EuroTimes Vol. 21 - Issue 11 by EUROTIMES

SPECIAL FOCUS

PAEDIATRIC OPHTHALMOLOGY

GLAUCOMA UNDERSTANDING PRESSURE:

A NEW WAY TO LOOK AT DISEASE

CATARACT & REFRACTIVE

TECHNOLOGY HAS REVOLUTIONISED IMPLANTATION OF TORIC IOLS November 2016 | Vol 21 Issue 11

EYE ON HISTORY

THE WORK AND LEGACY OF DUTCH PIONEER HERMAN SNELLEN

THE MYOPIA EPIDEMIC Can We Stop It?

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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 Lara Fitzgibbon Designer Monica De Iscar 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 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

CONTENTS

A EUROPEAN OUTLOOK ON THE WORLD OF OPHTHALMOLOGY

3 ESCRS Peter Barry

Fellowship: Society launches annual €50,000 award

SPECIAL FOCUS PAEDIATRIC OPHTHALMOLOGY 4 Cover Story: The myopia epidemic, examining the roles of genetics and environment

7 Refractive surgery

in children – indications for intervention

8 Keratoconjunctivitis:

Different treatment approaches for vernal, atopic forms of disease

9 A model for predicting early-onset myopia

10 US FDA doctor

addresses some key paediatric issues

FEATURES CATARACT & REFRACTIVE 12 ‘New technology

has revolutionised implantation of toric IOLs’

13 Large LASIK studies find

lower rates of all categories of visual symptoms

14 Good outcomes for postLASIK ectasia treatments

www.eurotimes.org

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15 Negative dysphotopsia – grooved IOL could be key to side effects

CORNEA 17 Myopia treatment

alternative – intrastromal corneal ring segments

18 New understanding of

corneal immunology could lead to novel therapeutic approaches

19 ‘Nasal neurostimulation could be a promising approach for dry eye disease management’

RETINA 20 Bringing ocular gene

therapies from bench to bedside

22 The critical role of the

blood-retinal barrier in retinal disease

23 Device enhances precision and safety for delivering stains and heavy liquids

GLAUCOMA 24 Benefits of new

minimally-invasive shunt

OCULAR 26 Screening for Alzheimer’s disease – a novel imaging device

REGULARS 28 Eye on Technology 31 JCRS Highlights 32 Research 35 Industry News 36 Outlook on Industry 37 ESCRS News 38 Eye on History 39 Calendar

25 Understanding pressure – a new way to look at glaucoma

Sponsored by

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As certified by ABC, the EuroTimes average net circulation for the 10 issues distributed between 01 January 2015 and 31 December 2015 is 46,515.

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Mini WELL The Progressive EDOF IOL: One Year Later

EuroTimes & JCRS 1996–2016

Included with this issue... Laboratoires Théa and SIFI Medtech supplements

Towards Less Drops in Cataract Surgery Laboratoires Théa Satellite Symposium XXXIV Congress of the ESCRS 11 September 2016 Copenhagen, Denmark

XXXIV Congress of the ESCRS, Copenhagen, Denmark Sunday 11 September 2016

G. Auffarth

D. Piñero

P. Rozot

G. Savini

E. Ng

EUROTIMES | NOVEMBER 2016

EDITORIAL A WORD FROM RAMESH KEKUNNAYA MD, FRCS

FIGHTING THE CAUSE WSPOS strives to bridge the gap between paediatric and adult eye care professionals

yopia in children is rapidly becoming an their ophthalmic practice, from all around the world. epidemic across the world. Parents are Paediatric cataract, strabismus (including nystagmus), and always anxious to know whether we can retinopathy of prematurity were among the main topics stop the progression of the ever-increasing discussed. It was an extremely instructive session with an power of their children’s spectacles. immense exchange of knowledge by all present. The cover story by Dr Soosan Jacob in We are now working on one of the biggest events in this issue of EuroTimes provides an insight into the most the history of paediatric ophthalmology – the 4th World common issues associated with myopia and the preventive Congress of Paediatric Ophthalmology and Strabismus aspect of its progression. It is an excellent article and I urge (WCPOS) in 2017, which is slated to take place in India. all my paediatric colleagues to read it. EuroTimes True to our Mission Statement would also welcome any comments or observations Expertise Does Not Reside In The Myopia Intervention on the story. One Part Of The World, we Consensus Statement is The scientific committee of the World Society are ensuring that our invited one such effort to provide of Paediatric Ophthalmology and Strabismus global experts will make a a concise guideline on (WSPOS) is constantly trying to provide Consensus difference in learning and the prevention of myopia Statements for controversial topics in the field sharing of knowledge for of paediatric ophthalmology, eye movement paediatric ophthalmologists progression. This document is abnormalities and strabismus. The Myopia residing in and around this very handy for parents as well Intervention Consensus Statement is one such effort part of the world. as treating ophthalmologists to provide a concise guideline on the prevention of We are expecting a large myopia progression. This document is very handy number of Southeast Asian for parents as well as treating ophthalmologists. delegates to attend the 4th WCPOS, thereby making In addition, WSPOS constantly engages in educating it a very big, and more importantly, very valuable ophthalmologists about childhood eye disorders. WSPOS meeting to attend. also encourages paediatric ophthalmologists to improve We look forward to seeing you in huge numbers for the their technique based on some unique surgeries done in 4th WCPOS IV in India, from 1-3 December 2017. Further adults by ophthalmologists. In a nutshell, WSPOS tries to information on the meeting is available at: wspos.org bridge the gap between paediatric eye care and adult eye care professionals, thereby finally providing the best eye care for children. Ramesh Kekunnaya is an The 2016 WSPOS Subspecialty Day on 9 September, Executive Bureau Member of WSPOS; which preceded the XXXIV Congress of the ESCRS in and Head, Child Sight Institute, Copenhagen, Denmark, was an event attended by close LV Prasad Eye Institute, to 150 ophthalmologists who tend to children’s eyes in Hyderabad, India

MEDICAL EDITORS

Emanuel Rosen Chief Medical Editor

José Güell

Thomas Kohnen

Paul Rosen

INTERNATIONAL EDITORIAL BOARD Noel Alpins (Australia), Bekir Aslan (Turkey), Roberto Bellucci (Italy), Hiroko Bissen-Miyajima (Japan), John Chang (China), Béatrice Cochener (France), Alaa El Danasoury (Saudi Arabia), Oliver Findl (Austria), I Howard Fine (USA), Jack Holladay (USA) , Soosan Jacob (India), Vikentia Katsanevaki (Greece), 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-José Tassignon (Belgium), Manfred Tetz (Germany), Carlo Enrico Traverso (Italy), Roberto Zaldivar (Argentina), Oliver Zeitz (Germany)

EUROTIMES | NOVEMBER 2016

ESCRS PETER BARRY FELLOWSHIP

FELLOWSHIP LAUNCHED ESCRS invites applications for €50,000 Peter Barry Fellowship. Dermot McGrath reports

he ESCRS has announced details of the annual fellowship set up to honour the immense contribution of Peter Barry FRCS to European and global ophthalmology. Dr Barry, who served as ESCRS President in 2012 and 2013, died after a short illness in May this year. ESCRS President David J Spalton said that the fellowship of €50,000 would enable a trainee ophthalmologist from Europe to study at a centre of excellence anywhere in the world. “The ESCRS Board decided that it would be a fitting memorial to Peter to commemorate him with an annual fellowship. We hope to make the first award of the fellowship at the congress next year in Lisbon, and I think this is going to train the future leaders of our society,” Prof Spalton said. Applications for the first fellowship award are now open to European trainee ophthalmologists who are 35 years of age or under, who wish to pursue a training programme or undertake research at a centre of excellence anywhere in the world.

DETAILED CV To apply for the fellowship, applicants must have been an ESCRS member for three years by the time they take up the fellowship. They are invited to submit a detailed curriculum vitae along with a letter of intent, outlining their choice of centre and the reasons why they feel they will benefit from such a fellowship. Candidates are also required to provide a letter of acceptance from their intended centre of excellence, as well as a letter of recommendation from their current head of department. The deadline for all applications is 30 April 2017. “The idea is really to keep the format as simple as possible and to invite as many young European trainee ophthalmologists as possible to apply for this fellowship,” said Prof Spalton. “A panel of ESCRS

Board members will select the winner, who will be officially presented with their award by Carmel Barry, Peter’s wife, at the ESCRS Congress in Lisbon in 2017. They would then be expected to pursue the fellowship at the centre of their choice in 2018,” he added. In applying for the fellowship, Prof Spalton urged candidates to orient their preferred choice of centre based on the quality of training and research rather than just its geographical location. “While the USA has traditionally attracted a lot of trainee ophthalmologists over the years, we would really urge applicants to think globally. There are first-class centres and research facilities now in Japan, Australia, India, Asia and elsewhere, and we would encourage candidates to think about what is available in these countries too,” he said. In opting to honour Dr Barry’s huge contribution to the ESCRS and European ophthalmology, Prof Spalton said that the Board had quickly settled on a fellowship as the most appropriate means to achieve this. “We all agreed that this is the most fitting way one could possibly remember Peter. He was a tremendous driver of the ESCRS and was particularly keen on the involvement of younger doctors, which he always insisted were the lifeblood of the organisation for the future. He was always looking for new ways to involve younger members through initiatives such as the Young Ophthalmologists Programme, bursaries to attend our annual meeting and the Observership Grants programme. He was also very passionate about teaching so I think he would definitely have approved of our choice,” he said. Prof Spalton discusses the fellowship in an Eye Contact interview with Sean Henahan at: player.escrs.org/eurotimes-eyecontact/peter-barry-fellowship

The ESCRS Board decided that it would be a fitting memorial to Peter to commemorate him with an annual fellowship

Peter Barry

APPLICANTS FOR THE ESCRS PETER BARRY FELLOWSHIP MUST MEET THE FOLLOWING CRITERIA: Be a European trainee ophthalmologist Be 35 years of age or under on the closing date for applications (30 April 2017) l Have been an ESCRS member for three years at the time of taking up the fellowship (if successful) l l

TO APPLY, PLEASE SUBMIT THE FOLLOWING: A detailed, up-to-date CV A letter of intent of 1-2 pages, outlining your choice of centre for undertaking the fellowship, and the reasons why you feel you would benefit from the fellowship l A letter of recommendation from your head of department l A letter from your potential host institution, agreeing to accept you on the fellowship (if successful) l l

All completed applications should be sent by email to Danielle Maher at: danielle.maher@escrs.org The deadline for submission of all applications is: 30 April 2017

Prof David J Spalton EUROTIMES | NOVEMBER 2016

COVER STORY: PAEDIATRIC OPHTHALMOLOGY

THE MYOPIA EPIDEMIC CAN WE STOP IT? It is now clear that genetics and environment both play a role in the development of myopia. Dr Soosan Jacob reports

he prevalence of myopia has rapidly increased over the last 30 years, with the World Health Organization (WHO) estimating a worldwide incidence of 23%, projected to increase to 50% by 2050. Asian populations, especially Japanese, Koreans and Chinese, have a much higher incidence, especially of high myopia. The increased incidence (myopia in 50% of young adults in the USA and Europe and 90-95% in many EUROTIMES | NOVEMBER 2016

East Asian countries) naturally begs the question as to what is driving this epidemic and if there is something that can be done to stop this. The risk of myopia is three times higher when both parents are myopic than when none are. In the last two decades, more than 20 genetic loci and variants have been identified. Visual feedback regulates eye growth and refractive development. Specific retinal neurons and signalling mechanisms (e.g. changes in normal diurnal dopamine levels that are released

by retinal amacrine cells) that regulate refractive development may cause myopia. Indeed, it is likely that genetic and environmental factors may interact towards development of myopia.

OUTDOOR EXPOSURE Studies have shown the protective effect of outdoor activities in reducing myopic onset and progression in schoolchildren. Increased dopamine release under high light conditions has been thought to reduce axial elongation. Retinal dopamine

is regulated by retinal illuminance, spatial frequency of image, temporal contrast etc. A Chinese study by He et al in six-yearolds showed reduced myopic incidence over the next three years by the addition of 40 minutes of outdoor activity at school. Though longer-term studies are needed, this and other similar studies may indicate a need for lifestyle modifications and change in public policies at school. The Sydney Myopia Study found that participation in indoor sports was not protective and the total time spent outdoors was more important. However, what about the harmful effects of increased UV exposure? Ken Nischal MD, Chief, Paediatric Ophthalmology and Strabismus, Children’s Hospital of Pittsburgh, USA, says: “There is always a balance needed. There is evidence that increased daylight exposure has a protective effect and studies suggest a minimum of two hours a day, however, as outlined by a WSPOS Consensus Statement (http://wspos.org/ sunlight-exposure-and-childrens-eyes), children’s eyes are at higher risk of UV damage and appropriate protection such as UVA/B blocking glasses and brimmed caps are important during sunlight exposure. Remember also that daylight exposure is not always linked to dangerous UV exposure. Climate and geography also play a role.” Ian Flitcroft MD, Consultant Ophthalmologist, Children’s University Hospital, Dublin, Ireland, however states: “Evidence to date has shown that outdoor activity has an influence, but this seems to relate mostly to younger children and has a small to moderate impact on myopia onset. There is now good evidence that it does not influence myopic progression in older children. As authors of studies in China have noted, results have not been as strong as they had hoped. It is therefore a viable but limited intervention for myopia prevention, provided it does not lead to increased UV skin damage. One thing is now certainly clear, claims that time outdoors is the answer are grossly overstated.”

