EuroTimes Vol. 20 - Issue 11

SPECIAL FOCUS PAEDIATRIC OPHTHALMOLOGY CORNEA

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Publisher Carol Fitzpatrick Executive Editor Colin Kerr Editors Sean Henahan Paul McGinn Managing Editor Caroline Brick Production Editor Conor Ward Senior Designer Janice Robb Designer Lara Fitzgibbon Circulation Manager Angela Morrissey Contributing Editors Howard Larkin Dermot McGrath Roibeard Ó hÉineacháin Contributors Maryalicia Post Leigh Spielberg Pippa Wysong Gearóid Tuohy Priscilla Lynch Soosan Jacob

CONTENTS

A EUROPEAN OUTLOOK ON THE WORLD OF OPHTHALMOLOGY

SPECIAL FOCUS PAEDIATRIC OPHTHALMOLOGY

18 Herpetic keratitis –

4 Cover Story: Infantile

19 Intraoperative imaging:

nystagmus – newer algorithms ease diagnosis and treatment

Colour and Print W&G Baird Printers Advertising Sales Amy Bartlett ESCRS Tel: 353 1 209 1100 email: amy.bartlett@escrs.org 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 managing 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

8 Subluxated lenses

in children: surgery at younger age may improve visual outcomes

9 Primary IOL implantation when operating on congenital cataracts in infants

10 MRI transforming

understanding of extraocular muscle anatomy and function

FEATURES CATARACT & REFRACTIVE 12 Endophthalmitis following 13 14 16 17

As certified by ABC, the EuroTimes average net circulation for the 10 issues distributed between 01 January 2014 and 31 December 2014 is 42,957.

CORNEA

intravitreal injections – prophylactic strategies Intraoperative OCT for measuring IOL position Novel parameter quantifying total corneal astigmatism Anterior segment imaging: better information could mean better outcomes Customising depth of focus provides good uncorrected near and intermediate vision

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antivirals for prophylaxis and treatment technology gives surgeons depth-based guidance

20 The important role of

preserved corneas in treatment of blinding disease

22 PDEK emerging as a

promising alternative to DMEK

23 Study sheds light on CMV endotheliitis

24 Tear film biomarkers for diagnosis and management of dry eye syndromes

25 Fungal keratitis –

targeted drug delivery may offer a solution

27 Dry eye diagnosis and management: tear film oriented therapy

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Cover image shows a nine-year-old with oculocutaneous albinism Type 1, showing characteristic hypopigmentation of eyes, skin and hair. Courtesy of Richard W Hertle MD

GLAUCOMA 28 Taking a slow and

considered approach to surgery

30 Stents may reduce IOP below TM options, and transform treatment

33 ‘There is a pressing need to create high-quality, high-volume, costeffective care’

RETINA 34 Printing of functional

retinal cells to help cure some forms of blindness

35 New lens can improve outcomes for macula disease

39 Novel IOL shows promise for improving vision in patients with dry AMD

REGULARS 41 Ophthalmologica Update 42 JCRS Highlights 43 Industry News 45 Travel 46 Review 48 Calendar EUROTIMES | NOVEMBER 2015

2

EDITORIAL A WORD FROM RICHARD W HERTLE MD, FAAO, FACS, FAAP

GLOBAL EXPERTISE

There are now over 42 member societies representing all continents in the World Society of Paediatric Ophthalmology and Strabismus

A

bout 10 years ago, a small group of eye care to the robust state of our profession, and how passionate professionals led by Dr David Granet (USA) and international colleagues are to share their experiences with Dr Ken Nischal (USA and UK) believed that the each other. international paediatric and strabismus eye care This historic time for WSPOS provided an open, relevant community needed an organisation free of the and trusted service to the worldwide community. The meeting burdens of geographic, political and societal borders. and the connections it created, the ideas it generated, and Its goals would be the open exchange of culture, skills, the relationships it built, all provide a foundation for future knowledge and new ideas. It would also be an organisation challenges. We made new friends, were challenged by new which promoted international clinical care, education and ideas, and were excited and inspired by our common goal of research collaboration, and thus was born the World Society of restoring and preserving the visual health of our children.

Paediatric Ophthalmology and Strabismus (WSPOS).

The increasingly global nature There are now over 42 member societies representing of expertise and the need for This congress was like no all continents. In addition to its meeting, other WSPOS enhanced knowledge sharing initiatives include: areas of Research collaboration were evident at the congress in other in that it allowed (aRc), networks of international individuals who Barcelona. Among the highlights those who care for children have common research interests, and organising was the first Kanski Medal Lecture, and their families to international training centres called Key Opportune honouring those whose work has equally share their varied Global Hubs (KOGHs). improved the lives of children An international committee of WSPOS members with ocular disease, given to Dr international and cultural (Global Advisory Council, or GAC) develop a KOGH. Helen Mintz-Hittner because perspectives, from clinical WSPOS supports members to attend a KOGH of her work with retinopathy care and research to cuisine ideally suited to them based on educational interest, of prematurity. WCPOS also geography, language and culture. featured the Oscars for its video and entertainment Over this past decade there have been three competition and a non-accidental international meetings, the most recent being the 3rd injury Mock Trial, where two World Congress of Paediatric Ophthalmology and Strabismus paediatric ophthalmologists took opposing sides in the case (WCPOS) in the breathtaking city of Barcelona, Spain. and discussed it as if they were actually in a court of law.

This congress was like no other in that it allowed those who The WSPOS core value – that expertise is a global care for children and their families to equally share their varied phenomenon – was clear throughout the entire congress, and international and cultural perspectives, from clinical care and its members continue to promote international collaboration research to cuisine and entertainment. as the cornerstone of its future development.

The programme was filled with blended and provocative information in the forms of keynote and named lectures, skills transfer and instructional courses, didactic sessions, Richard W Hertle is a member of the WSPOS electronic poster and video presentations, and novel Executive Bureau. He is also Chief of Paediatric audience-directed sessions.

Ophthalmology, Director, Children’s Vision WSPOS is a society that believes expertise is a global Center, Akron Children’s Hospital, Ohio; and phenomenon. This was evidenced by the presence of over 1,200 Professor, Department of Surgery, College of delegates representing over 100 countries. This is a testament Medicine, Northeast Ohio Medical College, USA

MEDICAL EDITORS

Emanuel Rosen Chief Medical Editor

José Güell

Ioannis Pallikaris

Clive Peckar

Paul Rosen

INTERNATIONAL EDITORIAL BOARD Noel Alpins (Australia), Bekir Aslan (Turkey), Peter Barry (Ireland), Roberto Bellucci (Italy), Béatrice Cochener (France), Hiroko Bissen-Miyajima (Japan), John Chang (China), Alaa El Danasoury (Saudi Arabia), Oliver Findl (Austria), I Howard Fine (USA), Jack Holladay (USA) , Soosan Jacob (India), Vikentia Katsanevaki (Greece), Thomas Kohnen (Germany), Anastasios Konstas (Greece), Dennis Lam (Hong Kong), Boris Malyugin (Russia), Marguerite McDonald (USA), Cyres Mehta (India), Thomas Neuhann (Germany), Rudy Nuijts (The Netherlands), Gisbert Richard (Germany), Leigh Spielberg (The Netherlands), Sathish Srinivasan (UK), Robert Stegmann (South Africa), Ulf Stenevi (Sweden), Emrullah Tasindi (Turkey), Marie-Jose Tassignon (Belgium), Manfred Tetz (Germany), Carlo Enrico Traverso (Italy), Roberto Zaldivar (Argentina), Oliver Zeitz (Germany)

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4

COVER STORY: PAEDIATRIC OPHTHALMOLOGY

INFANTILE NYSTAGMUS Newer algorithms ease diagnosis and treatment even with complex comorbidities. Howard Larkin reports

T

he nine-year-old boy arrived at the office of Richard W Hertle MD, who specialises in paediatric ophthalmology and ocular motor disorders, with oculocutaneous albinism (OCA). He displayed decreased acuity strabismus, anomalous head posture and nystagmus.

The boy’s visual acuity (VA) tested 20/200 binocularly, with 20/300 monocularly, Dr Hertle recalled. His parents had been told 20/200 was the best VA they could expect.

It is a story Dr Hertle hears often on referral, even in the USA, where he practises at Akron Children’s Hospital in Akron, Ohio. “They say, ‘there is nothing we can do, sign your child up for school for the blind, they are never going to drive.’ And this is the baby seeing the ophthalmologist for the first time, usually in the first two months of life.”

But Dr Hertle knew better vision was not only possible but likely. Over the past three EUROTIMES | NOVEMBER 2015

decades he has treated more than 4,500 nystagmus patients and operated on nearly 3,000. With colleagues he has developed diagnostic and treatment algorithms that improve many visual functions in all patients and letter VA in 75 per cent of nystagmus patients – particularly those related to dynamic function, such as target recognition time, gaze dependent vision, motion processing and contrast sensitivity.

Dr Hertle found the boy had iris transillumination, foveal and optic nerve dysplasia – and an uncorrected refractive error of -5.00D sphere, +6.25D cyl x 120° right and -5.00D sphere, +6.25D cyl x 60° left.

“It’s hard to believe some of these kids aren’t even given glasses,” said Dr Hertle.

In addition, the patient had typical infantile nystagmus, with its tell-tale increasing velocity slow phase that is a positive indication of infantile nystagmus syndrome (INS). He also showed a static chin-down head posture, which is common but underdiagnosed in albinism, Dr Hertle added.

Employing a staged approach of optical, medical and surgical treatment, Dr Hertle first prescribed spectacles – immediately improving bilateral VA to 20/180. Eye muscle surgery, consisting of bilateral 5.0mm superior rectus recession with inferior oblique myectomy and lateral rectus tenotomy with reatttachment, improved corrected VA to 20/100.

Switching to peripherally tinted contact lenses to block stray light and improve correction over the full range of eye motion brought VA to 20/80, Dr Hertle reported. With the medication baclofen to reduce the associated periodic component of the nystagmus, common in patients with albinism, final binocular letter VA reached 20/70 – good enough to drive with restrictions in most American states.

The outcome was no fluke. In a series of 85 OCA nystagmus patients undergoing the same approach, mean VA improved from a group mean of 20/170 before treatment to 20/80 after,

COVER STORY: PAEDIATRIC OPHTHALMOLOGY As a result, electronic eye movement recording, usually using infrared or highspeed video devices sampling at hundredths to thousandths of a second, is the gold standard for definitive nystagmus diagnosis, Dr Hertle said.

Much like electrocardiography (EKG) enables identification of specific heart arrhythmias by their electrophysiologic signatures, plotting the direction and amplitude of eye movement in time generates waveforms characteristic of specific nystagmus types and subtypes, and even layered coincident types, Dr Hertle noted. But unlike EKG, which is nearly universally available, most ophthalmology practices don’t have eye movement recorders.

So researchers, including Dr Hertle and long-time collaborator Louis F Dell’Osso PhD, have used eye movement technology to classify nystagmus diagnoses – and developed clinical algorithms useable without eye movement technology to diagnose and effectively treat many nystagmus patients.

DIAGNOSTIC CHALLENGES

In his book co-authored with Dr Dell’Osso, Nystagmus in Infancy and Childhood: Current Concepts in Mechanisms, Diagnoses and Management (Oxford University Press 2013 ISBN 978-0-19-985700-5), Dr Hertle provides diagnostic flowcharts that can reliably diagnose many nystagmus types, including many forms of INS, the most common form of nystagmus, based on clinical observation. Just as important, these flowcharts help identify ambiguous cases that will require eye movement studies for a definitive differential diagnosis.

The book also includes treatment algorithms, including specifying nine surgical procedures to treat INS based on clinical variables – a procedure for a chindown (up gaze eccentric null position) is surgical procedure number two in the algorithm, which also includes procedures for nystagmus associated with strabismus.

Dr Hertle calls the algorithms a “black box” approach that simplifies INS treatment.

“It is for surgeons all over the planet who are asking, ‘how can I help these patients, how can I operate and improve aspects of the patients' ocular motor oscillation and improve many visual functions?'” said Dr Hertle, who has helped set up nystagmus services in clinics all over the world.

One surgery algorithm user is Massimiliano Serafino MD, of San

Still, nystagmus is a complex disorder. It involves defects of both the afferent system, including the retina, optic nerve and lateral geniculate nucleus, and the efferent system controlling neurological image processing and ocular motor control. These include the smooth-pursuit, saccadic and vergence systems, Dr Hertle noted. He counts over 40 different types of nystagmus.

Nystagmus can result from multiple causes, some are present in infancy and others acquired later in life; some are benign and others are associated with neurological disease or injury. Its presentation can be inconsistent, with speed, amplitude and direction of the oscillation varying with a patient’s visual exertion and attention, gaze direction, target type and range, use of one or both eyes, fatigue, or even from social pressures or no identifiable reasons.

Moreover, variations in nystagmus eye movement are often subtle. Is the movement truly pendular or jerk? Is the slow phase speed constant or accelerating?

Does the direction and/or intensity change at regular or irregular intervals? Such features can be impossible to determine from unaided clinical observation. Yet distinguishing them is often vital for proper nystagmus diagnosis – and by extension, effective treatment.

This demonstrates a typical “chin-down”, up-gaze eccentric null position common in patients with Type 1 OCA when asked to fixate

NYSTAGMUS ALGORITHMS IN PRACTICE

Medical, optical and surgical combined treatment of the visual system of patients with nystagmus will improve their visual function Richard W Hertle MD

Courtesy of Richard W Hertle MD

Dr Hertle reported at the 3rd World Congress of Paediatric Ophthalmology and Strabismus in Barcelona, Spain.

Other outcomes also improved significantly, including contrast sensitivity and gaze-dependent VA. Non-albino patients, who make up about two-thirds of Dr Hertle’s patients, see similar gains.

Multiple comorbidities are common with nystagmus. Among Dr Hertle’s INS patients, 69 per cent have other eye diseases, 61 per cent associated systemic diagnoses, 62 per cent anomalous head posture, 21 per cent a periodic or aperiodic component, 71 per cent strabismus, and 71 per cent refractive error. Treating all these problems generally yields the most vision improvement, Dr Hertle said.

“Medical, optical and surgical combined treatment of the visual system of patients with nystagmus will improve their visual function. All contribute in different ways in different patients but, by and large, a contact lens or glasses can be as powerful as surgery. Every little bit helps these children and makes a big difference in their visual function.”

