EuroTimes Vol. 21 - Issue 5

SPECIAL FOCUS RETINA CORNEA

LATEST-GENERATION KERATOPROSTHETIC DEVICES MAY IMPROVE RESULTS May 2016 | Vol 21 Issue 5

HOSPITAL DIARY

TERROR IN BRUSSELS: DR LEIGH SPIELBERG’S EXPERIENCE ON THE FRONTLINE

RESTORING

THE RETINA

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

ESCRS RESOURCES

CORNEA

3 Exciting projects:

20 ‘When we do CXL we

SPECIAL FOCUS

24 Improved results with

Society adds new features to website

RETINA 4 Cover Story: Gene therapy and stem cell transplants for retinal disease

8 Zika virus infection: vision-threatening fundus lesions

are obviously initiating some healing cascades in the cornea’ the latest generation of keratoprosthetic devices

GLAUCOMA 26 Growing range

of drainage devices providing new treatment options

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10 New system for self-

testing visual acuity showing promise

11 Geographic atrophy –

phase 3 trials can help determine value of lampalizumab

12 The revolution in retinal pharmacology

FEATURES CATARACT & REFRACTIVE

OCULAR 28 ‘Iontophoresis offers many opportunities for non-invasive delivery of drugs’

36 Hospital Diary

PAEDIATRIC OPHTHALMOLOGY

39 Industry News

30 Anti-VEGF agent offers

42 JCRS Highlights

41 Ophthalmologica

hope for treating corneal neovascularisation

43 ESASO Update 45 Travel 46 Review

estimations of throughfocus acuity improve anterior segment outcomes

33 Book Reviews 34 ESCRS News

15 Aberrometry-based 16 Topical NSAIDs may

REGULARS

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48 Calendar

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

surgeon’s skills are still crucial to results’

19 New adaptive optics

simulator could assist in treatment of presbyopia

EuroTimes & JCRS 1996–2016 EUROTIMES | MAY 2016

2

EDITORIAL A WORD FROM LEIGH SPIELBERG MD

WHERE TO NEXT?

Gene therapy is one of the next frontiers in retinal disease, with exciting new research opening up opportunities for ophthalmologists

A

dvancement in the treatment of retinal disease MAKING A DIFFERENCE has come so far that I sometimes wonder where Prof Leroy has an active involvement in the gene therapy we can possibly go next. Retinal detachments are studies at the Children’s Hospital of Philadelphia, USA. successfully reattached in well over 90 per cent of This collaboration will lead to the participation of our cases after a single surgery, and macular hole closure centre, Ghent University Hospital, Belgium, in future gene is close to 100 per cent with the current techniques. therapy trials.

Neovascular AMD has been changed from a hopeless Until then, we as retinal specialists involved in dayordeal into a largely treatable condition, as has diabetic to-day clinical cases will concentrate our efforts on the retinopathy, at least in those patients who present early problems which we regularly enough and possess the willpower to follow through encounter: preventing the with their treatment regimens.

Retinal detachments are proliferative vitreoretinopathy Surgery can correct the structure of the retina, and that can destroy an otherwise successfully reattached intravitreal injections of anti-VEGF and steroids can successfully treated retinal in well over 90 per cent of improve its function. The respectable results across the detachment; figuring out why board allow me to be in quite good spirits after a day in cases after a single surgery, macular hole closure does not the vitreoretinal operating room. The same can be said and macular hole closure is necessarily mean visual recovery; for my colleagues in medical retina. and deciphering the reason(s) close to 100 per cent with But at the end of every day in the hospital, I why neovascular AMD, despite the current techniques walk past the ophthalmic genetics clinic, where optimal anti-VEGF treatment, Bart Leroy MD, PhD, the chairman of our can sometimes end up atrophic. ophthalmology department, diagnoses genetic disorders In this edition of EuroTimes, I have also reported on my such as Leber congenital amaurosis type 2 and retinitis experience of treating a victim of the recent terrorist attacks in pigmentosa. Within his field, his research and diagnostic Brussels. Ophthalmologists are occasionally called on to make work are world-renowned. But the therapeutic options a difference in people’s lives outside of routine, scheduled he, or anyone else, can offer to patients suffering from surgery. This can make our work engrossing, and motivates us inherited eye diseases leave much to be desired. They to stay sharp and expect the unexpected. are in a similar position as ophthalmologists were with The same mindset applies to the cutting edge of retinal neovascular AMD years ago: make the diagnosis, provide disease. If the gene therapy trials require surgical intervention, counselling, and irrationally hope it doesn’t turn out as my vitreoretinal colleagues and I would be delighted and poorly as one knows it will. honoured to participate.

So what is one of the next frontiers in retinal disease? Gene therapy. Although many remain sceptical, the trials that are now being reported show that the results are encouraging and that gene therapy has a strong and lasting effect in vivo. The Lancet will soon publish a paper, of which Prof Leroy is co-author, describing the results of gene therapy in Dr Leigh Spielberg is a vitreoretinal and cataract surgeon the second eye of patients suffering from childhood-onset at Ghent University Hospital, Belgium, and a member of blindness due to RPE65 mutations. This is exciting. the EuroTimes International Editorial Board

MEDICAL EDITORS

Emanuel Rosen Chief Medical Editor

José Güell

Thomas Kohnen

Paul Rosen

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

EUROTIMES | MAY 2016

ESCRS RESOURCES

EXCITING NEW PROJECTS Illustration by Eoin Coveney

The ESCRS is increasing its commitment to year-round education and training by developing the resources on its website. ESCRS President David Spalton reports We want to build a bank of clear and explicit surgical techniques, and Dr Richard Packard has kindly agreed to take charge of this project. Videos can be submitted to: videos@escrs.org Voice-overs will often be helpful but musical backgrounds not.

Videos will be credited to the author but we reserve the right to edit them appropriately. Videos will not be downloadable but only viewable by members through the ESCRS website.

ONLINE MUSEUM

T

he ESCRS has just had the two most successful meetings in its history, with over 8,500 delegates at the annual congress in Barcelona last September and over 2,200 delegates from 74 different countries at the winter meeting in Athens in February.

We face headwinds from financial stringency and changes in medical regulation over the next year, but we go forward in robust health and a strong financial situation.

In Athens, the Board agreed to increase our commitment to year-round education and training by developing the resources on our website: www.escrs.org At present, we have the very successful iLearn platform aimed at trainees, the Video of the Month, the Eye Contact studio interviews, and ESCRS on Demand to catch up on what you missed at the meetings.

SURGICAL REFERENCE VIDEOS The next development will be to offer a ‘Surgical Reference Video’ section illustrating high quality ‘how to do’ surgical technique and we would like you to submit material for this teaching archive.

There are many videos on YouTube of variable quality and content, but our site will offer only high-quality material selected for its teaching impact. Examples could be something simple such as a clip on how to perform stop and chop or divide and conquer, or how to handle a particular complication.

For example, Dr Brian Little showed a lovely clip in Athens of how to avoid disaster from a PC rupture during IA, which would be ideal. Other examples might be to show how to manage zonular dialysis, a subluxed lens or fixation in absence of capsular support, or procedures which cataract surgeons do from time to time such as removal of a pterygium, a trabeculectomy or MIGS procedures.

The aim is to have a tagged and searchable comprehensive collection, but not to have glitzy fascinomas – there are other forums for these enjoyable exercises of surgical dexterity.

Another development will be an online museum, which will be curated by Dr Packard and Prof Andrzej Grzybowski. Many of the younger generation of surgeons are oblivious to the rich history and the trials and tribulations that have led to modern cataract surgery.

I can personally recall the very emotional and heated controversy as implant and phaco surgery developed during the 1980s and 1990s.

This is part of our heritage and must not be forgotten.

We would like any material of historical interest such as video clips or still images of people, early IOL designs, operations and techniques – in fact anything of historical interest.

I shall be contributing my video of Sir Harold Ridley’s first operation and a video of the surgical logbook from St Thomas’ Hospital, London, showing that he did the first implant with the cataract surgery as a primary procedure and the implant as a secondary operation four months later – something glossed over in the later furore because he didn’t want to admit that he had put the patient’s eye in double jeopardy with the substantial risk in those days of a second operation.

Contributions will be acknowledged, and in this instance material will be downloadable by members to add interest to presentations and lectures. Please submit material to: museum@escrs.org I am very excited about these two new projects, as they will add greatly to the content of our website, and I look forward to receiving historical material and videos from you in the coming months.

David Spalton: president@escrs.org

True innovation comes from sharing knowledge.

Clinical Research Awards 2017 Call for Proposals

ESCRS has made available funding of €750,000 over three years for clinical research projects in the field of cataract and refractive surgery Deadline for expressions of interest: 27 June 2016

www.escrs.org EUROTIMES | MAY 2016

3

4

COVER STORY: RETINA

RESTORING

THE RETINA Gene therapy and stem cell transplants for retinal disease edging closer to clinical reality.

Roibeard O’hEineachain reports

EUROTIMES | MAY 2016

A

dvances in cellular biology that have taken place over the last half century are making a slow advance into the clinic in the treatment of retinal diseases.

The research has revealed in increasing detail the complex biomolecular interplay involved in maintaining the function and metabolism of the cells of the retina. Moreover, by combining that understanding with genome mapping, investigators have pinpointed the underlying molecular basis and genetic origins of several hereditary retinal dystrophies.

Recombinant DNA techniques first developed in the 1970s have since enabled the development of in situ gene therapy techniques that can restore the function of diseased retinal cells. The same technology has lead to the creation of genetically modified animal models of the diseases for testing new therapeutic strategies. Also important has been the mapping out of the evolution of stem cells, from the zygote to the retina.

Based on this research, there are already in routine clinical use a range of biomolecular agents designed to inhibit angiogenesis in eyes with exudative agerelated macular degeneration (AMD), and trials are now under way with the use of a monoclonal antibody in the treatment of geographic atrophy.

Gene therapy for hereditary retinal diseases and the use of stem cells to regenerate damaged or absent retinal tissues are two products of the scientific advances that are taking further steps towards clinical use. And while progress in the clinic has been slow, it has nonetheless in several instances yielded confirmation of the safety and potential efficacy of the new therapeutic techniques.

GENE THERAPY Of the two approaches, gene therapy has the most advanced pedigree in terms of clinical trials, dating back to 2008 with the publication of three separate gene therapy trials, conducted in the UK, Pennsylvania and Florida, and involving patients with Leber congenital amaurosis type 2 (LCA2).

In the UK study, one patient showed significant improvement in dark adapted perimetry and subjective testing of visual mobility. In the Pennsylvania trial, patients had improvements in visual acuity, light sensitivity and mobility. In the Florida study, patients had a functional improvement in the areas of the visual field corresponding to areas of the retinal pigment epithelium (RPE) injected with modified adeno-associated virus (AAV) carrying the gene for the RPE65 enzyme.

These early gene therapy studies established that it is possible to safely deliver billions of AAV particles into the subretinal space. Subsequent studies from

COVER STORY: RETINA the Philadelphia team also showed that a second injection into the fellow eye did not provoke an immune reaction. However, the long-term benefit has yet to be established with certainty. Follow-up reports from the Florida study indicate that there is improved visual function in the short-term but that it declines after a few years.

Robert MacLaren DPhil, FRCOphth, from the University of Oxford, UK, noted that the seeming loss of effect in RPE65 was more a result of a lower than optimum gene transduction in eyes with disease that was too advanced.

“The most important factor in the decline in vision is that it is unlikely that all of the RPE cells will be transduced.

If you look at some of the data from the Florida study you will see that there is a boost initially in visual function but then it diminishes. But it reaches a plateau which is still much higher than it was at baseline,” said Dr MacLaren.

“That is because, when only 50 per cent of cells have been transduced, you will suddenly get a boost from the improved function of those cells and you still have some residual output from the remaining cells which have not been transduced. Over a period of time, the 50 per cent of cells which have not received the virus will die off, so following that initial peak you will have a decline,” he explained.

However, another hurdle gene therapy techniques have to overcome is their regulatory approval for use in trials involving patients at an early stage of their disease. By necessity, early trials involve patients with advanced disease with less to lose but also less tissue to salvage.

“Gene therapy is always going to be much more efficacious when the treatment is applied before the onset of retinal degeneration,” Dr MacLaren said.

Meanwhile, recently published results involving six patients undergoing choroideremia have been involving gene therapy for choroideremia (MacLaren et al, The Lancet 2014, 29;383(9923):1129-37), showed that patients gained a mean of 3.8 letters of visual acuity, and that the two more severely affected individuals gained 21 letters and 11 letter letters, respectively.

In addition, regulatory approval has been granted in Germany for a gene therapy trial involving achromatopsia, a rare condition due to mutations in the CNGA3 gene that causes complete loss of function to the cone cells. Further

AAV gene therapy studies for X-linked retinoschisis (XLRS), Leber hereditary optic neuropathy (LHON) and retinitis pigmentosa due to mutations in the MerTK gene are also ongoing.

“I think we’ll see gene therapy used in a number of retinal diseases and it will simply be taken for granted as a treatment. We need to do more work on the surgery so that we can apply the virus safely in the early stages of disease and we need to work out a way of delivering larger genes. Apart from that, we’re en route,” Dr MacLaren added.

STEM CELL TRANSPLANTS Stem cell transplants for retinal diseases have only very recently been used in clinical trials in small numbers of patients.

Although it is too early to provide an assessment of their therapeutic value, in-vitro and animal studies indicate that the approaches have great potential, showing that it is possible using threedimensional stem cell culture techniques.

It is possible to generate stratified layers of retinal cells and that multilayered retinal stem cell implants can provide vision to genetically blind mice.

The two competing stem cell technologies for clinical use are those using embryonic stem cell techniques and those using autologous induced pluripotent stem (iPS) cells. Embryonic stem cells have the advantage of being producible on a grand scale at a fairly modest expense using closely monitored cell lines of proven safety and efficacy. In contrast, autologous iPS cell grafts take a year to create at an expense of around $400,000 to $800,000 per patient.

Both approaches have been used in phase1/2 trials to generate retinal pigment epithelial cells for implantation in the subretinal space of eyes with AMD. The RPE plays a pivotal role in the pathophysiology of AMD. The first application of stem cell therapy for dry AMD in humans was reported by Steven D Schwartz MD, Jules Stein Eye Institute, UCLA, USA. The researchers used cell cultures derived from blastocysts and induced them to differentiate into RPE cells. They then injected the cells in a suspension subretinally in nine patients with dry AMD and nine patients with Stargardt’s disease. The patients received strong immunosuppressant therapy.

(Schwartz et al, Lancet 2015 ;385 : 509-516) After the injection, clumps of hyperpigmented stem cells were visible.

I think we’ll see gene therapy used in a number of retinal diseases and it will simply be taken for granted as a treatment Robert MacLaren DPhil, FRCOphth EUROTIMES | MAY 2016

5

COVER STORY: RETINA Furthermore, there was no evidence of inflammation or rejection. And although the trial was mainly focussed on the safety of the technique, the researchers reported improvement in several different functional measures. However, there was no clear topographic correspondence between retinal regions with improved function and regions where there was hyperpigmentation.