NEAR WORK Near work has also been implicated in myopia development. Retinal defocus and retinal image contrast degradation are thought to trigger eye growth as a compensatory mechanism. Studies have shown that early-onset myopes and progressive myopes have significantly greater axial elongation than emmetropes

A 13-year-old girl doing her homework outdoors with the use of spectacles, in a park in Paris, France

following prolonged near task work. There have also been studies with no significant difference in magnitude of eye elongation in myopic and emmetropic subjects. Contraction of ciliary muscle during accommodation results in forward and inward pulling of choroid, thus decreasing circumference of the sclera, and elongating axial eye length. In individuals with high genetic risk, those with university level education had higher risk of myopia, while those with only primary schooling had a much lower risk. The combined effect of these two factors was far higher than their sum, showing synergy. Twin studies by Dirani et al conclude that degree of educational attainment is strongly associated with genes and these same factors may also be responsible for refractive error development. So, are the worldwide increasing levels of education and increased near work time responsible? Is staring at smartphones and laptops contributing? Do those born to be myopic naturally gravitate to academic studies and near-work occupations, or does engaging in these activities, particularly during development, cause myopia? Though there is no final conclusion on this, the World Society of Paediatric Ophthalmology and Strabismus (WSPOS) statement does suggest that intensity of near work, i.e. sustained reading at closer distance (less than 30cm) with fewer breaks, may be more important than total hours spent. The 20-20-20 rule (focusing 20 feet away for 20 seconds every 20 minutes of near work) may therefore be important not just for decreasing dry eyes but also myopia.

There is evidence that increased daylight exposure has a protective effect... Ken Nischal MD

Courtesy of the film ‘LOSING SIGHT - Inside the Myopia Epidemic’ by Jane Weiner, a co-production of ARTLINE FILMS & JP Weiner Productions, Inc. Camera: Boris Carreté. Copyrighted photos published with permission

COVER STORY: PAEDIATRIC OPHTHALMOLOGY

Evidence to date has shown that outdoor activity has an influence, but this seems to relate mostly to younger children... Ian Flitcroft MD

EARLY INTERVENTION So what can we do about the growing incidence of myopia in young people? Children on pirenzepine gel, cyclopentolate eye drops and atropine eye drops have been shown to have less myopic progression, however side effects such as blurred near vision, photophobia and concerns about long-term safety have discouraged this approach. These agents act not by eliminating accommodation but by anti-muscarinic receptor binding that causes a local retinal biochemical change which slows eye growth. Atropine is traditionally used in many East Asian countries. The landmark Atropine in the Treatment of Myopia (ATOM) studies found a beneficial effect for 1% atropine. Low-dose atropine 0.01% showed great promise for myopia control by over 50% with much lesser side effects. Various mechanisms have been proposed: increased dopamine release by atropine binding to muscarinic receptors of amacrine cells; reduction of γ-aminobutyric acid (GABA) levels; atropine binding to muscarinic receptors on scleral fibroblasts and EUROTIMES | NOVEMBER 2016

COVER STORY: PAEDIATRIC OPHTHALMOLOGY interfering with scleral remodelling etc. Surprisingly, its action may not be via an accommodative mechanism. David Granet MD, Director, Ratner Children’s Eye Centre, Shiley Eye Institute, University of California, San Diego, USA, says: “I already offer lowdose atropine to paediatric patients of Asian origin with advancing myopia. We have extensive discussions about risks, benefits and alternatives with parents. However, I am not sure it will work in eyes with differing iris pigment, genetics and epigenetic phenomenon. There is data suggestive that it will.” Dr Nischal notes: “With any new treatment, most important is for centres in different parts of the world to replicate results. Therefore, it is very important that doctors who start to recommend atropine 0.01% document accurately refraction, axial length and fundoscopy. The Singapore group lead by Audrey Chia have developed booklets for follow-up. "Treatment may be for several years and parents should be counselled about this. If no response, one has to be prepared to increase to perhaps 0.1% atropine. The only way to confirm if ATOM results will be universally applicable is by following the above recommendations. Indicators are that there is a subset of children who are non-responders and whether this subset is higher in non-Asian children is at present unknown.”

HUGELY IMPORTANT TRIALS However, Dr Flitcroft cautions that while ATOM1 and ATOM2 are hugely important trials, significant questions remain. The ATOM2 study relied only on historical controls. It was conducted in a Singaporean population between six-12 years of age, which both racially and in terms of pattern of myopic progression is very different to Europe. There are also questions regarding the effect on axial length from the study data, although a recent network meta-analysis indicates that low-dose atropine had significant effect on axial length. “Unresolved questions include when to start treatment, who benefits most (fast versus slow progressors, younger versus older patients, and possible results in less pigmented Caucasian eyes). Large-scale uncontrolled use of low-dose atropine at this stage carries the risk of muddying the waters enormously. Local compounding pharmacy dilutions also create issues of variable drug dosages, stability and increased risk of infections,” said Dr Flitcroft.

EUROPEAN POPULATIONS Well-organised, placebo-controlled trials in European populations would be needed in order to determine whether the ATOM trial data can be translated to Caucasian eyes. Dr Flitcroft’s group conducted the SHIELD pilot study, EUROTIMES | NOVEMBER 2016

The girl holding her glasses while doing her homework in a park in Paris, France

Done well, orthokeratology has supporting data with regards to rate of myopic progression David Granet MD

which looked at the impact of 0.01% atropine on pupil size, accommodation and quality of life, to assess likely acceptability in Caucasians. Concerns that low-dose atropine may have more side effects and reduced tolerability in lightly pigmented eyes were set to rest in terms of pupil size, accommodation and daily activity impact. “The SHIELD study was a prelude to what will be Europe’s first placebocontrolled trial on efficacy and acceptability of low-dose atropine in a European population. We (Dr Flitcroft and Prof James Loughman) have just received funding for this Dublin-based clinical trial and will begin recruitment in early 2017. It will also examine the mechanism of action of atropine with a detailed analysis of biometric changes during myopia progression with and without treatment," said Dr Flitcroft.

CORNEAL SHAPE Orthokeratology lenses are another approach. Patients wear overnight rigid gas permeable contact lenses flatter than the cornea to cause shape change. However, corneal shape is largely regained within three days of stoppage and most parameters reach baseline within one-eight weeks. Reported problems include glare and night vision driving issues, artificially low intraocular pressure recordings, and reduced contrast sensitivity. Dr Granet comments: “Done well, orthokeratology has supporting data with regards to rate of myopic progression. However, the risk of bacterial keratitis in a population prone to poor compliance

with hygiene makes me concerned about wholesale use of this modality.” To conclude, we are still far away from clearly elucidating all contributing factors to the alarming myopia epidemic. However, with increasing understanding, we find ourselves going full circle back to age-old treatment modalities such as atropine, bright light exposure and avoidance of near work. Guidelines and the science behind many of these proposed treatment techniques are becoming clearer. Three major approaches are emerging: 1) Promoting exposure to bright light and outdoor activity; 2) Optical corrections to generate growth inhibitory signals in retina, and 3) Applying atropine eye drops at low doses. Revolutionary techniques such as genetic engineering may yet be the ones that will make their mark, however, as of now, battle lines are drawn and the future seems more optimistic. Ken Nischal: nischalkk@upmc.edu Ian Flitcroft: ian@flitcroft.com David Granet: dgranet@ucsd.edu

For details of the WSPOS Consensus Statements, visit: wspos.org/world-society-of-paediatricophthalmology-strabismusconsensus-statements

SPECIAL FOCUS: PAEDIATRIC OPHTHALMOLOGY

REFRACTIVE SURGERY Atopia with keratoconus good indication for intervention.

THERAPEUTIC APPROACH Dr Cochener emphasised that refractive surgery in children is intended as a

elearning.escrs.org

Courtesy of Béatrice Cochener MD, PhD

efractive surgery in young patients should be reserved for very select indications, Béatrice Cochener MD, PhD, Brest University Hospital, France, told delegates at the 2016 WSPOS Subspecialty Day in Copenhagen, Denmark. “Refractive surgery in children is never the first choice, but rather a last option in case of failure of other optical corrections,” said Dr Cochener. Examples include high anisometropia, psychomotor handicap, keratoconus, severe contact lens intolerance, unilateral cataract and corneal scarring. Dr Cochener took a close look at a particular “indication niche”, namely the nexus of atopia and keratoconus, noting that this was a particularly good indication for refractive surgery in a young patient. Up to 30% of patients with keratoconus have allergies, which underpins the hypothesis that there is a mechanical factor involved, eye rubbing, in addition to a genetic predisposition. “In these patients, allergies prevent contact lens tolerance and the best-corrected vision loss due to the keratoconus cannot be corrected by glasses. In these cases, a posterior phakic intraocular lens (IOL), with or without intraocular ring segments, keratoplasty or crosslinking, can offer good results,” she said. Because it is commonly asymmetrical, with more than a three-dioptre difference between two eyes, the loss of best corrected visual acuity can often not be corrected by glasses.

Leigh Spielberg MD reports

Phakic posterior chamber IOL for unilateral high ametropia

therapeutic approach, in which the goal is the development or recovery of stereoacuity and binocular vision, not simply spectacle independence. “In fact, because long-term predictability of refractive outcome is difficult to achieve, spectacle independence is not even a primary goal,” she said. Further, pseudophakia in children should remain limited to cataract, and then potentially a multifocal IOL as a primary or secondary piggyback implantation, said Dr Cochener. A possible exception to this rule is refractive lens exchange for unilateral high hyperopia with a small anterior chamber depth. The question remains whether monofocal or multifocal IOLs are most

appropriate for this patient population. Surgeons need to be aware that long follow-up periods are required in children after refractive surgery. Postoperative complications that present in adults, such as haze after photorefractive keratectomy (PRK) or LASEK, and dry eye and ectasia after LASIK, can be very difficult to manage in children. “I realise that refractive surgery in children is a controversial topic. I believe it has a definite place in our arsenal. The goal should always remain: maximal efficacy associated with minimal risk,” added Dr Cochener. Béatrice Cochener: beatrice.cochener@ophtalmologie-chu29.fr

Keep learning. Stay relevant. EUROTIMES | NOVEMBER 2016

SPECIAL FOCUS: PAEDIATRIC OPHTHALMOLOGY

KERATOCONJUNCTIVITIS

Different treatment approaches required for vernal, atopic forms of disease in children. Sean Henahan reports

topic allergic keratoconjunctivitis is a diagnostic and therapeutic challenge in the paediatric population. Because of potentially vision-threatening complications, it is essential to know how to recognise and treat this rare disease, says paediatric ophthalmologist Dominique Bremond-Gignac MD PhD. “Usually we think of atopic allergic conjunctivitis as a disease of adults. When we have severe ocular allergy in children we tend to think it is vernal keratoconjunctivitis. But we know that in fact we do have younger patients with atopic disease and allergic conjunctivitis, and although it is rare, we need to be looking for it,” said Dr Bremond-Gignac, of Neckar University Children’s Hospital, Paris, France, who was speaking at the 2016 WSPOS Subspecialty Day in Copenhagen, Denmark. She noticed in her paediatric clinic that some patients with apparent vernal conjunctivitis also had ongoing atopic dermatitis. When she sees children with severe ocular allergic disease who also have atopic dermatitis, she now diagnoses this as atopic vernal keratoconjunctivitis. “It is important to make this distinction because the prognosis is different. Vernal keratoconjunctivitis stops in adulthood, while atopic vernal keratoconjunctivitis is a lifelong disease. It is Important to understand that this is a specific pathology of childhood,” she said.

FAMILY HISTORY Dr Bremond-Gignac recently published a survey article about 23 such patients (Ophthalmology, Vol. 123, Issue 2). Mean ages at onset of symptoms and at initial presentation to an ophthalmologist were 5.2 and 8.1 years, respectively. All of the patients suffered from eczema and conjunctivitis/keratitis. Most also had a family history of atopic disease and were affected by asthma and allergic rhinitis. The most common presenting symptoms included eczema, conjunctival hyperaemia, and keratitis, the latter including superficial punctate keratitis, shield ulcer and corneal erosions. Other symptoms included blepharitis, facial cutaneous fissures, papillae and madarosis. These patients are treated by a team of specialists which can include a paediatric ophthalmologist, a paediatric dermatologist, an allergist and an immunologist. Treatment starts with ocular washing, EUROTIMES | NOVEMBER 2016

Slit lamp examination: tarsal form of vernal keratoconjunctivitis

We tend to treat with the season, but depending on the allergen, the season could be very long period Dominique Bremond-Gignac MD, PhD which can help to remove the allergen and the inflammatory elements. The first level of treatment includes antihistamines and mast cell stabilisers in drop form, preferably without preservatives. “Depending on the severity of the disease, we may need to choose more intensive treatment. When standard antihistamines don’t suffice, we consider going to topical corticosteroids, but we know steroids have complications, so we would never use these long-term. We prefer a steroid-sparing approach,” said Dr Bremond-Gignac. She reported good results when using the topical calcineurin inhibitor cyclosporine as the next line of treatment. This is commercially available in the USA as a 0.05% drop (Restasis, Allergan), but is not available as such in Europe. She noted that she does expect this agent to be available commercially in Europe soon, with indication for vernal keratoconjunctivitis, and possibly at some point for allergic keratoconjunctivitis as well. Her clinic laboratory currently formulates cyclosporine in concentrations ranging from 0.05 to 2.0%. Patients receive drops in various strengths, one to four times per day, depending on the severity of the disease.

