EuroTimes Vol. 20 - Issue 12 - Vol21 - Issue 1

SPECIAL FOCUS RETINA GLAUCOMA

ONGOING ADVANCES IN DELIVERY METHODS AND MEDICATIONS Dec 2015 | Vol 20 Issue 12 Jan 2016 | Vol 21 Issue 1

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Publisher Carol Fitzpatrick Executive Editor Colin Kerr Editors Sean Henahan Paul McGinn Managing Editor Caroline Brick Production Editor Conor Ward Senior Designer Janice Robb Designer Lara Fitzgibbon Circulation Manager Angela Morrissey Contributing Editors Howard Larkin Dermot McGrath Roibeard Ó hÉineacháin Contributors Maryalicia Post Leigh Spielberg Pippa Wysong Gearóid Tuohy Priscilla Lynch Soosan Jacob Colour and Print W&G Baird Printers Advertising Sales Amy Bartlett ESCRS Tel: 353 1 209 1100 email: amy.bartlett@escrs.org Published by the European Society of Cataract and Refractive Surgeons, Temple House, Temple Road, Blackrock, Co Dublin, Ireland.

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CONTENTS

A EUROPEAN OUTLOOK ON THE WORLD OF OPHTHALMOLOGY

SPECIAL FOCUS

FEATURES

RETINA 4 Cover Story:

CATARACT & REFRACTIVE 17 Eyes with weak zonules

8 ‘Anti-VEGF agents

18 The ESCRS

9 Brolucizumab:

19 Accommodative

A diagnostic and therapeutic revolution for DME

have a key role in treatment of retinal vein occlusion’ its potential to improve visual outcomes

12 New drug type

showing promise in neovascular AMD

13 Intravitreal steroid implants – major improvements in patients with DME

14 New imaging device

aims to reinvent the way eye examinations are performed

need additional capsular support during cataract surgery Endophthalmitis Study – its effect on current practice

P.40

IOL mimics natural process

30 Ongoing advances in

20 Cataract surgery

delivery methods and medications improving standards of care

post-LASIK – contrast sensitivity can be reduced

21 Obituary: Prof Jan Worst,

OCULAR

a giant of the profession

35 New strategies in

CORNEA

the war against antibiotic resistance

25 Corneal transplantation – selective lamellar keratoplasty is taking hold

REGULARS 37 Outlook on Industry 40 Eye on History 41 Ophthalmologica Update 43 ESASO Update 44 JCRS Highlights 45 Industry News 46 Eye on Technology 48 Calendar

26 ‘Herpetic keratitis has lost much of its horror today’

GLAUCOMA

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29 Modern imaging technologies complementing clinical expertise

Included with this issue...

Abbott Medical Optics and Oraya Therapeutics, Inc. supplements

EUROTIMES | DECEMBER 2015/JANUARY 2016

2

EDITORIAL A WORD FROM LEIGH SPIELBERG MD

RETINAL CHALLENGE

Healthcare systems across the world have taken notice of the benefits of aggressive treatment of retinal disease

O

phthalmologists treating retinal disease today have we are not easily satisfied. Neither are our patients, who are now more resources at their disposal than ever before. less likely to accept the termination of treatment. They are often Imaging techniques have become fast, patient-friendly very well-informed and would like to remain highly active into and refined, as ever more detailed information can be old age, despite suffering from retinal disease that until 10 years gleaned within the blink of an eye. High-budget research ago was incapacitating. And because high-definition imaging has led to the development of several highly effective makes it impossible to ignore even the tiniest abnormalities, we new drugs, as well as lasers that are subtler and less destructive. strive for perfection.

Angio-optical coherence tomography (angio-OCT) is Significant challenges remain. Visual recovery rates after successful generating the same type of interest and enthusiasm that greeted reattachment of macula-involving retinal detachments have barely the introduction of fluorescein angiography and OCT. improved in the past century. LongNext-generation anti-VEGF molecules promise to either standing macular oedema is still often a For the retinal surgeon, extend the time between serial intravitreal injections, death sentence for central visual acuity. advances beyond thinneror at least supplement our arsenal in refractory cases.

There is still no effective prophylaxis Sustained-release intravitreal steroid depots allow us for proliferative vitreoretinopathy, gauge instrumentation to tackle stubborn macular oedema due to a range of nor is its treatment atraumatic for have expanded the different etiologies. the retina. Retinal ischaemia remains indications for surgery For the retinal surgeon, advances beyond thinner-gauge a serious challenge, and macular instrumentation have expanded the indications for surgery atrophy still threatens the success and have improved both and have improved both recovery times and final results. of well-controlled neovascular agerecovery times and LED light sources provide bright endo-illumination for related macular degeneration (AMD). final results more complete vitreous removal. Powerful dyes allow As for retinal vascular occlusions, more accurate epiretinal membrane peeling. And ultrathey can leave both doctor and patient high vitretomy cut rates reduce intraoperative vitreoretinal traction searching hopelessly for solutions. to nearly negligible levels, streamlining surgery.

What is most encouraging is that every new development, Healthcare systems across the world have taken notice of the whether diagnostic or therapeutic, is being studied in order to benefits of aggressive treatment of retinal disease. Sums that were determine not only the modalities’ value, but also the optimal use. previously reserved for life-threatening diseases are now being Which anti-VEGF should we use? And when? And how often? And spent on keeping foveas fluid-free. Many insurers are willing to based on which criteria? The results of large, well-organised trials spend thousands of euros to make sure that patients maintain seem to emerge in highly-regarded, peer-reviewed journals on a their sight. This is due, in part, to the realisation that visually monthly basis. When should we add laser to the treatment regimen? independent people are less likely to suffer other, potentially more How about steroids? And is angio-OCT worth all the hype? expensive ailments.

Rest assured, the best minds in our midst are tackling these questions with enthusiasm.

INTERNATIONAL CAMPAIGN

But it is also the result of an effective international campaign, advanced by leaders of both research and industry, to keep policymakers focussed on the importance of sight. On the other hand, our work has not necessarily gotten easier.

We are perpetually aware of the potential benefits of treatment given the right combination of the modalities at our disposal, so

Leigh Spielberg is Vitreoretinal Surgery Fellow, Rotterdam Eye Hospital, The Netherlands

MEDICAL EDITORS

Emanuel Rosen Chief Medical Editor

José Güell

Ioannis Pallikaris

Clive Peckar

Paul Rosen

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

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COVER STORY: RETINA

DME A NEW ERA IN TREATMENT OF DME The past decade has seen a diagnostic and therapeutic revolution. Leigh Spielberg MD reports

R

ecent advances in diagnostic imaging and various therapeutic modalities herald a new era in the management of diabetic macular oedema (DME). Progress is being made on several fronts: angio-optical coherence tomography (angio-OCT), EUROTIMES | DECEMBER 2015/JANUARY 2016

sub-threshold lasers, new anti-VEGF molecules and sustained-release corticosteroid implants are entering the clinic.

New insights into pathogenetic mechanisms and interindividual differences will lead to individualised treatments, and patients will benefit from these new insights and possibilities. “We have recently experienced a major revolution in the management of

DME. In fact, this is the second DME revolution. The first one took place in the 1970s, with the introduction of fluorescein angiography (FA) and macular laser treatment. The past decade has seen a similar diagnostic and therapeutic revolution, with the introduction of the OCT and anti-VEGF treatment. These are very fortunate times,� said Francesco Bandello MD, FEBO, Vita-Salute University, Milan, Italy.

COVER STORY: RETINA

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Courtesy of Niels Hoevenaars MD

WILL ANGIO-OCT REPLACE FA AND OCT? This revolution is ongoing. Angio-OCT is a non-invasive and dyeless technique that uses the movement of red blood cells in retinal vessels instead of dye to record the vascular network. Unlike other imaging methods that utilise contrast agents, angioOCT allows visualisation without the blurring or obscuring effects of leakage, staining or pooling. This allows the clinician to see the individual capillaries much more clearly than with FA, identifying abnormalities with more precision than might be possible with classical FA. Small capillary dropout is visible on angio-OCT very early in the disease process, when it might be missed on FA. Ursula Schmidt-Erfurth MD, Professor of the Department of Ophthalmology, Medical University of Vienna, Austria, and head of the Vienna Reading Center (VRC), a digital image analyses platform, foresees the eventual elimination of FA in the management of DME. “The strength of angio-OCT is in the early detection of macular vascular changes that are not visible in FA. I predict a switch from dye-based angiography to multimodal OCT, which will lead to a progressive replacement of FA in favour of angio-OCT,” she said.

She stressed the need for new pathogenic and clinical classifications of DME based on its appearance on angioOCT. In age-related macular degeneration (AMD), advantages of angio-OCT are already obvious regarding visualising neovascular recurrences.

Angio-OCT is poised to change the way we look at neovascularisation and vessel loss, according to Marc de Smet MD, PhD, Microinvasive Ocular Surgery Clinic, Lausanne, Switzerland.

“Because it can differentiate between the superficial capillary plexus and the deep plexus, it will allow us to determine the level at which ischaemia is present within the retinal tissue in DME. Current understanding suggests that the deep plexus probably plays a more important role than previously appreciated, because we could not see it with FA. At this level, Muller cells redirect retinal water to blood vessels by way of aquaporins (water) and potassium channels. Thus, ischaemic dysfunction in this deep layer contributes to the oedema we see clinically,” he said.

Besides several advantages in terms of imaging, clinicians can also expect economy in safety, insurance, time and various other costs associated with classical FA.

Anti-VEGF injections are a mainstay in the treatment of diabetic macular oedema

CURRENT STANDARD OF CARE According to a survey conducted by the American Society of Retina Specialists in 2013, 90 per cent of retinal specialists in the USA use anti-VEGF therapy for initial management of vision loss from DME involving the macular centre. But many experts have more nuanced ideas.

“We haven’t yet done enough to determine the various pathogenic mechanisms of DME. We tend to lump all patients together into one group, treat them with the same modality and then discover that a significant percentage of them do not respond,” said Dr Bandello.

“After all, approximately 30-40 per cent of patients insufficiently respond to anti-VEGF treatment. This suggests that other modalities will continue to play a significant role. I think the future of DME management lies in the subclassification of

The strength of angio-OCT is in the early detection of macular vascular changes that are not visible in FA Ursula Schmidt-Erfurth MD

DME phenotypes, so that patients can be treated as individuals,” he notes.

INDIVIDUALISED TREATMENT All of the experts interviewed for this article agree that DME is the result of a multifactorial pathogenesis. Acute and chronic inflammatory changes occur, both of which might contribute to the pathogenesis of DME. And while the current pharmacotherapeutic approach is mainly based on the administration of VEGF inhibitors, corticosteroids have again been gaining attention as an alternative, particularly with the introduction of sustained-release intravitreal implants.

Dr de Smet agrees that there is a role for each of the therapeutic modalities, each with distinct advantages and disadvantages.

“Targeting anti-VEGF is certainly effective, but it requires multiple injections. However, since DME is more than just VEGF-induced leakage, other approaches, including steroids, are certainly viable options. Indeed, sustained release steroid preparations have an important role to play in the long-term care of patients otherwise burdened by multiple doctor visits and juggling to EUROTIMES | DECEMBER 2015/JANUARY 2016

6

COVER STORY: RETINA maintain an active career. The problem with steroids is their side-effect profile.

All of them cause cataracts and a rise in intraocular pressure (IOP), though the latter does not necessarily lead to glaucoma and glaucoma surgery,” he told EuroTimes.

The FDA approval of two sustainedrelease intravitreal corticosteroid implants, Ozurdex® (dexamethasone) and Illuvien® (fluocinolone acetonide), has opened new doors. Besides the potential pharmacologic advantages, this type of long-acting drug may address the issue of compliance that is often a barrier to effective therapy in this subgroup of patients.

“I also still see an important role for laser. Not necessarily the laser in its current form, but maybe sub-threshold laser.

Articles published during the past 20 years suggest that this approach is less damaging while contributing to long-term control, and I think further studies will confirm this. As we gain a better understanding of the underlying mechanisms of Muller cell and retinal pigment epithelium (RPE) cell dysfunction in diabetes, we will begin to appreciate the role of non-destructive laser treatment,” predicted Dr de Smet.

Dr Schmidt-Erfurth is less optimistic regarding the future of laser treatment in DME. “We are in the midst of a paradigm shift. Laser will become a palliative and destructive modality of the past, and will in time be completely replaced by anti-VEGF injections,” she said.

Although this shift will take time to occur completely in clinical practice, she is confident that it will happen. In the age of anti-VEGF treatments, Dr SchmidtErfurth sees no benefit of macular laser, and indeed possibly even harm. She referred to microperimetry studies that demonstrate the damaging effect of macular laser, which can induce microscotomas which are undetectable by traditional measurements of visual acuity (VA), but which nevertheless decrease patients’ quality of vision.

“But even after patients are switched from anti-VEGF to laser treatment, some improvement is still possible.. The particular charm of anti-VEGF in DME consists in its reduced need over time,” she added.

Several points stand out which are clinically very relevant. First, a recent trial has demonstrated that aflibercept is superior to ranibizumab or bevacizumab for eyes with DME and poorer presenting VA. Secondly, clinical investigations have indicated that eyes with DME unresponsive to multiple injections of either ranibizumab or bevacizumab can demonstrate both anatomical and visual improvement upon conversion to aflibercept. Theories for this difference are based on the pharmacodynamics of aflibercept, which binds VEGF with much greater affinity, and also binds placental growth factor.

