great. We have to get to the point where we can improve vision, and we can only do this with a topography-guided procedure. Normally, when we do CXL now, we crosslink areas of the cornea where it is not actually necessary,” Prof Kohnen said. Many presentations at the ESCRS Congress focused on the EDOF, mono-EDOF, and trifocal IOLs that have recently entered the market—particularly notable among these was the Binkhorst lecture delivered by Gerd Auffarth MD, PhD, Germany. In his lecture, titled “There is no free lunch”, he explained the greater depth of field a lens provides, the greater too will be the amount of dysphotopsia a patient will experience. Similarly, the greater the amount of chromatic aberration a lens has, the worse the polychromatic modulation transfer metrics. Conversely chromatic aberration correction reduces an IOL’s depth of focus. The theme was expanded on further in the Main Symposium on Advanced IOLs. Joaquin Fernandez MD, PhD described several devices such as the SimVis and the VAO spatial light modulator that provide an estimation of a patient’s range of focus with a given IOL, based on preoperative simulations. In another presentation, Arthur Cummings MD, Ireland, described the use of Vivior monitor, a spectacle-mounted device that measures a prospective patient’s daily visual requirements, enabling choice of an IOL most suited to their needs. Prof Assia noted multifocal IOLs and EDOF IOLs will always remain, and only a truly accommodating IOL will eliminate those that compromise presbyopia treatment. Prof Kohnen countered that the increased understanding of optics, as illustrated in Prof Auffarth’s lecture, will allow accommodating IOL optimisation once they become available. EUROTIMES | DECEMBER 2021/JANUARY 2022 Dec-Jan_EuroTimes.indd 7

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Two Centuries of Progress ESCRS Heritage Lecture surveys 200 years of refractive surgery. Dermot McGrath reports from the 39th Congress of the ESCRS in Amsterdam


he history of refractive surgery over the past two centuries is a stop-start tale of innovation, inspiration, and the occasional sprinkling of good fortune, said Patrick I Condon MD in the annual ESCRS Heritage Lecture. In a broad survey of 200 years of innovation and progress in refractive surgery, Dr Condon took his audience on a journey beginning with the first surgical correction of astigmatism in the late nineteenth century through to the modern era of LASIK and femtosecond laser surgery. Going back to the roots of refractive surgery, Dr Condon said the oldest refractive procedure we know of is the surgical correction of astigmatism with two individual accounts in the mid1800s in which a large amount of astigmatism was corrected by a single Graefe knife incision. Toward the end of that century, the Dutch ophthalmologist Leendert Jan Lans described his meticulous experimental animal studies that produced the basic principles for astigmatism correction. “This is the basis of the corneal coupling effect and the basic principle for the treatment of astigmatism that we still use to this day,” Dr Condon said. Dr Condon related how myopia reversal was initially discovered by Saito in Japan in 1936 when he found that flattening the cornea with keratotomies in a young man with a severe corneal injury led to a reduction in his myopia. A further refinement came in 1974 when Fyodorov in Russia developed incisional keratotomy for removing corneal foreign bodies, which involved 16 radial corneal incisions using a metal blade. The technique’s popularity was to prove short-lived, however. George Waring MD was the chief investigator in a prospective evaluation of radial keratotomy (RK) in the United States that ran from 1982 to 1993, which showed a hyperopic shift of one dioptre or more. This proved catastrophic for patients approaching presbyopia and resulted in RK abandonment. José Ignacio Barraquer’s introduction of the microkeratome in 1964 began the era of corneal lamellar refractive surgery. The microkeratome was used to remove a corneal disc at a depth of 300 microns, which was then frozen and transferred to a cryolathe which removed 110 microns from the posterior surface and involved the refractive element of the surgery. A further enhancement came with Jörg Krumeich’s nonfreeze technique using the guided trephine system to remove the corneal flap, followed by combined research by Barraquer, Krumeich, and Casimir Swinger to perform the refractive cut using the same system. “This enabled us to perform the entire operation in a non-freeze technique using just one microkeratome,” Dr Condon said. He also highlighted technological developments in the 1970s

that ultimately led to the introduction of excimer laser technology into ophthalmology in the late 1980s—such as Lucio Buratto combining the microkeratome and the excimer laser to reshape the cornea. Around the same time, Greek surgeon Ioannis Pallikaris elaborated the concept of the nasal corneal hinge and in situ ablation. This made for easier cap repositioning, thus began the era of laser-assisted in situ keratomileusis (LASIK). In recent years, the femtosecond laser has increasingly supplanted the excimer laser in ophthalmology for refractive purposes, Dr Condon said, who noted how the technology is being used not only for refractive surgery but also therapeutically for keratoconus and corneal transplant surgery. Dr Condon rounded off his lecture with a round-up of the major advances in IOL technology over recent decades, including angle-supported anterior chamber IOLs and posterior chamber IOLs. Angle-supported anterior chamber IOLs fell out of favour due to issues with long-term endothelial cell loss and other complications, while encountered problems of subluxation, pupil block, glaucoma, and lens opacities, among others. “I think the biggest problem of all was the sizing of posterior IOLs within the eye to prevent them [from] moving. For this, the white-to-white measurements we used for anterior chamber lenses [were] not accurate enough and [were] replaced by sulcusto-sulcus measurements with ultrasound and laser scanning ophthalmoscopy,” Dr Condon said. Iris-fixated anterior chamber IOLs represented an “incredible advance” in lens technology, Dr Condon said, beginning with Jan Worst’s lobster-claw lens in 1979 through to designs of the Artisan IOL (Ophtec) for hyperopia and astigmatism and the Verisyse and foldable Artiflex lens in 2003. “The beauty of these lenses was there was very little endothelial cell loss with them, with one study showing there was a loss of between 0.7% and 8.8% over a 10-year period, which is a pretty good record,” he concluded. Patrick Condon MCh, FRCS, FRCOphth, lives in Waterford, Ireland. During his long career, Dr Condon acquired Fellowships from the Royal Colleges of Surgeons of Ireland, England, and Scotland and a Mastership in Surgery (National University of Ireland). He is currently a life fellow of the Royal Society of Medicine (London), an emeritus member of the International Intraocular Implant Club, and an active member of the Royal Academy of Medicine in Ireland and the Irish College of Ophthalmologists.

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No Free Lunch in Optics Binkhorst Lecture focuses on compromises and challenges in optics. Dermot McGrath reports from the 39th Congress of the ESCRS in Amsterdam


very intraocular lens designed to correct presbyopia, irrespective of its design properties and material, involves a trade-off in visual performance once implanted in the eye, said Gerd Auffarth MD, FEBO, during the annual Binkhorst Medal Lecture. In a wide-ranging lecture focused on the inherent compromises in multifocal and presbyopic-correcting IOLs, Professor Auffarth stressed the importance of neuroadaptation and brain function in the performance of any implanted lens, adding it was important to appreciate how intraocular lenses perform under real-life conditions once inside the eye. “If an intraocular lens company tells you that its new lens is perfect and that everything is great, we should be immediately on our guard as the reality is a lot more complex than that—there really is no such thing as a free lunch in IOL optics,” he said. Turning to the question of optical performance, Prof Auffarth noted presbyopia correction remains one of the greatest challenges in ophthalmology. He said any attempt to correct presbyopia, a natural but complex process of physiological insufficiency of accommodation associated with eye ageing, needs to take due account of three interrelated concepts: visual quality, depth of field, and dysphotopsia.

“Once again we are back to the reality of there being no free lunch in optics.” “If we want to increase the depth of field, we will reduce visual quality and increase dysphotopsia. We have to play with the aberrations of the eye and other factors to maximise visual quality and balance out a certain amount of depth of focus in order to achieve our goal,” he said. Dysphotopsias include a wide range of visual symptoms such as halos, glare, and starbursts, but not all of them are necessarily caused by the implanted IOL, he noted. “The optics of an intraocular lens are really the reason for the halos. However, glare and starbursts can also be introduced by refractive error, defocus issues, ocular surface diseases, or other opacification in the optical pathway,” he said. Chromatic aberration is another important influencing factor in IOL performance. It occurs when light rays pass through an optical media at different points according to their wavelength. Longitudinal chromatic aberration (LCA) causes shorter wavelengths to focus in front of longer wavelengths resulting in a difference of focus.

The cornea, the crystalline lens, and the implanted IOL can all contribute to chromatic aberration. The type of IOL material used also plays a role in the extent of the chromatic aberration, Prof Auffarth explained. “IOL material affects chromatic aberration and has a direct impact on it. For instance, hydrophilic IOLs have a lower LCA than hydrophobic lenses. While a refractive optic produces a given chromatic aberration, with a diffractive optic, the chromatic aberration can be manipulated and reversed to reduce the dispersion.” While this sounds beneficial in principle, the reality is LCA correction actually has a negative impact on the depth of focus in pseudophakic eyes, Prof Auffarth concluded. “Once again we are back to the reality of there being no free lunch in optics,” he said. Prof Auffarth said the variety of lenses on the market, using different optical principles, and the terminology used to describe them—enhanced monofocal, extended depth of focus (EDOF), extended range of vision (ERV), and trifocal lenses—was understandably confusing for many ophthalmologists. “These categories are overlapping and interacting, and it is really difficult sometimes to match the patient profile with the lens category being proposed,” he said. He noted that as a general rule, the further one moves away from monofocal designs towards EDOF-ERV and then trifocal lenses, the greater the propensity for dysphotopsias to occur. One compelling solution to try to maximise the specific advantages of different lenses is by adopting a mix-and-match approach Prof Auffarth calls “binocular trifocal”. “We can for instance put a bifocal lens in one eye for distance and near vision, and an EDOF lens in the other eye for distance and intermediate vision. Or we can try blended vision with an EDOF lens in both eyes but use different power additions to target different distance ranges,” Prof Auffarth said. Combining different lens types in an individualised manner can achieve better binocular visual outcomes with enhanced depth of focus and reduced incidence of dysphotopsias, he concluded.

Professor Auffarth is Head of the International Vision Correction Centre (IVCRC) and Director of the David J Apple International Laboratory for Ocular Pathology in Heidelberg, Germany.

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Light-Adjustable Lens Yields Positive Outcomes Cheryl Guttman Krader reports from ASCRS in Las Vegas, USA


eal-world outcomes with the Light-Adjustable Lens (LAL, RxSight) in clinical practice appear to be as good if not better than those seen in the US FDA clinical trial that led to its approval, Joshua K Duncan DO reported. Dr Duncan presented findings from a series of 600+ cases of LAL implantation. In addition, he discussed considerations for surgical planning and LAL removal, highlighted the benefit of the updated LAL featuring a new UV protective layer (ActivShield), and described a novel, interesting off-label case involving intrascleral fixation of the LAL using the Yamane technique. “We are all aware of the current challenges faced with achieving the refractive target in cataract surgery. Preoperatively we rely on accurate biometry, topography, and OCT imaging. Intraoperatively we use tools such as the femtosecond laser, aberrometry, and alignment aids. Still, we fall short and often resort to additional surgery with LASIK enhancement or IOL exchange,” Dr Duncan said. “In our practice, we have been very pleased with the refractive and visual outcomes using the LAL, and it has been a nice driver for our premium channel.” Dr Duncan added the LAL still has limitations because it is a monofocal lens. However, surgeons can achieve excellent visual acuity for their patients at all distances when implanting the LAL with a monovision approach. In a small study involving 25 patients, the functional results with LAL monovision rivaled those achieved with a trifocal IOL, while dysphotopsia and contrast sensitivity with the LAL were similar to results associated with a monofocal lens, Dr Duncan said.