“We tend to treat with the season, but depending on the allergen, the season could be a very long period,” she told EuroTimes. She emphasised that there are important differences in the treatment of atopic keratoconjunctivitis and vernal keratoconjunctivitis. Patients with atopic disease will likely need treatment for the dermatologic aspects of the disease with emollients, demulcents and possibly corticosteroids. “These differences in the optimal treatment of atopic and vernal keratoconjunctivitis highlight the importance of early and accurate diagnosis, in informing effective treatment strategies and improving patient outcomes,” she said. Dominique Bremond-Gignac: dominique.bremond@aphp.fr To view the Eye Contact interview with Dr Bremond-Gignac on this topic on the ESCRS Player, visit: player.escrs.org/eurotimes-eye-contact/ allergic-keratoconjunctivitis-in-thepaediatric-population-dominiquebremond-gignac

Courtesy of Dominique Bremond-Gignac MD, PhD

SPECIAL FOCUS: PAEDIATRIC OPHTHALMOLOGY

EARLY-ONSET MYOPIA Risk prediction method using readily available data. Cheryl Guttman Krader reports

model incorporating factors associated with axial length elongation performs well for predicting early-onset myopia and also shows the importance of lifestyle factors in myopia development, said Willem Tideman MD at the 2016 annual meeting of the Association for Research in Vision and Ophthalmology (ARVO) in Seattle, USA. The model was developed recognising that high myopia is characterised by a disproportional elongation of axial length during childhood. First, factors independently predicting axial length elongation during childhood between the ages of six and nine were determined using data from 4,734 children participating in Generation R, a multi-ethnic, birth-cohort study under way in Rotterdam, The Netherlands. Then, a risk score was created using betas from linear regression models of the associated variables. Finally, its accuracy for discriminating between children who had become myopes by age nine and those remaining non-myopic was estimated, based on the area under the receiver operation characteristic (ROC) curve. The variables found to be independently associated with axial length elongation were parental myopia, books read per week, time spent reading, reading distance, time spent outdoors, sports, ethnicity, and axial length/corneal radius curvature. Willem Tideman The risk score for all children ranged from zero to 30. Children at age six whose score was less than or equal to five were at almost no risk for developing myopia at age nine whereas the risk was 54% for those with a risk score of 13 or higher. The area under the ROC curve was 0.77, indicating good accuracy for discriminating between the children who did and did not develop myopia. “Our model using non-invasive ophthalmic measurements and easy-to-obtain data performs well for identifying children at risk for developing high myopia as adults,” said Dr Tideman, Department of Ophthalmology and Epidemiology, Erasmus Medical Centre, Rotterdam, The Netherlands.

LIFESTYLE FACTORS “In addition, it shows that interventions aimed at lifestyle factors may help to mitigate the risk. According to our model, lifestyle adjustments may reduce axial length elongation by about 20%,” he added. Of the 2,136 children who underwent cycloplegic refractive error measurement and were non-myopic at age six, by age nine, 215 (10%) had developed myopia. For all eyes, mean axial length increased from 22.34mm at age six to 23.10mm at age nine, and the mean rate of elongation was 0.21mm/ year. However, the annual axial length elongation rate was significantly greater in eyes that developed myopia at age nine compared with the non-myopes, 0.34 versus 0.19mm/year.

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SPECIAL FOCUS: PAEDIATRIC OPHTHALMOLOGY

DRUG UTILISATION In an article sponsored by ISOPT Clinical, Wiley Chambers MD of the US FDA addresses some key questions in paediatric ophthalmology Q: How does the FDA exert its influence in order to increase pharmacologic knowledge in children suffering from eye diseases? A (WC): The Food, Drug and Cosmetic Act was amended with the passage of the Best Pharmaceuticals for Children Act (BPCA) and the Pediatric Research Equity Act (PREA). In essence, BPCA provides a carrot, an incentive to study and label a product for use in children (in the form of a six-month extension of sales exclusivity). PREA is a stick for the regulatory agency, the ability to require that a product be studied in all relevant populations. Ultimately, PREA and BPCA have a shared goal of providing new paediatric information, drug labelling, and encouraging the appropriate use of medication to treat these patients. FDA is responsible for carrying out the intent of both laws simultaneously and effectively. Drugs and biologics are both covered by PREA and BPCA. There are differences and similarities between PREA and BPCA, including: l PREA studies are mandatory; BPCA studies are voluntary. l PREA requires studies only on indication(s) under review; BPCA studies relate to an entire moiety and may include unapproved and different indications. l Studies for orphan indications are exempt from PREA; however, written requests may be issued for orphan indications under BPCA. l Studies conducted for either PREA/BPCA must be included in the labelling after review by the FDA. l Within ophthalmology, we expect every drug product to be studied in all age groups unless a specific reason is provided. Q: Taking PREA and BPCA in mind, can you tell us briefly some examples where either were utilised to provide more data in ocular paediatric diseases? A (WC): Over the past 30 years, well before PREA and BPCA, ophthalmic anti-infective and anti-allergic studies have routinely included kids, as those diseases are highly prevalent in paediatric populations. Studies in these areas have continued under PREA and BPCA. Intraocular pressure (IOP)-lowering agents were often not studied in children until the FDA requested studies. For example, brimonidine paediatric information was added post-approval after receiving a BPCA request by the agency. Timolol happened to be studied along with other IOPlowering products in paediatric patients. The unanswered question for paediatric patients taking prostaglandin analogues is: what will happen after 20 years of melanosome stimulation. Melanosome stimulation has been shown to be safe in studies of up to five years. However, BPCA is not well set up to answer such long-term questions. Wiley Chambers MD

Within ophthalmology, we expect every drug product to be studied in all age groups unless a specific reason is provided...

EUROTIMES | NOVEMBER 2016

Q: Children are less prone to ocular diseases - how does the agency deal with scarcity of some indications in younger populations? A (WC): Within ophthalmology, we expect every drug product to be studied in all age groups unless a specific reason is provided. For many ophthalmic diseases, there is little if any difference between the eyes of children and adults, and most ophthalmic drug products for these conditions are approved for use in both adults and paediatric patients. Enrolment in clinical trials is generally opened to paediatric patients as soon as there is some expectation of benefit from the drug product. Drug products for pupillary dilation, cycloplegia and topical anaesthetics are approved for use in children. However, some ocular diseases, for example age-related macular degeneration, does not exist in children (or generally adults under 50 years of age) and therefore paediatric studies are not required. Glaucoma rarely occurs in patients under 18 years of age, and when it does, it is often treated with surgical procedures. Dry eye conditions rarely occur in individuals less than 18 years of age. Q: Is there guidance for specific child conditions such as retinopathy of prematurity (ROP), children's herpetic and bacterial keratitis, anti-myopic drugs and anti-inflammatory drugs for paediatric uveitis? A (WC): The agency does not have any formal guidance documents for any of the indications listed above. ROP studies are done today with great caution due to concern of the potential systemic effects of vascular endothelial growth factor (VEGF) inhibitors. Herpetic keratoconjunctivitis tends to be very rare before the age of three years. At that age the cornea has completed its development, and thus there are only minimal differences in drug effect from the adult disease. However, there have been very few new drug products studied in this area for years. Uveitis is often studied in patients of all ages, although the prevalence of uveitis in children is low. Q: Do you have any insights to share regarding reporting of adverse events in children and utilisation of drugs in children, with much information derived from adults and extended to children? A (WC): The agency strongly encourages the reporting of all adverse events, from all sources and all age groups. Since many of the drugs utilised in paediatric ophthalmology have been on the market for a long time, the adverse event profile is fairly well known. With the exception of ROP, it is common for ophthalmic drug products utilised in children to have obtained sufficient knowledge during initial development to support approval in children at the time of initial approval. Dr Wiley Chambers is Deputy Director, Division of Transplant & Ophthalmology Products, Center for Drug Evaluation & Research, at the US FDA Wiley Chambers: wiley.chambers@fda.hhs.gov 13

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CATARACT & REFRACTIVE

IMAGE-GUIDED TORIC IOL New technology makes axis alignment easier for better outcomes. Howard Larkin reports

n just six years, new technology has revolutionised implantation of toric intraocular lenses (IOLs), Hiroko Bissen-Miyajima MD, PhD told the 2016 ASCRS•ASOA Symposium & Congress in New Orleans, USA. Image-guided systems are doing away with manually marking the astigmatism axis, greatly increasing lens alignment precision. When Dr Bissen-Miyajima, who is Professor and Chair of the Ophthalmology Department at Tokyo Dental College, Japan, wrote her Japanese language text on toric IOLs in 2010, experts from around the world shared techniques for manually marking the astigmatism axis on the cornea and conjunctiva before surgery. They then confirmed the axis by superimposing it on a topography map. During surgery the compressed mark remained as a reference for manually aligning the lens, she said. Yet even the width of the mark can take up three to five degrees, limiting its precision. In 2016, image-guided systems, such as Carl Zeiss Meditec’s CALLISTO eye and Alcon’s VERION, make the process much easier, Dr Bissen-Miyajima said. During diagnostic workup, a reference image is taken of the eye and the axis noted. During surgery, the device matches the blood vessel landmarks seen through the microscope with those of the reference image, and projects the axis in the eyepiece as a reference for aligning the IOL.

SEWING MACHINE Dr Bissen-Miyajima likened the markerless image-guided system to a sewing machine. By comparison, manual marking is more like hand sewing. “There is extra cost for the device but it is

There is extra cost for the device but it is superior in regularity and reproducibility Hiroko Bissen-Miyajima MD, PhD

Courtesy of Hiroko Bissen-Miyajima MD, PhD

The difference between the image-guided system and conventional marking

superior in regularity and reproducibility. While it is lower in cost, manual marking is dependent on manipulation and observation by the surgeon,” she said. Other new technologies will further improve the precision and outcomes of toric IOLs, Dr Bissen-Miyajima said. These include measuring anterior and posterior corneal astigmatism, which will allow more accurate toric power calculations and more precise reference axis. Digital analysis of IOL position, including axis alignment, will enable precise alignment corrections during surgery. Intraoperative aberrometry will help determine the proper axis after lens removal. In addition, image-guided femtosecond lasers will better control incisions, astigmatic correction and induced astigmatism. Dr Bissen-Miyajima was one of the ASCRS’ Honoured Guests at this year’s symposium. She was lauded for her work investigating multifocal IOLs and femtosecond laser-assisted cataract surgery, her work as a reviewer for several journals worldwide, as President of the Japanese Society of Cataract and Refractive Surgery, and for her leadership in several international societies. Hiroko Bissen-Miyajima: bissen@tdc.ac.jp

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CATARACT & REFRACTIVE

LASIK STUDIES Lower rates of all categories of visual symptoms, and high patient satisfaction. Howard Larkin reports

wo large studies of patients receiving LASIK found lower rates of all categories of visual symptoms, including glare and halos, as well as fewer dry eye symptoms after surgery than before surgery, US Navy Captain Elizabeth M Hofmeister MD told the 2016 ASCRS•ASOA Symposium & Congress in New Orleans, USA. The anonymous online studies are among the first to compare preoperative with postoperative symptoms, and challenge widespread notions that LASIK causes dysphotopsias and dry eye. Patient satisfaction with vision was also very high, reported Dr Hofmeister, of the Naval Medical Center San Diego, USA. Just 16 of 496 patients, or 3%, in the two PROWL studies were not satisfied at three or six months after surgery. And while the numbers were too small to support a statistically valid analysis, these dissatisfied patients trended toward poorer visual outcomes and worse dry eye. The two studies used an anonymous online questionnaire to collect data on visual and dry eye symptoms and satisfaction with vision and surgical results from active duty sailors at one, three and six months following femtosecond LASIK surgery. Six-month data were available from PROWL 1, and limited three-month data from PROWL 2.

SUBSTANTIAL IMPROVEMENTS In terms of efficacy for PROWL 1, six months after surgery 13% achieved 20/10 uncorrected binocular vision, with 76% 20/12.5, 99% 20/20, and 100% 20/40 or better. These figures were substantial improvements over pre-op best corrected values, when only 1% had 20/10, with 34% 20/12.5, 96% 20/16, and 100% 20/25 or better. Similarly, baseline visual symptoms decreased significantly in every category after surgery, with ghost images, glare and starbursts declining at one month and

halos below pre-op rates at three months, with continuing improvement in all categories at six months. Dry eye symptoms, as measured by the Ocular Surface Disease Index, also declined substantially after surgery, from 19% with moderate to severe symptoms pre-op to 10% six months post-op. In terms of satisfaction, six months after surgery 98% of patients in PROWL 1 were satisfied with the result of LASIK surgery, and 2%, or four patients, were not.

