EuroTimes Vol.19 - Issue 2 by EUROTIMES

VOLUME 19 ISSUE 2 FEBRUARY 2014

COVER STORY

AGEING EYES

Breathtaking Ecknauer+Schioch ASW

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february 2014 Volume 19 | Issue 2 This ISSUE... Cataract & Refractive 4

Cover Story: Ophthalmologists treating the elderly have many issues to face

Big obstacle to femto cataract surgery is cost

10 Good preliminary results recorded with micro-incision IOL 11 New IOL aims to optimise quality of vision for the Japanese eye 12 Future looks bright for femtosecond laser in cataract surgery 14 The future of cataract surgery 15 Long-term effect of orthokeratology uncertain

16 Clinical outcomes with multifocal lens positive, but expectations must be managed

Cornea 17 Expert discusses management of infectious keratitis 18 Surgical Management of Keratoconus meeting unearths conflicting findings 19 Technology valuable for obtaining cornea measurements in LASIK patients 20 CMV infection must be considered prior to endotheliitis diagnosis 21 Bilateral keratoprosthesis implantation not without controversy 22 Reinforcing the cornea with carbon nanomaterials 23 Prevention seems to be the best intervention for HZO 24 Despite increase in cases, outcomes for patients affected by parasitic infection improving 25 How causes of incomplete visual rehabilitation after DMEK can be treated

Glaucoma

26 Evidence for the cerebrospinal fluid pressure theory 27 Are newer technologies in tonometry necessary? 28 Many patients could benefit from using preservative-free eye drops 29 Device generating excitement to potentially manage disease

Retina 30 Will geographic atrophy be treatable by 2020? 31 Adaptive optics may pave the way to better management of retinal pathologies 32 Trial shows biologic agent may effectively slow geographic atrophy progression 33 New diagnostic tools help to modify the management of retinal diseases 34 Genetic risk assessment provides important guidance for treatment decisions 36 Novel device showing promise in treating exudative AMD patients

Paediatric Ophthalmology

37 editorial staff

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Published by The European Society of Cataract and Refractive Surgeons Publisher Carol Fitzpatrick

Managing Editor Caroline Brick

Executive Editor Colin Kerr

Production Editor Angela Sweetman

Editors Sean Henahan Paul McGinn

Advertising Executive Mairin Condon Senior Designer Janice Robb

Designer Lara Fitzgibbon Circulation Manager Angela Morrissey Contributing Editors Howard Larkin Dermot McGrath Roibeard Ó hÉineacháin Contributors Devon Schuyler Eisele Stefanie Petrou-Binder Maryalicia Post

37 Femtosecond lasers becoming useful tools in some paediatric surgeries

Features 38 Journal Watch 41 JCRS Highlights 42 Ophthalmologica Highlights 43 Industry News 44 Calendar of Events

Leigh Spielberg Pippa Wysong Gearóid Tuohy Priscilla Lynch Colour and Print W&G Baird Printers Advertising Sales ESCRS, Temple House, Temple Road Blackrock, Co. Dublin, Ireland Tel: 353 1 209 1100 Fax: 353 1 209 1112 email: escrs@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

As certified by ABC, the EuroTimes average net circulation for the 11 issues distributed between 01 January 2012 and 31 December 2012 is 37,563.

EUROTIMES

Editorial

ESCRS

GUEST EDITORIAL

Medical Editors

Volume 19 | Issue 2

José Güell

Ioannis Pallikaris

Clive Peckar

Paul Rosen

AN EXCELLENT PROGRAMME

18th ESCRS Winter Meeting convenes in Ljubljana, Slovenia

by Vladimir Pfeifer

International Editorial Board

n behalf of the Slovenian Society of Cataract and Refractive Surgeons, I would like to welcome delegates to the 18th ESCRS Winter Meeting in Ljubljana. The ESCRS Winter Meeting is one of the highlights of the ophthalmology year and this meeting has an excellent programme. The full meeting agenda is available on the ESCRS website at www.escrs.org, but let me talk you through some of the highlights. The Annual Cornea Day, organised by ESCRS and EuCornea, takes place on Friday 14 February. The session will be chaired by the EuCornea president Dr José Güell and Rudy Nuijts, treasurer of the ESCRS. There will be keynote lectures and case presentations on a number of important topics. These topics include management of corneal complications after refractive surgery, tips and pitfalls in corneal graft surgery, ocular surface disease and miscellaneous cases including corneal inflammation, degeneration and infections. Friday is also an important day for young ophthalmologists with the Young Ophthalmologists Programme, chaired by Oliver Findl, Austria; Simone Morselli, Italy; and Kaarina Vannas, Finland. This three-hour programme is aimed specifically at ophthalmologists in training and will highlight several topics that will recur throughout the meeting. On Saturday, the Slovenian Society of Cataract and Refractive Surgeons will host Live Surgery which will be transmitted from the University Medical Centre, University Eye Hospital, Ljubljana. I am also pleased to announce that the Slovenian Society’s symposium on Sunday, the last day of the meeting, will have simultaneous translation from Slovenian to English. The symposia held during the meeting always attract large attendances and we look forward to lively presentations on Enhancements in Pseudophakia, Applications of the Femtosecond Laser, an Update on Endophthalmitis and a special symposium on The Perfect Phaco which will be organised by the Young Ophthalmologists Committee.

Emanuel Rosen Chairman ESCRS Publications Committee

Noel Alpins australia There are also a number of important courses including courses in Basic Optics, a Cataract Surgery Didactic Course, a Refractive Surgery Didactic Course and a Cornea Didactic Course. For those delegates who wish to see the sights of Ljubljana we have many beautiful attractions. I recommend that delegates should visit the National Museum of Contemporary History and the City Museum of Ljubljana. The city’s river bands are also very beautiful and visitors will get a chance to see the wonderful work of Ljubljana’s celebrated architect, Joze Plecnik. Of course, there is much more to see and even at a time when the weather may be cold, I urge you to take a walk through our beautiful city and enjoy the clean fresh air of Ljubljana

Bekir Aslan TURKEY Bill Aylward UK 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 Vikentia Katsanevaki GREECE Thomas Kohnen GERMANY Anastasios Konstas GREECE Dennis Lam HONG KONG

Vladimir Pfeifer

contact

Vladimir Pfeifer – pfeifer@pfeifer.si

Boris Malyugin RUSSIA Marguerite McDonald USA Cyres Mehta INDIA Thomas Neuhann GERMANY Rudy Nuijts THE NETHERLANDS

NEW ESCRS CEO

arol Fitzpatrick has been appointed chief executive officer of the European Society of Cataract and Refractive Surgeons with effect from January 1, 2014. Carol, who has worked with ESCRS since 1993 and has been deputy CEO since 2011,

EUROTIMES | Volume 19 | Issue 2

succeeds Mary D’Ardis who has retired after serving as CEO since 1998. Mary will retain her position as managing director of Agenda Communications. “It is a great honour and privilege to accept this position,” said Carol, “and I look forward to working with the Board, Executive and members of ESCRS in consolidating ESCRS’s position as the leading ophthalmology society in Europe. I would like to extend my best wishes to my good friend and colleague, Mary D’Ardis, who is stepping down as CEO after 15 years. Mary’s tenure as CEO was pivotal to the success of ESCRS.”

Gisbert Richard GERMANY Robert Stegmann SOUTH AFRICA Ulf Stenevi SWEDEN Emrullah Tasindi TURKEY Marie-Jose Tassignon BELGIUM Manfred Tetz GERMANY Carlo Enrico Traverso ITALY Roberto Zaldivar ARGENTINA Oliver Zeitz germany

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B I - F L E X P L AT F O R M BY MEDICONTUR

MICRO IN CIS ION CATARACT S URGE RY

Cover Story

Cataract & refractive

AGEING EYES

Ophthalmologists on the front lines are battling age-related public health issues by Sean Henahan

“

It is always a good idea to recommend that elderly patients upgrade their lighting conditions for reading and cooking and to get a night lamp in their bedroom so they can see the floor when getting up during night Mats Lundstrom MD

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It is important to measure patient satisfaction. You can do this very simply by asking the patients how happy they are with the outcomes of their operations Konrad Pesudovs

EUROTIMES | Volume 19 | Issue 2

he general global demographic shift in the US, Europe and Asia means that the number of cases of agerelated vision problems and agerelated dementia are both growing to near epidemic proportions. Ophthalmologists, whose patients are often elderly, increasingly have to play the part of neurologist, geriatrician and psychiatrist, in addition to helping with traditional eye care issues. The statistics are daunting. Thanks to increased life expectancy and the baby boomer population bubble, by the year 2030 the population of adults over 65 years of age is expected to double in the developed world, comprising 20 per cent of the total population. The US National Eye Institute estimates that 25 per cent of people over the age of 65 would be expected to develop cataracts. That number surpasses 50 per cent in those aged 80 years of age and older. Two per cent of 65-year-olds will have glaucoma, a number that will also double by age 80. Agerelated macular disease is believed to affect approximately 10 per cent of people over the age of 65, with the number climbing sharply with the years. With advancing years patients are at risk for developing slowly decreasing vision because of eye diseases and ageing of the visual system, notes Mats Lundstrom MD, adj. professor emeritus, Department of Clinical Sciences, Ophthalmology, Faculty of Medicine, Lund University, Sweden. “This gradual change in vision is usually not accompanied by relevant changes in home lighting conditions. Elderly patients typically go on reading the newspaper in too weak light and do not make proper arrangements in their bedroom. It is always a good idea to recommend that elderly patients upgrade their lighting conditions for reading and cooking and to get a night lamp in their bedroom so they can see the floor when getting up during night,” he suggested. The benefits of cataract surgery are well established. With improved vision comes

7341 patients that achieved 20/20 vision after cataract surgery

Courtesy of Mats Lundstrom MD

Patients’ self-assessed visual ability to perform daily life activities separated in ‘Near’ vision activities and ‘Distance’ vision activities. Blue bars: before surgery; red bars: after surgery. Patients with poorer ability after surgery than before = ‘No benefit’. Patients with better ability after surgery = ‘Benefit’. Note that in the ‘No benefit’ group the ability before surgery was good and after surgery the deterioration was most pronounced for near vision activities

significant improvement in functional ability, cognitive function and overall quality of life. Two recent studies indicate, for example, that patients undergoing cataract surgery appear to have a reduced risk of fall-associated hip fractures, as well as a lower chance of getting into an automobile accident. However, recent research suggests there may be a disconnect between what benefits surgeons think patients are experiencing versus what patients actually believe. Research by Drs Mats Lundström and Ulf Stenevi reveals some surprising findings in this regard. Prof Lundström is the clinical director of the European Registry of Quality Outcomes in Refractive Surgery. Dr Stenevi is professor and chair, Department of Ophthalmology, University of Gothenburg, Sweden, and past president of the ESCRS. Having observed that clinical and patientreported outcomes sometimes diverge, the Swedish researchers designed a study to

evaluate how patient-reported outcome measures could be connected to clinical outcome measures in cataract surgery. They looked at follow-up data from the massive Swedish National Cataract Register on more than 10,000 patients that underwent cataract extractions from 2008 to 2011.

Patient unhappiness The principal divergence was associated with patient unhappiness with poor near vision after surgery, in spite of an otherwise good clinical outcome. Other factors related to poor patient-reported outcomes after surgery included good preoperative selfassessed visual function, poor preoperative visual acuity in the better eye, postoperative astigmatism, ocular co-morbidity, surgical complications and large refractive deviation. “These findings indicate that some patients are too healthy and some too sick to benefit from cataract surgery. It is possible that

Patients with dementia? With evidence indicating that the incidence of dementia doubles every five years from ages 65 to 90 years, and the number of “old old’ EUROTIMES | Volume 19 | Issue 2

Courtesy of Mats Lundstrom MD

patients who are very satisfied with their vision and have no problems in performing daily life activities should not have cataract surgery at present," the researchers note. “Cataract surgery patients want good vision at all distances. This means comfortable near vision and distance vision. Specifically we need to be sure that patients with good near vision before surgery also get good near vision after surgery. If the postoperative refraction means glasses for near vision we must inform and advise the patient about this. It usually means a follow up visit after surgery. This is the responsibility of the surgeon so we can answer the most important question in healthcare: What happened to the patient?” Prof Lundström told EuroTimes. The findings add further support to the growing consensus that Snellen visual acuity testing is, by itself, an inadequate measure of visual outcome following surgery. They propose using patient reported outcomes as a measure of success in cataract surgery using instruments such as the Catquest-9SF questionnaire, with the goal of improving cataract surgery outcomes. “It is important to measure patient satisfaction. You can do this very simply by asking the patients how happy they are with the outcomes of their operations. Satisfaction rates are typically very high, around 95 per cent. It is the five per cent that you really want to know about, because that is where you can affect your care, for example not selecting patients who have very little visual disability to begin with, or some miscommunication about the need for reading glasses afterwards. You can identify patterns and possibly modify what you do,” Konrad Pesudovs told EuroTimes in a podcast interview. Prof Pesudovs is the foundation professor of optometry and vision science at Flinders University in Adelaide, South Australia. A recent study from Australia raises further potential issues cataract surgeons might want to discuss with patients. That study suggested a possible problem with patient safety following cataract surgery, between the time the first and second operations take place. (Age and Ageing, LB Meuleners et al., (2013) doi: 10.1093/ageing/ aft177.) The researchers assessed the risk of an injury due to a fall among 28,396 patients over the age of 60, looking at the periods two years before first-eye cataract surgery, between first-eye surgery and second-eye surgery, and two years after second-eye surgery. Patients waited an average of 10 months between first and second surgery. That study found that the risk of an injurious fall that required hospitalisation doubled between the first- and second-eye cataract surgery compared with the two years before first-eye surgery. The study also revealed a 34 per cent increase in the number of serious falls in the two years after second-eye cataract surgery compared with the two years before first-eye surgery. The researchers believe this may be related to differences in vision between the operated and unoperated eyes. They suggest surgeons provide appropriate refractive management between surgeries.

‘Cataract patients want good vision at all distances’

patients increasing around the world, the disease is now being labelled an epidemic. (EB Larson et al, N Engl J Med 2013; 369:2275-2277.) Ophthalmologists are on the front lines in this public health battle. Nowhere is this more apparent than when the question of driving comes up. Questions of public safety collide with issues of patient confidentiality. While assessing the patient, a history and physical may well reveal clues to potential unsafe driving. In some areas clinicians may risk legal liability for not reporting a potentially dangerous driver, while at the same time upsetting the doctor-patient relationship and facing potential liability for violating privacy rules. Consider the case of a patient, an 82-year old woman undergoing a routine eye examination, which revealed good visual acuity and no evidence of other eye disease. However, family members informed the ophthalmologist that the woman was in the early stages of Alzheimer’s disease and was showing considerable memory loss and trouble concentrating. Moreover, she had recently been involved in a series of minor accidents in her neighbourhood. The family members wanted the woman to stop driving, something the strong-willed patient refused to consider. “You have two ways to go with a case like this,” Louis Kartsonis MD, a general ophthalmologist in San Diego, California, US told EuroTimes. “One, you could say my job as an ophthalmologist is vision care, and my responsibility stops with evaluating the status of vision. But we have to recognise a larger picture, particularly in a case where driving accidents have already occurred. If there is an element of dementia, you want to talk to the family and say we need to take some steps.” One approach would be to immediately refer the patient to a neurologist for an evaluation of mental status, looking at the

“One approach would be to immediately refer the patient to a neurologist for an evaluation of mental status, looking at the ability to do the things required in daily life including driving” Louis Kartsonis MD

ability to do the things required in daily life including driving. One could also ask the family to have the patient take a driving test by an independent firm to see if the patient is safe on the road. “However, in a case like this, where you have a history of accidents, you need to be proactive. You can’t just concentrate on the eyes. You have to realise your larger sphere of responsibility as a physician, not just an eye specialist. This patient was clearly a potential risk to herself and others,” emphasised Dr Kartsonis. In this case, Dr Kartsonis followed a protocol common in the State of California, This involved filing a report with the Department of Motor Vehicles (DMV) questioning the patient’s fitness to drive. This triggers a sequence of events. The patient receives a letter from the DMV informing them that their license will be suspended. They are required to appear for a hearing test, a vision test, a written test and a driving test. In this case the patient passed the vision test, but failed both the written test and the driving test. Her license

was suspended permanently and she no longer drives. These cases are really difficult, as they alter the doctor-patient relationship, notes Dr Kartsonis. Patients from the World War II generation are particularly strong-willed and treasure their freedom. You may have had a long-term relationship with a patient who now may become angry and feel betrayed. “I tell the patient what I am going to do. She has a right to know. I’ll explain my concerns. I tell the patient exactly what I’m going to do, so it doesn’t look to them like I’m going behind their back. I then discuss it with the family. Then I’ll do some simple things to verify if there is an element of dementia. I’ll ask what year it is; who the president of the United States is, simple things like that. If I do simple screening and the patient breaks down, I tell them I have to make contact with government agencies about their health, because they’ve had this history, and they are showing signs that could signal trouble in the future,” he explained. He stressed the physician, in order to protect himself from legal liability, must also strictly document the discussion in his records, and must follow up. This would include noting that the discussion took place, a neurology examination was recommended, along with a driving test. If follow-up indicates that these steps have not been taken, the next step is informing the DMV. “When the patients are put through this, they don’t like it. But if they fail in the physical, mental, visual component, they at least recognise that the physician and family members have done everything they can to give them a chance to not fail.” George HH Beiko MD, assistant clinical professor of ophthalmology at McMaster University, Ontario, Canada, has written in the past about the problems of driving,

Cover Story

Cataract & refractive

The Power of Colour ToPograPhy

“

I would inform a spouse or family member of my concerns regarding the patient’s cognitive ability and advise them to restrict or prevent driving until proper assessment by the patient’s own family doctor George HH Beiko MD

vision and the elderly. Agreeing about the emotional difficulty such cases present, he concurred with Dr Kartsonis. “I would inform a spouse or family member of my concerns regarding the patient's cognitive ability and advise them to restrict or prevent driving until proper assessment by the patient's own family doctor. If the patient appeared to be unlikely to follow this advice, then I would report him directly to the Ministry of Transport. My experience has been that the spouse or family members have usually already had their own concerns and will intervene to prevent driving until the family doctor assesses the patient,” Dr Beiko said. There are some brief, simple cognition tests that a concerned ophthalmologist can conduct in the office setting. This would include trail making, where the patient is asked to draw lines connecting a series of letters and numbers, and the clock drawing test. This latter test is a favourite quick test to evaluate cognition. The patient is asked to draw a simple clock face, drawing in all of the hours and then setting the hands at five minutes before two o’clock. People who may otherwise appear cognitively intact on a conversation level, most often cannot complete this simple evaluation. Both Dr Beiko and Dr Kartsonis would consider allowing an older patient who is cognitively sound to return to driving following cataract surgery. “I would counsel the patient to restart driving when they felt they were ready to do so. I remind them that being legally fit for driving and being capable of driving are two different things. If they are confident in their driving abilities and have considerable previous experience driving, they are likely to start right away; however, if they rarely drove before, I would suggest that they start with short drives during off hours. High-speed, highway driving should be considered only once the patient is mentally set for this.” However, this advice might not extend to a mentally acute patient who shows some signs of being physically diminished. This might include a patient who appears in the office to be slow moving, can't turn his head, can't walk well, who is somnolent or

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obviously frail. A quick in-office evaluation could include testing the ability to walk 20 feet in nine seconds, showing good limb flexion and extension, and adequate strength and range of motion of neck, shoulders, trunk and arms. “I would inform that patient that although his vision is adequate for driving, I still have concerns regarding his physical ability to do so. I would tell him that I would be asking his family doctor to reassess him and to address my concerns regarding his physical limitations and that I would be informing the Ministry of Transport, as I am legally required to do, of my concerns,” Dr Beiko told EuroTimes. Because Snellen testing fails to measure patients' vision in real-world conditions, particularly in terms of contrast sensitivity and glare, Dr Beiko believes changes in driver assessment at the national level would be an important step to improving public safety. “Straylight testing has been advocated by European organisations as a means of assessing disability glare, and I strongly agree with this. Patients may have good visual acuity and full visual fields, and yet be impaired by disability glare. It has been found that although visual acuity may be decreased in 5.3 per cent of elderly patients, up to almost 30 per cent may be impacted by increased disability glare. Disability glare has been implicated in the causation of motor vehicle accidents.”