But what about the cost of repeated anti-VEGF injections, particularly in countries in which only the ranibizumab and/or aflibercept are approved for DME, as opposed to the far less expensive bevacizumab? The approximate cost for a single intravitreous injection is €1,700 for aflibercept (at a dose of 2.0mg), $44 for bevacizumab (1.25mg dose), and $1,060 for ranibizumab (0.3mg).

“While aflibercept injections are significantly more costly than bevacizumab, potential improvements that can be anticipated offer a justification for conversion to the newer molecule.

Further, you have to remember that DME is not AMD. The duration of the treatment regimen is not endless. Most patients need approximately four to five injections in the first year of treatment, two or three in the second year and only one or two in the third year. By the fourth year, most eyes are no longer receiving injections, so the investment in the superior molecules is worthwhile for this relatively short regimen,” Dr SchmidtErfurth pointed out.

Clearly, an absolute consensus has not yet been reached. While it is obvious that some patients respond less favourably than others to anti-VEGF treatment, it is at present impossible to predict treatment response in individual patients using conventional methods. “Currently, we only try something else when anti-VEGF treatment fails, but by then it’s often too late,” said Dr Bandello.

ANTI-VEGF AND THE PROMISE OF AFLIBERCEPT

What about patients with epiretinal tissue and persistent DME, despite maximum medical and/or laser therapy? Is surgery an option?

Jan van Meurs MD, PhD, Department of Vitreoretinal Surgery in the Rotterdam Eye Hospital, The Netherlands, is not particularly enthusiastic about surgery for DME. “There exists some wishful thinking regarding the role of vitrectomy for DME, but very few substantial studies to support these hypotheses. For example, it has been suggested that vitrectomy might improve posterior segment oxygenation, but it is more likely that the oxygen content of the infusion bottle was measured. There is substantial evidence from previous studies

So, for the ophthalmologist who has determined that a particular patient would be best treated with anti-VEGF injections, how does he or she decide which drug to use?

What are the current views on the various anti-VEGF molecules for the treatment of DME? Since the DAVINCI, VISTA and VIVID studies established that treatment with aflibercept yields greater visual gains than macular laser treatment, various trials have focused on the molecule´s value in relation to the other VEGF inhibitors already on the market. This comparison is particularly relevant considering the price differences between the various molecules.

EUROTIMES | DECEMBER 2015/JANUARY 2016

SURGICAL OPTIONS?

There is substantial evidence from previous studies that vitrectomy for DME without traction does not improve visual outcomes Jan van Meurs MD, PhD

that vitrectomy for DME without traction does not improve visual outcomes. In patients with obvious epiretinal traction, it may be beneficial however, as suggested by the DRCRnet studies. What would be ideal is a trial in which patients with DME and obvious traction would be randomised to vitrectomy plus anti-VEGF treatment versus anti-VEGF only,” he said.

IN THE PIPELINE Looking ahead, several drugs are in the pipeline. Luminate® (Allegro Ophthalmics) is an integrin antagonist that blocks the integrin receptors on vascular endothelial cells that help mediate several angiogenic processes.

Vasotide®, a peptidomimetic molecule, has been tested on three animal models in eye drop formulations. It has been shown to prevent VEGF from binding to both VEGF receptor-1 and neuropilin-1, both expressed by retinal vascular endothelial cells. Fovista® (Ophthotec), an antiplatelet-derived growth factor agent, has shown promise when added to an anti-VEGF regimen, as compared to antiVEGF monotherapy.

It appears that we are on the cusp of a second wave of this second revolution.

Angio-OCT might allow for more detailed analysis of the state of the retina, providing information on vascular patency without the burden of FA. At the same time, individualised treatment, based on pathogenetic and phenotypic differences between various types of DME, will produce results that we can currently only hope for and imagine.

Francesco Bandello: bandello.francesco@hsr.it Ursula Schmidt-Erfurth: ursula.schmidt-erfurth@meduniwien.ac.at Marc de Smet: doctors@retina-uveitis.eu Jan van Meurs: J.vanmeurs@oogziekenhuis.nl

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SPECIAL FOCUS: RETINA

MACULAR OEDEMA Growing support for anti-VEGF agents for retinal vein occlusion.

Leigh Spielberg MD reports

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nti-VEGF agents have a key role to play in the treatment of retinal vein occlusion (RVO), Francesco Bandello MD, FEBO told a session of the 15th EURETINA Congress in Nice, France.

Macular oedema is by far the most frequent cause of visual loss in RVO, and sequelae such as cystic degeneration, macular hole, epiretinal membrane and macular atrophy can be devastating, said Dr Bandello, Professor of Ophthalmology, Vita-Salute University, Milan, Italy.

“Both the BRAVO and the CRUISE studies offered unequivocal evidence that early treatment with anti-VEGF gives the best chance of visual recovery for patients with macular oedema,” he said.

What about patients who present late?

“It’s also important to remember these studies show that later treatment, for example six months after onset, remains worthwhile,” added Dr Bandello.

Francesco Bandello Patients who completed either BRAVO or CRUISE studies could enter the 24-month open-label extension, HORIZON study, to receive ranibizumab 0.5mg PRN. “After 12 months, best corrected visual acuity improvements from BRAVO were maintained in patients with branch retinal vein occlusion (BRVO), although a slight decrease was observed in patients with central retinal vein occlusion (CRVO). This suggests that more frequent assessments, by which I mean more than three-monthly, may be required to maintain visual acuity in these patients,” said Dr Bandello.

Additionally, Dr Bandello advocated an aggressive approach to treatment, which he considers superior to PRN treatment.

What about macular ischaemia? Is this a contraindication for anti-VEGF treatment in RVO? Dr Bandello does not think so.

“An article published by Campochiaro et al in Ophthalmology in 2013 showed that patients treated with ranibizumab had less retinal non-perfusion compared to sham-treated patients,” he said.

CONTRAINDICATION Therefore, physicians should not consider ischemia to be a contraindication. Further, sham-treated patients develop less non-perfusion after the switch has been made to ranibizumab, he noted.

In this respect, early fluorescein angiography is crucial. “It’s important to understand what’s going on in the retina. A paper once published in Ophthalmology analysed the reasons for mistakes in retinal disease, and discovered that CRVO was the disease most frequently misdiagnosed, especially in chronic cases. After initial evaluation, clinical evaluation and optical coherence tomography are sufficient,” said Dr Bandello.

He reminded delegates that, although there is no large-scale hard data for bevacizumab. “I think we can assume that this molecule is non-inferior to ranibizumab for RVO,” he said.

Francesco Bandello: Bandello.Francesco@HSR.it

EUROTIMES | DECEMBER 2015/JANUARY 2016

SPECIAL FOCUS: RETINA

NEW ANTIVEGF AGENT Brolucizumab has the potential to improve visual outcomes.

Dermot McGrath reports

T

he results of two phase II trials of brolucizumab (RTH258, Alcon Laboratories), a novel antivascular endothelial growth factor (anti-VEGF) agent, showed that the drug was safe and effective for the treatment of neovascular agerelated macular degeneration (AMD), Frank G Holz MD told delegates attending the 15th EURETINA Congress in Nice, France.

“The two trials clearly showed that brolucizumab has the potential to improve visual outcomes and increase duration of action for the treatment of neovascular AMD. The drug was well tolerated and raised no safety concerns,” said Dr Holz.

While there has been tremendous progress in the treatment of neovascular AMD in recent years, there remain unmet needs in daily clinical practice, said Dr Holz.

“We have made huge strides in treating macular disease but now we would also like to reduce the burden of care that frequent anti-VEGF injections place on the patient, the physician and the health system as a whole,” he said.

Brolucizumab is a single-chain antibody fragment that is significantly smaller than other anti-VEGF agents. The molecular weight of brolucizumab is 26kDa compared with 50kDa for ranibizumab and 149kDa for bevacizumab.

ACTIVE DRUG MOLECULES “This small size allows a 22 times greater molar concentration than ranibizumab, which may allow for more active drug molecules per volume injected and faster and better penetration into relevant ocular tissues.

It should also mean longer duration at the target tissue and make it more amenable to future drug delivery devices, with faster systemic clearance than current antiVEGF compounds,” Dr Holz said.

The SEE phase I/II trial tested ascending doses of brolucizumab in 194 patients at 51 sites worldwide compared to ranibizumab. The results showed reduction in central subfield Frank G Holz thickness at 4.5 and 6.0mg concentrations that were non-inferior to ranibizumab 0.5mg. There were also numerically greater mean gains in best corrected visual acuity for brolucizumab 6.0mg compared to ranibizumab 0.5mg.

A second trial, OSPREY, found that vision gains with brolucizumab were non-inferior to aflibercept, with rapid and sustained reductions in central subfield thickness, said Dr Holz. In a second phase of the OSPREY trial, half of brolucizumab patients were successfully maintained with Q12 dosing, which holds promise for longer injection intervals with this drug. Phase III studies of brolucizumab in larger population groups are currently ongoing.

Frank G Holz: Frank.Holz@ukb.uni-bonn.de EUROTIMES | DECEMBER 2015/JANUARY 2016

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Date of Prep: August 2015 L.GB.MKT.08.2015.12301 Copyright Š 2015 Bayer HealthCare Pharmaceuticals Inc. | www.bayerhealthcare.com | April 2015

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SPECIAL FOCUS: RETINA

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new anti-VEGF agent called brolucizumab (RTH258, Alcon), a single-chain antibody fragment, appears to provide gains in visual acuity (VA) equivalent to those of ranibizumab and aflibercept in eyes with neovascular age-related macular degeneration (AMD), but with a longer duration of action, according to the results of two phase II studies, said Dominik Escher PhD at the 15th EURETINA Congress in Nice, France.

“Phase III trials are currently ongoing. In case brolucizumab would come to market, this would represent the first single-chain antibody fragment and thus would open a new class of molecules,” said Dr Escher, who is the head of ESBATech, Switzerland, the Novartis company which developed brolucizumab.

PRIMARY ENDPOINT He noted that the first of the phase II trials, which involved 194 eyes of 194 patients, reached its primary endpoint of non-inferiority of brolucizumab to ranibizumab in terms of VA and central subfield foveal thickness.

Moreover, after a dose escalation phase, the median time to a return to standard of care based on pre-defined criteria was 75 days in eyes receiving 6.0mg brolucizumab, compared to only 45 days in eyes receiving ranibizumab.

The second of the phase II trials, the OSPREY Dominik Escher trial, involved 90 eyes of 90 patients. It compared brolucizumab and aflibercept. It reached the same endpoints in terms of VA, at week 12, and in terms of central subfield foveal thickness, at week 16. Furthermore, when the interval between injections was increased from eight weeks to 12 weeks, fewer patients needed rescue injections in the brolucizumab group.

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Brolucizumab is a humanised single-chain antibody fragment (scFv) which binds to all isoforms of VEGF-A. Dr Escher noted that scFvs are the smallest functional units of an antibody that can still bind to its target. Their molecular weight is only half that of Fab fragments like ranibizumab.

He added that the small size of scFvs gives them greater tissue penetration, and their high solubility means that larger amounts can be concentrated into a single intravitreal dosage.

They also have faster systemic clearance.

Dr Escher noted that ESBATech developed brolucizumab using a novel technology for the selection of fully human, highly stable and soluble scFv frameworks, which are then grafted with antigen-specific regions.

Other single-chain antibody fragments ESBATech are now investigating for ophthalmic use include one that is directed against tumour necrosis factor and is now in proofof-concept studies as a potential topical treatment for dry eye and uveitis.

Dominik Escher: Dominik.escher@novartis.com

EUROTIMES | DECEMBER 2015/JANUARY 2016

SPECIAL FOCUS: RETINA

STEROID IMPLANTS Significant improvements in patients with DME. Leigh Spielberg MD reports

I

ntravitreal steroid implants can provide significant improvements in patients with diabetic macular oedema (DME) in the long-term, Anat Loewenstein MD, Tel Aviv Medical Center, Israel, told the 15th EURETINA Congress in Nice, France.

Noting that steroids address the multifactorial nature of DME via inhibition of various signalling pathways within the eye, she reviewed the literature on intravitreal steroid implants for DME, with particular emphasis on the Illuvien® intravitreal fluocinolone implant and the Ozurdex® intravitreal dexamethasone implant.

“Both of these sustained-release devices have recently been approved by regulatory bodies for the treatment of DME. The implants’ sustained release of the active molecule over many months also allows for a decreased number of intravitreal injections, with a lower burden on both patients and the healthcare system,” Dr Loewenstein told the delegates.

Another feature of these agents it that patients also often respond after failure of anti-VEGF treatment regimens.

Dr Loewenstein highlighted the strong correlation between ETDRS retinopathy severity and intraocular concentrations of cytokines, a correlation that is lacking for VEGF concentrations.

Dr Loewenstein also addressed the well-known side effects of intravitreal steroids. “Although the incidence of cataract in phakic patients is very high, from 60 to 80 per cent, patients who underwent cataract surgery eventually gained the same visual benefit as pseudophakic patients. Approximately 40 per cent of eyes experienced increased intraocular pressure (IOP), and depending on the duration of the study, between one and five per cent of patients require a filtering procedure to control this increased IOP.” But what can physicians expect in daily practice, outside the highly organised confines of clinical trials? “Studies such as the MOZART trial suggest six to nine letter gains after two to three injections of Ozurdex®. Best corrected visual acuity improvement of at least 15 letters was greatest in patients with chronic DME,” she said.

What differentiates the longer-lasting Illuvien® from Ozurdex®? “Illuvien® is primarily intended for patients with DME that has been present for 1.7 or three years at least (according to different analysis), and has been insufficiently responsive to Ozurdex®, anti-VEGF or other available Anat Loewenstein therapies,” reported Dr Loewenstein.