5

Giuseppe Hospital, Milan, Italy. “Prof (Paolo) Nucci and I have been using it for five years and it is very useful,” Dr Serafino told the 3rd World Congress of Paediatric Ophthalmology and Strabismus in Barcelona, where he presented his experience with the clinical algorithm for diagnosing nystagmus without eye movement recorders.

THEORY AND FUTURE RESEARCH The theory underlying Dr Hertle’s surgical approach is that reducing nystagmus intensity and correcting head position improves many visual functions, largely by increasing the proportion of time the patient’s fovea spends time on an object of regard (“foveation”). Eye muscle surgery also restores peripheral visual fields (by decreasing esotropia), improves functional vision (contrast sensitivity, visual recognition time, gaze dependent VA, and also improves patients’ comfort and appearance.

Recent discoveries have elucidated that the portion of the surgery where the extraocular muscle is cut reduces nystagmus intensity regardless of whether any movement (recession) or removal (resection) is made – a phenomenon first recognised and reported by J Ringland Anderson MD, of Melbourne, Australia, in his 1959 textbook on ocularmotor surgery, Dr Hertle noted.

Dr Hertle’s working hypothesis is that INS is caused by a defect in the smoothpursuit system, which enables the eye to track moving targets by anticipating their motion, and directing the eye to move accordingly. In INS, this system is not properly damped, resulting in the eye running away, which accounts for the observed acceleration of slow phase EUROTIMES | NOVEMBER 2015

6

COVER STORY: PAEDIATRIC OPHTHALMOLOGY

Patient with OCA Type 1 and peripherally painted, toric, soft contact lens in place in both eyes

movement. The fast phase is corrective and employs the saccadic system to bring the eye back on target.

Dr Hertle further hypothesises that cutting the eye muscles, particularly at the point where the tendon attaches to the globe (its “enthesis”), constitutes a “rebooting” of the brain and taps into central nervous system plasticity similar to a traumatic brain injury during which the brain responds with a period of renewed plasticity. The entheseal damage stimulates the brain to recalibrate resulting in a dampening, or change in gain, of the smooth-pursuit system. The greater potential plasticity of younger brains may also help explain why nystagmus surgery is more effective in children under two and eight years old than in older patients, he noted.

Animal models suggest that proprioceptive nerve endings in the area where the ocular muscles tendons attach to the sclera (enthesis) may be especially

sensitive to disruption that promotes brain plasticity, Dr Hertle said (Dell’Osso LF, Wang ZI. Prog Brain Res. 2008;171:6775. Fackelmann L et al. Prog Brain Res. 2008;171:17-20). This is a current subject of neuroanatomy research.

The relationship between foveation time and VA has been established across populations, and formulae such as the expanded nystagmus acuity function (NAFX) have been developed that predict VA improvement based on how much foveation can be improved with treatment.

But whether the connection is causative on an individual basis is controversial, Larry Abel PhD, of The University of Melbourne, Australia, told the 3rd World Congress of Paediatric Ophthalmology and Strabismus in Barcelona.

Dr Abel noted that several clinical studies show improvements in both VA and foveation waveforms after medical and surgical treatment. However, basic research undercuts the notion that interrupting

Eye movement recording of OCA 1 patient with typical infantile periodic alternating nystagmus. Up on the figure are rightward eye movements and down are leftward eye movements. This figure shows the regular cycle of increasing right beating nystagmus followed by a slowing, then a change in direction to leftward beating nystagmus. This cycle repeats about every 90-100 seconds

EUROTIMES | NOVEMBER 2015

retinal images reduces VA, including one study that found no difference in perception of grating images presented under flashing illumination or steady illumination among subjects with and without nystagmus.

(Dunn MJ et al. Invest. Ophthalmol. Vis. Sci..

2015; 56(9):5094-5101) Another study in which nystagmus patients received small shocks when they made mistakes recognising figures found that the stress actually reduced foveation time, but improved VA (Jones PH et al. Invest Ophthalmol Vis Sci. 2013 Dec 5;54(13):7943-51). “The evidence for causation is weak and there is some contrary evidence,” Dr Abel noted.

Still, the positive effects of nystagmus surgical and medical treatment demonstrated again and again in clinical series cannot be ignored, Dr Abel said. Part of the problem may be that static VA is an inadequate indicator of functional visual performance, which generally includes dynamic and temporal elements in the real world. He suggested that further research is needed to develop outcomes measures that simulate tasks such as finding items in a grocery store or navigating in traffic.

Dr Hertle agreed, and pointed out that VA is not an outcome measure routinely reported when assessing the effectiveness of strabismus surgery. Improvement in eye and head posture, binocular function, reduction of patient effort to see, and improvements in social function are considered reason enough.

Most of all, Dr Hertle wants more surgeons to recognise that treating nystagmus is not a lost cause. “I’m really hoping that ophthalmologists who see these patients will go from ‘there’s nothing I can do’, to ‘maybe there’s something I can do’, to ‘there is something I can do,’ and then do it.”

Richard W Hertle: rhertle@chmca.org Massimiliano Serafino: massimiliano.serafino@multimedica.it Larry Abel: label@unimelb.edu.au

10–14 September

2016

XXXIV Congress of the ESCRS Bella Center, Denmark

www.escrs.org

SPECIAL FOCUS: PAEDIATRIC OPHTHALMOLOGY

SUBLUXATED LENSES Surgery at younger age, better pre-op VA may improve visual outcomes.

Howard Larkin reports

Y

oung children who underwent surgery earlier for subluxated lenses had better mean visual outcomes than those who waited longer between diagnosis and surgery, according to a review of cases treated during 16 years at Birmingham Children’s Hospital, UK. Patients with better visual outcomes also were younger on average at both the time of presentation and surgery.

The results, based on 49 eyes operated in 27 patients, suggest that opting for conservative management of significantly subluxated lenses in the early years of life may increase the risk of poor visual outcomes, Aditi Gupta FRCOphth told the 3rd World Congress of Paediatric Ophthalmology and Strabismus in Barcelona, Spain. This could be in part because the longer the duration of visual blur in the first few years of life, the more it may interfere with visual development during this critical period, she said. (see Figure 1) The study’s aim was to review management of children with nontraumatic subluxated lenses, and identify factors associated with poor visual outcome, Dr Gupta said. The retrospective case review covered 16 years, and included all patients diagnosed with subluxated lenses with mean follow-up of four years.

Lensectomy was offered to children with significant change in refractive error, the edge of the lens close to the pupillary plane (see Figure 2), pupillary block glaucoma, and an inability to correct visual acuity (VA) with refractive correction and amblyopia management.

After lensectomy, patients received aphakic spectacles or contact lenses.

Degree of lens subluxation and related complications were noted along with treatments provided, and best corrected visual acuity (BCVA) before and after treatment.

Overall, 36 patients with nontraumatic subluxated lenses in 66 eyes were identified. Of these, 49 eyes of 27 children underwent lensectomy, while

Courtesy of Manoj V Parulekar FRCS, FRCOphth

8

Figure 1: Optical aberrations induced by subluxated lens crossing the visual axis

Figure 2: Retcam image of subluxated lens

17 eyes of nine children were managed conservatively. Mean age at diagnosis was 4.2 years, ranging from 10 months to 12 years. Marfan disease was the most common presumed cause in 58.5 per cent of cases, with isolated ectopia lentis in 30.5 per cent, homocystinuria in 8.3 per cent and Stickler syndrome in 2.7 per cent.

The younger the age at surgery, the better the visual outcomes. BCVA was worse after treatment in the conservatively managed group than the surgically managed group, Dr Gupta reported.

Among the conservatively managed group, 18 per cent achieved BCVA of 0.3 logMAR, or 20/40, or better compared with 55 per cent in the surgically managed group.

Among the surgically managed group, mean post-op BCVA was better among patients with better pre-op BCVA, Dr Gupta said. “In the eyes with preoperative VA less than 0.6, we had a mixed outcome, whereas all the cases

Most authors do say that early treatment is beneficial but this is an ongoing debate Aditi Gupta FRCOphth EUROTIMES | NOVEMBER 2015

with preoperative VA 0.6 or better, had a uniformly good outcome.”

Of the 49 eyes operated, 11 with preop BCVA of 0.6 logMAR or better all achieved 0.3 or better postoperative vision.

However, among 38 eyes with pre-op BCVA worse than 0.6 logMAR, just 16 (42 per cent) achieved 0.3 logMAR or better post-op, another 10 (26 per cent) achieved between 0.3 and 0.6 logMAR post-op, and the remaining 12 (32 per cent) ended up worse than 0.6 logMAR post-op.

Younger age was also a success factor.

Patients who underwent surgery earlier in life had a better visual outcome and this was irrespective of preoperative visual acuity, Dr Gupta noted.

Among the 12 operated eyes ending up worse than 0.6 logMAR, mean age was 3.9 years at presentation and 6.3 years at surgery. By comparison, mean ages in the patients with 10 eyes between 0.6 and 0.3 logMAR and 27 eyes 0.3 or better were about 18 months younger at presentation, at 2.45 and 2.3 years respectively, and more than two years younger at surgery, at 4.2 and 4.1 years.

The interval between diagnosis and surgery was also about seven months shorter in the two better outcomes groups, which were nearly identical at 1.75 and 1.8 years compared with 2.4 years in the poorest outcome group.

RACE AGAINST TIME These results suggest that earlier surgery for subluxated lenses in young children contributes to better visual outcomes, Dr Gupta said. “Most authors do say that early treatment is beneficial but this is an ongoing debate. It is still not clear exactly when is best to intervene.”

However, she noted that subluxation does progress, and based on this study, preop BCVA less than 20/70, or logMAR 0.6, and age of about four years should also be considered as surgical indication because they are associated with better visual outcomes independent of pre-op BCVA. “It would be nice if we could identify the rate at which the lens subluxates – it would make our lives so much easier. But it is a race against time and a clinical challenge in trying to reduce the risk of amblyopia,” Dr Gupta said.

Aditi Gupta FRCOphth, Manoj V Parulekar FRCS, FRCOphth, Birmingham Children’s Hospital, UK Contact: manoj.parulekar@bch.nhs.uk

SPECIAL FOCUS: PAEDIATRIC OPHTHALMOLOGY

CONGENITAL CATARACTS Aphakia when cataracts removed in the first six months of life.

Cheryl Guttman Krader reports

T

he role of primary intraocular lens (IOL) implantation when operating on congenital cataracts in infants less than six months of age has been controversial. Speaking in Barcelona, Spain, at a joint symposium of the 3rd World Congress of Paediatric Ophthalmology and Strabismus and the XXXIII Congress of the ESCRS, M Edward Wilson MD said the decision should be individualised and evidence-based as much as possible.

The only Level I evidence on this issue supports leaving a baby aphakic if the surgeon believes that the family will likely be successful with contact lens correction, said Dr Wilson, Professor of Ophthalmology and Paediatrics, Storm Eye Institute, Medical University of South Carolina, Charleston, USA. He reviewed the findings from the Infant Aphakia Treatment Study (IATS), the only multicentre, randomised controlled trial evaluating outcomes of infants undergoing cataract surgery with and without IOL implantation.

Contrary to the investigators’ expectations, analyses of data from follow-up when children M Edward Wilson were ages one and 4.5 years showed no difference in median visual acuity between the group that underwent primary IOL implantation and children receiving a contact lens to correct aphakia. Findings of the safety review, however, showed rates of complications, adverse events, and additional intraocular surgeries were higher in the primary IOL implantation group.

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Bella Center, Copenhagen, Denmark Preceding the XXXIV Congress of the ESCRS 10 – 14 September 2016

POTENTIAL RISKS The IATS also found fewer returns to the operating room during the first year of life in the aphakic group, which is important considering the potential risks of repeated general anaesthesia during this critical period of neurodevelopment. In addition, cataract surgery is faster and less traumatic to the eye if the child is left aphakic, and children using contact lenses for correction do not need to wear glasses, said Dr Wilson.

“Furthermore, contact lens correction gives maximum flexibility to adapt for the rapid and unpredictable changes in axial length and refractive error occurring during infancy. I think it is better to choose IOL power at age five or six, at the time of secondary implantation, than when the child is just six weeks of age,” he told delegates.

Dr Wilson also pointed out that the circumstances of a particular case may influence the surgeon’s decision about IOL implantation. Such factors would include the complexity of the case or if the eye is very microphthalmic.

“Not all infant cataracts are alike, and there is not one best treatment for every case. In addition, participants in multicentre clinical trials must fit certain criteria, and so the evidence may not apply to every patient you see,” he added.

www.wspos.org

M Edward Wilson: wilsonme@musc.edu EUROTIMES | NOVEMBER 2015

9

SPECIAL FOCUS: PAEDIATRIC OPHTHALMOLOGY

IMAGING STRABISMUS MRI transforming understanding of extraocular muscle anatomy and function. Dermot McGrath reports

D

iagnostic scanning with magnetic resonance imaging (MRI) has dramatically altered current understanding of the anatomy and function of the extraocular muscles (EOM), Joseph L Demer MD, PhD told delegates attending the 2015 Congress of the European Society of Ophthalmology (SOE) in Vienna, Austria.

“In the 21st Century we have available to us MRI imaging of the actual anatomy of the EOM, which allows us to directly observe the function of the EOM. Orbital imaging is now available in living people at near microscopic resolution in the orbit,” he said.

Advances in imaging techniques have also enabled discovery of the extraocular muscle pulleys, which have fundamentally changed understanding of the actions of the muscles, said Dr Demer, Professor of Ophthalmology at Jules Stein Eye Institute and Professor of Neurology at University of California, Los Angeles, USA. “Imaging can demonstrate EOM function as well as anatomy, and can therefore distinguish neurological from mechanical causes of strabismus, and mechanical causes are a substantial proportion of all forms of strabismus,” he said.

Courtesy of Joseph L Demer MD, PhD

10

PRACTICAL APPLICATIONS There are numerous practical clinical applications of lessons derived from orbital imaging, Dr Demer said. “It allows us to make diagnoses and design surgeries on a rational basis that should give us better outcomes for our patients.”

Dr Demer said that while MRI has become the standard of care in many medical and surgical fields, ophthalmology has lagged behind in realising the enormous potential of this imaging technology.