PRACTICE OUTCOMES The 600+ cases from his practice series represented procedures performed by four surgeons. More than half of the eyes had a history of LASIK or radial keratotomy (RK). After LAL lock-in, residual spherical equivalent (SEQ) was ≤0.5 D in 97% of eyes and averaged 0.12 D in the total population and 0.15 D in the post-refractive surgery subgroup. Distance UCVA was 20/25 or better in 92% of all eyes and 91% of those with prior refractive surgery. UCVA of 20/20 or better was achieved by 74% of eyes, of which a significant proportion saw 20/15 or better. “The LAL is my ‘go-to’ lens for anyone with a history of LASIK, PRK, or RK,” Dr Duncan said. He added that his refractive targets for the dominant/nondominant eye are plano and -1.00 D for patients with a history of monovision and plano/-0.50 D for those without prior monovision. “These targets are a starting place and are adjustable,” Dr Duncan said.

He reiterated an often-mentioned tip to miss on the hyperopic side in the nondominant eye to increase depth of focus/ spherical aberration. “Initially, we aimed to miss the hyperopic side in both eyes, but patients were not happy with the hyperopia during the time they were waiting to achieve refractive stability. That is not helpful for building a refractive practice, and I think patients do not need so much depth of focus in their dominant eye.” The new LAL that incorporates a UV protective layer in the anterior portion has been helpful for patient satisfaction. According to RxSight, the layer is meant to provide redundant UV blocking along with UV glasses before lock-in. Dr Duncan believes it eliminates the need for patients to wear UV glasses around the clock. “I still ask patients to wear the glasses if they are outside during the day because Phoenix is very sunny. Before the new UV protective technology, however, being tied to UV glasses was a significant nuisance for patients. Now, it is easier to wait for better refractive stability, which in post-RK patients in particular can take some time.” Dr Duncan estimated that in total, he and his practice colleagues removed the LAL because of refractive error in only six to eight eyes. The patients involved in these cases all received the original LAL and either experienced a late refractive shift, perhaps because the adjustment and lock-in were performed prior to achieving refractive stability, or were noncompliant with wearing the UV glasses before lock-in. If removal is necessary, Dr Duncan said surgeons should be aware the LAL is somewhat brittle. “Be sure to use a lot of viscoelastic. Also, we used special IOL cutters that are a little finer and gentler,” he advised. The case where he used the LAL with the Yamane technique involved a referred patient who was left aphakic after undergoing complicated cataract surgery with tears of the anterior and posterior capsule, iris trauma, and vitreous loss. “I felt the patient was a great candidate for the LAL because his fellow eye was 20/20 uncorrected, and he wound up with 20/15 vision in the LAL eye after lock-in,” Dr Duncan said.

Joshua K Duncan DO is in private practice in Phoenix, Arizona, USA.

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Game Changer for Presbyopia? Optimised pilocarpine drop shows promise for presbyopia. Cheryl Guttman Krader reports from ASCRS 2021 in Las Vegas, USA


GN-190584, a topical optimised formulation of pilocarpine HCl 1.25%, is a safe, well-tolerated, and effective treatment for presbyopia, suggest the results of GEMINI 1, a phase 3 vehicle-controlled study. As reported in a series of presentations at the conference, the findings showed AGN-190584 was associated with statistically significant and clinically meaningful improvements in near and intermediate vision in addition to high patient satisfaction. Moreover, it did not compromise distance vision. “Marketing approval of AGN-190584 will be a milestone event, and its availability will be a big-time game changer for our patients,” George O Waring IV, MD said. The GEMINI 1 study was a multicentre, double-masked trial that randomised 323 patients aged 40 to 55 years in a one-to-one ratio to AGN-190584 or vehicle administered once daily, bilaterally, for 30 days. “Patients with severe dry eye were excluded, but those with a history of previous LASIK or PRK were encouraged to participate. Remarkably, 99% of patients in the AGN-190584 group and 96% of controls completed the study that involved marathonlength study visits,” William C Christie MD reported.

EFFICACY DATA The GEMINI 1 study met its primary endpoint. The percentage of participants with at least three lines of improvement or better in mesopic distance-corrected near visual acuity (DCNVA) at three hours post-administration on day 30 was significantly greater with AGN-190584 treatment compared to vehicle. A post-hoc analysis also showed no participants with less than a three-line improvement reported more than a five-letter loss in mesopic, corrected distance visual acuity (CDVA) on day 30, hour three. AGN-190584 also demonstrated statistical superiority to vehicle for the key secondary endpoint analysing the percentage of participants with at least three lines or better improvement in mesopic DCNVA at six hours post dosing. Data for other efficacy endpoints showed statistically significant differences favouring AGN-190584 versus vehicle for increasing the percentage of participants achieving 20/40 or better in DCNVA. Researchers observed a significant difference in the two-line or greater gain in mesopic, high-contrast binocular DCNVA. Significant treatment benefits were also observed for improvements in measures of distance-corrected intermediate acuity (DCIVA).

PUPIL MEASUREMENTS Pupil measurement data showed the onset and duration of improvement in mesopic DCNVA corresponded with the onset and duration of change in pupil size. Change in pupil diameter mirrored improvement in DCNVA with onset at 15 minutes. Pupil diameter returned to baseline within 24 hours after the last drop.

The pupillary response to light after AGN-190584 treatment was maintained under mesopic and photopic conditions, and its response to AGN-190584 remained consistent from day 1 to day 30, David C Wirta MD reported. “The latter finding is important for showing there was no tachyphylaxis to AGN-190584,” he said.

PATIENT-REPORTED OUTCOMES Questionnaires used to collect patient-reported outcomes included the Near Vision Presbyopia Task Questionnaire (NVPTQ) based on reading a book, newspaper, menu, and nutrition label. GEMINI 1 met the prespecified secondary endpoints evaluating mean change from baseline in mesopic NVPTQ performance and satisfaction at day 30, hour three. Additional analyses showed AGN-190584 significantly improved photopic NVPTQ performance and patient satisfaction. Dr Wirta presented results from the Presbyopia Impact and Coping Questionnaire that showed AGN-190584 was associated with statistically significant reductions in presbyopia impact and frequency of compensatory coping behaviours, such as squinting or changing font size, compared to the vehicle group. Results from the Presbyopia Patient Satisfaction Questionnaire showed that compared to controls, the AGN190584 patients were significantly more satisfied with aspects of their treatment.

SAFETY On average, “Loss of distance vision was not observed. In fact, there was a slight improvement in the mean distance vision in the AGN-190584 group relative to the control group at many of the timepoints during the study,” said Dr Waring, who attributed the finding to the optical effect of a small aperture. Headache was the most common adverse event in both the AGN-190584 (14.1%) and control (9.4%) groups. Dr Waring observed patients were prompted to report headache because it is a potential concern with ophthalmic pilocarpine. “There were no severe headaches or discontinuations for headache in the AGN-190584 group. Headaches were mostly mild, transient, and did not require treatment,” he reported. George O Waring IV, MD, FACS is the founder and Medical Director of the Waring Vision Institute in Mt. Pleasant, South Carolina, USA. William C Christie MD practices in Cranberry Township, Pennsylvania, USA. David C Wirta MD practices in Newport Beach, California, USA. EUROTIMES | DECEMBER 2021/JANUARY 2022

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Enhancements After Refractive Surgery Rates trending downward, but some determining factors remain under surgeon control. Cheryl Guttman Krader reports from the 39th Congress of the ESCRS in Amsterdam


review of the published literature shows that residual refractive error and poor optical quality are the main reasons for retreatments after corneal and lens-based refractive surgeries. Encouragingly, data also show that outcomes and patient satisfaction after the primary procedure have improved over time, reported Thomas Kohnen MD, PhD. Recognising however, that the risk of residual refractive error or poor optical quality is affected by a variety of preoperative, intraoperative, and postoperative factors, he counselled his colleagues to focus on prevention and be judicious when considering retreatment. “Avoid residual refractive error and optical disturbances by performing good surgery and for the correct indications. Second, only do retreatment for these issues if the patient is bothered and not because you think the outcome is not perfect. We have to consider our patients’ satisfaction, not just our own,” Prof Kohnen advised. Prof Kohnen discussed his centre’s experience and reviewed selected studies reporting outcomes for laser corneal refractive procedures, phakic IOL implantation, and refractive lens exchange. While the incidence of retreatment after refractive surgery has changed over time because of the ongoing procedure evolution, he concluded the overall incidence ranges from 1% to 5% and depends on the procedure and the refractive correction magnitude. Published data demonstrate how patient satisfaction after LASIK has increased over time. A 2009 article reviewing the world literature reported that 95% of patients were happy with their outcomes. In 2016, a paper that included data from 97 articles published between 2008 and 2015 encompassing approximately 68,000 eyes reported 99% of patients were satisfied, and

the rate of loss of fewer than two lines of CDVA was only 0.61%. Another paper published in 2020 reviewing a consecutive series of approximately 70,000 eyes treated with LASIK or PRK reported only 0.37% of eyes lost fewer than two lines of CDVA. Literature reports on phakic IOL procedures also show outcomes have improved over time in parallel with advances in technology. For example, a study of eyes implanted with an ICL (Staar Surgical) showed a better functional outcome using the newer iteration with the central hole versus the model without the hole. Prof Kohnen referenced results from a study his group submitted for publication that showed excellent refractive predictability was achieved in eyes implanted with the central hole model (ICL V4c). “The need for retreatment after ICL implantation will decrease significantly with the availability of the toric version that allows us to correct astigmatism,” he predicted. Two papers from his group analysed outcomes in patients undergoing refractive lens exchange with an implant of trifocal or quadrifocal presbyopia-correcting IOLs. Both papers showed high predictability of the refractive result and attainment of an outcome very close to emmetropia, which is the target in these cases, Dr Kohnen said. “Of course, these results were achieved in clinical studies, and we have to look at real-world outcomes,” he cautioned. Thomas Kohnen MD, PhD is Professor and Chair, Department of Ophthalmology, Goethe University, Frankfurt am Main, Germany.

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Cataract Surgery Post-Keratoplasty Knowledge of challenges and risks guides development of a clear plan. Cheryl Guttman Krader reports from the Virtual 12th EuCornea Congress


erforming cataract surgery in eyes with a corneal graft presents a variety of special considerations. Bruce Allan MD offered several practical insights to help guide surgical planning and technique in these cases. Preoperatively, knowing the risk of graft failure will not alter cataract surgery decision-making, but it is useful information for patient counselling and setting expectations about the possibility of needing further transplant surgery, Dr Allan said. “Failure becomes more likely when the endothelial cell count falls to below 800 cells/mm2, it becomes almost inevitable if the endothelial cell count is less than 500 cells/mm2, and it is certain to occur if the cornea is still oedematous at one month after cataract surgery,” he noted. For IOL decisions, Dr Allan said the general rule is to keep the choice simple. In particular, he advised against implanting either a multifocal IOL or toric IOL in a post-keratoplasty patient who is dependent on a rigid gas permeable contact lens to neutralise irregular astigmatism. In addition, he said he would be cautious about using a toric lens in eyes that are post-deep anterior lamellar keratoplasty or penetrating keratoplasty because the keratometry is often unstable in those cases.

“Don’t be afraid and don’t equivocate. The rule is that if you think about putting in a suture, you should probably do it.” For management of irregular astigmatism, Dr Allan suggested the possibility of performing transepithelial PRK with wavefront or topography guidance before cataract surgery if the irregularity is moderate. If the irregularity is beyond the surface ablation’s treatable range, surgery will be needed to achieve gross shape correction before using the transepithelial PRK as a finetuning intervention. As a third step in what he termed a “1-2-3” approach, an implanted IOL can correct lower-order aberrations.