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GRADING SATISFACTION Some 97% were satisfied with their current vision and 3%, or six patients, were not. In PROWL 2, 96% were satisfied with their vision at three months while 4%, or 10 patients, were not. The 16 unsatisfied patients from the two studies were more likely to have uncorrected vision of 20/40 or worse in either eye, residual myopia of 0.50D or more, at least one visual symptom, and moderate to severe dry eye symptoms, Dr Hofmeister reported. Grading satisfaction with present vision on a 100-point scale, mean satisfaction among seven patients in PROWL 2 with uncorrected vision of 20/40 or worse in either eye was 57.1 compared with 88.2 for 243 patients with better than 20/40 uncorrected. To prevent dissatisfied LASIK patients, Dr Hofmeister recommended striving for “super vision” of better than 20/20 using accurate cylinder axis treatment and carefully developing correction nomograms based on achieved results. She also recommended screening for dry eye and treating Meibomian dysfunction, and counselling patients on surgical risks and realistic outcome expectations. While satisfaction will be high if patient expectations are met, there will be a few patients who are not satisfied despite your best efforts, Dr Hofmeister concluded.

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The 16 unsatisfied patients from the two studies were more likely to have uncorrected vision of 20/40 or worse in either eye... Elizabeth M Hofmeister MD EUROTIMES | NOVEMBER 2016

CATARACT & REFRACTIVE

POST-LASIK ECTASIA

Study shows good outcomes for post-LASIK ectasia treatments. Dermot McGrath reports

The study showed that treatment is minimally invasive with a good chance of visual rehabilitation... Dominique Pietrini MD Clinique de la Vision, Paris, presented the results of a retrospective study of 148 eyes of 98 patients operated by LASIK between 1998 and 2013 who were subsequently diagnosed with ectasia. The rapid reduction in visual acuity leading to diagnosis of ectasia occurred on average six years after the initial surgery, with the earliest case manifesting just two months postoperatively and the latest 11 years after the LASIK procedure. OCT analysis showed that the corneal flap was created by microkeratome in 86 cases, femtosecond laser in 50, and undetermined in the remainder. “There was some suggestion when femtosecond lasers were first introduced that they might potentially protect against

Courtesy of Dominique Pietrini MD

lthough post-LASIK ectasia is an increasingly rare complication of refractive surgery, thanks mainly to more effective screening methods for at-risk patients, its occurrence can nevertheless be effectively managed with a combination of strategies to treat the underlying pathology and preserve patients’ quality of vision, according to Dominique Pietrini MD. “The incidence of post-LASIK ectasia has diminished in recent years thanks to more effective diagnosis of corneas at risk, using techniques such as epithelial mapping and optical coherence tomography (OCT),” Dr Pietrini told delegates attending the French Implant and Refractive Surgery Association (SAFIR) annual meeting in Paris. “When it does occur, however, ectasia can be managed effectively, either by treating the underlying pathology if the ectasia is evolving or obtaining an objective improvement in the patient’s quality of vision using intracorneal implants or topographic-guided photorefractive keratectomy (PRK),” he added. Dr Pietrini, in private practice at the

OCT analysis of the cornea before and after intracorneal ring segments implantation for post-LASIK ectasia

EUROTIMES | NOVEMBER 2016

the possibility of post-LASIK ectasia, which clearly hasn’t been borne out in reality,” Dr Pietrini said. The mean residual stromal bed was 288 microns (range 170 to 448), mean flap thickness was 147 microns (range 112 to 204), and mean pachymetry at the thinnest point was 437 microns (range 324 to 584). In terms of treatment options, a nonsurgical approach using contact lenses and regular monitoring was successfully employed in 46 patients whose ectasia was deemed to be stable and non-evolving. Treatment of the underlying pathology was necessary in 46 patients with progressive ectasia: 25 eyes received corneal crosslinking (CXL) alone, seven eyes underwent CXL associated with topography-guided PRK and 14 eyes received combination intracorneal rings/CXL. Surgical intervention to restore vision was carried out in 56 eyes: 49 using intracorneal rings combined with femtosecond laser, and seven eyes using topography-guided PRK. Dr Pietrini noted that the mean uncorrected visual acuity went from 2/10 preoperatively to 5/10 postoperatively. Cylinder was also significantly reduced from a mean of -4.2D preoperatively to -2.7D after surgery. Both keratometry and higher order aberrations also improved significantly after surgical treatment. “The study showed that treatment is minimally invasive with a good chance of visual rehabilitation without significant risk to the patient. Early intervention is also advised as this leads to better outcomes for the patient,” he concluded. Dominique Pietrini: docteurpietrini@gmail.com

CATARACT & REFRACTIVE

PREVENTING PROBLEMS Negative dysphotopsia – grooved IOL could be key to side effects.

OCULUS UB 6 Perfect Refraction

Leigh Spielberg MD reports

hat induces negative dysphotopsia?” asked Samuel Masket MD, of the University of California, Los Angeles, USA. “And more importantly, how can we prevent it?” Dr Masket provided a solution to delegates attending the XXXIV Congress of the ESCRS in Copenhagen, Denmark. His presentation covered the use of an anterior capsulotomy-captured/grooved intraocular lens (IOL) to prevent negative dysphotopsia. “Negative dysphotopsia, although likely multifactorial in cause, is prevented, relieved or improved when the IOL optic edge overlies the anterior capsulotomy. Corrective or preventative surgery is based on that concept,” said Dr Masket. This is significant information. If the common pathway for negative dysphotopsia is any “in-the-bag” IOL with the anterior capsulotomy edge overlying the optic, then a profound and systematic alteration of surgical technique is required to prevent this complication. Dr Masket reviewed his own surgical experience regarding both therapeutic and preventative measures taken against negative dysphotopsia. “Considering 38 of 39 eyes with reverse optic capture successfully treated or prevented negative dysphotopsia, we sought an IOL solution with this in mind,” he said. Simply replacing an in-the-bag IOL with Samuel Masket a lens in the sulcus is insufficient, and further, reverse optic capture and sulcus placement causes its own problems, including chafing of the posterior iris. Dr Masket thus designed an anti-dysphotopic IOL in which a groove on the anterior optic captures the anterior capsulotomy. “The IOL is fixated by the anterior capsule, so that part of the optic overlies the capsule rather than vice versa,” he explained.

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COMPLICATIONS The result of his research and development, the Masket Anti-ND IOL Morcher 90S lens, is currently CE marked in the European Union. Initial clinical results of 50 cases (different than the 39 described above) were very promising. “There were no cases of negative dysphotopsia, despite two failed optic captures,” he said. Complications included three cases of capsule block, of which two involved iris capture. There were, however, no cases of iris chafing. “We thus developed a modified version of the IOL with fenestrations to prevent capsule block,” he added. Because of the need for a highly precise anterior capsulotomy rhexis of 4.8-4.9mm, Dr Masket recommended using a femtosecond laser to perform the capsulorhexis. Besides the absence of negative dysphotopsias, fixation within the anterior capsulotomy ensures other advantages, such as highly stable fixation, avoidance of anterior capsule contraction, absence of lens tilt, a stable toric axis, excellent centration, a more predictable effective lens position and decreased higher order aberrations.

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Samuel Masket: avcmasket@aol.com EUROTIMES | NOVEMBER 2016

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CORNEA

MYOPIA ALTERNATIVE Intracorneal rings a good option for myopia in at-risk corneas.

GOOD ALTERNATIVE

Courtesy of Béatrice Cochener MD, PhD

Evaluations of corneal topography showed that 26 eyes (76 per cent) were considered normal, three were

Courtesy of Eve Durbant MD

ntrastromal corneal ring segments (Intacs®, Addition Technology, Inc.) offer a potentially compelling solution for patients with low amounts of myopia who are not suitable candidates for LASIK or other photoablative procedures, according to Eve Durbant MD, University Hospital Brest, France. “Intrastromal corneal rings have a legitimate place in the treatment of mild myopia for at-risk corneas. Their efficacy is satisfactory, they work best on virgin corneas, and they enable the possibility of a combined treatment strategy with corneal crosslinking (CXL) for ectasia or photorefractive keratectomy (PRK) and/ or CXL for residual astigmatism,” she told delegates attending the French Implant and Refractive Surgery Association (SAFIR) annual meeting in Paris. “The ring segments present a number of advantages for these corneas deemed at risk for traditional photoablative refractive surgery. Their implantation is straightforward, there is no ablation of corneal tissue and they respect the asphericity of the central cornea. They are ideal for the correction of myopia in the range of -1.0D to -4.0D and the technique is reversible in the event of any problems arising,” she said. Dr Durbant presented the results of a study of 34 eyes of 19 patients with a mean age of 33 years (range: 24-57) who were implanted with ring segments for myopia, the majority (23 eyes) with myopia less than -3.0D.

Dermot McGrath reports

asymmetric, one showed inferior steepening, one had forme fruste keratoconus, and three had secondary ectasia. Corneal hysteresis measurements (Ocular Response Analyzer/ORA, Reichert Technologies) were normal in eight eyes, pathological in nine (26 per cent) and unknown in 16.

GRADUAL IMPROVEMENT The visual acuity results at one year were satisfactory, said Dr Durbant, with a mean uncorrected visual acuity of 0.89 (SD=0.26) and a gradual improvement of acuity over the follow-up period. Additional surgery was required in three eyes (PRK) for correction of residual astigmatism and

one eye (CXL) for ectasia, and five eyes received combined PRK/CXL treatments. Complications in the series included infection of the incision, haze, and hyperopic shift of more than 0.75D. Visual symptoms included monocular diplopia/ deformations in five eyes, halos/glare in three, fluctuations in two, insufficient correction in one and dry eye in 10. Summing up, Dr Durbant said that the ring segments provide a good alternative to photoablative techniques with the attendant risk of induced keratoconus, and also to phakic implants which were more invasive for moderate myopia. Eve Durbant: eve.durbant@gmail.com

Their implantation is straightforward, there is no ablation of corneal tissue and they respect the asphericity of the central cornea An eye with Intacs

Eve Durbant MD EUROTIMES | NOVEMBER 2016

CORNEA

CORNEAL COMPLEXITY New understanding of corneal immunology could lead to novel therapeutic approaches. Priscilla Lynch reports

he cornea is far more complex than traditionally thought, and is actually a highly responsive tissue that is actively involved in the regulation of immunity and inflammation, the 2016 Irish College of Ophthalmologists Annual Conference in Killarney, Ireland, heard. Reza Dana MD, MSc, MPH, Professor of Ophthalmology and Director of the Cornea Service at Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, USA, gave the Annual Mooney Lecture entitled ‘Regulation of Corneal Inflammation and Immunity’. He noted that corneal disease is second only to cataracts as the leading cause of non-refractive visual impairment across all age groups globally. Corneal angiogenesis is not only a common complication of corneal inflammation, but also helps amplify the inflammatory response in the cornea, “but it is not always a bad thing”, Dr Dana explained. He said that in active infections, especially chronic fungal infections, growth of corneal neovascularisation can help clear the infection by facilitating delivery of immune cells.

TRANSPLANTATION In corneal transplantation, the immune response often interferes with success rates. Nearly 100,000 corneal transplants are performed worldwide every year, he said, with an increasing number done

both for quietening inflammation as well as using endothelial keratoplasty. In lowpromoting immunity,” he told EuroTimes. risk transplants, done in host beds with no inflammation or vascularisation, there is 85-90 per cent graft survival. However, in RESIDENT CELLS high-risk transplants, with an inflamed host He explained that 5-8% of the resident bed, there is less than 50 per cent survival cells of the cornea in all species evaluated despite maximum immune suppression. to date are bone marrow-derived, thus the While corticosteroids have been cornea is “much more than just epithelial a treatment revolution, in high-risk cells, stromal keratocytes, and endothelial transplants they are not as successful. cells, which is the old view”. He Dr Dana urged caution in the use of thus stated: “We now know that systemic immune suppression through these bone marrowin keratoplasty, saying while derived cells there is a it works, there are risks and constant communication side effects, with clinician and interchange between skill and experience vital for the cornea and the lymphoid a successful outcome. tissues of the body.” He then discussed Dr Dana said a key the successful use of antimessage is the manipulation vascular endothelial growth of the VEGF pathway, not factor (anti-VEGF) treatments only for suppressing angiogenesis, Reza Dana for increasing the survival of corneal but also regulating immune cell grafts. Other modalities could traffic to the cornea since several VEGF include use of low-dose interleukin-2 to pathways also regulate immune cell expand regulatory immune cells which are activation and trafficking. potently anti-inflammatory. “Although there are a whole array of “In chronic disease the regulatory inflammatory conditions that can lead to immune cells do not function normally, dysregulation of the cornea to regulate but again you can use biologic strategies inflammatory response, there are treatment to amplify their function and restore that strategies such as blocking certain normal balance,” he explained. VEGF pathways and using interleukin-2 In his presentation Dr Dana debunked to promote regulatory pathways. The a number of old concepts, or “myths”, beauty of the immune system is that it which had become popularised over can be modulated since the host immune the ages. The first was the idea of the response is highly plastic and modifiable,” cornea not having any resident immune he concluded. cells. "We now know that the cornea has many immune cells that are highly relevant, Reza Dana: reza_dana@meei.harvard.edu