“Orthopaedic surgeons, for instance, make very effective and complete use of MRI imaging in their surgical planning and diagnostic studies. As ophthalmologists we do make extensive use of imaging techniques for the anterior and posterior segments of the eye, including ultrasound, optical coherence tomography and fluorescein angiography. But as ophthalmologists we have not really taken full advantage of the capabilities of imaging of the back of the eye, of those anatomical structures behind the eye in the orbit,” he said.

UNIQUE CHALLENGES Imaging the living eye in all its dynamic complexity brings its own unique challenges, said Dr Demer.

“By optimising techniques to minimise the movements of the eye, controlling fixation with targets and using sequences like T2-weighted fast spinecho MRI imaging, we can now explore the functional anatomy of the orbit,” he said.

MRI imaging has already made a major contribution EUROTIMES | NOVEMBER 2015

A contracting extraocular muscle has an increase in volume and a relaxing one has a decrease in volume Joseph L Demer MD, PhD

High resolution, T1 weighted axial (top) and quasi-coronal (bottom) MRI of orbits of patient with left esotropia and axial high myopia. The quasi-coronal view at lower right shows inferior displacement of the left lateral rectus muscle associated with absence of the LR-SR band ligament

to understanding the functional anatomy of the orbit, thanks to the discovery of the connective tissue pulleys within the orbit, said Dr Demer.

The existence of these pulleys has profound implications for the kinematics or rotational properties of the globe, all of which can be summarised in the active pulley hypothesis, he added.

“The active pulley hypothesis proposes that the global layers of muscles do insert on and rotate the globe whereas the orbital layers of muscles do not. The orbital layers move the pulleys anteriorly and posteriorly during contraction and relaxation,” he said.

Imaging can also demonstrate directly the function of the EOM, said Dr Demer. For instance, recent work by Dr Demer and his colleague Robert A Clark has helped to define a metric for the contractility of the EOM. “A contracting extraocular muscle has an increase in volume and a relaxing one has a decrease in volume. By examining a mid-posterior region of the orbit between 8mm and 14mm posterior to the optic nerve junction, we can measure volume changes within that region which are very effective indicators of the contractility of the EOM,” he said.

This type of metric can be useful clinically in the diagnoses of certain conditions such as superior oblique palsy, he said.

Dr Demer concluded his lecture with an appeal to the assembled ophthalmologists. “Please consider incorporating MRI imaging of the orbit and the EOM into your practices in addition to the type of imaging that you have been doing all along for the retina, the cornea and the anterior segment.”

Joseph L Demer: jdemer@jsei.ucla.edu

FOUR EVENTS ONE VENUE Bella Center, Denmark

XXXIV Congress of the ESCRS

16th EURETINA Congress

7th EuCornea Congress

WSPOS Paediatric Subspecialty Day

10–14 September www.escrs.org

8–11 September www.euretina.org

9–10 September www.eucornea.org

9 September www.wspos.org

12

CATARACT & REFRACTIVE

ENDOPHTHALMITIS Endophthalmitis after intravitreal injections – current prophylactic strategies based on conjecture, not proof. Roibeard O’hEineachain reports

T

here is as yet no proven prophylaxis against endophthalmitis following intravitreal injections. However, increasing data from registries of patients receiving the treatments may yield some useful clues, said Ulf Stenevi MD, Sahlgrenska University Hospital, Mölndal, Sweden.

“With all the different types of combinations being used today, from giving nothing to giving antibiotics before and afterwards, nobody has the numbers to show which is best,” Dr Stenevi told the 19th ESCRS Winter Meeting in Istanbul, Turkey.

Dr Stenevi noted that it was data from the Swedish Cataract Register in a study by Per Montan that led to the ESCRS randomised study, which proved in 2006 that the incidence of endophthalmitis could be reduced five-fold following cataract surgery through the use of intracameral antibiotics.

On a similar basis EyeNet in Sweden has established a database, the Swedish Macula Register, comprising all patients in the country with exudative age-related macular degeneration (AMD) who qualify for intravitreal injections.

“EyeNet has gathered more information about this than anybody else. They not only gather information about every single injection given in our country, but also produce an annual report,” Dr Stenevi said.

GATHERED DATA From 2007 to 2013, the Swedish Macula Register gathered data from 16,000 patients and 110,000 injections. The data showed that the rate of endophthalmitis remained fairly stable throughout that time, although as the number of injections administered increased, so did the number of cases, from zero in 2007 to six in 2013. However, the following year there was a sudden rise in incidents of the complication, which is as yet unexplained.

“Something strange happened last year. Fifteen cases were reported and those cases are now being evaluated and looked at from every viewpoint. We don't know what it was that caused this significant increase,” he said.

Dr Stenevi noted that, overall, the Macula Register data showed that the incidence of endophthalmitis per intravitreal injections, 0.026 per cent, was already as low as that after cataract surgery using intracameral antibiotics, 0.027 per cent, in the Swedish Cataract Register. However, as patients receive several injections the incidence was magnified seven-fold to 0.18 per cent.

“But this is a mixed bag. We don't know if these patients got antibiotics before, during Ulf Stenevi MD or after,” he emphasised.

We will need to sort this out properly through the Macula Register when we have endophthalmitis prophylaxis data on 100,000 injections

EUROTIMES | NOVEMBER 2015

In 2013, EyeNet began to record data concerning the prophylactic antibiotics strategies taken with each patient as well as other measures taken against infection, such as gloves and masks, how the eye was prepared, and whether or not it was a surgeon who performed the procedure.

“EyeNet are now in their third year of accumulating this information and eventually they might come up with a strategy that is better than the one we're using now.

But we don't know that of course,” Dr Stenevi said.

EVIDENCE Regarding current practice, he noted that a survey of 41 Swedish clinics showed that 93 per cent performed the procedure in an operating room, and the rest performed them in an office setting. The survey also showed that four out of the 41 centres used preoperative antibiotics, 39 used postoperative antibiotics and two clinics used no antibiotics.

One study that actually examined the relationship between prophylactic antibiotics and endophthalmitis was conducted at Wills Eye Hospital in 2013.

It involved 117, 171 intravitreal injections and showed that the incidence of endophthalmitis was, in fact, marginally higher (0.049 per cent) when patients received postoperative topical antibiotics than when they received no postoperative antibiotics (0.032 per cent), but the difference did not reach statistical significance.

Given that the incidence per injection is already so low, the question arises whether it can be brought any lower with any available type of prophylactic measure, Dr Stenevi said.

“We will need to sort this out properly through the Macula Register when we have endophthalmitis prophylaxis data on 100,000 injections. If there seems to be a safer way of doing things, that would be the starting point of a prospective randomised study. You need to do that to be sure of your conclusions, otherwise it's just rumours,” he added.

PAN-EURPOEAN REGISTRY In the meantime, the ESCRS has joined forces with EURETINA to create a pan-European registry of endophthalmitis cases occurring after either cataract surgery or intravitreal injections.

Those submitting case data to the register are asked to include details of preparation of the eye, including antibiotic prophylactic measures. Also included is the species of bacteria identified, the treatment given and the patient’s outcome.

“When and if you run into an endophthalmitis case, you should report this to the ESCRS/EURETINA register to help gather further information about the aetiology, the treatment, and the result of treatments,” Dr Stenevi said.

Ulf Stenevi: ulf.stenevi@oft.gu.se For further information visit: www.eyenetsweden.se and www.escrs.org

CATARACT CATARACT & REFRACTIVE & REFRACTIVE

MEASURING IOL POSITION Intraoperative OCT allows precision of IOL position.

Tired of seeing those unhappy patients?

Leigh Spielberg MD reports

W

hat is a primary difference between the various intraocular lens (IOL) power formulas?” asked Oliver Findl MD, of Vienna, Austria. “It is how they take into account the effective IOL position,” Dr Findl told a session of the XXXIII Congress of the ESCRS in Barcelona, Spain.

“According to a study on IOL power calculation, postoperative anterior chamber depth, and thus IOL position, is the number one cause of error. So how can we get a direct measurement of future IOL position?”

Dr Findl proposed intraoperative optical coherence tomography (OCT) as a means to accomplish this.

Intraoperative OCT gives the opportunity to double-check preoperative findings, and allows a precise prediction of the IOL position in the aphakic eye, he said.

He discussed the results of his study using Visante from Carl Zeiss, an anterior segment OCT that is attached to the operating microscope and provides continuous intraoperative OCT videos. He also noted that, although intraoperative aberrometry might have value, intraoperative changes such as the effect of the lid speculum must be taken into account.

Further, aberrometry offers no prediction of IOL position.

In a study of 203 primarily short and long eyes, standard cataract surgery was performed and a capsular tension ring (CTR) was placed in the bag. Once the CTR had been placed, providing a taut, positionally stable capsular bag, the intraoperative OCT was used to measure the anterior chamber depth. The study compared the measurements provided by optical biometry (IOLMaster 500, Lenstar + ACMaster), autorefraction, subjective refraction and the intraoperative OCT. “The best predictor of IOL position turned out to be the anterior capsule at the edge of the rhexis, with the CTR in place. This was even better than using the axial length,” reported Dr Findl.

Two different IOLs were used in the study: an open-loop IOL (Tecnis one-piece from AMO) and a plate haptic IOL (Asphina from Zeiss).

The study results suggest that inserting the OCT results into an IOL power calculation formula would greatly improve the value of the anterior chamber depth variable within the formula.

The predicted OCT-based results compared favourably to those predicted by fourth-generation IOL power calculation formulas.

A future goal of Dr Findl’s would be to fuse intraoperative OCT measurements with ray tracing to further refine refractive outcomes, and to use the intraoperative OCT during corneal endothelial surgery.

It is how they take into account the effective IOL position

Oliver Findl: oliver@findl.at

Oliver Findl MD EUROTIMES | NOVEMBER 2015

13

CATARACT & REFRACTIVE

ASTIGMATISM MEASURE Novel parameter quantifying total corneal astigmatism offers best match with refractive cylinder. Cheryl Guttman Krader reports Figure 1: Corneal topographic astigmatism (CorT) is calculated using all the data captured during acquisition

Courtesy of Noel Alpins MD, NewVision Clinics

14

Figure 2: Ocular residual astigmatism (ORA) – the vectorial difference between corneal astigmatism and refractive cylinder (at the corneal plane) is expressed in dioptres

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orneal topographic astigmatism based on total corneal power (CorT total) provides an accurate and consistent measure of astigmatism, said Noel Alpins MD at the XXXIII Congress of the ESCRS in Barcelona, Spain.

CorT total is derived using individual data for anterior and posterior corneal power measurements. In 2012, Dr Alpins and colleagues reported that CorT anterior, a corneal power measure based on anterior corneal power measurements only, corresponded better with manifest refractive cylinder in both magnitude and orientation than simulated keratometry, corneal wavefront, manual keratometry, and automated keratometry (Alpins N et al. J Cataract Refract Surg. 2012;38(11):1978-88).

Now, a study evaluating the performance of CorT total showed that it corresponded better with manifest refractive cylinder, both in variability and closeness, than CorT anterior and consequently the other measures also.

“Accuracy for the total astigmatic power of the cornea and its meridian is of utmost importance when correcting astigmatism, and CorT gives more accurate information than other parameters because it is derived from all measured data rather than from only a limited area of the cornea,” said Dr Alpins, Medical Director, NewVision Clinics, Melbourne, Australia. (see Figure 1) “Therefore, when planning toric intraocular lens selection and orientation, or the length and orientation of limbal relaxing incisions, we believe cataract surgeons should use the CorT parameter, total or anterior depending on whether their tomography/topography system measures the posterior and anterior cornea or just the anterior surface,” he added.

The study comparing the performance of CorT total and CorT anterior has also been published (Alpins N et al. J Refract Surg.

2015;31(3):182-6). It included data from 526 surgically-naïve eyes of patients presenting for laser vision correction.

Corneal power measurements obtained with the Sirius tomographer (Costruzione Strumenti Oftalmici) were used to determine total and CorT anterior values for each eye.

Correspondence of the CorT values with refractive cylinder was analysed based on calculations for ocular residual astigmatism (ORA) mean magnitude and standard deviation. ORA is the vectorial difference between the corneal astigmatism and the refractive cylinder at the corneal plane. (see Figure 2) EUROTIMES | NOVEMBER 2015

Compared with CorT anterior, CorT total had significantly lower values for both mean ORA magnitude (0.30 vs 0.32D) and ORA variability (SD 0.53 vs 0.64D), that is the CorT total was closer to the manifest refractive cylinder than CorT anterior. (see Figure 3) “A lower mean ORA magnitude indicates closer correlation between refractive cylinder and corneal astigmatism, and a lower standard deviation indicates lower variability,” Dr Alpins explained.

CorT total is now available on these tomography platforms that measure total corneal power – CSO Sirius, Pentacam (Oculus), and Galilei (Ziemer). Those three systems, as well as the Atlas (Carl Zeiss Meditec) and OPD-Scan III (Nidek), have the capability of providing CorT anterior. The iAssort software is required for calculation of the CorT parameter (www.assort.com).

Noel Alpins: alpins@newvisionclinics.com.au Dr Alpins discusses the details of measuring CorT in an Eye Contact video interview at: www.eurotimes.org/eyecontact

Figure 3: The CorT total is closer in magnitude and orientation to the refractive cylinder than CorT anterior and Sim K

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CATARACT & REFRACTIVE

REFRACTIVE TARGET Better information from various devices could improve outcomes.

Leigh Spielberg MD reports

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e’re getting closer and closer to the best possible surgical results regarding refractive target after cataract surgery, Stephen Lane MD, Minnesota, USA, told the XXXIII Congress of the ESCRS in Barcelona, Spain.

His presentation, entitled “New & Precise Technologies to Evaluate Astigmatism”, described several commercially available machines that can help cataract surgeons achieve the desired results.

“Each modality provides different measurements, so we have to take this into consideration when planning surgery.

No one system is perfect, and there are variabilities between the measurements of each one. But when the results are all different, you can tell your patient, ‘We have the best equipment available, and they’re each telling us something different. So it’s possible that we’ll have to come back to perform a second procedure to perfect the result’,” he said.

For example, the Cassini uses multicoloured LED point-topoint ray tracing, combined with second Purkinje imaging technology and high-resolution images utilised for surgical guidance. Second Purkinje reflections are present on the posterior cornea. “Cassini allows you to import directly to Truevision, which is very convenient,” said Dr Lane.

Alternatively, the Galilei combines Placido-disk function with a dualScheimpflug analyser and ray tracing through the anterior and posterior corneal surfaces, Stephen Lane leading to more accurate representations of total corneal power, he said.

