EuroTimes Dec 2017 - Vol 22 Issue 12 | Jan 2018 - Vol 23 Issue 1 by EUROTIMES

SPECIAL FOCUS CATARACT & REFRACTIVE RETINA

GUT BACTERIA MAY HAVE AN IMPACT ON THE DEVELOPMENT OF AMD

CORNEA

DALK PROVIDES STABLE LONG-TERM VISUAL AND REFRACTIVE OUTCOMES Dec 2017 | Vol 22 Issue 12 Jan 2018 | Vol 23 Issue 1

GLAUCOMA

DIAGNOSING AND MANAGING GLAUCOMA IN MYOPIC EYES

Stressless. It’s touchless. SmartSurf ACE – the smoother way

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Publisher Carol Fitzpatrick Executive Editor Colin Kerr Editors Sean Henahan Paul McGinn Managing Editor Caroline Brick Content Editor Aidan Hanratty Senior Designer Lara Fitzgibbon Designer Monica De Iscar Circulation Manager Angela Morrissey Contributing Editors Howard Larkin Dermot McGrath Roibeard Ó hÉineacháin Contributors Maryalicia Post Leigh Spielberg Gearóid Tuohy Priscilla Lynch Soosan Jacob Colour and Print W&G Baird Printers Advertising Sales Amy Bartlett ESCRS Tel: 353 1 209 1100 email: amy.bartlett@escrs.org

Published by the European Society of Cataract and Refractive Surgeons, Temple House, Temple Road, Blackrock, Co Dublin, Ireland. No part of this publication may be reproduced without the permission of the managing editor. Letters to the editor and other unsolicited contributions are assumed intended for this publication and are subject to editorial review and acceptance. ESCRS EuroTimes is not responsible for statements made by any contributor. These contributions are presented for review and comment and not as a statement on the standard of care. Although all advertising material is expected to conform to ethical medical standards, acceptance does not imply endorsement by ESCRS EuroTimes. ISSN 1393-8983

CONTENTS

A EUROPEAN OUTLOOK ON THE WORLD OF OPHTHALMOLOGY

SPECIAL FOCUS CATARACT AND REFRACTIVE 4 We present the results of the groundbreaking PREMED study

6 Dr Boris Malyugin

highlights strategies for cataract surgery in high-risk eyes

7 Ray tracing for IOL

power calculation offers important advantages

10 Everything you ever wanted to know about manual small incision cataract surgery – Part 3

14 JCRS highlights

FEATURES CORNEA 16 Orphan drug for

Acanthamoeba keratitis enters phase III clinical development

17 DALK procedure provides stable longterm visual and refractive outcomes

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www.eurotimes.org

RETINA 19 Gut bacteria may have an impact on the development of AMD

20 Gene therapy and robotic systems pave the way for new treatments and techniques

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22 Anti-VEGF monotherapy remains insufficient for all DME patients

23 Many types of implants are now available for eyes with macular disease

24 Ophthalmologica update

PAEDIATRIC 30 Optical coherence

tomography is major tool in paediatric ophthalmology

31 Herpes simplex virus

GLAUCOMA 25 Researchers debate the future of glaucoma medical therapy with sustained release technology

26 Diagnosing and managing glaucoma in myopic eyes

27 The link between ocular

blood flow and glaucoma remains controversial

in children requires aggressive treatment

REGULARS 32 Outlook on industry 35 Book reviews 37 Random thoughts 38 Industry news 39 Calendar

OCULAR 28 Social media is a must for any ophthalmologist in private practice

29 Certain eye pathologies can show links to rheumatoid and gastro diseases

As certified by ABC, the EuroTimes average net circulation for the 10 issues distributed between 01 January 2016 and 31 December 2016 is 43,593.