Compliance issues also come into play, as a subset of patients are unable to attend even the relatively infrequent hospital appointments required for monitoring of the retinal response to Ozurdex®, let alone anti-VEGF agents.

And what about long-term use? “The Fluocinolone Acetonide for Diabetic Macular Edema (FAME) study, the first report of a five-year follow-up, indicated that 90 per cent of patients no longer need DME treatment two years after the end of a threeyear clinical study treatment regimen,” said Dr Loewenstein.

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Anat Loewenstein: anatlow@tasmc.health.gov.il EUROTIMES | DECEMBER 2015/JANUARY 2016

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SPECIAL FOCUS: RETINA

OCULAR IMAGING

Binocular OCT device seeks to reinvent eye examinations.

Dermot McGrath reports

A

new imaging device is aiming to reinvent the way eye examinations are currently performed. Pearse Keane MD, MSc, NIHR Clinician Scientist at UCL Institute of Ophthalmology, UK, described plans for the clinical testing and validation of binocular optical coherence tomography (OCT), a device capable of producing non-invasive high-resolution images of the eye in a fraction of a second and in greater detail than computerised axial tomography (CAT) or magnetic resonance imaging (MRI) scanning.

“The unique capability of this device is to provide comprehensive eye examination in an automated manner and reinvent the eye exam for the 21st Century. It certainly has the potential to replace the slit-lamp, a technology which is little changed since it was first developed more than 100 years ago by Gullstrand in 1911,” he told the 15th EURETINA Congress in Nice, France.

While the device provides “whole eye” OCT imaging of the anterior and posterior segments, Dr Keane told EuroTimes that there are three more important reasons why the device has the capability to reinvent the eye exam.

Courtesy of Dr Alex Walsh, Envision Diagnostics, Inc.

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DISPLAY CONTENT “Firstly, it is binocular in design. This allows the user to align the device with his or her own eyes without the need for a third party. So in other words, patients can scan their own eyes without the need for a photographer or doctor to be present. Secondly, it is a ‘smart’ device, meaning that the screen of the device can act like that of a smartphone or tablet computer to display content to the user.

For example, the screens can be used to display letters on a visual acuity (VA) chart to the user. The device can then use voice recognition technology to measure their VA level.

“Finally, the device allows for simultaneous imaging of both eyes. This means that, unlike other OCT devices, it can assess features such as pupils and extraocular movements,” he said.

As Dr Keane sees it, these three features taken together mean that binocular OCT goes far beyond structural imaging of the eye, allowing for a range of diagnostic tests EUROTIMES | DECEMBER 2015/JANUARY 2016

Various views of a handheld, automated, binocular OCT eye examination system

– from VA measurements, to visual field assessments, to pupillometry, among others – to be performed in a fully automated and quantitative manner.

PRIVATE PRACTICES The device will probably be used initially in hospital eye clinic settings before making its way into private practices, said Dr Keane.

“We believe, for instance, that it will greatly increase the efficiency and reduce the costs of retinal therapy clinics in the National Health Service (NHS). As such, we plan to conduct most of the initial testing in patients with chronic retinal diseases such as age-related macular degeneration (AMD) and diabetic retinopathy (DR),” he said.

... patients can scan their own eyes without the need for a photographer or doctor to be present Pearse Keane MD, MSc

SPECIAL FOCUS: RETINA Clinical tests in the UK will be funded by the National Institute of Health Research (NIHR) and will consist of a progressive framework of diagnostic accuracy studies.

As the first ophthalmologist to receive the NIHR research award, Dr Keane’s award of just under £1million will fund the research for the next five years.

GOLD STANDARD “The clinical tests will begin with studies to test the accuracy and reproducibility of each of the diagnostic features offered by the device as compared to gold standard examinations. In later studies we will look at real-world diagnostic accuracy studies – for example, evaluating whether the device is accurate for clinical decision-making in retinal clinics. We will also perform health economic analyses to determine what the potential cost savings and efficiency benefits of the device would likely be,” he said.

After the initial clinical studies are completed, Dr Keane sees potential for the device in other applications outside the hospital setting such as screening, telemedicine applications or even home monitoring of eye diseases.

The idea for binocular OCT was first formulated by Dr Alexander Walsh, an ophthalmologist and engineer based in

Above: Whole-eye imaging, of the anterior and posterior segments, using binocular OCT Left: An OCT-based ophthalmic testing centre could replace many expensive, labour-intensive diagnostic instruments

California, USA. The device is currently being developed in Los Angeles by his company, Envision Diagnostics, Inc. Dr Keane spent a number of years at the Doheny Eye Institute in Los Angeles under the mentorship of Dr Walsh.

Pearse Keane: pearse.keane@moorfields.nhs.uk

6TH EURETINA WINTER MEETING

ROTTERDAM Saturday 23 January 2016 Erasmus MC Querido Teaching Center Rotterdam, The Netherlands

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EUROTIMES | DECEMBER 2015/JANUARY 2016

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10–14 September

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XXXIV Congress of the ESCRS Bella Center, Denmark

Abstract Submission Deadline 15 March 2016

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CATARACT & REFRACTIVE

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Heavy silicone oil with moleculary design A case of post-traumatic subluxated cataract

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WEAK ZONULES Eyes with compromised zonules require additional capsular support. Roibeard O’hEineachain reports

I

n eyes with weak zonules, cataract surgery requires a slow and gentle approach with additional support for the capsule throughout the procedure, said Bekir Sitki Aslan MD, Liv Ankara Hospital, Ankara, Turkey.

“Weak zonules present a real challenge to the cataract surgeon, and careful planning and intraoperative care are required to increase the margin of safety in these potentially complex procedures,” he told the 19th ESCRS Winter Meeting in Istanbul.

When assessing an eye’s zonular integrity prior to cataract surgery, the first step is to review the patient’s history for risk factors, such as trauma, pseudoexfoliation syndrome, and Marfan’s syndrome. Eyes that have undergone previous intraocular surgery and highly myopic eyes are also prone to weak zonules.

Signs to look for under the slit-lamp include phacodonesis or other abnormal position of the lens and a red reflex beyond the lens periphery. When performing a capsulorhexis, difficulty with incising the capsule, because of a tendency for the capsular bag to be pulled along with the tear, is another sign of a weak zonule.

If the equator of the lens capsule is flat at the zonulolysis area, it is a sign of local zonular weakness which will not continue to extend after the surgery. However, if the equoatorial edge of the zonular weakness becomes rounder it is a sign of generalised and severe zonular weakness and zonular breakdown will continue after the surgery.

Dr Aslan noted that providing support to the capsule during cataract surgery is

essential in eyes with zonular deficiencies.

The two most commonly used tools for that purpose are iris hooks and capsular hooks. The capsular hooks differ from iris hooks in that they reach farther inside the capsule and can therefore provide a better stabilization of the lens with less likelihood of trauma to the capsule than is the case with the shorter iris hooks.

Capsular tension rings are another tool for stabilising the capsular bag.

However, they are best placed after phacoemulsification is complete, otherwise they will make cortical clean-up very difficult. The devices have several diameters, one should calculate the size of the ring to use in a particular eye by adding 1.0mm to its white-to-white measurements. For eyes with very poor zonular integrity, there are capsular rings like the Cionni rings and the Malyugin ring that have eyelets for fixation to the sclera.

During phacoemulsification, it is best to lower the fluidic settings and perform a thorough viscodissection with a dispersive viscoelastic, he said. That will relieve the zonular capsular tension and torsion and provide adequate access to the cortex without endangering the capsule. To reduce postoperative capsular contraction and capsular phimosis, Dr Aslan recommended using a three-piece hydrophobic IOL with stiff broad haptics. One technique he has found particularly useful is to place the haptics in the sulcus and capture the optic in the capsular bag, he said.

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Bekir Sitki Aslan: bsa@outlook.com EUROTIMES | DECEMBER 2015/JANUARY 2016

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CATARACT & REFRACTIVE

ENDOPHTHALMITIS Quick adoption of ESCRS guidelines seen, but only when Aprokam available. Sean Henahan reports

C

ontention has slowly given way to consensus in the cross-Atlantic debate on the merits of intracameral antibiotic prophylaxis following cataract surgery, suggests a debate held at the 2015 American Society of Cataract and Refractive Surgery Symposium in San Diego.

The landmark ESCRS Endophthalmitis Study was a large prospective randomised, multicentre cataract surgery study that compared various antibiotic regimes. The essential conclusion of the study was that the use of intracameral cefuroxime at the end of surgery significantly reduced the occurrence of postoperative endophthalmitis from 0.35 per cent to 0.05.

Since the study appeared in the JCRS in 2007, its recommendations were taken up more quickly and enthusiastically in Europe than in the USA. David F Chang MD and Peter Barry MD took the stage, representing the US and Europe respectively, to discuss the effect the study has had on current practice.

Dr Chang began by citing nine studies in the literature since 2007 confirming the efficacy of intracameral cefuroxime prophylaxis.

He highlighted a large US study conducted by the Kaiser health group showing a 22-fold decrease in endophthalmitis rates when its hospitals switched to the ESCRS study regimen. He noted that while the 2011 AAO guidelines and ASCRS white papers both stopped short of recommending this approach as standard of care, both concluded that the evidence supported the efficacy.

Dr Chang discussed how the original skepticism about the study expressed by many in the USA has evolved to increased acceptance with time. He compared the results of surveys of ASCRS members conducted shortly after the study (2007) with a similar study conducted in 2014.

In the initial survey, 77 per cent of respondents were not using intracameral antibiotics postoperatively. In the later survey, half of respondents were using intracameral antibiotics. The survey found that among US doctors not using the intracameral approach, two thirds stated they were not yet convinced of the merits. This was a significant decline from the 90 per cent who reported being unconvinced in the initial survey. Concern over the risk of mixing errors was also frequently cited as a reason for hesitation.

“Two thirds of US doctors surveyed say intracameral is important, and 84 per cent said they would use an intracameral antibiotic if one such as Aprokam were commercially available. But clearly the potential mixing risk is what is holding some people back.

I don’t think the US and European surgeons are that different in how they think. The difference is who has a commercial intracameral preparation available to use,” commented Dr Chang.

Dr Barry offered the European perspective. He cited multiple studies conducted since the original ESCRS study results, providing further support for intracameral prophylaxis.

“The important thing to understand is that these studies represent countries where a decision was made at one point in time to switch to intracameral cefuroxime.

Looking at collective data from almost one million patients, every study shows David F Chang MD that when the switch was

Two thirds of US doctors surveyed say intracameral is important

EUROTIMES | DECEMBER 2015/JANUARY 2016

Courtesy of David F Chang MD

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Data from the 2014 ASCRS Endophthalmitis Prophylaxis Survey

made where endophthalmitis rates were high, as in France, they became low; where they were low, as in Singapore, they got even lower,” said Dr Barry, chairman of the original ESCRS study.

ESCRS SURVEY Dr Barry noted that acceptance of this approach was undoubtedly stymied by the lack of an approved, licensed commercially available product. This has now changed, with the European Medicines Agency (EMA) approval of Aprokam (Thea), a single dose preparation developed specifically for this purpose. A single 50mg cefuroxime powder is mixed with a single dilution of 5.0ml normal saline. It is now available in 23 European countries.

A 2012 ESCRS survey looking at uptake of intracameral cefuroxime use throughout Europe surgeons found that 74 per cent of correspondents always or usually use intracameral antibiotics. However, a more detailed look across Europe shows practice patterns to be inconsistent.

For example, in France, which does the most cataract surgery in Europe, intracameral antibiotics are used 90 per cent of the time.

Similar numbers are also seen for Sweden, Denmark, Finland, Spain and Portugal. France and Denmark actually have official Government Health Agency guidelines supporting this approach, noted Dr Barry.

Intracameral prophylaxis is also used in more than 90 per cent of cataract surgeries in Italy. This is driven in part by concern over legal litigation. That country is currently the most litigious in the world for cataract surgery, Dr Barry explained.

However, in Germany, second only to France in terms of cataract volume, intracameral prophylaxis has yet to catch on, perhaps because of unresolved legal and budgetary issues.

A paper in the JCRS journal, authored by the clinical cataract committee of the ASCRS, concluded: “Intracameral injection of antibiotics ultimately should improve the safety of cataract surgery by providing better endophthalmitis prophylaxis. We’re calling on pharmaceutical companies and US FDA to make development and approval of such an agent a high priority.”

“The debate is over, we are actually all in harmony. The difference is you in the US have a brick wall that we don’t,” Dr Barry concluded.

David F Chang: dceye@earthlink.net Peter Barry: peterbarryfrcs@theeyeclinic.ie Dr Chang is Clinical Professor at the University of California, San Francisco, and has no relevant financial interest in this subject

CATARACT & REFRACTIVE

ACCOMMODATIVE IOL n innovative accommodative intraocular lens (IOL), the FluidVision® IOL (PowerVision), provided patients with good visual acuity (VA) at all distances, the results of a clinical study indicate. The FluidVision® IOL harnesses tiny natural muscular forces in the eye to move fluids inside the lens, mimicking natural accommodation through shape change, Frik Potgieter MD, FRCS, Pretoria, South Africa, told delegates at the XXXIII Congress of the ESCRS in Barcelona, Spain.

Dr Potgieter and colleagues completed a single-site, twosurgeon study of 26 patients to assess accommodation, visual quality and long-term visual outcome and stability. Follow-up was 24 months, and eight of the 26 patients received a second implant into the fellow eye at 15-21 months after initial surgery.