Dr Lane next discussed the Verion Image Guided System, a comprehensive astigmatism planner that is not only a measurement guidance tool, but also includes a microscopeintegrated display.

He pointed out what he considers to be a very useful feature in the interface: the astigmatism slider bar, which allows surgeons to select their preferred balance of astigmatic correction between toric intraocular lens (IOL) power and relaxing incisions in a single calculation.

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The ORA System with VerifEye, the last system discussed, uses wavefront aberrometry data in the measurement and analysis of the refractive power of the eye.

“It has a real-time, intraoperative refractometer and a working algorithm supported by a large clinical database of more than one hundred thousand cases,” said Dr Lane.

“And now, the question that you may want me to be able to answer definitively is, ‘Is there a gold standard?’ While many of these tools give us excellent information, the most important factor is the surgeon’s capacity to gather the correct information from what’s available and use it in the best possible way to achieve great outcomes,” asserted Dr Lane.

Stephen Lane: sslane@associatedeyecare.com

EUROTIMES | NOVEMBER 2015

CATARACT & REFRACTIVE

17

EFFECTIVE APPROACH Customising depth of focus provides good uncorrected near and intermediate vision. Cheryl Guttman Krader reports

DETERMINING THE TARGETS Patients were assessed at about two weeks after cataract extraction and LAL implantation with measurements of refraction, SA, depth of focus, and pupil diameter. Through-focus VA was measured using trial lenses, and a depth of focus curve was fitted using a normalised three-parameter Gaussian function. A

Courtesy of Eloy A Villegas PhD, Laboratorio de Óptica, University of Murcia

I

mplantation of the light adjustable lens (LAL, Calhoun Vision) with adjustment to customise depth of focus shows promise as an effective approach for presbyopia correction after cataract surgery in patients with a history of myopic LASIK, reported Eloy A Villegas PhD at the XXXIII Congress of the ESCRS in Barcelona, Spain.

Dr Villegas reported outcomes for six post-myopic LASIK eyes comprising two small subgroups classified and treated based on the initial magnitude of their positive spherical aberration (SA) and depth of focus. Following customised irradiation of the LAL, they achieved mean visual acuity (VA) of about 20/22 at far, 20/20 at intermediate, and 20/26 (J2) at near.

“We recently reported that in cataract patients implanted with the LAL, controlled induction of negative SA extends the depth of focus and improves near vision (Villegas EA et al. Am J Ophthalmol. 2014;157(1):142-9). However, post-myopic LASIK patients present a special challenge. As the refractive surgery can induce positive SA, these patients may present with high and variable SA,” said Dr Villegas, Associate Professor of Optics, University of Murcia, Spain.

“Our approach using the LAL takes the variability in SA into account and customises depth of focus both in terms of the range and power position by adjusting both refraction and SA to achieve optimal visual outcomes,” he added.

Average values of monocular visual acuity at different distances after lens adjustments

depth of focus parameter was estimated as the dioptric power range providing decimal VA of 0.8 or better.

Then, the LALs were irradiated with appropriate light profiles to adjust the SA and refraction in order to optimise depth of focus and the quality of near vision.

Myopic shift of best focus was customised in all eyes in order to optimise the depth of focus position according to the visual needs of each patient.

The two subgroups of post-LASIK eyes consisted of one cohort of four eyes with high positive SA (>+0.3μm and pupil diameter of 3mm), and the second cohort included two eyes with low positive SA (0.05μm to 0.15μm and pupil diameter of 4 to 5mm). Depth of focus averaged 3.1D (range 2.1 to 4.0D) for the eyes with high positive SA and was 1.5D and 1.7 D, respectively, for the two eyes with low positive SA. “Since the depth of focus was already good in the eyes with high positive SA, our

With this myopic shift we were able to increase VA at near and intermediate distances while maintaining good VA outcomes at far distance Eloy A Villegas PhD

target with the light customisation was to adjust the optimal position of the depth of focus. In contrast, the aim of the light adjustment in the eyes with low positive SA and lower depth of focus was to induce negative SA in order to increase their depth of focus,” Dr Villegas explained.

MYOPIC SHIFT The customisation goals were achieved.

Mean depth of focus remained 3.1D in the eyes with high positive SA. In the eyes with low positive SA, mean SA was -0.10μm after the customisation procedure and depth of focus increased to 2.5D and 3.0D, respectively, in the two eyes.

A mean myopic shift of -0.6D was induced in the eyes with high positive SA and of -1.34D in the eyes with low positive SA. “With this myopic shift we were able to increase VA at near and intermediate distances while maintaining good VA outcomes at far distance,” Dr Villegas added.

As a comparison, he showed functional data for a control group of five eyes that had no history of LASIK, low positive SA (0.05 to 0.15μm and pupil diameters of 4.0 to 5.0mm), and a mean depth of focus of 1.9D. While their mean VA was excellent at far distance (20/20), it was about 20/35 at intermediate, and J10 (20/100) at near.

Eloy A Villegas: villegas@um.es EUROTIMES | NOVEMBER 2015

CORNEA

HERPETIC KERATITIS Antivirals remain the mainstay of prophylaxis and treatment.

Roibeard O’hEineachain reports

H

at office, recurrences accounted for erpes simplex around 60 per cent of cases, and 30 keratitis (HSK) per cent of the episodes of herpes and herpes zoster keratitis were related to identified ophthalmicus triggering factors.

(HZO) are not “The risk factors for recurrence so uncommon may be divided between physical and conditions, which biological. The physical factors may account for a high cost to society in be ultraviolet light and ocular surgery, terms of visual disability and medical but also biological factors due to and surgical intervention. However, immunosuppressive treatment, as recurrences and the conditions’ well as ophthalmic solutions that more devastating ocular effects can may reduce the immunity or increase be prevented in about half of patients (or simulate) the inflammation, for through the use of antiviral therapy, example steroids and prostaglandins said Marc Labetoulle MD, Bicêtre respectively," he added.

Hospital, South Paris University, Eyes of patients with a previous Paris, France, in a keynote lecture history of herpes simplex that are at a Cornea Day Session at the undergoing keratoplasty therefore 19th ESCRS Winter Meeting in represent the perfect scenario for Istanbul, Turkey.

HSK. The procedure involves a HSK usually occurs after 20 years huge severing of corneal nerves, of age. In the European populations an acute inflammation following studied, the lifetime risk of it is 0.23 surgery and the application of per cent by 30 years, 0.49 per cent by steroids postoperatively to reduce 50 years, 0.94 per cent by 80 years, he A case of herpes ophthalmicus with several vesicules on the skin, including the tip of this inflammation. noted. The incidence of the disease is the nose, predictive of a high of ocular involvement (Hutchinson’s sign) For those reasons, antiviral about 30 per 100,000 population per prophylaxis against HSK is year and the prevalence is about 150 mandatory in patients with a history of HSV who are undergoing per 10,000. Herpes zoster generally occurs in patients older than 60 keratoplasty. Research going back 20 years shows that years. The lifetime risk of the disease is 10-30 per cent of people, and acyclovir 400mg twice daily reduces the recurrence rate of herpes that of zoster ophthalmicus is one per cent to four per cent. simplex by half.

Very severe damage to the cornea is not uncommon in the There is some evidence that increasing the duration of treatment natural history of both diseases. In the case of HSK, there is an from 12 months to 18 months will reduce the recurrence rate 11 per cent risk of vision less than 20/200 in an affected eye at 20 further. There are also alternative agents to consider such as years following the first occurrence. In addition, HSK accounts for valacyclovir, which is more bioavailable than acyclovir and can be about 10 per cent of graft indications and for about a third of graft taken with food without loss of effect. failures. The rate of HSK recurrence following a corneal graft is 25 per cent at one year and 45 per cent at two years.

Dr Labetoulle noted that almost everyone is at some risk for OCULAR COMPLICATIONS HSK and HZO. Studies suggest that antibodies to the viruses The same antiviral agents may be used for occurrences of varicella are present in up to 90 per cent of people by the age of 50 zoster keratitis, especially in the days to weeks following HZO. years. In addition, PCR studies of cadaveric Research has established that a dosage of 800mg acyclovir five times tissues, especially the trigeminal ganglia, have a day for seven days reduces the incidence of ocular complications detected the virus in around one in five of the keratitis and corneal hypoesthesia and neurotrophic keratitis. individuals at 20 years of age and in all More recent studies have indicated that 1000mg valacyclovir patients at 60 years of age, even in the three times a day for seven days may produce better results in rare patients without serum antibodies terms of reducing pain and inflammatory complications during to the virus. occurrences of HZO. Famciclovir produces equivalent results to After the first episode of herpetic valacyclovir, as does brivudine, he noted. keratitis, the risk for In those who have not yet had a reactivation of the varicella recurrence rises steadily virus, the best way to prevent HZO is to use the varicella vaccine during the years following during childhood and zoster vaccine during adult age. In the the first episode, from 10 per Shingles Prevention study, which involved over 38,000 patients cent at one year to 20 per cent over 60 years of age, a highly concentrated investigational vaccine at two years, 40 per cent at halved the incidence of herpes zoster and reduced the neurological five years and 60 per cent at aggressiveness of the virus in cases where the disease occurred: 20 years. Dr Labetoulle noted unlike antiviral therapy, the vaccine also halved the incidence of that a study he conducted post-herpetic neuralgia. with the late Prof Joseph Colin showed that among Marc Labetoulle: marc.labetoulle@bct.aphp.fr Marc Labetoulle MD patients presenting with HSK Courtesy of Marc Labetoulle MD

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The risk factors for recurrence may be divided between physical and biological

EUROTIMES | NOVEMBER 2015

CORNEA

INTRA-OP IMAGE

Vioron

4D technology brings depth-based guidance to surgeons in real-time. Cheryl Guttman Krader reports

4

Staining solution for intraocular use

4D imaging guidance of the descemetorhexis during Descemet’s stripping automated endothelial keratoplasty (DSAEK). The white box in the 3D volume marks the location of the 2D B-scan

bubbles and that there are no peripheral scrolls at the graft edges,” Mr Pasricha said.

4D imaging from a deep anterior lamellar keratoplasty (DALK) case showed how the technology guided accurate positioning of the needle before injecting air to separate Descemet’s membrane and stroma.

The value of 4D imaging as a training tool was investigated in a randomised controlled study evaluating the ability of ophthalmology residents to perform various depth-based anterior segment manoeuvres on porcine eyes. Residents who first performed the steps under direct MI-OCT guidance outperformed controls who trained without that real-time feedback. However, the performance of the controls improved when they operated with the 4D guidance.

The 4D imaging technique is also being developed for use in vitreoretinal surgery, and it has been evaluated during macular hole, retinal detachment and epiretinal membrane procedures.

Neel Pasricha: neel.pasricha@duke.edu

Courtesy of Neel Pasricha, Duke University

D imaging’ that integrates swept-source optical coherence tomography (OCT) in the surgical microscope to provide real-time volumetric visualisation has exciting potential as a clinical and teaching tool for ophthalmic surgery, reported Neel Pasricha at the 2015 annual meeting of the Association for Research in Vision and Ophthalmology in Denver, USA. “Currently used ophthalmic surgical microscopes can only provide an en face view of the surgical field and so the visual depth needs to be inferred. As OCT provides direct depth information, its integration with the microscope allows for simultaneous dynamic imaging and surgery,” explained Mr Pasricha, a medical student at Duke University, Durham, North Carolina, USA. He works with Dr Anthony Kuo in the Duke MI-OCT imaging team led

by Dr Cynthia Toth and Dr Joseph Izatt, the co-inventors of this technology.

The OCT system has custom tracking hardware, an A-scan rate of 100kHz with 500 A-scans per B-scan, and a volume rate of 2Hz, which means the information is updated twice per second. In its original iteration, the MI-OCT information was displayed only on a computer monitor.

Now a microscope-integrated stereoscopic heads-up display has been engineered that allows visualisation of the MI-OCT volumes through the surgical binoculars.

Presenting intraoperative videos, Mr Pasricha demonstrated use of the 4D system for actively guiding manoeuvres during cataract and cornea transplant surgeries.

The dynamic imaging captured creation of a biplanar cataract incision, grooving of the nucleus with the phaco probe, and verification of incision integrity at the end of the procedure during provocative testing.

Steps highlighted during Descemet’s stripping automated endothelial keratoplasty (DSAEK) included the descemetorhexis, graft unfolding, air tamponade, and final checking of the graft interface.

“With the 4D imaging, the surgeon can be confident that the interface is free of

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Neel Pasricha EUROTIMES | NOVEMBER 2015

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20

CORNEA

CORNEAL BLINDNESS Long-term preserved corneas can help reduce the burden of corneal blindness. Sean Henahan reports

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orneas preserved cases in the developing world, using glycerin or where a high proportion of corneal gamma irradiation transplants are often emergent have an important therapeutic grafts or tectonic role to play in the grafts,” said Dr Oliva, an Associate treatment of blinding Clinical Professor in the Division corneal disease in the of International Ophthalmology, developing world, at Casey Eye Institute and Oregon Matt Oliva MD told a session of the Health Sciences University, USA. World Cornea Congress VII in San Glycerin, or glycerol, is a Diego, USA. colourless, odourless substance with “There is a huge amount of corneaantimicrobial properties. It was first related blindness in the developing used to store corneas as far back as world, with a 2010 World Health 1955. Corneas stored in this medium Organization estimate putting can be stored for up to five years the number at 4.9million cases of and require no refrigeration. One of bilateral cornea blindness that could the benefits of glycerin processing potentially have vision restored is that it removes all cells, reducing with a cornea transplant. Factor in antigenicity, and potentially leading unilateral corneal blindness, and to less rejection episodes with the number goes up to 10million lamellar grafts. Another benefit is people who could benefit,” noted Dr that these corneas can be pre-cut Oliva, Associate Medical Director to be carriers for keratoprostheses for SightLife Eye Bank. and work well for glaucoma tube There are many factors related shunt coverage. They also produce to the current worldwide shortage good results when used for lamellar of corneal transplants being keratoplasty, he noted. performed, including lack of “One downside of using glycerinsurgeon training, availability of preserved corneas is the preparation supplies in the developing world, process. It takes about 20 minutes Preoperative and postoperative day 1 pictures of a patient with advanced fungal and transportation issues in getting to remove the cornea from the keratitis treated with therapeutic keratoplasty using glycerol preserved tissue corneas to surgeons and patients. glycerol, and rehydrate it in a saline However, the biggest issue continues and antibiotic solution. The cornea to be the lack of available tissue for corneal surgeons practising in becomes leathery and hazy, and it is a little bit tricky to work with. the developed world, he emphasised.