“It is a well-disseminated tip that dropping dispersive viscoelastic on the cornea instead of water really helps the view,” he said. Sealing the incision sites is another unique consideration in post-keratoplasty eyes—particularly if ectasia was the indication for the grafting procedure because late peripheral corneal thinning is likely in such cases. “Entry sites made through an area of thin cornea will not seal and must be avoided. It is very important to inspect the entire corneal periphery preoperatively and make a note in your surgical plan of where you will put the entry site.” While he observed that a scleral pocket incision is a useful alternative to a clear corneal incision in eyes with peripheral corneal thinning, Dr Allan noted that in the latter situation, surgeons might anticipate a need for incision suturing. “Don’t be afraid and don’t equivocate. The rule is that if you think about putting in a suture, you should probably do it,” he said.

INTRAOPERATIVE TIPS Most surgeons are probably routinely using a dispersive viscoelastic. But Dr Allan reinforced the value of this material for protecting the endothelium in post-transplant cases using an OCT image from a post-EK eye that showed colloidal gold-labelled viscoelastic adhering to the endothelium, even after extensive irrigation. Dr Allan added dispersive viscoelastic plays a dual role as an aid for enhancing visualisation.

Bruce D Allan MD is a Consultant Ophthalmic Surgeon at Moorfields Eye Hospital, London, UK.

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Keratoconus and Cross-linking Seeking consensus on disease progression in keratoconus. Dermot McGrath reports from the 39th Congress of the ESCRS in Amsterdam


tighter definition of “progressive keratoconus” is needed to allow clinicians to better plan treatment strategies for affected patients and facilitate the metaanalysis of data, Ingemar Gustafsson MD, PhD told delegates at this year’s hybrid conference. “It is difficult to perform a meta-analysis if we do not know how to define progressive keratoconus. This has also been suggested by the Cochrane Institute in a study in 2015 that stated the efficacy of corneal cross-linking in halting disease progression is very low, in part due to how we diagnose progressive disease. This lack of consensus could reduce the speed at which evidencebased protocols are implemented in clinical practice,” he said. The current absence of consensus is not purely a theoretical issue and can have a very real impact on everyday clinical practice, Dr Gustafsson explained. For instance, the lack of robust evidence-based results for corneal cross-linking (CXL) appears to have contributed to the late approval of CXL for the treatment of keratoconus in the United States. “The Food and Drug Administration (FDA) approved corneal cross-linking in 2016, but this decision appears to be based less on hard data and more on a lack of treatment options,” he said. Keratoconus progression is usually determined by comparing the results of corneal tomographic measurements on different occasions. However, one reason it is difficult to define progression in terms of changes in magnitude—for example, an increase of Kmax of 1.0 D—is the incongruences in results between scientific investigations, Dr Gustafsson pointed out. “We believe this is due to the association between measurement error and disease severity. We have demonstrated this in a published study last year that showed there is a five-times difference in the repeatability between the mildest and the more advanced keratoconus,” he told EuroTimes. Another issue is almost all research on repeatability is performed intra-day (within the same day), while progression is defined over time (between clinical visits). “This is rarely considered,” Dr Gustafsson explained. “We performed an inter-day assessment (i.e., on different days) and concluded it makes quite a difference if we compare one measurement against another single measurement or if we compare a mean of replicates against another mean of replicates. This needs to be accounted for. We also suggest limits at which we can detect progression for patients with stage 1 and 2 keratoconus as defined on the Amsler-Krumeich classification system.” Dr Gustafsson’s studies also suggest the Belin ABCD keratoconus Progression Display—integrated into the standard Pentacam software—appears to have the same stratification-limit need at which progression is detected for the A (anterior) and C (minimal corneal thickness) parameters.

Photo credit Tove Smeds

“With the exception of mild keratoconus, the ABCD Progression Display could overdiagnose keratoconus as progressive, at least according to our data,” he said. In the future, Dr Gustafsson invited colleagues to carry out their own investigations using the same methodology. “If our research is reproduced, then perhaps we could at least find limits on which we all can agree. Ultimately, a consensus on which parameters should be used may be less important than understanding the repeatability and the dynamics of the parameters used and designing the investigation accordingly,” he concluded.

Ingemar Gustafsson MD, PhD, conducts clinical research at Lund University in Sweden.

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Unregulated Anterior Segment Devices Show Their True Colours Cheryl Guttman Krader reports from ASCRS 2021 in Las Vegas, USA.

Before and after photographs of a patient with a scarred cornea who underwent keratopigmentation. Courtesy Dr Ronal Perino.


ight-threatening complications, including blindness, are being reported with unregulated anterior segment devices designed to change the cosmetic appearance of healthy eyes. The moral of the story, therefore, is simple and clear— “Do not insert unregulated devices in or around the eye,” said Sonal S Tuli MD, MEd. Dr Tuli reviewed complications associated with cosmetic iris implants, eye jewellery, eyeball tattooing, keratopigmentation, and coloured cosmetic contact lenses. She differentiated the cosmetic iris implants from the devices approved by the US Food and Drug Administration and other regulatory agencies for patients with aniridia. Unlike the latter devices put in the capsular bag after cataract removal, the cosmetic iris implants are placed in the anterior chamber over the iris to change iris colour in persons who otherwise have healthy eyes. The cosmetic iris implants have irregularities on their posterior surface and small prongs that insert into the anterior chamber angle. While these design features presumably serve to help maintain positional stability of the device, they cause iris and trabecular meshwork damage from chafing that can result in the development of the uveitis-glaucoma-hyphaema (UGH) syndrome.

Other complications associated with these devices include cataract, cystoid macular oedema, corneal oedema, corneal neovascularisation, and keratic precipitates. Even after undergoing device explantation, patients have suffered permanent visual loss and persistent severe glaucoma requiring surgical management, Dr Tuli said. Eye jewellery inserted as an adornment under the conjunctiva has also come into vogue in recent years. Because these articles are typically platinum, which is inert, they do not tend to cause inflammation.

“Do not insert unregulated devices in or around the eye.” “Thus far, no significant complications have been reported with the use of eye jewellery. Nevertheless, the potential for problems remains due to the theoretic risks for jewellery migration, infection, inflammation, and perforation,” Dr Tuli said. Eyeball tattooing, a procedure done for cosmetic reasons in which dye is injected under the conjunctiva, has also been associated with serious complications.

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OPHTEC | Cataract Surgery

“Some individuals undergo eyeball tattooing because they want to permanently change their eye colour, whereas others (erroneously) expect it is a way to temporarily change eye colour,” Dr Tuli explained. The dye used for eyeball tattooing is often the same material used for skin tattooing, which is highly inflammatory in the eye. Furthermore, the tattooing is usually done without microscopic visualisation, proper surgical instruments, or sterile conditions. Therefore, the risks of infection, inflammation with granuloma development, and globe penetration are high. Highlighting the complications associated with eyeball tattooing, Dr Tuli presented a case reported in the literature in which the dye migrated posteriorly, leading to posterior scleritis and loss of vision. Although treatment with tarsorrhaphy, high-dose corticosteroids, and antibiotics resulted in improvement, the patient was left with a green eye and green eyelids. Keratopigmentation is a technique that has been used for centuries to mask disfiguring corneal scars. Today, cornea specialists still do it to improve the cosmetic appearance of blind eyes or as a therapeutic intervention to address functional visual symptoms such as glare from large iris defects. However, untrained persons also perform it, using unregulated materials as a purely cosmetic procedure to change eye colour in healthy eyes. Historically, keratopigmentation compounds were composed of India ink, soot, or platinum chloride, but recent procedures use micronized mineral pigments with lower inflammatory potential. The pigments may be placed using a needle tattooing technique or in a femtosecond laser-assisted procedure where the laser creates channels in the cornea into which the specialist injects pigments. Despite the better safety profile of the current generation of mineral pigments used for keratopigmentation, significant complications have been reported, including corneal pannus, inflammation, and pigment migration to other parts of the eye. “In some cases, the inflammation has been severe enough that it resulted in cornea melting,” Dr Tuli said. Depending on the pigment material used, interaction with MRI is also a potential concern, as demonstrated by the case of a patient who had undergone keratopigmentation and developed severe eye pain during head MRI. “Even though micronised mineral pigments are thought to be somewhat ‘MRI compatible’, I warn patients undergoing keratopigmentation for a medical indication about the potential for an MRI interaction, even if the area of tattooing is very small,” Dr Tuli said.


COSMETIC CONTACTS NOT LOOKING GOOD Cosmetic contact lenses are often used by people dressing up in costume for Halloween and are frequently bought online or at a hair or cosmetic salon. Often unsterile, sometimes previously worn by multiple people, and coming without instructions on cleaning, these non-prescription contact lenses are notorious for causing ocular complications such as corneal abrasions and ulcers, which can result in permanent loss of vision.

Sonal S Tuli MD, MEd is Professor and Chair, Department of Ophthalmology, University of Florida College of Medicine, Gainesville, Florida, USA.

PRESBYOPIA & ASTIGMATISM CORRECTION REINVENTED 1) Broader Toric meridian designed to be more tolerant of misalignment. White paper: Evaluation of a new toric IOL optic by means of intraoperative wavefront aberrometry (ORA system): the effect of IOL misalignment on cylinder reduction. By Erik L. Mertens, MD Medipolis Eye Center, Antwerp, Belgium 2) The misalignment tolerance and the use of segments instead of concentric rings reduces photic phenomena, helping patients to adapt more naturally to their new vision. 3) The central zone of 1.4 mm in diameter is larger than most available mIOLs and allows a wider tolerance so that the visual axis passes through the wider central segment avoiding visual disturbances. 4) In cases of tilt or misalignment, the patient can still benefit from good near and far vision, as the segmented zones allow a balanced far/near light distribution in a steady optical platform.

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Dry Eye Therapies Corneal / Conjunctival staining (Van Bijsterveld)

Treatments targeting specific causes with new delivery mechanisms on the horizon. Howard Larkin reports from ARVO 2021 in Las Vegas, USA Baseline 4 weeks follow up

14 12 10



8 6

5.83 p 0.99 4.11


p 0.0015

2 0


Sham Group

Figure Legend 1: Corneal/conjunctival staining score (van Bijsterveld) comparing sham versus sirolimus injection.


esearchers introduced a range of dry eye treatments with novel targets and delivery mechanisms now entering clinical trials at the 2021 ARVO meeting.


AZR-MD-001 (Azura Ophthalmics) is an ointment containing selenium sulphide applied twice weekly that specifically addresses meibomian gland dysfunction (MGD), which is often the root cause of dry eye symptoms, said Laura Downie, BOptom, PhD, Associate Professor, and Dame Kate Campbell, Fellow, at the University of Melbourne, Australia. MGD is characterised by keratinisation blocking meibomian gland orifices and keratin debris combined with cross-linking of strong disulphide bonds, raising the melting point and viscosity of the meibum. Selenium sulphide targets aberrant keratins and chemically disrupts disulphide bonds, unblocking the glands and thinning secretions, Dr Downie explained. In a phase 2a trial, 0.1%, 0.5%, and 1.0% concentrations of AZR-MD-001 were tested against the medication vehicle alone. A three-month interim analysis of the first 33 patients found the 0.5% and 1.0% concentrations significantly increased the number of functional meibomian glands and improved meibum quality towards a clear liquid secretion while reducing OSDI dry eye symptoms compared with baseline. The 1.0% preparation also

improved these outcomes significantly compared with the vehicle control group, and clinically significant improvement in OSDI scores showed a dose-dependent relationship with AZR-MD-001 concentration. Patients tolerated the treatments well, although there was some transient burning, Dr Downie reported. “AZR-MD-001 has potential to be the first effective pharmacotherapy treatment specifically intended for MGD,” Dr Downie said. Full results will be reported later.