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EUROTIMES | NOVEMBER 2016

CORNEA

PROMISING NEW METHOD

Single-Use Instruments Leading Innovations in Ophthalmology

Neurostimulation device presents a new approach to dry eye disease. Sean Henahan reports

asal neurostimulation could be a promising new approach for the management of dry eye disease, suggest the results of an early clinical study presented at the 2016 ASCRS•ASOA Symposium & Congress in New Orleans, USA. Tear secretion is regulated by a complex of factors known as the lacrimal function unit. Sensory stimulation of the ocular surface initiates a sensory autonomic reflex that results in tear secretion. Afferent nerves in the nose contribute to the process, stimulating reflex tearing, explained Stephen C Pflugfelder MD, Baylor College of Medicine, Houston, Texas, USA. The lacrimal glands produce fluid and tear proteins, and the conjunctival goblet cells secrete gel forming soluble mucins that coat the ocular surface. Neural signalling of tear secretion may be interrupted by a variety of mechanisms. These include decreased corneal sensitivity, nerve damage, anticholinergic medications, and a variety of inflammatory cytokines. “The Oculeve neurostimulator takes advantage of these neurostimulatory pathways. Developed at Stanford University (California, USA), the device delivers a titratable intranasal electrical stimulus to stimulate tear secretion. This appears to be an exciting new treatment modality for dry eye,” reported Dr Pflugfelder. The nasal neurostimulation device includes a rechargeable base unit and disposable tip. It provides five levels of patient-adjustable stimulation to obtain tingling in the nose. After the tip is placed in the nostril, and the stimulus adjusted, patients begin to feel a gush of tears. Dr Pflugfelder and colleagues conducted a multicentre randomised controlled clinical trial evaluating the effects Stephen C Pflugfelder of neurostimulation on lacrimal gland and goblet cell secretion. Patients with dry eye disease in the study had to have tear breakup time of less than seven seconds and a tear meniscus height of less than or equal to 240 microns. Patients and controls had a screening visit and two treatment visits. All patients underwent optical coherence tomography (OCT) and impression cytology, before and after neurostimulation. The researchers took advantage of new OCT technology that allows measurement of the ocular surface at the micron level. They were able to measure the tear meniscus height to assess tear production using this technique. Measurement of inferior tear meniscus height showed significant increases following intranasal stimulation in both dry eye patients and normal controls. Cytological studies compared intact and degranulated goblet cells. Patients treated with intranasal stimulation saw an associated increase in goblet cell degranulation and mucin production compared with those who received extranasal control treatment. The researchers also noted a treatmentassociated increase in tear volume.

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Stephen C Pflugfelder: stevenp@bcm.edu EUROTIMES | NOVEMBER 2016

RETINA

GENE THERAPY

Regulatory representative and researcher provide perspectives to facilitate the journey. Cheryl Guttman Krader reports

early data on the number of investigational new drug submissions received by the US FDA provide a clear indication that gene therapy for ophthalmic diseases is an active and growing field of research. At a session during the 2016 annual meeting of the Association for Research in Vision and Ophthalmology (ARVO) in Seattle, USA, speakers shared insights aimed to help researchers bring ocular gene therapies from bench to bedside. Wilson W Bryan MD, Director, Division of Clinical Evaluation and Pharmacology/ Toxicology, Office of Cellular, Tissue, and Gene Therapies, Center for Biologics Evaluation and Research, US FDA, noted that successful clinical development of gene therapy for rare diseases that have been genetically defined requires understanding of the corresponding phenotype and disease course. This means there is a need for natural history studies to characterise the incidence, demographics, clinical presentation and prognosis of the targeted disorder. Natural history studies can also help identify novel outcome measures and biomarkers that may be used in clinical trials for optimising patient selection and/or as surrogate endpoints. At the same time, they provide an opportunity to collect blood samples for molecular definition. Recognising that natural history studies can take several years to complete, however, Dr Bryan encouraged basic scientists who are working on a gene for a particular disease to reach out early to clinicians, so that natural history studies can be

completed in parallel with the preclinical work, minimising any delay in initiating clinical testing when the time comes. If a novel endpoint is being considered as an appropriate clinical trial outcome measure, then validation study planning must also begin, said Jean Bennett MD, PhD. Dr Bennett is Professor, Ophthalmology, Cell and Developmental Biology, University of Pennsylvania, Philadelphia, USA, and a pioneer in developing RPE65 gene therapy for Leber congenital amaurosis (LCA). “Visual acuity and visual field results have been standard primary endpoints in ophthalmology, but they may not be relevant to patients with low and ultralow vision. Mobility testing is the primary outcome measure in the phase 3 studies of RPE65 gene therapy for LCA, and it took two years to complete the studies to validate its use,” she noted.

TECHNICAL ISSUES Numerous technical issues need to be addressed when developing a gene therapy product, one of which is picking the right vector. Factors to consider include availability, i.e. whether the vector is in the public domain, as well as genetic cargo capacity, transfection (or infection) efficiency, mode of delivery, and the existence of a GMP purification protocol facility, Dr Bennett said. She also stressed the importance of optimising the safety and potency of the construct early on through preclinical toxicity and efficacy studies, in order to avoid wasting time and money on re-engineering once clinical testing begins. Dr Bryan noted that for better translation, preclinical studies may ideally

Visual acuity and visual field results have been standard primary endpoints in ophthalmology... Jean Bennett MD, PhD EUROTIMES | NOVEMBER 2016

be performed in larger versus smaller animals. Dr Bennett concurred. “We can’t assume what we see in a mouse will be seen in a larger animal or that results in animal models are predictive of outcomes in humans,” she said. Illustrating her latter point, Dr Bennett noted that while robust restoration of ERGs was achieved with RPE65 gene therapy in dog and mouse models, this effect has not yet been reported in clinical trials. Dr Bennett also advised researchers to choose equipment and procedures that are already approved, readily available, and expected to remain accessible and practical for the duration of the project and even into the post-marketing phase. Referring to potency assays, she said: “It may be tempting to use animal models, but remember that this testing will still need to be done years after product approval.” With safety in mind, new therapies will be evaluated first in one eye only. Eventually, clinical trials will have to investigate bilateral treatment for genetic disorders that affect both eyes, and if there is loss of efficacy over time, the safety profile with repeat treatment. In addition, when gene therapy administration involves a new procedure, the developer may be asked to create a surgeon training programme along with monitoring plans, Dr Bryan said. Dr Bennett echoed that idea. “There is a learning curve in carrying out subretinal injections, and we think it is important to have a surgical training package to ensure proper delivery of the gene therapy. One bad move might derail the field,” she said. Finally, while clinicians may be encouraged by positive results, Dr Bennett advised caution in promising a specific timeline. “Patients are always asking when a new treatment will be available. Remember that is something over which you have no control,” she said. Wilson W Bryan: wilson.bryan@fda.hhs.gov Jean Bennett: jebennet@mail.med.upenn.edu

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RETINA

BLOOD-RETINAL BARRIER New OCT technique sheds light on critical role of blood-retinal barrier in retinal disease. Dermot McGrath reports

he blood-retinal barrier (BRB) plays a crucial role in the regulation of the microenvironment of the retina, with breakdown of the BRB directly implicated in the development of a range of retinal diseases such as diabetic retinopathy (DR) and age-related macular degeneration (AMD), according to José Cunha-Vaz MD, PhD. “There is a lot at stake in this issue as DR is the leading cause of blindness in the working age population, and AMD is the leading cause of blindness among individuals older than 50 years of age,” said Prof Cunha-Vaz in his EURETINA Medal Lecture at the 16th EURETINA Congress in Copenhagen, Denmark. Prof Cunha-Vaz noted that recent progress in the treatment of retinal diseases using intravitreal administration of antiVEGF drugs or steroids has completely changed the perspective of successful vision recovery. “These agents work by stabilising the BRB and correcting abnormal permeability in disease,” he said. In a broad overview of current knowledge pertaining to the BRB, Prof Cunha-Vaz, Emeritus Professor of Ophthalmology of the University of Coimbra, Portugal, said that the BRB plays a fundamental role in the microenvironment of the retina. “The BRB is involved in the regulation of the retinal cell environment. The BRB is particularly tight and restrictive and is a physiological barrier that regulates ion, protein and water flux into and out of the retina,” he said. He noted that the BRB consists of inner and outer components, with the inner BRB being formed of tight junctions between retinal capillary endothelial cells and the outer BRB of tight junctions between retinal pigment epithelial cells. Alterations of the BRB play a crucial role in the development of retinal diseases, said Prof Cunha-Vaz. “One of the nonspecific and ubiquitous signs of ocular disease is macular oedema, and this is a fundamental result of alterations in the BRB. It is an accumulation of fluid in the retina involving the macular region and often the central fovea with major vision consequences,” he said. Furthermore, the two most frequent and relevant retinal diseases, DR and AMD, are directly associated with alterations of the BRB, he said. EUROTIMES | NOVEMBER 2016

Courtesy of José Cunha-Vaz MD, PhD

Optical coherence tomography-leakage maps: identification of the site of leakage in a diabetic patient with subclinical macular oedema and minimal signs of fluorescein leakage on fluorescein angiography

CLINICAL EVALUATION DR is initiated by an alteration of the inner BRB and neovascular AMD is a result of an alteration of the outer BRB. Treatment of retinal diseases must also deal with the BRB, either by using its specific transport mechanisms or by circumventing it through intravitreal injections. Clinical evaluation of the BRB has evolved greatly over the past few decades, said Prof Cunha-Vaz, moving from earlier invasive techniques such as fluorescein angiography, vitreous fluorophotometry and retinal leakage analysis to more recent non-invasive methods such as optical coherence tomography-leakage (OCTL) measurement and quantification of extracellular space of the retina. An important breakthrough came with the finding that OCT-L can successfully measure retinal optical reflectivity ratios, said Prof Cunha-Vaz. “With this technique it is possible to reliably locate and quantify increases in the retinal extracellular space. Our studies

have shown that the changes in the retinal extracellular space correlate well with the occurrence and degree of retinal oedema. Furthermore, OCT-L is able to identify the location of the increases of retinal extracellular space in the different layers of the retina,” he added. Combining OCT-L with OCT microangiography (AngioPlex, Zeiss OCTA) allows for quantification of changes in the retinal extracellular fluid and non-invasive identification of sites of alteration of the BRB. Importantly for clinical use, it also enables evaluation of the status of the BRB in individual patients and their response to treatments, said Prof Cunha-Vaz. Prof Cunha-Vaz said that non-invasive monitoring of the BRB by OCT-L enables improved understanding of the role of the BRB in retinal disease, is useful in the testing and validation of new treatments, and contributes to the personalised management of retinal disease. José Cunha-Vaz: cunhavaz@aibili.pt

RETINA

PERFECT CONTROL Device enhances precision and safety for delivering stains, heavy liquids. Cheryl Guttman Krader reports

he ‘squeezer’ is a new disposable device that affords vitreoretinal surgeons perfect control for injecting stains and perfluorocarbon liquids (PFCLs) using a single-handed technique, said Claus Eckardt MD at the 16th EURETINA Congress in Copenhagen, Denmark. The device was conceived by Dr Eckardt with the goal of addressing the technical difficulties and risks associated with delivery of stains and PFCLs using traditional syringes. The squeezer consists of a silicone tube within a plastic frame. It incorporates one Luer Lock port for filling and a second Luer Lock port for attaching the squeezer to a cannula (23, 25, or 27G) in order to deliver the stain or PFCL.

Courtesy of Claus Eckardt MD

The squeezer device

Two models will be available that differ only in the volume they hold - a 1cc squeezer for stains (vital dyes, triamcinolone) and a 5cc version for PFCLs. The silicone tube can be pre-filled by a nurse. When needed, the surgeon holds the device in the same manner as one would grip a pencil and dispenses its contents simply by squeezing on both sides of the silicone tube with thumb and forefinger. A valve within the Luer Lock prevents backflow of vitreous into the fluid once squeezing pressure is released. “Using the squeezer, surgeons can control the start, speed and amount of dye injected. Furthermore, because the delivery is so controlled, the squeezer actually minimises the amount of dye used and allows surgeons to precisely stain even a very small area of the retina,” said Dr Eckardt, Professor of Ophthalmology, Klinikum Frankfurt Höchst, Frankfurt, Germany. When injecting PFCLs, surgeons using the squeezer can easily guide the cannula into the trocar and get close to the retina to inject a single bubble. Each squeeze releases approximately 1cc, so that delivering enough PFCL to fill an emmetropic eye would require about three or four squeezes, Dr Eckardt said. He reported that the results of a time study he conducted indicated that a PFCL injection takes about five seconds longer using the squeezer, compared with a traditional syringe. The benefits associated with using the novel device, however, more than compensate for the extra time. “Absolutely, it is much safer to use the squeezer than a conventional syringe,” Dr Eckardt said. Dr Eckardt developed the squeezer in collaboration with Oftavinci Research. It will be marketed by Vitreq. “These devices will be inexpensive, and so will not substantially increase the total cost of dye or PFCL injection,” Dr Eckardt added. Claus Eckardt: c.eckardt@em.uni-frankfurt.de EUROTIMES | NOVEMBER 2016

FEATURE GLAUCOMA

BENEFITS OF NEW SHUNT Device made from SIBS which conforms to the curvature of the eye.