“Emphasis needs to be placed on the fact that this is the first use of ESC-engrafting of any kind and that it established proof of principle, that the transplanted cells could survive without the feared adverse side effects like teratoma or immune reaction.

Much to our surprise, some patients had an improvement in their vision,” Dr Schwartz told EuroTimes in an interview.

He added that while iPS cell transplants avoid any ethical, religious or regulatory concerns regarding the use of embryonic stem cells, the stem cell line he used in his study were derived not from abortions but from unused zygotes obtained through fertility treatment. He added that, compared to iPS cell lines human which hold great promise and may eventually be safe and scalable, embryonic cell lines seem at present to be less likely to be tumorigenic. Induced stem cells have a tendency to revert to their original cell type and are more prone to mutation, he said.

Still open to question is whether embryonic stem cell therapy will be more immunogenic than techniques using autologous iPS cells, or whether the retina’s immune privilege will make any difference irrelevant, he said.

Courtesy of Robert MacLaren DPhil, FRCOphth

6

iPS CELL APPROACH Masayo Takahashi MD, PhD and her associates at the Riken Centre for Developmental Biology in Kobe, Japan, have described the subretinal implantation of sheets of autologous iPScell derived RPE cells (Kamao et al, Stem Cell Reports 2014; 2:205-208). They have so far implanted the autologous RPEsheet in one patient with neovascular AMD, observed no immune rejection without immunosuppression, but have had some setbacks.

The first trial they initiated with the treatment was halted because of a debate induced by mutation detected in one of the autologous iPS cell lines. In addition, subsequent changes in legislation meant that clinical research in Japan can no longer be led by research facilities, only by hospitals.

A 35-year-old man received a subfoveal injection of 100ul of AAV in a clinical trial for choroideremia (Patient 3, MacLaren et al, 2014).

Immediately after surgery at day one his vision fell to 6/18 and a thin layer of subretinal fluid is evident (red arrows). By one month his vision has returned to 6/6 and the subretinal fluid has reabsorbed. Subretinal gene therapy can be applied safely and provides a more targeted approach than intravitreal injections

However, Dr Takahashi told EuroTimes in an interview that although the first patient in the trial has not had any noticeable changes in vision, she has been able to cease her antiVEGF injections. She added that the type of mutation they have seen has been proved not tumorigenetic in the animal test. She also noted that she and her team are now planning clinical research involving the use of stem cells derived from a iPS cell bank derived from human blood cells.

“We confirmed with the animal experiments that no immune rejection

We confirmed with the animal experiments that no immune rejection occurred if the HLA is matched Masayo Takahashi MD, PhD EUROTIMES | MAY 2016

occurred if the HLA is matched. For the HLA-matched patients we may not use immunosuppression. For HLA-mismatched patients, of course we will use it.”

Regarding the future use of gene therapy and stem cell transplantation, Dr MacLaren said it is likely that, as experience grows with the techniques and research continues to expand in the area, possibilities will emerge that stretch the imagination.

“There are lots of different approaches.

We may be able to switch on the repair process in the stem cells already present for the retina so we need to stay open-minded, but what we also need to do is more clinical trials,” he added.

Robert MacLaren: enquiries@eye.ox.ac.uk Masayo Takahashi: mretina@cdb.riken.jp Steven D Schwartz, Contact – Stephanie Wynbrandt, Jules Stein Eye Institute, UCLA: wynbrandt@jsei.ucla.edu

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SPECIAL FOCUS: RETINA

ZIKA VIRUS & THE EYE Research indicates high rate of vision-threatening fundus lesions in newborns with microcephaly. Cheryl Guttman Krader reports

F

indings from examination of a growing cohort of infants born in Brazil with microcephaly indicate that vision-threatening fundus lesions may be another complication of Zika virus vertical infection.

Speaking on behalf of the Zika Virus Study Group at the WOC 2016 in Guadalajara, Mexico, Mauricio Maia MD, PhD said that the first description of a potential association between macular lesions in a microcephalic infant and intrauterine Zika virus infection appeared as a case report published online in The Lancet on 8 January, 2016.

An article published in the Arquivo Brasileiros de Oftalmologia in February 2016 reported the finding of ocular abnormalities in 17 (85 per cent) of 20 eyes of 10 infants with microcephaly born to mothers with a clinical diagnosis of Zika virus infection. In an online article in JAMA Ophthalmology on 9 February, 2016, the group’s series had grown to 29 infants, of which 10 (34.5 per cent) had ocular lesions and seven had bilateral involvement.

Dr Maia reported at the conference on 141 babies born with microcephaly to mothers thought to have Zika virus infection during pregnancy. In that cohort, about 30 per cent had fundus alterations.

The lesions, which differed from any previously described in relationship to other congenital infections, could be categorised into four major types: atrophic chorioretinal changes at the macula; atrophic chorioretinal changes outside the macula; atrophic optic nerve changes with increased excavation of the nerve and optic disc hypoplasia without intraocular pressure elevation; and mottling of the macula similar to retinal pigment epithelium defects.

“Advances in serologic studies for diagnosing Zika virus infection and prospective case-controlled studies of pregnant women with documented Zika infection are necessary to confirm an association between intrauterine exposure to the Zika virus and both congenital microcephaly and fundus abnormalities.

However, there is good evidence to support a causal relationship,” said Dr Maia, Assistant Professor of Ophthalmology, Federal University of São Paulo, Brazil.

“The finding of ocular lesions in these infants is an important issue for public health systems worldwide and the ophthalmology

The finding of ocular lesions in these infants is an important issue for public health systems...

Mauricio Maia MD, PhD EUROTIMES | MAY 2016

community, considering that Zika virus infection has potential to be a worldwide pandemic. Infants with microcephaly presumed related to maternal Zika virus infection should undergo an ophthalmological examination, and children with fundus lesions should receive early visual stimulation to minimise deleterious consequences and provide the best possible vision in the future,” he added.

HALLMARK SIGNS Dr Maia added that only 20 per cent to 30 per cent of people infected with the Zika virus are symptomatic with characteristic findings that include cutaneous rash, fever, and arthralgia lasting for about five days.

“Considering that we have been evaluating newborns of symptomatic mothers, there may be even more children with microcephaly and fundus lesions related to Zika virus infection,” Dr Maia told EuroTimes.

Retcam from infant shows an optic disc hypoplasia with double-ring sign associated with one sharply demarcated chorioretinal atrophy on the macula

For all cases, maternal Zika virus infection during pregnancy was established either clinically based on a history of the hallmark signs of infection or by real-time polymerase chain reaction (rt-PCR) performed during the acute phase of infection (which is the only method for diagnosing Zika virus infection available in Brazil).

“None of the women had evidence of conjunctivitis during their acute infection, and that seems to refute the idea that conjunctivitis with rash, fever, and arthralgia can help differentiate Zika virus infection from dengue fever and Chikungunya virus infection,” Dr Maia noted.

In all infants, other infectious or non-infectious risk factors for microcephaly were ruled out by serology or history.

SPECIAL FOCUS: RETINA

9

WHAT LIES AHEAD?

In addition to Dr Maia, coordinators of the Zika Virus Study Group include Rubens Belfort Jr MD, PhD; Paul Freitas MD; Liana Ventura MD; and Camila Ventura MD Mauricio Maia: retina@femanet.com.br

A - Fundus photograph of the right eye of a two-month-old female infant, showing granular, pigmentary mottling in the macula; B - Left eye of the same patient shows chorioretinal lobulated atrophic lesion and slight pigmentary mottling

Courtesy of Mauricio Maia MD, PhD

Further study is ongoing, including an attempt to correlate the ocular findings in the newborns with gestational age at the time of maternal infection.

“We believe that the choroidal atrophic changes at the macula are associated with maternal infection during the first trimester of pregnancy. Currently, we are unsure about whether the optic nerve abnormalities are caused by the virus or related instead to the microcephaly,” Dr Maia said.

In addition, pregnant women with documented Zika virus infection are being followed prospectively, and blood samples are being drawn and frozen from mothers with undocumented infection who give birth to children with microcephaly, anticipating the future availability of a specific serologic test for Zika virus.

Further research is also necessary to determine whether ophthalmic screening should be performed in infants born without microcephaly, but whose mothers were known or suspected to have had Zika virus infection during pregnancy.

Importantly, efforts are needed to reduce the risk of Zika virus infection. “We wait for the development of a vaccine that can prevent Zika virus infection. In the meantime, eradication of the mosquito vector is of critical importance, and pregnant women should be advised to avoid endemic areas, or use mosquito repellents if that is not possible,” Dr Maia said.

"The first report in the literature on the possible relationship between congenital Zika virus infection and retinal abnormalities was published for the group in The Lancet journal in January 2016," he added.

A - Fundus photograph of the right eye of a one-month-old infant, revealing an enlarged cup/disc ratio and macular pigmentary mottling; B - In the left eye there is a roundish macular chorioretinal atrophic lesion with a hyperpigmented halo and perilesional pigmentary mottling

Information to follow at a.org www.euretin

EURETINA is delighted to announce the

5th Retina Race at the 16th EURETINA Congress in Copenhagen

Date: Saturday 10 September, 6.30am Registration Fee: Ð30 in aid of Orbis EUROTIMES | MAY 2016

SPECIAL FOCUS: RETINA

PROMISING SYSTEM New device for self-testing visual acuity shows potential.

Dermot McGrath reports

A

self-testing system developed by researchers in the UK provides an effective means of testing low contrast near visual acuity in ophthalmic patients with a high degree of reliability, according to a study presented at the 15th EURETINA Congress in Nice, France.

“Our study showed an excellent level of repeatability with the system, which is of great clinical value as patient management decisions are frequently based upon change in vision. Moreover, the patients were able to collect data with no operator interference so the potential for self-testing has been clearly demonstrated,” said Humza Tahir PhD, adding that future studies of the device will include contrast sensitivity and colour vision testing using the same principles.

The project was initiated by principal investigator Prof Tariq Aslam, Senior Clinical Lecturer at the University of Manchester, UK, as one part in a series of devices being developed to help assess visual function in both children and adults.

The adult visual testing system team was led by Dr Tahir and co-workers at the University of Manchester and the Manchester Royal Eye Hospital, and is known as MAVERIC (Mobile Assessment of Vision by intERactIve Computer), which consists of an Apple iPad 3 with retina display running purpose-built software housed in a bespoke physical booth. The system has a variable viewing distance of 25cm to 50cm, a natural viewing angle, and it protects from reflections and glare.

“There is a real need for such a system as current devices have limited utility when used by patients on their own. Many eye diseases require ongoing assessments and the burden on patients and hospitals could be reduced through home vision monitoring,” said Dr Tahir.

GAMIFICATION The rationale for using a booth system to encase the table computer is to avoid problems associated with the significant changes in luminance and contrast that occur when the tablet is used at an angle

MAVERIC booth containing tablet computer

with a light source above, which is a typical scenario when reading, said Dr Tahir.

The MAVERIC system uses a letter acuity test based on “gamification” principles, which Dr Tahir explained is the concept of applying game mechanics and game design techniques to engage and motivate people to achieve their goals.

There were 20 available testing sizes used based on a 40cm testing distance and the current iPad screen resolution. The testing range was -0.08 (6/5 Snellen) to 1.2 logMAR (6/100).

To validate the system, 81 patients were recruited from clinics at the Manchester Royal Eye Hospital. Exclusion criteria were the physical possibility of performing a test that required use of a functioning hand and visual acuity of at least 1.22 logMAR (6/100) in one eye.

The study eye was given the best possible distance correction, with a near add of +2.5D in all presbyopic patients to correct for the near vision test with the fellow eye occluded.

Masked to the MAVERIC vision result, the examiner then tested near visual acuity using a near Landolt C chart (Precision Vision) according to standard protocols.

Approximately 15-20 minutes after the original MAVERIC test, a second MAVERIC test was initiated. Out of the 81 patients who agreed to the study, 78 (96 per cent) were able to complete the MAVERIC test without assistance, said Dr Tahir. In terms of pathology distribution, 12 patients had no ocular disease, five

There is a real need for such a system as current devices have limited utility when used by patients on their own Humza Tahir PhD EUROTIMES | MAY 2016

Courtesy of University of Manchester

10

Screenshot of MAVERIC testing procedure showing mouse graphic

had macular degeneration, 12 had other macular diseases, 16 had diabetic eye disease, eight had glaucoma, eight cataract, and 17 with miscellaneous pathologies such as retinal vascular diseases, naevi and vitreous detachment.

The results showed very good repeatability of the MAVERIC test as measured in intraclass correlation coefficient (ICC) units, said Dr Tahir. As a basis for comparison, repeatability with experienced optometrists using the gold standard acuity charts in patients with macular degeneration has been shown to be 0.96 for logMAR visual acuity and 0.75 for reading acuity. With the MAVERIC acuity test, the ICC was 0.96 for single measures.

“The study demonstrated the potential viability of the MAVERIC self-testing system as a means to test low contrast near visual acuity in ophthalmic patients with a high degree of reliability, and thus a potential method of both initial assessment and monitoring of near visual acuity in such patients,” concluded Dr Tahir.

Humza Tahir: humza.tahir@manchester.ac.uk

SPECIAL FOCUS: RETINA

GEOGRAPHIC ATROPHY Lampalizumab phase 3 programme can help determine efficacy.

Cheryl Guttman Krader reports

T

wo phase 3 clinical trials should help determine the efficacy of lampalizumab (Roche), a new category of drug being evaluated for the treatment of geographic atrophy, reported Arshad Khanani MD, MA at the WOC 2016 in Guadalajara, Mexico.

Lampalizumab, an antigen-binding fragment of a humanised monoclonal antibody directed against complement factor D, acts by blocking initiation and amplification of the alternative complement pathway. It is being evaluated in two phase 3 studies enrolling more than 1,872 patients at approximately 275 sites worldwide.

Two identically designed pivotal interventional trials, Chroma and Spectri, each plan to randomise 936 patients to intravitreal injection with lampalizumab or sham every four or every six weeks. Patients will have bilateral geographic atrophy without choroidal neovascularisation (CNV). Each treatment group will include complement factor I biomarker-positive (CFI+) and CFIpatients. Mean change in geographic atrophy lesion area from baseline at one year, measured Arshad Khanani by fundus autofluorescence, is the primary efficacy endpoint.

“At month 18 in the phase 2 Mahalo study, lampalizumab reduced geographic atrophy area progression versus sham by 20 per cent in the overall population, but by 44 per cent in CFI+ patients. The hypothesis that CFI is a biomarker for response is being confirmed in the current phase 3 programme,” said Dr Khanani, Clinical Assistant Professor, University of Nevada, Reno, USA.

VISUAL FUNCTION The studies are also designed to assess visual function using parameters that may be better than best corrected visual acuity (BCVA) for demonstrating the functional impact of geographic atrophy. They include low luminance VA, reading speed, the NEI Visual Function Questionnaire-25, and the Functional Reading Independence index (FRI, available online at: www.mapi-trust.org).

“We know that patients with geographic atrophy present with complaints about vision, but their BCVA can still be good.