Resuming driving Ultimately, this testing could also be a good indicator of the necessity for cataract surgery, after which some patients might expect to regain vision to again resume driving. Patients may need some convincing, notes Dr Kartsonis. “If you have a patient that is far enough along that it is reasonable to consider cataract surgery, they will often defer. They don't want to have surgery, even thought the technology is wonderful, it can restore eyesight to that of a young person. You have to be patient. Learn how to convince patients that they have access to a technological world that is far different than what they grew up with. Then when patients ask if it is safe to resume driving following cataract surgery, as long as the patient is cognitively sound and physically able, I tell them to go ahead and get tested, and if that goes well, go for it!”

contacts Mats Lundstrom – mats.lundstrom@karlskrona.mail.telia.com Ulf Stenevi – ulf.stenevi@oft.gu.se Konrad Pesudovs – konrad.pesudovs@flinders.edu.au Louis Kartsonis – DartmouthMan@mol.net George Beiko – georgebeiko@hotmail.com

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Cataract & refractive

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Update

FEMTO CATARACT FOR ALL

The laser is still surgery. It looks smart like a smart phone but you are still cutting and you are changing the anatomy of the eye. I see no appropriate education in the nurse compared with the medical doctor

by Howard Larkin

n 2010 and 2011, early clinical reports convinced Shachar Tauber MD that femtosecond laser-assisted cataract surgery would improve outcomes and reduce complications. But he also believed the technology should be available to all patients – not just those who can pay extra. “If we accept the premise that femtosecond laser surgery is better for the patient, then it’s the right thing to do for all patients,” said Dr Tauber, who is ophthalmology section chair for Mercy Clinic, a multispecialty medical group affiliated with Mercy health system, which operates 32 hospitals and 300 outpatient clinics serving three million people in four south-central US states. Despite equipment costs approaching $1m, Mercy managers signed on to the all-patient approach because it supported the system’s charitable mission. In March, Mercy opened its new eye and ear clinic in Springfield, Missouri, featuring two cataract surgery suites equipped with Catalys femtosecond laser systems (OptiMedica). Eight months and 2,296 cataract cases later, it’s well on its way to breaking even, without charging a penny extra – even though more than 60 per cent of patients are covered by public insurance. It may be the first clinic in the world to offer femtocataract for all at no extra charge. Mercy’s financial strength, as well as its expertise in purchasing, process engineering and management, were critical in making it financially possible. That the US Medicare program pays hospitals more than freestanding surgery centres didn’t hurt, either. But as the benefits of femto-cataract surgery, particularly in complicated cases, become clearer, a few surgeons around the world are finding a way to pay, and embracing it as their standard procedure. They believe that costs will eventually come down, and a combination of public and legal pressures could soon make femto-cataract the standard.

Expanding indications Femtocataract laser manufacturers still recommend excluding most complicated cases. But in the real world, cataract patients are mostly old, and many have co-morbidities, H Burkhard Dick MD, PhD told the annual symposium of the American EUROTIMES | Volume 19 | Issue 2

Shachar Tauber and Johann Ohly – sonya.kullmann@mercy.net Burkhard Dick – burkhard.dick@kk-bochum.de Gerd U Auffarth – gerd.auffarth@med.uni-heidelberg.de Mark Cherny – markcherny@cataract.com.au

“

As indications broaden, surgeons take on the big obstacle – cost

H Burkhard Dick MD, PhD

Courtesy of Mark Cherny MD

Catalys treatment planning screen with Malyugin ring in situ

“If we accept the premise that femtosecond laser surgery is better for the patient, then it’s the right thing to do for all patients” Shachar Tauber MD

Society of Cataract and Refractive Surgery in San Francisco. So with Ethics Committee approval, Dr Dick conducted a prospective controlled study comparing safety and outcomes of femto-cataract surgery in complicated patients with a conventional phaco control group at his University Eye Hospital clinic in Bochum, Germany. Out of 850 consecutive cataract cases, 26 per cent had some co-morbidity, including 91 on anti-coagulants, and 62 with floppy iris syndrome, 55 with corneal guttata, 53 with glaucoma, 40 with small pupils, 38 with pseudoexfoliation and 32 cases of mature cataracts. Among these, seven capsulotomy tags were seen, five in small pupil cases and two in mature cataracts, of which one resulted in an extension. Nine patients on anti-coagulants had minimal conjunctival alterations or conjunctival haemorrhage. No complications were seen in glaucoma patients.

“With standard phaco technique we would expect higher complication rates,” Dr Dick noted. Overall for the 850 cases, 99 per cent of capsulotomies were complete, Dr Dick reported. Effective phaco time was reduced 96 per cent overall, with a 100 per cent reduction in LOCS III grade 2, 98 per cent reduction in grade 3 and 95 per cent reduction in grade 4 using a Stellaris phaco machine. Dr Dick also noted a trend towards less phaco over time. Looking at his entire experience with femto-cataract, he used phaco in 59 per cent of his second 200 cases, but in just nine per cent in cases 1,200 to 1,400, with comparable mean cataract grades. “In my last 100 cases I didn’t need phaco in 97 per cent of cases.” Less phaco is associated with less endothelial cell damage, less corneal oedema, less inflammation and quicker

vision recovery. Dr Dick is currently conducting a contralateral eye study to quantify these effects, but has observed the benefits clinically in patients at risk of corneal decompensation, including those with small pupils, loose zonules, Fuchs' Dystrophy and cornea guttata. Other surgeons report similar results. In a study of 27 eyes in 26 patients, comparing complicated and uncomplicated cases undergoing femto-cataract surgery, Gerd U Auffarth MD, Heidelberg, Germany, reported three cases of transient corneal oedema as well as one case of subconjunctival bleeding in a patient on anti-coagulants and one posterior capsule tear at the end of phaco in a patient with pseudoexfoliation out of 11 patients with hard cataracts and other anterior segment pathologies. “Complicated cases are suitable for laser refractive cataract surgery. The complication rate is not zero but it is low,” he told the ASCRS symposium. Johann Ohly MD, a glaucoma specialist at Mercy, also believes femto-cataract surgery is easier on delicate eyes. In six months he has operated several eyes with Fuchs' Dystrophy with endothelial cell counts in the 1,400 to 1,500 range, and so far all have been successful with none requiring subsequent transplant. Safety is the major reason Mark Cherny MD, Melbourne, Australia, uses femtocataract for all his cases. “Just about every complication can be reduced in theory. After 700 cases, my own observation is cases go smoother and there is greater consistency in handling difficult cases. It makes every surgery better.”

Paying for it But cost remains a significant obstacle to making femtocataract available to all. Including the laser, maintenance, a technician to run the laser, per-case consumables and longer surgery times, Dr Cherny said it adds $800 to $1,000 to his costs, with consumables alone making up $400 to $500. A 2013 survey of more than 200 surgeons by market researcher SM2 Strategic found

Cataract & refractive

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Complicated cases are suitable for laser refractive cataract surgery. The complication rate is not zero but it is low Gerd U Auffarth MD

Catalys OCT image, treatment design and cross-sectional view of Malyugin ring in situ

Catalys image following octant segmentation, and lens softening, with Malyugin ring in situ

Johann Ohly MD, a glaucoma specialist at Mercy, also believes femto-cataract surgery is easier on delicate eyes. In six months he has operated several eyes with Fuchs’ Dystrophy with endothelial cell counts in the 1,400 to 1,500 range, and so far all have been successful with none requiring subsequent transplant. they charged an average of $1,058 more per case for femtosecond laser surgery with conventional IOLs, which would require about five years to break even doing 19 cases per month.

Don’t Miss

Calendar of Events, see page 44

EUROTIMES | Volume 19 | Issue 2

With cataract surgery already highly successful, justifying the extra cost is a hard sell for the cash-strapped publicly funded systems. Currently, surgeons’ ability to bring it to the masses depends on local

reimbursement rules and their own capacity to work within them. For Dr Dick, public payment restrictions are not an issue because he operates a private clinic. Under Australian rules, Dr Cherny bills patients $300 extra for femtocataract to cover consumables, absorbing the rest of the cost in his professional fee. Under US rules, Mercy breaks even on femto-cataract without charging patients extra. However, as a hospital-owned facility, it has advantages. On average, the US Medicare system paid hospital-based clinics $740 more per case in 2011 than it did free-standing ambulatory surgery centres or ASCs, of which $306 was paid out-of-pocket by patients, according to MedPac, which advises the US Congress. These higher payments are intended to offset higher costs in hospitals for standby emergency services and higher average patient acuity. Still, the list price for femto-cataract was beyond what Mercy could absorb when Dr Tauber first investigated it in late 2011. But working with system managers, he figured with a volume target of 4,000 cases annually, he could negotiate discounts and improve workflow efficiency enough to break even. With its expertise in purchasing, Mercy approached several laser providers with its concept, and OptiMedica responded with a workable offer, Dr Tauber said. Mercy’s five cataract surgeons also standardised anaesthesia, IOLs and OVDs, and obtained volume discounts that further reduced costs, and eliminated now-unneeded items including some disposable knives. Initially, femto-laser added about seven minutes to surgical times that had run nine to 10 minutes – more than anticipated. Over three months, this was trimmed three to four minutes with help from Mercy analysts trained in techniques such as SixSigma. Surgeons who had cut back to 12 cases a day are back to 16. Kevin Rash, Mercy’s vice president of operations for surgery services, is satisfied with the financial progress. “I’m not losing any sleep over it.”

New standard of care? Femtocataract is also a hit with patients. Before he received his laser, Dr Cherny gave patients the option of delaying surgery.

“

Just about every complication can be reduced in theory. After 700 cases, my own observation is cases go smoother and there is greater consistency in handling difficult cases. It makes every surgery better Mark Cherny MD

Despite the anticipated extra charge, many did, and he had a two-month waiting list when the machine arrived. Mercy is having no problem increasing its volume, Dr Tauber said. Continuing medical education for optometrists and its extensive primary care network is building referrals, while consumer outreach has created a buzz. Dr Cherny believes femto-cataract will become the standard of care. “Once it’s accepted that the laser adds safety, you will have to counsel patients that it is available as an option. All it will take is one malpractice case where the laser wasn’t used.” Many believe femto-cataract will become more affordable. “The cost will come down, but it will take time,” Dr Dick said. The technology may also have the potential to “de-skill” cataract surgery. Some managers in the UK National Health Service, where ophthalmic nurse practitioners already perform Nd:YAG laser capsulotomy and minor surgery such as chalazia, have already toyed with the idea of nurse-led cataract surgery, according to Oliver Findl MD, Vienna, Austria. But Dr Dick discounts the possibility. “The laser is still surgery. It looks smart like a smart phone but you are still cutting and you are changing the anatomy of the eye. I see no appropriate education in the nurse compared with the medical doctor.” Still, the technology’s complexity is likely to change cataract practice, Dr Cherny said. Surgeons likely will need to band together to share laser system expenses. “As [ASCRS President] Eric Donnenfeld said, we can no longer afford underutilised surgery centres.” Femto-cataract already has affected referral patterns in his community, and not all his colleagues are happy to see it, Dr Cherny added. “This is a very disruptive technology, but it is here to stay because of the precision it gives to surgeons, and the safety it gives to patients.”

Cataract & refractive

contacts

Update

David Spalton – dspalton@hotmail.com H Burkhard Dick – dickburkhard@aol.com Gilles Lesieur – g.lesieur@centre-iridis.fr Björn Johansson – bjorn.johansson@lio.se

NEW HYDROPHILIC MATERIAL

Micro-incision IOL has sharper edge than other hydrophilic lenses by Roibeard O’hEineachain

new hydrophilic acrylic micro-incision IOL is easily implanted though a sub-2.0mm incision and provides good predictable visual outcomes with good centration and possibly better protection against PCO than other hydrophilic acrylic lenses, according to a series of presentations at the XXXI Congress of the ESCRS in Amsterdam. The new lens, called the Incise® (Bausch + Lomb) is a customised version of the Akreos MI60 IOL and, like the older lens, is a one-piece aberration-neutral aspheric IOL with four angulated haptics. However, unlike the Akreos, it is composed of a new, stiffer material with 22 per cent water content and it has an optic edge that is sharper than that of many hydrophobic IOLs. “There is some evidence that the poorer posterior edge characteristics of hydrophilic IOLs is to blame for their poorer PCO performance in comparison to hydrophobic IOLs. The Incise IOL is designed to have enhanced PCO prevention performance,” said David Spalton FRCS, FRCP, FRCOphth, St Thomas' Hospital, London, UK. He noted that environmental scanning electron microscopy imaging of the IOL's profile at the optic edge and optic-haptic junction revealed that the IOL has an extremely sharp high-quality edge profile with a local radius of curvature of 5.0 microns throughout its periphery. “That is a really high-quality edge which would be expected to confer excellent PCO prevention. Clinical studies are required now to confirm this,” Dr Spalton added.

Good preliminary results

In a prospective clinical trial carried out in five European centres, implantation of the lens through a sub-2.0mm incision resulted in very satisfactory visual and refractive outcomes, said Burkhard Dick MD, Ruhr University Eye Hospital Bochum, Germany. Among 70 eyes with four to six months of follow-up in the trial, mean uncorrected visual acuity was 0.13 LogMAR (20/25) and mean corrected distance visual acuity was -0.03 LogMAR (20/20) and 97.1 per cent were 20/25 or better.

“

There is some evidence that the poorer posterior edge characteristics of hydrophilic IOLs is to blame for their poorer PCO performance in comparison to hydrophobic IOLs. The Incise IOL is designed to have enhanced PCO prevention performance

Courtesy of Gilles Lesieur MD

David Spalton FRCS, FRCP, FRCOphth

In addition, mean manifest refraction spherical equivalent was -0.22 D, compared to a target refraction of -0.25 D. Furthermore, 57 per cent were within 0.50 D of target refraction, 90 per cent were within 0.5 D and all were within 1.0 D. Dr Dick noted that patients in the study underwent either coaxial MICS with a 1.8mm incision or biaxial MICS with a 1.4mm incision and a wound-assisted implantation technique. In an additional investigation of patients in the study, digital slit-lamp biomicrosopy imaging after seven to 15 days postoperatively, after one to two months and four to six months postoperatively showed that centration was predictable and stable, said Gilles Lesieur MD, Albi, France. The absolute mean decentration was 0.31mm after seven to 15 days and 0.35mm, after one to two months and four to six months. That compares to mean decentrations of 0.2mm to 0.6mm for conventional one-piece and threepiece IOLs, he said.

“

In an additional investigation of patients in the study, digital slitlamp biomicrosopy imaging after seven to 15 days postoperatively, after one to two months and four to six months postoperatively showed that centration was predictable and stable Gilles Lesieur MD

Another study (carried out at St Eriks Eye Hospital, Stockholm) involving 60 of the 100 patients in the prospective trial examined the size of the incision used for implantation of the IOL with the injector tip inside the eye in coaxial MICS procedures. After insertion of the lens the incision size increased on average by 0.08mm, said Bjorn Johansson MD, PhD, Sweden.

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Update

Cataract & refractive

IOL ADVANCES

New version of single-piece implant aims to optimise outcomes with “customised” asphericity by Cheryl Guttman Krader

novel one-piece hydrophobic acrylic IOL featuring an aspheric design customised for Japanese eyes (W-60; Eternity Natural Uni, Santen) is safe and provides excellent visual and refractive outcomes after cataract surgery, reported ophthalmologists from Toho University School of Medicine, Tokyo, Japan, at the 26th Asia-Pacific Association of Cataract & Refractive Surgeons Annual Meeting in Singapore. The IOL optic is constructed of the same material found in the Eternity IOL (Santen), which was first marketed in Japan in 2008, and contains a blue lightfiltering chromophore. The optic measures 6.0mm in diameter, and based on Japanese population-specific spherical aberration (SA) data, it has -0.13 microns SA at the corneal plane. “The asphericity of the Eternity Natural Uni is designed to optimise quality of vision for the Japanese eye. It was chosen to achieve a total ocular SA of +0.1 microns, which represents the average for a 25-year-old Japanese person, and takes into account that the corneal SA in Japanese eyes averages +0.23 microns throughout adult life,” explained Nanae Yamazaki and Shinichiro Kobayakawa MD, PhD, Department of Ophthalmology, Toho University.

Dedicated injector system Results after implantation of the Eternity Natural Uni IOL were analysed in a retrospective review of data from 106 consecutive eyes of 86 patients, of which 72 eyes were seen at three months. All surgeries were performed through a 2.8mm sclerocorneal incision with implantation of the IOL into the capsular bag using a dedicated injector system (Accuject UniFit, Santen). Mean SA was -0.21 ± 0.91 microns preoperatively, 0.029 ± 0.03 at one month, and -0.03 ± 0.24 microns at three months. Mean logMAR BCVA was 0.28 ± 0.64 preoperatively and 0.014 ± 0.24 at three months. Mean postoperative refractive error improved during early follow-up from -0.73 ±0.76 D at one week (100 eyes) to -0.46 ± 0.69 D at three months. The achieved

“The asphericity of the Eternity Natural Uni is designed to optimise quality of vision for the Japanese eye” refractive outcome at three months was ±1.0 D of intended in 82 per cent of eyes, ±0.50 D in 43 per cent, and ±0.25 D in 19 per cent. The back-calculated A constant was 118.9 compared with the manufacturer’s recommended value of 119.1 that was used for selecting IOL power in this initial cohort.

Excellent clarity There were no problems with IOL stability, clarity or posterior capsule opacification (PCO) in the series. “The hydrophobic acrylic material used in the Eternity Natural Uni IOL was developed by Advanced Vision Science, a Santen company, and through a licensing agreement and is also found in the enVista IOL (Bausch + Lomb) in markets outside of Japan. Clinical experience with this material over the past five years together with findings from animal studies establish that it has advantages for being glisteningsfree and maintaining excellent clarity longterm,” said Dr Kobayakawa. He added that the Eternity Natural Uni lens has an advanced haptic design that maintains positional stability, and it was designed with features to prevent PCO. In addition to having a sharp optic edge, the lens incorporates an additional haptic-optic barrier edge (Advantedge) that prevents migration of lens epithelial cells via the haptic-optic junction.

contact Shinichiro Kobayakawa – covanet@aol.com

Don’t Miss Ophthalmologica, see page 42 EUROTIMES | Volume 19 | Issue 2

contact

Update

Cataract & refractive

FEMTOCAT ECONOMICS

Many things to be considered when assessing costeffectiveness of femtosecond laser by Priscilla Lynch

hile femtosecond laser cataract surgery is currently very expensive it will become more cost-effective as it becomes more established and its future looks bright, according to Paul Rosen FRCS, FRCOphth, consultant ophthalmic surgeon, Oxford Eye Hospital, UK. Dr Rosen discussed the economics of the surgery during a presentation at the XXXVII UKISCRS Congress in Manchester, maintaining that there are a number of variables that need to be considered when weighing up whether it is currently economically viable.

Pros As the latest big thing in ophthalmology, many are now looking at the option of introducing femto-laser surgery in their private and public practices. The pros of acquiring this technology include its potential benefits for the patient, the improved efficiency of surgery, the competitive advantage in having a femto machine before others, the increased revenue/profit potential and the fact it is a logical add-on to premium IOLs, Dr Rosen commented. While the machines are expensive, carrying out larger volumes of the surgery makes the procedure cheaper on a per-case basis, he said. Costs The revenue potential depends on who the payer is – ie, if it is the

patient, health insurance companies or the Government. The value proposition for private practice leans more towards quality, ie, can the patient see better, while in public practice the emphasis is on efficiency and cost-effectiveness, Dr Rosen stated. When practices are assessing the cost of introducing femtosecond surgery, Dr Rosen said there are many factors that have to be included beyond the cost of the physical machine, which include financing arrangements, maintenance, training, marketing costs, extra staff, consumables and potential loss of income if (but unlikely) the procedure takes longer. There are also other cost-effectiveness components that need to be considered such as potential savings from less complications and the calculation of the cost per quality-adjusted life years (QALY), Dr Rosen added. Dr Rosen provided a number of cost breakdowns for what femto would cost in a private versus a public practice. He estimated the costs of the machine at around £400,000 (GBP), financing at 4.5 per cent per annum, maintenance at £30,000 a year, consumables at £300 per eye, plus all the other aforementioned costs have to be considered. “Remember all the laser and click fees are not absolutes; they are subject to negotiation. And when you do buy a laser you need to have an ‘evergreen’ contract because it is a rapidly changing technology which you will

“

Remember all the laser and click fees are not absolutes; they are subject to negotiation. And when you do buy a laser you need to have an ‘evergreen’ contract because it is a rapidly changing technology which you will need to upgrade

Paul Rosen FRCS, FRCOphth need to upgrade,” he told the congress. When pricing the procedure, practices should add up all the outlined costs and then look at a price that creates an approximate 25 per cent profit margin, Dr Rosen said. Giving a costing example, Dr Rosen said in a public system, such as the NHS, in a practice carrying out 25 femto cases a month/4hr theatre session/week (the NHS standard) the price differential would be £700 more expensive than standard phaco, but if 50 cases were performed a month that would drop to £500, and with 100 cases a month (using two operating theatres simultaneously) it would be £300.