BIOCOMPATIBLE MATERIAL

The InnFocus MicroShunt is safe, effective and practical in eyes that are phakic... Isabelle Riss MD thermoplastic material, which conforms to the curvature of the eye and demonstrates clinically insignificant inflammation and tissue encapsulation. The device is placed in the anterior chamber through an ab externo fornix-based scleral needle track which is created posteriorly to the limbus. “The lumen of the device at 70 microns is sufficiently large to pass sloughed

Courtesy of Leonard Pinchuk PhD, DSc

She noted that the InnFocus MicroShunt is made from SIBS, a highly biocompatible

InnFocus MicroShunt two years post-op

Courtesy of Isabelle Riss MD

new minimally-invasive shunt has demonstrated significant reduction in both intraocular pressure (IOP) and use of glaucoma medication in a long-term study, according to Isabelle Riss MD. “This procedure is very simple, with immediate and safe pressure reduction. It can be effectively combined with cataract surgery and the postoperative treatment is very similar to cataract surgery,” Dr Riss told delegates at the XXXIV Congress of the ESCRS in Copenhagen, Denmark. The patients studied had an average preoperative fully medicated IOP of 24.8mmHg (±6.1mmHg). Two years after implantation of the InnFocus MicroShunt™ (InnFocus Inc., Miami, Florida, USA), the average IOP was reduced 47% from baseline to 13.0mmHg (±4.6 mmHg), and over 70% of eyes recorded an IOP equal to or less than 14mmHg. There was a 79% reduction in glaucoma medications to 0.6 medications per patient, and 74% of patients were entirely off glaucoma medications at two years. Dr Riss’s study included a total of 79 patients at two centres in Bordeaux, France and Santo Domingo, Dominican Republic. Prior to surgery, patients were either phakic (31/79), pseudophakic (30/79), or phakic with combined phacoemulsification and intraocular lens placement (18/79).

Dermot McGrath reports

IOP two years post-op in phakic, pseudophakic and combined surgery

EUROTIMES | NOVEMBER 2016

endothelial cells yet small and long enough to prevent hypotony. Planar fins on the shunt prevent the device from migrating into the anterior chamber and also serve to minimise aqueous humour leakage around the tube,” she said. Putting the results in context, Dr Riss stated that there were no significant differences in IOP and medication use in patients at one and two years in eyes that were phakic, pseudophakic and combined with cataract surgery at the time of implant. “The overall reduction in IOP at one and two years was 47% and 48%, and the overall reduction in medication use was 81% and 74%, respectively,” she said. The safety profile of the device was also excellent, she said, with no long-term sight-threatening adverse events. Transient hypotony of less than 5mmHg after day one was present in 6.3% of patients, all of which resolved spontaneously. There were no longterm sight-threatening adverse events such as endophthalmitis, chronic hypotony, or choroidal haemorrhage, she said. “The InnFocus MicroShunt is safe, effective and practical in eyes that are phakic, pseudophakic and require concomitant cataract surgery,” she concluded. Isabelle Riss: isabelleriss@orange.fr

GLAUCOMA

PATHOGENESIS THEORY Pressure differential hypothesis suggests a new way to look at disease.

Sean Henahan reports

new understanding of the role of intracranial pressure (ICP) in glaucoma may help to overcome some of the longstanding mysteries surrounding the disease and encourage development of new strategies for prevention and treatment. “We’ve never seen the dark side of the moon. Glaucoma is much the same, as ophthalmologists we have only looked at one side of glaucoma, the eye, but not the intracranial side, even though the optic nerve spends more time in the brain, than in the eye,” John P Berdahl MD, of Sioux Falls, South Dakota, told the 2016 ASCRS•ASOA Symposium & Congress in New Orleans, USA. While the received teaching is that glaucoma is a one-pressure disease, it now seems more likely that an imbalance between the intraocular pressure (IOP) and the ICP plays a role in the disease. Dr Berdahl proposes that the cupping of the optic disk seen in glaucoma is caused by posterior directed forces when the IOP is higher than the ICP. The optic nerve bows backward and cupping occurs. The other principal manifestation of glaucoma, visual field loss, is caused by ganglion cell death, as the axonal transport needs are not met by the optic nerve because it cannot get through the high pressure environment in the eye, he suggests. “We know that ICP affects the optic nerve. We see it in idiopathic intracranial hypertension, where high cerebrospinal fluid (CSF) pressure causes the optic nerve to bow forward. In glaucoma, you have the reverse, where high IOP and low ICP cause the optic nerve to bow backwards,” he explained.

CRITICAL DELIVERY He hypothesises that when IOP is elevated, axonal transport via the optic nerve is reduced, inhibiting the critical delivery of metabolic needs and waste removal within the eye. If the IOP is extremely high or the ICP is very low, axonal transport is stopped at the level of the lamina cribrosa, so the needs of the optic nerve are not met, the nerve slowly withers, and disease follows. Dr Berdahl and colleagues at the Mayo Clinic tested this hypothesis in a retrospective study of people who had undergone lumbar puncture, comparing the charts of those who had glaucoma with those who did not. It turned out the glaucoma patients did indeed have low ICPs compared with the control group. Patients with normal-tension glaucoma had even lower ICP. Those with ocular hypertension had higher ICP, balancing out their high IOP. These findings were subsequently confirmed by prospective studies conducted in China. A closer look at the glaucoma patients in the Mayo Clinic database also showed that ICP started to decline at age 65, the same age that glaucoma incidence begins to increase in the general population. John P Berdahl MD

We’ve never seen the dark side of the moon. Glaucoma is much the same, as ophthalmologists we have only looked at one side of glaucoma...

“Why does IOP, or transcorneal pressure difference as I prefer to call it, matter? Because it is a surrogate for the translaminar pressure difference, across the laminar cribrosa, the difference between the IOP and the ICP. I believe that glaucoma is the IOP minus the ICP divided by the thickness of the laminar cribrosa and its biomechanical properties, multiply by time, you get the disease,” he told the session.

LOCAL VACUUM He suggested that it might be possible to treat glaucoma by a applying a local vacuum against the ambient atmospheric pressure pushing on the eye. He conducted studies in cadaver eyes where he was able to ‘dial in’ eye pressure with the use of specially designed vacuum goggles. Dr Berdahl’s ideas may find an application in space travel. Visual impairment due to intracranial pressure (VIIP) has been observed in astronauts who spent extended amounts of time in the International Space Station. They developed symptoms including global flattening, hyperopic shift, choroidal folds and optic disk oedema. With a new programme under way looking to send humans to Mars as early as 2030, NASA is supporting Dr Berdahl’s research. He has started a company which is developing goggles that would potentially address this problem. John P Berdahl: john.berdahl@vancethompsonvision.com

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OCULAR

ALZHEIMER’S & THE EYE Polarimetry device could provide early diagnosis. Pippa Wysong reports

novel imaging device using polarised light can detect and measure amyloid deposits on the retina and could become an ophthalmic tool to help screen for Alzheimer’s disease (AD). Details of the device were presented by Melanie Campbell PhD, Professor of Physics and Astronomy, and Professor in Optometry and Vision Science at the University of Waterloo, Ontario, Canada, who was speaking at the 2016 Alzheimer’s Association International Conference in Toronto, Canada. Amyloid beta protein deposits in the brain are a known diagnostic biomarker for AD and can accumulate many years before the first symptoms occur. Currently, their presence is measured by PET scans of the brain. However, amyloid deposits also occur on the retina, an extension of the brain. Researchers hypothesise that amyloid protein is synthesised by neural cells within the eye, in the same way as in the brain in AD, appearing in both the retina and the vitreous. There is also evidence for fluid exchange between the cerebral spinal fluid

which contains amyloid and the vitreous. The imaging device uses polarised light, polarimetry, and could provide a “low-cost, non-invasive, comfortable and potentially widely available test for early detection of amyloid”, which could be done in the offices of ophthalmologists, Dr Campbell said.

POST-MORTEM RETINAS She presented results of a series of proofof-concept scans which were conducted on human and canine retinas. Scans were conducted on a series of post-mortem retinas from the Eye Bank of Canada (20 from people who had AD and 22 from healthy controls), as well on living and postmortem canine retinas. Human samples were excluded if there was a history of neurologic disease or any sort of cognitive impairment, apart from AD. In addition, the retinas from five canines were imaged in vivo using amyloid fluorescence and optical coherence tomography for comparison. The retinas were mounted flat for the post-mortem study, meaning whole retinas were scanned. There has been some debate in the Alzheimer’s community as to whether amyloids appear on the retina, since not everyone finds them, she said.

This could be due to sparse sampling of the retina using thin sections. Amyloid deposits in canine retinas had very similar properties to the deposits imaged in human retinas. They were close to nerve cells and interacted the same way with polarised light. The study found that the number of amyloid deposits present in the human retinas varied widely. Sometimes the researchers found just a few deposits, while other samples had many more. However, as with brain scans, the presence of amyloids does not always correlate with active disease. Deposits in the canines differed before and following cognitive dysfunction, potentially indicating disease progression. The device can also measure the size of amyloid deposits and variety of interactions with polarised light, an advantage over ophthalmic fluorescence imaging, she said. Fluorescence requires the use of a dye marker, whereas polarimetry does not. Polarimetry also demonstrated very high sensitivity and specificity, she said. The next step will be testing the device clinically on patients with AD. Melanie Campbell: mcampbel@uwaterloo.ca

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EYE ON TECHNOLOGY

BOWMAN’S LAYER TRANSPLANTATION New technique aims at restoring potential functionality of Bowman’s layer for corneal stabilisation in keratoconic corneas. Dr Soosan Jacob reports

eratoconus has seen many advances in treatment and outcomes and the old policy of wait and watch until a penetrating keratoplasty (PK) becomes inevitable is not acceptable anymore. Newer varieties of contact lenses, intracorneal ring segments, corneal crosslinking (CXL), toric phakic intraocular lenses (IOLs) and deep anterior lamellar keratoplasty (DALK) have all changed the management of keratoconus dramatically. Mild cases are amenable to CXL with or without intracorneal ring segments, whereas moderately advanced cases of keratoconus can be stabilised with CXL followed by optical correction with glasses or phakic IOL in corneas that are not too irregular. However, patients with very thin corneas, contact lens intolerance or lack of

improvement in vision with contact lenses, may need DALK or PK. It would be ideal to be able to abolish the need for DALK and PK completely.

NEW TREATMENT TECHNIQUE Recently, the Bowman’s layer (BL) transplantation has been advocated as a new treatment technique for preventing progression and to improve vision in keratoconus. The aim of this new technique is to strengthen and flatten the cornea in patients with advanced keratoconus by mid-stromal transplantation of an isolated BL graft, thus enabling continued contact lens wear and avoiding complications that may be associated with a PK or DALK. This technique was developed by Dr Gerrit Melles and his group at the Netherlands Institute for Innovative Ocular Surgery (NIIOS), Amsterdam.

Bowman’s layer graft in situ (arrows) without surrounding inflammation, oedema, or scarring

EUROTIMES | NOVEMBER 2016

“BL transplantation presents a new treatment option for patients with advanced keratoconus. By flattening and regularising the corneal surface, the operation aims to preserve/restore the recipient’s ability to wear rigid contact lenses, thereby enabling good functional vision and delaying or avoiding the need for either PK and DALK,” said Dr Melles. The principle behind BL transplantation is that the BL graft functions like a splint. Dr Jack Parker, also from the NIIOS, explained: “After manually dissecting a mid-stromal pocket within the recipient cornea, the donor tissue is slipped inside and unfolded. The subsequent healing response around the graft possibly flattens the cornea into a more normal and stable configuration. The perfect patients for the procedure are those with progressive advanced keratoconus, ineligible for UV-crosslinking and with good contact lens corrected vision, but with poor (or worsening) contact lens tolerance. Conversely, relatively poor candidates may include patients with large, dense central scarring.” BL transplantation consists of fashioning a mid-stromal pocket within the recipient cornea with the Melles DALK dissection spatulas, using the “airendothelial” reflection to guide the depth of dissection. Once the pocket is created, a Sheets glide is placed into the mouth of the wound, and the BL graft is placed on top, where it is pushed into the pocket, unfolded and stretched out to the corneal periphery using a blunt cannula. “Our experience with endothelial keratoplasty (EK) taught us that corneal surface incisions (as with PK and even DALK) may entail some intrinsic risks, since those operations predispose to a variety of problems, including suture

EYE ON TECHNOLOGY

related and wound healing difficulties, ocular surface challenges, and the risk of allograft reaction and graft rejection. Therefore, we sought a similar solution as with EK: namely, to replace full thickness corneal transplantation with a less invasive alternative. Because BL transplantation involves no cornea surface incisions or sutures, the operation may minimise these risks, and because the graft is acellular, theoretically the threat of allograft reaction and graft rejection may be diminished,” said Dr Melles.