The lampalizumab clinical trials are assessing visual function outcome measures for which changes may be identified before there is deterioration of BCVA. A letter supporting the FRI was recently published by the European Medicines Agency,” he told EuroTimes.

In addition to the phase 3 trials, two additional trials, Proxima A and Proxima B, are ongoing observational studies designed to contribute to the understanding of the anatomic and visual function changes in a broad population of patients with geographic atrophy. “It is hoped that the Proxima studies will significantly advance our knowledge of geographic atrophy natural history,” Dr Khanani said.

Arshad Khanani: arshad.khanani@gmail.com EUROTIMES | MAY 2016

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SPECIAL FOCUS: RETINA

BEYOND IMAGINATION In the first of a new series of articles sponsored by ISOPT Clinical, Baruch D Kuppermann MD, PhD looks at the revolution in retinal pharmacology

A

decade ago a revolution in the way we treat and therefore conceive retinal disease took place: the introduction of anti-VEGF therapy with the concept of multiple intravitreal injections has completely transformed wet age-related macular degeneration (AMD) treatment, with a major contribution to our understanding of the disease and its ramifications.

Following years of ablative laser therapy and drug-augmented photodynamic therapy, the opportunity emerged to actually treat the disease’s “main driving force”, i.e angiogenesis.

The wave of interest from the pharmaceutical industry resulted in class “A” data (derived of randomised double blind controlled clinical trials with sophisticated statistical analyses) to guide clinicians in their quest for the most appropriate treatment for their patients. Numerous studies such as MARINA and ANCHOR, followed by CATT, IVAN and many others have produced highlevel data and a basis for more advanced research.

Moreover, it became apparent that not only angiogenesis, but also macular oedema was amenable to anti-VEGF therapy. This opened the gate for other diseases such as diabetic macular oedema (DME) and macular oedema due to retinal vascular occlusion (RVO) as indications for anti-VEGF therapy.

Additional topics took on a life of their own – for example, research for better anti-VEGF delivery options, and though there are no new extended release anti-VEGF drug delivery technologies approved yet, extensive research has been carried out and the field is growing with new companies/technologies, which eventually will lead to better modes of therapy allowing lower frequency of injections. Another example of expanded research are the studies comparing the efficacy of the various anti-VEGF therapies.

These studies included thousands of patients, and have expanded our knowledge of the profile of the main anti-VEGF drugs: Avastin, Lucentis and Eylea. It has allowed the medical community to assess the comparative efficacy of those agents which have shown reasonable comparability for wet AMD, while observing the possible superiority of Eylea in DME in patients with worse baseline vision as shown in the DRCRnet Protocol T firstyear results.

APPROPRIATE DRUGS Overall, this helps practitioners choose the most appropriate drugs for their patients, adapted to their own local health systems. The advancement in therapeutic options have moved the field forward so much that wet AMD efficacy assessment has moved from rate of vision loss to rate of vision gained and vision maintenance, one decade following the inception of anti-VEGF therapy in the eye.

Long-term follow-up of patients treated for wet AMD with anti-VEGF therapy discloses yet additional lines of progressive pathology in EUROTIMES | MAY 2016

The progressive use of anti-VEGF intraocular injections also revived the possible role of corticosteroids for macular oedema...

Baruch D Kuppermann MD, PhD

the forms of atrophic macular changes that are either part of baseline choroidal neovascularisation (CNV) pathology, or could be a specific response to long-term use of anti-VEGF agents.

The progressive use of anti-VEGF intraocular injections also revived the possible role of corticosteroids for macular oedema, though here new technologies have been developed and approved utilising long-acting delivery modes, such as those seen in the dexamethasone implant Ozurdex and the fluocinolone implant Iluvien. Improving steroid performance via prolonged delivery modes had been a goal of long-standing research for more than two decades. The first long-term delivery steroid product, Retisert, for the treatment of posterior non-infectious uveitis, clearly showed the potential of long-term use of intraocular steroid with three years of drug delivery using an implant.

However, the adverse event burden of cataract and severe glaucoma leading to intraocular pressure-lowering surgery in approximately 40 per cent of patients did prevent a successful commercial experience. Thus, newer products, first Ozurdex and now Iluvien, with safer steroid concentrations, reveal a more desirable adverse event profile and have been shown to be effective for indications such as DME, RVO and potentially as an adjunct to anti-VEGF therapy. These successful results point to the important role of delivery methodologies for future utilisation of retinal pharmaceuticals.

DELIVERY TECHNOLOGIES The future therefore continues to evolve, with new products under research carrying promising mechanisms of action on one hand and better delivery technologies on the other. It seems that the principle of gaining high local drug concentration avoiding systemic adverse events via intraocular injections is capable of opening new horizons unique for retinal drugs, compared with other extraocular target organs. Leading technologies point to combining anti-VEGF with other anti-angiogenic agents, via one or two lead molecules packed together.

Extensive research on small anti-angiogenic molecules is reaching towards another long-standing goal of eye drops effective for the treatment of retinal diseases, however so far results have been disappointing. Additionally, new molecules are designed to treat other indications such as anti-complement H, 3, and 5 for dry AMD with preliminary results promising.

New delivery technologies are also being explored such as electroporation, iontophoresis, suprachoroidal injections, implantable refillable reservoirs, and specifically designed materials for extended release of proteins, with the goal of decreasing the burden from patients and doctors treating retinal disease.

It is the hope of all of us that the future will bring modes of therapy that are beyond our current imagination, though the first steps are definitely here right now.

Prof Baruch Kuppermann is the head of the retina section at ISOPT Clinical Baruch D Kuppermann: bdkupper@uci.edu

8–11 September 2016

COPENHAGEN 16th EURETINA Congress

Bella Center, Denmark

10 Main Sessions 20 International Society Symposia 30 Free Paper Sessions 45 Instructional Courses 4 Surgical Skills Courses

EURETINA Lecture Keynote Speaker: José Cunha-Vaz PORTUGAL The Blood-Retinal Barrier in Retinal Disease Management

Inaugural Richard Lecture Keynote Speaker: Gisbert Richard GERMANY Restoration of Sight: Prospects and Limitations of Artificial Vision and Stem Cell Therapy

Kreissig Lecture Keynote Speaker: Emily Chew USA Nutrition, Genes and Age-Related Macular Degeneration: What Have We Learned from the Trials?

/EURETINA

@EURETINA

EURETINA

www.euretina.org

16

C O P E N H A G E N

th

EURETINA CONGRESS

8–11 September 2016

Thursday 8 September

Friday 9 September

Saturday 10 September

Lunchtime Symposium

Lunchtime Symposia

Lunchtime Symposia

13.00 – 14.00

13.00 – 14.00

13.00 – 14.00

Boxed Lunch Included

Allergan Satellite Meeting Sponsored by

Friday 9 September

Morning Symposia 10.00 – 11.00 Bayer Symposium I Sponsored by

Boxed Lunch Included

Geographic Atrophy: The Patient Perspective Sponsored by

Optos Satellite Meeting

Nidek Satellite Meeting

Sponsored by

13.00 – 14.00 Bayer Symposium II Sponsored by

Novartis Satellite Meeting Sponsored by

Heidelberg Engineering Satellite Meeting Sponsored by

Topcon Satellite Meeting Sponsored by

Sponsored by

DORC Satellite Meeting Sponsored by

Sponsored by

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Boxed Lunch Included

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Alimera Satellite Meeting

Lunchtime Symposia

Novartis Satellite Meeting

Bayer Symposium III

ZEISS Satellite Symposium

Friday 9 September

Boxed Lunch Included

Second Sight Medical Products Satellite Meeting Sponsored by

Saturday 10 September

Morning Symposia 10.00 – 11.00 Alcon Satellite Meeting Sponsored by

Allergan Satellite Meeting Sponsored by

Santen Satellite Meeting Sponsored by

Spark Therapeutics Satellite Meeting Sponsored by

Théa Satellite Meeting Sponsored by

Topcon Satellite Meeting Sponsored by

Bausch + Lomb Satellite Meeting Sponsored by

CATARACT & REFRACTIVE

VISION QUALITY METRICS Aberrometry-based estimations of through-focus acuity following presbyopic treatments accord well with measured acuity. Roibeard O’hEineachain reports

N

ew aberrometry-based vision quality metrics can provide an objective measure of a patient’s throughfocus acuity, said Raymond A Applegate OD, PhD, University of Houston College of Optometry, Houston Texas, USA. “What is particularly powerful about using aberrometry-based vision quality metrics is that they are much more sensitive to subtle changes in vision than an acuity chart,” Dr Applegate told the XXXIII Congress of the ECSRS in Barcelona, Spain.

Dr Applegate noted that interactions between different optical aberrations can improve or decrease visual performance. The classic example is defocus and spherical aberration, which degrade retinal image quality, but in the correct combination provide improved image quality (despite the increase in the total amount of aberrations) over the adverse effect of each aberration independently. (see Figure 1) Therefore, wavefront error (WFE) measured by a typical wavefront aberrometer expressed as RMS WFE is not a good metric for predicting visual performance as measured by acuity, he said. On the other hand, by calculating the appropriate visual image quality metrics from the measured WFE, it is possible to predict acuity in through-focus experiments evaluating various presbyopic corrections.

Dr Applegate analysed WFE data from a throughfocus experiment conducted by a research team at Aston University in the UK, headed by Prof James Wolffsohn. The goal of Dr Applegate’s analysis was to determine if he could predict the acuity actually measured by the research team, using the measured WFE in patients implanted with one of three presbyopic intraocular lenses (IOLs) – the Lenstec Tetraflex, an accommodating IOL, the Rayner M-flex concentric multizonal bifocal IOL, and the Oculentis Mplus, a standard multifocal.

In the single-blind study, Dr Applegate was only given wavefront data obtained from the patients as they looked through a wavefront sensor at an eye chart placed at four metres distance, while defocus lenses were placed in front of their eye.

Only after Dr Applegate made his acuity predictions did the Aston group provide actual acuity measurements made at the time of WFE measurement.

DEFOCUS CURVE As can be seen in Figure 2, through-focus variation in measured visual acuity is mimicked by the predicted visual acuity from WFE measurement, with the predicted acuity being slightly better than the measured acuity. Dr Applegate noted that this small overprediction of acuity can be easily corrected given the results of

... aberrometry-based vision quality metrics... are much more sensitive to subtle changes in vision than an acuity chart Raymond A Applegate OD, PhD

Figure 1: A small amount of spherical error (0.2 micrometres of RMS WFE) decreases retinal image quality as does a small amount of spherical aberration (0.15 micrometres of RMS wavefront error).

However, when added together to produce 0.25 micrometres of RMS WFE, the image is improved

Figure 2: Measured (purple squares) and predicted visual acuity as a function of defocus lens power for six eyes implanted with a Tetraflex IOL (This figure originally appeared in the doctoral thesis of Sandeep Dhallu entitled ‘Evaluating techniques to improve visual performance with and assessment of premium intraocular lenses’, Aston University, January 2015, page 217, and was modified here for the purposes of this reporting by Dr Applegate)

the experiment, in the same way as cataract surgeons use actual surgical results to improve their outcomes.

For comparison, the red line in Figure 2 is the anticipated throughfocus acuity of subjects having a state-of-the-art monofocal IOL implanted and wearing glasses with a 2.5D add in a transition design.

In eyes with the M-flex and Mplus IOLs, the through-focus curves were very similar (to Figure 2), although the vision quality metrics missed a slight improvement in acuity, intended and achieved by the IOL design, in through-focus acuity, which was detected by subjective measurement of acuity.

“It is very hard for Zernike polynomials to represent the abrupt changes in WFE in these two designs, but I predict that when we resolve this issue the prediction will be even better,” Dr Applegate said.

Raymond A Applegate: raappleg@central.uh.edu EUROTIMES | MAY 2016

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CATARACT & REFRACTIVE

REDUCING INFLAMMATION

NSAIDs, new steroid delivery methods, may improve anterior segment outcomes. Howard Larkin reports

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reater use of topical non-steroidal anti-inflammatory drugs (NSAIDs), as well as sustained release and injected corticosteroids, may reduce inflammation following anterior segment surgery more than do the topical steroids now most commonly used, presenters told the Journal of Cataract & Refractive Surgery Symposium at the XXXIII Congress of the ESCRS in Barcelona, Spain.

While nearly twice as many European surgeons reported using topical steroids than NSAIDs after cataract surgery in 2014, published studies show that NSAIDs are more effective in preventing post-op flare, said Rudy MMA Nuijts MD, PhD, of the University Eye Clinic Maastricht, The Netherlands. Topical NSAIDs alone or combined with topical steroids also better prevent cystoid macular oedema (CME) than do steroids alone, and NSAIDs may generate better visual acuity (VA) outcomes among diabetic patients, he added.

Studies also show that intracameral and sustained release corticosteroids may reduce inflammation-related complications including CME, iritis, flare cells and corneal oedema better than conventional topical steroids after many types of anterior segment surgery, said Eric D Donnenfeld MD, of New York University, USA. Intracameral steroid injections may be particularly useful after complex procedures such as corneal transplants, and phacoemulsification with vitrectomy, he noted.

Emerging delivery methods and better understanding of the pathophysiology of inflammation may make it possible to avoid sight-threatening inflammatory complications altogether, Dr Donnenfeld said. “Our goal should be to eliminate inflammation rather than to treat it. This can be done with aggressive corticosteroid therapy pre-op and intracamerally to not only suppress inflammation but prevent it from occurring at all.�

NSAIDS UNDERUSED? In 2014, 87 per cent of 490 surgeons surveyed by the European Observatory of Cataract Surgery reported prescribing corticosteroid drops after surgery to combat inflammation, while EUROTIMES | MAY 2016

only 38 per cent prescribed NSAIDs, Dr Nuijts said. Yet several studies have shown that NSAIDs are more effective.

For example, a multicentre double-masked randomised controlled trial found that adding nepafenac 0.1 per cent two days before surgery and added to dexamethasone 0.1 per cent for three weeks after surgery reduced anterior chamber (AC) flare cells, as measured by laser photometry one day after surgery compared with dexamethasone alone (Zaczek. J Cataract Refract Surg 2014; 40:1498).

A systematic review and meta-analysis found NSAIDs more effective than steroids in reducing post-op flare at one week, and preventing CME at one month after surgery (Kessel.

Ophthalmology. 2014 Oct;121(10):1915).

Another meta-analysis found adding NSAIDs to topical corticosteroids reduced the odds of developing CME, and improved corrected distance visual acuity at three months more in diabetic patients than steroids alone.

However, the quality of the evidence is low to moderate, and better studies are needed, Dr Nuijts pointed out. To develop better evidence-based recommendations for preventing CME after cataract surgery, the ESCRS is currently sponsoring the PREMED study. It compares topical bromfenac alone with topical dexamethasone alone, and with a combination of the two in 823 non-diabetic patients. The topical NSAID and corticosteroid combination is also being tested alone, and combined with either a 40mg subconjunctival injection of triamcinolone acetonide, a 1.25mg intravitreal injection of bevacizumab, or both injected agents in 185 diabetic patients.