The average best distance corrected binocular acuities available for seven patients at one month were: logMAR -0.05 +/- 0.05 at distance; logMAR 0.05 +/- 0.06 at intermediate, 66cm; and logMAR 0.16 +/- 0.16 at near, 40cm. Binocular intermediate and near VAs were about one line better than monocular acuities.

Average monocular uncorrected distance VA at one month was logMAR -0.01 (20/20+), and binocular uncorrected distance acuity was logMAR 0.00 (20/20). Average monocular and binocular accommodative amplitude measured by defocus was 3.12D and 4.19D, respectively.

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urt

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In

CONTINUUM OF FOCUS “The FluidVision® accommodative IOL demonstrates excellent binocular VA at distance, intermediate and near. What further distinguishes this type of accommodative IOL is the continuum of focus from near to distance,” Dr Potgieter said.

“Contrast sensitivity was superior to standard diffractive multifocal IOLs in both mesopic and mesopic glare conditions. Indeed, contrast sensitivity is comparable to a monofocal IOL,” he added.

Stability and safety were observed out to 24 months after implantation.

Endothelial cell counts were normal for intraocular surgery.

"The FluidVision® consists of a refractive Schematic view of FluidVision ® AIOL index-matched silicone fluid-filled optic connected by channels to two fluid-filled haptics. The act of accommodation forces fluid from the haptics into the optic, thereby increasing thickness and optical power.

Upon dis-accommodation, fluid flows back into the haptics,” he explained.

The silicone oil inside the lens is the same as the oil used in vitreoretinal surgery. If the lens required removal, oil aspiration via a needle inserted into the lens cavity leads to collapse of the lens, making it possible to explant it similar to a conventional IOL.

The three-dimensional device is inserted into the capsular bag and then rotated...

Courtesy of Frik Potgieter MD, FRCS

A

Fluid-filled hydrophobic acrylic accommodative IOL mimics natural process. Leigh Spielberg MD reports

Oblique view of the accommodating mechanism of the FluidVision ® lens in situ

“The three-dimensional device is inserted into the capsular bag and then rotated so that the haptics come to rest in the horizontal position,” he said.

After the initial healing period, there were no signs of inflammation, and the lens remained stable and centred in all cases, he said.

Frik Potgieter: fjp@lasik.co.za

Positions of fellowships available in

Paediatric and Refractive Ophthalmology

Under the Direction of Professor Michael O’Keeffe FRCS

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Candidates must have at least 3 years experience FRCS or equivalent in clinical ophthalmology and have surgical experience. Candidates must be registered with the Irish Medical Council.

For further information contact: Helen Murphy Suite 5 Mater Private Hospital, Eccles Street, Dublin 7 Tel: 00353 1 8858626 Email: mokeefe@materprivate.ie

Frik Potgieter MD, FRCS EUROTIMES | DECEMBER 2015/JANUARY 2016

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CATARACT & REFRACTIVE

SURGERY POST-LASIK Contrast sensitivity can be significantly reduced.

Leigh Spielberg MD reports

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atients who have previously undergone LASIK for myopia are now undergoing cataract surgery in increasing numbers. These are patients who are accustomed to high quality, spectacle-free vision and are very likely to request implantation of a multifocal intraocular lens. It is therefore important for surgeons to be informed of the possible effects of myopic LASIK on the outcome of surgery, particularly in cases in which a premium intraocular lens (IOL) will be used.

“We sought to evaluate the impact of previous myopic LASIK on contrast sensitivity in patients who received diffractive multifocal IOLs at a single institution after myopic LASIK,” said Hiroko Bissen-Miyajima MD, PhD, Tokyo, Japan, to delegates at the XXXIII Congress of the ESCRS in Barcelona, Spain.

“Besides the well-known difficulty of IOL power calculation in post-LASIK eyes, contrast Hiroko Bissen-Miyajima sensitivity is an important concern in these patients. This is not something that has been evaluated in previous publications of multifocal IOLs in eyes with previous LASIK, despite its importance to outcomes and patient satisfaction,” said Dr Bissen-Miyajima, Tokyo Dental College Suidobashi Hospital.

Discussing the results of a retrospective case series of 18 patients who had received either a ZMA00 or a ZMB00 (AMO) diffractive multifocal IOL between 2011 and 2014, Dr BissenMiyajima noted that all patients had received their LASIK at other surgical centres between 1999 and 2011.

Relevant pre-phaco data included an average ocular axial length of 27.0mm; a mean central corneal thickness of 465μm; pre-op corneal refraction of 38 +/- 1.5D; and an average IOL power calculation of 20.0D. Also of note was the young age of patients undergoing cataract extraction, with a mean age of 48 +/- 10 years.

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Measurements performed at one month postoperatively included corneal higher-order aberration (HOA) and contrast sensitivity, with a calculation of the area under long contrast sensitivity (AULCSF). Using multivariable regression analysis, degradation in contrast sensitivity was assessed in relation to keratometry, corneal eccentricity, ocular axial length, central corneal thickness, HOA, corrected distance and near visual acuities, manifest refraction and patient age.

The results showed that AULCSF and contrast sensitivity were significantly decreased in eyes with a thinner central corneal thickness (P<0.05). This decrease was present at three and 12 cycles per degree (CPD, a measure of contrast sensitivity), although it was absent at 18CPD. “Thinner central corneas were the most significant ocular factor associated with decreased contrast sensitivity,” said Dr Bissen-Miyajima, who urged delegates to take this into account when planning on implanting a multifocal IOL in a post-LASIK eye.

Hiroko Bissen-Miyajima: bissen@tdc.ac.jp

EUROTIMES | DECEMBER 2015/JANUARY 2016

CATARACT & REFRACTIVE

OBITUARY Professor Doctor Jan Gerben Frans Worst, 30th March 1928 – 25th September 2015. By Prof Rudy Nuijts ur eyes are windows to the outside world’

the field of intraocular lens implantation. Their perseverance and passion resulted in the establishment of The Netherlands IntraOcular Implant Club (NIOIC, 1977) which is still the forum for exchanging innovations in anterior segment surgery in The Netherlands. Jan Worst communicated the affection for his profession and his vision on the innovations in our field in a passionate and unprecedented manner. His dedication in the quest for innovation led to the birth of Ophtec BV, the company that has been professionally directed by his wife Anneke Worst, and now prospers in the capable hands of his son Erik-Jan Worst.

The heritage of Prof Worst is, and will remain, visible in the performance of this innovative company.

Courtesy of Prof Rudy Nuijts

The news that Prof Dr Jan Worst had passed away reached me on my way to a presentation for the Dutch residents in Utrecht where I had to lecture on the history of intraocular lenses.

This topic was his passion throughout life and I realised how fortunate I was to transfer his knowledge to our residents.

Prof Worst was born in Arnhem, The Netherlands, in 1928.

He studied medicine in Utrecht. He specialised in ophthalmology at the University of Groningen, where he was admitted his doctoral degree summa cum laude with a dissertation on Pathogenesis of SCIENTIFIC CURIOSITY Congenital Glaucoma, His scientific curiosity in 1966. and interest in the Prof Worst was anatomy of the appointed Head of vitreous, which he Department, “Chef researched in his de Clinique”, in famous domestic Groningen after His scientific curiosity and interest into the anatomy basement laboratory admitting his doctoral in Haren, connected of the vitreous, which he researched in his famous degree. Nine years later, his name to scientific domestic basement laboratory in Haren, connected his he set up an ophthalmic discoveries and practice together with name to scientific discoveries and papers in this field papers in this field. ophthalmologists His discoveries and Ludwig and Massaro lectures played a at the Heresingel in significant part in the research of macula degeneration.

Groningen. He operated on in a regional hospital, Refaja Hospital Prof Worst was also awarded many recognitions, amongst in Stadskanaal, and later in one of the first extramural clinics called which was the prestigious “Binkhorst Award” by the American OMC North.

Intra Ocular Implant Society in 1976.

Improving the fate of the blind and visually handicapped was In 1990 Prof Worst was appointed Professor at the Boerhaave important to him and he travelled a lot to develop the ophthalmic Institute at the University of Leiden to enable further scientific profession worldwide. He always was aware of the needs of the less research of the anatomy of the vitreous. fortunate in the world and volunteered as an ophthalmologist in In 1994 Prof Worst was decorated with knighthood, in Dutch, countries such as India and Nepal.

“Officier in Orde van Oranje Nassau”, by Queen Beatrix. Prof

INTERNATIONAL RECOGNITION Prof Worst was a great inventor of intraocular lenses and surgical instruments. He put great effort in keeping solutions simple yet effective to help him and his peers perform better operations. The invention of the patented “iris-claw” lens yielded international recognition. This lens, nowadays known as ArtiLens, has been slightly updated through the years, but in its core is still the same.

The lens still is one of the best solutions for certain patients to regain sight. In many countries in Europe and Asia, this lens is still one of the first solutions for treating aphakia.

In The Netherlands, Binkhorst and Worst were pioneers in artificial lens implantation and saw the need for creating a platform to exchange scientific ideas and clinical results in

Worst also received many other honours.

In 1999, he was the first recipient of the IIIC’s GF Jan Worst Medal and Lectureship with which IIIC honors leaders and innovators in the field of ophthalmology. In 2000, the ESCRS awarded him the Binkhorst medal lecture at the XVIII Congress of the ESCRS in Brussels, Belgium.

Jan Worst will be remembered as one of the true pioneers of intraocular lens design and surgery. The ESCRS extends its sympathy to the family and friends of Prof Worst, a truly great man and a great ophthalmologist.

Prof Dr Rudy Nuijts is Chairman of The Netherlands IntraOcular Implant Club, and Treasurer of the European Society of Cataract and Refractive Surgeons EUROTIMES | DECEMBER 2015/JANUARY 2016

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CORNEA

CORNEAL TRANSPLANT DALK less popular than DSAEK, with few countries using it in more than one-quarter of cases requiring anterior keratoplasty. Howard Larkin reports

S

elective lamellar keratoplasty, both endothelial and anterior, is taking hold around the world and is almost certainly the future of corneal transplantation, 2015 Binkhorst Medallist Donald TH Tan FRCS, Arthur Lim Professor, Singapore National Eye Centre, told the 2015 American Society of Cataract and Refractive Surgery Symposium in San Diego, USA. But while endothelial keratoplasty (EK) has become the gold standard for treating endothelial dysfunction, loss of endothelial cells remains a challenge, Dr Tan observed. Similarly, deep anterior lamellar keratoplasty (DALK) remains technically challenging.

Advances in surgical technology and technique are improving cell survival rates and making all lamellar procedures more manageable, which should lead to better long-term outcomes.

For example, in 2006, the taco folding tissue insertion technique used in Descemet’s stripping automated endothelial keratoplasty (DSAEK) led to endothelial cell loss above 60 per cent at six months in Asian eyes, Dr Tan reported. Switching to the sheets glide technique cut that to about 30 per cent in 2007, and in 2009 the EndoGlide inserter, developed by Dr Tan and colleagues, then cut that to about 15 per cent – less than the 20 to 40 per cent seen with penetrating keratoplasty (PK).

“We have managed to halve our endothelial cell loss in DSAEK with each insertion transition,” said Dr Tan. DSAEK also produces better graft survival for repeat procedures than PK, Dr Tan noted. At year five, 51 per cent of grafts survived in eyes treated with PK after a failed PK, compared with 86 per cent of eyes treated with EK after failed PK (Ang, Mehta, Tan et al. In Press, AJO).

These results, along with a manageable learning curve and favourable economics, are making DSAEK the preferred procedure for treating endothelial dysfunction around the world, accounting for approximately half of procedures in the US, UK, Sweden and Singapore in 2012, and one-quarter or more in Italy, Germany and Australia, Dr Tan noted.

DMEK has also led to more donor tissue wastage and higher re-bubbling rates that DSAEK, Dr Tan noted. As a result it is not widely used, accounting for just six per cent of grafts and 11 per cent of EK procedures in the US in 2014.

However, the newly developed Descemet’s Mat (D-Mat) for use with the EndoGlide may make the membrane easier to handle, making DMEK a more similar procedure to DSAEK, and help reduce cell loss and donor tissue waste, Dr Tan said. This is still in the developmental stage, though whether it will enter the mainstream remains an open question, he added.

Similarly, DALK has proven superior to PK in graft survival outcomes and reduction in complications. Yet the surgery itself is technically challenging, prompting many to seek new solutions.

Indeed, some have moved away from the “big bubble” lamellar separation technique, which can result in accidental perforations, to manual blunt dissection, Dr Tan said.

But manual dissection, too, remains more an art than a science, Dr Tan said. As a result, DALK remains less popular than DSAEK, with only a handful of countries, including Singapore, Brazil and Italy, using it in more than one-quarter of cases requiring keratoplasty, although it should be recognised that the indications for DALK, i.e stromal diseases with healthy endothelium, are also less than EK. Possible technological solutions include microkeratomes and femtosecond lasers, but these also have their limits.

Donald Tan: donald.tan.t.h@snec.com.sg

Observership Programme

DMEK CHALLENGE Descemet’s membrane endothelial keratoplasty (DMEK) is anatomically the most perfect EK procedure, adding no excess stroma, which results in better visual acuity outcomes, Dr Tan noted. The procedure is also low-tech, requiring only an IOL shooter, BSS and air to accomplish.

Even so, DMEK is technically very challenging, Dr Tan said.

Dealing with its extremely thin and fragile donor tissue presents new challenges. The tissue is difficult to manipulate and touching it destroys endothelium. Even the masters of the technique, such as Gerrit Melles MD, Francis Price MD and Friedrich Kruse MD, see endothelial losses of 34 to 40 per cent, Dr Tan noted.