NORMAL SURFACE Korine van Dijk, who is also part of this project, said in their first cohort of patients to receive BL transplantation, the average amount of corneal flattening experienced was eight dioptres. "All were able to comfortably wear scleral contact lenses postoperatively, and 90% had their previously progressive disease arrested,” she said. “After BL transplantation, average spectacle corrected vision increased by two Snellen lines, whereas contact lens corrected vision remained generally unchanged. Surprisingly, though, the majority of all

patients – including those with stable or worsened objective vision after surgery – reported improved daily, subjective visual acuity, which may relate to a more ‘normal’ ocular surface,” she added. In the published study, it was encouraging to note that of the 20 patients included for analysis, the cornea stabilised in 18 and only two patients showed continued steepening of the corneal curvature despite the BL inlay. BL graft preparation remains a somewhat challenging prospect, and benefits greatly from a well-trained eye banking staff. A 9-11mm BL is harvested using a custom-made stripper. It is then submerged in ethanol 70% to remove remnant epithelial cells and stored in organ culture medium at 31°C until transplantation, at which time it is again washed sequentially in 70% alcohol followed by balanced salt solution and then stained with trypan blue before insertion. Performing the manual mid-stromal dissection without perforating may also be difficult, depending on the thinness of the recipient cornea, and in the original study two cases out of a total of 22 eyes

had an intraoperative perforation of Descemet’s membrane during manual dissection.

LIMITATION TO TRANSPLANTATION "The primary limitation to BL transplantation is that the operation may be unsuitable for patients with extremely poor contact-lens corrected visual acuity, since the operation does not generally result in a measurable improvement in that category. However, as with EK, the evolution of anterior lamellar surgeries will probably continue in the direction of selective, minimally invasive, targeted therapies for peculiar problems, rather than indiscriminate full (or nearly full) thickness corneal replacement,” said Dr Melles. To conclude, this new technique aims at restoring the potential functionality of the BL for corneal stabilisation in keratoconic corneas which generally show fragmentation of the BL. Once corneal stabilisation is achieved, the patient can continue contact lens wear for visual rehabilitation. The procedure does not aim at improving best corrected visual acuity (BCVA) and patients with a poor BCVA may benefit more with a DALK or a PK.

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JCRS

JCRS HIGHLIGHTS

VOL: 42 ISSUE: 9 MONTH: SEPTEMBER 2016

EXTENDED-RANGE-OF-VISION IOLS Innovative intraocular lenses (IOLs) designed to provide an extended range of vision do indeed appear to provide successful restoration of vision at all distances, concludes a prospective study conducted at 40 clinical sites throughout Europe. The prospective case series included 411 patients who had bilateral implantation of the extended-range-of-vision IOL (TECNIS Symfony), with intended micro-monovision in one group and intended emmetropia in the other group. By four to six months after cataract surgery, the mean decimal uncorrected distance (UDVA), intermediate (UIVA), and near (UNVA) visual acuities were 0.95, 0.81, and 0.69, respectively. Patients in the monovision group had significantly better intermediate vision. A majority of patients (85%) were able to achieve spectacle independence. Photic complaints were rare, reported by only 10% of patients. Patient satisfaction scores were very high, with more than 91% of patients reporting that they would recommend the same procedure to their friends and family. B Cochener et al, JCRS, “Clinical outcomes of a new extended range of vision intraocular lens: International Multicenter Concerto Study”, Volume 42, Issue 9, 1268-1275.

ROTATIONALLY ASYMMETRIC BIFOCAL IOL DESIGN Computer and experimental visual simulations show that rotationally asymmetric IOL designs tend to provide better visual quality than concentric IOL designs. Spanish researchers evaluated visual and perceptual performance for different orientations of a rotationally asymmetric bifocal IOL (Mplus), simulated optically using a simultaneous vision simulator. The prospective observational study included 20 people ranging from 21 to 62 years old. Horizontal orientation (near segment at 0 or 180 degrees ±45 [SD]) was preferred by 14 people and by 13 at far and near distances, respectively. Eight showed strong orientation preferences. The mean difference in preferred orientation between far and near was 27±22 degrees. No significant differences in high-contrast visual acuity (HCVA) were observed. Optical predictions correlated strongly and significantly with measurements (p< .0001). The mean difference between measurement and simulation in the preferred orientation was 28±29 degrees at far and 36±28 degrees at near. The researchers note that implanting a rotationally asymmetric IOL along the identified preferred orientation can optimise perceptual quality and visual performance. The preferred orientation was influenced by ocular optics and ocular and corneal aberrations, which can be used to predict the orientations in which the IOL should be implanted. A Radhakrishnan et al, JCRS, “Differences in visual quality with orientation of a rotationally asymmetric bifocal intraocular lens design”, Volume 42, Issue 9, 1276-1287.

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RESEARCH

CARROT OR STICK? Criticisms of the current EU Clinical Trial Directive will need to be addressed if clinician-led studies are to continue. Dr Gearóid Tuohy reports

onducting clinical research in an academic environment is significantly dictated by the availability of scarce resources. In contrast, clinical research in a commercial environment may avail of relatively generous funding. While both academic and commercial research often have fundamentally different objectives and risks, unfortunately they are at present obliged to comply with the same standards of Good Clinical Practice (GCP), including relevant adherence to national and EU legislation. The result of such a “one-sizefits-all” approach to regulation is a fundamental mismatch between risk and risk management, in which academicled studies lose out due to soaring administration and compliance costs. It is hoped that a new Clinical Trial Regulation (Regulation [EU] No 536/2014), scheduled for application either this year or next, should redress the current imbalances. It will be clear to most practitioners in the field of clinical studies that academic trials and commercial trials generally have quite different objectives - academic trials are often focused on real-world outcomes and routine clinical management, while commercial trials generally focus on assembling data to secure product approval and market authorisation. Such distinct objectives often lead to different study designs and different risk profiles, in

EUROTIMES | NOVEMBER 2016

turn leading to a potential wastage of scarce resources when the rules become misaligned. While all stakeholders readily agree with the foundational principles of patient protection and safety, as articulated in the Declaration of Helsinki, differences often arise in how best to deliver such protections. The current obligations for initiating, conducting, monitoring and reporting a clinical trial in the EU are set out in EU Directive 2001/20/EC, and laterally, EU Directive 2005/28/EC, and within the International Conference on Harmonisation (ICH) Guideline for Good Clinical Practice (ICH-GCP E6 R1, 10 June 1996). The purpose of the EU Directives on clinical trials is to set out the regulations and administration of GCP in the conduct of trials undertaken within the 28 Member States. However, a number of practices, including Guideline ICH-E6, detailing the expected clinical practice for human trials, have attracted significant criticism, as have additional obstacles which unnecessarily hinder the progress of non-commercial academic-led studies. In particular, concerns have arisen that ICH-E6 lacks transparency on the identity of the authors and the evidencebase upon which the guideline rests. The most recent version of the guideline, from June 1996, has not been updated in years, rendering it out-of-date (although work on a draft addendum is under way). It creates costly and complex approval procedures and is principally written with industry in mind, having had little or no input

from the academic research community. In addition, monitoring is criticised as disproportionately focused on minutiae of trial conduct rather than centralised oversight, while drug safety appears more focused on individual case reports than on the more material consideration of overall rates of adverse events.

CORE CHALLENGES While each of these criticisms is well-founded, they overlie three core methodological challenges which need to be addressed if application of the new regulation is to be a success: 1) Recognition that current rules deal with different processes. Academic and commercial trials are not the same, however current regulatory frameworks do not appropriately acknowledge the clear distinctions. A top-down imposed “one-size-fits-all” approach attempts to shoehorn one constituency of the research community (academic researchers) into a process designed for a different constituency (the pharmaceutical industry). While these constituencies have much in common, they differ in respect of why they do research. Academic research is primarily conducted to drive improvements in patient care and treatment, while pharmaceutical research is primarily driven by commercial interests. This is no slight on the pharma industry, as their drive to license and market new products is similarly directed at improving patient care even if the path to

RESEARCH such a goal is driven by the required profitmotive of any industrial pursuit. However, if current regulations persist in applying the same audit and management processes on both constituencies, then a significant body of research, of benefit to patients, clinicians and society, will increasingly struggle to find sufficient funding. 2) Risk management needs to be proportionate. It must be proportionate to the actual risk. Any reasonable assessment of risk must acknowledge the differences between, for example, an aspirin study conducted across a number of rural populations, versus a virally delivered experimental gene therapy study in an orphan neurological indication. Current EU regulations (and interpretations thereof) generally fail to accommodate such a distinction. Clearly, the actual risks of aspirin use and gene therapy are logarithmically different, however a voluminous body of documentation is required for both studies. Significantly, finding the funding required for an academic-led aspirin study in rural communities can be close to impossible, while funding a gene therapy study would likely attract several commercial players. More importantly, the beneficiaries of the aspirin study may far outnumber the beneficiaries of the orphan gene therapy study, resulting in a negative selection pressure against academic investigator-led research. Without academic-led research there would be an enormous gap in the evidence-based medicine upon which clinicians in ophthalmology and all other medical disciplines depend. 3) All stick, no carrot. Finally, there appears to be a fundamental contradiction in the basic message from the EU. The Commission stresses the importance of patient safety and validity of data, but remains silent on how to deliver same and on who is going to pay for it. The process appears to be all stick

and no carrot. If the EU wishes to impose homogenous regulations for the control of clinical trials, regardless of risk and costs, and then enforce such regulations through national legislation obliging governments to uphold them, then such obligations should come with the necessary resources to meet those obligations. Academic funding for administration and compliance is close to non-existent and so, ultimately, the message from the EU becomes both contradictory and confusing as it simultaneously seems to say: patient safety and validity of data are important, but not important enough to be paid for. The result is that patient welfare â&#x20AC;&#x201C; positioned at the core of the Declaration of Helsinki â&#x20AC;&#x201C; may become corroded. The core criticisms of GCP derive from a misunderstanding of risk management, coupled with the ever-increasing costs required for full compliance. The costs of such compliance are far from trivial and can quickly mount up to a

significant proportion of the funding required to fund even the most simple and straightforward of studies. Access to funding is materially different in academic and commercial environments, leading to an uneven playing pitch where universities and hospitals are being priced out of the clinical trial field due to increasingly burdensome obligations designed for industry. If such a trend remains unchecked, clinical trials may only be conducted by those with the deepest pockets, potentially resulting in an erosion of unbiased studies due to the inevitable conflicts of interest that may arise. A rebalancing of processes, risks and resources is required to produce a framework that maintains patient safety and data validity, but incorporates realistic management systems that protect and sustain a vibrant and independent clinical research environment. GearĂłid Tuohy: gearoid.tuohy@escrs.org

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STAINING SOLUTION Vioron is Geuder’s number one tissue staining solution for cataract surgeries, and is available as vial and syringe. “It consists of trypan blue and ensures an effective staining and thus brilliant visualisation of the anterior lens capsule,” said a company spokesman. “This staining solution enables an excellent distinction of the capsulorhexis margin. It is quick and easy to apply, and applicable to a variety of further indications, e.g. congenital or (hyper) mature cataract surgery,” added the spokesman. www.geuder.com

Steven C Schallhorn

NEW APPOINTMENT Carl Zeiss Meditec has appointed Steven C Schallhorn MD as Chief Medical Officer for Global Ophthalmic Devices, consisting of refractive lasers, surgical ophthalmology and ophthalmic diagnostics. Dr Schallhorn will serve on the Executive Leadership Team, providing strategic direction for the business and medical guidance on the clinical use of ZEISS’ portfolio of ophthalmic diagnostic and surgical technologies. The company said Dr Schallhorn will collaborate with key opinion leaders. www.zeiss.com

EXPANDED CUSTOMER REACH HOYA has announced a definitive agreement to acquire Performance Optics, including its subsidiaries VISION EASE and Daemyung Optical. Performance Optics is a global ophthalmic lens manufacturer specialising in polycarbonate, photochromic, polarised and highindex eyeglass lenses. “The acquisition of Performance Optics expands HOYA’s customer reach, particularly through VISION EASE’s presence in the Americas and its strengths in polycarbonate products and technologies,” said Girts Cimermans, CEO of HOYA Vision Care. “Performance Optics provides HOYA with additional capabilities,” he added. www.hoya.com

Our members aren’t just predicting the future of eye surgery and patient care, they’re creating it. Belong to something powerful. Join us. www.escrs.org

EUROTIMES | NOVEMBER 2016

OUTLOOK ON INDUSTRY

MAZZO MAKES HIS MOVE It’s all about customer service, says new Global President Ophthalmic Devices at Zeiss. Howard Larkin reports

ince beginning his career in ophthalmic products at Allergan 36 years ago, James V Mazzo always respected Carl Zeiss Meditec (CZM) as a technology leader. So when CZM Supervisory Board Chairman Michael Kaschke PhD asked Mazzo to lead its newly consolidated global ophthalmic business this summer, Mazzo was more than ready. If anything, Zeiss looks better from the inside, Mazzo told EuroTimes. “Now that I’m part of the team, I get to see behind the doors and I’m overwhelmed by how impressive the technology is. When you look at Zeiss technology, it’s top notch. It’s the best of anything I have ever seen,” he said. Coming from the man who built Advanced Medical Optics into the top refractive player worldwide, largely on the strength of technology following its 2002 spin-off from Allergan, that is high praise indeed. After leaving AMO in 2013, four years after its acquisition and name change by Abbott, Mazzo further burnished his tech development street cred as CEO of AcuFocus, where he shepherded the revolutionary Kamra small aperture corneal inlay for presbyopia to FDA approval. He is also executive chairman of Neurotech Pharmaceuticals, a biotech firm developing sight-saving therapies for a broad range of eye diseases.