Paul Rosen – phrosen@rocketmail.com

Thus, the more cases that are performed the more the cost decreases, Dr Rosen said, and if the "click fee" could be brought down to £100 it would become cost-effective. However, he also stressed that it is not just about the absolute procedure cost; surgical technology can help drive productivity and sustainable quality.

Is it better? The big question in relation to femto is – is it actually better? While still a relatively new technology, Dr Rosen said the data to date shows femto-assisted phaco surgery has fewer complications, patients heal faster and it is potentially safer, with more reproducible, accurate outcomes. It also may manage astigmatism. However, he acknowledged that in the absence of longerterm studies, much remains to be confirmed about the longer-term outcomes and risk increases/decreases. “Femto is an enabling technology that enables all surgeons to be as good as the most highly skilled surgeons,” Dr Rosen said, adding that it also would have an impact on training, for example facilitating capsulorhexis when required allowing the trainee to concentrate on the other parts of the procedure in the initial stages of learning. In addition, he pointed out that Europe has an increasing elderly population, which will mean increased demand for cataract surgery, and currently there appear to be less cataract surgeons than before. Acknowledging that currently the costs of femto in private practice are still too much for some healthcare systems, Dr Rosen suggested that co-payments and placement in multi-surgeon practices could be the answer. “While it is difficult to predict the future and the speed of progress, the potential for femto-assisted phaco is very bright,” he concluded.

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FEMTO CATARACT

Delegates at ESCRS Congress are told that femtosecond laserassisted cataract surgery represents the future of cataract surgery by Dermot McGrath

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here are a number of compelling reasons for making the switch from traditional phaco to femtosecond laser-assisted cataract surgery including faster visual rehabilitation, reduced complications and reduced exclusion criteria for cataract surgery, according to Burkhard Dick MD. “Femtosecond laser technology has come a long way in a very short space of time and I am amazed how quickly this technology is developing. In my practice, we are now close to completely eliminating ultrasound for cataract removal. Around 99 per cent of my last 400 cases have been performed without ultrasound,” Dr Dick told delegates attending the XXXI Congress of the ESCRS in Amsterdam. Beyond the often-cited advantages of customisable corneal and lenticular incisions and precise and reproducible capsulotomies with the femtosecond laser, Dr Dick emphasised some of the other key benefits of the technology. “In prospective, randomised trials of the femtosecond laser-assisted system, endothelial cell loss, corneal swelling and bag shrinkage were reduced compared to standard phacoemulsification. Visual rehabilitation was also faster, with best-corrected visual acuity better up to one week after surgery. By effectively eliminating the need for ultrasound, we can now perform surgery in routine cases without having to use viscoelastic. It works extremely well in complicated cases such as Marfan's Syndrome, intumescent and advanced cataracts and small pupils,” he said. Dr Dick uses the Catalys (OptiMedica) system incorporating a “Liquid Optics” patient docking interface and an image-guidance system, which identifies ocular surface and establishes safety zones to allow the physician to select and customise the treatment. “The interface is very smooth and stable and results in a minimal IOP increase of the order of 10 mmHg. The guidance system and automatic surface detection means that the laser pulses are delivered precisely to the intended location. Capsulotomy is performed in less than two seconds, with minimal cavitation bubbles and very quiet eyes postoperatively,” he said.

Learning curve Making the transition to femtosecond laser-assisted cataract surgery has made a dramatic difference to the need to use ultrasound energy in routine cases, said Dr Dick. “When we started we saw a clear decrease in the use of effective phaco time (EPT) by 96 per cent in a controlled trial across all grades of cataract. We also found that by tightening the fragmentation grid pattern from 500 to 350 microns, we were further able to reduce the EPT,” he said. As with any technology, there is a definite learning curve with femtosecond laser-assisted cataract surgery, noted Dr Dick. “It really is all about optimisation and that comes with experience. My first 200 to 400 cases showed that I still used ultrasound in 59 per cent of cases. Then changing to 350-micron grid spacing we were able to reduce this to 38

per cent for cases 700 to 900. For cases 1200 to 1400 with a new phaco tip and adjusted settings, it was less than nine per cent where I still had to use ultrasound. And in the last series of cases, ultrasound was required in just three out of 400 eyes. Those three cases were grade four cataracts, which means that for 99 per cent of my cases now I do not use any ultrasound at all, just irrigation and aspiration,” he said. Contrary to expectations, Dr Dick noted that the reduction in ultrasound energy being delivered into the eye did not result in either a higher fluidics usage or longer procedure times. “In a prospective intraindividual comparative trial we measured the fluidics turnover in standard phaco versus femtolaser-assisted group and we saw no significant difference. Likewise, the procedure time was measured from docking on to wound closed and it is very similar for both techniques – whether it is a standard procedure or a laser procedure,” he said.

Many advantages Other benefits which were confirmed by the prospective trial included a reduction of inflammation by about 20 per cent on day one after surgery, less corneal thickening up to one month postoperatively, less endothelial cell loss after three months, less capsular bag shrinkage and better visual acuity for the first week only, he added. Turning to complications, Dr Dick said that he experienced four capsular tears in his first 1,273 cases, which included patients with pseudoexfoliation and intumescent cataracts. “Three of these incidents were due to my lack of experience because I underestimated movement of the eye. This translates to an anterior capsule tear rate of 0.16 per cent and the same for posterior tears, which still compares favourably to the published data,” he said. With improved fixation of the eye and using a dimpledown technique with a cannula directed at the centre of the capsulotomy, Dr Dick said that he has reduced the tear rate even further, with an anterior capsule tear of 0.2 per cent and no posterior capsule tears for the most recent 1,000 cases. Overall, Dr Dick said that adopting the Catalys system has meant a reduction in the exclusion criteria for cataract surgery, as opacified corneas, loose zonules, intraoperative floppy iris syndrome, pseudoexfoliation and small, nondilating pupils no longer preclude from Femtosecond laserassisted surgery, he said. “I think this technology represents the future of cataract surgery. There are exciting ongoing improvements such as the new technique of intraoperative primary posterior capsulotomy which may help to reduce PCO, and the development of new IOLs which are specifically designed for this femtosecond laser technology,” he concluded.

contact

Burkhard Dick – burkhard.dick@kk-bochum.de

add_february.pdf

Cataract & refractive

ORTHOKERATOLOGY

Myopia and axial length growth slow, but long-term effect uncertain by Howard Larkin

Reverse geometry Orthokeratology utilises rigid contact lenses of a “reverse geometry” design, which incorporate a steeper “reverse” curve at the mid-periphery joining the flatter central base curve to the alignment curve in the periphery. Worn overnight, the lenses temporarily reshape the cornea, flattening and reducing power in the central optical zone, Dr Swarbrick explained. The corrective effect increases over about the first 10 nights of wear, and patients generally regress up to 0.5 D as the cornea reshapes over the course of each day, which can be compensated by slightly overcorrecting, Dr Swarbrick said. Orthokeratology is also reversible, with the cornea reverting to its original shape when lens use ceases. The lenses can correct up to -4.0 dioptres of sphere, but can be used up to -6.0 dioptres, and reduce astigmatism about half, Dr Swarbrick said. They are removed in the morning and there is no lens wear or use of any visual aid during the day if the treatment works well. New designs are also being used to correct hyperopia and presbyopia. The impact on myopic progression is less certain. In a 12-month contralateral eye study involving 26 patients that she conducted, axial length declined slightly at three and six months in eyes treated with overnight orthokeratology while it increased in fellow eyes using conventional day-wear rigid contacts. When lens-eye combinations were reversed, axial length again fell in the EUROTIMES | Volume 19 | Issue 2

1/14/14

10:22 AM

Update

ecent studies suggest that orthokeratology, using night-wear rigid contact lenses to reshape the cornea, is effective for correcting low to moderate myopia, and may slow progression by reducing axial length growth by about 45 per cent over three years, Helen Swarbrick PhD told the XXXI Congress of the ESCRS in Amsterdam. However, while nine published studies since 2005 all found that orthokeratology reduces axial length growth, most were not truly randomised, noted Dr Swarbrick of the School of Optometry and Vision Science, University of New South Wales, Sydney, Australia. Further research is needed to confirm long-term efficacy and evaluate the potential for rebound after temporary treatment, she said.

“

The corrective effect increases over about the first 10 nights of wear, and patients generally regress up to 0.5 D as the cornea reshapes over the course of each day...

Helen Swarbrick PhD

orthokeratology eyes, but increased about twice as fast in the previously treated eyes, suggesting a rebound effect, Dr Swarbrick said (Swarbrick et al 2010).

CMY

Safety

Orthokeratology works at least in part by thinning the central corneal epithelium, by about 15 to 20 microns over 90 days (Alharbi and Swarbrick Invest Ophthalmol Vis Sci. 2003 Jun;44(6):251823). Could this compromise the epithelial barrier, increasing the risk of microbial keratitis? Several studies suggest not, Dr Swarbrick said. Analysis of 129 cases of keratitis in orthokeratology patients reported in the literature from 2001 to 2007 found most occurred in children, and Pseudomonas and Acanthamoeba were the most common causes. “This suggested one of the issues was exposure to contaminated water in lens care.” (Watt and Swarbrick, Eye Contact Lens. 2007 Nov;33(6 Pt 2):373-7; discussion 382.) Further, about half the cases were reported in 2001 in Southeast Asia, when orthokeratology was largely unregulated in the region. Follow-up since 2007 shows a decrease in reported cases worldwide, suggesting improved prevention practices, Dr Swarbrick said. A study of 2,600 US patients also found an overall infection rate of 7.7 per 10,000 patient treatment years, with a slightly higher risk for children (Bullimore et al. Optom Vis Sci. 2013 Sep;90(9):937-44). “Safety is similar to other overnight contact lens modalities,” she said.

contact Helen Swarbrick – h.swarbrick@unsw.edu.au

Update

Cataract & refractive

contacts

Maria Sysoeva – D3@iol.it Matteo Piovella – piovella@piovella.com

MULTIFOCAL IOLS

Preoperative counselling is crucial, particularly in terms of managing expectations by Leigh Spielberg

he AT LISA 809M multifocal lens provides good near and distance vision with few untoward effects in the longer term, according to a series of reports at the Annual Congress of the ESCRS in Amsterdam. Maria Sysoeva MD, presenting for Dimitrii Dementiev MD, Centro di Microchirurgia Oculare, Milan, Italy, discussed the long-term results of the AT LISA 809M (CZ Meditec) multifocal lens. Dr Sysoeva’s study included 422 eyes of 211 patients, of whom 62 per cent were female. A single surgeon operated all patients under topical anaesthesia, using a 2.4mm incision and standard phacoemulsification. Patients were followed up for 36 months, with regular follow-up visits at one, three, six, 12, 24 and 36 months. There were no surgical complications. “Mean uncorrected distance visual acuity improved from 20/50 to 20/25, and average uncorrected near VA was 20/30,” said Dr Sysoeva. Spectacle independence was observed in all but five cases for intermediate vision and in all but one case for near vision. However, haloes were reported in three cases, or 1.4 per cent of the eyes. Nevertheless, all patients showed high levels of satisfaction regarding both near and far vision. “For many patients, cataract surgery has become a refractive surgery procedure. Whereas the main problem after cataract surgery was aphakia in the 1960s and 1970s, astigmatism in the 1980s and spherical aberration in the 1990s, the main problem in this era is the need for spectacle correction, particularly for near,” she commented. The AT LISA 809M lens is made of hydrophilic acrylate with hydrophobic surface properties, and has a +3.75 D near addition throughout the power range from 0.00 to +32.00 D. It was the first preloaded multifocal micro-incision IOL made available. Dr Sysoeva added that the standard AT LISA multifocal IOL exhibits good predictability in terms of refractive outcomes The AT LISA is also available with cylinder correction. Matteo Piovella MD, scientific director, Centro Microchirugia Ambulatoriale, Monza, Italy, presented his team’s two-year outcomes for distance and near vision after implantation of the AT LISA 909M toric IOL.

EUROTIMES | Volume 19 | Issue 2

Dr Piovella begun with a review of what are generally considered to be the disadvantages of the most popular multifocal IOLs. “The well-known problem of contrast sensitivity reduction is not the only potential pitfall,” said Dr Piovella. “Others include poor intermediate distance vision, light loss due to differing diffraction efficiency, along with haloes, glare and ghost images, which are particularly difficult to manage in suspicious patients.” Dr Piovella recommended toric multifocal IOLs for corneal astigmatism above 0.75 dioptres. He then introduced the lens, which he described as “an advanced-generation, multifocal IOL preferably indicated for bilateral implantation.” His study, which treated 33 eyes of 21 patients with a mean age of approximately 62 years, had a two-year follow-up. BCDVA, postoperative mean refractive astigmatism and mean sphere equivalent, as well as binocular near visual acuity were recorded. IOL calculations took into account the surgically induced astigmatism. IOL axis alignment during surgery was performed using limbal and iris patterns. Preoperative mean corneal astigmatism was 1.78 D. The preoperative mean total refractive astigmatism was 1.46 D. This was reduced to 0.47 at two years postoperatively, said Dr Piovella. Distance BCVA was also good, at 0.9 at two years postoperatively, while monocular near uncorrected visual acuity was 25/34, or J2. Photopic contrast sensitivity, measured using the Optec 6500, was within the normal range for lower spatial frequencies. “What is crucial to the long-term postoperative success of a toric lens is the rotational stability of the IOL, as well as its centration. Because of their 4-haptic design, the Zeiss IOLs have been shown to have excellent rotational stability and stable centration, as shown in a study by Dr Michael Georgopoulos, MD of Austria.” To illustrate his point, Dr Piovella showed sequential images of a lens that rotated two degrees over the course of one year postoperatively. A relatively high number of eyes, seven of 33 (21.2 per cent), underwent YAG posterior capsulotomy within one year postoperatively. “Preoperative counselling is crucial, particularly in terms of managing expectations. It doesn’t take very long, and it

Courtesy of Maria Sysoeva MD

AT Lisa position in postoperated eyes

is quite beneficial in the long term to avoid patient dissatisfaction due to unrealistic expectations,” emphasised Dr Piovella. “Clinical outcomes indicate that the AT LISA

The AT Lisa IOL

The “L” stands for “Light distributed asymmetrically.” This lens has asymmetric light distribution between distant (65 per cent) and near focus (35 per cent). This asymmetry purports to provide improved intermediate vision and reduced haloes and glare. The “I” stands for “Independence from pupil size”, due to a diffractive-refractive

909M toric IOL is an effective multifocal design for the correction of corneal astigmatism, providing effective uncorrected distance and near vision.”

microstructure that covers the complete 6.0mm optical mm diameter. “S” stands for “SMP technology,” for a lens surface without any right angles, in order to reduce light scattering. “A” stands for “Aberration-correcting optimised aspheric optic,” which is intended to provide improved contrast sensitivity and depth of field.

Update

Cornea

surgery options

Improving outcomes in eyes with treatmentrefractory infectious keratitis By Cheryl Guttman Krader

(a) (a)

(b) Figure 1: This figure illustrates (a) a sheet of corneal epithelium removed by alcohol delamination and (b) the excellent morphology that can be achieved by fixing the sheet flat

urgery has both diagnostic and therapeutic applications in the management of infectious keratitis and related ocular surface complications. Speaking at the 4th EuCornea Congress in Amsterdam, Harminder S Dua MD, discussed the role of various surgical techniques and provided an array of helpful tips. Alcohol delamination of the corneal epithelium by applying 20 per cent alcohol to the area of interest on the cornea for 30-40 seconds offers a method of obtaining tissue for biopsy and may be therapeutic as well. The removed sheet of epithelium can easily be spread flat, and when fixed, gives very good morphology for histological examination (Figure 1). However, due to the toxicity of the alcohol, the specimen cannot be used for culture, said Dr Dua, chair and professor of ophthalmology, University of Nottingham, Queens Medical Centre, Nottingham, UK.

EUROTIMES | Volume 19 | Issue 2

Discussing stromal biopsy, Dr Dua recommended acquiring two samples, one for microbiological assessment and the other for histopathology, and obtaining the histopathology specimen at the junction of the affected and unaffected tissue (Figure 2). The procedure can be performed using a skin biopsy punch, although depending on the depth of the infiltrate, it may be necessary to first raise a flap of the cornea before using the punch. If there is concern about inadvertently perforating through the cornea, an alternative technique is to create a superficial mark with a trephine, deepen the cut with a diamond blade and then use a crescent blade to shave off the base. Dr Dua discussed some applications using tissue glues. Small perforations may be sealed using cyanoacrylate products. However, safety and success with this technique requires that surgeons use just a minimal amount of glue and first debride away any loose epithelium, otherwise the glue will fall off. In cases of corneal perforation with iris incarceration, Dr Dua described a technique involving a double drape tectonic patch. The first patch is applied without glue to cover the exposed iris and the second larger patch with glue is applied directly over it. He also described the use of fibrin glue tissue adhesive to successfully address a persistent leak at the graft-host junction in an eye that had undergone a fourth penetrating keratoplasty (PK). The glue was injected at the graft-host junction and allowed to enter the anterior chamber underlying the leak. Dr Dua explained the idea occurred to him based on his experience using fibrin glue to manage leaking glaucoma filtering blebs, where he injects the glue in the bleb as an alternative to autologous blood. “This is an approach for surgeons to consider if they encounter a fluid leak post-PK, although my positive experience using it represents just a single case.” Fibrin glue is also being used as an alternative to sutures in amniotic membrane transplantation and has advantages for causing less irritation and avoiding the need for suture removal. With respect to the use of amniotic membrane, its transplantation in eyes with active infectious keratitis may serve a dual purpose, acting both as graft tissue and as a drug reservoir. “Emerging evidence indicates that amniotic membrane transplantation may improve outcomes in

Figure 2: Two sites of anterior stromal and epithelial biopsy with a skin biopsy punch. Fluorescein-stained cornea

eyes with treatment-refractory infectious keratitis, possibly because the material holds the topically applied antibiotic or antiviral agent and augments its delivery to the target site,” Dr Dua said (Figure 3). He reminded corneal surgeons that deep anterior lamellar keratoplasty (DALK) is a useful alternative to PK when the indication for a graft procedure is post-viral scarring since eyes with viral keratitis have a high risk of rejection post-PK. However, it is important to evaluate corneal sensation in these cases, as it is a prognostic indicator. “Failure of the graft in eyes with viral keratitis is not necessarily due to rejection but rather may be associated with neurotrophic non-healing of the graft-host junction and related problems,” he said. When performing a graft procedure in eyes with a history of herpetic infection, Dr Dua also reinforced the importance of antiviral prophylaxis to prevent viral recurrence. In patients who are undergoing a transplant procedure for infective keratitis and are in need of cataract surgery, he recommended following a staged approach if there is any suspicion of active infection, leaving the cataract operation for a later time. Dr Dua also discussed the use of fine needle diathermy using monopolar cautery as a method for occluding established corneal vessels and for treating lipid keratopathy, which is most often due to virus infectionrelated vascularisation (Figure 4). “Some surgeons may wonder if antiVEGF treatment is a better alternative for obliterating corneal vessels. However, anti-VEGF agents act only on vessels that are actively growing and do not affect

(a)

(b)

(c) Figure 3: (a) A non-healing chronic infective corneal abscess and ulcer which was covered (b) by a patch of amniotic membrane applied with fibrin glue. (c) The ulcer has responded and the adjacent vessels too are seen to regress with cattle trucking of the blood column

established, mature vasculature,” Dr Dua said. Anit-VEGFs and fine needle diathermy can be combined. He concluded his review with a discussion of “advances” that go back to the past. He suggested that when all else fails for treating infection, surgeons may consider destructive techniques, including cryotherapy, cautery with silver nitrate, or use of povidone-iodine. “These old methods may be useful to get rid of anything live, but in the effort to eradicate infection they will also kill the host cells. Collagen cross-linking for treatment of infective keratitis may prove to be a viable alternative,” Dr Dua said.