You need to thin it and debride the non-viable epithelium and “In the developing world setting, we often need to have corneas endothelial cells before it can be used,” Dr Oliva explained. we can pull off the shelf for an emergent case in order to save an Gamma irradiation for preservation of corneas using cobalt eye. Long-term storage medium offers an opportunity to stabilise or electron beam irradiation offers many of the same benefits. the situation until a fresh cornea becomes available. Although with This technique produces an acellular sterile cornea, with good long-term storage the corneal endothelium is not viable, placing maintenance of the stromal architecture. These corneas work much corneas into glycerin or irradiating them also offers us the ability like an optisol-preserved cornea, with no rehydration required, he to use corneas that may otherwise go to waste due to expiration. said, although there is not viable endothelium, as with glycerinThis also can allow high-quality fresh tissue to be used for optical preserved tissue.

EUROTIMES | NOVEMBER 2015

CORNEA

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INCREASE CORNEA SUPPLY

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Glycerol preserved cornea used as a patch graft to treat a patient with a limbal dermoid

Matt Oliva: moliva@cureblindness.org

Courtesy of Matt Oliva MD

In the developing world the biggest applications for long-term preserved corneas are for therapeutic and tectonic grafts. They can also be used for limbal dermoids, for therapeutic lamellar keratoplasty, or for optical deep anterior lamellar keratoplasty (DALK). In the developed world these corneas have an important role in glaucoma tube shunt surgery.

“I’m really excited about the use of long-term preserved corneas for optical-quality DALK. There are two retrospective clinical studies comparing DALK performed with glycerinpreserved corneas and optisol-preserved corneas. These showed no difference at one year in terms of thickness, spherical equivalence or best corrected visual acuity (BCVA) between the groups,” he said.

He stressed that it could take a little while for the surgeon to get used to using the glycerin-preserved corneas. They do need to be rehydrated, and they often need to be manually debulked.

Since the epithelium can heal very slowly there is a low threshold for tarsorrhaphy in cases.

“If we are going to combat corneal blindness worldwide we need to increase the cornea supply. Long-term preserved corneas allow use of corneas that would otherwise be discarded.

There are many benefits to having them on the shelf. While there are subtle differences between glycerin- and gamma irradiation-preserved corneas, both are really useful for increasing transplantation rates,” Dr Oliva concluded.

Preoperative and postoperative day 1 pictures of a patient with advanced fungal keratitis treated with therapeutic deep anterior lamellar keratoplasty using glycerol preserved tissue

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EUROTIMES | NOVEMBER 2015

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CORNEA

PRE-DESCEMET’S LAYER New technique associated with encouraging early results along with real and postulated benefits. Cheryl Guttman Krader reports

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escemet’s membrane endothelial keratoplasty (DMEK) is now considered the gold standard keratoplasty procedure for eyes with endothelial damage. However, pre-Descemet’s endothelial keratoplasty (PDEK) has now emerged as a promising alternative.

PDEK uses a graft comprised of Descemet’s membrane (DM) and endothelium splinted by the pre-Descemet’s layer (PDL or “Dua’s layer”), which was discovered by Harminder S Dua MD, PhD, Professor of Ophthalmology, University of Nottingham, UK. Speaking at the 6th EuCornea Congress in Barcelona, Spain, Dr Dua reviewed outcomes in an initial PDEK case series demonstrating viability of the new technique. In addition, he described potential advantages of PDEK and new instrumentation for PDEK graft harvesting designed to overcome one of the challenges of this new procedure.

The outcomes paper reported on five eyes, reported by Dr Dua with Amar Agarwal MD, Chennai, India (Agarwal A et al. Br J Ophthalmol. 2014;98(9):1181-5). Preoperatively, best corrected visual acuity (BCVA) ranged from 0.02 to 0.17 and central corneal thickness was between 604μm and 790μm.

Postoperative follow-up showed successful graft attachment, and no interface abnormalities. Corneal clarity was achieved with good visual acuity, and at one month after surgery, corneal thickness values ranged from 508μm to 591μm.

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Achievement

POSSIBLE BENEFITS Compared with the DMEK graft that is comprised of DM and endothelium only, the presence of the PDL in the PDEK graft improves handling ease, said Dr Dua. “The additional 10μm to 20μm of stromal support from the PDL reduces the scrolling tendency of the Descemet’s membrane, making the PDEK graft easier to unroll in the eye. It is also easier to centre the PDEK graft, which can be done by stroking the graft on the PDL with a blunt spatula,” said Dr Dua. Endothelial cell survival is also expected to be better after PDEK, in part because much of the endothelial cell loss after DMEK is attributed to the time and handling spent with graft unscrolling.

In addition, findings from a study performed by Dr Dua and colleagues measuring endothelial cell density before and after PDEK and DMEK grafts by pneumodissection suggest there may be better endothelial cell survival after preparation of the PDEK lenticule. (Altaan SL, et al. Br J Ophthalmol. 2015;99(5):710-3) “This was an ex vivo study, and the difference between PDEK and DMEK was not statistically significant. However, we can say that corneal endothelial cell loss after tissue handling and processing is at worst the same for PDEK compared with DMEK and possibly lower for PDEK,” Dr Dua said.

He noted that the opportunity to use younger donors, which bring higher endothelial cell counts, is another advantage of PDEK compared with DMEK. As reported by Dr Agarwal, PDEK has been performed successfully using tissue from donor eyes of infants as young as nine months. (Agarwal A et al. Cornea.

2015;34(8):859-65) “In contrast, most surgeons performing DMEK prefer using tissue from donors older than age 50 because of the strong adhesion of the DM to the underlying stroma (PDL) and increased risk of tearing,” Dr Dua said.

Whereas a large graft, up to 9mm in diameter, can be obtained when harvesting the DMEK lenticule, PDEK graft size is limited to 7mm to 8.5mm which represents the maximum diameter of a Type 1 bubble. If the Type 1 bubble that forms does not expand to the desired diameter, the margins can be extended using a blunt spatula because the PDL offers a surgical cleavage plane.

Formation of a Type 2 bubble, however, necessitates conversion to DMEK graft harvesting.

Aiming to avoid the latter situation, Dr Dua has been working to develop instrumentation for consistently achieving a Type 1 bubble. He reported that a third prototype device was in final testing and expected to become commercially available by the end of 2015.

“This instrument should almost completely stop a Type 2 bubble from forming and should give users greater confidence to perform PDEK because they will know they can obtain the tissue they need,” he said.

This was an ex vivo study, and the difference between PDEK and DMEK was not statistically significant Harminder S Dua MD, PhD

Harminder S Dua: harminder.dua@ nottingham.ac.uk

CATARACT & REFRACTIVE CORNEA

CMV CORNEAL DISEASE Japanese study sheds light on CMV endotheliitis.

Dermot McGrath reports

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arly diagnosis remains crucial in preventing loss of endothelial cells and unnecessary treatment resulting from misdiagnosis in patients with cytomegalovirus (CMV)-induced corneal endotheliitis, according to a recent study.

“Our research highlights the effectiveness of antiviral treatment for CMV endotheliitis, but further study is needed to establish treatment regimens for the disease in order to prevent corneal endothelial dysfunction,” reported Noriko Koizumi MD, PhD at the 2015 Congress of the European Society of Ophthalmology (SOE) in Vienna, Austria.

CMV endotheliitis was first reported by Prof Koizumi and her colleagues in 2006. Recently, attention has been focused on CMV as an etiologic factor of anterior segment inflammation in immunocompetent individuals.

While CMV endotheliitis is recognised as the most common virus implicated in corneal endotheliitis, diagnostic criteria and a standardised treatment protocol have yet to be established, said Prof Koizumi, Professor, Doshisha University/Kyoto Prefectural University of Medicine, Japan.

Nevertheless, much progress has been made thanks to the Japan Corneal Endotheliitis Noriko Koizumi Study Group, which proposed diagnostic criteria for CMV endotheliitis based on a viral examination

by PCR of aqueous humour in combination with clinical manifestations. A national survey was then retrospectively conducted among 1,160 members of the Japan Cornea Society to review the patient profiles, clinical manifestations, and treatment modalities of individuals who met the diagnostic criteria for CMV endotheliitis. “To the best of our knowledge, this is the largest case series of CMV endotheliitis to report the comprehensive clinical features of this newly identified infectious corneal disease,” said Prof Koizumi.

The study included 109 eyes of 106 patients from 30 different clinics and centres in Japan, with 79 diagnosed as typical CMV endotheliitis and 30 as atypical CMV endotheliitis. The mean patient age was 66.9 years, with 85 males (80.2 per cent) and 21 females (19.8 per cent) identified.

Patients were commonly diagnosed with anterior uveitis and ocular hypertension prior to confirmation of CMV endotheliitis. Coin-shaped lesions were observed in 70.6 per cent, and linear keratic precipitates in 8.3 per cent of the patients, respectively. In terms of treatment, anti-CMV drugs were administered in 95 per cent of cases, said Prof Koizumi.

The effect of anti-CMV treatment was clinically evaluated one month after initiation of anti-CMV treatment in 96 eyes.

While combined systemic and topical anti-CMV therapy was found to be more effective than systemic or topical antiCMV treatment alone, the difference was non-significant, said Prof Koizumi.

Noriko Koizumi: nkoizumi@mail.doshisha.ac.jp Study reference: Koizumi N et al. British Journal of Ophthalmol 2015;99(1):54-58

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DRY EYE SYNDROMES Tear film biomarkers could improve diagnosis of dry eye.

Leigh Spielberg MD reports

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ear film biomarkers offer the potential to significantly improve the diagnosis and management of dry eye syndromes, Franz Grus MD, PhD told a session of the 6th EuCornea Congress in Barcelona, Spain.

“We all know that there is a poor correlation between clinical parameters and disease severity in dry eye syndromes. More advanced and objective indicators of abnormalities would be very useful in the management of these diseases,” said Prof Grus, Head of Experimental Ophthalmology at the University Medical Center Mainz, Germany.

Presenting during a focus session on dry eye diagnosis and management, Prof Grus discussed so-called biomarkers, which are measurable indicators of a particular biological state or condition.

“Our goal is to identify and validate the potential protein biomarkers present in the tear film for the spectrum of dry eye diseases using Franz Grus a targeted proteomics strategy. This would allow us to take a very small tear film sample, identify a cluster of proteins and employ this to signal the presence of dry eye. We could then distinguish between different dry eye subgroups based on their expression levels,” said Prof Grus.

Protein and peptide expressions reflect the current state of disease or health, a ‘snapshot’ of body functions at any given time. Obtaining and analysing these molecules might be of great help in both diagnosis and prognosis of these varied and often complex conditions.

“Dry eye disease also currently suffers from a lack of objective criteria for clinical trials of new treatment options, and biomarkers might alleviate this need,” he added.

Protein microarrays are used to detect upregulation of proteins such as calgranulin, an inflammatory marker expressed by neutrophils that is elevated in all dry eye subgroups.

TISSUE COATING Microarrays can also detect downregulation of a biomarker like proline-rich protein 4 (PRR4), which mediates protective functions on the ocular surface, such as modulation of microflora. PRR4, which is abundant in tears but decreased in dry eye subgroups, is also thought to be of protective importance in the tear film.

“We have even noticed changes in biomarker profiles after patients switch from conserved to unconserved intraocular pressure-lowering drugs. Besides looking for the proteins themselves, we also try to discover post-translational modifications, which may largely determine the ultimate cell regulatory function of these proteins, as well as their resistance against degradation,” said Prof Grus.

The use of biomarkers is a promising approach for diagnosis and better understanding of the disease pathomechanisms within the dry eye spectrum, as well as personalised medicine based on the biomarkers present in each patient, he emphasised.

Franz Grus: grus@eye-research.org

EUROTIMES | NOVEMBER 2015

CORNEA

FUNGAL KERATITIS Intrastromal injections worth considering for recalcitrant fungal disease. Leigh Spielberg MD reports

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argeted drug delivery might offer a solution for the treatment of recalcitrant fungal keratitis, given the limitations of topical antifungal therapy, Namrata Sharma MD told a session of the 7th International Congress on Ocular Infections in Barcelona, Spain.

“Topical antifungal therapy has poor ocular penetration and bioavailability, so we have looked into both intrastromal and intracameral drug injection for those infections non-responsive to conventional topical and systemic antifungal therapy for four weeks,” said Dr Sharma, All India Institute of Medical Sciences, New Delhi, India.

Indications for intrastromal injections include deep mycotic keratitis, non-perforated corneal ulcers and postoperative interface lamellar infection, a complication that is likely to become more prevalent with the increasing number of lamellar surgeries performed.

Drugs that have been tested include amphotericin B (5.0-7.5μg/0.1ml/5% dextrose), voriconazole (50-100μg/0.1ml) and fluconazole 0.2 per cent. A single intrastromal injection of 10μg amphotericin B achieves an effective drug level in corneas for up to seven days in a rabbit model. However, corneal oedema can occur at high doses, she said.

In a study published in 2011, Dr Sharma and her team injected intrastromal voriconazole in 12 eyes of 12 patients with recalcitrant fungal keratitis. Of these, 10 eyes healed with scar formation, while two eyes required therapeutic penetrating keratoplasty (PKP).

RECENT STUDY In a more recent study of non-responders to topical two-hourly natamycin five per cent therapy for 14 days, 40 patients were randomised into treatment with either hourly topical voriconazole or at least three intrastromal voriconazole injections.

Both groups also received identical topical treatments, including natamycin, homatropine and ciprofloxacin. Baseline characteristics were comparable in both groups, including organism culture positivity rate of around 60 per cent.

There was no statistical difference in mean duration to healing between the two groups. Adverse events of perforation and posterior synechiae were similar, although pain was reported more frequently in the intrastromal group (p=0.05), reported Dr Sharma.

Dr Sharma suggested adding intracameral antifungals in cases in which hypopyon was present. Taking this concept to the next level, Dr Sharma reminded delegates of the 2014 study by Pallikaris et al in which the 150kHz Intralase iFS laser was used to create a corneal pocket into which antifungals can be deposited.