Supplement Dec 2017/Jan 2018

Included with this issue... Laboratoires Théa supplement

SIMPLIFIED MANAGEMENT OF THE CATARACT PATIENT

Laboratoires Théa Satellite Symposium XXXV Congress of the ESCRS 8 October 2017 Lisbon, Portugal

EUROTIMES | DECEMBER 2017/JANUARY 2018

EDITORIAL A WORD FROM OLIVER FINDL MD

QUALITY IN RESEARCH

Study outcomes pave way for first evidence-based clinical guidelines to prevent CME after cataract surgery in diabetic and non-diabetic patients

he ESCRS PREvention of Macular EDema after cataract with the Serbian Society of Cataract and Refractive Surgeons, surgery (PREMED) study is the first international, from 9-11 February 2018. multi-centre, randomised, controlled clinical trial The Young Ophthalmologists Programme on Friday, 9 specifically designed to answer questions relating to the February, will once again feature the very popular “Learning from prevention of CME after cataract surgery in diabetic and the learners” interactive session on cataract surgery for trainees, non-diabetic patients. where young ophthalmologists can The study outcomes pave the way for the first evidencepresent their own video cases. The PREMED Study based clinical guidelines to prevent CME after cataract As always, I am very grateful to surgery in diabetic and non-diabetic patients. my co-chairpersons Simonetta presentation was one of In this issue of EuroTimes, we are pleased to Morselli and Kaarina Vannas, who the highlights of this year’s announce the results of the study. These results were will discuss these cases with the ESCRS Congress, which was presented by Rudy MMA Nuijts MD, PhD, Professor of trainees and also present their own Ophthalmology at the University Eye Clinic Maastricht pearls of wisdom. attended by more than UMC+, the Netherlands, and lead investigator of the Finally, a quick reminder to all 9,800 delegates from PREMED Study, and his colleague Laura Wielders MD, of our YOs that the very popular 120 countries at the XXXV Congress of the ESCRS in Lisbon, Portugal. John Henahan Writing Prize is now On behalf of the ESCRS, I would like to congratulate open for entries for 2018. The topic Prof Nuijts, Dr Wielders and all of the research team for the essay is ‘Do We Need a for their excellent work on this groundbreaking study. One Randomised Controlled Clinical Trial in Cataract Surgery?’ of the features of this study was that it was an independent The winner will receive a €1,000 travel bursary to attend the study, funded by the ESCRS, without the backing of the 36th Congress of the ESCRS in Vienna, Austria, and further pharmaceutical industry. information is available on: www.escrs.org. Of course, we rely on, and are grateful for, the support of Finally, as we look back on the old year and look forward to the industry in helping to fund research, but it is also gratifying to note next 12 months, I would like to wish all readers of EuroTimes a that it is possible for centres like University Eye Clinic Maastricht very happy and prosperous 2018. to carry out such a major trial together with several study sites throughout Europe. The PREMED Study presentation was one of the highlights of this year’s ESCRS Congress, which was attended by more than 9,800 delegates from 120 countries. As my friend and colleague ESCRS president Professor David Spalton pointed out, the record attendance was a testimony to the Society’s mission of bringing the very best in high-quality clinical research and education to its members. I am also glad to note that the YO programme at the annual congress in Lisbon was very well received by delegates and that it Dr Oliver Findl is Secretary of the ESCRS, Chairperson of the continues to go from strength to strength. ESCRS Young Ophthalmologists Committee, and Chief of the We are now looking forward to the 22nd ESCRS Winter Department of Ophthalmology, Hanusch Hospital, Vienna, Austria Meeting, which will be held in Belgrade, Serbia, in conjunction

MEDICAL EDITORS

Emanuel Rosen Chief Medical Editor

José Güell

Thomas Kohnen

Paul Rosen

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

EUROTIMES | DECEMBER 2017/JANUARY 2018

I/A

SPECIAL FOCUS: CATARACT & REFRACTIVE

PREMED study highlights benefit of combination treatment to prevent CME.

combination of a topical corticosteroid and a nonsteroidal anti-inflammatory drug (NSAID) is more effective than either agent alone in reducing the risk of developing cystoid macular edema (CME) after cataract surgery in non-diabetic patients, according EUROTIMES | DECEMBER 2017/JANUARY 2018

Dermot McGrath reports to the results of the ESCRS PREMED European study presented at the XXXV Congress of the ESCRS in Lisbon. The ESCRS PREvention of Macular EDema after cataract surgery (PREMED) study is the first international, multicentre, randomised, controlled clinical trial specifically designed to answer questions relating to the prevention of CME after cataract surgery in diabetic and non-diabetic patients.