ONE-STOP SHOP If there’s a soft spot at Zeiss, it’s unfocused customer service, Mazzo said. “I would rather have weak service and great technology because I can fix the service easier than I can fix the technology. It’s a nice problem to have.” Historically, CZM’s sales and service have largely followed its products, a division of effort reflected in the firm’s long-time organisation into three separate ophthalmic business units. However, this previous structure was not aligned with customer needs, Mazzo said.

BUILDING A WINNER

James V Mazzo, who is heading up the global ophthalmic business at Zeiss

“We have a great diagnostic portfolio, a great cataract portfolio and a great refractive portfolio, but the retina specialist is the cataract surgeon is the refractive surgeon. The same customer may use many of the same products and the customer doesn’t care how the company is organised,” he added. At least they don’t care until they need service for both their Zeiss OCT machine and their Zeiss surgical microscope – and have to cope with not one but two service centres, two contacts, two phone mail systems... “We need to make it less complicated to deal with Zeiss,” Mazzo said. Every salesperson and customer service representative should know the entire product line well enough to help the customer or put the customer in contact with someone who can help. And when you call Zeiss, someone should answer the phone and make it their business to take care of you, Mazzo said. “When you go to the store and buy a suit, a tie and a shirt, you don’t want to have to go to three different people. We all remember where we’ve had great service, and if the products are good too – and ours are the best – it’s a winning combination.”

When you look at Zeiss technology, it’s top notch. It’s the best of anything I have ever seen James V Mazzo EUROTIMES | NOVEMBER 2016

Delivering integrated service requires an integrated company, and that’s why CZM has consolidated its three ophthalmic business units – ophthalmic diagnostics, surgical ophthalmology and refractive lasers – into one global ophthalmic device unit, led by Mazzo. He’s also hired Andrew Ihan Chang away from rival Bausch + Lomb as his global head of sales. It all comes down to efficiency, Mazzo said. “Doctors are required to be more and more efficient all the time. Anything we can do to make them more efficient helps.” That applies to ophthalmic office staff as well, Mazzo added. “If we can make an invoice easier to understand we can save them a phone call and some time.” Indeed, efficiency commands such a premium that Mazzo believes it’s the reason femtosecond laser-assisted cataract surgery (FLACS) has yet to take off. “We all thought femto would revolutionise cataract surgery. It really hasn’t, and it’s not because it’s expensive. I believe it’s because it makes surgeons a little bit slower right now, and that’s a problem,” he said. Mazzo believes FLACS has legs, and will be a runner when it’s better integrated into the surgical workflow, perhaps by incorporating it with the surgical microscope. “If you are going to introduce a product it has to make you more efficient,” he said. Zeiss has the expertise, long-term management commitment and capital resources to pull it off, even if it takes years. Mazzo also believes in professional education, and has hired Steven C Schallhorn MD as CZM’s new Chief Medical Officer. Dr Schallhorn’s extensive experience as a researcher, clinician, device developer and professor will help Zeiss partner with clinicians and academics to improve clinical outcomes. Pushing customer service one step further, Mazzo sees improving the patient experience as another key to success. He is planning education programmes on this. Mazzo is committed to working with other firms to advance the industry’s common interests. Yet he sees Zeiss grabbing a bigger share of the global ophthalmic market – and soon. “We have the broadest product technology portfolio across all the industry spaces and we sit here at No 4. Now the competitiveness comes out in me and we’re going to move that.”

ESCRS NEWS

ESCRS

NEWS

David Touboul presents on CXL with corneal rings at AAO, as Rudy Nuijts and Thomas Kohnen look on

ESCRS ON CXL AT AAO With corneal crosslinking (CXL) finally approved this year by the US Food and Drug Administration, ESCRS members schooled their American colleagues on the latest in CXL technology at Refractive Surgery Subspecialty Day, sponsored by the International Society of Refractive Surgery, at the 2016 American Academy of Ophthalmology (AAO) Annual Meeting in Chicago. In his review of indications and long-term outcomes for CXL in keratoconus, Rudy MMA Nuijts MD, PhD, of the Academic Hospital Maastricht, The Netherlands, noted that standard Dresden Protocol CXL provides stable long-term results for visual acuity and keratometry in 90% of patients. In children, epithelium-off CXL provides persistent treatment effect up to four years in 80-90% of patients. Preliminary data suggests CXL will lead to a decrease of at least 25% in corneal transplants for keratoconus. Topographyguided photorefractive keratectomy (PRK) combined with CXL has proven an effective treatment for post-LASIK ectasia and visual rehabilitation over 12 years, said A John Kanellopoulos MD of Athens, Greece, and New York University, USA. Other presenters were Thomas Kohnen MD, PhD, of Goethe University Frankfurt, Germany, on accelerated CXL; David Touboul MD, of the University of Bordeaux, France, on CXL with corneal rings; and Simonetta Morselli MD, of the University of Verona, Italy, on CXL for treating corneal infections.

Watch the latest video content from ESCRS and EuroTimes, FREE on the ESCRS Player l

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Video Journal of Cataract & Refractive Surgery Young Ophthalmologists Videos: “My Early Surgeries” Online Museum

CLINICAL METHODOLOGY ONLINE COURSE Applications are now being invited to the Miguel Hernandez University (Spain) online course on clinical methodology in refractive, cataract and corneal surgery. “In this course, we provide a comprehensive teaching curriculum and learning environment, applying an international model, covering the basic science related to refractive surgery,” said course director Jorge L Alió MD, PhD. The curriculum covers refractive surgery, lens surgery, fundamentals of corneal surgery, good

Jorge L Alió

clinical practice, guidelines and standard protocols, basic research methodology and advanced keratoconus. For more information, go to: www.refractivesurgery onlinecourse.com

player.escrs.org EUROTIMES | NOVEMBER 2016

EYE ON HISTORY

DUTCH MASTER

Herman Snellen (1834–1908) is still widely recognised for his visual acuity testing. Prof Andrzej Grzybowski reports

VISUAL ACUITY TESTING Snellen was the first assistant professor in The Netherlands who dedicated himself entirely to ophthalmology. In 1877, he became Professor of Ophthalmology at Utrecht University. He had 12 children, and was succeeded by Herman Snellen Jr. Snellen left behind comprehensive work on many topics including anterior synechiae, astigmatism, accommodation, keratoconus, defective colour vision, amaurotic eyes, sympathetic ophthalmia, inflammation, diseases of the retina and connective tissue, eyeball prosthesis, the history of glaucoma treatment and eye examinations. He is, however, best remembered today due to his improvements of eyelid operations, including ectropion, entropion and trichiasis (tarsal wedge resection) and his work on visual acuity testing. In 1862 he published his work Test-types for the determination of the acuteness of vision, in which he described in detail his concept: “Over each series of letters of the same size a number was placed indicating the distance (in feet or metres) at which the letters subtended an angle of five minutes. In calculating the size, the arc and not the tangent was taken. The degree of acuteness of EUROTIMES | NOVEMBER 2016

vision (V) is expressed by the relation of the distance at which the letter is actually seen (d), to that at which the letter is apparent at an angle of five minutes (D); V= d/D.” Snellen was not the first or last person to create test charts. The first known was Benito Daça de Valdes (1591–1634), who in 1623 proposed to present small objects of regular size and determine the distance at which they could not be discerned, and who measured the distance at which a row of mustard seeds could not be counted. He also varied the distance at which small print could be read. In 1843, Heinrich Georg Küchler (1811–1873), a German ophthalmologist from Darmstadt, invented a chart consisting of figures of various objects (birds, frogs, farm implements, cannons etc.) cut from calendars and almanacs, which he glued to a sheet of paper in decreasing size.

FIXED DISTANCE Eduard Jäger von Jaxtthal (1818–1884), an Austrian ophthalmologist, in 1854 made improvements to eye chart test types that were earlier developed by Küchler for testing near vision acuity. He introduced a card on which paragraphs of text were printed, with the text sizes increasing from 0.37mm to 2.5mm. The card was to be held by a patient at a fixed distance and the smallest print that the patient could read determined their visual acuity. Among Snellen’s innovations were the following: e n nS l Rather than using existing typefaces, he designed a m Her special characters, which he called optotypes, for the specific purpose of visual acuity measurement. l He arranged these optotypes in a letter chart format to be used as a test of distance vision. l He calibrated his characters based on an external standard (5’ arc), so that others who wanted to reproduce them or design their own, could calibrate them to the same standard. l He popularised his charts in different languages. Although Dutch ophthalmology has had many recognised experts and important achievements, so far no one has been able to contribute more to world ophthalmology than Donders and Snellen. ,1 83 4-1 908

here are few names in ophthalmology better known than Herman Snellen, mostly because of his work on visual acuity testing and the chart he introduced for this purpose. Snellen was born in Zeist, near Utrecht, The Netherlands in 1834. He was the son of the popular physician Dr F A Snellen. In Utrecht, he studied medicine and received his medical doctorate in 1858 based on his work on “Experimental examination about the influence of the nerves on the inflammation”. In the same year, he received a position as assistant physician in the ophthalmological clinic ‘Nederlandsch Gasthuis voor Ooglijders’, founded by his teacher and mentor Franz Cornelius Donders. In 1862 he became primary physician, and in 1884 director of the institution. During the first 10 years of institute work, 12,592 out- and 3,130 in-patients were treated and 2,885 operations were performed. The clinic’s history is closely connected with the modern history of Dutch ophthalmology. It was a training centre for Dutch as well as foreign physicians, and numerous theses and publications originated there.

lle n

Andrzej Grzybowski MD, PhD is Professor of Ophthalmology, Poznan-Olsztyn, Poland

CALENDAR

DECEMBER

ISOPT Clinical 2016

1–3 December Rome, Italy www.isoptclinical.com

↙

Joint Irish and UKISCRS Refractive Surgery Meeting

LAST CALL

NOVEMBER

BEAVRS 2016

10–11 November Southampton, UK www.beavrs.org

IMO – Trends in Glaucoma: Surgical & Medical Meeting 18–19 November Barcelona, Spain www.imo.es/glaucoma2016

2 December Dublin, Ireland Email: hmurphy@materprivate.ie

2017

JANUARY

8th International Course on Ophthalmic and Oculoplastic Reconstruction and Trauma Surgery

11–13 January Vienna, Austria www.ophthalmictrainings.com/ workshops

7th EURETINA Winter Meeting 28 January Vienna, Austria www.euretina.org

FEBRUARY

3rd Asia-Australia Congress on Controversies in Ophthalmology (COPHy AA) 9–12 February Seoul, South Korea www.comtecmed.com/ cophy/aa/2017/ default.aspx

21st ESCRS Winter Meeting

10–12 February Maastricht, The Netherlands www.escrs.org

FEBRUARY

Retina World Congress

23–26 February Fort Lauderdale, USA www.retinaworldcongress.org

MARCH

31st International Congress of the Hellenic Society of Intraocular Implant and Refractive Surgery 2–5 March Athens, Greece www.hsioirs.org/index.php/en

8th World Congress on Controversies in Ophthalmology (COPHy)

30 March –1 April Madrid, Spain www.comtecmed.com/cophy/ 2017/default.aspx

APRIL

AAPOS Annual Meeting

2–6 April Nashville, USA www.aapos.org/meeting/ annual_meeting_future_dates

FLOREtina 2017 27–30 April Florence, Italy www.floretina.it

MAY

ASCRS 2017

5–9 May Los Angeles, USA www.ascrs.org

NEW SFO 2017

6–9 May Paris, France www.sfo.asso.fr

ARVO Annual Meeting 2017 7–11 May Baltimore, USA www.arvo.org

MediterRetina Club International Meeting 11–13 May Parma, Italy www.mediterretina.com

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CALENDAR

JUNE

Barcelona, host city of the EURETINA Congress in 2017

30th APACRS Annual Meeting

1–4 June Hangzhou, China www.apacrs2017.org

SOE 2017

10–13 June Barcelona, Spain www.soe2017.org

World Glaucoma Congress

28 June–1 July Helsinki, Finland www.worldglaucoma.org

AUGUST

ASRS Annual Meeting 2017 12–16 August Boston, USA www.asrs.org/ annual-meeting

OCTOBER

8th EuCornea Congress

SEPTEMBER

6–7 October Lisbon, Portugal www.eucornea.org

17th EURETINA Congress 7–10 September Barcelona, Spain www.euretina.org

XXXV Congress of the ESCRS

DECEMBER

4th World Congress of Paediatric Ophthalmology and Strabismus 1–3 December India wspos.org/india-2017

7–11 October Lisbon, Portugal www.escrs.org

EVER – European Association for Vision and Eye Research Congress 2017

AAO 2017

11–14 November New Orleans, USA www.aao.org/ annual-meeting

DOG 2017

28 September–1 October Berlin, Germany www.dog.org

EURETINA WINTER MEETING Medical University Vienna, Austria

Saturday 28 January 2017 Registration available online www.euretina.org

EUROTIMES | NOVEMBER 2016

SEPTEMBER

18th EURETINA Congress 20–23 September Vienna, Austria www.euretina.org

21–22 September Vienna, Austria www.eucornea.org

NOVEMBER

27–30 September Nice, France www.ever.be

2018

9th EuCornea Congress

↙

XXXVI Congress of the ESCRS 22–26 September Vienna, Austria www.escrs.org

LISBON2017 7–11 OCTOBER

XXXV CONGRESS of the ESCRS FIL – International Fair of Lisbon, Portugal