(b) Figure 4: (a) Fine needle diathermy occlusion of a corneal vessel. The needle is being inserted along the main trunk of the vessel. (b) The appearance after application of diathermy. The coagulated area is visible as a white linear mark

Courtesy of Harminder S Dua MD

contact

Harminder Dua – harminder.dua@nottingham.ac.uk

contacts

Update

Cornea

Michael Assouline – dr.assouline@gmail.com Alfredo Vega-Estrada – alfredovega@vissum.com Albert Daxer – daxer@gutsehen.at

KERATOCONUS Courtesy of Alfredo Vega-Estrada MD, MSc

Investigators report conflicting findings on potential to halt disease progression by Cheryl Guttman Krader

orneal surgeons might agree that by flattening and regularising the cornea, intrastromal corneal ring segment/intracorneal continuous ring (ICRS/ICCR) implantation is a useful method for visual rehabilitation in eyes with keratoconus. However, there is no consensus of opinion about the benefit of this technique for arresting keratoconus progression. At the Expert Meeting on the Surgical Management of Keratoconus, Michael Assouline MD, PhD and Albert Daxer MD, PhD presented data showing disease stabilisation in eyes followed for periods of two to five years after ICCR/ ICRS implantation. However, evidence reported by Alfredo Vega-Estrada MD, MSc, showed only an early, temporary benefit. The meeting took place at the 4th EuCornea Conference in Amsterdam, The Netherlands. To address the question of whether there is significant progression of keratoconus following ICRS implantation without corneal collagen crosslinking (CXL), Dr Assouline analysed outcomes after two to four years of follow-up in 56 patients who underwent ICRS implantation [Keraring (Mediphacos) or Intacs (Addition Technology)] into femtosecond laser-created channels. Patients were included in the study only if they had to have at least two postoperative topography exams (Orbscan, Bausch + Lomb) performed at least two years apart. Progression was determined based on the differential numerical analysis of the Orbscan data recorder export files (rather than simple comparison of values from printed maps). Absolute changes in anterior axial curvature (Kmax, mean K) and elevation (Anterior elevation and best fit sphere) were plotted against time. Eyes with post-LASIK ectasia or that had CXL, contact lens wear within eight days prior to diagnostic imaging, or severe keratoconus (max K >68 D or minimum pachymetry <400 microns) were excluded. The results showed a tendency for progressive flattening over time and with the benefit still not reaching a plateau at four years. Dr Assouline acknowledged that the data he presented are not from a rigorously designed study. However, he noted that he has performed ICRS implantation alone in EUROTIMES | Volume 19 | Issue 2

“

However, the data suggest that at least in young patients with evolving keratoconus, ICRS implantation may not alter the progressive nature of the disease

Evolution of the mean keratometry reading during the follow-up period. Keratometric changes observed between the first visit and preoperative visit confirmed the keratoconus progression before the surgery. A significant improvement is observed six months after the procedure, nevertheless a significant regression of more than 3 D was found between the postoperative six months and five years

Alfredo Vega-Estrada MD, MSc

a total of 193 patients, of which none have subsequently undergone CXL. “It would be useful to establish a patient registry to collect data so that we could better understand the possible benefits of ICRS implantation for stabilising corneal shape,” said Dr Assouline, private practice, Centre Iéna Vision, Paris, France. “However, based on years of follow-up in a reasonable number of cases, I currently don’t see a need to routinely perform CXL with ICRS. In my opinion, there is no obvious benefit for routine CXL that would outweigh its risks, which include infection and potentially blinding corneal ulcers,” said Dr Assouline. Dr Daxer, private practice, Gutsehen Eye Centre, Linz, Austria, and associate professor of ophthalmology, Medical University Innsbruck, Austria reported on follow-up to five years in a series of 10 eyes implanted with the Myoring (MTP Medical) into a corneal pocket. He explained that when he first began using the Myoring in 2007, he performed CXL simultaneously in eyes with more advanced KCN. However, in 2008, he switched to Myoring implantation only as his initial procedure because the device became available in a broader range of dimensions and reasoning that if progression occurred, he could use the existing corneal pocket for riboflavin injection, allowing for an easy, safer and more comfortable CXL procedure. Preoperatively, the 10 eyes in his series had an average simK of 52 D and average logMAR UDVA of 1.3. After five years, mean UDVA had improved 9.2 (or 8.4) lines, mean simK had improved 5.5 D (or

Courtesy of Michael Assouline MD, PhD

Orbscan IIz® and Pentacam® differential elevation and curvature maps showing progression of keratoconus in a post-LASIK ectasia at two years. Both devices display consistent values

5.3), and corneal pachymetry was essentially unchanged. Two of the 10 eyes showed some progression based on simK and pachymetry values, but the changes were only about 1.0 to 2.0 D in mean simK and 20 microns in thickness. Dr Daxer acknowledged the need for a larger series to confirm his results, but he also proposed a mechanism of action to explain how ring implantation can halt keratoconus progression. Dr Vega-Estrada, Vissum Institute of Ophthalmology of Alicante, Alicante, Spain, noted there are some papers in the literature, including one from his centre [J Cataract Refract Surg. 2013;39(8):1234-40] showing no progression of keratoconus post-ICRS implantation. However, he suggested these reports represent analyses of cases specifically selected because they had stable disease. The study he presented at the Expert Meeting looked at young patients with

progressive disease defined by an increase in mean K or steep K ≥0.75 D, increase in cylinder and sphere ≥1 D, and CDVA loss ≥1 line over six months that was confirmed at two visits. Analyses of data from 18 consecutive eyes of 15 patients (ages 19 to 30) showed initial improvement in refractive and topographic status six months after ICRS implantation. However, the benefits regressed during follow-up to five years. Dr Vega-Estrada also noted that the study has some limitations as the small size of the sample under investigation and a heterogeneous cohort with different degrees of keratoconus. For this reason, conclusions of the present work should be taken with caution. “However, the data suggest that at least in young patients with evolving keratoconus, ICRS implantation may not alter the progressive nature of the disease,” he said.

contact

Sharita R Siregar – doktertasha@gmail.com

Update

cornea

POST-LASIK ECTASIA

Prospective study supports role of integrated optical coherence pachymetry by Cheryl Guttman Krader

he integrated optical coherence pachymetry (OCP) technology found on the Schwind Amaris 750S excimer laser (Schwind eye-tech solutions) is a valuable feature for obtaining intraoperative cornea and flap thickness measurements in patients undergoing LASIK, said Sharita R Siregar MD. In a study that she presented at the 26th Asia-Pacific Association of Cataract & Refractive Surgeons Meeting in Singapore, Dr Siregar used online OCP and a rotating Scheimpflug camera device (Schwind Sirius, Schwind eye-tech solutions) to

measure cornea, flap and residual stromal bed thickness in 100 eyes of patients undergoing LASIK. The study population represented a wide range of spherical errors (-12.0 to +0.75 D) and cylinder (-6.0 to +2.0 D). All flaps were created with the Femto LDV femtosecond laser (Ziemer Ophthalmic Systems) with an intended thickness of 110 microns. The results showed that the mean thickness values were consistently thinner using OCP compared with the Scheimpflug camera. The difference between technologies ranged from about three

microns for mean corneal thickness (536.6 vs. 539.7 microns) to about 10 microns for mean flap thickness (99.7 vs. 110 microns). “The importance of accurately measuring corneal thickness preoperatively and of obtaining intraoperative determinations of flap and residual stromal bed thickness for preventing post-LASIK keratectasia is well-recognised. The results of this study show the integrated OCP technology offers a convenient tool for obtaining these data,” said Dr Siregar, ophthalmologist, Jakarta Eye Centre, Indonesia. “The findings are also consistent with previous data from Maria-Clara Arbelaez MD, who reported OCP measures thinner than a rotating Scheimpflug camera. Dr Arbelaez also found that the readings with both techniques were thinner than when using ultrasound pachymetry. Based on this information, I am able to create a nomogram for predicting true residual stromal bed thickness to avoid keratectasia.” Dr Siregar noted that the integrated OCP also has the capability to continuously measure corneal thickness intraoperatively.

“Continuous monitoring provides another safeguard to ensure the residual stromal bed thickness is adequate to maintain biomechanical integrity of the cornea and limit the risk of keratectasia.” The patient data were also analysed to determine the ablation depth and rate using the Amaris 750S laser. Mean spherical equivalent correction for the population was -4.74 D, mean maximum ablation depth was 89.16 microns, and mean treatment time was 25.83 seconds. The calculations showed that the laser cut an average of 16 microns per dioptre in an average of three seconds. “Manufacturer data indicate mean ablation times of 1.5 seconds per dioptre of myopia and 2.7 seconds per dioptre of hyperopia using a 6.0mm optical zone. My average ablation time was longer because the treatments involved astigmatic corrections and also were performed with a larger optical zone, which averaged 6.76mm,” Dr Siregar said. “However, the Schwind Amaris 750S still has the advantage of a much shorter treatment time than other excimer lasers.”

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contact

Update

Cornea

John Dart – j.dart@ucl.ac.uk

VIRAL KERATITIS

Treatment for CMV endotheliitis may involve combined systemic and topical anti-CMV agents by Cheryl Guttman Krader

merging information indicates that ophthalmologists should now be considering cytomegalovirus (CMV) infection in their differential diagnosis for patients with endotheliitis or corneal transplant rejection, according to John Dart DM, FRCOphth, speaking at the 4th EuCornea Congress in Amsterdam. The importance of identifying epidemic keratoconjunctivitis (EKC), the most serious form of adenoviral ocular infection is well-known. Prof Dart, consultant ophthalmologist, Moorfields Eye Hospital, London, UK, provided an update on the management of EKC and discussed CMV as a recently described cause of endothelial decompensation and graft failure. Strategies for preventing cross-infection are an essential component for managing EKC since the virus is so highly contagious and there is the potential for long-term debilitating and sight-threatening sequelae. In order to address the problem of nosocomial adenoviral spread at Moorfields Eye Hospital, outpatients with conjunctivitis are segregated in a separate waiting area and examination room and receive expedited care to minimise the time they may be exposing others to infection by their presence in the department. In addition, because shedding of adenovirus continues for up to two weeks in 10 per cent of patients, the current infection control policy requires infected medical staff to stay away from work for 14 days, and until the eyes are free of inflammation. “With these two measures for isolating patients and employees, we have substantially cut down on the development of new cases of nosocomial adenovirus keratoconjunctivitis at our institution,” Prof Dart said. PCR is used for diagnosis of adenoviral ocular infection at Moorfields, and it is still considered the optimal technique. However, Prof Dart noted the now internationally available office-based immunoassay (AdenoPlus, RPS Sarasota, Florida USA) has high sensitivity and specificity according to the manufacturer’s studies, is cheaper than PCR, and provides immediate results. Currently, there are no licensed antiviral medications for treating EKC or other forms of adenoviral ocular infection. Ganciclovir is probably not very effective against

EUROTIMES | Volume 19 | Issue 2

adenovirus even though findings from in vitro and animal studies suggest it has activity. However, two novel investigational treatments show promise. They are povidone-iodine 0.4 per cent/dexamethasone 0.1 per cent, and Auriclosene (NVC-422, NovaBay Pharmaceuticals). Based on positive results reported with the use of dilute povidone-iodine, Prof Dart said that he would treat himself with povidoneiodine 0.5 per cent, prepared from the five per cent surgical solution, if he were to develop an adenoviral ocular infection. Topical corticosteroids are also used in the management of EKC, but their role is controversial. Results from a relatively small randomised controlled trial of patients with clinically diagnosed disease suggested corticosteroid treatment was safe and had a small benefit for reducing the severity of both membranous conjunctivitis and early corneal and conjunctival scarring. In addition, topical corticosteroid treatment has been shown to control chronic subepithelial infiltrates. However, evidence in an animal model steroid treatment increases the viral load early in the disease and because of this Prof Dart said that he avoids using steroid for the first seven days when treating patients with adenoviral infection. Thereafter, he will prescribe intensive corticosteroid treatment, dexamethasone 0.1 per cent every one to two hours, in individuals who develop membranous conjunctivitis which is uncommon before a week. In addition, he prescribes a “safe” steroid, eg, fluorometholone, for use one to three times daily as treatment for patients with symptomatic subepithelial infiltrates. If the lesions are very persistent, cyclosporine drops may be a reasonable steroid-sparing alternative according to experience in three small case series, said Prof Dart. CMV was first described as a cause of endotheliitis in Japan in 2006, and since then, the number of cases has been growing. While the reports are nearly all from Asia, Prof Dart believes ophthalmologists in Western countries should be thinking about CMV infection as a cause for unexplained and treatment-refractory endotheliitis or post-transplant rejection. “I have instituted a protocol for CMV diagnosis in these situations, and I would encourage others to consider it as well,” said Prof Dart.

Courtesy of John Dart DM, FRCOphth

Adenovirus membranous conjunctivitis

Adenovirus corneal subepithelial infiltrates

“Proper recognition of CMV endotheliitis will allow the initiation of effective antiviral treatment and hopefully prevent progression to corneal endothelial failure.” Characteristic signs that should raise suspicion of CMV infection include localised corneal decompensation with linear (pigmented or clear) and coin-shaped keratic precipitates along with owl’s eye cells in the endothelium on confocal microscopy. Patients may also have elevated IOP. However, not all patients with CMV endotheliitis have the typical clinical features. Prior to initiating antiviral therapy, laboratory confirmation of the diagnosis should be made using RT-PCR or antibody testing of an aqueous sample.

Treatment for CMV endotheliitis may involve combined systemic and topical antiCMV agents. Published reports describe the use of intravenous ganciclovir, oral valacyclovir or oral valganciclovir and topical acyclovir or ganciclovir drops 0.3 per cent to two per cent. Prof Dart said topical ganciclovir 0.15 per cent gel might be a reasonable alternative. Existing treatment with a corticosteroid or other immunosuppressive agent should be reduced. Patients should be monitored for treatment response with PCR and followed with measurements of endothelial cell count and pachymetry. Antiviral prophylaxis is indicated in patients who undergo a corneal graft procedure.

contact

Virender S Sangwan – vsangwan@lvpei.org

Update

Cornea

VISUAL REHABILITATION

Keratoprosthesis a viable alternative to ocular surface transplantation, but bilateral keratoprosthesis implantation controversial by Cheryl Guttman Krader

hile there has been tremendous progress in the field of ocular surface transplantation for eyes with limbal stem cell deficiency (LSCD) and excellent visual outcomes are being obtained using the Boston type 1 keratoprosthesis (Boston KPro, Massachusetts Eye and Ear Infirmary), visual rehabilitation of patients with bilateral corneal blindness due to LSCD still represents a challenge, said Virender S Sangwan MD, at the 26th APACRS meeting. “Patients with bilateral LSCD can be managed using a variety of techniques,”

said Dr Sangwan, Dr Paul Dubord Chair in Cornea, LV Prasad Eye Institute, Hyderabad, India. “However, there is limited literature on this topic and is no easy answer on the solution to this complex clinical problem.” Options for rehabilitation in eyes with bilateral LSCD and a wet surface include limbal allograft techniques, autologous cultivated oral mucosal epithelial transplantation (COMET), and the Boston KPro. Dr Sangwan reviewed experiences using these procedures at his institution over the past 10 years in a series of 62 eyes of 50 patients. Chemical injury was the leading

cause of LSCD. Counting the last surgery performed, there were 30 eyes in the Boston KPro group (mean follow-up 14 months), 31 allo-CLET eyes (mean follow-up 33 months), 13 COMET eyes (mean follow-up 10 months), and 11 eyes treated by living-related conjunctival limbal allograft (lr-CLAL, mean follow-up 16 months). Mean follow-up did not differ significantly between groups. Focusing on visual acuity outcomes, Dr Sangwan reported the result was significantly better for the Boston KPro eyes compared with all other groups. Eyes receiving the Boston KPro had a mean logMAR VA of 2.12

preoperatively with improvement to 0.67. “We have been using the Boston KPro at our centre for about four years. The visual outcomes are impressive in eyes without posterior segment disease, excellent results have also been reported in a published, large international series, and as another advantage, postoperative visual recovery occurs rapidly,” said Dr Sangwan. “Thanks to improvements in device design, retention rates are also good. However, it remains unclear if bilateral use of the Boston KPro is safe, and my personal opinion is that it may not be a good idea.” Mean logMAR VA improved significantly in eyes that underwent allo-CLET from 1.9 preoperatively to 1.0. In a recently published paper on allo-CLET, Dr Sangwan and colleagues reported that 71 per cent of 29 eyes maintained a completely epithelialised, avascular and stable corneal surface after a mean follow-up of almost five years. The main drawback of allo-CLET is that patients must receive lifelong immunosuppression that can result in sideeffects and adds cost, said Dr Sangwan.

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Cornea

CORNEAL REINFORCEMENT Light-free crosslinking: Tissue-engineering approach uses carbon nanomaterials to increase corneal rigidity by Cheryl Guttman Krader

Strong adhesion observed Post-mortem examination of the corneal tissue after three months found no evidence that the carbon nanomaterials induced any reactivity. There was no fibrous scarring, vessel formation, inflammatory reaction, giant body cell reaction or alterations of the mucopolysaccharides of the corneal stroma. Strong adhesion of the tissue in the area surrounding the carbon nanomaterials was observed. A stress-strain analysis showed no statistically significant differences comparing the mean Young’s modulus value for any of the operated groups with the controls. However, the outcome for the eyes injected with the higher concentration of carbon nanomaterials showed a trend for a benefit of increasing rigidity. “In this initial investigation we were aiming to find that there was at least a beneficial trend for a treatment effect, and we achieved that goal. Furthermore, our results are in coherence with data from other investigators showing adsorption and interaction of carbon nanomaterials with collagen fibrils and improvement in mechanical properties,” Dr Alió said. EUROTIMES | Volume 19 | Issue 2

Courtesy of Jorge F Alió MD, PhD

hile many investigators are focusing on modifications to the standard CXL technique, Jorge F Alió MD, PhD, Alfredo Vega-Estrada MD, MSc and colleagues at Vissum Corporacion Oftalmológica, Universidad Miguel Hernandez, Alicante, Spain, are developing a novel “lightfree” tissue engineering approach to reinforce the corneal tissue using carbon nanomaterials. Speaking during the Expert Meeting on the Surgical Management of Keratoconus, Dr Alió described the technology, presented outcomes of an initial preclinical study, and talked about the next steps for its development. “The results from our first in vivo study show biocompatibility of our product with corneal tissue and a positive trend for an increase in tissue rigidity. Now we are working to enhance the properties and chemical structure of our nanoplatform as well as its delivery,” said Dr Alió. The carbon nanomaterials product developed by the Vissum group is a mixture of graphene and carbon nanotubes dispersed in an original registered vehicle. Dr Alió noted that these and other carbon nanomaterials have several physicochemical and mechanical properties that make them attractive as a platform technology for strengthening the cornea. They are biologically inert, almost completely transparent and have high elasticity, hardness and resistance. The first in vivo study was designed primarily to test the safety of the carbon nanomaterials product for use in the cornea and also to obtain some preliminary information on its potential to affect corneal mechanical properties. The study involved New Zealand white rabbits and evaluated two different concentrations of the graphene/carbon nanotubes suspension (0.1 and 1.0 mg/ mL) compared with a control group.