Another possibility for intrastromal delivery is Natamatrix, which is a tiny, dissolvable matrix that can be inserted into the stroma. “The pharmacokinetics of intrastromal drug injection need further study, but this is a treatment modality that might offer hope to those with recalcitrant fungal corneal infections,” she concluded.

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Namrata Sharma: namrata.sharma@gmail.com EUROTIMES | NOVEMBER 2015

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CORNEA

MANAGING DRY EYE Tear film oriented therapy takes a layered approach.

Leigh Spielberg MD reports

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ear film oriented therapy, which tackles dry eye symptoms by separating the components of the disease, allows physicians to take a targeted approach to dry eye disease management, reported Serge Doan MD at the 6th EuCornea Congress in Barcelona, Spain.

“Tear film oriented therapy is an approach that I adapted from the Dry Eye Society of Japan.

In this approach, the components of the ocular surface are separated conceptually, allowing the clinician to target specific components of the system, such as the tear film, the epithelium or the underlying sensory nerves,” explained Dr Doan, Hôpital Bichat and Fondation A de Rothschild, Paris, France.

Dr Doan defined the tear film layers, namely the lipid, aqueous and mucous layers. Next comes the epithelium, with goblet cells and membrane associated mucins; the ocular surface inflammatory response; and the underlying sensory nerves.

He discussed both well-known treatments and newer therapeutic targets. He addressed the lipid layer first.

“Besides warm compresses and lid hygiene, oral tetracyclines are still the mainstay of treatment for meibomian gland dysfunction (MGD).

But azithromycin has a longer half-life and a better safety profile. It has high tissue penetration and both anti-inflammatory and antibacterial lipase activity,” he said.

A multicentre controlled randomised study conducted by the Théa company demonstrated benefits of topical azithromycin Serge Doan versus placebo, particularly with repeated treatment cycles, he noted.

Dr Doan also discussed LipiFlow®, a heated ocular surface device with a pump mechanism designed to express meibomian gland secretions during a 12-minute treatment session.

“The effects at two weeks are superior to lid hygiene, and 80 per cent of patients respond,” he reported. The aqueous layer was next. “Of course, artificial tears and sodium hyaluronate should be tried first, moving on to punctal plugs,” he said.

Dr Doan noted that added benefit might be seen when a second plug is also placed in the superior punctum.

“Despite other advances, I believe scleral lenses are among the best treatment options for severe dry eye. The point of contact is on the sclera so they don’t touch the cornea or limbus.”

Dr Doan pointed out that a reservoir of tears develops under the lens, offering continual hydration to the ocular surface.

Scleral lenses also have an analgesic effect, although some patients might find them difficult to insert, and cost, availability and the complexity of lens fitting remain barriers to their use.

Oral secretagogues such as pilocarpine and cevimeline are also used, but Dr Doan pointed out that their use was limited by side effects. Dr Doan advocated the use of cyclosporine eye drops such as Ikervis 0.1%®, approved in Europe since March 2015. The cationic emulsion of Ikervis offers electrostatic attraction, leading to higher corneal concentration of cyclosporine in animal models, he said.

Serge Doan: serge.doan@noos.fr EUROTIMES | NOVEMBER 2015

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GLAUCOMA

PROCEED WITH CAUTION

If patients have a basic understanding of what their doctors are doing and why, doctors will feel much safer doing the surgery. Roibeard O’hEineachain reports

A

beginner surgeon’s chances of success in their first cases involving eyes with cataract and glaucoma are greatly enhanced through a slow and well-considered approach, said Thiemo Rudolph MD, FEBO, Sahlgrenska University Hospital, Gothenburg, Sweden, at a Young Ophthalmologists Symposium at the 19th ESCRS Winter Meeting in Istanbul.

“Once you have mastered the basics of a new skill, there are two ways you can go, you can go faster or you can attempt more difficult challenges. Both are perfectly legitimate goals, but doing both things at the same time is something you should try to avoid. This is true in general, but I think it is particularly true when it comes to cataract surgery in glaucoma patients,” Dr Rudolph said.

The slow approach to cataract surgery in such cases begins early in the patient assessment and treatment planning stages of the procedure. Glaucoma patients require a very detailed preoperative work-up, with many more variables to consider than in a normal cataract patient.

The surgeon, together with the patient, must weigh the individual contribution of the two separate pathologies to the patient’s vision loss as well as the risks of the surgery to the optic nerve and future intraocular pressure (IOP) control.

TREATING TWO PATHOLOGIES In a glaucoma patient with a cataract and poorly controlled IOP, the first important EUROTIMES | NOVEMBER 2015

Crucial variables to consider before doing cataract surgery in a glaucoma patient

decision is whether to perform the cataract or the glaucoma procedure first, or alternatively, the two combined.

The current consensus supports the performance of the cataract procedure first, Dr Rudolph said. For example, the European Glaucoma Society’s guidelines state that modern phacoemulsification with clear corneal incisions will not reduce the efficacy of subsequent filtration surgery, and that cataract surgery following glaucoma filtration surgery can impair the functionality of the bleb. In addition, combined procedures are generally less

effective than trabeculectomy alone in lowering IOP. When choosing the filtration procedure first, the AGIS study showed that filtration surgery brings with it a 50 per cent risk of cataract within five years. Drainage tube implantation is as cataractogenic as trabeculectomy, but its functionality is less likely to be affected by subsequent cataract surgery.

IOP-LOWERING EFFECT Dr Rudolph noted that studies have consistently shown that

phacoemulsification alone has a small but significant impact on IOP reduction in eyes with open-angle glaucoma. Most of the studies indicate reductions of around 2.0mmHg by one year after surgery.

The reports have mainly concerned primary open-angle glaucoma, but there is also research suggesting that phacoemulsification has a slightly greater IOP-lowering effect in pseudoexfoliation glaucoma.

In eyes with angle-closure glaucoma, phacoemulsification should definitely be considered the first treatment option. Randomised trials show that phaco alone has similar results to phacotrabeculectomy, but with significantly fewer complications, he said.

“In eyes with a narrow angle, dehydrating the vitreous prior to phacoemulsification is essential. Even then, there is an elevated risk of iris prolapse, and for that reason, great care is required when making the main incision. And because you have a more confined space, it is best to keep the phaco tip in the iris plane as much as possible,” Dr Rudolph advised.

He also recommended that surgeons be thoroughly acquainted with the behaviour of the OVDs they use before proceeding with this type of surgery. He added that in his experience using a somewhat cohesive OVD provides a little bit more space in which to work. In all such cases

Courtesy of Thiemo Rudolph MD, FEBO

GLAUCOMA

Advanced cataract in a patient with Rieger’s anomaly and wellcontrolled IOP 20 years after a trabeculectomy

the surgeon should expect a small pupil, because sometimes a small pupil will only become apparent during surgery.

CASE STUDY When a patient who has already undergone glaucoma surgery presents with a cataract, a successful outcome is possible when appropriate precautions are taken, Dr Rudolph said. As an illustration, he described and demonstrated with a video clip the case of a woman who presented with cataract nearly 20 years after undergoing a trabeculectomy with a still-functioning bleb and well-controlled

IOP in one eye, while the other eye was practically blind due to severe amblyopia.

The patient had Rieger’s anomaly and had undergone a trabeculectomy with a large iridectomy in 1996. Following the glaucoma procedure she had a pressure of 10mmHg with a stable visual field defect.

However, in 2014 she began showing the signs and symptoms of cataract.

After receiving carefully considered and thorough information and having some time to think about her options and the risks involved, the patient opted for phacoemulsification and intraocular lens (IOL) implantation.

Special measures that Dr Rudolph used during the procedure included iris hooks to stabilise the pupil and the placement of a capsular tension ring for zonular support.

At her most recent follow-up more than three months after the phaco procedure, the patient’s IOP had returned to its preoperative level without local treatment.

“My take-home message for glaucoma surgeons is simply, don’t be hasty, don’t rush yourself and don’t rush the patient into a decision. If your patient has a basic understanding of what you’re doing and why, you will feel much safer doing the surgery,” Dr Rudolph concluded.

Thiemo Rudolph: thiemo.rudolph@gmail.com

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www.escrs.org EUROTIMES | NOVEMBER 2015

29

GLAUCOMA

SUPRACHOROIDAL MIGS

S

Stents may lower IOP below TM options, transforming glaucoma treatment. Howard Larkin reports

Courtesy of Transcend Medical

tents that shunt aqueous directly from the anterior chamber (AC) to the suprachoroidal space may reduce intraocular pressure (IOP) more than current minimally invasive glaucoma surgery (MIGS) procedures targeting the trabecular meshwork (TM), with fewer complications than traditional filtration surgery, Brian Flowers MD, Fort Worth, Texas, told the 2015 American Society of Cataract and Refractive Surgery Symposium in San Diego, USA. While TM-based MIGS, including implants such as iStent (Glaukos), and procedures such as Trabectome (Neomedix), are very safe and patientfriendly, their potential for reducing IOP is limited by the capacity and potential blockages of the drainage system beyond the TM. In contrast, the suprachoroidal space has almost unlimited IOP-lowering capacity due to its large surface area and negative pressure gradient, Dr Flowers pointed out.

But high outflow capacity also presents risk for hypotony and unpredictable IOP, Dr Flowers noted. So the question becomes: is suprachoroidal MIGS safe?

Several large-scale clinical trials suggest two new stents are not only safe and effective. It may even be possible to prevent or even rescue failures due to inadequate reservoir formation, Dr Flowers said.

Courtesy of Glaukos

30

IMPROVED PERFORMANCE In a US FDA trial of 505 patients completed in March, the CyPass MicroStent (Transcend Medical) met its primary endpoint of lowering IOP 20 per cent from unmedicated preoperative values, and reducing IOP more than phacoemulsification alone for 24 months after surgery.

Similarly, a European study of 83 patients saw IOP reduced 35 per cent among patients whose preoperative pressure exceeded 21mmHg, with mean medications reduced from 2.2 to 1.0 at 24 months, and no sight-threatening

complications or hypotony beyond one month. (Hoeh H. J Glaucoma. 2014 Oct 9.

Höh H. Klin Mondbl Augenheilkd. 2014 Apr;231(4):377-81) CyPass Vx uses viscoelastic injected through the stent to increase the size of the filtration reservoir. Injecting 30 microliters increased the aqueous lake volume 247 per cent, and injecting 60 microliters 321 per cent beyond the

Suprachoroidal surgery may indeed be transformative Brian Flowers MD

CyPass alone, generating reductions in mean IOP of an additional 24 per cent and 41 per cent respectively. This raises the possibility not only of improved performance, but possibly rescuing poorly performing implants, Dr Flowers said.

The iStent Supra (Glaukos) shows similar performance and safety, lowering IOP from 24.8 to 17.0 24 months after surgery. (Belda J. 2014 ESCRS, London) In Dr Flowers’ experience, patients take slightly longer to recover from suprachoroidal stent surgery versus TM-based MIGS. However, the potential for greater IOP reduction may be worth it, and the lack of hypotony is reassuring, he added. “Suprachoroidal surgery may indeed be transformative,” he said.

Brian Flowers: bflowers@oafw2020.com

EUROTIMES | NOVEMBER 2015

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digital.OphthalmologyBusiness.org

Explanted, spontaneously dislocated IOL–capsular bag complexes (see page 929) pages 909–1128

Corneal changes with accommodation Prediction of refractive outcome with toric IOLs Pseudoexfoliation and in-the-bag IOL dislocation Wavefront analysis of aspheric and spherical IOLs Prediction of accommodative response using ultrasound biomicroscopy

Elsevier

Table of contents P. 4, 6 ELSEVIER ISSN 0886-3350

— P. 28

An ASCRS Publication 30-05-2015 07:32:00

The honey bee colony: A model for practice success

Two cases of TASS caused by an oily substance in the anterior chamber

MAY 2015 Volume 41, Number 5

JCRS_v41_i5_COVER.indd 1

P. 24

An ASCRS Publication

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GLAUCOMA

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GLAUCOMA OVERBURDEN Paradigm shift needed for more cost-effective care.

Dermot McGrath reports Tuulonen A. The demand of eye care services in Finland in the 2010s. The Finnish Medical Journal 2014;37:2290-2295

W

ith the number of patients with glaucomarelated pathologies predicted to increase significantly over the next few years, there is a pressing need for health services to work towards creating high-quality, high-volume and costeffective glaucoma care for all citizens, according to Anja Tuulonen MD, PhD. “The overburden of glaucoma services demands a reappraisal of current management strategies. We know that the possibilities of care, demand for services and costs are increasing much more than the available resources, regardless of how our healthcare systems are financed. I believe it is our role as health practitioners to try to make wise decisions in this situation,” she told delegates attending her keynote lecture at the 2015 Congress of the European Society of Ophthalmology (SOE) in Vienna, Austria.

The basic task of glaucoma care is to promote the well-being of patients, said Prof Tuulonen, insisting that practitioners need to be aware that the decisions they make in everyday clinical practice impact, for better or worse, on the quality and cost of healthcare.

Prof Tuulonen, CEO of Tays Eye Centre, Tampere University Hospital, Tampere, Finland, noted that many problems stem from different interpretations as to what constitutes “high-quality” healthcare.

“One definition of excellence is to provide patients with only the care that they need at the optimum time in the most appropriate setting. Another version is that we should be aiming to serve everything to everybody including all new interventions entering the market,” she said.

Faced with ageing populations worldwide, the stark reality for all healthcare systems is to find ways to make their systems more cost-effective.

This raises many questions for glaucoma experts in terms of the right approach to adopt in the face of increasing demands: when is the right time to intervene?; should all patients be systematically screened?; what treatments should be used?; and so forth.

To highlight the way such choices translate to a national level, Prof Tuulonen cited the examples of Denmark and Finland, both of which have 5.4million inhabitants. From 2002 to 2007, Finland treated one-third more patients with

Trends of eye healthcare in Finland, 1986-2014

glaucoma compared to Denmark. Finland also spent more on glaucoma medications compared to Denmark.

“The question is, was Finland overtreating or was Denmark undertreating its patients? For decades we have known that there are enormous variations in performance within and between countries. These variations are produced by everyday clinical decision-making, they are also probably sometimes in conflict with professional ethics, and we do not talk about them a lot,” she said.

