Vol. 18 - Issue 11 by EUROTIMES

VOLUME 18 ISSUE 11 november 2013

Paediatric

Ophthalmology Genetic Medicine

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ESCRS

EUROTIMES

november 2013 Volume 18 | Issue 11 This ISSUE... Special Focus: Paediatric Ophthalmology 4

Cover Story: Experts discuss advances in genetic testing and surgical treatments

Multiple challenges to be faced when performing paediatric cataract surgery

Bag-in-the-lens method can also be applied successfully to children

10 New agents can provide more treatment options for uveitis 12 Keratoprosthesis device shows promise in selected paediatric patients 13 New study shows glaucoma drainage implants effective but complications likely 14 Managing orbital cellulitis in young patients

Cataract & Refractive 16 CME aetiology remains elusive and condition can occur in low-risk eyes 17 Benefits of using hydrogel ocular bandages after cataract surgery discussed 19 Good early reviews for IOL

Cornea 20 DMEK has many advantages but problems still remain 21 Biosynthetic corneal implants could help address current donor cornea shortage 22 Could fish scale-derived collagen provide alternative to human corneal tissue? 23 New technique could reduce graft detachment in DMEK 24 DSEK can significantly reduce graft rejection after corneal transplants

Glaucoma

26 Research in neuroprotection could be promising area 27 Laser could play important role in glaucoma treatment

Retina 28 French study compares drugs for AMD

Ocular 30 Experts believe understanding patients’ mindsets can help in decision-making

Global Ophthalmology 32 Smartphones could be the way forward in ophthalmic telemedicine

News 33 Residents’ issues a main focus of young ophthalmologists’ session

39 editorial staff

ESCRS

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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

Features 35 JCRS Highlights

41 Eye on Travel

37 Book Review

43 Ophthalmologica Highlights

39 Industry News

With this month’s issue... congress reports

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.

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EUROTIMES

Editorial

ESCRS

from the EDITOR

Medical Editors

Volume 18 | Issue 11

José Güell

Ioannis Pallikaris

Clive Peckar

Paul Rosen

A WONDERFUL EXPERIENCE

XXXI ESCRS Congress celebrated the history of the society and also looked forward to the future by Emanuel Rosen

International Editorial Board

years ago I was among a small group of 160 ophthalmologists in The Hague, The Netherlands, who came together for the first meeting of the European Intraocular Implantlens Council (EIIC), the association that eventually became the European Society of Cataract and Refractive Surgeons. I have just returned from the XXXI ESCRS Congress in Amsterdam, The Netherlands, which was attended by more than 7,000 delegates with a packed audience of 3,000 for each day’s major symposium. So much has changed since 1982. We have gone from being a small European group interested in developing the concept of IOL implantation to an organisation that promotes and discusses developments in cataract and refractive surgery not just in Europe but all over the world. The annual congress and the ESCRS publications ensure the dissemination of new and validated developments ensuring clinical standards are ever rising, for the benefit of all our patients. This year’s congress was a wonderful experience for me for two reasons. Firstly, after years of discussing the publication of a history of the ESCRS, I was finally able to hold a copy in my hands of European Society of Cataract & Refractive Surgeons – A History. This book tells the story of the society from the early years to the present day and is a wonderful account of the work of the people who have helped make our society so special. We are still a young society in many ways but the history is timely as some of those who were responsible for our foundation are no longer with us. It is important that we recognise the contribution of those who were with us in the early days and who are still active in the society and the book is a testimony to their achievements. It is important to point out that the history looks back on the society’s distinguished past but also looks forward to the challenges of the future. This brings me to my second reason for looking back on the XXXI Congress with particular fondness. When we came together in 1982, our group was made up of key opinion leaders in ophthalmology. Most of us were well-established in our profession and there were very few young ophthalmologists at our meeting in The Hague. As the society has developed over the last 31 years, we have done our best to encourage young ophthalmologists to get involved in ESCRS. I was particularly proud at our meeting in Amsterdam to see so many trainees and residents taking part in our scientific sessions and also in the Young Ophthalmologists Programme and the Young Ophthalmologists Session. Under the presidency of Peter Barry, we have worked very hard to ensure that not only do young ophthalmologists attend our meetings, they are also encouraged to help us decide how the Scientific Programme needs to be developed to meet their needs.

EUROTIMES | Volume 18 | Issue 11

Emanuel Rosen Chairman ESCRS Publications Committee

Noel Alpins australia Bekir Aslan TURKEY Bill Aylward UK Peter Barry IRELAND Roberto Bellucci ITALY Béatrice Cochener france Hiroko Bissen-Miyajima JAPAN John Chang CHINA Emanuel Rosen (left) with Peter Barry, president of the ESCRS

I have been very fortunate to work with Peter for almost 25 years. He is a great ophthalmologist and also a great friend and he deserves great credit for the success of this year’s congress and much more. Peter has been an outstanding and imaginative president popularising the ESCRS throughout the globe but is approaching the end of his two-year presidency and in January 2014, Roberto Bellucci will succeed him. I look forward to Roberto’s presidency but I am also happy in the knowledge that Peter will continue after his presidency to be a key figure in ESCRS. I also hope he enjoys his retirement and look forward to joining him at some time in the future in his holiday retreat in the beautiful town of Dingle, Co Kerry in Ireland.

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 Boris Malyugin RUSSIA Marguerite McDonald USA Cyres Mehta INDIA Thomas Neuhann GERMANY Rudy Nuijts THE NETHERLANDS Gisbert Richard GERMANY Robert Stegmann SOUTH AFRICA Ulf Stenevi SWEDEN Emrullah Tasindi TURKEY Marie-Jose Tassignon BELGIUM Manfred Tetz GERMANY Carlo Enrico Traverso ITALY

* Emanuel Rosen is chairman of the ESCRS Publications Committee and co-editor with Dr Peter Barry of, European Society of Cataract and Refractive Surgeons - A History.

Roberto Zaldivar ARGENTINA Oliver Zeitz germany

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See your success in the eyes of your patients

Defining the standard of care in DME* LUCENTIS® (ranibizumab) ABBREVIATED UK PRESCRIBING INFORMATION Please refer to the SmPC before prescribing LUCENTIS 10mg/ml solution for injection. Presentation: A glass single-use vial containing 0.23ml solution containing 2.3mg of ranibizumab (10mg/ml). Indications: The treatment in adults of neovascular (wet) age-related macular degeneration (AMD), the treatment of visual impairment due to diabetic macular oedema (DMO), the treatment of visual impairment due to macular oedema secondary to retinal vein occlusion (branch RVO or central RVO), and the treatment of visual impairment due to choroidal neovascularisation (CNV) secondary to pathologic myopia (PM). Administration and Dosage: Single-use vial for intravitreal use only. LUCENTIS must be administered by a qualified ophthalmologist experienced in intravitreal injections under aseptic conditions. The recommended dose is 0.5 mg (0.05ml). For treatment of wet AMD: Treatment is given monthly and continued until maximum visual acuity is achieved i.e. The patient’s visual acuity is stable for three consecutive monthly assessments performed while on ranibizumab. Thereafter patients should be monitored monthly for visual acuity. Treatment is resumed when monitoring indicates loss of visual acuity due to wet AMD. Monthly injections should then be administered until stable visual acuity is reached again for three consecutive monthly assessments (implying a minimum of two injections). The interval between two doses should not be shorter than 1 month. For treatment of visual impairment due to either DMO or macular oedema secondary to RVO: Treatment is given monthly and continued until maximum visual acuity is achieved i.e. the patient’s visual acuity is stable for three consecutive monthly assessments performed while on ranibizumab treatment. If there is no improvement in visual acuity over the course of the first three injections, continued treatment is not recommended. Thereafter patients should be monitored monthly for visual acuity. Treatment is resumed when monitoring indicates loss of visual acuity due to DMO or to macular oedema secondary to RVO. Monthly injections should then be administered until stable visual acuity is reached again for three consecutive monthly assessments (implying a minimum of two injections). The interval between two doses should not be shorter than 1 month. LUCENTIS and laser photocoagulation in DMO and in macular oedema secondary to BRVO: When given on the same day, LUCENTIS should be administered at least 30 minutes after laser photocoagulation. LUCENTIS can be administered in patients who have received previous laser photocoagulation. For treatment of visual impairment due to CNV secondary to PM: Treatment is initiated with a single injection. If monitoring reveals signs of disease activity, e.g. reduced visual acuity and/or signs of lesion activity, further treatment is recommended. Monitoring for disease activity may include clinical examination, optical coherence tomography (OCT) or fluorescein angiography (FA). While many patients may only need one or two injections during the first year, some patients may need more frequent treatment. Therefore, monitoring is recommended monthly for the first two months and at least every three months thereafter during the first year. After the first year, the frequency of monitoring should be determined by the treating physician. The interval between two doses should not be shorter than one month. LUCENTIS and Visudyne photodynamic therapy in CNV secondary to PM: There is no experience of concomitant administration of LUCENTIS and Visudyne. Before treatment, evaluate the patient’s medical history for hypersensitivity. The patient should also be instructed to self-administer antimicrobial drops, 4 times daily for 3 days

before and following each injection. Children and adolescents: Not recommended for use in children and adolescents due to a lack of data. Elderly: No dose adjustment is required in the elderly. There is limited experience in patients older than 75 years with DMO Hepatic and renal impairment: Dose adjustment is not needed in these populations. Contraindications: Hypersensitivity to the active substance or excipients. Patients with active or suspected ocular or periocular infections. Patients with active severe intraocular inflammation. Special warnings and precautions for use: LUCENTIS is for intravitreal injection only. Intravitreal injections have been associated with endophthalmitis, intraocular inflammation, rhegmatogenous retinal detachment, retinal tear and iatrogenic traumatic cataract. Monitor during week following injection for infections. Patients should be instructed to report symptoms suggestive of any of the above without delay. Transient increases in intraocular pressure (IOP) within 1 hour of injection and sustained IOP increases have been identified. Both IOP and perfusion of the optic nerve head should be monitored and managed appropriately. Concurrent use in both eyes has not been studied and could lead to an increased systemic exposure. There is a potential for immunogenicity with LUCENTIS which may be greater in subjects with DMO. Patients should report an increase in severity of intraocular inflammation. LUCENTIS should not be administered concurrently with other anti-VEGF agents (systemic or ocular). Withhold dose and do not resume treatment earlier than the next scheduled treatment in the event of the following: a decrease in best corrected visual acuity (BCVA) of ≥30 letters compared with the last assessment of visual acuity; an intraocular pressure of ≥30 mmHg; a retinal break; a subretinal haemorrhage involving the centre of the fovea, or if the size of the haemorrhage is ≥50% of the total lesion area; performed or planned intraocular surgery within the previous or next 28 days. Risk factors associated with the development of a retinal pigment epithelial (RPE) tear after anti-VEGF therapy for wet AMD include a large and/or high pigment epithelial retinal detachment. When initiating LUCENTIS therapy, caution should be used in patients with these risk factors for RPE tears. Discontinue treatment in cases of rhegmatogenous retinal detachment or stage 3 or 4 macular holes. There is only limited experience in the treatment of subjects with DMO due to type I diabetes. LUCENTIS has not been studied in patients who have previously received intravitreal injections, in patients with active systemic infections, proliferative diabetic retinopathy, or in patients with concurrent eye conditions such as retinal detachment or macular hole. There is also no experience of treatment with LUCENTIS in diabetic patients with an HbA1c over 12% and uncontrolled hypertension. In PM patients there are no data on the use of LUCENTIS in patients with extrafoveal lesions and only limited data on its use in those who have had previous unsuccessful therapy with verteporfin photodynamic therapy. Systemic adverse events including non-ocular haemorrhages and arterial thromboembolic events have been reported following intravitreal injection of VEGF inhibitors. There are limited data on safety in the treatment of DMO, macular oedema due to RVO and CNV secondary to PM patients with prior history of stroke or transient ischaemic attacks. Caution should be exercised when treating such patients. There is limited experience with treatment of patients with prior episodes of RVO and of patients with ischaemic BRVO and CRVO. Treatment is not recommended in RVO patients presenting with clinical signs of irreversible ischaemic visual function loss. Interactions: No formal interaction studies have been performed. In DMO and BRVO adjunctive use of laser therapy and LUCENTIS was not associated with any new ocular or non-ocular safety findings. Pregnancy and lactation: Women of

childbearing potential should use effective contraception during treatment. No clinical data on exposed pregnancies are available. Ranibizumab should not be used during pregnancy unless the expected benefit outweighs the potential risk to the foetus. For women who wish to become pregnant and have been treated with ranibizumab, it is recommended to wait at least 3 months after the last dose of ranibizumab before conceiving. Breast-feeding is not recommended during the use of LUCENTIS. Driving and using machines: The treatment procedure may induce temporary visual disturbances and patients who experience these signs must not drive or use machines until these disturbances subside. Undesirable effects: Most adverse events are related to the injection procedure. Serious adverse events reported include endophthalmitis, blindness, retinal detachment, retinal tear and iatrogenic traumatic cataract. The safety data below include adverse events experienced following the use of LUCENTIS in the entire clinical trial population. Those marked * were only seen in the DMO population. Very Common: Intraocular pressure increased, headache, vitritis, vitreous detachment, retinal haemorrhage, visual disturbance, eye pain, vitreous floaters, conjunctival haemorrhage, eye irritation, foreign body sensation in eyes, lacrimation increased, blepharitis, dry eye, ocular hyperaemia, eye pruritus, arthralgia, nasopharyngitis. Common: Urinary tract infection*, anaemia, retinal degeneration, retinal disorder, retinal detachment, retinal tear, detachment of the retinal pigment epithelium, retinal pigment epithelium tear, visual acuity reduced, vitreous haemorrhage, vitreous disorder, uveitis, iritis, iridocyclitis, cataract, cataract subcapsular, posterior capsule opacification, punctuate keratitis, corneal abrasion, anterior chamber flare, vision blurred, injection site haemorrhage, eye haemorrhage, conjunctivitis, conjunctivitis allergic, eye discharge, photopsia, photophobia, ocular discomfort, eyelid oedema, eyelid pain, conjunctival hyperaemia, cough, nausea, allergic reactions, hypersensitivity, anxiety. Product-class-related adverse reactions: There is a theoretical risk of arterial thromboembolic events, including stroke and myocardial infarction, following intravitreal use of VEGF inhibitors. A low incidence rate of arterial thromboembolic events was observed in the LUCENTIS clinical trials in patients with AMD, DMO, RVO and PM and there were no major differences between the groups treated with ranibizumab compared to control. Please refer to the SmPC for full listing of all undesirable effects.

For UK: Adverse events should be reported. Reporting forms and information can be found at www.mhra.gov.uk/yellowcard. Adverse events should also be reported to Novartis Pharmaceuticals UK Ltd on (01276) 698370 or medinfo.uk@novartis.com Legal category: POM, UK Basic NHS cost: £742.17. Marketing authorisation number: EU/1/06/374/001. Marketing authorisation holder: Novartis Europharm Limited, Wimblehurst Road, Horsham, West Sussex, RH12 5AB, United Kingdom. Full prescribing information, including SmPC, is available from: Novartis Pharmaceuticals, Frimley Business Park, Frimley, Camberley, Surrey, GU16 7SR. Telephone: 01276 692255. Fax: 01276 692508. Prepared July 2013.

*Visual impairment due to diabetic macular edema

Lucentis Indications may vary from country to country. Physicians should refer to their National Prescribing Information. Novartis Pharma AG CH-4002 Basel, Switzerland

August 2013

LUC.146879

Cover Story

PAEDIATRIC OPHTHALMOLOGY

Advances in GENETIC MEDICINE

Genetic testing, coupled with conventional drug and surgical treatments and new compounds targeting metabolic pathways, is advancing by Howard Larkin

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We can truly differentiate between a heritable risk and an initially occurring mutation Ian MacDonald MD

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You can imagine a world in which the impact of genetic medicine could be unbelievable. But the conversation quickly gets into should we test people, and what do we do with the information? David B Granet MD

EUROTIMES | Volume 18 | Issue 11

ot long ago, Ian MacDonald MD, professor and chair of ophthalmology and visual sciences at the University of Alberta, Edmonton, Canada, examined a young boy with presumed Leber’s congenital amaurosis (LCA). Based on the boy’s phenotype, Prof MacDonald, who is also a clinical geneticist, suspected a mutation in the LRAT gene. One of at least 17 identified genetic causes of LCA, the gene is named for its role in synthesising lecithin retinol acryltransferase. LRAT defects, along with those of the gene RPE65, promote retinal degeneration by producing an abnormal protein that disrupts recycling of photopigments. Gene sequencing confirmed the diagnosis of LRAT-involved LCA, also known as LCA14, in the boy. So Prof MacDonald referred him to a colleague conducting a clinical trial of an oral synthetic retinoid designed to bypass this biochemical blockade. “His vision improved,” recalled Dr MacDonald, who has studied and described the molecular basis of choroideraemia and is taking part in a gene therapy study for treating it beginning this fall. “I can count on one hand the patients I have treated for genetic eye diseases who have improved.” The case illustrates an important point about genetic medicine and its application in paediatric ophthalmology. Gene therapies designed to cure outright by replacing defective genes may grab more headlines. But genetic testing coupled with conventional drug and surgical treatments, as well as new compounds targeting specific metabolic pathways, are advancing much more quickly – and may be much more clinically useful, at least in the short to intermediate term. Indeed, in a phase 1b trial involving 17 retinitis pigmentosa patients due to mutations in either LRAT or RPE65 receiving an oral synthetic retinoid oral treatment for seven days, statistically significant increases in the area of visual fields at day seven and day 14 respectively

were observed, Hendrik PN Scholl MD, professor of ophthalmology at Johns Hopkins University, Baltimore, US, told the American Academy of Ophthalmology annual meeting last November. Two-thirds of all patients saw best-corrected vision improve in at least one eye at seven and 30 days. In addition, two patients tested with dark-adapted perimetry and full field sensitivity showed “significant improvement” of up to 36 dB, or 4,000-fold, in light sensitivity after prolonged dark adaptation within days of treatment, he added. Genetic diagnosis also results in better understanding of disease mechanisms, making it possible to repurpose existing compounds, Dr MacDonald noted. For example, dorzolamide, developed for glaucoma, has improved visual function and reduced macular oedema in some patients with x-linked juvenile retinoschisis. “We know what the gene is, we know what the gene product is and so we can address it.” And in the case of retinoblastoma, genetic testing has completely changed the treatment dynamic, enabling positive identification of those at risk. “We can truly differentiate between a heritable risk and an initially occurring mutation,” Dr MacDonald said. This allows early monitoring and surgical treatment of infants with inherited disease while sparing those without risk a lifetime of intrusive and expensive screening for tumours that will never develop. Nonetheless, genetic technology for confirming diagnoses and guiding conventional treatment is technically complex, challenging clinicians to keep up with increasingly rapid developments, said David B Granet MD, professor of ophthalmology and paediatrics at the University of California San Diego, US. Moreover, it is fraught with ethical and philosophical questions, especially when applied to children who cannot give informed consent.