TARGETING INFLAMMATION PL9643 (Palatin Technologies) is a melanocortin agonist that may be a novel therapeutic target to treat inflammatory ocular diseases, including dry eye. As a first-in-class treatment, it may be faster-acting and more tolerable than current anti-inflammatory treatments, said Kenneth R Kenyon MD, of Tufts University School of Medicine, Boston, USA. The melanocortin peptide receptor systems’ wide range of anti-inflammatory properties includes inhibition of leukocyte activation and protection of tissues from the inflammatory response. PL9643 is a melanocortin pan-agonist that promotes many of these anti-inflammatory effects, Dr Kenyon explained. In a phase 2 trial, researchers tested a 1.0 microgram/mL preparation of PL9643 against a placebo administered three times daily for 12 weeks. The treatment effects on dry eye signs and symptoms did not reach significance in the entire 160-patient study group.

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Avg N.I.B.U.T. 15



Avg N.I.B.U.T.









Figure Legend 2: Changes in NITBUT example in a patient treated with subconjunctival injection of sirolimus liposomal formulation. Pre-treatment (left) showing 8.5 seconds and post-treatment (right) 11.1 seconds.

However, in a sub-group of 61 patients with moderate to severe dry eye, significant improvements were seen in the primary sign endpoint of corneal staining as well as for conjunctival staining and tear film breakup time at week 12. Trends towards improvement in multiple ocular symptoms, including burning, grittiness, stinging, itching, and foreign body sensation also were noted. Data from week 2 showed significant improvement in overall ocular discomfort. Patients again tolerated treatment well, and there were fewer reported adverse events in the treatment group than the placebo group, Dr Kenyon reported. “These positive results across multiple signs and symptoms of dry eye very enthusiastically support continued development of PL9643 as a therapeutic option for dry eye disease,” Dr Kenyon said. There is a plan for a phase 2/3 trial for this year.

The results suggest OC-01 would benefit a broad population of dry eye disease in the real world, and the nasal administration may be an advantage, Dr Raizman noted. “Nasal sprays are well accepted by patients for treating many problems. Eye drops can be difficult to administer for some patients.”

INJECTED IMMUNOMODULATOR Sirolimus is an immunomodulating drug commonly prescribed in oral form to prevent rejection of solid organ transplants. A

NASAL SPRAY TARGETING THE LACRIMAL FUNCTION OC-01 (Oyster Point Pharma, now FDA approved as TYRVAYA™) is a nasal spray containing varenicline, a nicotinic acetylcholine receptor agonist. It activates the trigeminal parasympathetic pathway to activate the lacrimal functional unit to re-establish the natural tear film in patients with dry eye, said Michael Raizman MD of Tufts University School of Medicine, Boston, USA. In addition to the lacrimal glands, varenicline tartrate also stimulates the meibomian glands and goblet cells. The compound is water soluble, diffuses quickly across the nasal mucosa, increases tear production within seconds, and has limited systemic bioavailability, Dr Raizman said. In a phase 3 study involving 758 subjects, patients receiving 0.6 mg/mL (0.03 mg) and 1.2 mg/mL (0.06 mg) of varenicline three times daily saw a high statistically significant rise in Schirmer’s test scores of 10mm or more compared with placebo at day 28. The percentages of eyes showing 10mm improvement or more in the 0.03 mg, 0.06 mg, and vehicle control groups were 47.3%, 49.2%, and 27.8%, with mean changes of 11.3mm, 11.5mm, and 6.3mm, respectively. As early as day 14, patients in the treatment groups saw a significant improvement over placebo in 0–100 Eye Dryness Scores, regardless of their baseline symptom severity. Safety and tolerability were excellent, with sneezing after dosing the most common side effect.

Tyrvaya™ Nasal Spray and Trigeminal Nerves in Nasal Cavity33

patented subconjunctival injection preparation in which the water-soluble active ingredient is loaded in liposomes could help control immune-modulated inflammation in dry eye. This could reduce the need for topical immunosuppressants and related topical adverse effects and long-term use of corticosteroids with the attendant risks of glaucoma and cataract, said Alejandro Navas MD, PhD of the Institute of Ophthalmology “Conde de Valenciana” at the National University of Mexico, Mexico City. In a phase 2 trial involving 38 eyes in 19 patients, both treated and sham groups showed significant reductions in OSDI scores and conjunctival hyperaemia. The treatment group also showed significant improvements in corneal and conjunctival staining, lipid layer interferometry, and inferior meibomian gland dropout. EUROTIMES | DECEMBER 2021/JANUARY 2022

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No local or systemic adverse effects related to the medication were reported, and the administration route was well accepted. Other studies have shown intravitreal sirolimus reduces inflammation for non-infectious uveitis, Dr Navas noted. Loading the active ingredient in liposomes helps extend delivery time. “These findings suggest subconjunctival sirolimus could reduce signs and symptoms in patients with moderate to severe dry eye disease.”

NEUROTROPHIC AND REGENERATIVE PEPTIDE BRM421 (BRIM Biotechnology) is a synthetic peptide derived from Pigment Epithelium-Derived Factor (PEDF) with neurotrophic and stem-cell regenerative properties. It has shown an ability to promote the growth and expansion of limbal epithelial stem cells after severe ocular wounding better than PEDF in animal models. By speeding up the cornea repair process through stimulation of corneal stem cell proliferation and differentiation, and improving tear quality through the increase of mucin secretion resulting from goblet cell growth, it may reverse corneal damage and improve signs and symptoms of moderate to severe dry eye, said Pin-Yen Huang MD of BRIM Biotechnology, Taipei, Taiwan. In a five-week first-in-human study involving 157 patients comparing a topical preparation of BRM421 with a vehicle control, the treated group of patients with moderate to severe dry eye syndrome showed a significant improvement in total fluorescein corneal staining scores. The treated group also showed improvement in dryness symptoms on the Ora Calibra Ocular

Discomfort and 4-Symptom scale on day 14, with improved tear film break-up time on day 29. A second-in-human study involving 220 patients was shortened to three weeks due to the rapid onset of effects in the first study. It found a trend towards improvement in signs and significant improvement in symptoms, including VAS-eye dryness and VAS-burning scales, as well as VAS-photophobia on day eight. Post-hoc analysis showed greater improvement among patients with more severe baseline disease, and the drug had a strong safety profile with no patients withdrawing due to adverse events, Dr Huang reported. “The quick onset, especially in symptom improvement, is quite consistent,” Dr Huang said. “BRM421’s unique mechanism of action gives it the potential to treat not only moderate to severe dry eye syndrome but possibly severe corneal wounds.”

Laura Downie Kenneth R Kenyon Michael Raizman Alejandro Navas, alejandro. Pin-Yen Huang, yichun.chen@


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Ocular Surface Rehab Rapid techniques can improve refractive surgery outcomes. Howard Larkin reports from ASCRS in Las Vegas, USA


hether corneal- or lens-based, treating patients for existing ocular surface disease (OSD) a month to two before refractive surgery can improve vision outcomes and patient satisfaction, said Elizabeth Yeu MD at a Refractive Surgery Day session. Acute ocular surface rehabilitation before surgery could well spell the difference between patients perceiving OSD treatment after surgery as a normal part of care versus an unexpected complication they may blame on surgery. “We know if [patients] start out with bad OSD or even marginally compensated disease, they will decompensate with progression and chronicity to elevated disease even three to six months after surgery,” Dr Yeu said. Often OSD can be identified during dilated eye exams by staining to reveal any corneal damage. She recommended taking more chair time to counsel such patients on the difference between blur due to refractive error and vision fluctuation due to OSD before starting treatment.

TREAT AND OBSERVE While the goal is to rapidly turn OSD around before surgery, the specific treatment depends on the aetiology of the disease, Dr Yeu said. She reviewed several rapid techniques for acute treatment of OSD to both head off visual fluctuation and manage patient expectations. Perioperative therapies may be more aggressive to address acute disease, she noted. Topical steroids can be a quick way to rehabilitate damaged corneas—with loteprednol 0.5% ointment currently the only commercially available preservative-free option. Compounded preservative-free Dexamethasone (0.01%, 0.025%, or 0.1%) solution can be used, and so can the recently approved loteprednol 0.25% for treating acute dry eye flares. Both are excellent go-to drops for preoperative ocular surface normalisation. Preservative-free artificial lubricants are another go-to treatment, and self-retaining amniotic membranes may be suitable for some cases. For glaucoma patients, a temporary switch to oral agents rather than topical medications may help if clinically appropriate, she added. Observing how OSD responds to acute treatment is a critical step, Dr Yeu said. A poor response three to four weeks after treatment indicates a more recalcitrant disease that may require additional treatment and an altered surgical plan, possibly delaying surgery.

CHRONIC MANAGEMENT Chronic dry eye disease (DED) management is critical to improving long-term outcomes, Dr Yeu said. Patients with meibomian gland dysfunction may be treated with routinely scheduled microblepharoexfoliation and/or thermal pulsation and expression. This may include oral omega fatty acid supplementation and chronic, immunomodulation therapy. Anti-inflammatory strategies are important. Therapies that may not have worked when the eye was inflamed, such as punctal plugs, may be reinstituted with more success once it is under control, Dr Yeu said. Nanosuspensions of loteprednol can help reduce signs and symptoms of dry eye within two weeks. In addition to corticosteroids, cyclosporine A 0.05% and 0.09%

may increase tear production while lifitegrast has been shown to reduce higher order aberrations and improve the accuracy of refractive accuracy with cataract surgery. “That is a steroid-sparing opportunity to help turn their surface over.” Other anti-inflammatory agents include azithromycin, which can improve MGD and may be superior to tetracyclines for this purpose. Similarly, minocycline can eradicate bacteria and improve MGD, while doxycycline decreased inflammation and improves corneal wound healing, Dr Yeu observed. She said to observe the upper and lower lid margins for anterior blepharitis, particularly Demodex blepharitis and MGD. The BlephEx® (Alcon) device removes biofilm that can improve lid margin hygiene, greatly reducing collarette presence at the lash margin base, thus helping to treat the Demodex infestation. Heating devices followed by manual expression also help unblock meibomian glands, leading to increased tear film breakup time and improvement in symptoms lasting six months or more. These problems can occur even in younger patients, so look for meibomian gland dropout and other evidence of MGD, she advised.