Organic nanoparticles creating light-free CCL in an experimental eye

“

The results from our first in vivo study show biocompatibility of our product with corneal tissue and a positive trend for an increase in tissue rigidity Jorge F Alió MD, PhD The investigators proposed several reasons why their study was unable to demonstrate a statistically significant effect on corneal biomechanics. Insufficient power due to small sample size may be one factor. In addition, the chosen endpoint of Young’s modulus may not have been sensitive enough to identify a treatment effect on corneal biomechanics. However, the most important issue may be that the method of treatment, ie, injection into a stromal pocket, impregnated the cornea with only a single layer of the carbon nanomaterials, whereas more widespread tissue distribution may be more ideal. Based on the latter concept, Dr Alió and colleagues are now developing new methods for delivering the carbon nanomaterials, and they have achieved promising results in early testing.

contact Jorge Alió – jlalio@vissum.com

contact

Elisabeth M Messmer – Elisabeth.mesmmer@med.uni-muenchen.de

Update

CORNEA

HZO MANAGEMENT

Vaccination offers best strategy for reducing disease burden by Cheryl Guttman Krader

imely diagnosis of herpes zoster ophthalmicus (HZO) and prompt initiation of proper treatment with a combination of antiviral therapy and a corticosteroid can reduce acute and long-term morbidity for affected patients. However, prevention is the best intervention for HZO, and ophthalmologists can play an important role in this area by counselling patients about the live attenuated varicellazoster virus vaccine (“HZ vaccine”; Zostavax, Sanofi Pasteur MSD), according to Elisabeth M Messmer MD. Dr Messmer, professor, Department of Ophthalmology, Ludwig Maximilians University, Munich, Germany discussed the management of HZO at a symposium during the 4th EuCornea Congress in Amsterdam. She noted that HZO accounts for about 10 per cent to 20 per cent of cases of zoster. It can involve the entire eye, become chronic, particularly in older persons, and be associated with severe complications and debilitating pain during the acute episode, but particularly with the development of post-herpetic neuralgia. Antiviral treatment can reduce the severity of HZO, shorten its duration and reduce the risk of ocular complications. However, it does not reliably prevent HZO post-herpetic neuralgia. On the other hand, as documented in the Shingles Prevention Study, the herpes zoster vaccine is safe, well-tolerated and reduces the risk of herpes

zoster, the burden of illness from herpes zoster and the risk of HZO post-herpetic neuralgia. In 2006, the European Medicines Agency (EMA) issued marketing authorisation for routine use of the herpes zoster vaccine in persons aged 60 and over, excluding those with a few contraindications, and the EMA expanded the authorisation to individuals 50 years and older in 2007. Although there are no data available on herpes zoster vaccination rates in Europe, in the US, recent data show coverage is falling well below the target.

More awareness needed Cost appears to be one of the causes for the low uptake, but other explanations include low awareness of national recommendations issued by the US Centers for Disease Control and Prevention’s Advisory Committee on Immunization Practices along with lack of recommendation by primary care physicians. “According to one study in the US, only 66 per cent of primary care physicians thought the vaccine for preventing herpes zoster is important. Corneal specialists and other ophthalmologists should be aware of the vaccine and recommending it to their patients,” Dr Messmer said. Although it is recommended that antiviral treatment for HZO be started within 72 hours of disease onset, there is evidence that patients can also benefit if the medication is

started up to seven days after the appearance of skin lesions. Standard antiviral treatment for HZO involves a course of at least 10 days, although it is better to continue the medication until all ocular manifestations are healed, Dr Messmer said. “In collaborating with dermatologists or other physicians managing patients with HZO, it is the ophthalmologist who should be deciding when treatment can be discontinued,” she commented. Antiviral treatment options for immunocompetent patients with HZO include oral acyclovir, valacyclovir, famcyclovir and brivudin. However, immunosuppressed patients should be treated only with intravenous acyclovir and using a higher dose than that used for immunocompetent persons. Even with this more aggressive treatment, immunosuppressed patients may show resistance, and in that situation, intravenous foscarnet is indicated. Corticosteroids should be given only in combination with an antiviral. Systemic steroid treatment will hasten improvement of keratitis, uveitis and secondary glaucoma and also decreases the intensity of HZO post-herpetic neuralgia. A topical corticosteroid is indicated for treatment of mucous plaque keratitis, stromal keratitis, endotheliitis and uveitis. Patients who develop neurotrophic keratopathy should be treated with the same modalities used for neurotrophic keratopathy of any aetiology, including ocular lubricants and a bandage contact lens. They may be candidates for amniotic membrane transplantation, tarsorrhaphy, and use of cyanoacrylate glue for sealing corneal perforation. “Neurotrophic growth factor is now in clinical studies as a treatment for neurotrophic keratopathy secondary to herpes zoster ophthalmicus, and so I think there may be some light at the end of the

“According to reports in the literature, there is a low rate of recurrence after keratoplasty for herpes zoster ophthalmicus, and so there are no clear guidelines on the need for prophylaxis with systemic antiviral medication” tunnel for management of this condition,” Dr Messmer said. Oral NSAIDs can be tried for alleviating pain in patients with HZO and HZO post-herpetic neuralgia, but clinicians should recognise that more aggressive therapy may be needed. Options for pain control include oral morphine derivatives, tricyclic antidepressant medications (eg, amitriptyline), or anticonvulsants (eg, gabapentin) and topical capsaicin ointment. HZO-related disease is an uncommon indication for keratoplasty. However, if a graft procedure is necessary, the surgery should be performed only when the eye is quiet. “According to reports in the literature, there is a low rate of recurrence after keratoplasty for herpes zoster ophthalmicus, and so there are no clear guidelines on the need for prophylaxis with systemic antiviral medication. However, attention should be given to the proper management of ocular surface complications that are often encountered postoperatively,” Dr Messmer emphasised.

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Update

CORNEA

Elmer Tu – etu@uic.edu

ACANTHAMOEBA KERATITIS

With increased awareness and diagnostic acumen, outcomes for patients affected by parasitic infection improving by Cheryl Guttman Krader

canthamoeba keratitis remains a rare condition and particularly in developing countries. However, the numbers of these infections have been rising significantly in the US and other industrialised nations, and as the populations in underdeveloped areas become more affluent, there is the potential for a geometric increase in cases, said Elmer Tu MD, speaking at Cornea Day during the 26th Asia-Pacific Association of Cataract & Refractive Surgeons meeting in Singapore.

“In every large series, about seven per cent to 11 per cent of patients who present with Acanthamoeba keratitis in one eye either have infection in the fellow eye at the time of presentation or develop it within the next few months” Dr Tu, professor of clinical ophthalmology and director of the cornea service in the Department of Ophthalmology and Visual Science at the University of Illinois Eye and Ear Infirmary, Chicago, US, explained that contact lens wear is the main risk factor for Acanthamoeba keratitis. Therefore, whereas environmental conditions in developing countries are much more conducive to the development of corneal infection overall, the relative rate of Acanthamoeba keratitis has been disproportionately low in these areas compared with developed nations. “Currently, most cases of Acanthamoeba

keratitis in underdeveloped countries have been in patients who are not contact lens wearers. Nevertheless, the level of Acanthamoeba keratitis is still higher than would be expected given the population characteristics,” he said. “Recently, however, we are seeing increases in Acanthamoeba keratitis in Brazil and urban areas of China corresponding with growth in contact lens use. As the number of lens wearers increases in other developing countries in the future, these nations may be facing an enormous health burden from Acanthamoeba keratitis.” Dr Tu also pointed out that investigations conducted following Acanthamoeba keratitis outbreaks in the US indicate the importance of environmental exposure through contaminated water. Whereas a specific multipurpose contact lens solution was identified as a risk factor, it was used in fewer than half of the cases, and the number of cases of Acanthamoeba keratitis did not return to the baseline level after recall of the lens solution. “Acanthamoeba keratitis is clearly not just a solution problem. Rather, there is an increase in load from the environment that is overwhelming most of the commonly used disinfection systems, which, almost universally, are not very effective against Acanthamoeba cysts,” Dr Tu said. Dr Tu observed that ophthalmologists fully recognise that Acanthamoeba keratitis is a treatment challenge. However, he proposed that part of the problem in managing these cases has been lack of suspicion resulting in delayed diagnosis. “Thankfully, with increased awareness and diagnostic acumen, outcomes for patients affected by this parasitic infection are improving.” Issues to keep in mind are that in contrast to cases of contact lens-related bacterial keratitis that are more likely in patients wearing soft versus hard contact lenses, the incidence of Acanthamoeba keratitis is similar regardless of lens material type. Clinicians should also be aware that orthokeratology lenses are associated with a very high rate of Acanthamoeba keratitis, and they should recognise there is an appreciable risk of bilateral infection.

Don’t Miss JCRS highlights, see page 41 EUROTIMES | Volume 19 | Issue 2

Courtesy of Elmer Tu MD

Acanthamoeba keratitis

“In every large series, about seven per cent to 11 per cent of patients who present with Acanthamoeba keratitis in one eye either have infection in the fellow eye at the time of presentation or develop it within the next few months. The take-home message is to be careful not to concentrate solely on the symptomatic eye,” noted Dr Tu. Discussing some recent research findings regarding treatment issues, Dr Tu noted that in trying to identify factors associated with a poor outcome, univariate analysis showed an interesting association with treatment with an antibiotic not containing benzalkonium chloride (BAK) prior to diagnosis of Acanthamoeba keratitis. Corresponding with that information, results of a recent in vitro study undertaken by Dr Tu and colleagues showed that concentrations of BAK equal to or below those found in commercially available ophthalmic anti-infectives have significant anti-Acanthamoebal activity. “The activity of BAK against some strains of the parasite even matched that of hydrogen peroxide. I would impart to clinicians that BAK is an effective amoebacidal agent that may have an effect on the patient’s presentation and diagnosis

as well as possibly having a therapeutic effect, although the latter requires further study,” he said. Standard medical treatment for Acanthamoeba keratitis that includes propamidine plus a biguanide can be very effective. In addition, systemic voriconazole appears useful in the management of patients with deep corneal infection. Recently published data also indicate that corticosteroid use is largely unnecessary in managing Acanthamoeba keratitis. “However, in patients with severe inflammation, it may be possible to salvage the eye only by adding a corticosteroid or other immunosuppressant,” Dr Tu said. He noted that while there has been excitement about cornea collagen crosslinking (CXL) for treatment of infectious keratitis, this procedure has no in vitro effect on the viability of Acanthamoeba cysts. “CXL is probably not curative for Acanthamoeba keratitis and should not be used as primary therapy. However, it may be a good adjunctive therapy in the future because of its benefit for stabilising the corneal collagen,” he said.

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Isabel Dapena – dapena@niios.com

Update

CORNEA

DMEK VISUAL REHABILITATION

How causes of incomplete visual rehabilitation after DMEK can be identified and treated by Cheryl Guttman Krader

“

If there are signs of corneal clearance, the graft is functional and the eye can be followed for up to two to three months to see if the cornea clears by itself. If there are no signs of clearance, then rebubbling should be performed within the first postoperative weeks. Only if these measures do not help will the patient need to undergo retransplantation Isabel Dapena MD, PhD

Courtesy of Isabel Dapena MD, PhD

The management decision tree divides patients as to whether they have reduced visual acuity or visual discomfort. Examination of eyes with reduced visual acuity begins with evaluation for corneal oedema. If absent, the surgeon can assume that a patient-related cause explains the decreased vision and should conduct further examinations to identify if there is anterior corneal scarring or irregularities, which may be correctable with a contact lens; or any posterior pole pathology, cataract or posterior capsule opacification (PCO) requiring treatment.

new decision tree for the management of eyes with incomplete visual rehabilitation after DMEK offers a systematic approach for determining the underlying cause and guidance on targeted intervention for improving clinical outcomes. Developed by investigators at the Netherlands Institute for Innovative Ocular Surgery (NIIOS), the decision tree is based on findings from a retrospective study analysing data from 178 DMEK eyes. The information was recently published [AJO, 2013;156:780-8], and presented by Isabel Dapena MD, PhD at the 4th EuCornea Congress in Amsterdam. Dr Dapena reported that 69 (39 per cent) of the 178 eyes had incomplete visual rehabilitation at six months after surgery. The cause could be determined in nearly all cases. “The presence of undefined imperfections in corneal optical quality can limit visual recovery after other endothelial keratoplasty procedures, but is not an issue with DMEK. Therefore, we undertook this study to test the hypothesis that incomplete visual rehabilitation after DMEK should be explained by identifiable and potentially treatable causes,” said Dr Dapena. EUROTIMES | Volume 19 | Issue 2

Management decision tree

Eyes included in the study were identified from a consecutive series of 200 DMEK cases after excluding those with incomplete follow-up or ocular pathology recognised prior to DMEK. Incomplete visual rehabilitation was defined as either BCVA ≤0.7, which was present in 57 eyes, or BCVA ≥0.8 with subjective visual complaints, which affected 12 eyes.

Common patient-related causes Categorisation of the causes for incomplete visual rehabilitation showed that the problem was primarily patient-related in 40 of the 69 eyes, primarily related to a graft issue in 21 eyes, and involved a combination of patient and graft factors in eight eyes. The most common patient-related causes were noncorneal ocular pathology, mainly maculopathy that was frequently suspected but not recognised prior to surgery, followed by corneal irregularities and/or scarring, which could often be attributed to longstanding corneal oedema. Graft detachment was the leading graft-related cause, but a smaller subgroup of eyes had “delayed graft function” with delayed time to clearing of an attached graft.

Incomplete visual rehabilitation The presence of corneal oedema indicates a graft-related cause for incomplete visual rehabilitation and is an indication for anterior segment OCT to determine if the graft is detached or has delayed function. “If there are signs of corneal clearance, the graft is functional and the eye can be followed for up to two to three months to see if the cornea clears by itself. If there are no signs of clearance, then rebubbling should be performed within the first postoperative weeks. Only if these measures do not help will the patient need to undergo retransplantation,” Dr Dapena said. Patients with visual discomfort and BCVA ≥0.8 should be evaluated to rule out cataract and/or PCO. Unexplained visual symptoms may be managed successfully with a soft contact lens or may resolve spontaneously with time.

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FLUID PRESSURE

Optic nerve may be more prone to damage when cerebrospinal fluid pressure is low by Roibeard O’hEineachain

vidence is accumulating that, rather than the intraocular pressure (IOP) itself, it is the impact of a pressure imbalance between IOP and cerebrospinal fluid pressure on the lamina cribrosa, in favour of IOP, that makes the optic nerve more vulnerable to damage in eyes with open-angle glaucoma, said Jost B Jonas MD, University Eye Clinic, Mannheim, Germany. “The ocular cerebrospinal pressure is the real anatomical and physiological counter-pressure against the IOP across the lamina cribrosa. The trans-lamina cribrosa pressure is physiologically the critical factor, not the transcorneal pressure that we typically call IOP,” Dr Jonas said at a Glaucoma Day session of the XXXI Congress of the ESCRS in Amsterdam, The Netherlands. He emphasised that IOP must be understood in the context of its place in the eye’s fluid dynamics, which involves a complex interplay between IOP, systemic arterial blood pressure and cerebrospinal fluid (CSF) pressure. The correlation between elevated IOP and glaucomatous damage is well established, yet eyes with normal pressure glaucoma have a very similar pattern of damage to the optic nerve head to that of eyes with highpressure glaucoma. The defining morphological characteristics of glaucoma are loss of the neuroretinal rim and the deepening of the cup; second a development of beta zone of peripapillary atrophy and also the development of glaucomatous disk haemorrhages. Another characteristic finding in eyes with glaucoma is a thinning of the retinal arteries, leading some to suggest that glaucoma is a vascular disease. However, vascular optic neuropathies have a different pattern of nerve damage than glaucoma, and have neither disc-cupping nor the development of an area of peripapillary atrophy.

Evidence for the cerebrospinal fluid pressure theory Meanwhile, there is an increasing body of

evidence supporting a central role for low CSF pressure in the aetiology of open-angle glaucoma. Moreover, a reduced CSF pressure could explain the optic nerve’s reduced degree of tolerance to even normal IOP levels in eyes with normal pressure glaucoma, Dr Jonas said. He noted that in a prospective study carried out in Beijing, lumbar CSF pressure was significantly lower in normal-pressure glaucoma patients (9.5 mmHg) than in glaucoma patients with elevated IOP (11.7 mmHg) and those without glaucoma (12.9 mmHg). Similarly, the pressure difference between the IOP and CSF pressure was significantly (P<0.001) higher in both the normal-IOP glaucoma group (6.6 ± 3.6 mmHg) and the high-IOP glaucoma group (12.5 ± 4.1mmHg) as compared to the control group (1.4 mmHg) (Ren et al Ophthalmology 2010; 117: 259-266). Other evidence includes the marked thinning of the laminar cribrosa that occurs in eyes with glaucoma and the EUROTIMES | Volume 19 | Issue 2

resulting decrease in the distance between the intraocular compartment on one side, and the optic nerve and the CSF space on the other, Dr Jonas noted. “If the distance between these two compartments is decreased, trans-lamina cribrosa pressure gradient gets steeper at any given IOP and CSF pressure,” he added.

Non-invasive CSF calculation To test the theory further, Dr Jonas and his associates have developed a non-invasive means of estimating the orbital CSF pressure that uses magnetic resonance imaging (MRI) of the orbital subarachnoid space surrounding the optic nerve as a surrogate. After an independent group confirmed a correspondence between MRI images and lumbar CSF pressure measurements, they devised a formula for using the MRI-based measurements to calculate CSF pressure. The formula took into account other variables including age, diastolic blood pressure and body mass index ( Xie et al. Crit Care. 2013;17(4):R162). The researchers then applied the calculation formula to data from participants in the Beijing Eye Study and other medical studies. They found that, in glaucoma patients, the IOP was significantly higher (p=0.008) and the CSF pressure was significantly lower (p<0.001) than they were in those without glaucoma. The trans-laminar pressure difference was also significantly higher in glaucoma patients. Moreover, the intergroup difference was highest for the trans-laminar cribrosa pressure difference, followed by CSF pressure and IOP. Furthermore, in a binary regression analysis there was a statistically significant association between open-angle glaucoma and translaminar cribrosa pressure difference (p<0.001), but there was no statistically significant relationship between openangle glaucoma and IOP. Similarly, retinal nerve fibre layer thickness had a statistically significant positive association trans-laminar cribrosa pressure but not with IOP in eyes with open-angle glaucoma, after adjusting for gender, age, religion, region of habitation, optic disc area and refractive error. On the other hand, angle-closure glaucoma was significantly associated with higher IOP but not with translaminar cribrosa pressure difference after adjustment for age and anterior chamber depth. “In open-angle glaucoma, but not in angle-closure glaucoma, the calculated trans-laminar cribrosa difference versus IOP showed a better association with glaucoma presence and the amount of glaucomatous optic neuropathy. Our findings support the notion of a potential role of low cerebrospinal fluid pressure in the pathogenesis of open-angle glaucoma,” Dr Jonas said.

contact Jost B Jonas – Jost.Jonas@augen.ma.uni-heidelberg.de

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Michele Iester – iester@csita.unige.it

Update

GLAUCOMA

TONOMETRY UPDATE

Reproducibility of IOP measurements more important than physiological accuracy by Roibeard O’hEineachain

he Goldmann applanation tonometer (GAT) remains the gold-standard in tonometry, but newer devices are currently available or are under development that may help provide a more accurate picture of the effect of IOP-lowering therapy in eyes with glaucoma, said Michele Iester MD, PhD, associated professor of the University of Genoa, Genoa, Italy. “IOP measurement is of fundamental importance in the management of glaucoma because, as numerous large multicentre studies have demonstrated, IOP reduction can reduce the amount of retinal ganglion cell loss in eyes during the follow-up of the disease,” Prof Iester said at a Glaucoma Day session of the XXXI Congress of the ESCRS in Amsterdam. The GAT mounted on the slit-lamp was the first applanation tonometer to employ variable force and it has remained the gold-standard in tonometry for more than 50 years. However, there are a number of factors that can affect GAT measurements and can lead to an under- or overestimation of the real IOP. They include differences in central corneal thickness, astigmatism, corneal oedema, decentration of the measurement and the variability of tear film properties. With regard to central corneal thickness, Prof Iester noted that GAT measurements are based on the assumption that the central corneal thickness is 520 microns. Therefore,

GAT will give erroneously low IOP in eyes with thinner corneas and erroneously high IOP values in eyes with thicker corneas. However Goldmann and Schmidt predicted that an infinitely thin and flexible cornea would require a correction of 2.5 mmHg, and it seems improbable that the error in Goldmann tonometry induced by an abnormally thin cornea would ever exceed 2 or 3 mmHg. (Goldmann H, Schmidt T. Uber Applanationstonometrie. Ophthalmologica 1957; 134:221–242.)