“ ...two patients tested with dark-adapted perimetry and full field sensitivity showed ‘significant improvement’ of up to 36 dB, or 4,000fold, in light sensitivity after prolonged dark adaptation within days of treatment” Hendrik PN Scholl MD

Uncovering genetic markers for incurable diseases is a particular challenge, Dr Granet noted. It may present opportunities for early treatment in cases where the gene is strongly associated with a disease phenotype, as with retinoblastoma. But more often, heritable diseases involve multiple genes and even non-genetic factors, complicating the risk calculation and any treatment or management decision. For diseases with multiple genes involved, such as age-related macular degeneration and glaucoma, the presence of some genes suggest a higher risk, but it is currently not possible to predict who will manifest the diseases when and to what degree. Other diseases, such as retinitis pigmentosa, result from defects in single gene pairs, but more than 50 different gene causes have been identified, and even these do not account for all cases. About one in five individuals carries one copy of an RP-causing gene, though only about one in 5,000 develop the disease, which requires inheriting two copies of the same defective gene segment. Even diseases caused by defects in just one gene and that are fairly

common are relatively low incidence. For example, one in 25 Caucasian people carry one gene for cystic fibrosis, but there is no risk of their children developing the disease unless they mate with another carrier. “You can imagine a world in which the impact of genetic medicine could be unbelievable. But the conversation quickly gets into should we test people, and what do we do with the information? If you are a prospective parent, do you avoid having children, or test embryos for selective implantation or terminate a pregnancy if a foetus has a genetic disease or is a carrier? Who gets to decide? Who pays? These are the sort of questions we face with what we do now,” Dr Granet said. Effectively and ethically harnessing the power of genetic medicine require that ophthalmologists understand what tests are available, what their limits are and how they relate to clinical observation, Dr Granet said. Above all, physicians or expert genetic counsellors must be able to work through these questions with patients in a way that both informs and helps them determine their own reasons for seeking and using genetic information.

Early treatment: promise and peril Technical difficulties aside, the

potential advantages of genetic medicine in paediatric ophthalmology are obvious. Identifying and treating heritable eye diseases before they manifest or advance presents the prospect of reducing or completely preventing vision loss. But at this early stage of development, the risks are just as obvious. “It is generally easier to justify the risks of experimental gene therapy in adults than in children. Adults are better able to evaluate the risks for themselves, and are relatively protected against the impact of side effects because they typically have more advanced sight loss.” said James W Bainbridge PhD, FRCOphth of Moorfields Eye Hospital and the UCL Institute of Ophthalmology, London, UK. “It is obviously critical to ensure that the gene defect is responsible for a particular phenotype,” noted Dr Bainbridge, whose pioneering work targeting RPE65-related Leber’s congenital amaurosis established the short-term safety and efficacy of viral vectors for delivering gene therapy to the retina. These risks are why it will take longer for gene therapy – of which only a handful exist and none yet past human clinical trials – to enter clinical practice in paediatric ophthalmology, Dr Granet said. “This technology is in a translational stage. When you are looking at kids, you have to be careful.” Still, early treatment is the goal, Dr Bainbridge said. Many experimental studies of gene therapy for retinal degenerations demonstrate that earlier intervention improves outcomes, and the same is anticipated in clinical application. However, potential therapy targets and agents are highly specific, and further development is required before gene replacement is reliable and robust, Dr Bainbridge said. “There are many questions to be answered about the magnitude and durability of the response, and whether the impact can be sufficient to protect against on-going degeneration. These are all relevant to the optimal timing of intervention in children.” EUROTIMES | Volume 18 | Issue 11

‘Technical difficulties aside, the potential advantages of genetic medicine in paediatric ophthalmology are obvious’

“Broad parallel tests such as whole exome tests should be limited to diagnosis of unknown genetic diseases and research as they are more expensive, more difficult to interpret and also may reveal genetic defects beyond the scope of the clinical situation at hand of even ophthalmology” Edwin M Stone MD PhD

Indeed, patients treated with experimental genetic replacement therapy for RPE65-related LCA, also known as LCA2, have generally continued to lose vision over time, as have patients receiving new genes for choroideraemia, Dr MacDonald noted. Similar issues crop up in other gene therapy fields, he added. For example, transplanted pancreatic islet cells seemed to cure Type 1 diabetes, but most patients eventually again required insulin or other supportive treatment. Dr MacDonald suggests that treating inherited eye disease may require multiple interventions along the lines of chemotherapy for cancer or long-term management of blood pressure and diabetes. “These aren’t infectious diseases, these are degenerative diseases. Chronic management may require many additional changes in lifestyle, preventive measures and perhaps neuroprotective agents supplementing gene therapy. What they might be I don’t know.” Such approaches also may be amenable to gene insertion therapy, Dr Bainbridge said. He envisions adding genes for suppressing toxic proteins created by single-gene dominant mutations as well as genes that express anti-VEGF or neuroprotective

factors for treating a broader range of genetic disease. Dr Bainbridge also remains confident that early diagnosis and treatment will eventually become common. “The increasing power of genetic screening will enable us to identify children at an age when they are most likely to benefit from intervention .” In the popular mind, genetic testing is conceived as a mechanical process in which identification of specific genes or gene combinations infallibly predicts disease. It’s just a matter of time before all genetic disease is catalogued, screened for and prevented. The reality, of course, is much messier. While more genetic causes of heritable disease are continuously discovered, many remain unknown; for example in 30 per cent or so of LCA cases, none of the 17 known gene defects are present. Technical issues also can interfere, leading to false positives and false negatives. In addition, many diseases are influenced by multiple genes, and every human genome includes many, many mutations that increase risk for specific diseases to varying degrees. Many more mutations are harmless. And, of course, many genetic diseases are as-yet incurable.

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It is obviously critical to ensure that the gene defect is responsible for a particular phenotype

James W Bainbridge PhD, FRCOphth

contacts

Cover Story

PAEDIATRIC OPHTHALMOLOGY

Pedigree key to identifying paediatric genetic eye disorders

s a paediatric anterior segment surgeon, Ken K Nischal MD, FRCOphth has a big interest in genetics. The corneal diseases, glaucoma and cataracts he treats in children often result from genetic abnormalities – but busy practising ophthalmologists can be hard pressed to identify them. So given the chance to collaborate on research with high-volume paediatric glaucoma clinics in India, Dr Nischal focused on improving genetic counselling. Through the World Society of Paediatric Ophthalmology and Strabismus (WSPOS), Dr Nischal, who is director of paediatric ophthalmology at the University of Pittsburgh Medical Centre, Pennsylvania, US, developed a pilot programme that trains paramedical professionals in the basics of genetic education. Under an institutional review board-approved protocol, Dr Nischal and a student completing studies in ophthalmic genetic counselling at Pittsburgh developed a seven-week online module course distributed through the WSPOS website. 12 clinics in India each chose two paramedical staff members, either optometrists or nurses, to take the course. A baseline survey found a fairly low level of understanding of genetics among participants. Genetics knowledge improved measurably after each module. In July, Dr Nischal travelled to India and met with participants to refine the project. The biggest issue was defining the role of the paraprofessionals as genetic educators, rather than full-fledged genetic counsellors, Dr Nischal said. As educators they interview patients and provide information to doctors, who counsel patients on their conditions, as well as diagnostic, preventive and treatment options. Incidents of educators counselling patients, for example telling a patient that a defect could have resulted from a consanguineous marriage, were defined as adverse events. The greatest need was for detailed family histories, Dr Nischal said. “Doctors in these huge centres in India are seeing 200 to 300 glaucoma patients a day. They need someone who can do an accurate pedigree so the doctors could pick up possible genetic components.” Results, including whether better access to pedigrees leads to increased diagnosis of genetic components in glaucoma, are being compiled. However, Dr Nischal said the clinics already are identifying more genetic glaucoma cases as well as more cases in which glaucoma is related to a genetic syndrome, such as AxenfeldRieger or nail-patella.

EUROTIMES | Volume 18 | Issue 11

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Doctors in these huge centres in India are seeing 200 to 300 glaucoma patients a day Ken K Nischal MD

“It is absolutely clear that they were seeing patients who they felt might have a genetic problem but they didn’t have time to delve into it.”

Lessons for the developed world The need for better genetic

education and understanding is hardly limited to developing countries. Dr Nischal pointed out that even in the US there are just 38 dedicated ophthalmic genetic counsellors, though many general genetic counsellors also address ophthalmic issues. He suggests ophthalmologists routinely do family histories for children with congenital or developmental eye problems. “If you draw a threegeneration pedigree and see affected people in all three generations, they need a genetic counsellor, and likely this child needs genetic testing,” Dr Nischal said. Because of the complexity and rapid advance of genetic diagnosis, he recommends a referral to a centre with specific ophthalmic experience for genetic tests. “The tests are complicated and sophisticated. It is difficult to know what to test without experienced help,” Dr Nischal said.

Genetics information sources n GeneTests – Summaries of inherited

diseases with links to articles and labs specialising in specific genetic tests around the world, www.gentests.org n eyeGene – US NEI program collects genetic samples from ophthalmologists, enabling incorporation of genetic testing and participation in clinical trials, www.nei.nih.gov/resources/ eyegene/asp n Carver Lab – University of Iowa provides clinical genetic testing on a wide range of ocular genetic disease, www.carverlab.org n OMIM – Online Mendelian Inheritance in Man provides continuously updated overview of peer-reviewed publications on genes, clinical syndromes and mutations, www.ncbi.nlm.nih.gov/entrez/query. fcgidb=OMIM

contact Ken K Nischal – nischalkk@upmc.edu

In other words, the noise-to-signal ratio in genetic testing is extremely high. Making sense of the sheer volume of data requires clinical expertise and explaining them to patients in a way that supports meaningful decision-making is also essential. Indeed, the American Academy of Ophthalmology’s recommendations for genetic testing for inherited eye diseases call for offering genetic testing only if there is clinical evidence that a genetic condition is present, interpreting results in the light of evidence and counselling patients on its meaning (Ophthalmology 2012;119: 2408–2410). “The role of the clinician is central,” said Edwin M Stone MD, PhD, chair of the AAO genetic testing task force. In many cases, he recommends focusing testing on suspected genetic causes rather than doing broad parallel sequencing, especially for conditions known to be caused by one or just a few genes. Many laboratories now offer test panels that include most or all of the known genes for specific conditions. Broad parallel tests such as whole exome tests should be limited to diagnosis of unknown genetic diseases and research as they are more expensive, more difficult to interpret and also may reveal genetic defects beyond the scope of the clinical situation at hand of even ophthalmology, Dr Stone pointed out. The cost of revealing genetic defects such as risk for cancers or degenerative neurological diseases can be high both economically and psychologically, and can even disrupt family relationships. Dr Stone also emphasises the importance of interpreting test results in light of published literature linking specific genotypes to phenotypes, and databases that track the percentage of cases linked to a genotype as well as how often a genotype is associated with an observed phenotype. He recommends dealing with labs that include reports that put results in the context of relevant literature and statistical information. He also stresses the need to keep costs reasonable and consider lab turnaround time in the context of the clinical situation. When considering genetic testing, Dr Granet suggests that clinicians first ask if it will change the course of treatment. The answer may well be a moving target. He recommends consulting with or referring to colleagues and querying databases, such as the Online Mendelian Inheritance in Man (http://www.omim.org) or genetests.org for up-to-date information.

James Bainbridge – j.bainbridge@ucl.ac.uk Ian MacDonald – macdonal@ualberta.ca Edwin M Stone – stonee@zeus.eng.uiowa.edu David Granet – dgranet@ucsd.edu Hendrik Scholl – hscholl1@jhmi.edu

“You need scientists to interpret the data, but you also need to translate it into language understandable to parents” David B Granet MD

“You need scientists to interpret the data, but you also need to translate it into language understandable to parents,” Dr Granet noted. Though this is time-consuming, he usually does it himself, though using specially trained genetic counsellors is increasingly common (see sidebar). Some insurance arrangements even require counselling as a condition of payment for certain genetic tests. In counselling, Dr Granet probes parents’ reasons for seeking genetic testing. Do they expect a genetic cure? Are they interested in tissue banking for research and possible participation in current or future clinical trials? Are they considering additional children? Counselling is also an opportunity to share positive stories of patients with genetic disease. About a decade ago, Dr Granet saw a fifth-grade girl who had trouble seeing the blackboard. The problem was too subtle to diagnose at first, but over the next few months it became clear she had Stargardt’s disease and she would progressively lose her vision. One of her two brothers also was diagnosed. The young lady was active in basketball, soccer and other sports, but soon could no longer participate. So she turned to rowing. Last year she was on the US Paralympic team, and now is on crew at the University of Washington – and has a shot at the US Olympic team. “If we could cure her with an injection, that would be great, but she’d be a different person. In the meantime, she’s awesome,” Dr Granet said. Dr Stone also emphasises the positives of genetic testing in counselling. Instead of telling patients “there’s nothing we can do,” a test affirms that the medical and research community is working on a cure. It provides real hope for progress.

COMING SOON IN decemBER/january EUROTIMES... Older population raises new issues Ophthalmologists, whose patients are often older, often have to play the part of geriatrician, dietician, neurologist and psychiatrist, in addition to helping with ocular issues. Every demographic study suggests the number of elderly patients is only going to increase. EuroTimes looks at the challenges encountered when treating the older patient group and talks to experts on how best to meet those challenges.

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Special Focus

PAEDIATRIC OPHTHALMOLOGY

contact

Marcelo Ventura – marcelovhope@gmail.com

SURGERY PEARLS

Leading surgeon offers tips on tools and techniques by Cheryl Guttman Krader in Singapore

here are multiple challenges to achieving a good outcome in paediatric cataract surgery. Speaking at the 26th Asia-Pacific Association of Cataract & Refractive Surgeons, Marcelo C Ventura MD, PhD, discussed some of the techniques he finds useful for minimising complications and facilitating postoperative care. Dr Ventura is vice-president of the Altino Ventura Foundation and chief of the Department of Cataract and Retina of the Hospital de Olhos de Pernambuco (HOPE), both in Recife, Brazil. He has been performing paediatric cataract surgery since 1994 and has accumulated one of the largest experiences with surgery for congenital cataract in the Americas. Considering the increased risk of posterior capsular opacification in paediatric eyes and the difficulty of doing Nd:YAG laser capsulotomy in young children, Dr Ventura performs posterior capsulotomy and anterior vitrectomy in all infantile cataract surgery cases involving children ages eight weeks to six years old. His preferred tool for the capsulotomy is a radiofrequency (RF) cautery device (Easy Rhex, Loktal Medical Electronics), which is easy to use and has other important advantages. “With RF cautery, I can easily control the diameter and shape of the capsular opening and also enlarge it if I am not satisfied with the original size,” Dr Ventura said. He also favours using RF cautery rather than the Utrata forceps or scissors to create the anterior capsulorhexis in eyes where there is significant fibrosis or calcification on the anterior capsule. “These areas of fibrosis or calcification are usually thick. Therefore, if attempting capsulorhexis using the Utrata forceps, there is an increased risk for causing a radial tear or zonular dehiscence,” Dr Ventura explained. “RF cautery cuts through these plaques effectively without causing zonular stress, and this technique does not compromise rhexis strength,” Dr Ventura said, adding that he has not encountered problems with radial tears or other signs of rhexis weakness during more than 10 years of using RF cautery. He added that if there is localised excessive fibrosis or calcification on one side of the anterior capsule that lies in the

path of the planned capsulorhexis, it may be possibly avoided by slightly enlarging the capsular opening on that side. “However, when enlarging the anterior capsulorhexis in this situation, keep in mind that to avoid anteriorisation of the IOL, the haptics must be in the bag, and the border of the capsular opening should ideally overlap the lens optic rim by approximately 1.0mm around most of its circumference,” Dr Ventura said. Insertion of an endocapsular tension ring (Visiontech Medical Optics) is also part of Dr Ventura’s routine in infantile cataract surgeries. Rare exceptions include eyes with extreme microphakia, those that will remain aphakic, or cases in which there are intraoperative complications such that the risk of ring insertion outweighs the benefit. By fully expanding and stabilising the capsular bag, the endocapsular tension ring enables implantation of Dr Ventura’s preferred IOL – a 12.5mm-long, 3-piece, foldable, hydrophobic acrylic IOL – and reduces capsular contraction to maintain a circular, central capsulorhexis and minimise IOL decentration. Dr Ventura plans primary IOL implantation in-the-bag in patients older than eight weeks of age, using an age-based algorithm that he developed for hypocorrecting IOL power in children up to four years old. He favours the 3-piece style implant because its haptics maintain bag expansion better than the haptics of a single-piece IOL, and it can still be placed through a small incision. If he anticipates the haptics of the 3-piece IOL cannot expand properly because the capsular bag is too small, Dr Ventura amputates part of both haptics and implants what remains into the capsular bag. “The haptics’ stubs will maintain IOL stability, particularly if the stubs penetrate into the capsule,” Dr Ventura said. To modulate postoperative inflammation, Dr Ventura injects 1.2 mg/0.03 mL of preservative-free triamcinolone acetonide (Triancinolona Ophthalmos, Laboratorio Ophthalmos) in the anterior chamber at the end of the case in patients younger than two years of age. After reforming the anterior chamber with a single air bubble, he injects the corticosteroid into the angle so that it occupies the 360° circumference of the space between the anterior chamber angle and the air bubble. Based on one-year follow-up results

Posterior capsulorhexis and anterior vitrectomy follow-up

EUROTIMES | Volume 18 | Issue 11

Past

Present

Courtesy of Marcelo C Ventura MD

Anterior capsulorhexis using RF cautery in thick capsule

from 53 eyes of 34 patients operated on for congenital cataract when younger than two years of age, this use of triamcinolone does not appear to increase the risk of glaucoma or adversely affect central corneal thickness [J AAPOS. 2012;16(5):441-4]. “For us, secondary opacification of the visual axis is no longer a frequent issue in infantile cataract surgery. I believe the development of this complication has been limited in our hands by the combination of endocapsular tension ring placement, primary posterior capsulorhexis, anterior vitrectomy, and intracameral triamcinolone acetonide,” Dr Ventura said. Finally, Dr Ventura closes the main and sideport incisions with 10-0 Vicryl. His choice of dissolvable suture material obviates any need to remove the stitches postoperatively – a procedure that would necessitate examination under anaesthesia.