The quality of the evidence is low to moderate, and better studies are needed Rudy MMA Nuijts MD, PhD

CATARACT & REFRACTIVE

17

Early PREMED data suggest that one of the four diabetic treatments does a much better job of preventing central macular subfield swelling, but which one and whether it is significant is uncertain as the data are still masked, Dr Nuijts said. One question the study may help answer is whether NSAIDs plus steroids are more effective than NSAIDs alone.

IMPROVED DELIVERY

Courtesy of Rudy MMA Nuijts MD, PhD

Injecting anti-inflammatory drugs has several advantages over topical drops, Dr Donnenfeld said. Intraocular delivery of corticosteroids places medication at the site of inflammation and should have higher efficacy. Intraoperative delivery also avoids non-compliance, potentially reducing dosing error risk associated with eye drops in the largely elderly cataract population.

In one study, a single intracameral injection of triamcinolone acetonide cleared transplanted corneas that remained cloudy after maximum topical steroid treatment (Maris et al, Cornea 2008).

Injecting Triesence (Alcon), 0.1ml of preservative-free triamcinolone, into the AC also reduced post-op inflammation in cataract surgeries with vitrectomy (Bar-Sela. J Cat Refractiv Surg 2014).

“It improves outcomes quite dramatically, with many patients coming in the next day with 20/20 VA,” Dr Donnenfeld said.

A range of anti-inflammatory drugs including extended release inserts are already approved for treating retinal disease, and Dr Donnenfeld expects they will soon be routine for cataract and corneal surgery as well. “We are already placing steroids in the posterior segment, why shouldn’t we place them in the anterior segment as well?”

Extended release eye drops, subconjunctival delivery, punctal plugs and other external devices that will keep drug levels more stable with less bother for patients are also in the pipeline, Dr Donnenfeld said.

“I predict that over the next five years topical drugs will change greatly and will cease to exist as we know them today,” he added.

Rudy MMA Nuijts: rudy.nuijts@mumc.nl Eric Donnenfeld: ericdonnenfeld@gmail.com

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ESCRS

Practice Management

& Development 11–12 September 2016 Copenhagen, Denmark

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Winner of a €1,000 bursary will be announced during the XXXIV Congress of the ESCRS in Copenhagen, Denmark UTILISE BUSINESS

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EUROTIMES | MAY 2016

CATARACT & REFRACTIVE

THE HUMAN FACTOR Surgical skills to optimise capsulotomy outcomes.

W

hile the automated technology of the femtosecond laser has simplified and improved the capsulotomy phase of cataract surgery, the surgeon’s skills remain key to optimal outcomes, according to H Burkhard Dick MD, PhD, Chairman and Head of the University Eye Clinic, Bochum, Germany.

“We started to perform femtosecond laser capsulotomy in late 2011, in part because we considered this technology to be able to provide us with a more accurate approach, resulting in more reproducible sizings, shapings and centrations of the anterior capsule. The laser changes this essential step in cataract surgery from tearing (‘-rhexis’) to cutting (‘-tomy’), which is more appropriate for the concept of any kind of surgery,” he told EuroTimes.

Dr Dick was an early adopter of femtosecond laser-assisted cataract surgery (FLACS). He now does 35 per cent of his cases using this approach, using little or no phaco. While acknowledging that there are still questions remaining about the procedure as compared with conventional surgery, he maintains that careful technique will reduce some of the issues reported with the capsulotomy phase of the procedure.

GREATLY IMPROVED He notes that overall, the quality of femtosecond laser capsulotomies has greatly improved in the last couple of years. The rate of incomplete capsulotomies has gone down from approximately four per cent to less than one per cent. A study by Dr Neil Friedman and colleagues demonstrated that femtosecond laser capsulotomy improved precision in sizing the capsulotomy by 12 times, and improved accuracy in shaping the capsulotomy by a factor of approximately three compared with the manual capsulorhexis technique (JCRS 2011; 37:1189–1198).

He also stressed that the surgeon’s skill still plays a key role. When he first started doing FLACS, he saw four capsular tears in his first 1,273 cases, which included patients with pseudoexfoliation and intumescent cataracts. However, with increasing experience he has been able to reduce the rate of capsule tears to near zero.

“There is, as in any procedure, a learning curve. The incidence of anterior tags, incomplete capsulotomy and, during the manual part, capsular tear, have been shown EUROTIMES | MAY 2016

Sean Henahan reports

Courtesy of H Burkhard Dick MD, PhD

18

An intraoperative photo of Dr Dick using the LENSAR Laser System

to greatly decrease with experience. Surgical skill is also required when performing the dimple-down technique, a gentle pulling of the disc centrally or paracentrally to confirm that there is a continuous 360-degree cut with a free disk that we strongly recommend (JCRS 2013; 39:1796-1797).

Therefore, the operation's success is still to a greater part dependent on how good the doctor is,” added Dr Dick.

He emphasised that many factors can influence the outcomes of FLACS. Particularly during the laser application, the set-up of the procedure (the systems differ regarding their energy settings, numerical aperture and spacings) plays a role.

“The cooperation of the patient is probably the most important thing. He or she has to lie perfectly still for these few seconds. Movements of the head or the body, coughing and other commotions will negatively affect the quality of the capsulotomy. An optimal positioning of the patient’s head and an adequate sedation – in some patients – are part of the surgeon’s responsibility and, if you will, of his skill in managing not only the procedure but also his patients.”

SPECIAL FEATURES Special features of the patient's anatomy must also be taken in account. Deep-set eyes or chemosis, for instance, can result in pseudosuction: the interface is not really connected to the globe. This will move on the conjunctiva and a proper capsulotomy may become impossible.

“These situations all prove that the experience and skill of the doctor are – as they have been since the beginnings of medicine – crucial in determining the patient’s well-being, even when assisted by the most sophisticated technology,” he said.

Recent reports have suggested that the capsulotomy edge created with the laser is not as smooth as that seen with manual surgery, with the suggestion that this could account for an increase in the rate of anterior capsule tears. Dr Dick and colleagues recently reported a study looking at this (Schultz T et al., EJO,2015; 25: 112-118). While the capsular edges of continuous curvilinear capsulorhexis were microscopically much smoother than those created with the laser, he does not think it makes a difference in clinical terms.

“Does it make a clinical difference? Not at all, other than supporting the use of the dimple-down technique to detach any tags that might be present. We will certainly see technical enhancements as the laser systems will continually improve, but the microscopic shape of the edges, due to its clinical irrelevance, is not among the most pressing concerns.”

Dr Dick uses the CATALYS platform (AMO) when performing FLACS. He commented that the feature of optical coherence tomography-guidance offered by the system provided a revolutionary new way of treatment by giving the surgeon real-time visualisation.

H Burkhard Dick: burkhard.dick@kk-bochum.de

CATARACT & REFRACTIVE

BENEFIT OF SIMULATORS New device could assist in treatment of presbyopia.

Roibeard O’hEineachain reports

A

new binocular adaptive optics simulator, AOneye (Voptica), may allow for a more customised approach to the surgical treatment of presbyopia, providing patients with a preview of their postoperative vision in terms of both visual acuity and visual quality, said Pablo Artal PhD, University of Murcia, Spain, who is co-founder and chairman of the Voptica company.

“In my opinion, customisation is the key in the binocular correction of presbyopia. If you provide patients with the optical values they require, they will be happy. And we can do this with adaptive optics customisation,” Dr Artal told the XXXIII Congress of the ESCRS in Barcelona, Spain.

He noted that the new instrument which he and his associates have developed consists of a wavefront sensor and a liquid crystal device that projects any proposed optical profile into the patient’s eye. It can therefore provide patients with a preview of what their postoperative vision will be following any proposed treatment.

Furthermore, using the system binocularly allows presbyopic patients to sample the various presbyopic treatments that are based on binocular retinal disparity. Those treatments include conventional monovision, where one eye is targeted for emmetropia and the other for up to -1.5D of myopia, and more sophisticated techniques, such as those employing asphericity.

When tested with conventional defocus curves, all of the treatments appear to provide similar results. However, patients are sometimes unhappy despite achieving a large range of good visual acuity. Sometimes, two patients receiving the same treatment and achieving the same results in terms of throughfocus visual acuity will express markedly different levels of satisfaction, Dr Artal said. “Depth-of-focus visual acuity is not enough. We also need to consider contrast sensitivity, binocular summation, stereoacuity, and neuroadaptation,” he added.

BEST VISUAL ACUITY Dr Artal noted that studies they have conducted with adaptive optics simulations of conventional monovision closely mirrors clinical experience, showing that binocular summation will be maintained so long as the focal disparity between the two eyes is less than 1.5D. Beyond that, there is inhibition, with the result that binocular acuity is worse than monocular acuity.

Pablo Artal: pablo@um.es

If you provide patients with the optical values they require, they will be happy. And we can do this with adaptive optics customisation

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19

CORNEA

HEALING CASCADES Complications rare in corneal crosslinking.

Dermot McGrath reports

C

orneal crosslinking (CXL) offers an effective means of halting the progression of keratoconus in the majority of patients, with an excellent safety profile and a low rate of complications, Theo Seiler PhD told delegates attending the 6th EuCornea Congress in Barcelona, Spain.

“Five to ten year reports in the scientific literature demonstrate that CXL using 3mW/cm2 has a complication rate ranging from zero to 13 per cent and a failure rate of zero to three per cent.

Complications such as scars and infiltrates are rare, and we should remember that the cornea is at its most vulnerable during the re-epithelialisation period of three to five days postoperatively. It should also be borne in mind that CXL induces structural changes in the cornea that may go on for many years after the treatment,” Prof Seiler said.

A complication in a surgical procedure in ophthalmology, according to the FDA definition, is defined as a loss of two or more Snellen lines of visual acuity, said Prof Seiler.

“If we look at one of the early studies we conducted in 2005 in over 100 eyes, we found a complication rate at one year postoperatively of around three per cent. Further analysis of the data showed two main risk factors to have a complication: age older than 35 and preoperative best corrected visual acuity (BCVA) greater than 20/25,” he said.

Ten-year evolution of corneal topography after epi-off crosslinking. The surgery was performed in December 2005

RECENT EVIDENCE Looking at more recent evidence in the scientific literature, Prof Seiler said that PubMed now lists around 155 publications relating to complications after CXL. Perhaps the highest complication rate of 13.7 per cent comes from a study by Hashemi et al (Ophthalmology 2013;120:1515-1520) in a group of 40 eyes of 32 patients with five years follow-up, while at the other end of the scale O’Brart et al reported a rate of zero per cent for more than 30 eyes with four to six years follow-up (Br J Ophthalmol 2013;97:433-437).

“We might well ask what is different in Iran compared to the UK to account for such a difference and it might well be that the postoperative or perioperative hygienic situation is different in each country,” he said.

Failure rates, defined as a progression of the keratoconus with a Kmax increase of more than 1.0D in a year, also need to be considered, said Prof Seiler. “We found in our own prospective study carried out in Zurich in 2007 a failure rate at one year postoperatively in more than 100 eyes of three per cent. The only risk factor identified was if the keratoconus was too far advanced at the time of treatment, there was a greater chance of progressions.”

Theo Seiler PhD

When we do CXL we are obviously initiating some healing cascades in the cornea that go on for years after the treatment

EUROTIMES | MAY 2016

Courtesy of Theo Seiler PhD

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Looking at other published studies, one study from France reported a failure rate at one year in more than 100 eyes of 2.8 per cent (Asri et al, JCRS, Vol. 37, Issue 12, 2137-2143), while O’Brart et al’s rate at four years postoperatively in more than 40 eyes was zero per cent. Patient selection perhaps accounted for the difference between the two outcomes, noted Prof Seiler.

INTRIGUING CASE He then discussed the intriguing case of a patient who first received CXL treatment in 2005 for his progressive keratoconus and who continued to experience a progressive flattening effect on the cornea over the follow-up period.

“In 2006, I was his hero because his eyesight was improving and he needed new glasses, and then in 2009 he was running around without glasses. He came back to the clinic last year and he was wearing glasses again: that flattening effect of crosslinking continued for more than 10 years,” he said.

Some other similar cases have also been reported in the literature, said Prof Seiler, who estimates that less than 10 per cent of patients will be affected in this way.

“This goes to show that CXL is not just switch-on and switch-off. When we do CXL we are obviously initiating some healing cascades in the cornea that go on for years after the treatment,” he said.

Other complications to watch for include stromal haze, sterile infiltrates and late-onset stromal scarring, all of which can usually be treated successfully without loss of vision, concluded Prof Seiler.

To contact Theo Seiler, email: claudia.kindler@iroc.ch

10–14 September

2016

XXXIV Congress of the ESCRS

Ridley Medal Lecture José Güell SPAIN 30 Years of ‘Iris Claw’ IOLs

Main Symposia 

Modern Corneal Transplantation



Cataract, AMD and Beyond



Astigmatism Management in Cataract Surgery



Femtosecond Laser Ophthalmic Surgery





www.escrs.org /ESCRS @ESCRSOfficial ESCRS

Management of the Ocular Surface before and after Refractive Surgery Better Outcomes in Glaucoma

C

XXXIV

Congress of the ESCRS

10–14 September 2016

O P E N H A G E N

Saturday 10 September

Saturday 10 September

Sunday 11 September

Lunchtime Symposia

Lunchtime Symposia

Lunchtime Symposia

13.00 – 14.00

13.00 – 14.00

13.00 – 14.00

Ziemer Satellite Meeting

Pentacam® AXL and Corvis® ST: New Approaches for Combining Tomography with Biometry and Biomechanics

Mini WELL Progressive EDOF IOL: One Year Later

Sponsored by

Alcon Satellite Meeting

Boxed Lunch Included

Sponsored by

STAAR Surgical Satellite Meeting

Boxed Lunch Included

Sponsored by

Rayner Satellite Meeting

Optovue Satellite Meeting

Sponsored by

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LENTIS Comfort & Comfort Toric – Pioneers in Modern EDOF Technology!

Acufocus Satellite Meeting

Sponsored by

Sponsored by

Abbott Satellite Meeting Supported by an unrestricted educational grant from

Boxed Lunch Included

Sponsored by

Sponsored by

Complex Cataract Cases, The Simple Truths Sponsored by

Bausch + Lomb Satellite Meeting Sponsored by

STAAR Surgical Satellite Meeting Sponsored by

C O Sunday 11 September

Sunday 11 September

Monday 12 September

Lunchtime Symposia

Lunchtime Symposia

Lunchtime Symposia

13.00 – 14.00

13.00 – 14.00

13.00 – 14.00

Heidelberg Engineering Satellite Meeting

Abbott Satellite Meeting

Alcon Satellite Meeting

Supported by an unrestricted educational grant from

Sponsored by

Boxed Lunch Included

Sponsored by

Nidek Satellite Meeting Sponsored by

Boxed Lunch Included

Santen Satellite Meeting ZEISS Satellite Symposium Sponsored by

Ellex ABiC Symposium Sponsored by

Sponsored by

Topcon Satellite Meeting Sponsored by

Sponsored by

A New Era of FineVision

by PhysIOL

Théa Satellite Meeting Sponsored by

New Technology for Improved Refractive Outcomes with the LENSTAR

Boxed Lunch Included

Sunday 11 September

Sponsored by

VSY Biotechnology Satellite Meeting Sponsored by

Evening Symposia 18.00

Alcon Satellite Meeting

Ellex Laser Vitreolysis Symposium Sponsored by

Sponsored by

Paediatric Cataract.