Are newer technologies necessary?

Prof Iester noted that laboratory research involving human cadaver eyes show that dynamic contour tonometry may provide better accuracy than GAT (Kniestedt et al, Arch Ophthalmol. 2004;122(9):12871293). Moreover another study showed that the dynamic contour tonometry measurements have a close concordance with true manometric IOP measurements obtained through intracameral cannulation during cataract surgery (Boehm et al, Invest Ophthalmol Vis Sci. 2008; 49:2472–2477). However, superior accuracy in determining the actual IOP values may not necessarily yield clinically superior information, he pointed out. What is most important is that the measurements be reproducible and that changes in the measured IOP values following treatment will correspond to an effect on the glaucomatous pathology.

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All the most important clinical trials have used Goldmann applanation tonometry Michele Iester MD, PhD

“All the most important clinical trials have used Goldmann applanation tonometry, so even if there was some error in the IOP measurements, the studies’ results showed that the measured IOP reduction was related to a reduction in the worsening of the optic nerve head damage and visual field,” Prof Iester said. Some of the newer tonometers can offer some advantages in difficult cases. For example, the Tono-pen® (Reichert) and the pneumotonometer can be used in eyes with corneal oedema, irregular cornea and corneas with scars, although the pneumotonometer gives readings higher than the Goldmann tonometer. The Icare® tonometer (Icare) has the advantage of requiring no topical anaesthetic and only a minimum amount of cooperation from the patient. Compared to GAT its readings are higher in children but are lower in older adults.

The Pascal® dynamic tonometer (Ziemer) has the advantage of providing dynamic measurements that are independent from corneal structure and it also measures ocular pulse. The ocular response analyzer is able to measure, in addition to IOP, corneal biomechanical properties including corneal hysteresis. Several studies have implicated IOP fluctuation as a factor in disease progression, although other studies have contradicted those findings, he noted. However, measurement of fluctuation to date has been imperfect since even the most reliable method, sleep laboratory, involves placing patients in conditions that are very different from those of most patients’ daily lives. In the future possible alternative systems able to detect the IOP during all of the day and the night will use the so-called “MEMS” (Micro Electro Mechanical Systems). Actually the SENSIMED Triggerﬁsh® (Sensimed AG), a contact lens-based device designed to record corneal radius change continuously over 24 hours, is under evaluation. It consists of a strain-gauge sensor embedded in a soft silicone contact lens and it detects circumferential changes in the region of the corneo-scleral junction and transmits its measurements wirelessly to portable recorder. However, the device still awaits clinical validation, it is not clear what it measures and is therefore not ready for general use, Prof Iester said. “Goldmann applanation tonometer is still highly recommended in clinical practice. What we need for management is a baseline value not absolute number but a reproducible IOP measurement to assess the effect of treatment during the followup. Probably in the future we could have a different device able to analyse IOP data all day long,” he added.

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GLAUCOMA MEDICATION

Benefits of preservative-free eye drops will outweigh the costs in some glaucoma patients by Roibeard O’hEineachain

he preservatives contained in some glaucoma eye drops have side effects which can reduce the quality of life over the short term and the efficacy of treatment over the long term, said Frances Meier-Gibbons MD, Rapperswill, Switzerland. “The adverse effects of preservative agents lead to reduced compliance and therefore to higher costs. There are alternatives to preserved eye drops and many patients would benefit from using them,” she said at a Glaucoma Day session of the XXXI Congress of the ESCRS in Amsterdam. Almost all topical IOP-lowering eye drops contain preservative agents to reduce the risk of microbial contamination. Benzalkonium chloride (BAK) is the most widely used preservative agent. It is a cationic surfactant that leads to cell lysis. The concentration of BAK in glaucoma eye

drops typically ranges from 0.004 per cent to 0.02 per cent. However, BAK is unreliable as a means of maintaining the sterility of eye drops, she said. In fact, one study showed that up to 34.8 per cent of eye drop bottles with the preservative are contaminated after two weeks of use. (Tasli et al, ent Eur J Public Health. 2001;9(3):162-4.) Furthermore, IOP-lowering drugs that contain BAK have been linked to adverse reactions and ocular surface disease. The typical side effects of preservative agents, especially BAK, include allergic reactions such as photophobia, stinging and burning, which occur in up to 11 per cent of patients. Other side effects include dry eye sensations that increase with increasing number of BAK containing drugs. “BAK has a direct toxic effect on the ocular surface. It decreases tear film stability. It causes inflammatory

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EUROTIMES | Volume 19 | Issue 2

cell infiltration, it induces epithelial abnormalities and it leads to inflammation in the eye that can be found even in the posterior part of the eye,” Dr MeierGibbons said. Dr Meier-Gibbons noted that a very important side effect in the long term of eye drops containing preservatives is a reduction in the success rate of glaucoma operations.

Ocular surface disease Ocular surface disease frequently occurs in patients using glaucoma medications, she noted. In a study involving 630 glaucoma patients receiving topical medications, 14 per cent had severe ocular surface disease and a further 14 per cent had moderate ocular surface disease and 21 per cent had mild ocular surface disease, comprising together 49 per cent of the glaucoma patients (Fechtner et al, Cornea 2010. 29(6):618-621). “Ocular surface disease is a multifactorial disease with intrinsic and extrinsic factors. It involves tear-film disturbances and dryness and ocular surface changes with ocular discomfort, reduction of the visual acuity and a reduction of the quality of life,” Dr MeierGibbons said. A study published recently showed that the risk factors for developing ocular surface disease include the number of medications used, the prolonged use of preserved drugs and the total BAK exposure (Rossi et al, Eur J Ophthalmol. 2013 May-Jun;23(3):296-302). She added that after inadequate IOP reduction, the occurrence of side effects is the second most important reason glaucoma patients change their medication. Treatment becomes more expensive when patients have to change from one agent to another. A review of 500 patients treated at a centre in The Netherlands showed that cost of treating a patient rose from $347 (€256) when patients had no adjustments in their medication to $1,765 (€1,304) when patients required three or more adjustments to their medication. Outpatient visits to the ophthalmologist and medication contributed most to total costs. (Oostenbrink et al, 2001, J Glauc ; 10: 184-191.)

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Ocular surface disease is a multifactorial disease with intrinsic and extrinsic factors. It involves tear-film disturbances and dryness and ocular surface changes with ocular discomfort, reduction of the visual acuity and a reduction of the quality of life

Frances Meier-Gibbons MD

Preservative-free eye drops

Preservative-free single-use IOP-lowering eye drop preparations are now commercially available. Studies involving patients who change to BAK-free treatment have shown that there is a reduction in ocular surface disease and improvement of quality-oflife. (Uusitalo et al Acta Ophthalmolgica. 2010;88:329-36 . Katz et al, Clin Ophthalmol. 2010; 4: 1253–1261.) “The European Glaucoma Society supports the utilisation of preservative-free ophthalmic agents for chronic glaucoma treatment because they recognise the problems the preservatives can cause for the ocular surface,” Dr Meier-Gibbons said. Glaucoma patients who are most likely to benefit from preservative-free medication are those with a known allergy to the preservative, those with severe dry eye and children. Additional indications for preservative-free eye drops are patients who have a long life expectancy, ocular surface disease or who are at a high risk for surgical intervention. “I would probably not change a patient to preservative-free drops if they were 80 years old and doing well on their current drops and were not likely to require surgery. However, I would change a patient below the age of 60 to a preservative-free regimen and would also do so in patients taking two or more drugs and also those showing signs of ocular surface disease,” Dr MeierGibbons added.

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GLAUCOMA

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IOP SENSOR

What is Triggerfish telling us? by Cheryl Guttman Krader

tudies conducted so far with a noninvasive contact lens-based system (Triggerfish®, Sensimed) designed to provide continuous IOP-related monitoring demonstrate it is safe, welltolerated and reproducibly records 24-hour patterns. The contact lens sensor (CLS) measures IOP indirectly by detecting three-dimensional changes in eye shape near the corneoscleral junction, and it records the fluctuations in units of millivolts for which there is no calibration for direct conversion to mmHg. While the device is generating excitement for its potential to bring new understanding about the pathophysiology of glaucoma and the development of personalised approaches to disease management, research is still focusing on the basic issue of how to interpret the data it provides. “The CLS is speaking to us about IOP in a new language, but first we need to decipher the alphabet,” said René Goedkoop MD, chief medical officer, Sensimed, Lausanne, Switzerland, speaking at the 2013 ARVO meeting in Seattle. “Elucidation of the relationship between the CLS measurements and IOP is an important, but complicated issue because the data cannot be obtained concurrently in the same eye. Furthermore, we know that tonometry itself is relatively unreliable and has a lot of variability.” As of May, 2013, more than 630 patients had been entered into clinical trials using the CLS and 26 studies were ongoing. Researchers aiming to validate the device have conducted studies to determine whether it can capture patterns that are known for IOP and to see if its measurements can be related to tonometrydetermined IOP. At ARVO 2013, Ungaro and colleagues from Parma, Italy, reported on using the CLS in healthy subjects undergoing a water drinking test to provoke increased IOP. A similar study enrolling patients with primary open-angle glaucoma (POAG) washed out from treatment was reported by Mansouri et al. at the American Glaucoma Society 2013 meeting. In both investigations, the CLS output correlated with IOP measured by Goldmann applanation tonometry (GAT) in the contralateral eye. Both studies found that the peak measurement occurred later using the CLS than with GAT.

EUROTIMES | Volume 19 | Issue 2

Other investigations at ARVO 2013 found that changes in the CLS signal were not related to changes in IOP measured by tonometry. In a multicentre study including POAG patients who underwent continuous CLS monitoring in one eye for 3-24 hours, results from regression modeling showed a low correlation between the CLS and tonometry readings (GAT and iCare Pro) in fellow eyes and in the same eyes after removing the CLS. “The low correlation between these techniques may be due to a difference in measurement methodology and/or location (central vs. peripheral cornea), or to some unknown reasons. We believe that better understanding is needed before this device can be applied to patient care and in research studies,” said Milko Iliev, MD, professor of ophthalmology, consultant and head of the glaucoma service, University of Bern, Switzerland. The CLS is also being used to profile IOP patterns in a number of treatment intervention studies that are actively accruing patients, and a registry capturing pre- and post-intervention 24-hour curves is active at 10 sites and will be expanded to more than 25 sites worldwide. At ARVO 2013, investigators from the Singapore National Eye Centre reported their experience using the CLS sensor to study circadian IOP in newly diagnosed primary angle closure glaucoma treated by laser peripheral iridotomy. In France, Nordmann et al. are studying POAG patients treated by selective laser trabeculoplasty (SLT). Data available from the first three patients showed dramatic post-SLT decreases in night-time IOP in two patients and no change in the third. “These data have to be interpreted with caution given the low number of subjects in the two aforementioned studies,” Dr Goedkoop said. Further studies are warranted, which is why the CLS is also being used to profile IOP-related patterns in a number of active interventional treatment studies and a registry capturing pre- and post-intervention 24-hour curves that is active at 10 sites and will be expanded to more than 25 sites worldwide, he concluded.

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Update

RETINA

GEOGRAPHIC ATROPHY

GA represents an unmet medical need as there is currently no medical or surgical treatment for the disease by Dermot McGrath

ill geographic atrophy (GA) be treatable by 2020? Based on current rates of progress and the growing momentum behind clinical trials related to the disease, the answer is a guarded “yes”, according to Monika Fleckenstein MD. Addressing delegates at the 13th EURETINA Congress in Hamburg, Dr Fleckenstein, a research and clinical fellow in the Department of Ophthalmology at the University of Bonn, Germany, said that while she is optimistic that an effective treatment will be available to treat GA by 2020, or perhaps even earlier, she is less confident that all subtypes of the disease will be amenable to treatment. “There are promising drugs in the pipeline for GA treatment. However, we need to bear in mind that there might exist GA subtypes with differential pathogenesis, and non-critical merging of different GA

types may obscure a therapeutic effect in distinct subgroups. For this reason, precise phenotyping in GA is crucial in interventional trials and individualised therapy might be key for treatment of GA in the future,” she said. Dr Fleckenstein reminded the audience that GA represents an unmet medical need as there is currently no medical or surgical treatment for the disease. “There is a clear need for an effective treatment as GA is a common cause for severe visual loss in the elderly and is characterised by expanding areas of outer retinal atrophy with corresponding absolute scotoma,” she said.

Differant pathways In advanced AMD, the disease is characterised by progression and regression of drusen deposits, hypopigmentation and ultimately RPE cell death, with focal thickening of Bruch’s membrane and atrophy of the

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There are promising drugs in the pipeline for GA treatment Monika Fleckenstein MD

underlying choriocapillaris. Dr Fleckenstein noted that different pathways in the pathogenesis of GA have been described, allowing for subsequent therapeutic targets in dry AMD to be identified. “This includes, for example, the accumulation of toxic by-products of the visual cycle and so-called modulators of the visual cycle appear to be promising as a therapeutic approach. Also complement system dysregulation and inflammation appear to be crucial in the AMD process and different targets have been identified in the pathways,” she said. Oxidative stress also seems to be a key player in the AMD pathogenesis, added Dr Fleckenstein, with antioxidants and neuroprotective compounds showing some potential in treating the disease. However, the role of the choriocapillaris in the pathogenetic cascade is not fully elucidated at this point, she said. “The role of the choriocapillaris is still under debate and it is not known if changes in the choriocapillaris are a primary factor in the disease process or if these changes are of secondary character. Choroidal perfusion may be beneficial in this particular pathway,” she said. The encouraging news for patients, however, is that a lot of effort is currently being directed towards finding an effective treatment for GA, said Dr Fleckenstein. “Entering the term ‘geographic atrophy’ into the database at clinicaltrials.gov gave 63 hits and most of these studies involve therapeutic intervention. I think this is promising news for patients with this blinding disease,” she said.

GA subtypes Dr Fleckenstein specified that the realistic goal for the immediate future is to halt or slow down the progression of the GA. EUROTIMES | Volume 19 | Issue 2

Monika Fleckenstein – Monika.Fleckenstein@ukb.uni-bonn.de

“This target might well be achievable provided there is a potent compound. By contrast, the actual healing of GA with the restoration of functional photoreceptors, retinal pigment epithelium, Bruch’s membrane and choriocapillaris in areas of existent atrophy appears to be a nonachievable ambition at present,” she said. Dr Fleckenstein said that a lot of her own research has been geared to identifying different GA subtypes and understanding whether each subtype has a distinct pathogenesis. “If the answer is ‘yes,’ the question is, will the different subtypes be treatable by the same compound?” she said. Dr Fleckenstein showed how fundus autofluorescence (FAF) imaging can be used to classify distinct subtypes of GA. One such subgroup, GPS+, is characterised by a fine granular pattern with peripheral punctate spots and is similar to the phenotype in patients with Stargardt’s disease. “The data suggests that the GPS phenotype is accounted for by monoallelic variants in the ATP-binding cassette transporter 4 (ABCA4) gene and we hypothesise, therefore, that there is a differential underlying pathogenesis in GPS compared to other GA subtypes. This means that complement inhibition in GPS patients may be less effective than in other GA subtypes,” she said. FAF imaging has also helped to identify another variant of GA associated with a lobular appearance of atrophy, rapid progression and an earlier age of onset compared to patients with other GA subtypes. Patients with the trickling phenotype also seem to have a significantly thinner choroid than other GA subtypes, she said. “These characteristics point to a primary involvement of choroidal perfusion in the trickling phenotype and we hypothesise that there is a differential underlying pathogenesis of trickling compared to other GA subtypes. Patients with this phenotype may profit from choroidal perfusion enhancers.” Dr Fleckenstein said that the recent results of the phase II MAHALO study of the complement inhibitor lampalizumab (Genentech Inc., Novartis) underscore the progress being made in this field of research. “MAHALO is the first study to demonstrate a positive treatment effect with a complement inhibitor in GA. Lampalizumab-treated eyes showed a 20.4 per cent reduction in atrophy progression, and a biomarker-defined subpopulation showed a 44 per cent reduction in GA progression at 18 months. The compound was also found to have an acceptable safety profile with no intraocular infections, inflammation or IOP issues and no serious adverse events suspected to be caused by the study drug,” she said.

Update

RETINA

Abstract submission deadline: 1 March 2014

ADAPTIVE OPTICS

Three core technologies incorporated in one device by Dermot McGrath

daptive optics scanning laser ophthalmoscopy (AOSLO) allows non-invasive, in vivo visualisation of the retinal microstructures of a living human eye and may help to pave the way to earlier detection and better management of a range of retinal pathologies, according to Wolf M Harmening PhD. “Adaptive optics compensate for ocular blur and create access to clinically relevant retinal structures in the living eye. But we can go a step further with the AOSLO by delivering light to microscopic cellular targets in order to conduct single cell psychophysics. This gives us the opportunity to correlate retinal structure and visual function directly,” he said. Addressing delegates attending the 13th EURETINA congress in Hamburg, Dr Harmening, a postdoctoral fellow at the University of Bonn, Germany, said that adaptive optics imaging techniques allow for direct visualisation of cellular intraretinal structures that were previously inaccessible with traditional imaging systems. “Utilising adaptive optics really brings us forward and allows us a deeper view into microscopic structure of the retina in living eyes. We are now able to see rods and cones in vivo and with a little bit of tweaking we can even see the retinal pigment epithelial cells. We can also observe blood flow and analyse it in the smallest capillaries around the fovea and also focus on the retinal nerve fibre layer if required,” he said. Dr Harmening explained that the utility of the AOSLO moving towards functional tests derives from three core technologies incorporated in one device. “First, adaptive optics allows us to compensate for aberrations in the eye, giving cell-level access to the retina. Second, the effects of chromatic aberration can be measured and corrected with sub-cellular resolution, and finally to be able to target and hit single cells repeatedly, AOSLO imaging enables us to correct for eye motion with high-speed, real-time eye tracking functionality,” he said. Much of Dr Harmening’s research has focused on what he terms “Single-cell psychophysics,” studying the relationship between physical stimuli delivered to individual cells in the retina and the sensations and perceptions they result in. EUROTIMES | Volume 19 | Issue 2

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Adaptive optics compensate for ocular blur and create access to clinically relevant retinal structures in the living eye

14th EURETINA Congress

LONDON 11-14 September 2014

Wolf M Harmening PhD By targeting individual cones and neighbouring cells with multiple scans, the AOSLO enables researchers to classify and map complex retinal circuitry, said Dr Harmening. In a recent study, for instance, AOSLO was used to distinguish L-cones from M-and S-cones using psychophysical testing. “Using this approach the cones can be mapped and classified. Of course there is still a lot of work to be done on understanding why the map looks a particular way, but we are making progress in this direction,” he said. Another interesting application of AOSLO technology lies in trying to understand more about colour perception and the role of surrounding cones in the living human retina. “Once you have mapped out a particular area of cones, then you can start to ask about retinal circuitry and how these signals from single cones integrate in a specific observer,” said Dr Harmening. He cited in particular the work in this field of Ramkumar Sabesan et al who showed how it is possible to directly test colour perception from single cone stimulation. “He found that the colour perceived can be quite different and is a function of the position where the stimulus actually landed on the cone. So this can tell us something about the receptive field properties of these cells and the ganglion cells behind them,” he said. Stimulating two cones at the same time is a useful way of studying how signal integration works on single-cell level, concluded Dr Harmening.

contact Wolf M Harmening – wolf.harmening@ukb.uni-bonn.de

www.euretina.org

contact

Update

RETINA

MAHALO TRIAL

Biologic agent appears to be effective in slowing geographic atrophy progression

Courtesy of Frank Holz MD

by Roibeard O’hEineachain

Progression of geographic atrophy over four years documented on fundus autofluorescence images (Spectralis, Heidelberg Engineering, Germany)

onthly injections of the biologic agent lampalizumab (Roche) can significantly reduce the rate of progression of geographic atrophy (GA), according to the results of the MAHALO phase II trial, which Frank Holz MD presented at the 13th EURETINA Congress in Hamburg. “The results of MAHALO phase II study with a complement inhibitor are promising. It is the first study to demonstrate a positive treatment effect in geographic atrophy due to age-related macular degeneration, said Dr Holz, University of Bonn, Germany. In the multicentre study, 123 patients with GA were randomised to receive injections of 10.0mg of lampalizumab or sham injections in one eye, either monthly or every other month. At 18 months’ follow-up, the mean amount by

which the area of GA had increased from baseline values was 20.4 per cent lower in eyes receiving the monthly lampalizumab regimen compared to eyes in the sham injection groups. All of the patients in the study had bilateral GA secondary to AMD and were free of choroidal neovascularisation at baseline. None of the study eyes had undergone previous intravitreal injections, had a history of retinal surgery or other retinal therapeutic procedures. The treatment groups were well-matched in terms of demographics and disease severity. The mean total area of atrophy in study eyes was roughly 3.4 disc areas or approximately 8.6mm². In no cases was the total area of atrophy greater than five disc areas or less than one disc area. In addition, hyperautofluorescence was

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present adjacent to the GA at baseline in all eyes.