Special Focus

PAEDIATRIC OPHTHALMOLOGY

OCULUS Corvis® ST

avoiding pco

‘Bag-in-the-lens’ method safe and well tolerated in paediatric population by Priscilla Lynch in Killarney

he bag-in-the-lens’ implantation method is safe and well tolerated in the paediatric population and addresses many of the risks of treating cataracts in this age group, according to Sorcha Ni Dhubhghaill MB, PhD, anterior segment fellow to Marie-José Tassignon MD, PhD, University of Antwerp, University Hospital Antwerp, Belgium. Dr Ni Dhubhghaill presented the results of a Belgian long-term follow-up study of bag-in-the-lens at the 2013 Irish College of Ophthalmologists Annual Meeting in Killarney, Co Kerry, Ireland in collaboration with Dr Jan Van Looveren, from University Hospital Antwerp. The treatment of cataracts in the paediatric population has long been known to pose more difficulties than in adult patients, she noted. For example, if the posterior capsule is left intact at the time of surgery, posterior capsule opacification (PCO) occurs in up to 80 per cent of cases. The bag-in-the-lens approach for inserting intraocular lenses addresses the high risk of visual axis opacification, Dr Ni Dhubhghaill explained.

Avoiding PCO Under the study that she presented, the long-term results of all 31 paediatric cataract surgeries performed using the bag-in-the-lens method between July 1999 and September 2007 by a single surgeon (Prof Tassignon) were assessed. Prof Tassignon developed the innovative bag-in-the-lens technique to avoid the development of PCO, the main complication of the traditional implantation technique for cataracts. 16 of the cases in the study were unilateral and 15 were bilateral, with a wide range of cataract types involved including nuclear fetal cataract and spherophakia. The age at the time of surgery ranged from two months to 14 years (mean of six years), while the follow-up periods ranged from 60 to 157 months (mean of 78 months). 15 children who underwent bilateral bag-in-the-lens surgery showed significant visual acuity improvements, from a preoperative range of 0.0 to 0.4 (mean 0.2) to a postoperative range of 0.2 to 1.0 (mean Don’t Miss Book review, see page 37 EUROTIMES | Volume 18 | Issue 11

“

The bag-in-the-lens approach is a beneficial long-term treatment for the treatment of paediatric cataract

Sorcha Ni Dhubhghaill MB PhD

Highspeed Scheimpflug camera visualizes the future of diagnosis

of 0.83). While one patient showed no improvement, there was no worsening of vision recorded in any patient. Overall, visual acuity of greater than 0.5 was achieved in the vast majority – 86.7 per cent – of these patients. Meanwhile, all the 16 paediatric patients who underwent unilateral surgery showed improvement from a preoperative range of 0.0 to 0.4 (mean of 0.07) to a postoperative range of 0.0 to 0.7 (mean 0.27). These patients had poorer visual acuity outcomes than the bilateral cases and no unilateral patient achieved a postoperative visual acuity of 1.0. Dr Ni Dhubhghaill noted that unilateral cataracts have a high predilection for amblyopia and therefore still have a more guarded prognosis. She suggested that earlier surgical intervention and follow-up might yield more promising results in the future for these patients.

Well tolerated Concluding her presentation, Dr Ni Dhubhghaill maintained that the bag-in-the-lens IOL implantation approach has been demonstrated to be safe and well tolerated in the paediatric population. “The bag-in-the-lens approach is a beneficial long-term treatment for the treatment of paediatric cataract," she told EuroTimes.

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PAEDIATRIC OPHTHALMOLOGY

contact

Special Focus

PAEDIATRIC UVEITIS

“

What we need is more prospective studies looking at the effect of biologic agents and identification of parameters predicting the efficacy of different treatment regimes

Treatment of paediatric uveitis is complex and is based on subtype and severity of the condition by Dermot McGrath in Copenhagen

Lisbeth Sandfeld MD, PhD

Courtesy of Lisbeth Sandfeld MD, PhD

ew biologic agents are altering the therapeutic management of paediatric uveitis and increasing the chances of disease control in these patients, although intensive monitoring is needed to avoid systemic and ocular complications. “Biologic agents have certainly given us more treatment options, although the evidence to date suggests that clinical remission is time limited both for methotrexate and the more commonly used biologic agents. What we need is more prospective studies looking at the effect of biologic agents and identification of parameters predicting the efficacy of different treatment regimes,” Lisbeth Sandfeld MD, PhD, told delegates attending the 2013 Congress of the European Society of Ophthalmology (SOE). Presenting the results of a retrospective study to evaluate the efficacy of systemic treatment in childhood uveitis, Dr Sandfeld said that the treatment of paediatric uveitis is complex and is based on subtype and severity of the condition, and must take account of concomitant systemic disease and side effects. In many patients, corticosteroids alone are not sufficient to control the inflammation and immunomodulatory therapy will be necessary. The study carried out at the Eye Clinic, Rigshospitalet, Copenhagen, Denmark, included children aged younger than 18

Lisbeth Sandfeld – l.sandfeld@dadlnet.dk

Clinical effect of different treatment regimes in paediatric uveitis. (CR: clinical remission)

years at the time of their uveitis diagnosis between 2007 and 2012. The efficacy of the patients’ systemic treatment and side effects were registered. Treatment was topical/systemic steroid, with clinical remission defined as no uveitis during medical treatment for more than one year. In the event of recurrent uveitis, patients were treated with methotrexate, and biologic response modifiers – adalimumab, infliximab, etanercept – or a combination of methotrexate and one of the biologic agents. The study included a total of 73 children treated for uveitis: 52 were identified as juvenile idiopathic arthritis (JIA)-associated

uveitis, 19 were idiopathic uveitis, one patient had sarcoidosis and one had glomerulonephritis. 61of the patients were receiving systemic treatment. Out of these 61 patients, 25 needed three or more different systemic treatments after one year to obtain sufficient disease control. The mean age of the patients at uveitis debut was seven years and four months ranging from one year to 17 years. The mean age at systemic disease debut was four years and six months (range six months to 13 years). In four cases, data was not obtainable regarding previous medication, said Dr Sandfeld.

Dr Sandfeld reported that methotrexate induced and maintained clinical remission for at least one year in 33 of 47 patients, adalimumab in 18 of 23 patients, infliximab in six of nine patients and etanercept in nine of 17 patients. A combination of methotrexate and adalimumab resulted in clinical remission in seven of 18 patients, methotrexate and infliximab in 21 of 26 patients and methotrexate and etanercept in six of seven patients. Severe side effects were noted for infliximab – anaphylaxis in four cases, and for methotrexate – nausea and increasing liver enzymes in seven patients. Putting the overall results into context, Dr Sandfeld said that methotrexate had a limited effect in idiopathic uveitis while etanercept had a limited effect in polyarticular JIA-associated uveitis. The effect of treatment also seemed to be unrelated to antinuclear antibody, rheumatoid factor, HLA-B27 haplotype, sex, anatomic location of uveitis or the patient’s age at uveitis debut. “Going forward we need more prospective, randomised clinical trials to help us define clearer indications for different biologics in refractory paediatric uveitis and criteria for successful outcome prediction,” she concluded.

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Special Focus

PAEDIATRIC OPHTHALMOLOGY

ARTIFICIAL CORNEA

Device gives clinicians treatment option for corneal disease not amenable to standard penetrating keratoplasty or corneal transplant by Dermot McGrath in Copenhagen

Boston KPro keratoprosthesis device has shown considerable promise as a safe and viable alternative to penetrating keratoplasty in selected paediatric patients, Kathryn Colby MD, PhD, told delegates attending the 2013 Congress of the Society of European Ophthalmology. “The Boston KPro is a wonderful device which has successfully restored vision to thousands of patients throughout the world. While paediatric patients are particularly challenging and require extremely rigorous follow-up, we have already achieved very positive outcomes using the implant in children with minimal complications,” said Dr Colby, associate professor of ophthalmology at Harvard Medical School, Boston, MA, US. She explained that the Boston KPro gives clinicians a treatment option for corneal disease not amenable to standard penetrating keratoplasty or corneal transplant. “We know that penetrating keratoplasty outcomes in children are very variable and unfortunately not optimal. Although graft survival can range from 44 per cent to 67 per cent several years after surgery, it is nevertheless very difficult to get good vision in paediatric patients and especially in younger children after keratoplasty. The most common reason for this is high astigmatism after keratoplasty, which limits amblyopia management in these patients,” she said. Dr Colby noted that the concept of an artificial cornea is not a new one and dates back to the time of the French revolution when Guillaume Pellier de Quengsy first suggested the idea for keratoprostheses in 1789. The need for an artificial cornea, said Dr Colby, stems from situations where the traditional tissue transplant does very poorly, and includes indications such as repetitive graft failure. “After the first regraft the rate of success to achieve corneal clarity several years after surgery is approximately 30 per cent, but for subsequent regrafts this falls to virtually zero fairly quickly,” she said. Discussing the characteristics of the device, Dr Colby said that the Boston KPro comes in two models: type I, the most commonly used version, utilises a donor cornea and leaves the eyelids intact, and type II which is reserved for severe end-stage ocular surface disease desiccation. The device is made up of three components: a front plate with optical stem, a back plate and a titanium locking c-ring. The type I Boston KPro is available in either a single standard pseudophakic plano power or customised aphakic powers with 8.5mm diameter back plates for adults and 7.0mm for children. There are several advantages to using the implant in adult populations, said Dr Colby. “First of all the surgery for the Boston KPro is relatively straightforward and well within the skills set of a trained corneal surgeon. Furthermore, the retention is generally excellent in non-autoimmune diseases and the visual

CMY

EUROTIMES | Volume 18 | Issue 11

recovery is rapid to the point that we are now using this device as primary corneal surgery before failed transplantation for those situations where traditional keratoplasty has a poor success rate, including for anaesthetic and vascularised hosts and those with stem cell deficiency,” she said. Dr Colby stressed, however, that the benefits of the implant can only be achieved in the presence of comprehensive ongoing postoperative care. “Postoperative care is really where the art of keratoprosthesis comes into play as these patients require very close follow-up by someone trained to understand and manage the complications following Boston KPro implantation. Patients need to wear a soft contact lens for life which helps reduce the chance of cornea melting, and they use not only topical steroids but also topical antibiotics to prevent subsequent endophthalmitis,” she said. For paediatric patients, the device provides rapid visual recovery in days to weeks rather than months, which aids in amblyopia management, said Dr Colby. “The lack of corneal astigmatism also helps in this respect. Another advantage is that the device allows us to have a reduced number of examinations under anaesthesia since we are not counting on the corneal tissue itself to stay free of vascularisation. Retinoscopy is also easy through the device and it is very straightforward to correct residual refractive error through the bandage contact lens, so this can be helpful as the child grows,” she added. Dr Colby said that the incidence of retroprosthetic membranes, which was one of the principal complications associated with implantation of the Boston KPro and typically occurred in two-thirds of all patients, seems to have been resolved thanks to design modifications of the back plates. “Histopathologic studies of the explanted implants with retroprosthetic membranes showed that the membranes came from activated keratocytes from the host cornea that migrated through gaps in the posterior graft host junction. To address the issue, we introduced a larger titanium back plate which results in a decreased graft-host junction thickness. None of the patients implanted with this new back plate have developed retroprosthetic membranes so we are hopeful that the problem is now resolved,” she said. She added that there is a lot of help available to surgeons interested in using the Boston KPro device, including training packs, newsletters, users’ meetings and on-site training in Boston. Further information can be obtained from the Boston KPro coordinator Larisa Gelfand (Larisa_gelfand@meei.harvard.edu).

contact Kathryn Colby – kacolby@meei.harvard.edu

Special Focus

PAEDIATRIC OPHTHALMOLOGY

GLAUCOMA

Glaucoma drainage implants effective long-term by Pippa Wysong in Vancouver

The power of one

aediatric patients do well with glaucoma drainage implants (GDI) in the long-term, according to findings from a new study, but a relatively high rate of complications should be expected. “Close monitoring and active management of complications are of paramount importance to ensure successful paediatric GDI surgery," according to Achilleas Mandalos MD, Birmingham and Midland Eye Centre in Birmingham, UK. GDIs are generally reserved for paediatric glaucoma cases that respond poorly to goniotomy or trabeculectomy. Their use in this population has been on the increase in the last decade, however, long-term outcomes and safety from the implants in this age group has not been fully determined.

GDI surgery A retrospective study of all paediatric patients less than 18 years of age who underwent GDI by the same surgeon (Velota Sung, MD), between 2004 to 2011, was performed. Successful outcome was defined as IOP between 6 and 22 mmHg (with or without medication), and at least 20 per cent reduction in IOP from the surgery, no devastating vision loss and no need for further glaucoma surgery according to details in a poster presented by the researchers at the 5th World Glaucoma Congress. The study included 52 patients (half were female) who underwent 69 GDI procedures. Close to 32 per cent had aphakic glaucoma, about 22 per cent had congenital glaucoma and 20 per cent had uveitic glaucoma. A total of 55 per cent were given the Baerveldt-250 implant, while the remainder had either the Molteno or Baerveldt-350 implants. Mean follow-up was 45.7 months, ranging from three to 101 months. “The data were collected at the last preoperative visit and at three months, one year and six monthly visits up to the last clinic visit,” he said. At the start of the study, success was defined as a postoperative IOP between 6 and 22 mmHg with or without medication, and a drop in IOP of at least 20 per cent

Two types of incisions – one module

“

The data were collected at the last preoperative visit and at three months, one year and six monthly visits up to the last clinic visit Achilleas Mandalos MD

after surgery, according to details in the poster. Researchers found that at the last clinic visit, overall success was attained in 66.6 per cent of cases, with 49.3 per cent being defined as a complete success. Within the first six months after surgery, 39.1 per cent had developed hypotony, 21.7 per cent had choroidal effusion, 20.5 per cent of phakic patients had cataracts and a small number, 2.9 per cent, developed endophthalmitis. Six months or more after surgery, 13.4 per cent had hypotony, 5.9 per cent had choroidal effusion, 22.9 per cent of phakic patients had cataracts. Endophthalmitis occurred in 5.8 per cent of patients.

Close monitoring Overall, the outcomes in this group compared favourably to those in other studies in the medical literature. But because of the relatively high rate of complications in this age group, "close monitoring and active management of complications are of paramount importance to ensure success of paediatric GDI surgery," Mr Mandalos told EuroTimes.

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Special Focus

PAEDIATRIC OPHTHALMOLOGY

Orbital cellulitis

New guidelines improve treatment

by Dermot McGrath in Copenhagen

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ffective management of orbital cellulitis in children requires a multidisciplinary team approach to ensure that patients receive prompt and effective treatment for this rare but potentially debilitating disease, according to a study presented at the 2013 Congress of the European Society of Ophthalmology. “Our study showed that we need to improve our compliance with diagnostic imaging and treatment guidance to effectively deal with orbital cellulitis in our paediatric patients,” Adam Bull, Stepping Hill Hospital, Stockport, UK, told delegates. Dr Bull presented a retrospective review of diagnosis and antibiotic treatment options in a large district general hospital focusing on a 90-month period following the introduction of new orbital cellulitis guidelines. “The main features of these guidelines included the introduction of diagnostic criteria for performing CT scans, and also given the similar bioavailabilty between oral and intravenous preparations, the administration of oral antibiotics ciprofloxacin and clindamycin as first-line treatment to minimise delay,” he said. Dr Bull said it was important to try to distinguish the disease from the less severe preseptal cellulitis. “Whereas traditionally hallmark symptoms such as abnormal pupil reactions, pain associated with eye movement, double vision and proptosis have been used to distinguish orbital cellulitis from the milder preseptal cellulitis, this differentiation can be much more difficult in practice. The general consensus, therefore, is that if you cannot differentiate between the two, it is prudent to treat as orbital cellulitis,” he said.

Differentiation is difficult Dr Bull’s joint study with Anna Maino FRCOphth, FEBO, included 40 children with an average age of six years, 32 of whom had been referred by their general practitioner, six by the emergency department and two by other hospitals. The most common findings were the presence of significant swelling encroaching on the visual axis, reduction in visual acuity which ranged from mild to severe loss and the presence of temperature at initial assessment.

“We realise that we have to improve our compliance with diagnostic imaging and treatment guidance” To determine the necessity or otherwise of performing a CT scan, the diagnostic guidelines are comprised of colourcoded criteria to help guide the treating physician, said Dr Bull. “Our guidelines have orange and red criteria, which stipulate that if the patient has any of the orange criteria alone then this warrants discussion with a consultant to determine whether a diagnostic CT scan is indicated. If, however, a patient has any of the red criteria then this automatically fast-tracks them for emergency CT scanning,” he said. The review showed that while six patients had the orange criteria, none of these cases were discussed with the consultant with regards to whether a CT scan was warranted. A further six patients had red criteria and all were scanned within a 24-hour time frame. The review found that seven patients were diagnosed as preseptal cellulitis and were discharged. Of the remaining 33 patients, two were vomiting and therefore were not suitable for oral antibiotic therapy and were duly started on intravenous treatment.

Oral antibiotics Of the initial total of 31 eligible patients, only nine received oral antibiotics as per the guidelines. The average time to treatment was 198 minutes in the intravenous group and 115 minutes in the oral group. Twenty-two patients who were suitable for oral antibiotic therapy were started on IVs, said Dr Bull. “We realise that we have to improve our compliance with diagnostic imaging and treatment guidance. To that end, we are disseminating the findings of our review both locally and internationally and have put on topic-specific training sessions for triage nurses and ophthalmic paediatric trainees,” he concluded.

18TH

ESCRS Winter Meeting In conjunction with the Slovenian Society of Cataract & Refractive Surgery

Ljubljana, Slovenia

14-16 February 2014 Preliminary Programme, Hotels & Registration Available

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EUROPEAN SOCIETY OF CATARACT & REFRACTIVE SURGEONS

Update

Cataract & refractive

contact

Gilles Lesieur – g.lesieur@centre-iridis.fr

CME AETIOLOGY

Comparison study CME after four different hydrophilic acrylic microincision IOLs by Dermot McGrath in Paris

aster, less traumatic microincision cataract surgery techniques and sophisticated IOL designs have done much to reduce the incidence of cystoid macular oedema (CME) in recent years, but the specific aetiology of the disease remains elusive and the condition may occur even after uncomplicated surgery in low-risk eyes, according to a French researcher. “Along with posterior capsule opacification, CME remains a persistent but relatively rare problem for the modern cataract surgeon,” Gilles Lesieur MD told delegates attending the annual meeting of the French Implant and Refractive Surgery Association (SAFIR). Characterised by the collection of fluid in the macula and most often associated with inflammation following cataract surgery, CME is the main source of visual deterioration following uncomplicated cataract surgery. The incidence of macular oedema in the scientific literature is usually about one per cent to two per cent, noted Dr Lesieur, an ophthalmologist in private practice in Albi, France. While the specific aetiology is not fully understood, factors believed to contribute to its development include light toxicity, vascular pathologies, uveitis, diabetes, epiretinal membrane, IOL sterilisation, prostaglandin use, complicated surgery and long surgery times, he said. “We should bear in mind J R Wolter’s famous quote that every time a surgeon performs a phacoemulsification he opens a Pandora’s box, provoking potentially a range of complex and dangerous ocular reactions,” he said.