REFRACTIVE DIAGNOSTIC CLUES Inconsistencies in readings among different diagnostic devices can be a sign of evaporative dry eye disease (EDDE) with early tear break-up time, Dr Yeu said. “You can have great imaging per device, but it doesn’t correlate with one another because of that evaporation. This is where we want to treat the patient for the MGD, for the Demodex because we know with Demodex it can populate anteriorly as well as in the meibomian glands, it can induce higher MMP-9, it does decrease tear break-up time.” Treating Demodex blepharitis can improve evaporative disease as well, she noted. For patients with severe disease not responsive to steroids, such as with central staining, a self-retaining amniotic membrane can be the solution, Dr Yeu said. She presented a case in which a 71-year-old who had been treated for a year with steroids for DED but still wasn’t ready for surgery responded well to this treatment. “We want to identify and rapidly rehabilitate the surface. There are going to be different silos of treatment. What we do for acute rehabilitation may be different, but we also have to take them back and lead them into what we will do chronically for them,” Dr Yeu concluded. Dr Elizabeth Yeu is a Cornea, Cataract, External Disease, and Refractive Surgery specialist. She is an Assistant Professor of Ophthalmology, Eastern Virginia Medical School, Norfolk, Virginia, USA, and the medical director of the Virginia Surgery Center. She is also the co-host of the popular Ophthalmology Quicksand Chronicles podcast. EUROTIMES | DECEMBER 2021/JANUARY 2022

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Healing Treatment— Refractory Neurotrophic Keratopathy Retrospective study highlights utility of topical insulin. Cheryl Guttman Krader reports from the 39th Congress of the ESCRS in Amsterdam


opical insulin, an old treatment to enhance wound healing, appears promising in a new indication as a treatment for refractory neurotrophic keratopathy (NK), according to Ricardo Machado Soares MD. Dr Soares presented the findings of a recent clinical study looking at the potential role of insulin for this indication. The study included 21 eyes of 20 patients with NK stage 2 (epithelial defect without stromal ulceration, n = 11) or NK stage 3 (corneal ulceration and/or stromal lysis, n = 10) that were refractory to multiple standard medical and/or surgical treatments. Complete re-epithelialisation of the persistent epithelial defect or ulcer was the primary endpoint. Ninety percent of the eyes achieved the endpoint within 7 to 45 days of starting treatment. There were no reported side effects associated with the topical insulin. “We recognise that our study, which is an uncontrolled and nonrandomised case series of patients, has some limitations. However, our results suggest topical insulin could be an effective therapeutic in refractory NK. Furthermore, it may prove extremely useful due to its low cost, high accessibility, and low morbidity compared to surgical alternatives. However, more clinical studies are needed to evaluate the efficacy, posology, duration, and side effects of this treatment,” Dr Soares told delegates. The insulin drops were prepared by mixing 1 unit of fast-acting insulin per 1 mL of an artificial tear with a propylene glycol base and kept refrigerated. The drops were applied four times daily. Treatment also included placement of a therapeutic contact lens with a topical fluoroquinolone drop, used to prevent complications related to the contact lens. The treatment continued until the NK epithelial defect or ulcer resolved, and then the regimen was tapered. Mean follow-up for the group was 20 months.

ADDITIONAL DATA Fitting problems prohibited placement of the therapeutic contact lens in the two eyes that did not achieve complete re-epithelialisation. However, one eye went on to heal with the addition of a lateral temporal tarsorrhaphy.

Two eyes experienced recurrence of the epithelial defect after stopping topical insulin. After patients restarted insulin, both eyes went on to complete re-epithelialisation. Thereafter, the patients maintained a low dose of the topical insulin. Analyses of outcomes with eyes stratified by NK stage showed that eyes with stage 2 disease benefited from faster re-epithelialisation than eyes with stage 3 NK (mean 18 days vs 29 days). The difference between subgroups was statistically significant. Analyses of BCVA showed a statistically significant improvement from baseline in the NK stage 2 and NK stage 3 subgroups. However, the magnitude of improvement and final BCVA was better in the stage 2 subgroup than in eyes with stage 3 NK. “The faster re-epithelialisation time and differences in BCVA outcomes between eyes with stage 2 NK were to be expected,” Dr Soares said.

“Importantly, the study also proved that topical insulin is safe for human ocular usage.” HISTORICAL PERSPECTIVE Dr Soares noted that insulin’s role in wound healing is well-known and was first described as a treatment for corneal ulcers in 1945. “But its use was lost over time,” he said. Recently, there have been a few published papers describing success using topical insulin for corneal wound healing. Dr Soares discussed two of those articles. One was a randomised placebo-controlled trial investigating three topical insulin concentrations to treat corneal epithelial defects that developed in patients with diabetes who underwent corneal debridement during vitreoretinal surgery. The results showed topical insulin 0.5 units/mL was more effective than higher concentrations and placebo for promoting healing.

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Figure 1 A–C: Three patients with Neurotrophic Keratopathy (NK) treated with topical insulin. Before and after photographs are presented (with and without cobalt-blue filter and fluorescein stain). Days until complete re-epithelialization are also reported in each case. A: A case of NK due to repeated Herpetic keratitis; B: Case of NK post-penetrating keratoplasty; C: NK developed after craniocerebral gunshot injury.

“Importantly, the study also proved that topical insulin is safe for human ocular usage,” Dr Soares said. The second report described a case series of six patients with treatment-refractory NK ulcers. All eyes in the cohort achieved complete corneal re-epithelialisation within 7 to 25 days of treatment. “This series is similar to ours. Although some of our cases required a higher number of treatment days, we believe the difference is mostly due to the larger size of our study population and its more diverse aetiologies for NK,” Dr Soares said. He added, “Our study also has a longer duration of follow-up, which attests to the long-term efficacy and safety of topical insulin.”

MECHANISM OF ACTION Dr Soares suggested dual activities might explain the benefit of topical insulin for promoting corneal epithelial cell wound healing. First, through binding to insulin receptors present in the eye, insulin promotes the mitosis and migration of corneal epithelial cells. In addition, by activating insulin and insulinlike growth factor 1 receptors, insulin can induce the PI3k/ Akt/mTOR pathway that results in a total block in autophagy, including mitophagy, in corneal epithelial cells. The study was published recently and is available online. [Soares RJDSM, Arêde C, Sousa Neves F, et al. Cornea. 2021 Sep 4. doi: 10.1097/ICO.0000000000002858.]

Ricardo Machado Soares MD works at Centro Hospitalar de Vila Nova de Gaia e Espinho, Vila Nova de Gaia, Portugal.

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Vitreomacular Traction New biomarker holds promise in treating vitreomacular traction disorders. Dermot McGrath reports from the EURETINA 2021 Virtual Congress

Figure: Scatter plot comparing the traction area of the successful (responders) with the unsuccessful patients (non-responders). The steep increase in non-responders starting at an adhesion diameter of 480 µm (scattered line) is clearly visible.


he extent of preoperative traction is the most significant predictive factor for the success of ocriplasmin therapy in vitreomacular traction (VMT) disorders, according to a study presented at the 2021 congress. “We found the optimal cut-off value of the VMT diameter for ocriplasmin therapy could be statistically defined as 480 µm and may thus be a new quantitative biomarker to predict treatment success,” Sami Al-Nawaiseh MD said. Further factors with significant predictive influence on outcomes included age, lens status, hypertension, and absence of diabetes mellitus. Vitreomacular traction is characterised by anomalous posterior vitreous detachment accompanied by anatomic distortion of the fovea, which may include pseudocysts, macular schisis, cystoid macular oedema, and subretinal fluid. The current classification for vitreomacular traction is set by the International Vitreomacular Traction Study Group, explained Dr Al-Nawaiseh, and can be subclassified by the diameter of vitreous attachment to the macular surface as measured by OCT. Approved by the US FDA in 2012, ocriplasmin works by dissolving the proteins that link the vitreous to the macula, resulting in posterior detachment of the vitreous from the retina. Dr Al-Nawaiseh’s retrospective, consecutive, interventional study included 106 patients with symptomatic VMT with a deformed foveal contour. All of the patients received ocriplasmin through intravitreal injection. Exclusion criteria included diagnosis of full-thickness macular hole, presence of other vitreoretinal pathologies such as epiretinal membrane, and missing or substandard OCT images. Among the grouped risk factors analysed, phakic patients had a higher success rate than pseudophakic patients. Hypertension

and diabetes mellitus type 2 absence also had a significant influence on the resolution of the VMT. For the continuous factors, patients with younger age and a smaller adhesion diameter before injection were shown to be predictive of anatomical success, Dr Al-Nawaiseh said. “The statistically optimal threshold value for the adhesion size was 480 µm. Eyes below this limit had a 6.84-fold better chance of VMT resolution compared to eyes with a larger adhesion diameter,” he said. Looking at the results in more detail, Dr Al-Nawaiseh said the overall success rate in this cohort was 60.4%. Broken down by traction diameter, this equated to 0% success for VMT greater than 1,500 µm, 64% for focal VMT less than 1,500 µm, and 76.5% for VMT less than 480 µm. Comparing the results to earlier studies in the scientific literature, most of which reported a success rate in the range of 42% to 46%, Dr Al-Nawaiseh said patient selection was key to obtaining optimal outcomes. “I think this emphasises the importance of rigorous patient selection as many of the earlier studies included patients with epiretinal membranes and other macular comorbidities,” he said.

Sami Al-Nawaiseh MD is a Resident Physician in the Department of Ophthalmology, University Hospital, Muenster, Germany.

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Studying Progression in Early Geographic Atrophy



Dermot McGrath reports from the EURETINA 2021 Virtual Congress


he complement C5 inhibitor avacincaptad pegol (Zimura, Iveric Bio) could have a therapeutic benefit in the early stages of geographic atrophy, suggests a recent analysis of phase 3 clinical trial data. “As this is a post-hoc analysis the results should be considered as hypothesis-generating only, but they do suggest that further exploration of Zimura in dry AMD is definitely warranted,” noted SriniVas R Sadda MD, PhD. The post-hoc analyses focused on the progression of drusen and nascent GA using terminology derived from the Classification of Atrophy Meetings (CAM-Group), an assembly of experts in imaging and AMD that established consensus terminology for the description of early atrophic features. One of the key outcomes of the CAM-Group meetings was the introduction of a Spectral Domain-OCT based nomenclature for early atrophy including the terms cRORA (Complete RPE and Outer Retinal Atrophy) and iRORA (Incomplete RPE and Outer Retinal Atrophy). “I think we would all agree that if effective treatments for AMD could be developed it may actually be ideal to intervene earlier prior to the development of irreversible loss of photoreceptors and vision. This requires the development of earlier endpoints to describe the progression of early AMD to atrophy,” Dr Sadda said. Zimura achieved its primary endpoint in the GATHER1 trial, showing a reduction of GA relative to sham of 28% with 2 mg dosage up to 18 months and 30% less with 4 mg up to 18 months. The post-hoc analysis showed that Zimura 2 mg was associated with greater numerical reduction compared to sham in the progression of iRORA to cRORA. “This was evident as early as six months and with an increasing separation between Zimura and sham over time,” Dr Sadda noted. Zimura 2 mg was associated with a greater numerical reduction compared to sham in progression of drusen to iRORA or cRORA with no additional patients developing iRORA or cRORA lesions following month 12 in the Zimura 2 mg arm in contrast to the sham arm, he added.

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SriniVas R. Sadda MD, is the Director, Artificial Intelligence & Imaging Research, Doheny Eye Institute at the University of California–Los Angeles (UCLA), USA.