Based on the World Health Organisation’s 1948 definition of health as “complete physical, mental and social well-being”, most people alive would be defined as sick most of the time, said Prof Tuulonen. A new and more relevant definition of health, suggested by the British Medical Journal, is “the ability to adapt and self-manage in the face of social, physical and emotional challenges during our lifetimes”.

Efforts have been made in some countries to cut down on waste and target health resources more wisely. In the USA, for instance, there has been the ‘choosing wisely’ campaign to help patients choose evidence-based care and avoid tests and procedures which are not truly necessary, she said.

FUNDAMENTAL CHANGES There are two approaches to making glaucoma care more cost-effective: making the existing system work better,

or by changing the system in more fundamental ways.

The experience of the UK in introducing a national guideline for glaucoma illustrates the side-effects of intrinsically sincere intentions, said Prof Tuulonen.

“The National Institute for Health and Care Excellence (NICE) guidelines for glaucoma in 2008 sought to find patients earlier and follow them more frequently, resulting in suffocating the healthcare system: in some areas it led to a 600 per cent increase in referrals, no gain in finding new glaucoma cases, and a reduction in accuracy in detecting abnormal optic disc,” she added.

More targeted screening programmes for older populations may prove more effective, said Prof Tuulonen, as well as closer follow-up of patients who are deemed to be high-risk.

Advances in tele-ophthalmology applications and home screening devices, as well as other technological innovations, could foresee fundamental changes and help healthcare systems to do more with less money in the future, she said.

“Sustainable glaucoma care means preventing visual disability, producing a feeling of well-being, dealing with a chronic disease or disability with allocated resources and taking into account other eye diseases. To do this we need a paradigm shift. As Einstein said, we cannot solve our problems with the same thinking which created them,” she concluded.

Anja Tuulonen: anja.tuulonen@pshp.fi EUROTIMES | NOVEMBER 2015

RETINA

PRINTING CELLS Printing of functional retinal cells to help cure some forms of blindness could be within reach. Dermot McGrath reports

A

team of researchers at the University of Cambridge, UK has succeeded in using inkjet printing technology to print viable cells of the adult rat central nervous system (CNS), retinal ganglion cells (RGC) and glia.

The research has important implications for the survival and growth of these cells in culture and represents an important step in the development of tissue grafts for regenerative medicine, according to Keith Martin FRCOphth, Professor of Ophthalmology at the University of Cambridge, who led the study.

“This study is proof of the principle that retinal neurons and glia can be inkjet printed and opens up the possibility of using this technology to organise cells in very precise arrangements relative to each other,” he told EuroTimes.

“In the short-term, this may allow us to do new types of experiments on how retinal cells interact, but in the longer-term we are keen to develop ways to start to engineer retinal tissue for retinal repair,” he added.

Prof Martin’s team showed that a piezoelectric print head does not significantly affect the viability of printed adult RGC and glial cells. The research paper, published in the journal Biofabrication (Lorber B et al, 2014 Biofabrication 6 015001; doi:10.1088/17585082/6/1/015001), reported that even though the cells are subjected to very high shear rates and acceleration during jetting, no significant distortion of the cell structures was observed either immediately before or after cell ejection.

“The observations suggest that either the cell membranes possess sufficient strength and elasticity to resist a brief period of high stress, or the geometry of the print head nozzle used results in rather little shear or deformation of the cells during jetting,” the authors reported.

The fact that RGC and retinal glial cells do not appear to be affected by the printing process and retain their phenotype in culture opens up the possibility for studying interactions of these cells when printed in precise locations and patterns, explained Prof Martin. This could enable the creation of cell arrays mirroring the in vivo situation, which would allow screening the effect of novel compounds on cell-cell interactions before application in vivo.

NEW AVENUES The research also opens new avenues for creating printed tissue grafts for use after CNS injury in vivo. While this has only been demonstrated thus far with a few cell types using thermal inkjet printers, Prof Martin and co-workers suggest that RGC and glia may potentially be organised in the future using piezoelectric inkjet printers.

“We have previously used crosslinked fibrin gels to deliver cells to the injured spinal cord in animal models. Given the growth promoting effects of a substrate of printed glial cells, as observed in the present study, it will be interesting to investigate in future studies if a printed fibrin-glial construct might promote functional recovery following optic nerve or spinal cord injury in vivo,” the authors said.

From an ophthalmology perspective, it will be important to extend the research

to other cells of the retina and investigate if light-sensitive photoreceptors can be successfully printed using inkjet technology, said Prof Martin.

“If this can be proven, printing of functional retinal cells to help cure some forms of blindness could be within reach. I think RPE cells and possibly photoreceptors are good candidates, although we have yet to complete these experiments,” he added.

Prof Martin notes, however, that many hurdles still need to be overcome to translate the findings of the research to the living human retina.

“We are a long way from repairing the human neural retina. It remains to be seen if these techniques could be used inside a living eye or whether a better approach will be to engineer tissues outside the eye and transplant later. However, we are a very long way from being able to recreate the complexity of a living human retina which is of course characterised by hugely complex interactions between many different cell types,” he concluded.

Keith Martin: krgm2@cam.ac.uk

Courtesy of Wen-Kai Hsiao, University of Cambridge

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This study is proof of the principle that retinal neurons and glia can be inkjet printed...

Keith Martin FRCOphth EUROTIMES | NOVEMBER 2015

An adult retinal ganglion cell being inkjet printed

RETINA

MACULA LENS HAS PROMISE discover New add-on IOL can improve outcomes for macula disease.

Cheryl Guttman Krader reports

T

he Scharioth Macula Lens (A45SML, Medicontur, Hungary), an add-on intraocular lens (IOL) for near visual rehabilitation in patients with macula disease, was designed to overcome the limitations of existing options and has demonstrated positive results in a proof of concept study enrolling patients with advanced age-related macular degeneration (AMD), according to its developer Gábor B Scharioth MD, PhD. Speaking at the XXXIII Congress of the ESCRS in Barcelona, Spain, Dr Scharioth said that the simple bifocal lens provides about 2X magnification at 15cm, although the exact amount depends on anatomical factors. Made of hydrophilic acrylic, the optic has a central 1.5mm +10.0D optical zone, and a peripheral zone that is optically neutral or can have other powers. The IOL has polished round edges and a special haptic design to prevent iris chafing and/or iris capture.

The lens is implanted through a 2.2mm incision into the ciliary sulcus in the betterseeing eye, and its patented haptics design optimises centration.

“This add-on IOL can be implanted independent of lens status in a safe and easy procedure. It provides sufficient magnification to improve near vision, does not Gábor B Scharioth adversely affect the visual field, distance vision, or retina diagnostics, and is less expensive than other implants as well as reversible,” said Dr Scharioth, Senior Consultant, Aurelios Augenzentrum, Recklinghausen, Germany.

The proof of concept study was launched September 2013 and included eight eyes. There were no complications related to the surgery or implant, and Scheimpflug imaging showed adequate spacing between the add-on and primary IOL.

NEAR VISION Outcomes assessments showed near vision tested with a Radner reading chart improved in seven eyes, with most patients achieving the ability to read newspaper size print.

The patient who had no improvement had very advanced AMD in both eyes and still reported subjective improvement.

Excluding that individual, visual acuity (VA) improved at 40cm by five lines and by 2.4 lines at 15cm. Best-corrected distance VA was unchanged in all eyes.

Dr Scharioth said that any patient with maculopathy complaining about difficulty with near vision is a candidate for the add-on IOL. As a simple screening test, patients are evaluated for improvement in near vision with testing at 15cm (+6.0D) versus at 40cm (+2.5D).

Although the add-on IOL can be implanted at the time of cataract surgery, Dr Scharioth said he prefers patients to undergo cataract surgery first, and then the VA screening test if they are unsatisfied with their vision postoperatively.

He acknowledged that there are financial issues to be solved in terms of coverage and that the selection criteria for the addon IOL also need to be improved.

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Gábor B Scharioth: gabor.scharioth@augenzentrum.org EUROTIMES | NOVEMBER 2015

35

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DRIVING MEDICAL EDUCATION FOR IMPROVED PATIENT CARE

The Vision Academy serves as a forum for retina specialists to exchange knowledge and build best practices. As such, it provides an opportunity to discuss and address new challenges and treatments in ophthalmology driving optimized, compassionate patient care.

The Ophthalmology Global Preceptorship Program facilitates engagement with ophthalmologists and aids their professional development by sharing knowledge and best practice in the in-clinic management of retinal diseases.

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FACILITATING SCIENTIFIC PROGRESS IN EYE CARE

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Global Ophthalmology Awards Program (GOAP) is helping to tackle the growing global health issue of retinal diseases by supporting the research community in their quest for breakthroughs that can significantly impact patients’ lives.

The EyeFocus Accelerator is the world’s first eye care focused tech accelerator for startups that address unmet needs surrounding the detection, prevention and available support for people living with visual impairment or blindness and strive to improve patients’ quality of life.

For more information, please contact: Jennifer Pluim (jennifer.pluim@bayer.com)

For more information, please contact: Melissa Chen Montes de Oca (melissa.chenmontesdeoca@bayer.com)

Date of Prep: August 2015 L.GB.MKT.08.2015.12302 G.SM.STH.04.2015.0500

8–11 September 2016

COPENHAGEN 16th EURETINA Congress

Bella Center, Denmark

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RETINA

VISION BOOST FOR DRY AMD Novel telescopic IOL delivers significant benefits in early trials.

Cheryl Guttman Krader reports

A

new intraocular lens (IOL) based on a Galilean telescope concept (iolAMD) is promising technology for safely and effectively improving vision in patients with dry age-related macular degeneration (AMD), Fritz Hengerer MD, PhD told the XXXIII Congress of the ESCRS in Barcelona, Spain.

Dr Hengerer reported that nine patients have received the novel IOL after undergoing surgery for comorbid cataract at Goethe University Frankfurt, Germany.

Outcomes from follow-up to one year were presented for three eyes of two patients.

All patients regained reading vision and achieved better than expected improvements in visual acuity (VA). In addition, there were no IOL-related complications or cases with posterior capsule opacification.

“We can conclude that this system is ready for routine implantation during a standard cataract surgery,” said Dr Hengerer, of the Department of Ophthalmology, Goethe University Frankfurt.

The concept for the iolAMD was developed by Bobby Qureshi MD, who sought collaboration from Pablo Artal PhD, to refine the optics. It is an injectable two-lens system comprised of a capsular bag-placed -49D 4.0mm optic lens and a sulcus-placed +63D 5.0mm hyperaspheric optic lens with asymmetrical haptics that results in an offset between the two lenses. Together, they create a 1.3X image magnification on the retina with three degrees of foveal displacement.

“A 15° vault of the capsular bag IOL haptics ensures spacing is maintained between the two lenses, which has been confirmed with Scheimpflug imaging,” Dr Hengerer said.

SIMULATION TEST Assessment for potential benefit and to determine proper orientation of the sulcus-placed IOL is done preoperatively in a simulation test. Dr Hengerer noted that the sulcus IOL can also be rotated after implantation if needed to compensate for changes in the macula.

The patients implanted with the telescopic IOL had moderate (stage 3) dry AMD with drusen in the fovea leaving them unable to read. Cataract surgery was performed with standard techniques using a superior postero-limbally placed incision to avoid astigmatism induction.

Preoperatively, distance-corrected visual acuity in the three eyes ranged from 20/125 to 20/800; two eyes had no reading vision and corrected near visual acuity (CNVA) was 20/800 in the third eye. Predicted CNVA ranged from 20/100 to 20/200.

By day four, uncorrected near acuity was equal to or exceeded the predicted CNVA. CNVA at day 30 ranged from 20/25 to 20/40, and the results were the same at six months.

Dr Hengerer said that additional indications for the telescopic IOL include stable wet AMD, myopic macular degeneration, Stargardt disease, Best disease, and residual macular hole after vitrectomy.

Fritz Hengerer: fritz.hengerer@kgu.de EUROTIMES | NOVEMBER 2015

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OPHTHALMOLOGICA

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Not all heads are the same…

VOL: 234 ISSUE: 3

BETTER PREOPERATIVE VISION MEANS BETTER VISUAL OUTCOMES AFTER ILM PEELING Better preoperative best corrected visual acuity (BCVA) is predictive of better postoperative BCVA after pars plana vitrectomy (PPV) with internal limiting membrane (ILM) peeling for idiopathic epiretinal membrane (ERM), a review of the outcomes in 80 patients suggests. A linear regression analysis of the patients’ baseline clinical characteristics, optical coherence tomography (OCT) characteristics and three-month postoperative BCVA showed that only preoperative BCVA was an independent determinant of postoperative BCVA (r = 0.31; p < 0.01) and BCVA difference (r = 0.68; p < 0.01). KG Laban et al, “Prognostic factors associated with visual outcome after pars plana vitrectomy with internal limiting membrane peeling for idiopathic epiretinal membrane”, Ophthalmologica 2015; 234:119-126.

THE MORE OXYGEN REQUIRED, THE GREATER THE RISK FOR SEVERE ROP Longer duration and greater intensity of oxygen supplementation required in premature infants are strongly associated with severe retinopathy of prematurity (ROP), a new study indicates.

In a review of the clinical records of 143 newborn infants with a gestational age of 32 weeks or less, a univariate analysis showed a significant association between severe ROP and gestational age, birth weight, duration of oxygen supplementation, duration of directional positive air pressure and maximum fraction of inspiratory oxygen (FiO2). A multivariate analysis similarly showed a significant association between severe ROP and a longer duration of oxygen supplementation and a higher maximum FiO2.

H Enomoto et al, “Evaluation of oxygen supplementation status as a risk factor associated with the development of severe retinopathy of prematurity”, Ophthalmologica 2015; 234:135-138.

Hand-made in Germany

BETTER VISION AND BETTER HELP MAKE AN IMPROVED LIFE FOR EXUDATIVE AMD PATIENTS The main predictors of quality of life (QoL) in exudative age-related macular degeneration (AMD) patients treated with ranibizumab are visual acuity (VA) outcomes and the quality of the home healthcare and social services patients receive, a new survey suggests. The study involved 416 patients with a mean age of 78.0 years with exudative AMD who had at least one intravitreal injection of ranibizumab within the last six months. They provided responses to the National Eye Institute Visual Function Questionnaire (NEI-VFQ-25). In a bivariate analysis, with long-term illness status, worse vision and higher number of unpaid aids were risk factors for worse QoL, with odds ratios of 2.4, 5.2 and 11.6, respectively. E Matamoros et al, “Quality of life in patients suffering from active exudative age-related macular degeneration: The EQUADE Study”, Ophthalmologica 2015; 234: 151-159.