“

Along with posterior capsule opacification, CME remains a persistent but relatively rare problem for the modern cataract surgeon Gilles Lesieur MD

EUROTIMES | Volume 18 | Issue 11

“We need further research to elucidate the possibility of a correlation between the haptic design and irritation of the ciliary muscle and we are currently conducting a ultrasound biomicroscopy study to examine this very question” The goal of Dr Lesieur’s retrospective study was to analyse the incidence of CME after implantation of four different hydrophilic acrylic microincision implants in 3,871 patients between 2006 and 2012. The Akreos MICS (Bausch + Lomb) was implanted in 376 patients, with nine cases of CME; the CT Asphina (Carl Zeiss Meditec) in 780 patients, with 17 CME cases; the MicroSlim (PhysIOL) in 670 patients, with two cases of CME; finally, the Micro AY (PhysIOL) was implanted in 2,045 patients, with 13 CME cases. The total CME incidence for all four lenses combined was 1.06 per cent, said Dr Lesieur, which is in conformity with that found in the scientific literature. Looking at the overall results, Dr Lesieur said that there was no statistically significant difference between the CME rates found with the MicroSlim and Micro AY lens or between the Akreos and Asphina IOLs. However, a statistically significant difference was found between the two PhysIOL lenses and both the CT Asphina and the Akreos MICS lenses. Interestingly, Dr Lesieur noted that while the contralateral eye of affected patients was not systematically implanted with the same IOL as that of the study eye, many still presented with CME in that eye as well.

Courtesy of Gilles Lesieur MD

In terms of aetiology, Dr Lesieur said that epiretinal membrane, diabetes and vascular pathology were all implicated to some degree in patients implanted with Akreos MICS, CT Asphina and Micro AY lenses. All of the CME cases resolved after medical treatment, with the exception of two patients that required surgical intervention for ablation of epiretinal membrane and injection of intravitreal dexamethasone 0.7mg. No anomaly was found in the sulcus or the angle of the various IOLs, which he said seemed to rule out, for the moment, the theory of possible contact between the haptic and the ciliary body as being responsible for the CME.

He concluded that the differences found between the CME rates of the IOLs in his study may partly be explained by the presence of comorbidities in these patients. “We need further research to elucidate the possibility of a correlation between the haptic design and irritation of the ciliary muscle and we are currently conducting a ultrasound biomicroscopy study to examine this very question,” he said. * Dr Lesieur would like to especially thank Laure Gobin PhD, statistical analysis; Sophia Fredéric and Sabrina Vieusses, orthoptists.

contact

Matteo Piovella – piovella@piovella.com

Update

Cataract & refractive

OCULAR BANDAGES

Benefits support routine use in cataract surgery

he opportunity to improve patient comfort together with the potential to reduce the risk of postoperative endophthalmitis by improving incision integrity provides a rationale for routinely sealing clear corneal incisions with a hydrogel ocular bandage after cataract surgery, said Matteo Piovella MD, at the 26th Asia-Pacific Association of Cataract & Refractive Surgeons Annual Meeting. Dr Piovella, medical director, Centro Microchirugia Ambulatoriale, Monza, Italy, reported on his four-year experience using hydrogel ocular bandages (ReSure Adherent Ocular Bandage, Ocular Therapeutix and OcuSeal Liquid Ocular Bandage, Beaver Visitec International). He noted that he was initially impressed by analyses he conducted showing that use of these products significantly reduced patient reports of foreign body sensation on postoperative day one, and did so without compromising early visual recovery or causing any other adverse events. However, his decision to incorporate a hydrogel ocular bandage into his standard surgical protocol was fortified by experimental and clinical findings indicating that these products increase

EUROTIMES | Volume 18 | Issue 11

the watertight properties of the surgical incision. Dr Piovella said that he is now using a hydrogel bandage in all cases excluding those with significant epithelial loss where the product will delay ocular surface recovery. For patients having bilateral surgery, Dr Piovella uses one of the commercially available products in the first eye and the other for the fellow eye procedure. “It is very difficult to prove scientifically that a hydrogel ocular bandage reduces the risk of post-cataract surgery endophthalmitis. However, if it does prevent these horrible infections by preventing incision leakage, I am protecting my patients. And in using these products, I am at the least serving them better by giving them greater comfort,” said Dr Piovella. Several lines of evidence indicate that the hydrogel bandage products protect against corneal incision leakage. In a cadaver eye study, researchers from the Moran Eye Institute, University of Utah, Salt Lake City, reported that the mean IOP at which leakage occurred was increased significantly and by more than three-fold in eyes with corneal incisions closed with the OcuSeal bandage compared with untreated controls.

Courtesy of Matteo Piovella MD

by Cheryl Guttman Krader in Singapore

In a controlled clinical trial, findings from postoperative OCT imaging, IOP measurements and Seidel testing were consistent in supporting the conclusion that use of the ReSure ocular bandage prevented incision microleaks. In addition, Dr Piovella reported his observation that the anterior chamber depth achieved after BSS inflation at the end of the cataract surgery case is increased when the incision is sealed with a hydrogel ocular bandage. Dr Piovella acknowledged that there are barriers to more widespread adoption of the hydrogel bandages. Cost is an issue as is the logistics of their use, which involves precise timing for mixing the components

together and applying the final solution onto the cornea before the material begins to polymerise. In fact, he reported that in a study of one of the products enrolling 256 eyes, the material could not be applied in two per cent of cases due to imperfect mixing of the components and in another six per cent because it was not applied fast enough after mixing. “Surgeons should anticipate a learning curve for using these products and to sometimes need a second attempt. However, they should be open-minded because the learning curve is not too difficult or too long,” Dr Piovella said.

13-17 September

2014

London XXXII Congress of the ESCRS www.escrs.org

add_november_ok.pdf

10/11/13

Update

Cataract & refractive

IOL OUTCOMES

Surgeons weigh in on intraoperative performance and clinical results by Cheryl Guttman Krader in Singapore

urgeons using the monofocal and toric versions of the single-piece, aspheric hydrophobic acrylic enVista IOL (Bausch + Lomb) give the implant good early reviews with high ratings for patient outcomes. Speaking at the 26th Asia-Pacific Association of Cataract & Refractive Surgeons, Hyo Myung Kim MD, PhD, reported results achieved in a consecutive series of 33 eyes of 30 patients followed to three months after implantation with the monofocal aspheric enVista IOL (MX60). The surgeries were performed at the Anam Hospital of the Korea University College of Medicine, Seoul, South Korea, where Dr Kim is a professor of ophthalmology. The patients had typical characteristics for a cataract surgery population, with a mean age of 68 years. Follow-up ranged from just one month to 4.7 months. Dr Kim described the BCVA results as “nearly perfect”; 31 (92 per cent) eyes achieved 20/20 or better BCVA. Poorer vision in the remaining two eyes was explained by comorbidities. Refractive outcomes were also good with achieved mean SE at one month and three months being very close to the target refraction (-0.30 ± 0.74 D and-0.14 ± 0.54 D vs. -0.40 ± 0.76 D respectively). Consistent with marketing claims for the enVista IOL that emphasise its glisteningfree material and design characteristics for minimising posterior capsular opacification (PCO), Dr Kim reported that retroillumination photography found no evidence of PCO within the central 3.0mm of the capsule. He observed no cases with glistenings in the IOL material. “However, longer follow-up is needed to assess the optical clarity of the lens and the posterior capsule,” Dr Kim said. Dean Corbett MD, private practice, Auckland, New Zealand, reported on his initial experience using the toric version of the enVista IOL (MX60T) in 12 eyes with astigmatism ranging from 0.93 to 3.32 D (mean 1.53 D). At the time of the surgeries, the IOL was available in three cylinder powers correcting 1.25, 2.00, or 2.75 D at the IOL plane. The toric line is now being expanded with the addition of models correcting 3.50, 4.25, 5.00, and 5.75 D of astigmatism in the IOL plane. Dr Corbett performed the procedures through a clear corneal temporal incision

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measuring 2.4 to 2.65mm and used the manufacturer’s free online calculator (www.envistatoric.com) to determine astigmatic power and axis of implantation. His technique included preoperative axis marking at the slit-lamp using a needle and gentian violet staining to guide alignment of the IOL intraoperatively. Postoperative IOL rotation was measured using a reticule on the slit-lamp, and the results showed good in-the-bag stability of the toric IOL. At three months, mean rotation from surgery was five degrees, and 11 (92 per cent) of the 12 IOLs were within seven degrees of intended axis. In the one outlier, the IOL was 15 degrees off axis, but the IOL had rotated only two degrees since postoperative day one, and the patient had good vision and declined additional intervention, Dr Corbett reported. “My experience in this series compares well with the outcomes in the US FDA enVista toric trial where postoperative rotation was five degrees or less in 92 per cent of 101 IOLs evaluated at three to six months after surgery,” he said. In addition to being glistening-free, the novel hydrophobic acrylic material of the enVista IOL is noteworthy for its surface hardness and rigid nature. The surface hardness increases the IOL’s resistance to scratching from surgical manipulations, and its rigidness results in slow unfolding. Dr Corbett pointed out that the latter characteristic allows for precise positioning of the toric IOL within the capsular bag, as it enables implant rotation to the desired axis as well as thorough removal of the ophthalmic viscosurgical device (OVD) from behind the lens. However, Dr Kim noted that the rigidness of the IOL created some minimal handling concerns in terms of difficulties with unloading and unfolding. To address the latter issues, and taking into account that the hydrophobic acrylic polymer transitions from a rigid to a more flexible material when the temperature exceeds 28º to 30ºC, Dr Kim suggested using warm OVD (30º to 33º C) when filling the anterior chamber and capsular bag for IOL implantation. C

CMY

contacts Dean Corbett – dlcorbett@xtra.co.nz Hyo Myung Kim – hyomkim@hanmail.net

Strawinskylaan 1265, 1077 XX Amsterdam - The Netherlands www.vsybiotechnology.com

contact

Update

CORNEA

Friedrich Kruse – Friedrich.Kruse@uk-erlangen.de

ENDOTHELIAL KERATOPLASTY

Unravelling the sticky question of DMEK graft adhesion by Dermot McGrath in Copenhagen

esearchers are working hard to understand the complex interaction of factors behind the high graft detachment and re-bubbling rates associated with Descemet’s membrane endothelial keratoplasty (DMEK), according to a presentation here. “We are all well aware of the advantages of DMEK in terms of the visual results, rapid recovery and low rejection rates, but primary graft detachment is still a problem that remains to be solved in order for DMEK to reach its full potential,” Friedrich Kruse MD told delegates attending the 2013 Congress of the European Society of Ophthalmology (SOE). Dr Kruse, University of ErlangenNürnberg, in Erlangen, Germany, outlined some of the key factors believed to play a role in graft detachment and high re-bubbling rates in DMEK patients. Compared to Descemet’s stripping automated endothelial keratoplasty (DSAEK), the donor preparation for DMEK is more difficult given the need to consistently separate Descemet’s membrane without tearing, which may result in loss of that donor. "Older donors are also preferred for DMEK since their Descemet’s membrane tends to be less adherent than in younger corneas and therefore easier to separate.” Graft thickness is also likely to play a role in graft adhesion and donor age is again a factor here, said Dr Kruse. “Younger donors are only to be used by very experienced surgeons because the

Descemet’s membrane roll is usually very tight. It relates to the age of the patient - in general the older the patient the thicker the membrane. So while we can use young donors for DSAEK, it is probably not a good idea for DMEK, at least for less experienced surgeons, because unfolding the tight graft tends to result in more trauma for the endothelial cells and a higher risk of detachment,” he said. Another factor to watch for in selecting donor tissue is the presence of pathologies such as cataract and pseudoexfoliation syndrome, said Dr Kruse. “A donor who has undergone cataract surgery means a corneal incision and also side port incisions and this is a very big problem in preparing the tissue. Pseudoexfoliation syndrome also needs to be watched for because it renders an abnormal structure of Descemet’s membrane and increases the likelihood of eventual graft detachment,” he said. Current research is also seeking to shed light on the complex role played by adhesion proteins in Descemet’s membrane in increasing the risk of detachment, said Dr Kruse. “The fact is that we do not really know why a graft sticks in certain cases and not in others. There are significant interindividual variations in the concentration of proteins such as fibronectin, vitronectin, amyloid P and the various fibulin glycoproteins, among others, in the interfacial matrix layer of Descemet’s membrane. There are more of these proteins concentrated in the central corneal zone, so that might also go some

EUROTIMES

ESCRS

“

A donor who has undergone cataract surgery means a corneal incision and also side port incisions and this is a very big problem in preparing the tissue Friedrich Kruse MD

way towards explaining why the detachment always starts in the periphery,” he said. Host characteristics are also not to be overlooked in the search for reduced detachment rates, said Dr Kruse. “In our experience, we get much better results from Fuchs’ endothelial dystrophy patients than those with pseudophakic bullous keratopathy. Additional pathologies are also a problem, as a shallow anterior chamber can make DMEK surgery even trickier,” he said. Graft overlap also needs to be borne in mind. A recent study carried out by Dr Kruse’s group found that complete removal of Descemet’s membrane in the area of the graft allows better adhesion following DMEK surgery. Looking at 100 eyes that underwent DMEK by the same surgeon, the study examined the zone between donor and graft Descemet’s membrane.

Based on the size of descemetorhexis, patients were divided into three groups: group one of 15 patients in which the graft and the membrane overlapped completely (100 per cent), group two of 21 patients in which no overlap was seen and in which the graft was separated from Descemet’s by a small gap and group three of 69 patients with variable overlap. Significant graft detachment appeared in 10 eyes of group one and three eyes of group two. The area of peripheral detachment was significantly greater in group one than in group two. Re-bubbling was performed in three eyes of group one due to persistent major detachment but was not necessary in group two, said Dr Kruse. “Our results suggest that complete removal of Descemet’s membrane in the area of the graft allows better adhesion of the graft and greater overlap is a risk factor leading to graft detachment. Thus patients with greater overlap have to be followed up more carefully,” he said. Insertion of the graft also poses a significant problem for DMEK procedures at the moment, said Dr Kruse. “This is a big problem because there is no specially adapted insertion technique. Our group is currently using an intraocular lens shooter, but this is not available in the United States, and so they have to improvise to put the graft into the anterior chamber. We are currently working with a manufacturer to design a shooter so hopefully this will be resolved in the near future,” he said.

™

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EUROTIMES | Volume 18 | Issue 11

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Update

CORNEA

corneal implants

Transplants looking good in longer term by Dermot McGrath in Copenhagen

May Griffith – may.griffith@liu.se

Corn

contact

LONDON e

12-13 September 2014

C o r n

or complications have been reported. The team has submitted a manuscript detailing the overall long-term performance of the corneas as well. The biocompatibility of the implants has also stood the test of time. Apart from a prophylactic six to seven weeks of steroid treatment, the implanted patients have had no recourse to the long-term use of steroid immunosuppression typically required for traditional allotransplantation, and no incidence of rejection has occurred in the implanted corneas. After this initial success, Dr Griffith and co-workers are now seeking to extend the technique into more difficult indications such as chemical burns, severe dry eye and herpes simplex keratitis. “The challenge with these cases is that we have to deal not only with the regeneration but also with the disease or neovascularisation,” she said. The basic concept is to use a range of novel peptides or nanoparticles to improve further on the results obtained with the recombinant human collagen implants. “We have taken biomimetic recombinant human collagen scaffolds from the bench to bedside and are conducting on-going work with novel peptides because we need to put in new functionalities to try to deal with more difficult cases. These techniques can also be extended to the incorporation of stem cells and nanoparticle delivery systems and to other organ systems,” she concluded.

5th EuCornea Congress

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“The results have been very positive. At two years we observed regeneration of the epithelial cell layer and stromal cells were recruited into the implant in all patients”

iosynthetic corneal implants could offer a safe and effective alternative to the implantation of human tissue to help address the current donor cornea shortage, suggests research presented at the 2013 Congress of the European Society of Ophthalmology meeting. “Recombinant human collagen has now been successfully tested as immune compatible implants in humans. The biomaterials can be used to induce endogenous host stem cells to affect regeneration or to deliver exogenous stem cells. We are now looking at ways that the techniques can be extended to the incorporation of stem cells systems and to other organ systems,” said May Griffith PhD, director of the Integrative Regenerative Medicine Centre (IGEN), at Linkoping University, Sweden. Given the current shortage of donor corneas worldwide, especially in developing countries, Dr Griffith said that the biosynthetic substitute could provide a viable supplement to eye bank supplies. Working in partnership with a private company, Fibrogen, which engineered yeast cells to manufacture the human protein collagen, Dr Griffith’s team has succeeded in chemically cross-linking the recombinantly-produced human collagen (RHCIII) and using it to replace the damaged cornea layers of 10 patients with keratoconus and central scarring in the first trial back in 2008. As Prof Griffith noted, recombinant human collagen provides a source of safe, stable material that is ideal for tissue engineering as it minimises the risk of disease transmission or immune reaction which could result after implantation of animal source collagen. “The results have been very positive. At two years we observed regeneration of the epithelial cell layer and stromal cells were recruited into the implant in all patients. The tear film was also restored and nerve regeneration and touch sensitivity was observed as well. While the morphology is obviously not as good as a healthy human cornea, it is nevertheless as good as or better than that found in a human donor cornea in some aspects,” she said. Four years after the first human trials of the biosynthetic corneas, no adverse effects

European Society of Cornea and Ocular Surface Disease Specialists

www.eucornea.org

contact

Update

CORNEA

CORNEAL TRANSPLANTATION Fish scale-derived collagen offers advantages as a potential material for artificial cornea by Dermot McGrath in Copenhagen

Martine J Jager – m.j.jager@lumc.nl

“

It is still very early days, but the initial results in animal models show a lot of potential for fish scale-derived collagen matrix as a possible alternative for human donor corneal tissue Martine J Jager MD, PhD

Primary human corneal epithelial cells cultured on the FSCM are positive for the differentiation marker CK3/12 (red). Blue = cell nucleus; Green = F-actin

iosynthetic corneal implants made of fish scalederived collagen may in the near future provide a potentially safe and effective alternative to the implantation of human tissue to help address the current donor cornea shortage worldwide, report researchers. “It is still very early days, but the initial results in animal models show a lot of potential for fish scale-derived collagen matrix as a possible alternative for human donor corneal tissue,” Martine J Jager MD, PhD, told delegates attending the 2013 Congress of the European Society of Ophthalmology during a symposium organised by the Academia Ophthalmologica Internationalis.