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Designer Optogenetics to Restore Vision Leigh Spielberg MD reports from EURETINA 2021 Virtual Congress

Figure: modified from Kleinlogel S, Vogl C, Jeschke M, Neef J, Moser T. Physiol Rev. 2020 100(4): 1467–1525. doi: 10.1152/physrev.00035.2019.


ptogenetics offers researchers a chance to take a designer approach to restoring vision in the blind, Professor Sonja Kleinlogel told a session of the virtual conference. “Optogenetics targets photoreceptor degenerative diseases independently of the underlying pathology. This stands in contrast to gene replacement therapy, which is mutation-specific. Optogenetics turns remaining inner retina cells into replacement photoreceptors by introducing a light-sensitive protein,” Prof Kleinlogel explained. The primary indication for optogenetic therapy is retinitis pigmentosa. The optogenetic approach will probably be applied in the future for wider indications such as geographic atrophy, she predicted. Prof Kleinlogel said optogenetic vision restoration recently reached a milestone with a publication by JA Sahel and colleagues that reported the first case of partial functional recovery in a retinitis pigmentosa patient after optogenetic therapy. Their patient—injected with a microbial optogenetic tool that mainly targeted the macular ganglion cells—regained the ability to locate and count objects while using biomimetic goggles, adjusting light intensity and wavelength. “We don’t target the ganglion cells of the retina but instead the bipolar cells. [These cells] are the first-order interneurons that receive direct input from the photoreceptors. The reason for this is we want to restore the fundamental features of inner retinal signalling,” she said. “By this diversification of retinal ganglion cell output, we can restore direction selectivity, underlying motion detection, or restore the on-off channels, which indicate light getting dimmer or brighter,” Prof Kleinlogel continued. “And we can restore some aspect of light adaptation. Also, when we consider optogenetic restoration outside the fovea, targeting the bipolar cells will restore higher special resolution than targeting the ganglion cells.”

The optogenetic “toolbox” requires three elements: First, the delivery vehicle, which in this case is a synthetic adeno-associated virus. Second, the optogene, for which Prof Kleinlogel’s team used a human chimeric light-sensitive protein, Opto-mGluR6. Lastly, a synthetic short promoter that is bipolar cell-specific. “In order to activate endogenous signalling in our target cells—the bipolar cells—we replaced the intercellular domains of melanopsin with those of the bipolar-specific mGluR6 receptor,” she said. This triggers endogenous mGluR6 signalling directly by light through the melanopsin photo-switch—rather than via glutamate released by the photoreceptors since these degenerate. OptomGluR6 is thus a light-sensitive receptor that activates endogenous bipolar cell signalling by light, obviating the need for photoreceptors. Prof Kleinlogel said intravitreal vector injection leads to very nice panretinal expression and correct subcellular protein localisation. “We have also demonstrated that our treatment is very consistent, is independent of treatment time point, and lasts until the death of the mouse.” Experimentally, functional restoration of the optomotor reflex of a fully retinal degenerated (rd1) mouse treated with OptoGluR6 restored visual acuities, on some occasions, as high as the visual acuity and contrast sensitivity of wild-type C57BL/6 mice, Prof Kleinlogel said. “That, of course, gives us hope for humans,” Prof Kleinlogel concluded.

Sonja Kleinlogel is the group leader of the Translational Optogenetics Lab at the University of Bern, Switzerland. Sonja.

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Choosing Combined Surgery for Cataract and Glaucoma Multiple issues factor into the decision to add a trabecular bypass MIGS procedure to phacoemulsification. Cheryl Guttman Krader reports the 39th Congress of the ESCRS in Amsterdam


ombined phacoemulsification and minimally invasive glaucoma surgery (MIGS) with a trabecular bypass device can be an excellent option for some patients with cataract and high-risk ocular hypertension or early to mild glaucoma, but it is not the best option for all patients, noted Julián García-Feijoo MD. “Cataract surgery is a good opportunity to reconsider treatment for lowering IOP, and I think it is worth adding the MIGS procedure in many cases, even if IOP and the disease is medically controlled, considering it offers the chance for medication-free time and better quality IOP control,” Dr García-Feijoo said.

“Undertaking combined surgery assumes the procedure adds value and will increase quality of life.” “Undertaking combined surgery assumes the procedure adds value and will increase quality of life. Considering the downsides of medication for IOP-lowering, it is probable that adding a trabecular bypass MIGS procedure to cataract surgery for appropriately selected patients can improve quality of life. However, we still need more data from real-life experiences and well-designed studies investigating the impact on quality of life,” he added. Trabecular bypass MIGS devices include two options—the iStent inject® W (Glaukos), which creates two bypass pathways through the trabecular meshwork, and the Hydrus® Microstent (Ivantis). Both technologies have benefits for such a risk: benefit profile, an expectation of IOP results in the mid to high teens, and evidence supporting their cost-effectiveness. Dr García-Feijoo described two clinical scenarios where he believes adding trabecular bypass MIGS to cataract surgery would be a good option. The first involves patients with stable early to

mild glaucoma whose IOP is medically controlled. The objective for performing the glaucoma procedure in these cases is to eliminate or reduce the medication burden and improve quality of life. Secondly, the combined procedure can be an option for patients whose IOP or glaucoma is suboptimally controlled on medications if their target IOP is in the range reachable with combined cataract-trabecular bypass MIGS. “If the target IOP is in the mid or high teens, combined surgery with a trabecular MIGS device is an excellent option. Other types of surgeries, however, are better if there is a need to achieve a lower IOP,” Dr García-Feijoo said. He added that surgeons should consider individual patient preferences, recognising that some patients would rather undergo surgery than undertake chronic topical treatment. “Remember that we need to listen to our patients because they may have a different perspective of their disease and its treatment. In addition, medical treatment is just not feasible for some patients,” Dr García-Feijoo said. Surgical success when performing trabecular bypass MIGS depends on the surgeon’s ability to place the implant in the correct location. Dr García-Feijoo advised his colleagues to take their time finding a comfortable position that enables good angle visualisation, becoming familiar with the inserter and the device, and checking both pieces of hardware before entering the anterior chamber. “If surgeons are comfortable in the operating theatre, surgery will be easier, results will be better, and we will be more confident offering the surgery,” he said.

Dr García-Feijoo is a Professor and Chairman of Ophthalmology, Universidad Complutense, Hospital Clinico San Carlos, Madrid, Spain.

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ESCRS Pioneer Awards • Support, encourage, and fund individuals interested to start clinical research activities in the field of cataract and refractive surgery • Introduce and develop a body of clinical research work, addressing a challenging “problem” in order to devise a practical “solution” • Facilitate and support an independent culture of study for the ultimate benefit of patients

Announcement of 2021/2022 Pioneer Award th

26 Winter Meeting February 2022

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My Aching Back! New survey confirms ophthalmologists are suffering. Cheryl Guttman Krader reports from ASCRS 2021 in Las Vegas, USA


recent online survey confirms previous research showing musculoskeletal complaints are common among ophthalmologists, providing new information about causes, severity, and interventions for management. “In previous studies, 50% to 70% of ophthalmologists reported musculoskeletal complaints—most commonly in the neck and back. Our study was designed to quantify the frequency of musculoskeletal complaints as well as the setting, location, intensity, and effects of these musculoskeletal issues,” explained Nicholas E Tan, BA. The researchers emailed a SurveyMonkey questionnaire to a total of 245 US ophthalmologists, including comprehensive ophthalmologists and cornea, glaucoma, and retina specialists. They received 144 partially completed surveys in return. The responding ophthalmologists had an average age of 50 years, were predominantly male and White, and worked an average of 45 hours per week.

HIGH PREVALENCE AND FREQUENCY Overall, 72% of respondents reported a history of a musculoskeletal diagnosis, and 81% reported musculoskeletal pain, discomfort, or disability episodes in the 12-month period preceding the COVID-19 pandemic. Nearly 50% of the respondents reported experiencing pain daily or weekly. The neck, low back, and shoulders were the most affected locations. “Our survey suggests there may an underdiagnosis of musculoskeletal pathology, especially involving the shoulder,” he commented. While frequent, the musculoskeletal problems had a minimal impact overall. On the validated Total Disability Index (TDI), the mean score corresponded to mild disability, and the worst reported score indicated moderate disability. There was a trend for women to experience worse pain than men, but no found associations between the TDI score and other demographic characteristics, years in practice, or practice volume.

EXACERBATORS AND SOLUTIONS Among respondents reporting pain, almost two-thirds indicated their pain worsened by performing surgery and approximately half identified working in the clinic as an aggravator. Approximately 20% of the respondents reporting pain indicated it made operating or conducting clinic exams moderately more difficult or worse. Furthermore, pain episodes often extended beyond the workplace, Mr Tan said.

“In previous studies, 50% to 70% of ophthalmologists reported musculoskeletal complaints.” Changing posture was the most common modification implemented to attempt to reduce or prevent pain. Changing equipment was an infrequent modification. Increasing the frequency of stretching or exercise was the most common strategy used to treat pain. Over-the-counter oral medications and manual therapy were also common treatments. “Those with greater disability, measured by a higher TDI score, were more likely to attempt modifications or treatments for pain,” Mr Tan said.

Nicholas E Tan is a medical student, SUNY Downstate College of Medicine, Brooklyn, NY, USA.,

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THOMAS KOHNEN European Editor of JCRS

JCRS HIGHLIGHTS TRIFOCAL IOLS AFTER REFRACTIVE SURGERY Are current trifocal IOLs effective in eyes that have previously undergone photorefractive surgery? A retrospective comparative case study evaluated 868 eyes of 543 patients who had undergone corneal laser refractive surgery prior to receiving trifocal IOLs. This included 319 eyes treated for myopia and 549 eyes that had undergone treatment for hyperopia. Three months postoperatively, visual outcomes were poorer in the hyperopic group than those in the myopic group for mean CDVA (0.06 ± 0.05 vs 0.04 ± 0.04, P < .01) and safety (21% vs 12% of CDVA line loss, P < .05) outcomes. However, precision outcomes were worse in the myopic group, with a mean spherical equivalent of −0.38 ± 0.3 vs −0.17 ± 0.3 (P < .01). Patients with either high myopia or high hyperopia had poorer visual and safety results. R Cobo-Soriano et al., “Trifocal intraocular lens implantation in eyes with previous corneal refractive surgery for myopia and hyperopia”, 47(10): 1265–1272.

OPTIC EXCHANGE WITH MODULAR IOLS A new modular IOL system with an exchangeable optic component compares favourably with standard IOL implantation both in terms of initial implantation and optic exchange procedures, concludes a prospective clinical study. Surgeons implanted 114 patients with a Harmoni Modular Intraocular Lens (HMIOL) in one eye (monovision target −1.50 dioptre) and a standard monofocal IOL in the contralateral eye. Patients could elect optic exchange three months after primary implantation. Sixty-five patients elected to have an optic exchange because of unsatisfactory visual outcomes from high monovision. No posterior capsular rupture occurred during optic exchange procedures. Short-term (12month) posterior capsule opacification (PCO) evaluation showed that all eyes had PCO grade 1 or less at 12 months. No Nd:YAG capsulotomy was performed in the exchange cohort. The HMIOL is a hydrophobic acrylic foldable posterior chamber IOL system for implantation in the capsular bag. The HMIOL has an exchangeable optic (5.8mm diameter) and separate base component (13.0mm diameter) with an annular groove for attachment of the optic component. R Ang et al., “Evaluation of safety after optic exchange of a modular intraocular lens”, 47(10): 1273–1278.