Challenges and Successes in Developing Countries Sponsored by

P E N H A G E N

CORNEA

THE LATEST DEVICES Treatment options improving for severe ocular surface disease.

TREATMENT OF CHOICE “The choice of KPro device to use will depend on a number of factors, such as whether the disease is unilateral or bilateral, if there is a complete loss of stem

Courtesy of Günther Grabner MD Loss of OOKP following resorption of dental lamina

OOKP after healing prior to the fitting of a cosmetic shield

Successful Boston type 1 KPro, four years post-surgery

cells and whether the ocular surface is wet or dry,” added Dr Grabner.

When there is a bilateral loss of stem cells but a wet surface, a Boston KPro is the treatment of choice, but if the eye is dry and the patient has usable, healthy teeth, then the modified OOKP is usually the best option, said Dr Grabner.

“The new types of Boston KPro are very acceptable for cases with a wet ocular surface, but very difficult to handle in the long-term in cases with insufficient wetting such as Stevens-Johnson syndrome and graft-versushost disease,” Dr Grabner added.

Furthermore, the progressive nature of the disease means that constant vigilance is necessary even after successful implantation of a KPro device, he warned.

“These are cases that have an innate progression in the disease course which also involves the surface of the eye. So while you might be doing quite well in the beginning with the Boston KPro and the eye looks quite nice with a wet surface, as time goes on the disease progress also catches up on the eye. We

then find ourselves with a patient who has been doing well for six months and comes back after a year or two with a disastrous outcome,” he said.

... we are definitely making steady progress in achieving better outcomes for patients with severe ocular disease...

Günther Grabner MD EUROTIMES | MAY 2016

OOKP at the time of fixation

Courtesy of Günther Grabner MD

A

dvances in biomaterials and design allied to enhanced surgical techniques are helping to deliver improved results with the latest generation of keratoprosthetic devices, according to Günther Grabner MD. “We still have a lot of work to do, but we are definitely making steady progress in achieving better outcomes for patients with severe ocular disease who are at high risk for donor graft failure,” Dr Grabner, Paracelsus Private Medical University, Salzburg, Austria, told EuroTimes.

Implantation of a keratoprosthetic device is generally undertaken when other surface reconstruction methods for visual rehabilitation have failed, or are deemed unfeasible, said Dr Grabner. Candidates would include those with severe bilateral chemical or thermal injury, and patients with ocular cicatricial pemphigoid or StevensJohnson syndrome.

While there are several designs of keratoprosthesis available, only two are widely used today: the Boston KPro type 1, developed at the Massachusetts Eye and Ear Hospital by Dr Claes Dohlman; and osteo-odonto-keratoprosthesis (OOKP), first developed by Strampelli in the 1960s and later improved upon

by Falcinelli.

“They are generally used as a last resort to avert corneal blindness and are indicated for a variety of diseases that have not responded to treatments such as stem cell or amniotic membrane transplantation and penetrating keratoplasty,” Dr Grabner said.

As surgeons have become more familiar with the various devices, so treatment protocols have evolved to help ensure the best chance of a favourable outcome for the patient.

Courtesy of Prof Giancarlo Falcinelli, Rome

Dermot McGrath reports

Courtesy of Prof Giancarlo Falcinelli, Rome

24

BETTER SOLUTIONS There is, however, still some hope for such patients in the form of the Boston type II device designed specifically for severe endstage ocular disease, said Dr Grabner.

“The type II device is much more difficult to implant surgically, but we will know more about the outcomes when the Boston group publishes its results in the near future,” he said.

While OOKP has successfully saved sight in patients with severe bilateral end-stage disease, the procedure is still only performed by a handful of surgeons worldwide, said Dr Grabner.

“The field of ocular surface reconstruction urgently requires better solutions to deal with surface and secondary issues such as dry ocular glaucoma. New innovations, such as the bioengineered cornea from LinCor Biosciences or the biocoated MIRO CORNEA (Miro GmbH), could give even better results combined with corneal crosslinking and newer topical drugs such as the Cacicol eye drops (Laboratoires Théa),” he concluded.

Günther Grabner: g.grabner@ophtha-consult.at

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7th EuCornea Congress

OPENHAGEN2016 9–10 September

Bella Center, Denmark

2 Days. 4 Symposia.

8 Focus Sessions.

4 Courses. 6 Free Paper Sessions.

EuCornea Medal Lecture Friday 9 September

16.00 – 17.00 (At the Opening Ceremony) Cultivated Stem-cells for Ocular Surface Disorders: Current Application and Future Perspectives

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Paolo Rama ITALY

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European Society of Cornea and Ocular Surface Disease Specialists

www.eucornea.org

Friday 9 September | 13.00 – 14.00 Théa Satellite Meeting Sponsored by

GLAUCOMA

AQUEOUS OUTFLOW Growing range of drainage devices providing new options in the treatment of glaucoma. Roibeard O’hEineachain reports

A

number of new drainage devices are now available which can provide significant reductions in intraocular pressure (IOP) with much less trauma to the eye than conventional filtration procedures, said Ingeborg Stalmans MD, PhD, Katholieke Universiteit Leuven, Belgium, at the XXXIII Congress of the ESCRS in Barcelona, Spain.

The new devices are designed to provide a channel for the outflow of aqueous to the subconjunctival space, Schlemm’s canal or the suprachoroidal space. The surgery involved includes ab interno techniques that can be performed in conjunction with cataract surgery and ab externo techniques that are meant to be simpler and safer than trabeculectomy, Dr Stalmans said.

Courtesy of Ingeborg Stalmans MD, PhD

26

SUBCONJUNCTIVAL DRAINAGE The Ex-PRESS shunt is an ab externo device that directs aqueous from the anterior chamber into a subconjunctival bleb. The stainless steel device consists of a 27-gauge shaft with an outer diameter of 0.4mm and a 50-micron or 200-micron axial lumen.

The shunt’s implantation procedure is similar to a trabeculectomy and involves the creation of a scleral flap, but does not involve an iridectomy or removal of scleral tissue.

Several studies conducted over the past 10 years suggest that it is as effective as trabeculectomy and is less traumatic to the eye, Dr Stalmans said.

For example, in a prospective randomised study, the IOP reductions were statistically similar from three months onward in patients who underwent trabeculectomy and those who underwent implantation of the Ex-PRESS shunt (p=0.594).

However, in the Ex-PRESS group, there was significantly less early hypotony (four per cent vs 32 per cent; p<0.001), and choroidal effusion (eight per cent vs 38 per cent; p<0.001).

(Maris et al. J Glaucoma. 2007; 16:14-19) More recent comparative studies have shown similar results regarding IOP as well as showing quicker visual recovery (BeltranAgullo, Journal of Glaucoma 2015;24: 181-186) and less endothelial cell loss (Casini et al, Am J Ophthalmol 2015:1185-1190) with the Ex-PRESS implant than with trabeculectomy.

The XEN Gel Stent (AqueSys/Allergan) implant is another subconjunctival filtration device. However, it creates a filtration pathway from inside the eye. It is composed of a soft pliable collagen-derived gelatine material. It is inserted using a 27-gauge needle and (optionally) visualising the meshwork with a gonio mirror.

The results in 216 open-angle glaucoma patients from the still ongoing APEX study showed that, 12 months following implantation of the XEN device, mean IOP was reduced from 21.4mmHg on a mean of 2.6 medications, to 13.8mmHg on a mean of 0.6 medications. Results were similar between patients who underwent phaco in combination with XEN implantation versus XEN Ingeborg Stalmans MD, PhD implantation alone.

These implants may not be the best choice for advanced glaucoma patients

EUROTIMES | MAY 2016

An overview of the surgeries

SCHLEMM’S CANAL There are also now a range of ab interno devices that are designed to direct aqueous out through Schlemm’s canal. They include iStent® (Glaukos) and the Hydrus™ (Ivantis). Studies show that when combined with cataract surgery they generally reduce IOP just slightly more than cataract surgery alone, but also reduce the need for medications, Dr Stalmans noted.

“These implants may not be the best choice for advanced glaucoma patients. But, if you have a patient with mild glaucoma in which a higher target pressure is sufficient, then you might consider using them,” she added.

The iStent is a trabecular bypass device composed of nonferromagnetic titanium. The L-shaped device has a 1.0mm-long shaft, which fits into Schlemm’s canal, and a snorkel with a 120-micron lumen, which extends into the anterior chamber.

In an independent randomised controlled study, the mean IOP at 15 months was just 0.9mmHg lower in eyes that underwent cataract surgery and implantation of a single iStent than it was in eyes that underwent cataract surgery alone (14.8mmHg vs 15.7mmHg). However, patients with the iStent required significantly fewer medications (0.4 vs 1.3; p=0.007). (Fea et al, J Cataract Refract Surg 2010; 36:407-412) The Hydrus micro-stent is an intracanalicular scaffold which is eight times longer than the iStent. Results with the device so far suggest that, like the iStent implants, combining it with cataract surgery does not reduce IOP much more than cataract surgery alone, although it does reduce the need for medications.

SUPRACHOROIDAL CHANNEL There are now also a number of new implants designed to direct the outflow of aqueous into the suprachoroidal space. They include implants designed for implantation using an ab externo approach, such as the Gold Shunt (SOLX), the STARflo™ (iSTAR) and the Aquashunt™ (OPKO), or for implantation with an ab interno approach, such as the CyPass® (Transcend Medical) and the iStent Supra® (Glaukos).

The ab externo devices are invasive and limit further surgical options. The ab interno devices are still under investigation and their longer-term efficacy remains to be determined, Dr Stalmans said.

Ingeborg Stalmans: ingeborg.stalmans@mac.com

Glaucoma Day 2016 ESCRS

Friday 9 September

on & i t a r t s i Reg ings k o o B l Hote

OPEN

Immediately preceding the XXXIV Congress of the ESCRS 10â&#x20AC;&#x201C;14 September

Scientific Programme organised by

www.escrs.org

28

OCULAR

OCULAR DRUG DELIVERY Iontophoresis offers a new approach to treating infections.

Leigh Spielberg MD reports

I

ontophoresis offers many opportunities for non-invasive delivery of drugs in a large number of ophthalmic applications, Joseph Frucht-Pery MD told a session of the 7th International Conference on Ocular Infections in Barcelona, Spain.

“Iontophoresis is a non-invasive technique in which a small electric current is applied in order to enhance penetration of ionized drug into tissue. When applied transcorneally, it can deliver a high drug concentration to the cornea, aqueous humour, ciliary body, iris and lens. This has the potential to treat corneal ulcers, keratitis, glaucoma, dry eyes and ocular inflammation,” said Dr Frucht-Pery.

The limitations of the current modalities of ophthalmic drug delivery are well known. Topical solutions are diluted by tears and washed away within minutes. Suspensions provide longer contact with the ocular surface, but the drug particles can cause irritation.

Ointments and emulsions can blur vision and do not offer controlled drug release. And gels, although comfortable, also do not allow for a controlled rate of diffusion. Regarding more invasive treatments, intravitreal injections carry risks of infection and retinal detachment, while subconjunctival drug application can in rare instances lead to scleral perforation.

Joint IRISH and UKISCRS

Refractive Surgery Meeting GIBSON HOTEL, DUBLIN Friday 2nd December 2016

Dermot Pierse Memorial Lecture and Tom Casey Memorial Lecture Grand Round Topics

• Multifocals • Capsulotomy • • IOL Exchange • Stem Cell Management • • Management of PC Tear • Further Details from: Helen Murphy Secretary to: Prof. Michael O’Keeffe Level 5, Mater Private Hospital, Eccles Street, Dublin 7 Tel: 00353 1 885 8626 Email: hmurphy@materprivate.ie

Registration Fees: Euro: €250.00 Sterling: £220.00

EUROTIMES | MAY 2016

Iontophoresis has several advantages over traditional topical medications. Retention of the drug at the administration site, forming a depot that allows for prolonged drug release, increases bioavailability.

The absence of preservatives helps avoid topical toxicity. This combination might lead to increased compliance, in part due to a reduction in the number of required administrations. Also, because the drug is delivered locally and enters the ocular tissue immediately, the chances of systemic side effects are diminished.

SAME CHARGE “In iontophoresis, the drug and the electrode carry the same charge, while the ground electrode, which in the case of ocular administration is attached to the ear, is of the opposite charge.

It works best when the drug in question is a small, charged molecule such as an antibiotic,” said Dr Frucht-Pery, of Hadassah University Hospital, Jerusalem, Israel.

Two types of devices are the eye cup and the gel probe.

Dr Frucht-Pery helped design an iontophoresis device with a disposable hydrogel probe. The hydrogel, 5mm in diameter, is soft and flexible and is first placed in a drug solution, where it becomes saturated with the treatment drug. This is then pressed against the cornea, for anterior segment disease, or against the sclera for posterior segment pathology.

“The possibility of targeting internal ocular tissue through noncorneal routes is intriguing,” noted Dr Frucht-Pery.

SUCCESSFUL PENETRATION Experiments in rabbits demonstrated successful penetration of antibiotics into the cornea and anterior chamber. Gentamicin, applied via transcorneal iontophoresis, was detected at therapeutic levels in the cornea more than eight hours after treatment. This allows less frequent administration than hourly drops now used for severe keratitis.

“In experimental keratitis in rabbit eyes by intrastromal injection of pseudomonas aeruginosa, transcorneal iontophoresis of gentamicin, tobramycin and ciprofloxacin resulted in significantly fewer bacterial colony-forming units in the cornea, as compared with frequent instillation of eye drops,” said Dr Frucht-Pery. The difference was three log units, or a factor of one thousand fewer units after iontophoresis.

Drugs delivered transcorneally cannot reach the posterior segment, due to the lens barrier. However, transscleral iontophoresis can also deliver drugs directly into the vitreous and retina.

“The iontophoretic device is placed on the conjunctiva. This must be located over the pars plana, to avoid electrical toxicity to the retina,” said Dr Frucht-Pery. The goal is to avoid the complications of intravitreal injection, and studies have demonstrated successful delivery of antibiotics to the vitreous of rabbit eyes.

But what about the potential for toxicity using this technique? In toxicity studies in rabbit corneas, toxicity was related to the strength of the current and the duration of the procedure. Aberrations included epithelial defects and mild stromal oedema. However, transscleral iontophoresis showed no damage on light microscopy.

Transscleral iontophoresis with low current densities can provide effective concentration of antibiotics for hours in the cornea, aqueous humour, vitreous and retina, he said.