SEBASTIAN WOLF Editor of Ophthalmologica

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42

JCRS

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EUROTIMES | NOVEMBER 2015

OCT AND PHAKIC IOL SIZING Anterior segment optical coherence tomography (AS-OCT) can be useful for sizing a posterior chamber phakic intraocular lens (IOL), a Russian study suggests. In the first stage of the study, the researchers developed an algorithm using OCT to measure the distance from the iris pigment end to the iris pigment end.

The sulcus-to-sulcus distance was measured using ultrasound biomicroscopy. In the second stage was a retrospective evaluation of 29 eyes of 16 patients. The mean sulcus-to-sulcus distance was similar to the mean distance from iris pigment end to iris pigment end. The posterior chamber phakic IOL sized using the new AS-OCT algorithm had a mean vault of 0.53 ± 0.18mm and did not produce adverse events during the 12-month follow-up. In 16 of 29 eyes, the posterior chamber phakic IOL vault was within an optimum interval. B Malyugin et al, JCRS, “Posterior chamber phakic intraocular lens sizing based on iris pigment layer measurements by anterior segment optical coherence tomography”, Volume 41, Issue 8, 1616-22.

TRIFOCAL VS BIFOCAL IOL Researchers in the Netherlands compared visual outcomes in patients with cataract surgery and bilateral implantation of a trifocal (FineVision Micro F) or bifocal IOL (AcrySof IQ ReSTOR) in a prospective randomised clinical trial. Six months postoperatively, there were no significant differences in refractive outcomes, reading speed, or patient satisfaction. The trifocal group showed a more continuous defocus curve and better results at -1.0D of defocus (P < .01). The mean mesopic contrast sensitivity was higher in the bifocal group (P = .02).

Complete spectacle independence was reported by 80 per cent of trifocal patients and 50 per cent of bifocal patients. S Jonker et al, JCRS, “Comparison of a trifocal intraocular lens with a +3.0 D bifocal IOL: Results of a prospective randomized clinical trial”, Volume 41, Issue 8, 1631-40.

EVALUATING THE CORRECTION OF MILD ASTIGMATISM A group of US researchers conducted a study to re-evaluate the analysis of the correction of astigmatism. Referencing the previous work of Drs Alpins and Edelman, they used mathematical simulations to this end. They determined that correction index (correction ratio) is a useful vector-based metric for the evaluation of refractive procedures. They urged caution when judging the clinical significance of correction index analyses applied to treatments of low amounts of cylindrical refractive error. They emphasise that the decision to surgically correct small amounts of astigmatism should consider the visual demands of patients, the knowledge of the effects of small cylindrical errors on vision, and our ability to precisely measure astigmatism preoperatively and postoperatively.

M Bullimore et al, JCRS, “Correction of low levels of astigmatism”, Volume 41, Issue 8, 1641-49.

THOMAS KOHNEN European editor of JCRS

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“The NAVIS-EX is an image filing software that enables data from various NIDEK diagnostic devices to be stored in a centralised database. With the AL-Scan Viewer, an unlimited NAVIS-EX database is available for reviewing AL-Scan measurement data on an external computer,” said the spokesman. www.nidek.com

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“As part of the agreement, URSAPHARM obtains the exclusive licence for the commercialisation of EvoTears, Novaliq’s first commercially available ophthalmic product for the treatment of evaporative dry eye diseases,” said the companies, as they announced the partnership.

“The cooperation with Novaliq is part of URSAPHARM’s longterm commitment to delivering tomorrow’s ophthalmic therapies by accessing innovative products and platforms with high therapeutic value for patients,” the statement added. www.ursapharm.com www.novaliq.com

METTLER TOLEDO has announced the launch of a new spectroscopic instrument line, UV/VIS Excellence.

“The new UV/VIS Excellence product portfolio includes four models that provide outstanding optical performance: UV5, UV7, UV5Bio and UV5Nano,” said a company spokeswoman.

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TRAVEL

The spectacular view from above Athens

ATHENS

3

TO NOTE...

ATHENS

COUNTRY CODE FOR GREECE: +30 CURRENCY: EURO TIPPING: IF NO SERVICE CHARGE, LEAVE 10-20% BENAKI MUSEUM

Take advantage of the seasonal lull to visit the famous Benaki Museum. It has several satellite buildings, but the main museum is in the Benaki family’s former home, a mansion in downtown Athens. Among much else, the three floors of this beautifully preserved neoclassical building house Greek works of art from prehistory to the present. Exhibits reflect a wider view of the country’s history, tracing the impact of foreign influences on Greek culture. For more information visit: www.benaki.gr

GIFT SHOP The gift shop in the Benaki Museum is itself worth a detour. There’s something for everyone in its selection of unusual and beautiful gifts and souvenirs. These include a range of reproduction Byzantine icons, as well as reproduction jewellery and specially commissioned works by Greek jewellery designers. Some of the shop’s top sellers are: a tree of life paperweight incorporating the design of a Coptic bread stamp for €30; a key ring featuring a reproduction of a silver coin for €105; and a head of Athena on a marble base (42cm high) for €240. View them on the shop’s website at: www.benakishop.gr. If you’ve come on an evening when the museum is open late, follow your visit with dinner in the museum restaurant on the second floor. The restaurant terrace offers panoramic views of the Acropolis, Lycabettus Hill and the National Gardens.

ANCIENT MONUMENTS Off-season is the prime time to view the city’s ancient monuments. They never look more enchanting – or enchanted – as when the old stones are set off by the fresh green following the season’s rains. It’s remarkable how alone you can find yourself on the trails through the Ancient Agora and Kerameikos.

If you have the time and energy, climb up to the Acropolis itself. Simply keep it in view and head up towards it via twisting old streets and overgrown paths. Wear walking shoes, carry a bottle of water, and don’t forget your camera – the views are spectacular.

WINTER IN ATHENS

Despite the economic difficulties, it’s ‘business as usual’ in Greece’s capital. Maryalicia Post reports Athens may have received some bad publicity over the last 12 months, but delegates at the upcoming 20th ESCRS Winter Meeting will find what they’re looking for.

This beautiful and historic city is as welcoming and fascinating as ever, and winter shows it at its best. The city’s museums spotlight treasures; its iconic sites are free of the summer crowds; and Athens’ restaurants, a haven of warmth and hospitality, are bustling with appreciative diners.

Sharing a meal with friends holds a special place in Greek culture; dinner starts late and proceeds at a leisurely pace. Laughter and conversation are as important as the food, so restaurants have an informal vibe. So take your time, and enjoy the experience.

Here are four addresses to enjoy. Bon appetit… or, as the Greeks say, “Kalí óreksi!”

Karamanlidika, in the Omonia district, is only five to 10 minutes away from Monastiraki station. It is a small butcher and delicatessen that also serves as a restaurant.

Housed in a neoclassical building with high ceilings, the restaurant’s bare wooden tables are arranged around a counter displaying cheeses, meats, and condiments. Garlands of smoked meat hang from the ceiling.

The staff will lead you through the menu choices – or even choose for you if you prefer. Try the house Ouzo in any case.

Karaminanlidika is located at: 1 Sokratous and 52 Evripidou St, Central Athens. Tel: +30 210 325 4184; or visit the website (in Greek) at: www.karamanlidika.gr Eleas Gi is a restaurant with a view.

This upmarket establishment in the Kifisia district in the north of Athens is certainly worth a visit. It offers two tasting menus – 14 and 24 “tastes.” Even the smaller menu might present a challenge to the average appetite. A favourite dish is pork and sweet potato baked in a clay pot and served with

a flambéed wine sauce. Among many delights, the chocolate mousse is perhaps the outstanding dessert. Best to book. Tel: +30 210 62 00 005, +30 210 62 06 433; or visit: www.eleasgi.gr Two blocks south of the Acropolis, the Strofi is an established restaurant with a firm fan base. Fine dining is the theme. The food is traditional Greek taverna style, but served in a chic setting. Try kid in parchment and the milk pudding. Booking is highly recommended (and essential for the terrace).

The address is: Rovertou Galli 25, Acropolis, Athens 11742. The Strofi is closed on Mondays but open Tuesday through Sunday.

For more information visit: www.strofi.gr Sometimes a glass or two of wine and a platter of cheese is all you’re looking for.

Try Heteroklito, one of the best wine bars in Athens. Very small, with a few stools at the bar and a couple of tables inside (more on the terrace), it offers a huge selection of Greek wines and a great cheese plate. Visit the website at: www.heteroklito.gr Historical neighbourhood in Athens

EUROTIMES | NOVEMBER 2015

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REVIEW

E L B M U T D N A TILT

lt and

out ti b a w o n k o nted t

ts ever wa u o y g Jacob repor n i n h a t s o y o r e S v r E rolapse. D p o r d y h r o tumble

T

he tilt and tumble technique of phacoemulsification was first described by Dr Richard Lindstrom and is a type of supra-capsular phacoemulsification. It is a useful technique for soft cataracts and up to grade 2 nuclear sclerosis. However, it is not suitable for hard nuclei or mature cataracts. It involves using the pressure built up from a hydrodissection wave to prolapse a pole of the nucleus out of the capsular bag, following which the nucleus is emulsified in parts.

TECHNIQUE A rhexis that is sized slightly larger than normal is important for this procedure.

Ideally, it may be sized between 5-6mm but the denser the nucleus is, the larger the rhexis should be. Once the rhexis is completed, a hydrodissection cannula is used to tent up the capsular rim and a continuous fluid wave is gently irrigated into the sub-capsular space.

As the wave travels forwards, the pressure behind the nucleus increases and causes the opposite nuclear pole to tilt out of the rhexis rim. The anterior chamber (AC) is then filled with viscoelastic which is injected above the prolapsed nuclear pole and also under to prevent it from falling back into the capsular bag with the force of the irrigating fluid from the phaco probe. The phaco probe is then used to engage the nucleus and emulsify it. Once the prolapsed pole is emulsified, the other half of the nucleus is tumbled out of the bag and also emulsified in a similar manner. This is followed by routine cortex aspiration and intraocular lens (IOL) implantation.

EUROTIMES | NOVEMBER 2015

The hydrodissection cannula is inserted under the capsular rim

A hydrodissection wave can be seen initiating a tilting of one pole

ADVANTAGES This is an easy technique to learn with a relatively short learning curve. It may be used in a variety of cases and is especially useful in managing soft cataracts as these are difficult to chop. Attempting to chop a soft cataract within the bag generally

results in cheese-wiring of the nucleus.

Endocapsular emulsification of a soft nucleus also has greater risk of posterior capsular rupture (PCR), as the phaco probe can cut through the soft cataract and rupture the posterior capsule before the surgeon has time to react. Bringing the soft cataract out into a supra-capsular plane allows it to be emulsified safely and being soft, the amount of energy used is less even if emulsified within the AC. The hydroprolapse technique may also be used in patients with denser nuclei. The size of the rhexis, however, needs to be larger depending on the size and density of the nucleus. A minimum size of 5mm is generally adequate for a soft nucleus, but as the nuclear density increases the rhexis should be made correspondingly larger to avoid excessive build-up of pressure within the capsular bag behind the nucleus which can result in a capsular blow-out syndrome.

Soft nuclei may be hydrodelineated and completely prolapsed out into the AC, as the nucleus is small and can be aspirated easily with the phaco probe using vacuum alone without the need for excessive phaco energy.

Larger nuclei may be chopped into two in a posterior chop technique. This is done by embedding the phaco probe into the prolapsed nuclear pole and pulling it further out of the bag. The chopper in the left hand is then held posterior to the prolapsed nucleus and used to divide the nucleus into two halves. These can then be rotated out of the bag and sequentially emulsified.

Hydrodelineation instead of a hydrodissection wave allows only the endonucleus to be prolapsed out and retains the epinuclear shell within the bag. This decreases the size of the nucleus and in turn the amount of phaco energy that is used within the AC. This technique may also be

REVIEW

One pole has been tilted and brought out of the bag

Being soft and small, the entire nucleus is brought into AC for emulsification. In harder nuclei, the prolapsed half is emulsified followed by tumbling out and emulsifying the second half

advantageous in subluxated cataracts where intracapsular chop and other manoeuvres such as nuclear rotation that place stress on the zonules are better avoided.

inadequately sized rhexis. The fluid wave that is seen travelling across the posterior pole of the nucleus gets released by the tilt and prolapse of one pole of the nucleus.

However, if the pole does not seem to prolapse out, excessive and repeated hydrodissection can cause capsular blowout. In this case, the trapped fluid should be decompressed before attempting repeated hydroprocedures. Multi-quadrant hydrodissection may also help to free the nucleus up first, following which a hydroprolapse can be attempted.

Hydroprolapse may also not be preferred in patients with shallow AC or with borderline endothelial function, as emulsification releases phaco energy within the AC closer to the endothelium.

If unavoidable, it is especially important to follow the classical tilt and tumble

DISADVANTAGES Dense nuclei may be too large to be prolapsed out of the rhexis and may therefore cause a capsular bag blow-out and consequent nucleus drop. Mature cataracts that fill the capsular bag completely may not move adequately within the bag with the fluid wave, and are also too large to prolapse out of the rhexis.

Continuing the fluid wave can cause a capsular blow-out syndrome in these cases. Small rhexis may result in a similar blow-out because of excessive pressure behind the nucleus. Even a soft cataract may become difficult to prolapse out of an

in these patients where only one pole is prolapsed and emulsified in the iris plane before tumbling the other half to emulsify as far from the endothelium as possible. In case the entire nucleus does prolapse out, it is easy to push one pole back into the capsular bag.

Hydrodissection and prolapse should never be attempted in a posterior polar cataract, though hydrodelineation may be carried out without risk of PCR. With a small pupil, even though the hydrowave tilts the nuclear pole out of the capsular bag, the iris may not allow it to come into the AC for phacoemulsification. Thus, it is more difficult and should be performed with caution.

CONCLUSION This is a useful technique to learn, which is also easy and safe when performed in the correct manner.

Dr Soosan Jacob is Director and Chief of Dr Agarwalâ&#x20AC;&#x2122;s Refractive and Cornea Foundation at Dr Agarwalâ&#x20AC;&#x2122;s Eye Hospital, Chennai, India, and can be reached at: dr_soosanj@hotmail.com

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