The transparent Fish Scale-derived Collagen Matrix (FSCM)

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Case of an FSCM (arrow) implanted intra-stromal in the cornea of a rat at 13 days postoperatively

Dr Jager, Leiden University Medical Center, Leiden, the Netherlands, said that the development of a viable artificial cornea would go some way towards addressing the current deficit of donor corneas. “Corneal blindness is still the second major cause of blindness in the world. There is a shortage in donor corneas for lamellar or perforating corneal transplants, and this is especially the case in developing countries. If you look at the deficit between available corneas and needed corneas in India, for example, we see just how acute the problem is,” she said. An ideal artificial cornea, said Dr Jager, would be one which was easy to obtain, easy to insert and cheap to produce. She said that the idea of using fish scales for this purpose is credited to Dr Julio Lin, whose research with the tilapia fish identified it as a potentially viable source of type-I collagen with an amino-acid composition very similar to humans. Through a complex process, the decalcified scales of the fish are stripped of their cells, leaving a collagen scaffold with properties similar to natural human cornea. Stem cells can then be cultured on the collagen scaffold to create a sheet of limbal-corneal epithelium for research as well as clinical transplantation. Research performed by Dr Herbert van Essen in Leiden showed that the fish scale-derived collagen offers several inherent advantages as a potential material for artificial cornea. First, the transparency of the fish-scale derived collagen is very good and is comparable to human corneas. Studies

conducted to measure light scatter and light transmission showed that the amount of scattered light was comparable to that seen in early cataract and the percentage of light transmission was similar to the transmission through the human cornea. The material is also suturable, although considerable care is needed in handling the collagen matrix to avoid tearing. Biocompatibility testing of the collagen matrix has also been largely positive in the rat model, said Dr Jager. To test its tolerance in rodent eyes, three separate placement techniques were used: anterior lamellar keratoplasty (ALK), interlamellar corneal pocket (IL) and subconjunctivally. Implantation of the matrix as an ALK led to mild haziness only, not obscuring the pupil, despite the development of neovascularisation around the sutures. Interlamellar placement led to a moderate haze, partly obscuring the pupil, and to partial melting of the anterior corneal lamella. The subconjunctival group exhibited local swelling and induration, which decreased over time. Histology showed a chronic inflammation varying from mild and moderate in the ALK- and interlamellar group, to more severe in the subconjunctival group, said Dr Jager. Going forward, Dr Jager said that further clinical studies are necessary for better understanding of the immunogenicity of the matrix and to resolve problems of mechanical irritation induced by some of the initial transplants in animal models.

Courtesy of Herbert van Essen

HE-staining of subcutaneous implanted FSCM after 2.5 months follow-up, showed only a mild to minimal immune reaction, with hardly any granulocytes and no giant cells

X XXI c ongress of the e s c r s 5 -9 O C TOBER 2 0 1 3

Amsterdam 2013

Youth, education and research driving progress

ontinuing the strong upward momentum of recent years, over 7,400 delegates from all over the world gathered in Amsterdam, The Netherlands for the XXXI Congress of the ESCRS. Addressing the Opening Ceremony, Peter Barry, president of the ESCRS, welcomed delegates to Amsterdam and stressed the strong links between the society and the Netherlands. “These links between the ESCRS and Amsterdam and the Netherlands are particularly strong. It was in 1982 when Cornelius Binkhorst founded the EIIC in The Hague and I understand there were 160 delegates at that congress, some of whom are still with us today. We returned in 1995 for the 13th annual congress where the number of delegates increased to 1,100 and six years later we held the 14th annual congress in Amsterdam with 2,300 delegates. Now, 12 years on, I am delighted to

Douglas Koch (left), who gave the Binkhorst Medal Lecture pictured with Peter Barry, president of the ESCRS

report that the number of delegates attending this congress is over 7,000,” he said.

Reflecting on his term of office, Dr Barry said that youth, education and research have been

the thematic cornerstones of his presidency. “For young ophthalmologists we offer free membership for any three years of their training, bursaries to the annual congress and the winter meeting, and we also have the Observership grant programme which enables them to visit clinics in Europe for a period of one or two weeks,” he said. In terms of support for research, Dr Barry highlighted initiatives such as the ESCRS PreMed study on macular oedema after cataract surgery, a new femtolaser-assisted cataract surgery study and the EUREQUO patient outcomes register which has recorded almost two million cataract surgeries in its database. An Endophthalmitis Registry has also been instituted to track patterns of bacterial breakthrough and microbial resistance, and a new 2013 version of the Endophthalmitis Guidelines has been made freely available to all delegates.

Dr Barry also emphasised the society’s ongoing commitment to supporting the excellent work of Oxfam and ORBIS in their various projects in the developing world. ESCRS treasurer and chairman of the Netherlands Intraocular Implant Club, Rudy Nuijts, welcomed delegates to Amsterdam. “It was in 2001 when the last ESCRS meeting was organised in Amsterdam and it is my great pleasure on behalf of the Netherlands Intraocular Implant Club and the Dutch Ophthalmological Society, to welcome you to this year’s congress in this wonderful city,” he said. Dr Nuijts outlined the rich history of the Netherlands in IOL surgery and development, citing the major contributions of Cornelius Binkhorst and Jan Worst in laying the foundations for much of the progress that was to follow in the developing field of IOL surgery.

Innovations in technology

he Michael Blumenthal Award in the 2013 Video Competition went to Makoto Kishimoto, Japan, for “New type torsional phaco tip advantages”. Dr Kishimoto described how a close examination of the physics of ultrasound phacoemulsification inspired the design of new phaco tip that is less likely to cause disruptions of flow and scattering of lens fragments. The aim of the new design is to prevent cavitation, a phenomenon that can occur when a sudden reduction of pressure reduces the boiling point of water. In an experiment using a piece of Gouda cheese, Dr Kishimoto was able to demonstrate how cavitation alone can generate a very strong flow. That led them to design a tip in which flow would switch from positive to negative in a way that the pressure differentials averaged out within a very short temporal frame.

Educational Sheraz Daya, UK, received First Prize in EUROTIMES | Volume 18 | Issue 11

the Educational Category for “Femtosecond deep anterior lamellar keratoplasty,” which provides a demonstration of donor and host preparation using the “modified mushroom” trephination profile created with the laser in a DALK procedure. The Second Prize went to Soosan Jacob, India, for “And the Twain shall meet: retinal and corneal convergence Descemet membrane detachment – new classification and management,” and Third Prize to Renato Ambrosio Jr, Brazil, for “Thin or thinned, thick or thickened: that is the question”.

Innovative First Prize in the Innovative Category went to Ronaldo Badaro, Brazil, for “RKology”, in which he describes a novel suturing technique that he used to even out the contours of the cornea of a patient who developed a progressive loss of spectacle corrected vision many years after undergoing radial keratotomy. Pavel Stodulka, Czech Republic, took Second

Prize for “Simultaneous laser assisted cataract surgery and silicone oil removal through laser posterior capsulotomy”. The Third Prize went to Yichieh Shiuey USA for “Femtosecond implantation of a foldable artificial cornea”.

Scientific In the Scientific Category, First Prize went to Hisaharu Suzuki, Japan, for “Temperature in the anterior chamber during phacoemulsification”. Special Cases First Prize in the Special Cases Category went to Fernando Trindade, Brazil for “Customize me”. In his video, he presents two very different cases where customised lenses brought about successful outcomes that could not have been achieved with the usual commercially available variety. The Second Prize went to Partha Biswas, India, for “Spherophakia with corneal endothelial adhesion: challenged to the limits”. Third Prize went

Makoto Kishimoto, winner of the Michael Blumenthal Award in the Video Competition (left), with Peter Barry, president of the ESCRS

to Milan G J Izak, Slovakia, for “Challenging cataract surgery”.

Young Ophthalmologists

Denise Wajnsztajn, Israel, received First Prize in the Young Ophthalmologists category for “Surgical approach to post-

traumatic epithelial ingrowth in visual axis area two years after LASIK surgery: a challenging case”. The Second prize in the category went to Soumya Nanaiah, India, for “Techniques of Scleral-fixated capsular tension segment implantation”.

Amsterdam 2013

4TH EUCORNEA CONGRESS

4-5 OCTOBER 2013

Successful congress with excellent programme

uCornea may be a young society in comparison to some of the older, more established ophthalmological societies, but in four short years it has made a major impact and there are exciting plans for its future development. José Güell MD has been a driving force in the promotion and exposition of corneal research and surgery, in addition to his pioneering work in refractive surgery. Four years ago he helped found EuCornea, the first Europewide organisation devoted to the treatment of corneal disease so it was fitting that Dr Güell was given the opportunity as president of EuCornea to address delegates at the 4th EuCornea Congress in Amsterdam, The Netherlands. Speaking at the Opening Ceremony, Dr Güell said the success of EuCornea was due to

the high calibre of the scientific programme. “I am pleased to announce that this looks set to be another successful congress,” said Dr Guell. “I would like to thank all the organisers and speakers for their invaluable role in creating such a high calibre scientific programme for the 4th Congress.” This year’s congress, which was attended by over 700 delegates, featured an excellent programme with world leaders in the field of cornea and ocular surface disease speaking across 12 symposia, six courses and 12 free paper sessions. This included a joint ESCRS/EuCornea symposium on Refractive Surgery in Risky Cornea chaired by Beatrice Cochener and Rudy Nuijts with co-chairperson Roberto Bellucci. “At a time when we all have to choose carefully which congresses we attend, offering delegates more

than one meeting at the same time seems to be very valuable,” said Dr Güell. Dr Güell said he was also pleased to announce that in September 2014, EuCornea will be partnered with the ESCRS and EURETINA congresses in London. “We hope that this alliance of related meetings will be highly beneficial for members and delegates from all organisations,” he said. The Opening Ceremony was also addressed by Michel Zaal, president of the Dutch Cornea Society, and Donald Tan, president of the Asia Cornea Society and president of The Cornea Society. Dr Güell said they were honoured to have Prof Gabriel van Rij present this year’s EuCornea Medal Lecture. Dr van Rij received the EuCornea Medal after his presentation on “The Cornea: How Many Endothelial Cells are Necessary?”

José Güell, president of EuCornea, addresses delegates at the Opening Ceremony

An alternative to endothelial keratoplasty?

n a minority of Fuchs’ dystrophy patients, corneal clearance after Descemetorhexis without endothelial keratoplasty is possible, said Gabriel van Rij MD in the EU Cornea Medal Lecture. However, many questions remain, including appropriate patient selection and optimal follow-up to support endothelial cell regrowth, added Dr van Rij, who is ophthalmology chair at Erasmus Medical College, Rotterdam, The Netherlands. Dr van Rij noted that transcorneal freezing has been shown to stimulate endothelial cell migration in monkeys and to a limited extent in humans. One monkey study freezing a 7mm zone also demonstrated that ROCK inhibitors doubled cell density. However, Fuchs also involves deposition of an extracellular matrix which persists after freezing, Dr van Rij said. Descemetorhexis removes the endothelium and any remaining matrix. He noted that inadvertent Descemetorhexis EUROTIMES | Volume 18 | Issue 11

EuCornea president José Güell with Gabriel van Rij, who delivered the EuCornea Medal Lecture

in cataract surgery followed by spontaneous corneal clearance has been reported in the literature. Dr van Rij reported a study his group conducted involving eight consecutive Fuchs patients scheduled for Descemet-stripping automated endothelial keratoplasty (DSAEK). They instead received

standard phaco and IOL insertion and Descemetorhexis. Descemet’s membranes were scored just outside the area of corneal guttae. Dexamethasone was administered after surgery and tapered over several weeks, though in hindsight, this may not have been a good idea, Dr van Rij

noted. “Corticosteroids inhibit cell migration and mitosis.” At six months’ follow-up, three patients were considered successfully treated, with best spectacle-corrected vision of 20/25 or better and a mean central corneal thickness of 554 microns and mean endothelial cell density of 458 cell per square mm, though two had corneal oedema just outside the pupillary border. A fourth patient achieved 20/60 and further corneal clearance is awaited. The other four patients had none or almost no corneal clearance with mean best spectacle corrected vision between 20/100 and 20/400 in two. One had an epithelial defect and one a burst bullae. Three of these patients went on to uneventful DSAEK, Dr van Rij said. The two patients with good visual acuity but corneal oedema also underwent DSAEK to relieve discomfort. One patient, though, achieved 20/25 and cell density of 657 per square mm and pachymetry of

544 microns 3.5 years after surgery with only Descemetorhexis. The cornea was initially cloudy but has remained clear since six months after surgery, Dr van Rij reported. She even saw better with the eye receiving only Descemetorhexis than with her fellow eye, which had received DSAEK and phaco two years before the experimental procedure. Further, her cell count rose and pachymetry progressively declined from 584 at six months to 559 at two years and 544 at 3.5 years. “The cornea is thinning still. The patient is very pleased and we are pleased with it.”

Viable alternative Future study of the possible genetic basis of variation in endothelial cell migration and regeneration, and the possible role of drugs may also help make Descemetorhexis a viable alternative to lamellar corneal transplants with its complexity, supply problems and related risk of rejection. “Right now we mostly do endothelial keratoplasty. In the future we will prevent disease progression through gene therapy or SFN, delaying the need for surgery,” Dr van Rij said.

Picture Gallery

EUROTIMES | Volume 18 | Issue 11

XXXI Congress of the ESCRS 4th EuCornea Congress

III

Hamburg 2013

26–29 September 2013

Five days of stimulating exchange at EURETINA

etinal experts and researchers from all over the world converged on the vibrant German port city of Hamburg for the 13th Congress of EURETINA. At the official Opening Ceremony, Gisbert Richard MD, president of EURETINA, welcomed delegates to Hamburg for five days of stimulating exchange, scientific debate and education in the fast-moving field of retinal research. “It is our great pleasure to welcome you to the 13th annual Congress of EURETINA in Hamburg. The success story of our society is of the kind that is probably unparalleled in European medicine. After starting in Hamburg 13 years ago with 300 attending guests, the meeting this year might be the largest retinological meeting worldwide,” he said. Prof Richard said that while much has been achieved, there was no question of allowing the momentum to falter.

Gisbert Richard, president of EURETINA, speaking at the Opening Ceremony at the 13th EURETINA Congress

“Our task is to preserve what we have reached, to carry it forward and to develop it further, without losing sight of the unit of the whole field of ophthalmology. This is a challenge because the

general framework is rapidly changing,” he said. Prof Richard said it was important to improve the exchange of ideas between European retinal specialists and to

give them a voice in Europe. “The progress in our subspecialty in the last few years has been immense, for example in the development of vitreoretinal surgery, the treatment of macular degeneration and many others. Other major advances are knocking on the door such as the development of the retinal chip, the application of stem cells, gene therapy and new drugs,” he said. Education is another key priority for EURETINA, said Prof Richard. “One especially vital task is to support young talented and motivated scientists to become well-trained ophthalmologists and we achieve this by expanding the education programme and introducing new courses,” he said. The third focus for EURETINA is a political one, said Prof Richard, noting that the society needs to back-up innovations in diagnoses and therapies in guidelines, to draw up training curricula and to harmonise at a European level. As part of the Opening Ceremony, the EURETINA

Medal Lecture was delivered by Prof Leonidas Zografos on the topic of “Radiotherapy in Ocular Oncology.” First prize in the EURETINA Video Competition Awards was presented to Juan B Yepez from Venezuela for his video entitled “Illuminated chopper for phacovitrectomy in PDR”. Second prize went to Antonio Valladares Moreno from Spain for “Ahmed valve implantation associated with 23-gauge phacovitrectomy – placement of valve tube directly into vitreous chamber by 23-gauge sclerotomy” and third prize to Mounir Lezrek from Morocco for “Pars plana vitrectomy incidents – management and prevention”. Musical entertainment during the Opening Ceremony was provided by the Die Hamburger Klabautermänner Shanty Choir. Francesco Bandello, presidentelect of EURETINA, brought proceedings to a close by wishing delegates a productive and stimulating meeting.

Evolution in radiotherapy treatments for ocular tumours

adiotherapy has made major advances in recent years in offering a viable treatment modality to patients with ocular tumours that were once deemed inoperable, according to Leonidas Zografos, who delivered the 2013 EURETINA Medal Lecture as part of the official Opening Ceremony at the 13th EURETINA Congress. In a broad overview of the past, present and future of radiotherapy treatments in ocular oncology, Prof Zografos, honorary professor of ophthalmology and consultant at the JulesGonin Eye Hospital, Lausanne, Switzerland, told delegates that technology has come a long way since the pioneering German ophthalmologist Richard Deutschmann’s first successful treatment of uveal melanoma in 1915 with seven

EUROTIMES | Volume 18 | Issue 11

episcleral applications of filtered mesothorium. While the earliest treatment for uveal melanoma was removal of the eye, this has now been supplanted by radiotherapy as the standard of care for patients with uveal melanoma, offering preservation of an intact eye and, in many cases, preservation of visual function, said Prof Zografos. Discussing other key moments in the history of the development of radiotherapy for ocular tumours, Prof Zografos highlighted the research of R Foster Moore, H B Stallard, and Martin and Reese, among others, in ushering in the modern treatment of ocular tumours. While ocular brachytherapy has made major strides in recent years, there are still treatment limitations in terms of tumour height, position

Prof Gisbert Richard, president of EURETINA; Dr Dorothee Stapelfeldt, senator; Prof Leonidas Zografos, who delivered the Medal Lecture: and Dr F Green at the presentation of the certificate for the EURETINA Medal Lecture

and shape, said Prof Zografos. Much of Prof Zografos’ lecture focused on the breakthrough provided by proton beam irradiation of intraocular tumours. At present, there are more than 10 major units worldwide

performing this type of therapy, with an estimated 25,000 to 30,000 cases of uveal melanoma now performed. Over 6,000 cases have now been carried out at the Swiss treatment centres alone, said Prof Zografos.

Survival rates with this type of therapy are excellent. After 10 years, local tumour control is 98.8 per cent and eye retention probability around 95.6 per cent, he said. While proton beam irradiation represents a step forward in the treatment of uveal melanoma, there is always scope for further progress, said Prof Zografos. “The key challenges are the reduction of tumour-related mortality rate, the reduction of the irradiation induced side effects and the preservation of a low tumour recurrence rate,” he said. Putting the evolution of radiotherapy in the treatment of ocular tumours over the past century into context, Prof Zografos quoted the Greek statesman and orator Demosthenes: “Bad things of the past benefit the future and this applies to our patients as well,” he said.