Joseph Frucht-Pery: josefr@hadassah.org.il

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VITREORETINAL SURGERY

PAEDIATRIC OPHTHALMOLOGY

Courtesy of Department of Ophthalmology, Great Ormond Street Hospital, London, UK

30

Photographs of a child with keratitis ichthyosis deafness (KID) syndrome, before and after limbal injection of bevacizumab, showing marked reduction in vessel calibre but ‘ghost’ vessels still present

TRIALS SHOW EFFICACY Anti-VEGF agent offers hope for treating corneal neovascularisation, but paucity of data limits use. Cheryl Guttman Krader reports

A

s is often the case with clinical decision-making in paediatric ophthalmology, the use of an anti-vascular endothelial growth factor (anti-VEGF) agent for treating corneal neovascularisation should be assessed on a case-by-case basis, said William Moore BSc, MBBS, FRCOphth, at the 3rd World Congress of Paediatric Ophthalmology and Strabismus in Barcelona, Spain.

Reviewing the published literature on this topic, Dr Moore concluded that there is evidence from animal and human trials showing efficacy of anti-VEGF treatment for reducing corneal neovascularisation. However, the clinical experience is limited, mostly involved adults, and represents off-label use.

“While anti-VEGF agents are giving us some hope for treating corneal neovascularisation, there is no established safe dosage or mode of administration. Therefore, further investigation is needed before anti-VEGF drugs can become the useful therapeutic agents for inhibiting corneal angiogenesis that we all wish them to be,” said Dr Moore, consultant ophthalmic surgeon, Great Ormond Street Hospital, London, UK. “Nevertheless, there are children under our care whose corneas are failing, rejecting and clouding, and so we must continue to try to help them, using anti-VEGF agents based on our best judgment calls,” he added.

RESEARCH NEEDED Most reports on anti-VEGF treatment for corneal neovascularisation in human eyes describe the use of bevacizumab, which is also the least expensive of the available agents. It has been administered topically and also as an intrastromal, subconjunctival or intraocular injection.

Topical use has been associated with epitheliopathy, with a 60 per cent incidence in one study evaluating 1.25 per cent bevacizumab applied three times daily. More research is needed to understand the safety of subconjunctival and intrastromal injections.

Of note, one case report described regression of extensive vessel growth in the stroma, with no recurrence during six months of follow-up after an intrastromal injection of bevacizumab.

“It makes sense that the intrastromal injection might be a more effective route of administration since the medication will not diffuse away as quickly,” said Dr Moore.

EUROTIMES | MAY 2016

Compared with bevacizumab, ranibizumab binds with higher affinity to VEGF-A, and aflibercept has even higher affinity for VEGF-A while also binding to placental growth factors 1 and 2.

Its broader binding profile may provide aflibercept with greater anti-angiogenic activity. Dr Moore noted that aflibercept also has the longest duration of anti-VEGF action (twofold longer than ranibizumab after intravitreal injection), which may be a drawback when treating children.

Although pegaptanib, which binds only to the VEGF165 isoform, seems to be less effective than the other anti-VEGF agents for reducing corneal neovascularisation, its good safety profile when used for retinal neovascularisation suggests the potential for it to have a role as maintenance therapy, Dr Moore said.

The idea that maintenance therapy may be necessary derives from observations that available anti-VEGF agents can stop new vessel growth if treatment is started early, but are less effective once the blood vessels become covered with pericytes, which occurs after about two weeks.

“If we watch the eyes and wait, it may be too late. However, if we also treat the underlying cause for the corneal neovascularisation aggressively, the eye may stay calm,” Dr Moore said.

Investigational anti-angiogenic agents with novel mechanisms may offer greater activity than the available anti-VEGF agents, but much more work is needed to define their efficacy and safety.

Compounds in development include silencing RNA molecules (bevasiranib and Sirna-027, for example) that can block both the intracellular and extracellular effects of VEGF and its receptors.

In addition, there are tyrosine kinase inhibitors being developed that target a pathway initiated after VEGF binds to its receptors.

Agents within the latter class include pazopanib, which improved graft survival in a mouse model of corneal transplantation, and sunitinib, which has been shown to reduce pericytes in established vessels. The effect of tyrosine kinase inhibition on normal vasculature needs to be determined, Dr Moore said.

He concluded by stating that development of anti-VEGF agents as a treatment for corneal neovascularisation will require large randomised, controlled trials.

In the meantime, Dr Moore encouraged ophthalmologists who see large numbers of patients with corneal neovascularisation to collaborate and publish their data.

William Moore: william.moore@gosh.nhs.uk

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Registration, Hotel Bookings & Preliminary Programme Online

www.wspos.org

Preceding the XXXIV Congress of the ESCRS 10 â&#x20AC;&#x201C; 14 September 2016

Bella Center, Copenhagen, Denmark

FOUR EVENTS ONE VENUE Bella Center, Denmark

XXXIV Congress of the ESCRS

16th EURETINA Congress

7th EuCornea Congress

WSPOS Paediatric Subspecialty Day

10–14 September www.escrs.org

8–11 September www.euretina.org

9–10 September www.eucornea.org

9 September www.wspos.org

BOOK REVIEWS

EASY ACCESS With current fellowships generally providing in-depth training, and with so much information readily available online, there seems to be little enthusiasm among most practitioners for big, heavy textbooks. Thus, “high-yield” handbooks, easily accessible educational references, have PUBLICATION proliferated in their stead.

HANDBOOK OF RETINAL OCT The Handbook of Retinal EDITORS OCT, by Jay S Duker, Nadia K JAY S DUKER, NADIA K WAHEED, Waheed and Darin R Goldman DARIN R GOLDMAN (Elsevier Saunders), is a 170page gem of insight into optical PUBLISHED BY ELSEVIER SAUNDERS coherence tomography (OCT).

Each pathologic entity receives one page of concise text on the left-hand side and a series of well-illustrated, high-quality OCT pictures on the right.

The text follows a standard and logical progression of information: Introduction, Clinical Features, OCT Features, Ancillary Testing and Treatment. What makes this book a pleasure is the precisely defined structural abnormalities indicated on the OCTs. For example, the description of subretinal perfluorocarbon: “… shows a completely hyporeflective space occupied by the perfluorocarbon. There is a distinct rim of hyper-reflectivity. The overlying retina is very thin due to a mechanical effect of the dense liquid.”

The publication covers the usual suspects like age-related macular degeneration and central retinal vein occlusion, but also less common and/or newly identified entities like domeshaped macula and vitreoretinal lymphoma. Diseases with several stages, or with morphological variability, are portrayed in multiple scans in order to cover the full spectrum.

BOOK

REVIEWS

IN-DEPTH GUIDANCE For those looking for more in-depth guidance in retinal disease, the Handbook of Retinal Disease: A Case-Based Approach (JP Medical) is a new option. Also written by Dr Duker and Dr Goldman, along with three other colleagues, the theme of this book is: “How to approach a patient with…”

It features 77 cases, each presented with a table summarising clinical findings, differential diagnosis, questions to ask the patient and recommended imaging.

After a discussion of the diagnostic imaging results, a final diagnosis is proposed with a summary of prognosis, recommended treatment and follow-up.

The handbook is a practical one, intended to assist in the clinic those who are already familiar with the range of medical and surgical retinal pathologies, but who might appreciate a reminder regarding the specifics of less commonly encountered diseases. It is easy to use and well illustrated with up-to-date imaging and a clear, logical progression. This book is intended for both trainees and practising physicians, whether general ophthalmologists or retinal specialists.

Have you made your choice yet?

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Medicel AG Luchten 1262 CH-9427 Wolfhalden Switzerland

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LEIGH SPIELBERG Books Editor

If you have a book you would like to have reviewed please send it to: EuroTimes, Temple House, Temple Road, Blackrock, Co Dublin, Ireland

EUROTIMES | MAY 2016

33

34

ESCRS NEWS

Sidath Liyanage (right) receives the 2015 award from Roberto Bellucci

delivering surgical

innovation

Q-Rinse Altomed now manufacture Q-Rinse in the UK. It is a convenient simple device, designed to flush instruments such as phaco handpieces.

ESCRS

NEWS

JOHN HENAHAN PRIZE

Malhotra Endo Nasal DCR Nibbler A unique delicate bone nibbler designed for Endo Nasal approach DCR.

Young ophthalmologists are invited to write a 900-word essay on the topic of “Why Should I Publish?” for the 2016 John Henahan Writing Competition.

The competition is open to ESCRS members aged 40 or under on 1 January 2016. The essays will be judged by Thomas Kohnen, chairman of the ESCRS Publications Committee; Emanuel Rosen, chief medical editor of EuroTimes; José Güell, former ESCRS president; Oliver Findl, chairman of the ESCRS Young Ophthalmologists Committee; Sean Henahan, editor of EuroTimes; Paul McGinn, editor of EuroTimes; and Robert Henahan, contributing editor of EuroTimes.

Last year's winner was Dr Sidath Liyanage of Moorfields Eye Hospital, London, UK. The winner will receive a travel bursary worth €1,000 to attend the XXXIV Congress of the ESCRS in Copenhagen, Denmark, and a special trophy will be presented at the Video Awards Session on Sunday, 11 September 2016.

Closing date to enter: Friday, 27 May. Entry forms available from Colin Kerr, executive editor, EuroTimes, at: henprize@eurotimesorg

MARKETING CONTEST

Distributor enquiries welcome

2 Witney Way, Boldon Business Park, Tyne & Wear, NE35 9PE. UK

Tel: +44 (0)191 519 0111 Fax: +44 (0)191 519 0283 Email: sales@altomed.com Web: altomed.com

EUROTIMES | MAY 2016

The ESCRS Practice Management and Development Committee has launched the third ESCRS Practice Management and Development Marketing Competition.

The competition judging panel, chaired by Dr Paul Rosen, is looking for entries that best capture the spirit of the competition – use of the marketing ideas that are shared during the Practice Management and Development workshops and applied by an ophthalmologist and her/ his team.

Entries should consist of a three-to-four-slide

Paul Rosen

presentation illustrating the campaign, costs, as well as the results. The winner will receive a €1,000 bursary and an invitation to present during next year’s XXXV Congress of the ESCRS in Lisbon, Portugal.

To enter, email: colin@eurotimes.org.

Submission deadline is 15 August, 2016. More details: www.escrs.org

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HOSPITAL DIARY

TERROR STRIKES

Dr Leigh Spielberg was among the ophthalmologists who joined medical

colleagues to treat victims of the recent terror attacks in Brussels

A

victim of by the hour. These eyes are the Brussels doomed to any combination terrorist attack of chronic epithelial defects, has just been corneal stromal ulceration, admitted to permanent scarring, the burn unit,” conjunctivalisation of the said my colleague, Thierry cornea, multiple surgeries and Derveaux. “He has ocular often a terrible combination trauma. I’ll arrange emergency of pain and blindness, leading access to the operating room. to enucleation.

When can you be there?”

Clinical examination of “Now,” I answered. the patient revealed what I “First things first,” he had expected. Yet, despite replied. “He’s currently my prior experience with this undergoing external fixation type of injury, I thought it of his femur, but once that’s prudent to get the advice of done, it’s our turn.” Dr Jan-Tjeerd de Faber, an Derveaux showed me the ophthalmologist who has orbital CT scan. There was a volunteered for each of the past metallic foreign body lodged 20 New Year’s Eves to be on in or under the superior surgical call in the Rotterdam rectus of the right eye. The Eye Hospital to treat the globe looked intact.

Dutch fireworks victims.

But I suspected there He is The Netherlands’ leading might be more than just the campaigner against amateur foreign body. Having spent fireworks. We discussed nearly six years training in the case via WhatsApp, as The Netherlands, I was well he was in Taiwan, presenting aware of the damage bombs blast injury cases at the can inflict on the eyes. The Asia-Pacific Academy of normally sober Dutch let Ophthalmology Congress. loose on New Year’s Eve, With one look at a photo igniting do-it-yourself of the eye, Dr de Faber fireworks and homemade confirmed my suspicion: That was the “easy” part. The real "knallers" (“boom-booms”, “White conjunctivae. Looks which are essentially like caustic trauma. My challenge was identifying and treating the small bombs, capable of advice: initiate fireworks chemical-caustic burns of the ocular surface inflicting immediate death) treatment protocol.” at home, dozens of which While the nurses of the end up exploding in hands burn unit were preparing the and faces. ocular irrigation system and ordering the extensive list of eye Those with extensive craniofacial trauma ended up at the drops from the hospital pharmacy, I performed fundoscopy. university hospital. Those with primarily ocular injuries The view was hazy, because of the cloudy cornea, folds in were sent to the Rotterdam Eye Hospital, where we treated Descemet’s membrane, and the hyphema that had settled on their blast injuries: orbital fracture, globe rupture, and the anterior surface of the lens. corneoscleral laceration.

“Can we position him upright for a little while, so the blood in the anterior chamber can settle inferiorly?” I asked the nurse.

“Not really,” she replied.

A TERRIBLE COMBINATION “Why not?” I asked.

That was the “easy” part. The real challenge was identifying “Because his hip joint was destroyed and is being held and treating the chemical-caustic burns of the ocular surface. in place by pins and screws,” she said. “Strict orders from The corneal erosion is so complete that it’s surprisingly easy orthopaedics.” to miss. It resembles simple fluorescein pooling, as there’s no “edge” between present and absent epithelium. And the PROCEED SLOWLY conjunctivae look, at first glance, quite normal, reassuringly So be it. I proceeded. Indirect ophthalmoscopy revealed a white. But this is classic fool’s gold. The eye is white because small, dense, localised vitreous haemorrhage, very peripheral the superficial and deep vessels have been cauterised by the at 12 o’clock. It coincided with the location of the foreign combination of thermal and chemical injury. body on the CT scan. But there was no vitreous detachment, Deep in the fornix, highly alkaline bits of charred gunpowder so the blood hadn’t displaced at all. Had the sclera been soot continue to seep chemicals onto the eye. Limbal stem cells penetrated?! Damn! start to die, and the likelihood of epithelial repair diminishes Illustration by Eoin Coveney

36

EUROTIMES | MAY 2016

HOSPITAL DIARY Here I was, a vitreoretinal surgeon fresh out of residency, facing the possibility of performing an emergency vitrectomy on a 30-year-old patient in an induced coma who was unable to give consent. Hazy cornea. Hyphaema. Phakic. No PVD. As I completed the examination, the operating room had called to say they had freed up space for us in a surgical unit.

The patient could be transferred immediately. I had an hour to prepare, and I went over the steps in my mind. Careful placement of the eyelid speculum. Conjunctival peritomy. Very careful isolation and hooking of the superior rectus. Removal of the shrapnel. Localisation of potential scleral laceration or port of entry into the globe…

I was happy to hear that an experienced resident, Laura Leysen, would be assisting me. As we were scrubbing up, a senior vitreoretinal consultant, Fanny Nerinckx, called to offer some last-minute advice. She had treated several terrorist bombing victims with similar injuries earlier that day in another hospital.

As Dr Leysen deftly assisted me with peeling away the inflammatory mess, I spotted a sparkle shining through the muscle fibres. Shrapnel “Proceed slowly. Avoid undue pressure on the globe. If you detach the rectus muscle, don’t let it disappear into the orbit.

And if you have to convert to vitrectomy… call me!” I was thankful to have potential backup for this tricky case.

The patient arrived in the theatre. We could start immediately, as he was already anaesthetised. Here we go!