Donald TH Tan FRCS

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EUROTIMES | DECEMBER 2015/JANUARY 2016

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CORNEA

HSV KERATITIS A chameleon which has lost its horror.

W

Dermot McGrath reports

hile herpes simplex virus (HSV) remains a very frequent cause of unilateral keratitis in adults and bilateral keratitis in children, the prognosis is usually quite good given that the various forms of appearance are known and provided that the therapeutic regimens, both medical and surgical, are adequately chosen, according to Berthold Seitz MD. “Herpetic keratitis is a chameleon. However, given adequate medical and microsurgical management it has lost much of its horror today,” Prof Seitz told delegates attending the 2015 Congress of the European Society of Ophthalmology (SOE) in Vienna, Austria.

In a broad overview of HSV-related ocular infections, Prof Seitz said that the classification of herpes simplex keratitis has

EUROTIMES | DECEMBER 2015/JANUARY 2016

evolved in recent years and now includes distinct forms such as infectious epithelial keratitis (dendritic or geographic keratitis), neurotrophic keratopathy, stromal keratitis (necrotizing and non-necrotizing), and endotheliitis.

The most well-known herpetic infection and the most common is infectious epithelial keratitis, said Prof Seitz. It may take the form of dendritic keratitis with branching linear lesions that typically break through the basal membrane of the cornea, with terminal enlargements, and swollen epithelial margins with living virus. If the dendrites become confluent, it may evolve into geographic keratitis.

It is also important to distinguish infectious epithelial keratitis from acanthamoeba keratitis, a rare opportunistic infection that presents with similar non-specific symptoms as bacterial and viral keratitis.

“We did a survey in Germany, and saw that over the last 20 years more than 50 per cent of acanthamoeba keratitis cases were misdiagnosed as epithelial herpetic keratitis. To make this differential diagnosis, confocal microscopy, histopathology and especially polymerase chain reaction (PCR) tests are indispensable,” he said.

Infectious epithelial keratitis is typically treated with topical trifluorothymidine or acyclovir/ganciclovir, no steroids and epithelial abrasion if a surgical option is required.

Neurotrophic keratopathy, often referred to as meta-herpetic keratitis, is a late stage, burned out herpetic keratitis, said Prof Seitz, with no immune reaction, no infection, reduced corneal innervation and diminished tear secretion. It is treated with non-preserved artificial tears, hyaluronic acid gels and autologous serum. Surgical approaches include amniotic membrane transplantation (AMT), botulinum toxin application in the upper lid for temporary iatrogenic ptosis, or temporary tarsorrhaphy.

CORNEA

27

However, given adequate medical and microsurgical management it has lost much of its horror today

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Courtesy of Berthold Seitz MD

THERAPEUTIC STEP APPROACH Necrotizing stromal keratitis, or the classic herpetic ulcer, typically presents with a lot of active HSV in the stroma, initially without hypopyon, and corneal neovascularisation is also frequently present. Therapy is topical antivirals, antibiotics and cycloplegics and initially no steroids, said Prof Seitz. Systemic antiviral treatment is also recommended, while AMT and emergency keratoplasty are surgical options.

“I propose a therapeutic step approach using appropriate topical and systemic antibiotics, AMT, elective keratoplasty in the quiet interval, while reserving emergency keratoplasty only in the case of perforation,” he said.

Non-necrotizing stromal keratitis, or interstitial keratitis, is treated with topical and systemic acyclovir and steroids, which are tapered over a few weeks or even months, said Prof Seitz, Department of Ophthalmology at the Saarland University Medical Centre in Homburg, Saarland, Germany.

For endotheliitis, topical treatment is with acyclovir, steroids and antiglaucoma medication to treat associated ocular hypertension but no prostaglandin analogues.

Systemic treatment is oral acyclovir, steroids and potentially anti-glaucoma drugs such as Diamox.

On the question of penetrating keratoplasty (PKP), recent research has shown that graft to host transmission of HSV seems to be a real phenomenon, said Prof Seitz, with potential major negative impact on graft Berthold Seitz MD

survival. “To enable an appropriate prophylactic acyclovir treatment in distinct cases after PKP we advocate the screening of both patient and donor corneas for HSV-1 by use of PCR testing. We also need to be aware that resistance of acyclovir may occur during long-term prophylaxis in immunocompromised patients,” he added.

Berthold Seitz: Berthold.seitz@uks.eu

7th EuCornea Congress

OPENHAGEN2016

9–10 September Bella Center, Denmark

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Eu

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www.eucornea.org

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C o r n

European Society of Cornea and Ocular Surface Disease Specialists

EUROTIMES | DECEMBER 2015/JANUARY 2016

aegean cornea XIII 1-3 July

2016

Topics 

Including a symposium organised by ESCRS

years of Lasik

 



 

The transition

Institute of Vision and Optics



University of Crete



Organizing Committee Ioannis Pallikaris, MD PhD  Perry S. Binder, MS MD  Marguerite McDonald, MD  Sonia Yoo, MD









25 Years of LASIK, historical approach The new face of “SMILING LASIK” Femtosecond lasers applications for anterior segment surgery Femtosecond laser cataract surgery and RLE The role of Phakic IOLs Current and experimental approaches to management of Dry Eye Diagnostic equipment for screening and managing anterior segment and refraction Collagen cross-linking: 10 years later Presbyopia surgery: Inlays, onlays, lasers, and lens approaches Endothelial keratoplasty: DMEK, DALK, DSAEK New and experimental treatments for ocular infections

www.aegeancornea.gr aegean@med.uoc.gr

GLAUCOMA

29

IMAGING GLAUCOMA Modern imaging technologies complement clinical expertise in diagnosis and monitoring of glaucoma. Roibeard O’hEineachain reports

STEREO PHOTOGRAPH INTERPRETATION CAN BE UNRELIABLE Studies show that changes in the optic nerve head can be highly predictive of future visual field loss, whether detected by stereo photography (F Madeiros et al, Arch Opthalmol 2009, 127:1250 1256) or newer technologies like HRT (BC Chauhan et al, Ophthalmology 2009; 116:2110-2118).

However, because of the subjective nature of optic nerve head photograph interpretation, its accuracy in the detection of glaucomatous change is highly dependent on the expertise of the clinician viewing the images. Furthermore, even glaucoma specialists viewing serial optic disc

Courtesy of David F Garway-Heath MD, FRCOphth

M

odern imaging techniques are becoming increasingly accurate in identifying structural changes in the optic nerve head that correspond to, or are predictive of, visual field changes in glaucoma patients, said David F GarwayHeath MD, FRCOphth, International Glaucoma Association Professor of Ophthalmology at the UCL Institute of Ophthalmology, London, UK, in a Glaucoma Day session at the XXXIII Congress of the ESCRS in Barcelona, Spain.

“Over the last 20 years, new technologies have become available that have enabled us to quantify imaging data with increasing precision, and the question we need to ask is: ‘With this sophisticated technology, are we actually any better off?’” Dr GarwayHeath said.

He noted that optic nerve head stereo photography is likely to remain a mainstay of glaucoma diagnosis and monitoring. It is the only technique that can provide trueto-life colour imaging and therefore it is the only means for detecting features like optic nerve haemorrhages, which are an important predictor of visual field progression.

Meanwhile, newer technologies like the GDx (Carl Zeiss Meditec) and the Heidelberg Retina Tomograph (HRT, Heidelberg Engineering), and optical coherence tomography (OCT) are providing increasingly detailed imaging and have at their command a large normative database with which to compare individual images. As a result, the machines can outperform most clinicians using stereoscopic photographs in distinguishing eyes with glaucoma from healthy eyes (Reus et al, Ophthalmology 2010;117:717-723).

Heidelberg Retina Tomograph (HRT) image and visual field test from a patient. The HRT Moorfields Regression Analysis is ‘Outside Normal Limits’. The visual field Glaucoma Hemifield Test is ‘Within Normal Limits’

photographs will not always agree as to whether glaucomatous change has occurred, Dr Garway-Heath pointed out.

For example, among the trained technicians at the optic disc reading centre for the Ocular Hypertension Treatment Study (OHTS), the kappa value for the agreement between repeat gradings of stereoscopic photographs was relatively high, ranging from 0.65 to 083 (RK Parrish et al . Am J Ophthalmol 2005;140:110-344).

By comparison, in another study, the inter-observer kappa value was only 0.2 for non-expert ophthalmologists, and 0.51 for glaucoma experts. Moreover, the level of agreement between non-experts and the experts was only 68 per cent (Breusegem et al, Ophthalmology 2011;118:742-746). An agreement level of 50 per cent is the same as would be expected from flipping a coin.

In another study, involving 10 glaucoma experts simultaneously presented with sets of two time-distinct disc photographs from each of a series of eyes, the level of inter-observer agreement as to whether progression had occurred was only modest to fair, with kappa values ranging from to 0.34 to 0.68 (Azuaro-Blanco et al, Am J Ophthtalmol 2003:136:949-950).

He suggested that modern imaging technologies might therefore be a useful adjunct to optic disc photographs in determining if glaucoma progression has occurred. He cited a study which showed that HRT is at least as accurate in detecting evidence of progression as are experts using monoscopic photographs (BC Chauhann et al, Invest Ophthalmol Sci 2009; 50:1682).

Modern imaging devices also include software that maps the structural glaucomatous changes over time to

corresponding areas of the visual field. In this way, imaging can be used to help tip the balance one way or the other in cases where visual field testing yields equivocal results, he said.

When structure and function disagree Dr Garway-Heath noted that, in some eyes with glaucoma, the visual field loss will appear to occur prior to structural changes, while in others the opposite will occur.

There are several possible reasons why these discrepancies may occur, but the most likely explanation is measurement error. A sure sign that this is the case in a particular patient is a seeming fluctuation of structural and/or functional change over time.

Factors leading to disagreement include poor image quality and normative databases which are inappropriate for a particular patient because of the patient’s age, their level of refractive error or other factors.

Some errors of interpretation can therefore be avoided by taking those factors into consideration.

For example, in an eye with an abnormal HRT scan but normal visual fields, if the patient is 95 years old and has an intraocular pressure (IOP) of 10mmHg, it could just be the effect of age on the optic nerve. However, if the patient was 35 years old and had a high IOP, then they would be a glaucoma suspect.

“So, to conclude, imaging can support a diagnosis, but it cannot make the diagnosis for you. Similarly, imaging can provide additional evidence on patients’ progression status, but clinicians need to be aware of the source of error in interpreting the reports and consider clinical context,” he said.

David F Garway-Heath: david.garway-heath@moorfields.nhs.uk EUROTIMES | DECEMBER 2015/JANUARY 2016

30

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linicians should avoid become overly obsessed with intraocular pressure (IOP) reduction and pay greater attention to broader glaucoma treatment strategies that positively affect patients’ quality of life, according to Norbert Pfeiffer MD. “There is a growing trend in glaucoma care to concentrate on the patients’ quality of life and I think this is a positive development because ultimately our patients are more interested in their overall quality of life than their target IOP,” Dr Pfeiffer, Medical Director, Mainz University Medical Centre, Mainz, Germany, told delegates attending the 2015 Congress of the European Society of Ophthalmology (SOE) in Vienna, Austria.

In a broad overview of current and future trends in glaucoma treatments, Dr Pfeiffer said that ongoing advances in delivery methods and medications are improving standards of care for glaucoma patients.

“Individualised target IOP is becoming more the norm as per the European Glaucoma Society guidelines. We also know today that patients are far less compliant than we assume in taking their medications, so I Norbert Pfeiffer think we will continue to see a trend towards fixed combinations and probably long-term medication where compliance does not play such a key role,” he said.

New delivery methods for glaucoma drugs may play a major part in transforming the clinical management of the disease, said Dr Pfeiffer. “We will probably soon see something that I thought was impossible ten years ago – an injectable glaucoma medication into the vitreous cavity which will perhaps require twice-yearly injections. Certainly for some patients this may be preferable to the daily burden of using eye drops,” he said.

ENV 515 (Envisia Therapeutics Inc.), an implantable, ophthalmic, sustained-release formulation of the prostaglandin travoprost, has shown effective IOP reduction for up to six months in early trials, said Dr Pfeiffer.

There are also other promising new medications in the pipeline such as Rho-kinase (ROCK) inhibitors and TGFbeta antagonists. ROCK inhibitors such as AR-13324 (Aerie Pharmaceuticals) alter the cell shape and extracellular matrix of the trabecular meshwork to improve outflow of aqueous humour and reduce fibrosis.

“There are three identified IOP-lowering mechanisms with AR-13324: ROCK inhibition relaxes the trabecular meshwork and increases outflow, reduces fluid production and also lowers episcleral venous pressure,” said Dr Pfeiffer.

Another drug currently under development, PG324 (Aerie Pharmaceuticals), adds latanoprost into a fixed combination therapy. This may potentially add another IOP-lowering mechanism to the mix by increasing fluid outflow through the uveoscleral pathway in addition to the same mechanisms identified with AR-13324, he said.

Another compound, DE-117 (Santen Pharmaceutical Co. Ltd.), a non-prostanoid selective EP2 receptor agonist, is currently in trials.