Effect evident from six months

The researchers tracked the changes in the atrophic area throughout follow-up using fundus autofluorescence imaging with a confocal SLO system. Their findings showed that the reduction in growth rate among the monthly lampalizumab group was evident from six months' follow-up until the end of the trial. However, the atrophic lesion growth rate in the group receiving lampalizumab every two months was virtually identical to that of the sham injection groups throughout the same follow-up period, Dr Holz pointed out. In terms of visual acuity, there was no significant difference between the groups at any point of follow-up, indicating that the treatment did not have any deleterious effect on retinal function, he noted. The lampalizumab injections were well tolerated, overall, Dr Holz said. The most common of ocular adverse effects were eye pain and conjunctival haemorrhage, which were associated with the injection procedure and occurred with a frequency similar to that in eyes undergoing antiVEGF injections. There were no serious adverse ocular events that could be related to the biologic agent and there were no serious systemic side effects and there were no deaths. Some 30 patients dropped out of the study for various reasons. Treatment was discontinued in six eyes due to choroidal neovascularisation, which makes measurements of the atrophy very difficult. The most common cause for discontinuation was the decision of the patient or physician or because of a patient’s condition requiring another treatment.

Results varied between subgroups

One potentially very useful finding of the study was that there were certain subgroups of patients who did markedly

Frank Holz – Frank.Holz@ukb.uni-bonn.de

better than others. In particular, the MAHALO study researchers found that among patients with certain exploratory biomarkers, the amount of GA progression among those receiving monthly injections of lampalizumab rate was 44 per cent lower than it was among those receiving sham injections. In addition, among patients who were positive for the exploratory biomarkers and who presented with a visual acuity from 20/50 to 20/100, the growth of the GA was reduced by 54 per cent (p<0.005) among those receiving monthly lampalizumab. Dr Holz noted that 57 per cent of patients were positive for the exploratory biomarkers.

Damping down the alternative complement pathway

Lampalizumab is an antigen-binding fragment (Fab) of a humanised, monoclonal antibody that is active against complement factor D, a rate-limiting enzyme involved in the activation of the alternative complement pathway. The aim of treatment with the agent is to inhibit the alternative complement pathway. Research has implicated hyperactivity of the complement pathway in the pathogenesis of AMD and geographic atrophy, Dr Holz explained. Moreover, many studies have shown that there are polymorphisms in the genes for proteins involved in the complement pathway that are strongly associated with the risk of AMD. “What we have learned from various studies including the FAM and the AREDS study is that atrophy will continue to grow once it gets started. And so, although we don’t expect improvement of vision, it makes sense to try and slow down the growth of the atrophy. And if the phase II results are reproduced in the phase III trial and we find that we can preserve the foveal function over several years, that will be of high clinical relevance to patients,” he added.

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Francesco Bandello – bandello.francesco@unisr.it

Update

RETINA

DME DEVELOPMENTS

New therapies and imaging technologies revolutionising DME management by Dermot McGrath

“

visual function, Dr Bandello said. “No examination alone can tell us everything about the prognosis and management of DME. While we have seen a major improvement in the quality of morphological information that we can obtain from our instruments, we still need more precise, functional information to be able to bridge the gap which exists sometimes between what the patient is experiencing and what we are seeing on our images,” he said. Imaging modalities such as fluorescein angiography, spectral domain optical coherence tomography (OCT), retromode imaging, fundus autofluorescence, adaptive optics and microperimetry are now available to help clinicians in the diagnosis and management of DME, said Dr Bandello. While fluorescein angiography alone is not sufficient for DME diagnosis, it is nevertheless useful for providing a qualitative assessment of vascular leakage. “It helps in identifying treatable vascular lesions and is essential for assessing the presence of the foveal avascular zone (FAZ) associated with poor prognosis. It also gives us valuable information on the capillary network or to understand why we may have a drop in visual acuity in cases where there is no obvious explanation based on fundus imaging,” he said. The real game-changer for DME management in clinical practice, however,

Q-LAS PCL5

The prognosis of diabetic retinopathy has really improved thanks to the progress made in recent years...

Francesco Bandello MD, FEBO has been undoubtedly the progress made in OCT, said Dr Bandello. “Nothing else has been able to modify the day-to-day management of patients like OCT. The combination of potent intravitreal therapies and a non-invasive diagnostic tool that is reliable and gives good results in terms of the quantification of lesions has made a huge difference to our understanding and management of DME,” he said. With OCT now being used routinely in clinical practice, hard data is emerging to guide clinicians in their management of patients. “We now know that around 60 per cent of patients with foveal thickening and intraretinal optical reflectivity on OCT have focal leakage on fluorescein angiography. But more than 90 per cent of patients with diffuse cystoid leakage exhibit foveal thickening with decreased optical reflectivity on OCT,” he said.

dvanced imaging techniques allied to potent new anti-VEGF and steroid therapies have radically transformed the prognosis and management of patients with diabetic macular oedema and other debilitating retinal diseases over the past decade, according to Francesco Bandello MD, FEBO. “We are living in exciting times for retinal experts. We have new diagnostic tools and new therapeutic options where we are able to modify the management of many retinal diseases. The prognosis of diabetic retinopathy has really improved thanks to the progress made in recent years, which is good news for us as retinal specialists but more importantly for our patients who are suffering the effects of DME,” he told delegates attending the 13th EURETINA Congress in Hamburg. In a broad overview of recent developments in the diagnosis and treatment of DME, Dr Bandello noted that the disease remains the leading cause of visual impairment in people with diabetes mellitus. “If untreated, more than 50 per cent of patients lose more than two lines of visual acuity in two years. DME affects the working-age population, thereby imposing a significant burden both on society and the individual,” he said. While imaging modalities have improved greatly over the past decade, DME imaging must always be correlated to

OCT is also helpful in quantifying changes over time and assessing the presence of intraretinal and subretinal fluid, added Dr Bandello. “This is useful for charting the natural history of the disease, as well as response to treatment and retreatment evaluation. We tried unsuccessfully for a long time to do the same thing with fluorescein angiography for leakage, whereas OCT enables us to objectively evaluate different treatment effects. This explains why it is being so widely used now in clinical trials,” he said. With so many imaging options available to clinicians, Dr Bandello advised drawing on as many different modalities as possible in order to build up the most complete picture possible of the disease. “I think it is important to consider all these diagnostic tools together in order to be able to classify our patients in a better way. I am always repeating that the old definition of clinically significant DME based on topography of lesions may not be the best way of classifying our patients. We should try to use the different options available to us in order to interpret each single clinical case and be able to attribute different treatment options based on that information,” he said. With a variety of treatment options now available for DME, Dr Bandello said that his group has created a treatment algorithm to help guide the treatment for each patient. “For vasogenic DME we perform laser treatment and then only in cases where we have no response we use anti-VEGF drugs or steroids. In non-vasogenic oedema we start with anti-VEGF and steroids and use laser afterwards in cases where it is possible to obtain a thin retina after the injections. This means that you perform the laser treatment using less energy for better results. For tractional DME, we usually advocate surgery plus steroids or anti-VEGF injections,” he said.

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Update

RETINA

AMD GENOTYPING

Genetic risk assessment provides valuable guidance for treatment decisions by Cheryl Guttman Krader

G 5th EuCornea Congress

LONDON 12-13 September 2014 Abstract submission deadline: 1 March 2014

www.eucornea.org

EUROTIMES | Volume 19 | Issue 2

enetic risk assessment for agerelated macular degeneration (AMD) should be part of the patient selection process for multifocal IOLs, Steve A Arshinoff MD told delegates at the XXXI Congress of the ESCRS in Amsterdam. Dr Arshinoff also believes the information provided by AMD genetic testing allows him to optimise clinical care of his patients in other ways as it allows him to individualise recommendations on follow-up for AMD and use of vitamin-mineral supplements to prevent AMD progression. Dr Arshinoff is in private practice, Toronto, Ontario, Canada. The recommendation for testing in patients wanting a multifocal IOL recognises that both multifocal implants and AMD reduce contrast sensitivity. Thus there is concern that patients implanted with a multifocal IOL may experience a synergistic reduction in their quality of vision should they develop even mild AMD in the future. Since the patients most interested in an accommodating IOL tend to be younger, they are unlikely to have developed drusen at their initial presentation to their ophthalmologist. Results from commercially available genetic testing (Macula Risk) can be useful for informing the surgical decision for these patients, in Dr Arshinoff’s view. “Previously we considered the phenotypic appearance of the eye, macular pigment levels and patient-related non-genetic factors to determine AMD risk. Now, using available genetic testing, we can predict with 90 per cent accuracy an individual’s 10-year risk for progression to advanced AMD.” Dr Arshinoff said he tells his patients that if they develop significant drusen from AMD in the future after being implanted with a multifocal IOL, they will see worse than if they had a monofocal IOL. The only way to assess their risk for that outcome is with genetic testing. The test assesses 15 genetic markers across 12 genes that are known to confer AMD risk and integrates information on findings of AMD from the clinical exam plus non-genetic risk factors (age, smoking history, BMI and education) to calculate risk. Dr Arshinoff said that in his experience so far, most patients agree to the evaluation, which costs about $300. As a caveat, he observed that his current practices reflect understanding of the limitations of existing IOL technology and the power of genetic

testing, and his recommendations may change over time. “In the future, we can anticipate availability of presbyopiacorrecting IOL technology with less or no effect on contrast sensitivity as well as advances in genetic testing that will allow us to be more accurate and specific in providing prognostic information for patients,” he said. Determination of a patient’s risk for developing advanced AMD not only provides useful information on the decision to choose multifocal IOLs, but it identifies people who should be monitored more carefully for AMD. “Retinal specialists see patients only after they have lost vision from AMD in at least one eye, whereas cataract surgeons see everybody. We have an opportunity to make recommendations that may minimise their risk of progression and achieve early detection of CNV.” In addition, pharmacogenetic testing that is now available as part of the AMD genetic risk assessment provides guidance for recommendations on the use of ocular multivitamin-mineral supplements by patients with moderate AMD. The latter testing was developed based on a recently published study analysing data from patients enrolled in the Age-Related Eye Disease Study (AREDS) who had category 3 AMD [Awh CC, et al. Ophthalmology. 2013;120(11):2317-23]. When patients were profiled with respect to complement factor H (CFH) and agerelated maculopathy sensitivity 2 (ARMS2) inherited genetic polymorphisms and type of nutritional supplement they received (antioxidants and/or zinc), the results showed that the components of the AREDS formulation could be harmful, beneficial or have no effect on progression risk depending on the individual’s genotype. The only patients who benefited from the combination of antioxidants and zinc were those with one CFH and one ARMS2 risk allele, and they comprised only 23 per cent of the population. Nearly half of the study population would have been better off if they used antioxidants or zinc alone versus the combination, and the risk of disease progression was actually increased among persons having 1 or 2 CFH risk alleles with no ARMS2 risk alleles if they took zinc.

contact Steve A Arshinoff – ifix2is@sympatico.ca

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Save the Date

Friday, April 25 – Monday, April 28, 2014 Make the most of your time at the ASCRS•ASOA Symposium & Congress and attend our EyeWorld programs for additional CME and an opportunity to network with your colleagues.

BO S TON 2014

Registration opens January 2014 www.EyeWorld.org EUROTIMES | Volume 19 | Issue 2

EPISCLERAL DEVICES

Positive outcomes with novel episcleral brachytherapy device for wet AMD

by Dermot McGrath

minimally invasive retrobulbar episcleral brachytherapy device (SalutarisMD™, Salutaris Medical Devices) has shown promise in the treatment of a small cohort of exudative AMD patients, according to Kamaljit Balaggan MRCOphth, PhD. Dr Balaggan, Moorfields Eye Hospital, London and Department of Genetics at the University College London Institute of Ophthalmology, reported the feasibility and tolerability of the SalutarisMD investigational treatment for wet AMD using a single dose of episcleral brachytherapy in conjunction with intraocular anti-VEGF injections. “The objectives of the study, carried out at the University of Arizona by Reid Schindler and Leonard Joffe, were achieved in terms of safety and efficacy in a small set of six patients. The device was adequately placed over the macula and the radiation dose was delivered with minimal patient discomfort. The total procedure time is about 15 minutes and there were no serious adverse events,” he told delegates attending the 13th EURETINA Congress in Hamburg. After two years' follow-up, three out of the four treatment naive patients and one of the chronically treated patients maintained their best-corrected visual acuity levels. Of these, two treatment naive patients did not require any further injections beyond the initial mandated injections. Two patients did, however, deteriorate, noted Dr Balaggan. “One was treatment naive who had an early disciform lesion at the time of enrolment and this matured to a disciform scar within the first year and therefore received no further injections. The other patient was also quite advanced at enrolment and developed a submacular haemorrhage after 11 months and therefore received no further injections. But generally at two years all patients had reduced macular thickness and there were no other adverse events in terms of radiation-related retinopathy,” he said. Dr Balaggan said that the brachytherapy device potentially allows the radiation dose to be targeted to the treatment zone in a precise, controlled and customised manner for each patient. “There is a strong rationale for using therapeutic radiation in exudative AMD.

Radiotherapy is potentially advantageous in that it has anti-angiogenic, anti-inflammatory and anti-fibrotic properties,” he said. The brachytherapy device is designed to be used as a one-off, adjunctive treatment to anti-VEGF injections, said Dr Balaggan. “Combining this therapy with antiVEGF injections may result in synergy and a reduced anti-VEGF treatment burden for the patients, as well as hopefully increasing the proportion of patients that respond to treatment. It may also enhance the potential of patients to preserve their visual acuity,” he said.

Minimally invasive procedure

One of the advantages of the episcleral device is that it offers a minimally invasive procedure performed under sub-tenon’s anaesthesia and remains episcleral at all times, said Dr Balaggan. The device consists of a curved cannula with a fibre-optic light source at the tip which is attached to a plastic housing in which radioactive strontium-90 seeds, are stored. The seeds are attached to a flexible cable which is, in turn, attached to a plunger. Using an indirect ophthalmoscope, the surgeon guides the probe tip to the CNV area and then depresses the plunger in order to deliver the radioactive seeds to the tip for the treatment duration of around five minutes. As well as being minimally invasive, the surgeon can target AMD lesions irrespective of their lesion centre, said Dr Balaggan. “By measuring scleral and choroidal thicknesses non-invasively in patients we can also customise the dosing for each patient. It is also important to note that the highest dose is received by the sclera, not the retina and the episcleral probe remains in firm contact with the macula throughout the entire period and this is an inherently stable position,” he said. Summing up, Dr Balaggan said that this initial prospective study supports the safety and tolerability of this novel device, and further evaluation is planned in larger phase I/II trials in 2014.

contact Kam Balaggan – kambalaggan@yahoo.co.uk

contacts

Luca Buzzonetti – luca.buzzonetti@opbg.net H Burkhard Dick – burkhard.dick@kk-bochum.de Tim Schultz – tim.schultz@kk-bochum.de

Update

PAEDIATRIC OPHTHALMOLOGY

Femtosecond laser surgery

Lasers can improve safety and efficacy of cataract and keratoplasty procedures in children by Roibeard O’hEineachain

EUROTIMES | Volume 19 | Issue 2

Intrabubble DALK Femtosecond laser can also enhance the outcomes of deep anterior lamellar keratoplasty (DALK) in paediatric eyes, reducing the risk of perforation and improved visual acuity results, said Luca Buzzonetti MD, Bambino Gesù Children’s Hospital, Rome, Italy. Dr Buzzonetti said he performs DALK procedures in children’s eyes using a 60 KHz Intralase femtosecond laser (AMO). In addition he uses an alternative to the big-bubble technique called the intrabubble technique. In the big-bubble technique, air is injected beneath the stroma remaining after an anterior lamellar trephination in order to remove as much stroma as possible and leave a smooth interface. The intrabubble is different primarily in that it involves the use of a femtosecond laser to create a channel for the air injection part of the procedure. When performing the procedure he first creates the intrastromal channel by creating a partial side-cut angled at 30 degrees with an arc length of 25 degrees in a position corresponding to a 6.0mm diameter trephination. The intrastromal channel extends to just 50 microns above the endothelium. He then performs a full lamellar cut 100 microns above corneal thinnest point which intersects the intrastromal channel and which he uses for the base of a mushroom trephination. In addition, because the suction ring of the Intralase laser is too big for the smallest eyes, in those cases he applies the laser cone directly onto the eye surface and uses silk sutures to attach the conjunctiva to the patient's skin in order to immobilise the eye. He noted that the intrabubble DALK procedure appears to greatly reduce the chance of graft rejection compared to penetrating keratoplasty also in paediatric patients. For example, at his own centre the rate of graft rejection among paediatric patients was only 10 per cent at one year’s follow-up in eyes undergoing intrabubble DALK during the years 2010 and 2012 compared to 40 per cent in those who

Courtesy of Luca Buzzonetti MD

manuals – the principal contraindication is a patient below the age of 22, you therefore can perform this kind of surgery only 'off label' with the respective mandatory permissions including the fully informed consent of the parents,” Dr Dick added.

Docking without suction ring in six-month-old patient

Courtesy of Tim Schultz MD

emtosecond lasers are becoming very useful tools in paediatric patients with cataracts and those who require corneal transplantation, according to two presentations at Femto 2013, an international meeting on anterior segment surgery, in Verona. Burkhard Dick MD, PhD, Ruhr University Eye Hospital, Bochum, Germany, noted that he has developed a technique for performing cataract surgery in the eyes of infants using the Catalys femtosecond laser system (AMO, Santa Ana, CA) for anterior and posterior capsulotomy and lens division (if necessary at all). “The most difficult capsulotomies are those in paediatric eyes, and these are among those that will benefit most from femtosecond laser-assisted cataract surgery,” Dr Dick said. He noted that using this femtosecond laser platform he can employ an “allcomers” approach for femtosecond laserassisted cataract surgery including many difficult cases, such as hard cataracts, small pupils, intraoperative floppy iris syndrome and eyes with co-morbidities such as corneal guttata and glaucoma. He added that the Catalys system is particularly well suited to performing cataract surgery in paediatric eyes because its fluid-filled interface raises intraocular pressure only slightly, making it possible to re-dock the laser to the eye after lens aspiration and perform a posterior capsulotomy. In addition, its integrated three-dimensional optical coherence tomography provides easy visualisation of the posterior capsule. His experience to date in 20 infant eyes has yielded a few important pearls, he said. For example, he has found that the elasticity of the anterior and posterior capsule in young eyes appears to cause capsulotomies to widen after they are created. It is therefore necessary to make capsulotomies smaller initially in infant eyes. He and his associates (Tim Schultz MD) are evaluating a correction factor they have devised to compensate for this phenomenon. Another finding is that the new interface with 12mm inner diameter (LOI12) is designed for small palpebral fissures which makes it easier to perform surgery in small infant eyes. “One drawback currently is that with all of the platforms – based on the

Treatment Screen of the laser during femtosecond laser-assisted anterior capsulotomy in an Infant

underwent penetrating keratoplasty by mechanical trephination. In addition, during those same years the mean refractive and visual outcomes were better in eyes that underwent keratoplasty with the femtosecond laser-assisted intrabubble technique than it was in those who underwent big-bubble DALK with a mechanical trephine. That is, the mean spherical equivalent at one postoperative year was -1.3 D in the femtosecond laser group, compared to -4.0 D in the mechanical trephination group.