Update

CORNEA The solution for demanding cases

DMEK ADVANCES

LENSTAR LS 900®

New endothelial keratoplasty technique facilitates graft positioning by Roibeard O’hEineachain in Verona

new technique for manipulating endothelial grafts onto the posterior corneal stroma of eyes undergoing Descemet’s membrane endothelial keratoplasty (DMEK) can speed up the surgical procedure and reduce the graft detachment and partial detachment rate, said José Güell MD, Autonomous University of Barcelona, Barcelona, Spain. “This technique allows us to significantly reduce our intraocular membrane manipulation time, independent of donor age or preservation method, and also reduces our re-bubbling rate,” Dr Güell said at Femto 2013, an international meeting on anterior segment surgery. The new technique involves the use of bimanual infusion with inferior iridectomy and transitory 20 per cent partial tamponade with sulphur hexafluoride (SF6) gas. As in air and gas tamponades in vitreoretinal surgery, the technique requires the postoperative cooperation of the patient, who, for the first postoperative week must position the head in three different positions, 15 to 20 minutes at each position, for two hours in the morning and two hours in the afternoon. In a study involving 15 consecutive eyes of 15 pseudo-phakic patients who underwent the new technique, mean uncorrected and best spectacle corrected visual acuities were 0.4 and 0.85, respectively at one month follow-up. That compares to respective values of 0.20 and 0.52 preoperatively. In addition, the mean time period between the main incision closure and final membrane positioning was four minutes and 10 seconds. That compares to a mean of 10 minutes and six seconds for the classic DMEK technique at his centre, Dr Güell said. Furthermore, re-bubbling was only necessary in one case (6.6 per cent) compared to a rate of 18 per cent in eyes undergoing classical DSEK.

Advances in endothelial keratoplasty He noted that endothelial

keratoplasty has undergone a steady evolution since first introduced into clinical practice at the close of the last century, with endothelial grafts becoming thinner and thinner, up to the point where now, with DMEK, the graft consists completely of EUROTIMES | Volume 18 | Issue 11

■ Olsen formula on board

“

This technique allows us to significantly reduce our intraocular membrane manipulation time... José Güell MD

endothelium and Descemet’s membrane. All of the endothelial keratoplasty techniques have the advantages over penetrating keratoplasty of improved tectonic strength, minimal induction of astigmatism and speedier visual recovery. However, in all except DMEK, the bestcorrected visual acuity patients can achieve with endothelial grafts is limited by the reduced corneal clarity caused by a stromato-stroma interface. In addition, research shows that the immune rejection rate of DMEK grafts at two year’s follow-up is only one per cent, compared to 12 per cent for DSEK and 18 per cent for penetrating keratoplasty. There are also fewer posterior corneal higher order aberrations and visual distortions associated with DMEK. However, classical DMEK is a more difficult technique than DSAEK, and the graft tissue has a higher rate of detachment or partial detachment postoperatively, necessitation re-bubbling procedures to manipulate the graft back into place. Dr Güell said that as he gains experience with his new technique his results have continued to improve. In 30 eyes in which he has carried out the procedure since November 2012 up to April 2013, not a single case has required re-bubbling. “Multicentre prospective long-term studies are needed to evaluate this technique and possible future improvements in research on substances to initiate and/or stimulate cellular proliferation will definitely improve this approach,” he added.

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01.10.2013 16:06:41

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EUROTIMES | Volume 18 | Issue 11

Update

CORNEA

GRAFT REJECTION

DSEK data shows downward trend in graft rejection rates of 7.5% after one year

by Dermot McGrath in Copenhagen

he growing popularity of posterior lamellar keratoplasty techniques in recent years has led to a significant reduction in the risk of graft rejection after corneal transplants, according to researchers at the 2013 Congress of the European Society of Ophthalmology (SOE). “The primary reason for graft failure after penetrating keratoplasty (PKP) remains immune rejection, but thanks to the introduction of techniques such as Descemet’s stripping automated endothelial keratoplasty (DSAEK), and Descemet’s membrane endothelial keratoplasty (DMEK) we are now seeing a much better survival rate for these grafts in addition to improved visual outcomes,” Bjoern Bachmann MD, FEBO, told delegates. Dr Bachmann said that even though keratoplasty is renowned as the most successful form of solid organ transplantation, there is a graft failure rate of 20 per cent after five years in low-risk keratoplasty, with immune rejection the main cause. By comparison, the most recent data for DSEK procedures shows a downward trend in graft rejection rates of 7.5 per cent after one year and 12 per cent after two years. Dr Bachmann cited the recent study by Price et al. which showed that DMEK had a graft rejection rate of one per cent at both one and two years, compared to PKP which had a rejection rate of 14 per cent at one year and 18 per cent at two years. “This shows that overall DMEK had a 15-fold lower risk of rejection than DSEK and a 20-fold lower risk than PKP,” he said. In his own clinical experience, Dr Bachmann said he had encountered only one DMEK rejection episode and that was a patient that had undergone the lamellar procedure after a previous PKP. Dr Bachmann noted that when graft rejection does occur in DSAEK or DMEK procedures, the clinical signs are different from those typically found with PKP. “In a lot of patients we see only quite subtle inflammatory signs. One recent study found that 35 per cent of such cases were asymptomatic with the diagnosis obtained only after routine examination. “Other signs to watch for are isolated precipitates in almost 70 per cent of cases, diffuse corneal oedema in 11 per cent and

“

The primary reason for graft failure after penetrating keratoplasty remains immune rejection...

Bjoern Bachmann MD, FEBO combined precipitates and oedema in around one-fifth of patients,” he said. Endothelial rejection can present with an endothelial rejection line (Khodadoust line) that often begins at a vascularised portion of the peripheral graft-host junction and progresses, if untreated, across the endothelial surface over several days, said Dr Bachmann. The predominant cells are lymphocytes and macrophages that damage endothelial cells as the line moves across the endothelium. Such lines are more commonly associated with PKP procedures and are rarely found in lamellar keratoplasty, he said. The process leading to graft rejection is complex and multifactorial, said Dr Bachmann. The immune cascade begins when lymphatic vessels allow the transport of antigen-presenting cells from the graft bed to the regional lymph node in which they induce the activation and clonal expansion of alloantigen-specific T cells. These activated T cells subsequently migrate to the graft bed and initiate graft rejection, he said. Dr Bachmann added that the lack of sutures in minimally-invasive DMEK procedures may also play a role in helping to reduce graft rejection rates, as sutures are known to induce corneal angiogenesis and lymphangiogenesis, which contribute to subsequent graft rejection. In addition, the graft transferred during DMEK does not contain corneal stroma and therefore probably lacks donor derived antigen presenting cells. These cells are important for the initiation of a donor specific alloimmune response. The fact that DMEK induces less disruption to the blood-aqueous barrier compared to PKP is also likely to play a role in the reduced rejection rate, he said.

contact Bjoern Bachmann – bjoern.bachmann@uk-erlangen.de

E R IP FR EA SH ES 3 Y ER NE B AI EM R M RT FO

ESCRS

contacts

Update

GLAUCOMA

GLAUCOMA RESEARCH

Several methods are being developed to deliver stem cells to replace RGCs and their axons to restore vision By Pippa Wysong in Vancouver

esearch in neuroprotection in glaucoma appears to be on the wane, but it should be looked at with excitement, Francesca Cordeiro MD, PhD, told the 5th World Glaucoma Congress. Dr Cordeiro called on ophthalmologists to keep this area of research alive and noted that work in other areas of medicine show this is a promising and exciting area. "It's time we looked at colleagues in other fields," he said. "We have a lot to learn about neuroprotection and neuroregeneration in Parkinson's, Alzheimer's and stroke. Clinical trials in neuroprotection in glaucoma have been hit very badly and it's something we need to embrace as a community with industry, academia and other clinicians in trying to resurrect this potentially very rewarding area of research," said Dr Cordeiro, UCL professor of glaucoma and retinal neurodegeneration studies, London Institute of Ophthalmology, UK. EuroTimes found Dr Cordeiro is not alone in her optimism. In a recent review of optic nerve-related research in the Canadian Journal of Ophthalmology (CJO), James C Tsai MD, Yale University noted that glaucoma is now considered a chronic, multi-factorial neurodegenerative disease of the central nervous system (CNS), and that future treatment and prevention techniques need to go beyond pressure-lowering. Strategies such as neuroprotection, neuro-

enhancement and even neuroregeneration all show promise. It is also important to better understand what happens in the brain in glaucoma since along with retinal ganglion cell (RGC) death, there is atrophy and loss of neurons in parts of the brain. "But we won't get there if research isn't done," Dr Tsai told EuroTimes in an interview. Neuroprotection aims to prevent optic nerve head damage, RGC death or both, and lowering IOP is one neuroprotective strategy that has been very helpful. But causes of RGC death include ischemia, defects in axon communication, loss of electrical activity in the RGCs and more. Each cause presents a potential target for treatment, he said.

Neuroprotection But which are the most promising areas for neuroprotection? Medication is one. Work with oral memantine, a neuroprotective agent used in Alzheimer's disease has not shown it to be helpful in glaucoma, but a recent trial suggested some neuroprotection occurred in glaucoma patients with topical brimonidine. It may do more than lower IOP. Several neurotrophic factors are being investigated in various neurodegenerative diseases and may have potential use in glaucoma, he said. Related to this, inhibitors of both Rho kinase (ROCK) and Rho GTPase enhance ocular blood flow, RGC survival, and axon

“Clinical trials in neuroprotection in glaucoma have been hit very badly and it’s something we need to embrace as a community...” Francesca Cordeiro MD, PhD

regeneration. Animal studies suggest the Rho antagonist C3-07 helps repair and promotes nerve growth. Erythropoietin (EPO), a cytokine already used to treat anaemia, has neuroprotective effects in animal models of glaucoma by inhibiting programmed cell death or apoptosis. Some labs are testing gene therapy and stem cell implantation. A recent human phase-I safety trial demonstrated the successful delivery of CNTF (ciliary neurotrophic factor) to the back of the eye. Gene therapy has shown promise in promoting RGC survival in experimental models of optic nerve injury, Dr Tsai said. Research from the University of Toronto showed that adult retinal stem cells can be programmed to produce photoreceptors.

James C Tsai – james.tsai@yale.edu M Francesca Cordeiro – m.cordeiro@ucl.ac.uk

The same researchers also developed an injectable, biodegradable cell delivery system that successfully delivered stem cells to the sub-retinal space in mice.

Nerve tissue Indeed, several approaches are being tested for the microencapsulation of compounds with the idea they would provide timed-release treatments that could protect the nerve, repair it or possibly even regenerate nerve tissue. Some work is even looking at electrical stimulation to improve the function of surviving nerve tissue. Immune system modulation may be another approach. While parts of the immune response in glaucoma can cause neural injury, there is some suggestion that other parts offer a protective role. The research in this area is fairly complex, Dr Tsai said. In addition, some researchers are investigating tumour necrosis factor (TNFa), known to play a role in apoptosis, as a possible target. Another area of interest is neuroregeneration. The myelin around central nervous system cells contains compounds which inhibit nerve growth, and various research groups are trying to modulate or block these compounds. Several methods are being developed to deliver stem cells to replace RGCs and their axons to restore vision, said Dr Tsai, but neuroprotection by any of these means is likely 10 to 20 years away. “It’s not that we don’t have promising neuroprotective agents today, it's because we haven’t proven neuroprotection unequivocally in human clinical trials,” he said.

Nano-Laser 100% Cataract Surgery. “laser assisted” cataract surgery is not enough.

EUROTIMES | Volume 18 | Issue 11

Update

GLAUCOMA

LASER VERSUS DROPS

Laser will not replace drops for glaucoma treatment but it has an important role by Pippa Wysong in Vancouver

hen it comes to laser trabeculectomy versus drops for the treatment of glaucoma, both can be effective for lowering intraocular pressure (IOP), but neither is perfect. Some of the downsides to laser include a need for retreatments over time, and possible damage to the trabecular meshwork. And while drops can have their downside, the newer ones show greater effectiveness and fewer side effects than older ones, according to Anton Hommer MD, from the Medical University of Vienna, Austria. He spoke at the 5th World Glaucoma Congress where he reviewed the evidence for both forms of treatment. In short, laser won't be replacing drops, though there is certainly an important role for it, he said. Laser trabeculectomy is attractive because it tends to lower IOP between 20 to 30 per cent from baseline. However, there is about a 10 per cent loss of efficacy over a year, meaning at least 50 per cent of patients are not well-controlled after five years, he said.

First-line option The Glaucoma Laser Trial from 1990 compared argon laser (ALT) to beta-blocker drops, and determined that laser was safe and could be considered as a first-line option. However, some evidence in the literature shows ALT (especially with repeat treatments) can destroy the trabecular meshwork, and slowly loses efficacy over the long-term, Dr Hommer said. Since then, medications have improved. There are better combinations, preservative-free versions and improved tolerability. The downside is that these too can lose efficacy over time, with only about 60 per cent of patients having continued lower IOP after two years of treatment. He noted that prostaglandins seem to fare better than other medications. As for select laser trabeculoplasty (SLT), the IOP-lowering effect is similar to that of ALT, plus, again, patients likely need to be retreated – defined as using the laser on the same area of the eye. One study investigated the longterm IOP-lowering effects of doing 360-degree SLT treatment. After the first laser treatment, after two years there EUROTIMES | Volume 18 | Issue 11

“

... laser trabeculoplasty is a good option for some patients. In my mind, there is no real superiority concerning efficacy or tolerability of SLT versus ALT and I use both.” Anton Hommer MD

was efficacy in only 36 per cent of the patients. Efficacy was less after the second treatment, and after a third treatment, the numbers of patients getting a strong IOPlowering effect gets very weak, Dr Hommer reported.

Less damage Overall, SLT is about as effective as ALT, but has the advantage of offering less damage to the trabecular meshwork. "But the retreatment is not any more effective than ALT," Dr Hommer said. There is some variation in terms of what guidelines recommend, but they lean towards using drops first. One, UK's NICE Guidelines "don’t even mention the laser treatments," for ocular hypertension or glaucoma, he noted. “Still, laser trabeculoplasty is a good option for some patients. In my mind, there is no real superiority concerning efficacy or tolerability of SLT versus ALT – and I use both. And it is a reasonable option in patients who have difficulties taking the drops. On the other side, a potential disadvantage of laser trabeculoplasty is that the patient is not reminded every day – like with the drops – that he has a disease," he said.

contact Anton Hommer – a.hommer@aon.at

Update

RETINA

EYE CHAT Exclusive interviews Up to date information Problem solving

DRUGS COMPARABLE

Clinical efficacy for the treatment of neovascular age-related macular degeneration

by Dermot McGrath in Hamburg

Goodbye Phaco, Hello Femto Dr Oliver Findl talks with Dr Burkhard Dick about how femto cataract surgery appears to offer greater accuracy and consistency, while reducing or eliminating the need for phaco.

podcast

www.eurotimes.org

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EUROTIMES | Volume 18 | Issue 11

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multicentre French study comparing bevacizumab (Avastin, Genentech) and ranibizumab (Lucentis, Genentech) found that both drugs were comparable in terms of clinical efficacy for the treatment of neovascular age-related macular degeneration (AMD). Presenting the results of the Group d’Evaluation Français Avastin versus Lucentis (GEFAL) study at the 13th EURETINA Congress, Laurent Kodjikian MD of the University Hospital of Lyon, said that the outcomes are in line with those of the Comparison of AMD Treatment Trial (CATT) published in 2012. The GEFAL study was a prospective, double-masked, randomised study to evaluate the relative safety and efficacy of bevacizumab versus ranibizumab for the treatment of neovascular AMD. The study was conducted in 38 public and privatesector French ophthalmology centres from June 2009 to November 2011. A total of 501 patients aged 50 years or older were randomised to receive either 1.25mg of intravitreal bevacizumab (n = 255) or 0.50mg of ranibizumab (n = 246). Patients were treated with a loading dose of three intravitreal injections during the first three months, followed by an as-needed regimen, with one injection in case of active disease, for the remaining nine months with monthly follow-up. In terms of the primary outcome, which was the change in best-corrected visual acuity at one year, bevacizumab was shown to be non-inferior to ranibizumab, Dr Kodjikian said. The mean visual acuity difference between the two drugs was 1.89 letters, which is clinically insignificant, nor was there any significant difference in adverse events between the groups, he concluded. Safety was a special focus of the GEFAL study, said Dr Kodjikian. Serious gastrointestinal events occurred in 1.2 per cent of bevacizumab-treated patients versus 2.1 per cent for ranibizumab. Three digestive haemorrhages occurred, all in the ranibizumab group in predisposed patients. In terms of serious infections, the overall rate was 1.6 per cent for bevacizumab versus 0.8 per cent for ranibizumab. Two cases of endophthalmitis were reported in a single patient in the ranibizumab group.