Norbert Pfeiffer: pfeiffer@augen.klinik.uni-mainz.de

EUROTIMES | DECEMBER 2015/JANUARY 2016

Nanosecond Laser Cataract Emulsification

All-Video Live Surgery Interactive Meeting Thursday February 25th at 20:30 - 22:30 Tsocha 17, Athens 11521, Greece The LaserVision Clinical & Research Institute

Guest Faculty: • Ivan Tanev, MD Bulgaria • J.C. Vryghem, Belgium • Gangolf Sauder Germany • A. John Kanellopoulos, MD-USA & Greece

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ESCRS

Winter Meeting In conjunction with the 30TH International Congress of HSIOIRS

Athens 26–28 February 2016 MEGARON CONGRESS CENTRE, ATHENS, GREECE

/ESCRS @ESCRSOfficial ESCRS

Main Symposia Friday 26 February

Saturday 27 February

17.00 – 18.30

16.30 – 18.00

Explantations of Ocular Implants

IOL Solutions for Posterior Capsular Tears

Chairpersons: J. Güell SPAIN P. Papadopoulos GREECE

Chairpersons: S. Georgaras GREECE B. Malyugin RUSSIA

Saturday 27 February

Sunday 28 February

11.30 – 13.30

11.30 – 13.00

Are There any Untold Secrets in Refractive Surgery?

Young Ophthalmologist Symposium Postoperative Complications: What Can Go Wrong after Cataract Surgery?

Chairpersons: V. Katsanevaki GREECE S. Morselli ITALY

Chairpersons: M. Severinsen DENMARK P. Viola ITALY

other highlights l

Basic Optics Course

l

Cataract Surgery Didactic Course Part 1

l

ESCRS/EuCornea Cornea Day

l

Refractive Surgery Didactic Course Part 1

l

Young Ophthalmologists Programme Learning from the Learners: Interactive Video Session on Cataract Surgery for Trainees

Sunday 28 February l

Hellenic Society of Intraocular Implant and Refractive Surgery Symposium Controversies in Presbyopia Surgery

25

OVER

Friday 26 February

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Surgical Skills

Training Courses

Book early to avoid disappointment

Saturday 27 February l

Cataract Surgery Didactic Course Part 2

l

Cornea Didactic Course

l

Live/Near Surgery

(Organised by the Hellenic Society of Intraocular Implant and Refractive Surgery)

l

Refractive Surgery Didactic Course Part 2

Full Programme, Registration and Hotels available online

www.escrs.org

20TH ESCRS

Winter Meeting

ATHENS

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Evening Symposium 18.30

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OCULAR

35

BEYOND ANTIBIOTICS New strategies in the global war against antibiotic resistance.

Courtesy of Terrence P O’Brien MD

Leigh Spielberg MD reports

Severe keratitis on day four after LASIK surgery in a healthcare worker due to culture proven methicillin-resistant Staphylococcus aureus (MRSA)

Suppurative endophthalmitis with hypopyon in an otherwise healthy individual after uncomplicated phacoemulsification with intraocular lens implantation. Cultures from vitreous tap grew coagulase-negative staphyloccus that was resistant to methicillin (MRSE)

he growing threat of antimicrobial resistance will require new ways of looking at treating infection, Terrence P O’Brien MD warned the 7th International Congress on Ocular Infections in Barcelona, Spain. “We are falling woefully behind in the war between microbe and man, which means we need to continue learning more about microbes,” said Dr O’Brien, Professor of Ophthalmology, Charlotte Breyer Rodgers Distinguished Chair, Bascom Palmer Eye Institute, Palm Beach, Florida, USA. Dr O’Brien described our current approach to infection as a so-called “Exorcist” approach, in which we try to saturate the eye with high antibiotic concentrations at frequent intervals in order to rid the eye of “evil” microbes.

“Yet this is not ideal, as humans are colonised by germs, and symbiosis is more important than asepsis. A better understanding of the pathophysiology of infections might allow us to develop more nuanced treatment, from rapid, reliable diagnostic methods to new treatments with novel targets and specialised delivery modalities,” he said.

This is an interesting development, considering a quotation from 1960 by then American Surgeon General, the government’s top physician: “It is time to close the book on infections diseases and declare the war against pestilence won.”

Not exactly! Those were exciting times, when new antibiotics were continuously being developed and S aureus had not yet acquired methicillin resistance.

Other options must be found, he stressed, starting with naturally occurring antibacterial agents already present in our bodies. These include hypochlorous acid, antimicrobial peptides and defensins.

Hypochlorous acid (HOCL), which is released from neutrophils as part of the body’s immune response, kills microorganisms and helps suppress the body’s inflammatory response.

“Hypochlorous acid 0.01 per cent has excellent activity against a broad range of pathogens, including those commonly found on the eyelids and lashes. And it’s one thousand times less toxic then Betadine®,” he noted.

Antimicrobial peptides, such as lactoferrin, dermcidin and the defensins, take advantage of basic differences between prokaryotic and eukaryotic cells, such as their electric charge, that allow for targeted cidal activity. They are present in everything from amoebas to humans, and in vertebrates are particularly abundant in external mucosa, immune cells and the intestinal tract.

T

MAGIC BULLET “The ideal antimicrobial, the perfect ‘magic bullet’ would demonstrate a broad spectrum of activity, good tolerance, low toxicity, microbicidal efficacy, rapid kill, good penetration and coverage of emerging resistant organisms,” said Dr O’Brien.

Dr O’Brien further discussed new treatment delivery technologies such as smart polymers, intraocular inserts, iontophoresis and intravitreal gene therapy, before placing the emphasis back on antimicrobial resistance.

“Bacterial isolates from ocular infections have been showing increasing resistance to fluoroquinolones. In the early 1990s, cultures from keratitis, conjunctivitis and endophthalmitis cultures demonstrated organisms that were nearly 100 per cent susceptible to this class of antibiotics, but by the early 2000s this had dropped by nearly 50 per cent for keratitis and conjunctivitis, and by nearly 100 per cent for endophthalmitis. Similar trends exist regarding coagulase-negative staphylococcal endophthalmitis.”

ANTIMICROBIAL PEPTIDES Present in keratocytes, antimicrobial peptides permeabilise cell membranes and can destroy cell walls. They also stimulate both innate and adaptive immune responses, cause autolytic enzyme release and block cell envelop synthesis. But can they be developed as new clinical antibiotics active against eye infections?

“Manufacturing these peptides is currently very expensive, although organic mimics or modular design may help. It may also be possible to produce in bacteria or plants, although degradation by proteases might remain a problem,” said Dr O’Brien.

One investigational agent, peptide antibiotic MX-226, has been shown to significantly limit catheter colonisation in phase IIIa clinical trials.

An alternative is brilacidin, a polymer-based antibiotic currently in human clinical trials. Brilacidin is a small, defensin-mimetic compound modelled after host proteins that is easy to synthesise from commercial agents. It has demonstrated activity against MRSA, MRSE and VRE, he reported.

Brilacidin, with its long tissue half-life, has a rapid bactericidal effect that minimises the possibility of bacterial mutations and thus resistance. It is currently being developed by Cellceutix for ophthalmic indication.

“Not all of the structural characteristics of what makes a good peptide antibiotic are known at this time, so more research is needed to move development forward,” he concluded.

Terrence P O’Brien: tobrien@med.miami.edu EUROTIMES | DECEMBER 2015/JANUARY 2016

8â&#x20AC;&#x201C;11 September 2016

COPENHAGEN 16th EURETINA Congress

Bella Center, Denmark

www.euretina.org

OUTLOOK ON INDUSTRY

2007 - 2013

2014

$500-$800

$1.3

million investments

$12 billion

billion investments

global market growing 4 to 5% annually

STRONG MARKET

I

Rising volume and higher prices drive company value in $12billion global market. Howard Larkin reports

n early September 2015, Valeant Pharmaceuticals, Quebec, Canada, through its Bausch + Lomb subsidiary, bought Synergetics USA, which manufactures vitreoretinal and neurological microsurgical instruments, for US$198million – a premium of nearly 50 per cent over the firm’s closing stock price the day before.

What drove Valeant, one of the world’s most aggressive players in medical business acquisitions, to such an offer? Steady growth in ophthalmic procedure volume worldwide along with higher prices per procedure, as patients pay more out-of-pocket for premium services, Brian Scullion MD told the Ophthalmology Futures Forums, Barcelona 2015.

ATTRACTIVE MARKET Ophthalmology is currently a $12billion global market, growing four to five per cent annually, with about three per cent of that increased procedure volume, said Dr Scullion, Managing Director and Partner at investment bank William Blair & Company, Chicago, USA. Blair, which advised Synergetics in the Valeant transaction, is one of the most active investment banks in ophthalmology.

Rising income outside Europe and the USA is also driving growth. “As more people get access to the resources necessary to purchase advanced medical services, one of the things they tend to spend it on is ophthalmology,” Dr Scullion said.

Proliferation of advanced technology is also increasing volume, as procedures such as LASIK and premium intraocular lenses (IOLs) become common.

Refractive error correction and vitrectomy are currently the fastest growing segments.

Pricing also makes ophthalmology more attractive to investors, Dr Scullion said.

“Ophthalmology is somewhat unique in that we see patients going out-of-pocket for premium care.” In most other healthcare segments governments cap prices for advanced services.

Brian Scullion MD

Ophthalmology is somewhat unique in that we see patients going out-of-pocket for premium care

“It’s a trend that shows no sign of abating and it leads to sufficient profits to generate continued innovation, which for the foreseeable future makes this an area of high interest for investors,” Dr Scullion added.

The consolidated nature of the ophthalmic community also makes it attractive, Dr Scullion said. Where selling to primary care physicians requires marketing to hundreds of thousands of individuals, and hospital-based specialists face purchasing committee hurdles, the smaller number of ophthalmologists making their own buying decisions makes it easier to market ophthalmic products.

RISING INVESTMENT Ophthalmology’s growth potential has produced a surge in venture capital investment, Dr Scullion said. From 2007 to 2013, investments in ophthalmic companies ranged from $500million to $800million with an average deal between $10million and $16million. In 2014, that jumped to a total of $1.3billion with an average of more than $28million.

Venture capital investments drive innovation that makes smaller firms attractive acquisition targets, Dr Scullion said. The three large firms currently dominating the global ophthalmic device market, Novartis/Alcon, Abbott Medical Optics and Valeant/ Bausch + Lomb, and Allergan, which remains a big ophthalmic pharmaceutical player, acquired 15 firms in the last five years, including Optimedica, LenSx and Technolas.

But the big players are highly selective in their acquisitions, leaving initial public offerings (IPOs) as another route to cashing in on innovation, Dr Scullion said. In 2014, 10 US medical device companies went public, finally exceeding the 2007 level of eight, after six years with no more than two new offerings. Another seven went public so far this year.

However, the IPO market is also highly selective, with companies at a commercial stage and sales of $20million or more annually doing best, Dr Scullion noted. With 2014 sales of $40million, Glaukos, whose June 2015 IPO Blair underwrote, is a good example.

At the end of October, the firm had a market capitalisation of about $700million, providing a good return to investors. But it took 10 years and $200million in investment to get there.

Overall the future looks very bright, Dr Scullion concluded.

“I would encourage everyone to continue developing these new products, because there very clearly is a market for innovative products.”

Brian Scullion: bscullion@williamblair.com EUROTIMES | DECEMBER 2015/JANUARY 2016

37

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40

EYE ON HISTORY

A RICH HISTORY Prof Andrzej Grzybowski looks at Greece’s impressive

heritage in the development of ophthalmology

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here is hardly a European country with as rich a history in medicine and ophthalmology as Greece. Democritus first described the eye around 450BC. Later, Hippocrates of Kos, Herophilus of Chalcedon, Erasistratus of Chios (who firstly described the retina) and Galen contributed greatly to the development of eye anatomy and pathology.

In modern times, Greek ophthalmologists have also been responsible for many important innovations.

ANDREAS ANAGNOSTAKIS (1826–1897) Prof Andreas Anagnostakis was famous for the modification of the ophthalmoscope, which led to a great advancement in the design and use of the original ophthalmoscope invented by Hermann von Helmholtz.

Born in 1826 on the small island of Antikythera in Greece, he graduated from the medical faculty of Athens University in 1849, after which he pursued his training in Paris and Berlin, under Prof Desmarres and Prof Von Graefe respectively.

His modification of the original Augenspiegel von Helmholtz was published in 1854 in the French language. His instrument was called the ‘ophthalmoscope’, a word derived from the Greek words ‘οφθαλμός’ (ophthalmos = eye) and ‘σκοπός’ (skopos = observer).

It was hand-held, gathered light with a small concave mirror and had a central viewing hole. This publication was also the first systematic study in ophthalmoscopy including descriptions and illustrations of the normal and pathological retina.

Since then the word ophthalmoscope and ophthalmoscopy increased in popularity until they were adopted in the international ophthalmological community.

Dr Benediktos Adamantiades

Anagnostakis returned to Greece in 1854 and became the first director of the newly founded University Eye Hospital in Athens (Ophthalmiatreion).

In his classical work Study in Optics by the Ancient Greeks, published in 1879, he noted that the ancient Greeks were generally successful in the interpretation of natural phenomena and natural laws despite the lack of support by experiment or practical application.

Studying the ancient writings he found, for example the basic law governing the reflection of light when the reflected ray lies in the plane of incidence of the incident ray, the knowledge of the focus and the straight lines under which the objects reflected in flat and spherical mirrors are seen.

In his other work The Medicine of Aristophanes, published in 1891, he investigated every medical subject mentioned in Aristophanes’ plays. In The Antiseptic Methods of the Ancients, published in 1889, Anagnostakis proved the great extent of the ancient medical knowledge concerning asepsis and antisepsis as presented in the work of Hippocrates, Galen and Paulus Aeginitis.