ANGLE α AND OCULAR BIOMETRY There is a significant inverse correlation between axial length and the angle α magnitude, a prospective, cross-sectional study concludes. The study evaluated 74 eyes in 74 healthy patients. Patients underwent a complete ophthalmological assessment, including biomicroscopy and biometry. The investigators used an OPD-Scan III analyser to assess both the angle α distance and biometry parameters. Hyperopic patients tended to demonstrate significantly higher angle α values when compared with myopic patients. Hyperopic eyes with steeper mean keratometry and lesser white-to-white distance also had an increased α angle. C Velasco-Barona et al., “Impact of correlation of angle α with ocular biometry variables”, 47(10): 1279–1284. JCRS is the official journal of ESCRS and ASCRS

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Clare Quigley Details have been changed to preserve patient anonymity. “The neighbours were arguing,” Some weeks later, he still comes back he explained. “Stupid fight. I was to clinic, with hand-motions vision. trying to calm things down.” Serial B scan ultrasounds reveal a retina “Right,” I said. “What happened?” still in position, though it is not vis“A bowl, one of them threw a ible behind dense sheets of vitreous bowl….” He lapsed into silence. haemorrhage. We liaise with the vitreoHis seeing eye was looking off and retina team and hope that he improves. away, recalling. That patient had been unlucky. I imagined it too. My patient had What were the chances, of all the posbeen the good Samaritan, stepping sible flight paths the shard could have in to cool heated tempers and talk taken—it had to rip a tear in his sclera? some sense between quarrelling But I see lucky patients too. neighbours. I had read the triage “Remind us of what happened,” nurse’s notes, but I wanted to hear I asked recently, for the benefit of the story in his own words. the Oculoplastics fellow and Senior “A piece flew?” House Officer, who had not heard He nodded, indicating with his the story. Georgios, Mehera, and I finger jabbing towards his traumawere gathered in the theatre for this tised eye, the trajectory of the shard man’s surgery. that had hit him. “Well, I was in the parlour—” I grimaced. “The milking parlour,” I interjected. “You’ve had a very severe injury,” This injury had not happened in an I started. elegantly turned-out reception room. He nodded. “Yes, the milking parlour”, our “At the moment, you cannot see patient, a dairy farmer, agreed. “So, in anything; you’ve lost the vision in the parlour, hooks hang from above, the eye.” I continued, talking about from the ceiling. They’re used to hang surgery. I explained that at this equipment for milking. That day, the stage his eye was open, leaking. day it happened, I was a little distractWe wanted to reduce the risk of ed. Busy you know, under pressure. I any infection getting in, as if that turned, ’course forgetting there was an happened, he could lose the eye empty hook right there behind me.” “I was unlucky, altogether. Primary repair was the He paused, like that explained but I suppose I was lucky.” first procedure he needed, involvwhat had happened. ing stitches to seal the eye. He “And the hook?” would need further surgery down the line, as there was a high “Yes well,” he continued, “the upturned end of the hook just likelihood intraocular structures had been disrupted—the retina caught me, slid right in under my eyelid, against the eye. And I being our biggest fear. pulled back straight away when I felt it…” “Any questions?” I remembered seeing him later that day on call. Lid lacerations He shook his head, signing the consent form. are not uncommon, but this one was more dramatic than the othWithin a few hours, he was on the table asleep, and I was ers I had seen. The upper lid was torn in half, hanging down in operating. My Consultant, Professor Lorraine Cassidy, scrubbed a curved line that extended from the medial canthus up and out. to assist and advise when it emerged that the perf went far posteWhen he blinked, the lid flapped about freely. I knew the levator riorly. I had to take off the lateral rectus to even start to visualise had been at least partially transected and hoped he did not have an the scleral laceration. Hooking and taking off the muscle (with ocular injury behind it. care so my hook did not go right into the eye), I was thankful That evening on call, I had done a primary repair of the eyelid, for my squint surgery training. With the muscle off and out of closing the lid margin and suturing the skin, but without dissectthe way, we could finally see the tear. Unfortunately, it extended ing out and re-attaching levator. back past the equator of the globe. In this position, placing Now he was back, a few months later, for an exploration and sutures was very awkward; as I went further and further back, advancement of his levator to treat his ptosis. His eye itself the pressure we could put on the eye reached a maximum—it was perfect. was not possible to displace it further to reveal the end of the “I was unlucky, but I suppose I was lucky,” the patient conceded, lac. Already we had seen a little spurt of clear fluid—liquefied at the conclusion of his story. We agreed with him, reassuring him vitreous—coming out. After some gentle cryotherapy, I put the that he was lucky overall to be coming back for a ptosis repair. muscle back on and closed the conjunctiva. There are worse things. EUROTIMES | DECEMBER 2021/JANUARY 2022 Dec-Jan_EuroTimes.indd 32

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Presbyopia Eye Drop Approved

The US FDA granted approval to VUITY™ (pilocarpine HCL ophthalmic solution 1.25%, Allergan) for presbyopia treatment. This is the first eye drop approved for this indication. Clinical studies showed that a daily instillation worked in as little as 15 minutes and lasted up to six hours, as measured on day 30. Improvements were seen in near and intermediate vision without affecting distance vision. The drop uses a proprietary pHast™ technology to help rapidly adjust to the physiologic pH of the tear film. The most common treatment-emergent, non-serious adverse events seen in clinical studies were headache and eye redness occurring in less than 5% of patients.

OCULAR IMPLANT FOR WET AMD Susvimo™ (Genentech, Roche), an ocular implant that delivers ranibizumab (Lucentis) 100 mg/mL, gained US FDA approval for treating wet age-related macular degeneration in patients who have previously responded to at least two anti-vascular endothelial growth factor injections. Susvimo provides up to six months of the active drug between refills. The device is implanted in a quick outpatient procedure.

EXPANDED APPROVAL FOR DEXTENZA The US FDA has approved a supplemental new drug application for DEXTENZA® (dexamethasone ophthalmic insert, Ocular Therapeutix). The new approval adds ocular itching associated with allergic conjunctivitis to the drug’s current indications. DEXTENZA is an ophthalmic insert placed in the lower lacrimal punctum and into the canaliculus. A single treatment releases a 0.4 mg dose of dexamethasone for up to 30 days following insertion. The device was already approved for treating ocular inflammation and pain following eye surgery.

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Everything you always wanted to know about…

Posterior Capsular Rent: IOL Fixation This is the third part of a series taking a detailed look at posterior capsule problems encountered during cataract surgery. Dr Soosan Jacob MS, FRCS, DNB


he type of IOL fixation to be employed after a posterior capsular rent (PCR) depends on residual capsular support as well as other ocular characteristics. Comorbidities such as iris structure and support, the presence of coexistent nucleus drop, and retinal or corneal pathology all need to be considered. In the case of fragment drop, it may be wiser to involve a vitreo-retinal colleague. IOL placement before referring to the retinal colleague depends on the size and density of the dropped nucleus/fragments. With small fragments or soft nucleus an IOL may be implanted. However, in case of large, dense fragments which may need to be brought up to the anterior chamber (AC), the eye may be left aphakic if the surgeon is insufficiently experienced with alternate IOL fixation techniques. All incisions should be sutured after a PCR to avoid wound leak and decrease the risk of endophthalmitis. The anterior or posterior segment surgeon may perform IOL fixation. Vitreous clearance using limbal, pars plana, or combined approach with 23/25-gauge instruments and vitrectomy systems in a closed globe technique via small incisions/sclerotomies and preservative-free triamcinolone to enhance visualisation are important. Hypotony during IOL fixation techniques should be avoided, preferably by using infusion by a trocar anterior chamber maintainer (ACM), simple ACM, or pars plana infusion cannula. Or, alternately, using viscoelastic.

SULCUS PLACEMENT OF IOL A single-piece PMMA IOL or three-piece IOL with rounded edges may be placed in the sulcus. The preferred model is the three-piece foldable IOL because of the lack of a need to enlarge incisions. Avoid single-piece acrylic IOLs in the sulcus because of the risk of UGH (Uveitis-Glaucoma-Hyphaema) syndrome. The Staar AQ2010 IOL with firm 14mm long polyamide haptics and large 6.5mm optic generally allows stable sulcus placement, good centration, and vision. If there is possibility for posterior segment surgery required in the future, use acrylic three-piece IOLs as silicone IOLs interfere with vitrectomy procedures. Acrylic IOLs, however, have shorter haptics with a higher risk of decentration over time and are therefore ideally combined with optic capture. Avoiding IOL drop can be done by careful injection and direct visualisation of the leading haptic entering the sulcus. If needed, consider iris hooks to dilate the pupil. Unflexing the leading haptic tip within the cartridge, avoiding wound-assisted implantation, and holding a rod below the unfolding IOL optic also help prevent IOL drop. The trailing haptic is carefully dialled or flexed using a single-handed or bimanual handshake technique, ensuring release into the sulcus.

An optic capture may then be performed. This allows central and stable IOL fixation, provided the rhexis is centred and smaller than the IOL optic, as described by Dr Howard Gimbel. After sulcus placement, the optic is gently captured by tilting each side downwards under the rhexis rim one after the other. In the absence of adequate capsular support for a sulcus IOL, choosing IOL fixation depends on the surgeon’s skill, experience, and individual preference. Whichever mode of fixation, the change in effective lens position results in necessary IOL power adjustment. AC-IOLs and iris fixated IOLs need proper iris support and tone, whereas scleral fixated IOLs are independent of the iris condition.

ANTERIOR CHAMBER IOL When positioned carefully and properly sized, open-loop, angle-supported, four-point-fixated PMMA ACIOLs—such as Kelman Multiflex (Alcon)—are well tolerated. If not, however, they can cause long-term chronic endothelial damage and pseudophakic bullous keratopathy. Avoid ACIOLs in patients with inadequate AC depth, uveitis, glaucoma, or compromised corneal endothelium.

IRIS FIXATED IOL Retro-iridial fixation is the preferred site and may be achieved either with a three-piece IOL using suture fixation or with an iris-claw lens. Poor iris tone may cause excess IOL mobility and consequent complications. Dr Garry Condon described how it’s possible to suture an IOL to the iris by placing the IOL behind the iris with an anterior pupillary capture of the optic. The iris is pulled inwards, and the pupil made round. Viscoelastic is used to contour the haptics, then sutured to the mid-peripheral iris using a modified Siepser sliding knot or a McCannel technique—using 9-0 or 10-0 polypropylene suture on a long, curved needle. The optic capture is then released. Retro-iridal fixation is also preferred over anterior fixation for the iris-claw lens to avoid the risk of long-term endothelial loss. Each haptic is introduced sequentially under the iris and enclavated. The optic should be released only after stable fixation. The site for iris enclavation should be chosen with care to avoid pupillary distortion.

SUTURED SCLERAL FIXATED IOL There are reports of an association between both 9-0 and 10-0 Prolene sutures with the risk of long-term suture degradation. The 8-0 polytetrafluoroethylene (Gore-Tex) sutures may provide better long-term fixation. Numerous techniques have been described.

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Glued IOL in PCR: A—Anterior chamber maintainer inserted, scleral flaps and sclerotomies created, vitrectomy done via sclerotomies; B,C,D—Haptics externalized using handshake technique. This is followed by haptic tuck and gluing of flaps and conjunctiva.

Sutured scleral fixation can be performed ab-externo where a straight needle entering from one side under a scleral flap or via a scleral groove or Hoffman pocket is railroaded into a hollow bore needle passed in a similar fashion into the eye from the opposite side and externalised. A suture loop is brought out through a limbal incision, cut, and tied to each haptic of the IOL, then internalised. The suture is tied down to the sclera to fixate the IOL. In the ab-interno approach, sutures are tied to the IOL and passed from inside out. Various other techniques of suture IOL fixation have been described, such as Snyder’s cow hitch technique which gives four-point fixation, thus avoiding both tilt and torque.