“

... the primary outcomes were evaluated on the per protocol population and this was a truly representative population treated at public and private sites. Laurent Kodjikian MD

Discussing the known weaknesses of the study, Dr Kodjikian cited the drop-out rate of around 20 per cent, which he said was anticipated in the sample size calculation. Despite this, he said that the GEFAL study had several strong points in its favour. “It was a double-masked trial, with identical masked syringes prepared by local hospital pharmacies and all ophthalmologists and patients were masked. Moreover, the primary outcomes were evaluated on the per protocol population and this was a truly representative population treated at public and private sites. Finally the study was independently funded by public grants,” he said. In terms of take-home messages, Dr Kodjikian said that bevacizumab and ranibizumab were equivalent for visual acuity at final evaluation. A mean of seven injections was necessary within the year irrespective of the drug type being used. There was a rapid and substantial decrease in thickness and fluid with both drugs. While neither drug eliminated fluid in all eyes, more retinas were completely dry with ranibizumab. Furthermore, no statistical difference between the drugs was reported in terms of dye leakage on fluorescein angiography, although slightly less leakage was observed with ranibizumab. There was a slight decrease in CNV area with both drugs. Systemic or ocular serious adverse events were similar for both drugs.

contact Laurent Kodjikian – laurent.kodjikian@chu-lyon.fr

See your success in the eyes of your patients

Defining the standard of care in wet AMD* LUCENTIS® (ranibizumab) ABBREVIATED UK PRESCRIBING INFORMATION Please refer to the SmPC before prescribing LUCENTIS 10mg/ml solution for injection. Presentation: A glass single-use vial containing 0.23ml solution containing 2.3mg of ranibizumab (10mg/ml). Indications: The treatment in adults of neovascular (wet) age-related macular degeneration (AMD), the treatment of visual impairment due to diabetic macular oedema (DMO), the treatment of visual impairment due to macular oedema secondary to retinal vein occlusion (branch RVO or central RVO), and the treatment of visual impairment due to choroidal neovascularisation (CNV) secondary to pathologic myopia (PM). Administration and Dosage: Single-use vial for intravitreal use only. LUCENTIS must be administered by a qualified ophthalmologist experienced in intravitreal injections under aseptic conditions. The recommended dose is 0.5 mg (0.05ml). For treatment of wet AMD: Treatment is given monthly and continued until maximum visual acuity is achieved i.e. The patient’s visual acuity is stable for three consecutive monthly assessments performed while on ranibizumab. Thereafter patients should be monitored monthly for visual acuity. Treatment is resumed when monitoring indicates loss of visual acuity due to wet AMD. Monthly injections should then be administered until stable visual acuity is reached again for three consecutive monthly assessments (implying a minimum of two injections). The interval between two doses should not be shorter than 1 month. For treatment of visual impairment due to either DMO or macular oedema secondary to RVO: Treatment is given monthly and continued until maximum visual acuity is achieved i.e. the patient’s visual acuity is stable for three consecutive monthly assessments performed while on ranibizumab treatment. If there is no improvement in visual acuity over the course of the first three injections, continued treatment is not recommended. Thereafter patients should be monitored monthly for visual acuity. Treatment is resumed when monitoring indicates loss of visual acuity due to DMO or to macular oedema secondary to RVO. Monthly injections should then be administered until stable visual acuity is reached again for three consecutive monthly assessments (implying a minimum of two injections). The interval between two doses should not be shorter than 1 month. LUCENTIS and laser photocoagulation in DMO and in macular oedema secondary to BRVO: When given on the same day, LUCENTIS should be administered at least 30 minutes after laser photocoagulation. LUCENTIS can be administered in patients who have received previous laser photocoagulation. For treatment of visual impairment due to CNV secondary to PM: Treatment is initiated with a single injection. If monitoring reveals signs of disease activity, e.g. reduced visual acuity and/or signs of lesion activity, further treatment is recommended. Monitoring for disease activity may include clinical examination, optical coherence tomography (OCT) or fluorescein angiography (FA). While many patients may only need one or two injections during the first year, some patients may need more frequent treatment. Therefore, monitoring is recommended monthly for the first two months and at least every three months thereafter during the first year. After the first year, the frequency of monitoring should be determined by the treating physician. The interval between two doses should not be shorter than one month. LUCENTIS and Visudyne photodynamic therapy in CNV secondary to PM: There is no experience of concomitant administration of LUCENTIS and Visudyne. Before treatment, evaluate the patient’s medical history for hypersensitivity. The patient should also be instructed to self-administer antimicrobial drops, 4 times daily for 3 days

*Neovascular (wet) age-related macular degeneration (AMD)

Lucentis Indications may vary from country to country. Physicians should refer to their National Prescribing Information. Novartis Pharma AG CH-4002 Basel, Switzerland

August 2013

LUC.146879

contacts

Update

OCULAR

TREATMENT DECISIONS

Understanding patients’ mindsets can help navigate medical grey areas by Howard Larkin

very day, physicians and patients weigh complex treatment decisions – decisions made more difficult when experts publicly disagree. For example, the use of cancer screening techniques including mammography and prostate-specific antigen tests have been hugely controversial in recent years. Government, research and medical specialty panels have recommended divergent courses based on identical evidence, generating much confusion. Closer to home, selecting among treatments for presbyopia, astigmatism and even glaucoma and wet macular degeneration, are complicated by conflicting clinical opinions and competing treatment goals. Patients are bombarded with media messages about the virtues or pitfalls of specific approaches, often from sources with vested interests, which further complicates sound medical decision-making.

Understanding the underlying “medical mindset” of your patients, yourself and experts may be the key to sorting it all out, oncologist Jerome Groopman MD and endocrinologist Pamela Hartzband MD told the American Society of Cataract and Refractive Surgery symposium. Research they conducted for their book, Your Medical Mind (The Penguin Press 2011), suggests that while specific medical decisions are highly individual, they are heavily influenced by a few identifiable factors.

Minimalist or maximalist?

Drs Groopman and Hartzband, who are at Harvard Medical School, began by asking how patients can make the best decisions in the face of controversy. “We didn’t have a ready answer so we began to search,” Dr Hartzband said. The classic model of medical decision-making, based on economic

Excellence in Education Diploma Examination 2014 EBO 2014 will take place in Le Palais des Congrès, Paris, on 9-10 May 2014 Application period is open until 31 December 2013 For all further information log on to

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“

If you told my first cousin her life is worth 0.5 on a scale of 0 to 1, she would slug you.… This entire structure of medical decisionmaking is deeply flawed. Jerome Groopman MD

theory developed by the 18th century mathematician Daniel Bernoulli, proved problematic, said Dr Groopman, a medical writer for the New Yorker magazine. It attempts to quantify choices by multiplying the probability of a given outcome by the utility it will produce for the patient. This may work in business, where the outcome and utility are both measurable in money, Dr Groopman noted. In medicine, the chance of specific outcomes, such as side effects like incontinence or impotence after prostate surgery, may also be predictable. “But how do you put a number on the second part of the equation – the utility or impact that it has on your life?” One common way is to ask healthy people how much they think a given medical condition would affect their quality of life, from 0.0 being death to 1.0 perfect health. Blindness typically ranks 0.5. This methodology is used to quantify the value of outcomes in quality-adjusted life years for purposes of assessing the cost-effectiveness of medical treatments by agencies around the world, including the UK’s National Institute of Comparative Effectiveness. Problem is, these estimates by people who have not had a particular medical condition are very different from the selfreported quality of life of people who have the condition, Dr Groopman said. He has a cousin who is blind from birth, worked as a teacher, speaks four languages, is on the board of her synagogue and volunteers teaching visually impaired people how to use Braille keyboards.

Jerome Groopman – jgroopma@bidmc.harvard.edu Pamela Hartzband – phartzband@bidmc.harvard.edu

“If you told my first cousin her life is worth 0.5 on a scale of 0 to 1, she would slug you.… This entire structure of medical decision-making is deeply flawed.” So, Dr Hartzband said, they turned to the advice of William Osler MD, a founder of modern medical practice, on making difficult diagnoses: Listen to the patient. If you know how to listen, he is telling you the answer. The two interviewed scores of patients of different ages from different backgrounds with different conditions on how they made medical decisions. Three major themes emerged, Dr Hartzband said, which are the following: – Some people are maximalists, who want "everything" done while others are minimalists who want the least treatment necessary; – Some people have a naturalism orientation, looking for natural solutions such as herbal medications and yoga while others have a technology orientation wanting the latest high-tech, cutting-edge treatment; – Finally, there are believers, who are certain that they will find a good solution for their condition, while others are doubters, who worry about side effects and poor outcomes. Regular PSA screening and aggressive surgical intervention for prostate cancer reflects a maximalist technologist believer mindset, while watchful waiting is more of a minimalist doubter approach, Dr Hartzband noted. Both approaches are supported by research, and patients following both report similar quality of life, Dr Groopman noted.

Three steps to better decisions

Matching the approach to the patient’s mindset may be the best way to begin medical decision-making, Drs Groopman and Hartzband said. Be aware that you and an expert panel may have a different orientation, and allow for that. Then look at the numbers, framing them in both a negative and positive way, and in both relative and absolute terms. For example, a one per cent to nine per cent complication rate also means a 91 per cent to 99 per cent success rate. A 30 per cent reduction in heart attack risk sounds great, but if the patient’s baseline risk is only two per cent, the absolute reduction is just 0.6 per cent. This helps cut through some of the confusion, they explained. Finally, both patients and physicians are deeply influenced by dramatic stories, what cognitive scientists call "availability". These stories may be misleading or helpful and should be balanced by the numbers, they concluded.

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EYE PHONES

Smartphones and their apps look set to open a new era in ophthalmic telemedicine

Maasai man testing vison on Peek

EUROTIMES | Volume 18 | Issue 11

of the world’s 39 million blind people live and among whom 80 per cent of blindness is avoidable, and in many cases curable. The geo-tagging ability of smartphones means that once a patient has been examined at their home using Peek, it will record and upload the patient’s data and geographic position for future reference. It could, therefore, enhance the follow-up of such patients and also enable health workers to target their efforts more efficiently, said Andrew Bastawrous MRCOphth, International Centre for Eye Health (ICEH) | London School of Hygiene & Tropical Medicine who is co-founder of Peek. “Currently eye care follows the inverse care law. That is, most human and technological resources are in the areas of least need. With Peek, patients can be examined in their homes and we can have coordinated efforts to deliver appropriate care to the point of need, or transport to the nearest facility,” he told EuroTimes in an email he sent from his mobile phone as he travelled on a bus on a poorly paved road in a remote area of Kenya. Dr Bastawrous and his associates are currently testing the Peek device in conjunction with a large cohort study involving 5,000 people in Kenya to determine its efficacy as compared with the much bulkier equipment that is generally used for eye examinations. The team of investigators are examining the patients with the usual equipment and a healthcare worker who is part of the team separately examines the same study patients with the Peek Smartphone based system – the two sets of findings will be compared. As part of the study, Dr Bastawrous and his associates are currently analysing the results of over 1,000 retinal images obtained by a healthcare worker using the Peek system against images of the same eyes obtained with a top-of-the-range desktop fundus camera. Both sets of anonymised images are being graded at the Moorfield's Reading Centre in London. Dr Bastawrous noted that the system’s lens adapter enables retinal imaging with a resolution and a field of view that is superior to that of a conventional ophthalmoscope. Moreover, the software provides greater ease-of-use and enhances image acquisition and quality.

Retinal imaging by Peek

ew smartphone tools for ophthalmologists are proving increasingly useful everywhere from the suburban office to the most remote areas of the developing world. Some of the more advanced products feature software and lens attachments that could serve as viable and very portable replacements for much more bulky and expensive equipment. For example, Peek, the Portable eye examination kit, includes a special lens attachment and a suite of diagnostic software that provides an affordable and portable means for comprehensive eye examinations anywhere. In addition to providing visual acuity testing through the screen display, the Peek system has a clip-on lens adapter that enables it to serve as an ophthalmoscope capable of taking high-resolution fundus photographs. Moreover, the Internet connectivity now common in mobile phones means that the measurements and photographs taken can be uploaded to dedicated facilities for assessment. Andrew Bastawrous, Stewart Jordan, Iain Livingstone and Mario Giardini, developers of the Peek instrumentation and software, therefore, hope that their device will help bring modern eye care to people in low-income countries, where 90 per cent

by Roibeard O’hEineachain

The study team lead by Dr Bastawrous in Nakuru

“We developed a functioning ophthalmoscope adapter for the phone but when we put it in the hands of our team in Kenya it proved to be too challenging to use without a significant amount of training. Thus, I turned to Dr Mario Giardini at University of Strathclyde who has a wealth of knowledge in optics and rapid prototyping with 3D printers. He was able to miniaturise and improve our set-up to use an adapter which modifies the phone's own optics and uses the native flash as a light source to image the retina. We are currently developing software algorithms for image stitching to further increase the field of view through our partnership with Dr Iain Livingstone at the Glasgow Centre for Ophthalmic Research,” he explained. Additional applications the Peek team are developing for the Peek system include visual field testing, for which they are assessing different approaches designed

to be more user friendly than current techniques, and a prototype slit-lamp camera for imaging the anterior segment. Dr Bastawrous noted that Peek may also find a place in general practice in highincome countries. “Although it is designed for low-resource settings, there is huge scope for this to be used in primary care by GPs, optometrists on ambulatory visits and non-ophthalmic doctors. It is much easier to use than an ophthalmoscope. Most people are able to obtain a non-mydriatic view of the optic disc with their first attempt of using it. We hope that it might increase routine retinal examination and be cost-saving within the NHS in the UK,” he said. n Further

information or requests for collaboration through the Peek website: www.peekvision.org.

News

YOUNG OPHTHALMOLOGISTS

Courtesy of Thiemo Rudolph MD, FEBO

contacts

Paul Rosen – phrosen@rocketmail.com Thiemo Rudolph – thiemo.rudolph@gmail.com Nino Hirnschall – nino.hirnschall@gmail.com Oliver Findl – oliver@findl.at Wim Weber – wim.weber@mumc.nl

Young ophthalmologists identify issues that confront residents by Leigh Spielberg in Amsterdam

he 2013 ESCRS Congress in Amsterdam saw a great deal of activity organised by the Young Ophthalmologists’ Committee. While most of the sessions were intended for early-career ophthalmologists as well as trainees, the session entitled, “Taking Training into Your Own Hands” was aimed at those delegates who have not graduated. “On average, residents comprise approximately 10-20 per cent of the total ophthalmologist workforce across Europe, although that depends on the absolute numbers of ophthalmologists in each particular country,” said Thiemo Rudolph MD, FEBO. The percentage is particularly high in the UK and The Netherlands, which have far fewer ophthalmologists per capita than the European mean of approximately 80 per million. More variation is evident in the residents’ duration of training, with countries like Spain and Greece requiring only four years and the UK and Ireland seven years. The latter countries and the Netherlands offer a great deal of surgical training during residency, whereas many European countries do not. For graduates who might be considering working in another country, Dr Rudolph also had encouraging words regarding freedom of movement within the European Union. “The most important thing to remember is that you have the law on your side,” he said. Nino Hirnschall MD, of Austria, placed the emphasis of his talk on online learning. EUROTIMES | Volume 18 | Issue 11

He provided delegates with an overview of the ophthalmology training resources available online, with their relative strengths, weaknesses and unique characteristics. Dr Hirnschall evaluated 13 different online resources and divided them into three categories based on content, quality and ease of use. “After spending a lot of time looking at these sites, I’d like to share my opinions on these sites, whether ‘Excellent,’ ‘Useful’ or ‘Not Useful’ in my hands,” he said. Evaluated as “Excellent” were the ESCRS iLearn; the Atlas of Ophthalmology; the Atlas of Gonioscopy; Ophthalmology UNIMAS; and the American Academy of Ophthalmology’s (AAO) Resident Hub. Paul Rosen MD, MBA, of the UK also discussed preparation, but his presentation concerned the development of surgical skills, in which the preoperative planning plays a major role. “Plan every procedure as if it were your first,” suggested Dr Rosen. “It doesn’t matter whether it’s your thousandth case. You have to be prepared for what can go wrong.” This includes review of all patients prior to surgery, to be able to predict possible complications and to plan alternative routes to successfully complete the procedure. “Plan your escape route.” Besides planning, there are many things that can be done to develop surgical skills. “Reading about cataract operations and observing surgery, either live or on video, is very useful for the developing surgeon,” said Dr Rosen, “as are face-to-face discussions

to a conference in which the applicant will present research. On how to fund research, Dr Findl said, “Generally speaking, there are two types of research grants: Unrestricted grants, which offer less money but in which the data belong to the investigator; and sponsored trials, which are better paid but often less exciting.” Once funding has been obtained, research can commence. Wim Weber MD, PhD, the European editor of the British Medical Journal, spoke about how to take an idea from conception to publication. “Make sure your research plan matches the question you want answered,” he said. “You cannot use a case report to prove the validity of an intervention. “A great deal of the work involved in research is very lowly, but as soon as you get to the end of the process, you will make many friends who will want to share the glory,” said Dr Weber. “So make sure you agree authorship before starting the study.” He referred delegates to the International Committee of Medical Journal Editors (ICMJE) authorship guidelines.

Courtesy of Nino Hirnschall MD

training days

with colleagues and postoperative case reviews with your mentors.” Dr Rosen advised the delegates, “Don’t be too ambitious, but definitely push the boundaries while maintaining a perfectionist mindset. Take the opportunity to learn in a protected training environment and don’t be afraid to seek advice.” The question of financial assistance is a frequent concern for residents. “I’ll focus on sources of financial support that are available outside the confines of standard ophthalmology training,” said Oliver Findl MD, MBA, of Austria, and the current chairman of the ESCRS Young Ophthalmologists’ Committee. Dr Findl discussed three categories of funding: observerships, travel grants for congresses and research grants for scientific work. “Observerships, which are usually for a period of one to four weeks, are offered by the various organisations across Europe, and mostly offer €1000 each to around 50 residents per organisation per year,” he said. Dr Findl also discussed travel grants, which are widely available to help fund travel

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Review

JCRS Highlights

Journal of Cataract and Refractive Surgery

Femto cataract safety Cataract surgery outcomes have improved over the years with the ongoing technical developments. However, manual capsulorhexis continues to be the most difficult part of the procedure, and is highly dependent on the surgeon’s skill. Proponents of femtocataract surgery believe this new approach may reduce complications and improve outcomes. Investigators at MaxiVision Eye Hospital, Begumpet, Hyderabad, India, conducted a randomised controlled open-label multisurgeon prospective trial comparing cataract surgery using femtosecond laser–assisted lens fragmentation and anterior capsulotomy versus manual cataract surgery. 56 eyes underwent the femtosecond laser procedure, and 63 had manual cataract surgery. The mean effective phacoemulsification time was significantly lower in the laser group than in the manual group. There was also a significant difference in the mean phaco energy between the two groups. Laser-assisted capsulotomies were significantly more accurate and precise in terms of intended diameter, circularity, centration. The safety profiles of the procedures were equivalent, with no adverse events at the one-day follow-up. n KP

Reddy et al., JCRS, “Effectiveness and safety of femtosecond laser fragmentation and anterior capsulotomy versus the manual technique in cataract surgery”, Volume 39, Issue 9 Pages 1297-1306.

Femto cataract surgery and small pupils Femtosecond laser–assisted cataract surgery requires adequate dilation for imaging and treatment. Germany researchers report strategies for treating eyes with small pupils. 40 eyes with an intraoperative pupil size smaller than 5.5mm received sequential treatments to achieve a pupil larger than 5.5mm in three steps: (1) intracameral administration of epinephrine solution, (2) additional viscomydriasis, and (3) implantation of a Malyugin ring pupil expander. When a step enlarged the pupil to at least 5.5mm, femtosecond laser–assisted cataract surgery with an anterior capsulotomy diameter of at least 4.5mm and 350 μm nuclear fragmentation grids, ultrasound phacoemulsification and intraocular lens implantation were performed. Seven per cent of eyes required only epinephrine to achieve a pupil larger than 5.5mm. Additional viscomydriasis was necessary in 25 per cent, and the pupil expander was implanted in 68 per cent. The most frequent comorbidities were EUROTIMES | Volume 18 | Issue 11

pseudoexfoliation of the lens capsule (30.0 per cent) and intraoperative floppy-iris syndrome (12.5 per cent). Tongue-like lesions of the capsulotomies were detected in five eyes. The researchers report that this approach allowed the surgeon to increase the efficiency and safety of femtosecondassisted cataract surgery in eyes with a small preoperative pupil, providing good safety margins at the pupil boundary for the capsulotomy and the softened nuclear volume.