BENEDIKTOS ADAMANTIADES (1875–1962)

Prof Andreas Anagnostakis

EUROTIMES | DECEMBER 2015/JANUARY 2016

Dr Benediktos Adamantiades was another famous Greek ophthalmologist. Born in 1875 in Proussa, Asia Minor (now known as Bursa, Tukrey), he studied medicine in the University of Athens and had the

chance to attend the lectures of Prof Anagnostakis, which aroused his interest in ophthalmology.

After his graduation in 1896, he had to work as a general practitioner in Proussa for about 10 years due to financial problems, before leaving for Paris, where he specialised in ophthalmology. After World War One he returned to Proussa and was elected president of the Greek community of the city, where he became involved with the re-establishment of Greek health administration and Greek language schools for minors and adults.

Later, he started to practise as an ophthalmologist in Athens, and in 1924 he was appointed Director of Ophthalmology at the Department of the Refugee Hospital of Athens.

During the annual meeting of the Medical Society of Athens on 15 November 1930, Adamantiades presented “A case of relapsing iritis with hypopyon”, a 20-year-old man, with the three cardinal signs of a new clinical entity, the nowadays so-called Adamantiades-Behcet disease (recurrent iritis, genital ulcers and arthritis). In 1946, Adamantiades reported on two further patients and defined thrombophlebitis as the fourth major sign of this disease. The first classification of the disease was also presented by Adamantiades in 1953, when he described the ocular, mucocutaneous and systemic forms in a systemic review.

He pointed out that the disease can occur for years as a monosymptomatic or oligosymptomatic disorder and that eye involvement and severe prognosis are more common by men than women.

In 1958, he published his last work on the neurologic complications of this disease. Apart from AdamantiadesBehcet disease, Adamantiades described the interstitial keratitis in trachomatic patients as a bacterial infection, and worked on marginal corneal degeneration, posterior vitreous detachment, the measurement of ocular pressure, as well as the pathogenesis of glaucoma.

Andrzej Grzybowski MD, PhD: Department of Ophthalmology, Poznan City Hospital, Poland; Department of Ophthalmology, University of Warmia and Mazury, Olsztyn, Poland; Department of Ophthalmology, Klinikum Chemnitz, Academic Hospital of the Universities of Leipzig and Dresden, Germany

OPHTHALMOLOGICA

OPHTHALMOLOGICA VOL: 234 ISSUE: 4

SELECTIVE RETINA THERAPY Selective retina therapy (SRT), including retreatment if necessary, might be a valuable treatment alternative for central serous chorioretinopathy (CSC), even in chronic-recurrent cases, the results of a new study suggest. The two-centre trial included 10 patients with acute CSC and 16 patients with chronic-recurrent CSC. All underwent SRT with a prototype laser system with adjustable pulse duration. In patients with acute CSC, all had completely resolved fluid and mean visual acuity (VA) increased from 76.6 ETDRS letters to 85.0 ETDRS letters three months after SRT. In the 16 patients with chronic-recurrent CSC, subretinal fluid was absent in three (19 per cent) and leakage had stopped in six (38 per cent) but VA improved only slightly, from baseline 71.6 to 72.8 ETDRS letters. Among six patients with persistent leakage who underwent repeat SRT, subtretinal fluid resolved in five patients (83.3 per cent) after only 25 days. C Framme et al, “Selective Retina Therapy in Acute and Chronic-Recurrent Central Serous Chorioretinopathy”, Ophthalmologica 2015; 234:177-188.

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ANTI-VEGF AND ARTERIAL THOMBOEMBOLIC EVENTS The findings of an in vitro study indicate that exposure of platelets to ranibizumab or bevacizumab does not increase platelet activation and aggregation, which are critical processes in the pathogenesis of arterial thromboembolic events. However, high levels of bevacizumab may prevent platelet activation, which may explain the increased risk of bleeding associated with high doses of the anti-VEGF agent. In the study, platelets were isolated from healthy volunteers and exposed to different concentrations of ranibizumab, bevacizumab or their solvents for 10 or 30 minutes prior to the addition of TRAP (25μM), PAR-4-AP (25μM) or thrombin (0.02U/ml). All ranibizumab concentrations as well as the bevacizumab concentration of 3.0μg/ml had no influence on platelet activation and aggregation. On the other hand, the highest level of bevacizumab caused a downregulation of platelet activation markers. B Sobolewska et al, “Different Effects of Ranibizumab and Bevacizumab on Platelet Activation Profile”, Ophthalmologica 2015; 234:195-210.

INTRA-ARTERIAL CHEMOTHERAPY Intra-arterial chemotherapy (IACT) in eyes with retinoblastoma is efficient and repeatable and reduces the need for enucleation and radiotherapy with limited toxicity, a retrospective study indicates.

A total of 56 eyes of 46 consecutive patients (30 males and 16 females) were included in the study. The enucleation-free survival rate following IACT was 56.7 per cent after a median follow-up time of 11.9 months (range 0.27-27.6 months). C Akyüz et al, “IntraArterial Chemotherapy for Retinoblastoma: A Single-Center Experience”, Ophthalmologica 2015; 234:211-217.

SEBASTIAN WOLF Editor of Ophthalmologica The peer-reviewed journal of EURETINA

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EUROTIMES | DECEMBER 2015/JANUARY 2016

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GET TO THE SOURCE Become an ASCRS member to receive the latest clinical advances, research, and information on issues affecting your practice.

YEAR-ROUND EDUCATION Annual meetings, clinical reports, legislative and regulatory resources, and the ASCRS MediaCenter (surgical videos, symposia, and paper sessions)

COMMUNITY Daily online discussions in eyeCONNECTIONS

TOOLS Post-refractive IOL and Barrett Toric Calculators, Toric Results Analyzer, and more online tools

PUBLICATIONS Journal of Cataract & Refractive Surgery, Ophthalmology Business magazine, and EyeWorld News magazine OB Cover_July 2015-DL.qxp_Layout 1 7/15/15 10:00 AM Page 1

Tribute to Robert Sinskey, MD — P. 16 The latest on mydriatic agents — P. 26 Pearls for MIGS success — P. 42

KEY FUNCTIONALITIES IN AN OPHTHALMOLOGY EHR P. 8

A GUIDE TO INVISIBLE LEADERSHIP P. 14

digital.eyeworld.org

digital.OphthalmologyBusiness.org

Featuring …

Femto cataract clinical update Evolution of laser cataract surgery — P. 44 Femtosecond cataract laser upgrades — P. 46 Experiences around the world — P. 48 Forgoing the femto laser — P. 50 Embracing the technology — P. 52

in

se rt

USA

The news magazine of the American Society of Cataract & Refractive Surgery

July 2015

Vol. 41 No. 5 • May 2015

ad ve rt

Journal of Cataract & Refractive Surgery

TM VOL. 20, NUMBER 7 July 2015

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

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

Elsevier

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

— P. 28

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

The honey bee colony: A model for practice success

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

MAY 2015 Volume 41, Number 5

JCRS_v41_i5_COVER.indd 1

P. 24

An ASCRS Publication

START YOUR MEMBERSHIP TODAY. ascrs.org

ESASO

ADVANCED LEARNING If you are a talented postgraduate, consider ESASO’s advanced educational programme for 2016

T

he ESASO training modules offer exciting opportunities to learn from world-leading faculty, to expand your collegial network and to reach a new level in your professional skills. ESASO’s modules for young ophthalmologists have become an internationally recognised success in recent years.

“In 2015, we organised 10 modules in different countries, which 320 participants attended altogether. We awarded the prestigious one-year ESASO fellowship to two aspiring ophthalmologists, out of 55 applicants,” said Borja Corcóstegui, President of the ESASO Foundation and Scientific Council.

Feedback from students as well as from faculty has been enthusiastic overall. One of many similar student statements summarised the ESASO experience: “It has been an awesome experience, with participants from all over the world. It was a pleasure and a privilege to learn from colleagues from all corners of the world. A dense timetable in a relaxed but full of enthusiasm atmosphere.”

2016 EDUCATIONAL PROGRAMME As in recent years, the entire field of ophthalmology is covered

by ESASO'S advanced five-day modules. These cutting-edge courses offer unique opportunities to learn in close contact with primary experts, as well as to team up with aspiring colleagues from various countries. The stateof-the-art facilities include wetlabs and the most innovative technology. And soon there will be a state-of-the-art laboratory, “The ESASO LAB of the Future”. An example of a typical ESASO Module was the fully booked course in January 2015, dedicated to oculoplastic surgery in Valletta, Malta.

The programme directors Ramón Medel and Borja Corcóstegui Luz María Vásquez, from Spain, together with faculty from Belgium, Germany and UK President, ESASO Foundation provided insights into orbital, lacrimal and ophthalmic plastic surgery. Theoretical and practical training covered a broad spectrum of anatomical and physiological, diagnostic and therapeutic subjects: from facial nerve palsy to eyelid and orbital tumours, from upper and lower eyelid blepharoplasty to trauma and fractures management.

An ESASO Course Series book on that topic can be ordered online at the ESASO website. The module and its faculty received excellent feedback. Generally, both experienced and starter surgeons in oculoplastic surgery could find pearls for themselves in this module.

The one-year ESASO Fellowship offers doctors the opportunity to acquire hands-on surgical expertise at a prestigious affiliated institution and to learn from globally-renowned ophthalmologists. To apply go to: www.esaso.org/fellowships The ESASO educational programme is open to all young ophthalmologists who have completed residency training and work in ophthalmic hospital departments or clinics. Become a part of the ever-growing ESASO family. Visit our website at www.esaso.org to find out more and take your ophthalmological expertise to the next level!

www.esaso.org

EUROTIMES | DECEMBER 2015/JANUARY 2016

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JCRS

JCRS HIGHLIGHTS

VOL: 41 ISSUE: 9 MONTH: SEPTEMBER 2015

ic atr s i d Pae smu

GEL STENT FOR GLAUCOMA

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A novel gel stent combined with phacoemulsification reduced intraocular pressure (IOP) and medications without significant complications in patients with open-angle glaucoma and cataract.

A non-randomised prospective clinical trial enrolled 37 eyes of 37 patients with a mean preoperative IOP of 22.4mmHg on a mean of 2.5 medications. Two patients were intolerant to medications and were not on topical therapy before surgery. Three patients had previous cyclodestructive procedures. No patient had previous incisional glaucoma surgery. Patients received one of two models of a gelatine stent (Xen140 and Xen63) at the time of cataract surgery without mitomycin-C. Twelve months postoperatively, the mean IOP was reduced to a mean 15.4mmHg on a mean of 0.9 medications (P < .0001). This resulted in a qualified success of 85.3 per cent, and a complete success rate off medications of 47.1 per cent. There were no failures. A Sheybani et al, JCRS, "Phacoemulsification combined with a new ab interno gel stent to treat open-angle glaucoma: Pilot study", Published online 15/10/15.

BLUE LIGHT SPECIAL

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

www.wspos.org

Do blue light-filtering (yellow-tinted) intraocular lenses (IOLs) make a difference in terms of fundus autofluorescence over time? Japanese researchers compared imaging studies in patients who received blue blocker IOLs or conventional colourless ultraviolet light-filtering IOLs. The prospective study enrolled 52 eyes with yellow-tinted IOLs and 79 eyes with conventional colourless IOLs. Abnormal fundus autofluorescence did not develop or increase in the yellow-tinted IOL group over a two-year period. However, progressive abnormal fundus autofluorescence developed or increased in 12 eyes (15.2 per cent) in the colourless IOL group. New drusen, geographic atrophy, and choroidal neovascularisation were observed mainly in the colourless IOL group. H Nagai et al, JCRS, "Prevention of increased abnormal fundus autofluorescence with blue light– filtering intraocular lenses", Published online 12/10/15.

ADD-ON IOL FOR AMD A new IOL with a central magnifying portion that is implanted in the ciliary sulcus of pseudophakic eyes shows promise for improving near vision in patients with AMD. Eight patients with advanced AMD received the macular add-on IOL (Scharioth Macula Lens A45SML).

Near vision improved in seven eyes and was stable in one eye. The corrected near visual acuity improved by 4.4 lines with the macular add-on IOL at 15cm versus with glasses at 40cm. It improved by 2.1 lines with the macular add-on IOL at 15cm versus with glasses at 15cm. Distance vision was stable in all eyes. No intraoperative or postoperative complication occurred.

G Scharioth, JCRS, "New add-on intraocular lens for patients with age-related macular degeneration", Volume 41, Issue 8,1559–1563.

THOMAS KOHNEN European editor of JCRS

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

EUROTIMES | DECEMBER 2015/JANUARY 2016

INDUSTRY NEWS

INDUSTRY

NEWS

MOBILE SOLUTION The US Food and Drug Administration (FDA) has granted approval for use of the Ziemer FEMTO LDV Z8 in the USA. “The FEMTO LDV Z8 was launched in Europe and selected Asian countries in mid-2014, with adoption steadily increasing since that time. It is the first truly mobile femtosecond laser solution for refractive, cornea and cataract procedures to be performed on an all-in-one system,” said a spokeswoman for Ziemer Ophthalmic Systems AG. Zeimer say the FEMTO LDV Z8 uses unique technology that provides precision in the cornea and power in the lens, with use of adjustable pulse energy combined with a high repetition rate to provide a precise capsulotomy and lens fragmentation. www.femtoldv.com

FLACS INSTRUMENTS I/A INSTRUMENTS FOR FEMTO LASER ASSISTED CATARACT SURGERIES WITH DISTALLY OPEN CANNULA TO REMOVE FRAGMENTS WITHOUT PHACO POWER Medicel‘s new I/A cannula is available in 20G and 21G with a 30° bevel tip. The bevel tip has rounded edges to enhance safety during surgery.