INTRA-SCLERAL HAPTIC FIXATION These have become popular techniques for IOL fixation in the absence of sufficient capsular support. They allow sutureless trans-scleral haptic fixation. Advantages include the absence of suture-related complications, independence from iris structure, ease of surgery, easy centration, long-term stability, and decreased pseudophakodonesis. It’s important to have sufficient vitrectomy prior to IOL implantation. And to prevent intraoperative hypotony, use an anterior chamber maintainer or pars plana infusion. Scharioth technique: Using 25-gauge end-gripping forceps, the IOL haptics are sequentially externalized through two ab-externo 24-gauge sclerotomies created 1.5 to 2mm behind the limbus. These are then fed into the 24-gauge, limbus parallel, half-thickness intra-scleral Scharioth tunnels that lead from the sclerotomies.

Glued IOL: Introduced through 20- or 23-gauge sclerotomies (created under scleral flaps), 23- or 25-gauge end-gripping microforceps sequentially externalize both IOL haptics. Both haptics are then tucked into limbus parallel Scharioth tunnels, and the scleral flaps and conjunctiva sealed with glue. The intrascleral haptic tuck within the Scharioth tunnel gives the glued IOL its stability, and therefore, a sufficient tuck is important. Double needle flanged intra-scleral haptic fixation (Yamane Technique): The haptics of a three-piece IOL are railroaded into the bore of 30-gauge thin-walled needles that are passed transconjunctivally and tunnelled through the sclera to enter intravitreally. Both needles are then externalized simultaneously, thus also externalizing the haptics. Low-temperature cautery is applied on the haptic tip to create a bulb-shaped flange that is then tucked back under the conjunctiva into the scleral tunnel. Dr Soosan Jacob is Director and Chief of Dr Agarwal’s Refractive and Cornea Foundation at Dr Agarwal’s Eye Hospital, Chennai, India, and can be reached at EUROTIMES | DECEMBER 2021/JANUARY 2022

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What Have We Been Missing? By Dr Diana Dragnea HAS COVID-19 CHANGED LONG-TERM CLINICAL PRACTICE? Definitely, at least on an individual level. Over the past ten years, I have noticed a gradual and striking change in myself. I became aware of many things I had learned in the previous years and often wondered: How come I didn’t know these obvious things before? But in 2020, I initially thought that my personal development had stopped.

WHEN THE BODY PUNISHES YOU I was in a constant loop. Waking up > driving to the clinic > driving back > having dinner > working on my computer > going to bed > waking up... I was stuck in a constant state of fatigue and stuffiness. My body began to protest giving me neck and back pain. I ignored it. It increased. After a while it turned into a kind of numbness mixed with episodes of severe ache. The problem worsened on OR days, as in full concentration I would completely forget the pain which helped me to hold whatever position I wanted. Immediately after surgery, my body would start screaming. A friend said to me one day: “Just because you have a Ferrari doesn’t mean you have to drive it full speed.” Very slowly I came to realise that working at that pace was making me sick and this was also affecting the quality of care I was giving to my patients. Finding peace of mind even in hard times is crucial. But this is a long process.

DEATH During the first lockdown I realised that as ophthalmologists we are far from being exposed to death. I only spent a week in a COVID ward and I still remember vividly the first patient who died. I was standing in the staff kitchen, staring at the monitor and suppressing as much as I could. The monitor showed from above a man who was agonising alone in his bed. I was somehow calm as this was a story from another dimension that I could turn off at any moment. The black and white screen was also helping. All the actors from black and white movies are dead by now and I feel no tragedy in that. But the thing that really saddened me was that his family decided not to pay him a visit. They were given the option of going in with full protection for a short time or staying with him as long as they wanted, but to remain in quarantine as well. The answer was no. I became much more aware of my patients’ fears and anxieties and decided to listen more.

YOU DON’T KNOW WHAT YOU HAVE UNTIL YOU LOSE IT It was never difficult for me to distance myself because I was never particularly “that warm” with my patients. Not because I didn’t want to put my hand on their shoulders, but because I was taught that it might be inappropriate. In the midst of the pandemic, while accompanying an 88-year-old lady who thought I was a student, I witnessed a somewhat natural lapse that reminded me of what I had been missing even before that. She was abiding by hospital rules and, despite her age and the sudden onset of double vision the previous evening, had brought no relatives and remained alone

Dr Diana Carmen Dragnea is the winner of the 2021 John Henahan Prize is for her essay What Have We Been Missing. Dr Dragnea received a specially commissioned trophy created by Irish designer Shane Holland.

in the waiting room with her mask fallen under her mouth. The moment I asked her to follow me for consultation, she immediately approached and slipped her hands under my arm as if it were the most natural thing in the world. My righteousness was instantly disturbed. But I immediately began to feel an immense warmth fill my heart as I slowly guided her to the doctor’s room. She said smiling to me: “Don’t worry, I had my injection this morning.” ...She must have felt my rigidity. Since she had partial gaze palsy in downward direction, I called my orthoptist colleague to do a full examination of her eye movements. During the examination, the lady reminded me that if I hadn’t started university yet, I should consider staying in the department as it is a great place to learn. With the suspicion of a brain stem insult, she had to be sent to the emergency department for possible admission to neurology. Instead of calling the transport service, I decided to personally bring her down two floors so I could enjoy a few extra minutes arm in arm with her. Maybe this pandemic is a reminder of what we missed long before it started. Some of our humanity and care for ourselves and others. Because of my upbringing and exposure, I never paid much attention to small physical closeness with patients (except when a Polish patient wanted to kiss me for joy), but now I long for it and want to experience it more once our lives are safe again. As well as taking better care of myself and listening to my patients more. These will be long-term changes in my individual clinical practice. And perhaps in many others.



Dr Diana Dragnea is pursuing a PhD and a fellowship in anterior segment surgery at the University Hospital of Antwerp (UZA), Belgium.

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EuroTimes 2021— Are Live Conferences Worth the Trouble? The last 18 months had a great impact on online education. Webinars were popping up everywhere, and the demand was huge during lockdown. For me, as a resident in the third year, this really was a chance to have access to loads of online material. The pros are obvious: Online education is barrier free, no additional costs for travelling, and still international exchange is possible thanks to easily accessible technology. So, why even attend a live congress? Is it worth it? The answer after visiting ESCRS 2021 is clear: Yes, it was absolutely worth it. As a co-organiser of many webinars and a fully held online congress in 2020 (Ophthalmology Congress, Linz, Austria), I am an advocate for this type of knowledge exchange. Still, human interaction cannot be reduced to a screen. Since I haven’t visited any international congresses during the pandemic, the attendance at the ESCRS 2021 convinced me about the importance of on-site events. Is there anything nicer than having a coffee with colleagues after a great lecture to exchange ideas and thoughts? Running into friends, mentors, idols, and meeting new people really strengthens our community and makes this meeting so exciting. Holding the Congress at the RAI-centre Amsterdam offered advantages regarding a very easy connectivity to the city and the airport as well a spacious congress hall making it possible to hold several lectures simultaneously. The Congress was well organised—I could easily orientate and filter out significant lectures. The programme itself offered a wide range of lectures, talks, and courses throughout the four days and sometimes made it hard for me to decide where to go. Starting Friday, I first visited the lecture by Prof Gerd Auffarth, “There is no free lunch in optics.” A brilliant and comprehensive lecture by this year’s Binkhorst Medal winner, his enthusiasm

was infectious. It was followed by the Main Symposium, “Managing Herpetic Keratitis,” giving a clinically relevant and structured overview—information I can make use of in my routine. The video sessions on Saturday (“You make the call”) and Sunday (“Getting into trouble”) were very entertaining and made the Congress even more diverse. Also, the Young Ophthalmologists sessions were very interesting and helpful. In summary, a colourful mix was put together and there was something for everyone. “Real” interactions with companies are much more vivid than in online appearances. Obviously, it’s not just the raw information and the numbers that count and can be looked up by anyone online in a brochure. It is about seeing and touching products and instruments and maybe even visiting a wet lab and trying a new phaco machine. The satellite symposia also gave scientific insight on newly designed IOLs and products. As a balance to a long day at the ESCRS, Amsterdam offered numerous off-site activities with a variety of restaurants and bars. This is a buzzing, lively city with international character. Strolling through the streets of this city is worth it. I am very glad to have attended this year’s meeting and am looking forward for the 40th anniversary of ESCRS next year.

Haidar Khalil MD Kepler University Clinic, Linz, Austria

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#EyeFamily— Reflections on Clinical Conferences “Are you going to the ESCRS Congress? I can’t be bothered…” This sentiment echoed in many conversations around ophthalmic departments in the UK when the invitation to attend the first in-person European clinical conference for nearly two years arrived. With a range of presentations and posters accepted and a speaking engagement, I always intended to go and support my trainees as they also delivered their talks. However, even they had become reluctant to attend in person! COVID restrictions and concerns had changed attitudes, and constantly changeable travel rules rendered the whole trip unattractive to some. As I checked and re-checked the multitude of paperwork required to both enter and leave Amsterdam, such thoughts also crossed my mind—why am I doing this? Is Zoom not easier? How do I put on a tie again?! Having negotiated government websites, travel guidance, and the jeopardy associated with pre-flight COVID testing, finally getting into a taxi at Schiphol airport felt an achievement by itself. Receiving my name badge following passport and vaccine status checks prior to entering the conference venue will certainly account for some managerial CPD points at my next appraisal! Despite these minor impositions, it was reassuring to know that my health (and that of others) was being protected by the organisers. However, I don’t think I had emotionally prepared myself adequately for entering the arena, which was a totally surreal moment. People had smiles, not obscured by masks! Hugs and handshakes abounded as delegates re-connected with each other and the industry. Dinner plans were made, and tourist locations recommended. Although the in-person delegate numbers were lower than normal, this was not a negative, as it permitted more opportunities to see and speak to “the great and the good” in the world of ophthalmology. There was the wide programme of educational content as always, but with sufficient time to grab some lunch and wander around the trade exhibition, looking for friends and colleagues, and even engage in “Selfies with the Stars” to document on social media! From the big-name speaker to the first-time attendee, everyone had space and time to learn and share with each other. As I returned to Schiphol to make my journey home, I took time to pause and reflect on the true purposes of such conferences. In-person conferences permit a break from your normal work constraints and provide you space to expand your horizons. You can attend a range of clinical talks to confirm or challenge your clinical practice. New technologies and techniques can be engaged with, and your patients will

benefit when you learn from someone else’s learning curve, avoiding similar difficulties. Even attending some of the Young Ophthalmologists’ sessions helped me refine my teaching strategies. Furthermore, I have always taken the opportunity at conferences to approach a podium speaker or expert and ask them informally for their advice on a complex clinical case I might have. This type of peer discussion is good for our patients, and we have all missed out on that extra opinion over the past few years. Such interactions are often the first steps in developing clinical networks and supportive mentorships, and certainly laid the foundations for my eventual corneal fellowship in New Zealand more than eight years ago. Ultimately, engaging in person with friends and colleagues again was cathartic and a small glimpse of what normal life can be like—it was good to have been there. Some of the most difficult circumstances of the pandemic have involved restrictions that prevented us from visiting and supporting friends and family. People are made for people, and attending this ESCRS Congress in Amsterdam clearly demonstrated that ophthalmology is a community at heart. It is always worth the effort to stay connected with your relatives, and I am glad I bothered to make the time to be with my international Eye Family. Hope to see you at our next reunion! Dr David Lockington MB, BCh, BAO (Hons), FRCOphth, PhD practices at the Tennent Institute of Ophthalmology, Glasgow, UK.

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The 26th ESCRS Winter Meeting will be held at the Tivoli Marina Vilamoura Algarve Resort | Vilamoura Portugal


26th ESCRS Winter Meeting

18 – 20 February Vilamoura, Portugal 178x130 AAFF.pdf 3 26/07/2021 8:53:05









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