The globe was encouragingly firm. Displacement of the conjunctiva and tenon revealed an unusual fibrinous reaction

around the superior rectus. As Dr Leysen deftly assisted me with peeling away the inflammatory mess, I spotted a sparkle shining through the muscle fibres. Shrapnel! But how deep did it extend? I hadn’t fully isolated the muscle, so I couldn’t simply pull it out. What if it were lodged in the sclera? I had no desire to induce suprachoroidal haemorrhage or incarcerate the retina even before I had the hooked the muscle.

But then, miraculously, as I further isolated the muscle, the metal slipped to the superior surface of the rectus. I removed it and asked the nurse to keep it for me. I held my breath as I peered under the muscle to explore the sclera. Manipulating a rectus muscle attached to a globe with a potential scleral laceration is not an enjoyable experience. Deep inside, I suspected the globe would be intact, as it was normotensive, but the presence of vitreous haemorrhage kept me doubting and vigilant. I expected the worst and hoped for the best.

The sclera looked perfect. I looked once, twice and three times just to be sure, and then asked Dr Leysen what she thought.

“I think we’re safe,” she said.

“I think so too,” I replied, happy that we were of the same opinion. “Will you close the conjunctiva?”

Dr Leysen closed the conjunctiva as I watched on the monitor. As she placed the fine sutures, I reflected on how lucky we were to be operating under such good conditions.

Many acts of terror and war occur in highly disorganised locations, where delivering medical care is difficult, highly demanding and often dangerous. Here, I had everything at my disposal to do my work and deliver care.

My thoughts then shifted back to our patient, a previously healthy and presumably happy young man whose life had been made immeasurably more difficult in the blink of an eye.

Dr Leigh Spielberg is a vitreoretinal and cataract surgeon at Ghent University Hospital, Belgium

JOHN HENAHAN

PRIZE 2016

CALL FOR

ENTRIES Young ophthalmologists are invited to write a 900-word essay on

“Why Should I Publish?” and win a travel bursary worth €1,000 to attend the XXXIV Congress of the ESCRS in Copenhagen, Denmark

Closing date Friday 27 May 2016 Entries to be sent to henprize@eurotimes.org For further information see www.escrs.org

EUROTIMES | MAY 2016

37

INDUSTRY NEWS

OCULUS Centerfield® and Easyfield®

INDUSTRY

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MAJOR LANDMARK Heidelberg Engineering says the company has reached an important corporate milestone with the 10,000th SPECTRALIS® diagnostic imaging platform, which has been delivered to a French retina specialist, Dr David Sayag, who is based in Paris.

“These kinds of milestones provide a good opportunity to think about the present, past and future. Considering the current market trends and our robust development pipeline, we are excited about our prospects and are enjoying our work just as much now as we did in the early days,” said Dr Kester Nahen, managing director of Heidelberg Engineering. www.heidelbergengineering.com

ONE MILLION RINGS MicroSurgical Technology, Inc. (MST ) recently shipped the one millionth Malyugin Ring since the device was first introduced in September 2007.

Developed by Boris Malyugin MD, PhD, chief of the cataract and implant surgery department and deputy director general of the S Fyodorov Eye M icrosurger y Complex in M oscow, Russia, the Malyugin Ring is designed to enhance Boris Malyugin

phacoemulsification surgery in complicated IFIS and small-pupil cases refractory to traditional protocols.

“It is with great pride and gratitude that we are announcing the shipment of the one millionth Malyugin Ring,” said MST president and CEO Larry Laks.

“We would like to thank our customers for helping us achieve this important patientsafety milestone, and of course, Dr Malyugin for transforming the way surgeons manage small-pupil cases. It is an incredible achievement,” added Mr Laks. www.microsurgical.com

Tradition and innovation in visual field measurement – OCULUS perimeters bring you the best of both worlds

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EUROTIMES | MAY 2016

39

CUTTING-EDGE EDUCATION FOR ANTERIOR SEGMENT SURGEONS THE MOST EFFICIENT TOOL TO FIND CURRENT TECHNIQUES AND INNOVATIONS

ascrs.org/learn CURATED BY THE AMERICAN SOCIETY OF CATARACT AND REFRACTIVE SURGERY

OPHTHALMOLOGICA

OPHTHALMOLOGICA VOL: 235 ISSUE: 3

SD-OCT SHOWS SUBCLINICAL RETINAL CHANGES IN DIABETES PATIENTS The results of a new study indicate that type 1 diabetic patients without clinically diagnosed diabetic retinopathy have degenerative changes in the inner retinal layers that are not evident in the eyes of healthy non-diabetic individuals. In the study, spectral-domain optical coherence tomography (SD-OCT) showed that whole retinal nerve fibre layer (RNFL), the superior and inferior quadrants, and the superior half of the peripapillary RNFL were significantly thinner in 90 type 1 diabetic patients than they were in 90 healthy controls. The degree of RNFL thinness compared to controls correlated significantly with the duration of the diabetes and the level of HbA1c (p<0.05). FC Gundogan et al, “Early Neurodegeneration of the Inner Retinal Layers in Type 1 Diabetes Mellitus”, Ophthalmologica 2016; Volume 235, Issue 3.

Worldwide fastest

SLT Laser EDITION 2016

RANIBIZUMAB EFFECTIVE FOR DME WHERE BEVACIZUMAB FAILS Intravitreal treatment with ranibizumab can be effective in eyes with diabetic macular oedema (DME) that have failed to respond to bevacizumab, according to the findings of a retrospective study. The study involved 26 eyes of 22 patients with a mean age of 66 years. They had received a mean of 7.3 intravitreal injections of bevacizumab prior to switching to ranibizumab.

After three ranibizumab injections, 57 per cent of eyes showed improvement in visual acuity. The visual improvement reached statistical significance (p=0.044) in those eyes where the pretreatment acuity for the second-line therapy was less than 20/40. In addition, central macular thickness decreased from 435.95µm to 373.69µm (p=0.01). R Ehrlich et al, “The Effectiveness of Intravitreal Ranibizumab in Patients with Diabetic Macular Edema Who Have Failed to Respond to Intravitreal Bevacizumab”, Ophthalmologica 2016; Volume 235, Issue 3.

LESS MYOPIC SHIFT WITH RED LASERS IN ROP In retinopathy of prematurity (ROP) patients, therapy with red lasers seems to cause less myopic shift than does therapy with diode lasers, according to the findings of a randomised doublemasked clinical trial. The study involved 150 eyes of 75 infants with a mean gestational age of 28.6 weeks. Seventy-four eyes received diode laser and 76 received red laser therapy. Following treatment, refraction shifted by a mean of 2.6 dioptres overall, and the amount of shift was significantly greater in the diode group (p<0.001). R Roohipoor et al, "Comparison of Refractive Error Changes in Retinopathy of Prematurity Patients Treated with Diode and Red Lasers", Ophthalmologica 2016; Volume 235, Issue 3.

z. >10 H e t a r . st rep RE Faste CEDU PRO RAPID

lay p disp u d a y he ED energ CUSS e s l u P AY FO T CAN S S E Y E

y. tabilit s e s l -pu lse-to u TS p t s ESUL R E Highe L IB ODUC REPR

www.arclaser.com info@arclaser.com SEBASTIAN WOLF Editor of Ophthalmologica

Bessemerstr. 14 90411 Nuremberg Germany  +49 (0) 911 217 79 -0

The peer-reviewed journal of EURETINA

EUROTIMES | MAY 2016

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42

JCRS

JCRS SYMPOSIUM

Monday, May 9, 2016, 1:00 to 2:30 PM Room 243, Ernest Morial Convention Center

Controversies in Anterior Segment Surgery Chairpersons: Nick Mamalis, MD, USA (U.S. EDITOR) William J. Dupps Jr, MD, PhD, USA (ASSOCIATE EDITOR) 1:00 Complications in Femtosecond Laser–Assisted Cataract Surgery Compared with Manual Phacoemulsification ESCRS FLACS Study Update Results Peter J. Barry, MD, IRELAND Better Femtosecond Results Shachar Tauber, MD, USA 1:20 Discussion 1:30 Topographic-Guided Ablation in LASIK Why You Use Topography-Guided Treatments for All LASIK Cases Doyle Stulting, MD, PhD, USA Why You Don’t Use Topography-Guided Treatments for Irregular Eyes Simon P. Holland, MB, FRCSC, CANADA 1:50 Discussion 2:00 Corneal Crosslinking: When Do You Treat Keratoconus?

Safety and Efficacy Peter S. Hersh, MD, USA Adolescence Ronald N. Gaster, MD, USA 2:20 Discussion 2:30 End of Session

JCRS HIGHLIGHTS

VOL: 42 ISSUE: 1 MONTH: JANUARY 2016

MULTIFOCAL IOL BIOMETRY Varying designs and differing near additions among available multifocal intraocular lenses (IOLs) complicate preoperative prediction of individual patients outcomes. To seek clarity on this issue an international collaborative group conducted an experimental study to calculate the near focal distance of different multifocal IOLs, as a function of the two parameters that are measured before cataract surgery: axial length and refractive corneal power (keratometry [K]). Investigators calculated the IOL power for emmetropia in an eye model with the axial lengths ranging from 20 to 30mm and K from 38 to 48 dioptres. They then calculated the predicted myopic refraction for any given IOL add power (from +1.5 to +4.0D). From this value the near focal distance was obtained.

Calculations were also performed for the average eye (K = 43.81D; AL = 23.65mm). This revealed that the near focal distance increased with increasing values of keratometry and axial length for each near power add. Longer eyes with steeper corneas showed the longest near focal distance and could experience more difficulties in focusing near objects after surgery. The opposite was true for short hyperopic eyes. Since the effective lens position is predicted from the preoperative keratometry and axial length, the surgeon can use these parameters preoperatively to estimate the near focal distance, the study concludes. G Savini et al, JCRS, “Influence of the effective lens position, as predicted by axial length and keratometry, on the near add power of multifocal intraocular lenses”, Volume 42, Issue 1, 44-49.

FEMTO INTRASTROMAL AK Nearly one half of eyes having cataract surgery are believed to have corneal astigmatism greater than 1.0 dioptre, with more than 10 per cent having greater than 2.0D of cylinder. Intrastromal astigmatic keratotomy (AK) provides a safe and effective approach to astigmatic correction during cataract surgery, without additional cost, report researchers from Moorfields Eye Hospital, UK. The study included 196 eyes of 133 patients undergoing laser cataract surgery with concurrent astigmatism management by intrastromal AK. All eyes had greater than 0.7 corneal dioptre cylinder. The mean correction index was 0.63 ± 0.32 (range 0.00 to 1.93), indicating that the mean astigmatism correction was 63 per cent. Fourteen eyes (7.1 per cent) and seven eyes (3.6 per cent) had an astigmatism correction of greater than 100 per cent and greater than 120 per cent, respectively. Overall, 0 per cent, 48.5 per cent, and 51.5 per cent of eyes had 0.50D or less, 1.0D or less, or greater than 1.0D, respectively, preoperatively compared with 32.1 per cent, 85.7 per cent, and 14.3 per cent, postoperatively. There were no cases of corneal endothelial perforation or inadvertent placement within the visual axis. Further understanding of the factors influencing femtosecond laser intrastromal AK efficacy are required to optimise outcomes, the researchers note. A Day et al, JCRS, “Nonpenetrating femtosecond laser intrastromal astigmatic keratotomy in eyes having cataract surgery”, Volume 42, Issue 1, 102-109.

THOMAS KOHNEN European editor of JCRS

Become a member of ESCRS to receive a copy of EuroTimes and JCRS journal

EUROTIMES | MAY 2016

ESASO

43

ESASO RETINA ACADEMY 2016 A talent hub and top-rated advanced educational event for young ophthalmologists

T

his year’s 16th ESASO Retina Academy will take place in Estoril, Portugal, from 23-25 June 2016. For promising young eye doctors and scientists, this ESASO Retina Academy provides a unique learning opportunity with world-leading faculty who will discuss the latest scientific, technical and clinical developments in the field of eye care.

This year’s programme includes several plenary sessions, which together aim to train practising clinicians on the most current clinical challenges.

TOP SCIENTIFIC HIGHLIGHTS INCLUDE: • “Dry AMD: a new challenge”: foremost experts will provide the latest information on the pathophysiology and classification of dry macula degeneration. The session will cover ongoing research in retina centres around the world in geographic atrophy, as well as studies exploring evidence regarding signs of disease progression.

• “PDR treatment”: The current controversy regarding the treatment of proliferative diabetic retinopathy (PDR) with laser or with anti-VEGF therapies is an important topic of interest to clinicians. After presentation of data from clinical trials and analysis of several case studies, a panel of experts will discuss controversial points with their pros and cons.

• “CSC”: A full plenary session of this year’s Retina Academy is dedicated to the multifaceted clinical appearance of central serous chorioretinopathy (CSC). Internationally renowned specialists will provide the most current insights into the etiopathogenesis and manifestations, diagnosis and treatment.

Over 150 abstracts from close to 20 countries were submitted to eight subcategories and the best ones will be presented during the congress. All others will be displayed as posters and are available for discussion with the attending authors during congress hours.

Submitted case studies will be presented and discussed during the Retinamour session, where unusual cases will be discussed by the chair and questions answered by the panel. The ESASO Style Debates will highlight controversial standpoints on important topics. Opponents share their presentations, present and substantiate their preferred treatment for 10 minutes, and challenge each other together with a vivid audience.

ACTIVE LEARNING ESASO is also introducing a new concept of active learning.

Each session will start and end with test questions, which will allow an immediate evaluation of the individual learning curve.

ESASO’s scientific committee believes that this new concept underpins its objective to actively address unmet training needs and learning outcomes of its delegates. ESASO Retina Academies have excellent scientific and clinical presentations, but another feature is the collegial spirit and friendly atmosphere. The innovative educational formats are varied and tailor-made to give the best possible learning and social experience.

www.esaso.org

For further information visit: www.esaso.org/16th-esaso-retina-academy-2016 EUROTIMES | MAY 2016 08_1603_05 ESASO_Anz_EUT_93x266_05.2016_RZ.indd 1

22.03.16 16:24

TRAVEL

Magasin du Nord

COPENHAGEN

3

TO NOTE...

COPENHAGEN

DEBIT CARDS: THEY ARE WIDELY ACCEPTED SURCHARGE: EXPECT THIS IF USING A CREDIT CARD PIN CODE: MAY BE REQUESTED

The now famous Little Mermaid bronze statue of Andersen’s fairy tale heroine was a gift to Copenhagen from Carlsberg brewer Carl Jacobsen. Ellen Price, who portrayed the little mermaid in the ballet of the same name, modelled for the head; the artist’s wife, Eline Eriksen, posed for the body. The Little Mermaid took her seat on the harbour rocks in August 1913. If you won’t settle for a Little Mermaid key ring or paper weight souvenir, but insist on an authentic “Little Mermaid” statue of your own, that can be arranged. The heirs of the artist, Edvard Eriksen, offer replicas of various sizes on their website: mermaidsculpture.dk Maya Bjørnsten designs unique, artisanal jewellery featuring rough diamonds, a sophisticated alternative to the usual cut stones.