FEMTOSECOND LASER PLATFORM Heidelberg Engineering has signed a new agreement with Valeant to continue to supply the swept-source optical coherence tomography (OCT) module for the VICTUS® Femtosecond Laser Platform, commercialised under the Bausch + Lomb/Technolas brand. The VICTUS® Femtosecond Laser Platform is used for cataract and corneal applications.

“Heidelberg Engineering delivers its advanced sweptsource OCT module, which allows for real-time visualisation during every step of the surgery, from docking through planning and treatment,” said a company spokeswoman.

“The swept-source OCT module features high-quality images at video frame rate. It provides excellent imaging contrast and sensitivity for the autorecognition of key landmarks (pupil, lens, anterior and posterior capsule), boosting surgeons’ confidence and control during surgical procedures,” she said. www.heidelbergengineering.com | www.valeant.com

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EUROTIMES | DECEMBER 2015/JANUARY 2016

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EYE ON TECHNOLOGY

DESCEMET’S DETACHMENT Rhegmatogenous, tractional, bullous and complex, and a new technique – relaxing descemetotomy.

Dr Soosan Jacob reports keratoplasty (DMEK) or due to loculated blood. A BDD is intentionally achieved in Anwar's big bubble technique.

LASSIFICATION OF DESCEMET’S DETACHMENT: Descemet’s detachment (DD) is most commonly seen postoperatively and has classically been treated by injecting air or long-acting gas into the anterior chamber (AC) to appose Descemet’s membrane (DM) against the overlying stroma. This is sometimes combined with stab incisions in the overlying cornea to drain supraDescemetic fluid (SDF).

However, though this works in the vast majority of cases, there are specific situations when this is not effective. I have described a classification for DD based on etio-pathogenesis, clinical features, optical coherence tomographic, intraoperative features and also described a management protocol for these detachments based on this classification. Analogous to retinal detachment, DD may be classified as – rhegmatogenous DD, tractional DD, bullous DD and complex DD. I have also described a new surgical technique called relaxing descemetotomy which can be used in a few select situations of tractional or bullous DD.

RHEGMATOGENOUS DESCEMET’S DETACHMENT (RDD): This includes detachments secondary to tear, hole or dialysis of the DM from its attachment at Schwalbe's line. Though tear is the most commonly seen variant (insertion of blunt instruments/intraocular lens in phaco), hole (microperforation in deep anterior lamellar keratoplasty) and dialysis of DM at Schwalbe's line (complication during trabeculotomy, viscocanalostomy, punch insertion in trabeculectomy or with peripheral extension of descemetorhexis during endothelial keratoplasty) may also occur.

RDD is seen as an undulating membrane clinically and are freely mobile on irrigation with balanced salt solution (BSS) during surgery.

EUROTIMES | DECEMBER 2015/JANUARY 2016

COMPLEX DESCEMET’S DETACHMENT (CDD): This type of DD features DM macrofolds/ rolls/scrolled edges and combinations of other variants. These may be seen more frequently while learning DMEK secondary to large, improperly repositioned RDD.

ANTERIOR SEGMENT-OCT:

Tractional Descemet’s detachment managed with relaxing descemetotomy. A: Preoperative picture shows a TDD with the DM adherent to the iris. B: AS-OCT shows the detached DM

TRACTIONAL DESCEMET’S DETACHMENT (TDD): This is less common and is caused by traction on or foreshortening of DM secondary to inflammation/fibrosis or its incarceration in a wound/graft-host junction in penetrating keratoplasty/ peripheral anterior synechiae or suture. The DD is seen as taut and stretched out. These are not freely mobile on irrigation with BSS.

BULLOUS DESCEMET'S DETACHMENT (BDD): This is seen as a convex bulge of DM into the AC in the absence of DM break or traction. This is commonly due to introduction of fluid (BSS/viscoelastic/ air/blood) in the supra-Descemet’s space during viscocanalostomy or cataract surgery. A possible presentation may be as a localised island of DD in an otherwise attached graft after DM endothelial

Overlying corneal oedema may make visualisation of the DM difficult in DD. Anterior segment-optical coherence tomography (AS-OCT) is therefore very useful for detecting and classifying DD. A rhegmatogenous DD is seen as an undulating linear hyperreflective signal, whereas a tractional DD is seen as a straight taut linear signal with two points of attachment. In tractional DD, the arc length of the detached DM is shorter than that of the overlying cornea, whereas in rhegmatogenous DD these are equal. A bullous DD is seen as a convex hyperreflective signal on AS-OCT, whereas a complex DD shows complex folds, scrolls, adhesions etc.

MANAGEMENT OF DD: Classifying DD appropriately is important as treatment differs. All DDs require internal air/gas tamponade (pneumodescemetopexy) and SDF drainage.

However, a tractional DD also requires relief or removal of the element of traction to allow the DM to settle on to the stroma.

RELAXING DESCEMETOTOMY: This is a technique described by the author wherein careful small incisions are made on the DM in a can-opener, circumferential pattern in the periphery outside the optic zone. Relaxing descemetotomy relieves traction forces and foreshortening of the DM in a procedure similar to that of relaxing retinotomy described by

EYE ON TECHNOLOGY

PROGNOSIS: The final clarity achieved by the cornea depends not only on whether the DM reattaches, but also on the functionality and count of the endothelial cells. Manoeuvres such as repositioning of graft or relaxing descemetotomy may lead to varying levels of endothelial loss and therefore, I do not recommend these in cases with small, localised DD where the patient is asymptomatic. Similarly, in cases where the endothelium is unhealthy and unlikely to recover, it is preferable to perform an endothelial keratoplasty rather than a relaxing descemetotomy or repositioning.

CONCLUSION:

C: Day 1 postoperative appearance after releasing adhered DM from iris and pneumodescemetopexy. D: Seven months postoperative picture showing a cleared cornea. E: AS-OCT image showing an attached DM and non-oedematous cornea

Machemer in 1979 for tractional retinal detachment to address peri-retinal traction and retinal foreshortening. This is done under pressurised air infusion through an AC maintainer via an air pump in order to perform a controlled surgery. A 26-gauge needle bent upwards similar to a reverse Sinskey at its tip as well as at mid-shaft is introduced into the AC and relaxing descemetotomy incisions are made. The number and extent of the incisions are determined during surgery by assessing the degree of foreshortening. Relaxing descemetotomy incisions break the stress forces acting on the DM, relieving its tautness enabling an air or gas bubble

to appose the now lax DM against the overlying stroma. External drainage alone without relaxing descemetotomy does not appose the DM to the overlying stroma because of the DM foreshortening.

A bullous DD requires an outlet for either internal drainage of the SDF by means of descemetotomy incisions or external drainage by stromal stab incisions.

Postoperatively, a YAG Descemetopuncture may also be tried. Treatment for complex DD is individualised to the case and could require observation, re-DMEK/re-PDEK with same or different graft, Descemet’s stripping automated endothelial keratoplasty (DSAEK) or penetrating keratoplasty.

Rhegmatogenous DD is the most commonly seen form of DD, however tractional DD, bullous DD and complex DD are rarer types of detachments. These should be recognised to facilitate appropriate management in these rarer entities. The configuration of DD should be evaluated clinically as well as by AS-OCT to diagnose the type of DD. Relaxing descemetotomy may be an option in a few select cases.

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

Scan this QR code to view award-winning video from the ESCRS Video Awards 2013 (Amsterdam)

THE

TO BE REACH

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Advertise with the highest audited circulation for any ophthalmic news magazine in Europe 59 per cent of our readers surveyed in an independent research survey have decision-making power when it comes to the purchase of surgical/medical equipment or supplies. A further 20 per cent are usually consulted before a final decision is made** * Average net circulation for the 10 issues circulated between 1 January 2014 and 31 December 2014. See www.abc.org.uk ** Results from the EuroTimes Readership Study 2011

EUROTIMES | DECEMBER 2015/JANUARY 2016

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CALENDAR Copenhagen

FEBRUARY 2016

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

↙

1–5 February Naples, Italy www.echography.com

LAST CALL

DECEMBER 2015/ JANUARY 2016

6th Emirates Society of Ophthalmology Congress 10–12 December Dubai, UAE www.eso-congress.org

13–17 January Naples, USA www.cstellingitlikeitis.com

10th EGS European Resident Glaucoma Course

6th EURETINA Winter Meeting 23 January Rotterdam, The Netherlands www.euretina.org

5–9 February Guadalajara, Mexico www.woc2016.org

25–27 February Rimini, Italy www.sitrac.it

XXXIV Congress of the ESCRS 10–14 September Copenhagen, Denmark www.escrs.org

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

42nd Annual EPOS Meeting

JUNE

12th EGS Congress

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

JULY

The European Association for Vision and Eye Research (EVER) Congress 2016

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

20th ESCRS Winter Meeting

OCTOBER

NEW Aegean Cornea 2016

MARCH

NEW 1st International Meeting Update on Optic Nerve Degeneration: a European Network 18–19 March Milan, Italy www.jaka.it

7th World Congress on Controversies in Ophthalmology

5–8 October Nice, France www.ever.be

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

AAO 2016

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

29th APACRS Annual Meeting 27–30 July Nusa Dua, Bali www.apacrs.org

SEPTEMBER

16th EURETINA Congress

31 March–3 April Warsaw, Poland www.comtecmed.com/cophy/2016

CONTACT

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

NEW 14th SOI International Congress

NEW XX National Meeting of the Italian Cornea Transplant Society (S.I.Tra.C)

EYE

SEPTEMBER

7th EuCornea Congress

6–10 May New Orleans, USA www.ascrs.org

↙

15–16 January Geneva, Switzerland www.eugs.org

4–8 May Manama, Bahrain www.meaco.org

ASCRS 2016

WOC 2016 World Congress of Ophthalmology

26–28 February Athens, Greece www.escrs.org

Cataract Surgery: Telling It Like It Is

MAY

Middle East Africa Council of Ophthalmology (MEACO) XIII International Congress

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

STUDIO INTERVIEWS with leading ophthalmologists EXCLUSIVE TO EUROTIMES! ADVANCES IN OCULAR GENETICS Dr David Granet interviews Dr Alex Levin

Available at www.eurotimes.org/eyecontact and the EuroTimes App

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Please refer to the product Summary of Product Characteristics for full details.

Product Name: IKERVIS® 1 mg/mL eye drops, emulsion. Composition: One ml of emulsion contains 1 mg of ciclosporin and 0.05mg cetalkonium chloride as an excipient. Please refer to the Summary of Product Characteristics (SmPC) for a full list of excipients. Indication: Treatment of severe keratitis in adult patients with dry eye disease, which has not improved despite treatment with tear substitutes. Dosage and administration: IKERVIS® treatment must be initiated by an ophthalmologist or a healthcare professional qualified in ophthalmology. The recommended dose is one drop of IKERVIS® once daily to be applied to the affected eye(s) at bedtime. Response to treatment should be reassessed at least every 6 months. To reduce systemic absorption, advise patients to use nasolacrimal occlusion and to close the eyelids for 2 minutes after instillation. If more than one topical ophthalmic product is used, 15 minutes should separate their administration. IKERVIS should be administered last. Contraindications: Hypersensitivity to any of the ingredients. Active or suspected ocular or peri-ocular infection. Warnings and Precautions: Use with caution in patients with a history of ocular herpes . Contact lenses: Patients wearing contact lenses have not been studied. Monitor carefully inpatients with severe keratitis . Contact lenses should be removed before instillation of the eye drops at bedtime and may be reinserted at wake-up time. Concomitant therapy: Use with caution in patients with glaucoma, especially in those receiving concomitant beta-blockers which are known to decrease tear secretion. Immune system effects: Medicinal products which affect the immune system, including ciclosporin, may affect host defences against infections and malignancies. Contains cetalkonium chloride which may cause eye irritation. Interactions with other medicinal products: Coadministration with eye-drops containing corticosteroids may potentiate effects on the immune system. Pregnancy and Breast Feeding: Not recommended in women of childbearing potential not using effective contraception or during pregnancy unless the potential benefit to the mother outweighs the potential risk to the foetus. Benefits of treatment must be weighed against the benefits of breast feeding. Driving and using machines: Moderate influence on the ability to drive and use machines. If blurred vision occurs on instillation, the patient should be advised to not drive or use machines until their vision has cleared. Undesirable Effects: Consult SmPC for full details. The most common adverse reactions in clinical studies were eye pain, eye irritation, lacrimation, ocular hyperaemia and eyelid erythema.

Patients receiving immunosuppressive therapies including ciclosporin, are at an increased risk of infections. Special Precautions for Storage: Do not freeze. After opening of the aluminium pouches, the single-dose containers should be kept in the pouches in order to protect from light and avoid evaporation. Discardany opened individual single-dose container with any remaining emulsion immediately after use. Package quantities and basic NHS cost: 30 x 0.3ml single-dose containers £72.00. Product Licence Holder: Santen Oy, Niittyhaankatu 20, 33720 Tampere, Finland (PL 16058/0012) (EU/1/15/990/001 & 002) Date of Authorisation: March 2015 Legal Category: POM Date of last revision of Prescribing Information: 07/07/2015 IKERVIS® is a registered trademark of Santen Pharmaceuticals Co., Ltd. Job code: STN 0617 IKV 00004b 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 Santen UK Limited (Email medinfo@santen.co.uk or telephone: 0845 075 4863).

1 3

Lallemand F et al. J Drug Deliv 2012: 604204 2 SANSIKA study, Santen Data on File 0001 SANSIKA study, Santen Data on File 0002

Date of preparation: September 2015 Job code: STN 0717 IKV 00019f(eu)