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Femto laser thin flap LASIK Greek researchers evaluated the predictability of LASIK flap creation using an updated femtosecond-laser platform FS200 femtosecond-laser platform (Wavelight GmbH) that provides an increase in pulse frequency. 50 eyes of 25 patients underwent the procedure, of which 42 eyes were available for six month's follow-up. No eye lost lines of corrected distance visual acuity (CDVA), 29 per cent gained one line, and seven per cent gained two lines. The mean spherical equivalent was −0.03 ± 0.42 D (range −0.88 to +0.88 D); 86 per cent had an uncorrected distance visual acuity of 20/20 or better. The mean central flap thickness at one month was 102.98 ± 6.33 μm (range 91 to 114 μm). There were no intraoperative or postoperative complications.

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Review

Book REVIEW

Endophthalmitis guidelines Endophthalmitis is an uncommon but serious complication of cataract surgery that often carries a poor prognosis. It has thus garnered a great deal of attention in terms of how to avoid this devastating condition. However, due to the low incidence, high-quality studies of postoperative endophthalmitis are difficult to perform. In order to help bring the current knowledge into focus, the ESCRS recently published the new 2013 “Guidelines for Prevention and Treatment of Endophthalmitis Following Cataract Surgery: Data, Dilemmas and Conclusions.” The authors acknowledging that “although cataract surgery ranks among the most frequently performed surgical procedures worldwide, data to define the most effective prophylactic measures have been nearly impossible to generate, given the large patient numbers needed to conduct clinical trials”. Nevertheless, the 39-page document comprises an extensive summary and attempts to develop a consensus regarding postoperative endophthalmitis. Central to the recommendations contained in the Guidelines are the results of the ESCRS Endophthalmitis Study1, which investigated the effects of perioperative antibiotic prophylaxis. Published in 2007, it evaluated effects of an intracameral injection of cefuroxime 1mg at the close of surgery, and compared postoperative endophthalmitis rates with other study groups that included perioperative antibiotic drops and controls. The study was conducted in 24 medical centres in nine European countries and included over 16,000 patients. The endpoint of the study was infective endophthalmitis, whether proven or presumed.

Among the four study groups, the lowest incidence rate was observed in Group D, where both intracameral cefuroxime and perioperative topical levofloxacin were used, with a rate of 0.049 per cent for presumed endophthalmitis and 0.025 per cent for proven endophthalmitis. Five cases of endophthalmitis did occur in cefuroximetreated groups in the ESCRS study. In the unfortunate situation of postoperative endophthalmitis, the management is largely dictated by the results of the Endophthalmitis Vitrectomy Study2, which concluded that patients who presented with hand motion or better vision may be treated with tap or biopsy; patients presenting with light perception only vision should be considered for immediate vitrectomy; and that intravenous antibiotics were of no proven benefit.

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1. Endophthalmitis Study Group, European Society of Cataract & Refractive Surgeons. Prophylaxis of postoperative endophthalmitis following cataract surgery: results of the ESCRS multicentre study and identification of risk factors. J Cataract Refract Surg 2007; 33: 978-88. 2. Endophthalmitis Vitrectomy Study Group. Results of the Endophthalmitis Vitrectomy Study. A randomized trial of immediate vitrectomy and of intravenous antibiotics for the treatment of postoperative bacterial endophthalmitis. Arch Ophthalmol 1995; 113: 1479-1496

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Postoperative endophthalmitis

All four study groups received standard preoperative povidone-iodine as well as topical levofloxacin drops four times daily postoperatively for six days, and were randomised then into four groups in a 2x2 factorial design: Group A: Placebo perioperative drops and no intracameral cefuroxime injection; Group B: Placebo perioperative drops and an intracameral cefuroxime injection; Group C: Topical perioperative levofloxacin but no intracameral cefuroxime injection; Group D: Topical perioperative levofloxacin and an intracameral cefuroxime injection. The ESCRS study found that the risk of contracting postoperative endophthalmitis was significantly reduced, approximately five-fold, by an intracameral injection of 1mg cefuroxime at the close of surgery. EUROTIMES | Volume 18 | Issue 11

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Recent developments in the vision care industry

Retinal disease diagnosis

New multifocal IOLs Abbott has announced the European launch of two new measurements (optical add powers) for the TECNIS® Multifocal intraocular lens (IOL), which the company says will provide more customised treatment options for cataract patients. “With the addition of these TECNIS Multifocal IOLs, Abbott is able to provide physicians the ability to offer a more precise lens option for their patients, allowing them to maintain quality vision at near, intermediate and far distances,” said a company spokesman. “The TECNIS Multifocal +2.75 add power IOL is suited for patients who prefer intermediate vision activities, such as seeing an automobile dashboard. The TECNIS Multifocal +3.25 add power IOL is suited for patients favouring activities at longer reading distances such as working at a computer, while still providing a full range of vision,” he said. n www.abbott.com

New Staining Solution Geuder has introduced a new tissue dye for cataract surgeries. “Vioron consists of trypan blue and ensures an effective staining and thus brilliant visualisation of the anterior lens capsule,” said a company spokeswoman. “The new staining solution enables the excellent distinction of the capsulorhexis margin, is quick and easy to apply and applicable to a variety of further indications, eg, congenital cataract surgery. Vioron is available as vial and syringe,” she said. n www.geuder.com/viorondye

Canon Europe has announced the launch of new software for the Canon OCT-HS100 spectral domain optical coherence tomography (OCT) device and retinal cameras. “The combination of the Canon OCT-HS100, the industry’s first fully automated spectral domain OCT device, and the new Canon software will deliver improved usability and an extensive normative database to enable even more reliable and earlier diagnosis of retinal diseases. The software’s new features also include increased retinal image scan width from 10mm to an extremely wide 13mm and an extensive radial scan mode,” said a company spokesman. Canon also launched an updated version of its retinal imaging control software for Canon retinal cameras, RICS 4.2, which includes an optional mosaic function that enables multiple retinal images to be combined into a single mosaic image for extremely wide views into the periphery of the retina. n http://www.canon-europe.com/

Preloaded IOL product

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Rayner Intraocular Lens launched the company’s first preloaded IOL product – C-flex® Advance Aspheric – at the XXXI ESCRS Meeting, in Amsterdam, The Netherlands. “The C-flex Advance Aspheric combines all the clinically proven benefits of the aberrationneutral C-flex Aspheric IOL, with a mini incision and a preloaded IOL delivery system that eliminates handling of the acrylic lens in theatre. It also helps reduce the chances of IOL damage or contamination and allows for an SIA neutral implantation through an incision size of 2.2mm or 2.4mm into the bag. C-flex Advance Aspheric is available in power range +8.0 D to +34.0 D in 0.5 D increments,” said a company spokesman n www.rayner.com

Katena has announced the launch of the Donnenfeld Micro IOL soft cutter designed to perform IOL explantation through a 1.5mm incision. “This new scissors features a lightweight titanium handle and 4mm-long stainless steel blades to cut foldable silicone or acrylic lenses,” said a company spokeswoman. “ The blades have multiple notches on the surface to securely grasp the IOL and prevent slippage during cutting. Additionally, three circular openings along the 18-gauge straight shaft allow for more thorough and efficient cleaning,” she said. n www.katena.com

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Feature

EYE ON TRAVEL

SIX THINGS TO DO IN LJUBLJANA

Some suggestions for delegates attending the 18th ESCRS Winter Meeting by Maryalicia Post

Winter fishing on the Ljubljanica river

Scout for souvenirs On Sunday morning check out the flea market along the river where you are sure to find if not a treasure, then something that will be a great souvenir. Browse medals and memorabilia, antiques and art, jewellery and junk. When I was there in February, stalls ran for a block or two beginning at St Jacob's Bridge. Market is open from 8am until 2pm.

who defended it against demolition and successfully developed it into a conglomerate of galleries and clubs. The graffiti alone is worth a detour. A former military prison on the site, decommissioned when Slovenia gained its independence, was turned into the bright and colourful Hostel Celicia . (For an overview of 'what's on' in Metelkova's clubs and galleries, www.metelkovamesto.org)

Catch up on history The National Museum of Contemporary History, housed in the baroque Cekin Mansion in Tivoli Park, tells the story of the most turbulent period in Slovenian history: personal experiences of WW2, post-war turmoil, socialism and the industrialisation of the former Yugoslavia. The museum is open Tuesday to Sunday 10-18. http://www.muzej-nz.si Check out the exhibition ‘5,200 years of the wheel’ in the City Museum of Ljubljana (until 20 April 2014). The oldest set of wheels and axle in existence, now the museum’s prize artefact, was discovered in the marshes south of Ljubljana in 2002. The museum is housed in a Renaissance Palace and is open Tuesday-Sunday, 10-18. Thursday until 21:00. www.mgml.si. About 2,000 years ago, a Roman city called Emona existed where Ljubljana is now. A film at the City Museum illustrates the evolution of the city over the centuries. An open display on the ground floor reveals the archaeological artefacts found right under the museum building.

Take a boat ride Enjoy an eye-level view of the refurbishment of the city’s river banks. From the 1930s, Ljubljana’s celebrated architect, Joze Plecnik, marked the river’s course with buildings, squares, canals, embankments and riverside parks. He always saw the development of the riverbanks as integral to the design of the city but war and politics ended his interventions. Recently, several bridges, parks, a pavilion, a floating pier and other improvements on the river banks were part of a project that embraced Plecnik’s dream. Carried out by coordinated teams of local professionals the project was joint winner of the European Urban Planing Prize 2012. Boat tours on the Ljubljanica river last about an hour. From January to April, tours are scheduled twice a day: 13:00 and 15:00. Tickets from the tourist board office at the Triple Bridge.

Explore Metelkova It's not a long walk from the old town to this newly regenerated outskirt. The extraordinary Metelkova city was destined for destruction not long ago; the area was 'occupied' by artists and others EUROTIMES | Volume 18 | Issue 11

Do some wine tasting Movia, which the New York Times called ‘the superstar producer of the Brda region’ has its own wine bar right next to the Ljubljana town hall. No better place to familiarise yourself with Slovenian wine.The Movia estate dates from 1700; its vineyards straddle the border with Italy. Vintages include the so-called orange wine, ribolla gialla which must stand upright for an extended period – a week is suggested

Graffiti as an art form in Metelkova

– before being carefully decanted. The 2008 vintage was described by the New York Times critic as ‘complex and fruity with just a hint of funk”. Also recommended, the 2007 Veliko, a blend of ribolla gialla, sauvignon blanc and pinot grigio. http://www.movia.si

Fashion foray Gallerija Emporium is an elegant Art Deco building off Preseren Square. Stocked with international designer fashions for men and women, its services include personal shoppers and made-tomeasure options. Open 10:00 -21:00, Monday through Friday, 10:00-20:00 on Saturday and 11:00 -17:00 on Sunday. www.galerijaemporium.si Ljubljana designer Jelena Leskovar showcases an integrated wardrobe of simple, stylish dresses, coats and separates at Cliche at Novi Trg 6. A carefully curated selection of accessories from European, US and Japanese designers compliments them. The shop is open Monday to Friday 12:00-20:00, Saturdays and Sundays 10:00-14:00. Almira Sadar, an architect, is also a professor of fashion design at the Faculty of

Sunday flea market stalls

Textiles, Ljubljana. She established her own fashion studio in 1997. View her innovative collection online at: www.almiradadar.com and at her shop at Beethovnova 12. Open 11:00-18:00, Sat 11:00-14:00. Closed Sun.

Congress delegates may not be aware that over their heads on one of Cankarjev dom’s rooftop terraces three families of honeybees make their home. The hives each house 40,000 Carniolan bees, the gentle, non-aggressive subspecies of the Western Honeybee that has adapted to life in Slovenia. Honey and products made with honey are the perfect souvenir of Ljubljana and so are the primitively painted boards that were used for doors in the hive. From the 18th to the 20th centuries, these folk art paintings, usually commissioned from itinerant artists, were believed to help the bees find their homes. Look for reproductions on sale in souvenir shops in sizes ranging from the original boards (about 30 cm x 12) to fridge magnets.

Physicians Program (subject to change)

Faculty Brock K. Bakewell, MD John D. Banja, PhD Robert J. Cionni, MD Terry Kim, MD Nick Mamalis, MD Nancey McCann E. Ann Rose, MD Thomas W. Samuelson, MD Steven R. Sarkisian Jr, MD R. Doyle Stulting Jr, MD, PhD …more to come

Program Topics

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• Cataract: Challenging Cases & Complications Management • Ethics Interactive • Glaucoma • Interactive Cornea • Legislative Update • Medicare Update • Rapid F-Eye-R: You Make the Call • Refractive Surgery • Top Pearls • Video Presentations Highlight • What’s New in Technology

Program Chairs Edward J. Holland, MD Stephen S. Lane, MD Roger F. Steinert, MD

Program Planning Committee David F. Chang, MD Eric D. Donnenfeld, MD Richard A. Lewis, MD Keith A. Warren, MD

Review

OPHTHALMOLOgica w

Enzymatic vitreolysis likely to play an increasing role in treatment of retinal disease Ocriplasmin has risen to the fore as an effective pharmacological agent in relieving vitreomacular traction in eyes with macular holes and its use may in the future extend to other indications inducing neovascular AMD, according to the authors of an article in this month's issue. Phase III trials have shown that among a total of 464 eyes with macular holes administered with the agent, vitreomacular adhesion resolved completely in 26.5 per cent and non surgical resolution of macular holes was achieved in 40.6 per cent. By comparison, resolution of vitreomacular traction and non surgical resolution of macular holes occurred in only 10.1 per cent and 10.7 per cent, respectively, of 188 eyes receiving placebo injections. n F.

Bandello et al, Ophthalmologica “Review and Perspectives on Pharmacological Vitreolysis” 2013 DOI:10.1159/000354547.

Subclinical diabetic macular oedema raises risk for progression Eyes with subclinical diabetic macular oedema had a greater than three-fold higher risk of developing clinically significant diabetic macular oedema in a prospective observational study. In the single-centre study, which involved 348 Type 2 diabetes patients, six of 32 eyes (18.7 per cent) with signs of subclinical diabetic retinopathy – as determined by fundus photography and stratus OCT – went on to develop clinically significant diabetic retinopathy within a follow-up period of two years. That compared to only 20 of 316 eyes (6.3 per cent) that had no signs of subclinical diabetic retinopathy

with few intraoperative or postoperative complications. The patients in the study underwent a total of 179 20-gauge transconjunctival vitrectomies, 93 per cent of which were completed without the use of sutures. The indications for the surgery included idiopathic epiretinal membranes, macular holes and retinal detachments. Intraoperative complications included premature dislodging of the cannulas in two sclerotomies and an iatrogenic horseshoe tear at one sclerotomy site. Postoperative complications included transient hypotony in 14 cases, subconjunctival gas in two cases and choroidal effusion in one case. There were no cases of endophthalmitis. n Papaefthymiou

et al, Ophthalmologica “Safety of 20-Gauge Transconjunctival Sutureless Vitrectomy”, 2013; DOI:10.1159/000346393.

Genetic factors influence response to anti-VEGF treatment A study involving 168 neovascular AMD patients who underwent treatment with intravitreal ranibizumab showed that patients with different variants in the rs11200638 portion of the HTRA1gene had significant differences in the amount of letters they gained during six months of treatment. That is, those with the AA variant gained a mean of 3.5 letters, those with the AG variant gained a mean of 9.4 letters and those with the GG variant gained a mean of 10.6 letters. In contrast, there was no significant difference between variants of the genes for CFH and VEGF rs1413711 in terms of visual acuity. n Yuan

D. Ophthalmologica “Genetic Association with Response to Intravitreal Ranibizumab for Neovascular Age-Related Macular Degeneration in the Han Chinese Population” 2013; DOI:10.1159/000355068.

Ophthalmologica, “Subclinical Macular Edema as a Predictor of Progression to Clinically Significant Macular Edema in Type 2 Diabetes”2013; DOI:10.1159/000354550.

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Micro-incision sutureless vitrectomy a safe procedure

EUROTIMES | Volume 18 | Issue 11

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n Pires,

The findings of a retrospective study indicate that 20-gauge transconjunctival sutureless vitrectomy is a safe procedure

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.org s r c s

www.linkedin.com/company/eurotimes www.linkedin.com/company/escrs José Cunha-Vaz EDITOR OF OPHTHALMOLOGICA, The peer-reviewed journal of EURETINA

Reference

CALENdAR OF EVENTS

Dates for your Diary

2013

2014

NOVEMBER

Queen Victoria Hospital NHS Foundation Trust - Corneoplastic Professional Education Meeting 1 November Lingfield, UK www.qvh.nhs.uk

Practice Management Weekend 1-3 November Frankfurt, Germany http://pmfrankfurt.escrs.org/

AAO Annual Meeting 16-19 November New Orleans, USA www.aao.org

93rd SOI National Congress 27-30 November Rome, Italy www.congressisoi.com

The MCLOSA 20th Annual Scientific Meeting 29 November London, UK www.mclosa.org.uk

JANUARY

5th International Course on Ophthalmic and Oculoplastic Reconstruction and Trauma Surgery 8-10 January Vienna, Austria www.ophthalmictrainings.com

4th EURETINA Winter Meeting 25 January Rome, Italy www.euretina.org

MARCH

18th ESCRS Winter Meeting 14-16 February Ljubljana, Slovenia www.escrs.org

AUGUST

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

20-23 August Stockholm, Sweden http://www.nok2014.se/Default.aspx

20-23 March Lisbon, Portugal http://www.comtecmed.com/cophy

APRIL NEW ENTRY World Ophthalmology Congress 2-6 April Tokyo, Japan www.woc2014.org

NEW ENTRY 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/

12th International Ocular Inflammation Society Congress 27 February – 1 March Valencia, Spain http://ioisvalencia.org/

Nordic Congress of Ophthalmology (NOK 2014)

The 5th World Congress on Controversies in Ophthalmology (COPHy)

FEBRUARY

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

ESCRS Glaucoma Day 12 September London, UK www.escrs.org

WSPOS Paediatric Sub Speciality Day

ASCRS•ASOA Symposium and Congress 25-29 April Boston, USA www.ascrs.org

12 September London, UK www.wspos.org

5th EuCornea Congress 12-13 September London, UK www.eucornea.org

JUNE NEW ENTRY 11th EGS Congress

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

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

Advertising Directory: Abbott Medical Optics: Page: OBC; Allergan: Page: IBC; Alsanza Medizintechnik und Pharma GmbH: Page: 35; A.R.C. Laser Ag: Pages: 26, 39; ASCRS/Eyeworld: Pages: 36, 40, 42; Benz Research & Development: Page: 11; Croma-Pharma GmbH: Page: 37; D.O.R.C. International BV: Page: 14; Haag Streit Ag: Page: 23; Nidek: Page: 27; Novartis: Pages: 3, 29; Oculus Optikgerate GmbH: Page: 9; Oertli Instruments AG: Page: IFC; Rayner Intraocular Lenses Ltd: Page: 12; Schwind Eye-Tech-Solutions: Page: 7; VSY Biotechnology: Page: 19; Ziemer Ophthalmic Systems: Page: 13

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

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