In addition, best corrected visual acuity was 0.8 in the laser group compared to 0.6 in mechanical trephine group and the respective values for refractive astigmatism were -2.8 D and -5.8 D. “Paediatric keratoplasty is still a challenging surgery, but the femtosecond laser may improve the outcomes because the lamellar geometry increases the contact between the donor and recipient corneal tissues providing ideal suture settings and improving the refractive result,” Dr Buzzonetti concluded.

Journal Watch Undetected Glaucoma

Prevalence of undetected glaucoma significantly higher among older patients

cross-sectional study of patients screened for recruitment into the Early Manifest Glaucoma Trial indicates that the incidence of undetected glaucoma increases with age although the severity of undetected disease may be similar in all age groups with one-third of cases having severe disease and a small percentage actually blind in one eye from the disease.

The authors of the study noted that these findings support those of previous research which has shown that around half of cases of glaucoma in the general population are undetected The study’s investigators invited all people aged from 55 to 79 years who were living in the catchment area of Malmö, Sweden and for whom there were no recent records at the Malmö University Hospital Ophthalmology Department to participate. Of a total of 32,918 invited citizens, 77.5 per cent participated, and among these, 406 (1.23 per cent) had previously undetected glaucoma. The researchers found that the prevalence of undetected glaucoma was significantly higher among older patients, rising from 0.55 per cent among those aged 55 to 59 years to 2.73 per cent among those 75 to 79 years. Early-stage glaucoma was more frequent in the youngest group, those aged 55 to 59 years. The extent of field loss was similar in all patients aged 60 years and older. Most of the glaucomatous eyes in each age cohort had early disease.

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Among those identified as having glaucoma, visual field defects were mild in 35 per cent and moderate in 32 per cent. Around two-thirds of those screening positive for glaucoma had unilateral disease, and 134 subjects (33 per cent) had advanced visual field loss in at least one eye. Although none of those screened were blind in both eyes, 3.4 per cent of the newly diagnosed patients were unilaterally blind because of glaucoma. The screening examination involved measurement of visual acuity, refractive error and intraocular pressure using Goldmann tonometry and monoscopic fundus colour photography. Those who screened positively underwent a postscreening examination which included visual field testing with the 24-2 Full-Threshold program of the Humphrey Field Analyzer. In 86 per cent of eyes, the diagnosis of glaucoma was based on the presence of repeatable visual field defects. In nine per cent of eyes the diagnosis was based on visual field loss plus corresponding optic nerve changes. In five per cent of eyes, the diagnosis was based on disc appearance only because useful visual fields were not available. The authors of the study noted that these findings support those of previous research which has shown that around half of cases of glaucoma in the general population are undetected. However, they pointed out that the rate of undetected glaucoma in their population was most likely an underestimate since the criteria they used may have missed some cases with normal IOP. Moreover, in other populations with higher proportions of patients of African descent the incidence of undetected glaucoma could be considerably higher. n

(Heijl et al, Ophthalmology, “Prevalence and Severity of Undetected Manifest Glaucoma, Results from the Early Manifest Glaucoma Trial Screening”, 2013 doi: 10.1016/j. ophtha.2013.01.043).

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Additional Programming Cornea Day ASCRS Glaucoma Day ASOA Workshops Technicians & Nurses Program

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www.ascrs.org www.asoa.org The Only U.S. Meeting Dedicated to the Anterior Segment Specialist & The Leading Practice Management Program in Ophthalmology Follow @ASCRStweets on Twitter. #ASCRSASOA2014

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20.11.2013

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Seite 1

Review

JCRS Highlights Journal of Cataract and Refractive Surgery

When not to correct astigmatism Should refractive surgery be employed to correct 0.75 D or less of cylinder? The question poses a dilemma for surgeons since even standard ablations in photorefractive keratectomy and LASIK to correct myopia can induce a mean astigmatism of approximately 0.50 D. While toric intraocular lenses (IOLs) are an option for pseudophakic patients with astigmatism, the possible astigmatism induced by the corneal incision and the rotational and tilt errors during IOL positioning can limit the efficacy of correcting small amounts of astigmatism. Spanish researchers conducted a study to evaluate how small amounts of astigmatism affect visual acuity and the minimum astigmatism values that should be corrected to achieve maximum visual performance. They used wavefront sensing to measure astigmatism and higher-order aberrations in 54 normal young eyes with astigmatism ranging from 0.0 to 0.5 D. They corrected astigmatism using a purpose-designed cross-cylinder device. They calculated optical image-quality metrics for three conditions: natural astigmatism, corrected astigmatism and astigmatism only (with all HOAs removed). There was no significant correlation between the amount of astigmatism and visual acuity. The correction of astigmatism improved visual acuity for only high-contrast letters from 0.3 D, but with a high variability between patients. Lowcontrast visual acuity changed randomly as astigmatism was corrected. The correction of astigmatism increased the mean imagequality values but there was no significant correlation with visual performance. The deterioration in image quality given by astigmatism higher than 0.3 D was limited by higher order aberrations. The researchers conclude that under clinical conditions, the visual benefit of precise correction of astigmatism less than 0.5 D would be limited. n EA

Villegas et al., JCRS, “Minimum amount of astigmatism that should be corrected”, Volume 40, Number 1, 13-19.

to cut within endothelial layer in three per cent and suction break in two per cent. No complications required vitrectomy. However, all of these complications occurred within the first 100 cases. The researchers conclude that with cautious surgical technique, the complications seen in this study can be avoided. n Z

Nagy et al. JCRS, “Complications of femtosecond laser-assisted cataract surgery”, Volume 40, Number 1, 20-28.

PCO and different IOL types In spite of ongoing improvements in IOL design and surgical technique, posterior capsule opacification (PCO) remains the most prevalent complication after cataract surgery. A randomised controlled clinical study conducted over a 12-year period compared PCO incidence seen in three types of IOL: a round-edged heparin-surfacemodified PMMA IOL, a round-edged silicone IOL or a sharp-edged hydrophobic acrylic IOL. After 12 years, there was no significant difference in the fraction or severity of PCO between the silicone IOL and acrylic IOL. The HSM PMMA IOL had a significantly higher PCO fraction than the silicone IOL, but not more than the acrylic IOL. There was no difference in PCO severity between the HSM PMMA IOL and the other two IOLs. The silicone IOL had higher median capsulotomy-free survival (>150 months) than the acrylic IOL (108 months) and the HSM PMMA IOL (53 months). Overall survival without Nd:YAG capsulotomy did not differ between the acrylic and silicone IOLs or between the silicone and HSM PMMA IOLs. However, overall survival was significantly better with the acrylic IOL than with the HSM PMMA IOL. n M

Rønbeck et al., JCRS, “Posterior capsule opacification with 3 intraocular lenses: 12-year prospective study”, Volume 40, Number 1, 70-76.

Frankfurt Retina Meeting Live Surgery · Lectures Video Presentations

March 15th - 16th 2014 Dear colleagues and friends, it is my great pleasure to invite you to the next Frankfurt Retina Meeting, March 15th - 16th, 2014. As usual the meeting will include live surgery, presentations, panel discussions and videos from invited guests and participants. We look forward to welcoming you to the Frankfurt Retina Meeting 2014. Claus Eckardt, MD

Faculty

Ahmed Bedda - Egypt Ferdinando Bottoni - Italy Donald D’Amico - USA Morten de la Cour - Denmark Claus Eckardt - Germany Tillmann Eckert - Germany Ehab El Rayes - Egypt Marta Figueroa - Spain Heinrich Heimann - Great Britain Frank Holz - Germany Birgit Lorenz - Germany Tamer Mahmoud - USA Carlos Mateo - Spain

Andreas Mohr - Germany Marco Mura - Netherlands Sengul Ozdek - Turkey Grazia Pertile - Italy Stanislao Rizzo - Italy Ursula Schmidt-Erfurth - Austria Peter Stalmans - Belgium Peter Szurman - Germany Ramin Tadayoni - France Asheesh Tewari - USA Marc Veckeneer - Netherlands Wei-Chi Wu - Taiwan David Wong - China

Femtocat learning curve Femtocataract surgery has purported advantages of improved accuracy and safety. However, it is not without complications. In order to assess the incidence of complications investigators conducted a retrospective analysis of hundreds of femtosecond laser-assisted cataract surgeries. Overall, the study revealed miosis in 32 per cent of cases, conjunctival redness or haemorrhage in 34 per cent, capsule tags and bridges in 20 per cent, anterior tears in four per cent, endothelial damage due EUROTIMES | Volume 19 | Issue 2

Frankfurt Retina Meeting March 15th - 16th 2014

Thomas Kohnen associate editor of jcrs FURTHER STUDY Become a member of ESCRS to receive a copy of EuroTimes and JCRS journal

Congress Centrum Mainz Gutenbergsaal · Rheinstraße 66 55116 Mainz · Germany

For further information & registration please visit:

www.eckardt-frankfurt.de

FR M FO EM 3 Y E R BE EA E TR R R AI SH N IP EE S

Review

OPHTHALMOLOGICA

Become an ESCRS Member Integral to your continuing education

Focus on polypoidal choroidal vasculopathy

Monthly ranibizumab preserves vision

This month’s issue of Ophthalmologica features a series of articles concerned with polypoidal choroidal vasculopathy (PCV), a variant of AMD. In the first of the articles, Shigeru Honda MD, PhD and associates, explain the phenotypical differences between PCV and typical AMD in terms of its morphology and its generally poorer response to conventional anti-VEGF injection. Their review also cites the results of the recent, randomised controlled trial, the EVEREST study, in which combination therapy with photodynamic therapy (PDT) and intravitreal ranibizumab produced significantly greater improvements in visual acuity than ranibizumab alone in patients with PCV.

The results of a prospective, non-comparative study showed that among 13 eyes of 13 patients with PCV, none lost 15 or more letters of visual acuity and three patients gained 15 or more letters after receiving monthly ranibizumanb for one year. In addition, there was a resolution of subretinal haemorrhage in all nine eyes with the condition, and macular oedema improved in all five eyes with the condition. Furthermore, among nine eyes with subretinal fluid the condition completely resolved in four, decreased in two and increased in three. However, branching vascular networks persisted in all eyes and only five eyes had a decrease in polypoidal complexes.

n S

Honda et al., Ophthalmologica, “Polypoidal Choroidal Vasculopathy: Clinical Features and Genetic Predisposition” 2014 (DOI:10.1159/000355488)

FREE TO MEMBERS: ESCRS On Demand iLearn – online CME accredited learning platform In addition to: Subscription to the Journal of Cataract and Refractive Surgery Reduced ESCRS Congress Fees

PDT plus anti-VEGF combo effective in polypoidal choroidal vasculopathy The results of a new retrospective study appear to support the results of the EVEREST study, and furthermore indicate that treatment with PDT alone may be better than anti-VEGF treatment alone in patients with PCV. The authors of the study reviewed the case-notes of 62 eyes of 62 patients with PCV. All had at least two years' follow-up after initiating treatment with PDT alone, in 11 eyes, anti-VEGF therapy alone, in 23 eyes and a combination of the two treatments in 20 eyes. At the twoyear follow-up examination, the PDT and combination groups maintained significant visual improvement compared with the baseline (p = 0.041 and p = 0.021), whereas the anti-VEGF alone group failed to do so (p = 0.673).

n GT

Kokame et al. Ophthalmologica, “Polypoidal Choroidal Vasculopathy Exudation and Haemorrhage: Results of Monthly Ranibizumab Therapy at One Year” 2014 (DOI:10.1159/000354072).

Bevacizumab carries higher cardiovascular risk This month’s issue of Ophthalmologica also included a review article addressing a growing concern that intravitreal bevacizumab poses a greater risk of strokes and heart attacks than intravitreal ranibizumab. The review’s authors note that, when used systemically, bevacizumab raises the risk of cardiovascular pathologies such as hypertension, arterial thrombosis and cardiomyopathy. Furthermore, retrospective studies have consistently shown a higher risk for stroke among patients receiving intravitreal bevacizumab, compared to those receiving ranibizumab. n A

F Cruess et al. Ophthalmologica, “Cardiac Issues of Noncardiac Drugs: The Rising Story of Avastin in AgeRelated Macular Degeneration” 2014 (DOI:10.1159/000355569).

n H.M.

visit www.escrs.org today

Kang et al. Ophthalmologica, “TwoYear Outcome after Combination Therapy for Polypoidal Choroidal Vasculopathy: Comparison with Photodynamic Monotherapy and Anti-Vascular Endothelial Growth Factor Monotherapy” 2014 (DOI:10.1159/000354546).

ESCRS

José Cunha-Vaz EDITOR OF OPHTHALMOLOGICA, The peer-reviewed journal of EURETINA EUROTIMES | Volume 19 | Issue 2

Feature

industry news

Recent developments in the vision care industry

Canaloplasty business

Anterior segment surgery In cooperation with Prof Dr Lars Olof Hattenbach (Ludwigshafen) Geuder has developed the instrument series “Hybrid” for anterior segment surgery. "These tubeguided instruments transfer all advantages of a vitreoretinal surgery into the anterior segment and enable surgery in the narrowest spaces ensuring minimal damage to the surrounding tissue," said a company spokeswoman. "The instrument set for intraocular suturing for the first time facilitates stitching within the anterior chamber via a paracentesis and it is not necessary any longer to have to insert and remove long needles in an uncomfortable way," she said. n

www.geuder.com

Excimer Laser SD Healthcare attended a two-day CME-approved laser refractive surgery course held at leading eye hospital Moorfields, to demonstrate the SCHWIND excimer laser. “Our courses for ophthalmic practitioners have been provided at Moorfields for over 25 years. Continued support from the private sector including SD Healthcare is essential in allowing us to run educational courses and to maintain our world-famous reputation as experts in the field,” said Bruce Allan MD, FRCS, consultant ophthalmic surgeon, at Moorfields. “With over half the ophthalmologists practising in the UK, and many more overseas, having received specialist training at Moorfields – we are the go-to place for treatment, teaching and research,” said Dr Allan. The two-day course covering all areas of refractive surgery – from the basics to femtosecond laser flap creation – saw SD Healthcare experts on hand to demonstrate the SCHWIND Amaris 750s excimer laser during the wet lab sessions. n

www.sdhealthcare.com

EUROTIMES | Volume 19 | Issue 2

Ellex Medical Lasers Limited has recently acquired the canaloplasty business of US-based iScience Interventional, Inc which comprises the iTRACK 250 catheter and suture device for the treatment of mildmoderate glaucoma. “This acquisition is very exciting. The new canaloplasty business will allow us to provide our existing customers with a complementary product offering for the treatment of glaucoma. We are also pleased to have existing iTRACK 250 customers join Ellex,” said Ellex CEO, Tom Spurling. n

www.ellex.com

2014

APRIL 25–29

BOSTON

Discover the latest surgical techniques and technologies for the anterior segment specialist. Special Events Binkhorst Lecture Microinvasive Glaucoma Surgery: An Idea Whose Time Has Come Ike K. Ahmed, MD

Intraocular lens portfolio Carl Zeiss Meditec has acquired, through its subsidiary Carl Zeiss Meditec Inc., 100 per cent of the shares in Aaren Scientific Inc., a US-based manufacturer Ludwin Monz of intraocular lenses (IOLs). Aaren Scientific, headquartered in Ontario, California, has been manufacturing IOLs for more than two decades. The majority of shares in Aaren Scientific had previously been owned by a private investment company as well as other investors, including the CEO and co-founder of Aaren Scientific, Rick Aguilera, who along with the entire management team will stay on board after the transaction. “The two companies, ZEISS and Aaren Scientific, are highly complementary and enable ZEISS to offer ophthalmic surgeons a broader portfolio of solutions” said Dr Ludwin Monz, member of the Executive Board of ZEISS AG and president and CEO of Carl Zeiss Meditec AG. n

www.meditec.zeiss.com

Science and Medicine Lecture Creation: The History and Future of Life, DNA and Genes Adam Rutherford, PhD

2014 Charles D. Kelman Innovator’s Lecture Something Borrowed, Something New: Improved Accuracy for IOL Power Selection Warren E. Hill, MD, FACS

www.ascrs.org AMERICAN SOCIETY OF CATARACT AND REFRACTIVE SURGERY AMERICAN SOCIETY OF OPHTHALMIC ADMINISTRATORS

Reference

CALENDAR OF EVENTs

Dates for your Diary

2014 FEBRUARY

APRIL

18th ESCRS Winter Meeting

World Ophthalmology Congress

14-16 February Ljubljana, Slovenia www.escrs.org

2-6 April Tokyo, Japan www.woc2014.org

28th International Congress of the Hellenic Society of Intraocular Implant and Refractive Surgery 20-23 February Athens, Greece http://www.hsioirs.org/index.php/en/

International Symposium on Cornea: Clinical Approach 11 April Belgrade, Serbia www.cornea-belgrade2014.org

ASCRS•ASOA Symposium and Congress

12th International Ocular Inflammation Society Congress (IOIS)

25-29 April Boston, USA www.ascrs.org

27 February – 1 March Valencia, Spain www.ioisvalencia.org

ARVO

4–8 May Orlando, Florida, USA www.arvo.org

Frankfurt Retina Meeting 2014 15-16 March Frankfurt, Germany www.eckardt-frankfurt.de

The 5th World Congress on Controversies in Ophthalmology (COPHy) 20-23 March Lisbon, Portugal http://www.comtecmed.com/cophy

NEW ENTRY SOI International Congress 21-24 May Milan, Italy www.congressisoi.com

JUNE 11th EGS Congress

APRIL XIII International Congress of Cataract and Refractive Surgery 2-5 April Rio de Janeiro, Brazil http://www.cataratarefrativa2014.com.br/

SEPTEMBER

Nordic Congress of Ophthalmology (NOK 2014) 20-23 August Stockholm, Sweden http://www.nok2014.se/Default.aspx

SEPTEMBER 14th EURETINA Congress 11-14 September London, UK www.euretina.org

7-11 June Nice, France http://www.eugs.org/eng/default.asp

NEW ENTRY The 112th DOG Congress of Ophthalmology 25-28 September Leipzig, Germany www.dog-kongress.org

2nd Asia-Pacific Glaucoma Congress 10th International Symposium of Ophthalmology 26-28 September Hong Kong http://www.apgc-isohk-2014.org/

ESCRS Glaucoma Day

MAY

MARCH

AUGUST

12 September London, UK www.escrs.org

OCTOBER AAO Annual Meeting

WSPOS Paediatric Sub Speciality Day 12 September London, UK www.wspos.org

18-21 October Chicago, Illinois, USA www.aao.org

NOVEMBER

5th EuCornea Congress

NEW ENTRY SOI National Congress

12-13 September London, UK www.eucornea.org

XXXII Congress of the ESCRS 13-17 September London, UK www.escrs.org

12-15 November Rome, Italy www.congressisoi.com

27th APACRS Annual Meeting

NEW ENTRY International Annual Course and Workshop on Diagnostic Ultrasound in Ophthalmology

13-16 November Jaipur, India www.apacrs2014.org

22-26 September Vienna, Austria www.echography.com

Advertising Directory: Abbott Medical Optics: Page: 7; Alcon Laboratories: Page: 13, IBC; A.R.C. Laser Ag: Pages: 21, 23, 33; ASCRS/Eyeworld: Pages: 36, 40, 43; Croma-Pharma GmbH: Page: 38; D.O.R.C. International BV: Page: 41; Haag Streit Ag: Page: 29; Kowa: Page: 19; Medicontur: Page: 3; Nidek: Page: 11; Oculentis: Page: 22; Oculus Optikgerate GmbH: Page: 6; Oertli Instruments AG: Page: IFC; Rayner Intraocular Lenses Ltd: Page: OBC; VSY Biotechnology: Page: 15;

If you would like to see your classiﬁed ad here, please contact Mairin Condon: mairin.condon@escrs.org.

Corn

C o r n

European Society of Cornea and Ocular Surface Disease Specialists

XXXII Congress of the ESCRS 13-17 September

14th EURETINA Congress 11-14 September

5th EuCornea Congress 12-13 September

WSPOS Paediatric Sub Specialty Day 12 September

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