Her boutique is set in a charming courtyard at Bredgade 56, where Maya is happy to welcome you for a “non-committal visit”. It’s an interesting stop, even if you are “just looking”. But if you are actually hunting for something special, your search may end here. Raw diamonds are graded according to different qualities, so there’s a big price range. Stones come in a variety of shapes and colours; they are mounted as earrings, necklaces, cufflinks and, of course, rings, which will cost from €900 for either a ready-made piece or one conceived just for you. The shop is open on Tuesday from 11.00 to 16.00, on Thursday and Friday from 11.00 to 17.30, and on Saturday from 11.00 to 15.00. You can also make an appointment outside regular hours by telephoning +45 20 20 70 86. For a preview, check the website: roughdiamonds.dk The lavish flagship store of Royal Copenhagen is at 6 Amagertorv Square, a short walk down Strøget from Kongens Nytorv. All its china patterns, including the first – Blue Fluted, which was first produced in 1775 for the royal family – can be seen (and bought) here. For Royal Copenhagen at a reduced price, browse the ‘seconds’ at the Royal Copenhagen Outlet in Frederiksberg, a 25-minute taxi ride from the Bella Center. The china company acquired Georg Jensen in 1971, so Jensen bargains can be found here too.

SPOILED FOR CHOICE

Delegates to the ESCRS Congress will find great shopping in Copenhagen. Maryalicia Post reports From Scandinavia’s biggest department store to local flea markets, Denmark’s capital has an interesting variety of shopping opportunities. Here are some of the highlights.

MAGASIN DU NORD The stylish Magasin du Nord, the oldest and largest department store in Scandinavia, was established in 1890 in the hotel that once housed Hans Christian Andersen. It has its own museum at nearby Vingardstradestraede 6. The Magasin showcases an enormous range of Scandinavian and international brands, while its food hall prompts comparison with London’s Harrods.

There’s a commission-free foreign exchange, an international news kiosk, a coffee shop with free WiFi, plus a basement chocolate factory (try the chocolate-covered marshmallows called ‘flødebolle’). Magasin offers a 10 per cent discount to all foreign visitors, though some departments/brands are excluded - and you’ll need proof of a foreign address. Non EU-residents are entitled to an extra tax free refund.

Centrally located at Kongens Nytorv, the building has direct Metro access. A few steps away from Kongens Nytorv is the famed shopping street Strøget, one of the longest pedestrianised streets in Europe.

The Royal Copenhagen Factory is here – along with the usual high-street names.

Explore the streets off Strøget for more individual boutiques.

of these is Nina Saunders' “melting piano” on a balcony in the atrium. It appears to be turning liquid, forming a puddle on the level below.

In a nod to the fish market that preceded the mall on this site, there are three installations by Dominic and Frances Bromley aka Scabetti: Shoal No 8 is an intricate skein of over 8,500 steel fish.

FLEA MARKETS For a shopping spree crossed with a treasure hunt, try a Copenhagen flea market. From May through to September/ October, they pop up on weekends.

There’s an outdoor vintage and art market at Kongens Nytorv, while Copenhagen’s oldest and trendiest flea market is on Israels Plads. Established flea markets – whether seasonal or year-round, indoor or outdoor, daily or on weekends only – are listed on: fleamapket.com See more travel reviews at: www.maryaliciatravel.com

FISKETORVET Fisketorvet is an attractive mall with 120 shops, an IMAX cinema, numerous dining choices, and some impressive pieces of modern art on the city’s waterfront. One

Flea market goods

EUROTIMES | MAY 2016

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REVIEW Figure B: Symfony IOL Figure A: Monofocal IOL implanted in-the-bag

B A

D C

Figure C: Marks on toric IOL lined up with alignment marks on cornea body text

Figure D: Toric IOL needs careful thorough viscoelastic removal to prevent postoperative rotation

UNAIDED VISION

Everything you ever wanted to know about IOLs.

T

Dr Soosan Jacob reports he perfect aim of an ideal cataract surgery is to be able to implant the intraocular lens (IOL) in-the-bag and give perfect unaided vision for all distances. Various factors play a role, right from accurate biometry to the type of IOL selected. Setting realistic patient expectations, as well as understanding patient requirements and personality, are also important.

BIOMETRY:

An accurate biometry is key. Scheimpflug topography and posterior corneal curvature are gaining importance to avoid postoperative refractive surprises, especially for toric IOLs. A poor ocular surface may give erroneous keratometric values and this needs treatment prior to surgery. Though axial length measurement is accurate with optical methods (IOLMaster速, LENSTAR速), contact or immersion ultrasound may be advantageous in eyes with media opacities or in those with inability to fix.

IOL power calculation depends on numerous factors, such as the average central corneal power, axial length, effective lens position, EUROTIMES | MAY 2016

desired postoperative refraction, vertex distance, A constant etc. The A-constant should be calculated and fixed according to the IOL type, biometric technique and surgeon factor. Most modern formulae provide reliable results with average keratometry and axial lengths.

IOL power calculation is problematic in short and long eyes; eyes with staphyloma or silicone oil-filled eyes; post-refractive surgery eyes; patients with nystagmus and inability to fix; dense cataracts and uncooperative patients such as children.

Various formulae are available such as Holladay, Holladay I and II, Hoffer Q, SRK-T etc, and these should be used in the appropriate situations. For piggyback IOLs, a power equal to myopic and 1.5 times a hypermetropic error is planned. IOL power is underestimated post-myopic LASIK and overestimated post-hyperopic LASIK. The Hill, Wang and Koch ASCRS IOL power calculator for eyes that have undergone previous LASIK/PRK/RK (iolcalc.org) is very useful.

IOL TYPE: Aspheric IOLs aim at eliminating positive spherical aberration present in traditional IOLs. They are available as either negative spherical aberration IOLs that compensate almost completely

REVIEW

(Tecnis®, AMO, with -0.27 microns of spherical aberration) or partially (Acrysof IQ Aspheric®, Alcon, with -0.20 microns of spherical aberration) for the positive aberrations of the average cornea or as zero spherical aberration IOLs (Akreos AO®, B&L).

With smaller pupil size, this may not be a significant advantage.

Some residual spherical aberration improves depth-of-field, and this is an advantage of zero spherical aberration IOLs as is decreased impact of IOL decentration and pupil eccentricity.

Hyperopic LASIK induces negative spherical aberration and such patients benefit with traditional spherical IOLs. Negative spherical aberration IOLs benefit patients with previous myopic LASIK. They may also be better in patients with larger mesopic pupils and those with night-time driving.

MONOFOCAL IOLS: These aim to provide clear focus at a fixed distance, either near, intermediate or far, depending on the patient’s wishes, requirements and the visual acuity and refraction of the other eye.

Patients opting for monovision have one eye focussed for distance and one for near/intermediate by aiming for slight myopia. These patients should be given a monovision trial prior to surgery to check suitability.

Modified monovision refers to a similar use of accommodating or multifocal IOLs to combine the expanded range-of-vision offered by different multifocals. Micro-monovision aims at a very low level of myopia in the non-dominant eye.

TORIC IOLS: These correct both sphere and, depending on the manufacturer, variable degrees of astigmatism. In patients with high cylinder, it may need to be combined with LRIs to get full correction. Postoperative LASIK may be needed in some patients. Posterior corneal curvature plays an important role in avoiding post toric IOL surprises.

Accurate preoperative marking, correct alignment of IOL and complete removal of viscoelastic including under the IOL are vital.

Intraoperative aberrometer and limbal registration systems can help in making power and axis alignment much more accurate.

The right IOL design that prevents postoperative rotation should be chosen. Toric IOLs may be avoided in very large eyes with a higher chance of rotation. Multifocal and accommodative torics are also available.

CONCLUSION: Ultimately, a satisfied patient is one who is happy with the postoperative quality and range of vision that matches the patient’s expectations set by the surgeon preoperatively. Uncomplicated surgery with a round and appropriately sized rhexis, complete cortical removal and in-the-bag IOL placement should be aimed for. Bioptics in the form of postoperative LASIK/PRK may be needed for any residual refractive error.

Dr Soosan Jacob is Director and Chief of Dr Agarwal’s Refractive and Cornea Foundation at Dr Agarwal’s Eye Hospital, Chennai, India, and can be reached at: dr_soosanj@hotmail.com

MULTIFOCAL IOLS: These aim at decreasing patient dependency on glasses. They work on refractive, diffractive and apodization principles. Patient selection and education is a must. Patients should be warned of the possibility of glare, halos, decreased contrast, difficulty in night-time driving and the necessity to wear glasses for particular viewing conditions. Patients should be warned that it may take some time to get used to the new visual quality. Refractive lens exchange patients used to good quality vision may be less tolerant of multifocal IOLs than cataract patients.

Large or decentered pupil, poor IOL centration, large angle kappa (>5.2 on OrbscanII), irregular astigmatism or a significant amount of regular astigmatism, dry eyes, previous corneal refractive surgery and macular pathology can all contribute to suboptimal results. An IOL explantation may be required in unhappy patients.

Astigmatism control is important when implanting a multifocal, and a toric multifocal and/or simultaneous LRI may be required.

Scan these QR codes to view live surgeries

ACCOMMODATIVE IOLS: These attempt to mimic natural accommodation. Various IOLs include the CrystaLens®, Tetraflex®, Synchrony dual optic®, FluidVision® lens, DynaCurve® lens etc. Crystalline lens replacement with polymer as well as the Light Adjustable Lens® are other options. The basis of accommodative IOLs include anterior movement and steepening of the anterior surface of the IOL as a result of ciliary muscle contraction or anterior vaulting and axial movement of the IOL. These IOLs have less glare, halos and contrast sensitivity loss.

Disadvantages include inability to read minute print and changes secondary to bag fibrosis and posterior capsule opacification (PCO). Also, though their distance vision quality may be better than that of multifocals, near correction may not be as good. They may therefore require some micro-monovision or may be used with a multifocal in the other eye in suitable patients.

EXTENDED-RANGE-OF-VISION/ EXTENDED-DEPTH-OF-FOCUS IOLS: The EDOF IOLs use extended depth-of-focus to achieve near vision. Symfony® (AMO) uses spherical and chromatic aberration control as well as diffractive optic to expand a single focal zone as opposed to creating multiple foci. The EDOF small aperture IOL uses a small aperture principle similar to the Kamra® inlay.

aegean

summer school in Visual Optics

EUROTIMES | MAY 2016

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48

CALENDAR

Chicago

JUNE

SEPTEMBER

12th EGS Congress

12th JOI (Journées d’Ophtalmologie Interactives)

19–22 June Prague, Czech Republic www.eugs.org

↙

JULY

42nd Annual EPOS Meeting

Aegean Cornea 2016

LAST CALL

MAY 2016

Middle East Africa Council of Ophthalmology (MEACO) XIII International Congress 4–8 May Manama, Bahrain www.meaco.org

23–25 September Zurich, Switzerland www.epos-focus.org

1–3 July Crete, Greece www.ivo.gr/en/aegean-cornea/ meeting.html

114th DOG Congress

29 September–2 October Berlin, Germany http://dog2016.dog-kongress.de

XXXth Meeting of the Club Jules Gonin 6–9 July Bordeaux, France www.clubjulesgonin.com

46th ECLSO Congress (European Contact Lens Society of Ophthalmologists)

29th APACRS Annual Meeting

30 September–1 October Paris, France www.eclso.eu

27–30 July Nusa Dua, Bali www.apacrs.org

OCTOBER

AUGUST

NEW Echography Teaching Services – International Annual Course and Workshop on Diagnostic Ultrasound in Ophthalmology

ASCRS 2016

6–10 May New Orleans, USA www.ascrs.org 7–10 May Paris, France www.sfo.asso.fr/congres/congres-sfo-2016

CFSR (Club Francophone des Spécialistes de la Rétine) 8 May Paris, France www.cfsr-retine.com

29 August–2 September Munich, Germany www.echography.com

SEPTEMBER

16th EURETINA Congress

The European Association for Vision and Eye Research (EVER) Congress 2016 5–8 October Nice, France www.ever.be

8–11 September Copenhagen, Denmark www.euretina.org

15–18 October Chicago, USA www.aao.org

NOVEMBER

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

DECEMBER

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

FEBRUARY 2017

NEW 21st ESCRS Winter Meeting 10–12 February Maastricht, The Netherlands www.escrs.org

7th EuCornea Congress

14th SOI International Congress

OCTOBER

AAO 2016

ISOPT Clinical 2016

↙

SFO Congress 2016

18–21 May Milan, Italy www.congressisoi.com

23–24 September Toulouse, France www.joi-asso.fr

9–10 September Copenhagen, Denmark www.eucornea.org

XXXIV Congress of the ESCRS

10–14 September Copenhagen, Denmark www.escrs.org

EYE CONTACT

STUDIO INTERVIEWS with leading ophthalmologists EXCLUSIVE TO EUROTIMES! CICATRISING CONJUNCTIVITIS

Prof Harminder Dua interviews Prof John Dart Available at http://player.escrs.org/eurotimes-eye-contact and the EuroTimes App

Stressless.

It’s touchless.

SmartSurf ACE – the smoother way

SmartSurf ACE

SmartSurf ACE is an innovative surface ablation method that combines the benefits of touch-free TransPRK surface treatment with

• Gentle: No touch, no suction, no incision, no cut • Safe: High cornea stability • Stress-free: Faster treatment - in a single step

SmartPulse technology.

It works without touching the eye, so there is no blade, no flap and no

• Excellent clinical outcomes

incision, and the procedure results in a very smooth corneal surface

• Economical: Easy to use, time-saving, low investment

even right after surgery. Your patients will experience less discomfort and enjoy good vision sooner. Treatment is faster, and outcomes are excellent. It’s the smoother way to good vision.

SCHWIND eye-tech-solutions · fon: +49 6027 508-0 · email: info@eye-tech.net · www.schwind-smartsurf.com

Introducing Malyugin Ring 2.0 Nothing’s Changed... Except For Everything Less Compression Force

New Smaller Gauge Material

Easier Pupil Margin Placement

Increased Scroll Gap

New Smaller Cannula

Smaller Cannula means room to spare in incisions larger than 2.0 mm

When contemplating what the next version of the Malyugin Ring should provide surgeons and their patients, we established three goals: 1. Provide the same or better safety as surgeons have experienced and has made the Malyugin Ring “classic” the standard of care for pupil management.

2. Make it easier to place and remove from the pupil margin.

3. Allow for entry in 2.0mm incisions and more room in wounds larger than that.

After several years of work, we are proud to introduce the Malyugin Ring 2.0. The second generation of the Malyugin Ring that also can be used in 2.0mm incisions.

Mayugin Ring 2.0 requires no surgical technique changes for you, and we believe that you will find it easier to use, that you will appreciate the extra room it affords, and be glad to know that it has softer compression characteristics (in fact Malyugin Ring 2.0 exerts less than half as much pressure on the iris than the “classic” Malyugin Ring).

Malyugin Ring 2.0 Only from MST

Malyugin Ring 2.0 MST (MicroSurgical Technology), 8415 154th Avenue NE, Redmond, Washington 98052 425.861.4002 • 1.888.279.3323 • email: info@microsurgical.com • www.mst-surgical.com