The study outcomes pave the way for the first evidence-based clinical guidelines to prevent CME after cataract surgery in diabetic and non-diabetic patients. â&#x20AC;&#x153;CME remains one of the most prevalent postoperative complications in cataract surgery and especially in the diabetic population, where the incidence can be as high as 31%,â&#x20AC;? said Rudy MMA Nuijts MD, PhD, Professor of Ophthalmology at the University Eye Clinic Maastricht UMC+,

SPECIAL FOCUS: CATARACT & REFRACTIVE the Netherlands, and lead investigator of the PREMED Study. “This landmark study in over 1,000 patients will give us the foundation to draw up concrete evidence-based recommendations for clinical guidelines to prevent the occurrence of CME after cataract surgery in patients with and without diabetes,” he said.

ESCRS PREMED study investigators pictured at the XXXIV Congress of the ESCRS in Copenhagen

Dr Nuijts said that the rationale for the study stemmed from the lack of any real consensus regarding the optimal means of preventing the occurrence of CME after cataract surgery. “There is a wide disparity in opinion about the most effective anti-inflammatory drops to use. For instance, the American Academy of Ophthalmology (AAO) has stated that there is a lack of level one evidence supporting the long-term visual benefit of NSAID therapy when applied solely or in combination with corticosteroid therapy. By contrast, the American Society of Cataract and Refractive Surgery (ASCRS) says that there is compelling evidence of the efficacy of NSAIDs as an anti-inflammatory drug whether used alone, synergistically with steroids or for specific high-risk eyes. Our study sought to answer the question once and for all backed by clinical evidence,” he said. Dr Nuijts presented the results of the non-diabetic arm of the study while his colleague Laura Wielders MD focused on the implications for diabetic patients. Carried out at 12 surgical centres across the European Union, the PREMED Study was carefully designed to evaluate the effect of different preventive strategies on the occurrence of macular edema in 914 non-diabetic and 213 diabetic patients. All patients in the study received standard phacoemulsification for cataract and placement of an intraocular lens. Intraoperative and postoperative antibiotics were administered according to local protocols. In the non-diabetic population, the 914 patients received either a topical NSAID (bromfenac 0.09%) or a topical corticosteroid (dexamethasone 0.1%), or a combination of both. The primary outcome was the difference in central subfield mean macular thickness (CSMT) at six weeks postoperatively. Important secondary outcome measures included

Courtesy of Laura Wielders, MD

RATIONALE

A single subconjunctival TA injection effectively prevents the development of CME Laura Wielders MD postoperative corrected distance visual acuity (CDVA), as well as the incidence of CME and clinically significant macular edema (CSME) within six and 12 weeks postoperatively. At the six-week point, the CSMT was 9.6 microns higher in the dexamethasone group compared to the combination treatment group. Furthermore, the incidence of CSME within 12 weeks postoperatively was found to be lower in the combination treatment group, at 1.5%, compared to 3.6% for bromfenac alone and 5.1% for dexamethasone alone. “The conclusion is clear – patients treated with a combination of topical bromfenac 0.09% and dexamethasone 0.1% have a lower risk of developing clinically significant macular edema after cataract study compared to patients treated with either bromfenac or dexamethasone alone,” said Dr Nuijts.

DIABETIC OUTCOMES The 213 diabetic patients in the study were randomly allocated to receive no additional treatment, a subconjunctival injection with 40mg triamcinolone acetonide (TA), an intravitreal

CME remains one of the most prevalent postoperative complications in cataract surgery and especially in the diabetic population...

injection with 1.25mg bevacizumab or a combination of both after cataract surgery. The main outcomes were the difference in CSMT, CDVA, and the incidence of CME and CSME within six and 12 weeks postoperatively. The macular thickness and volume was found to be significantly lower in patients who received a subconjunctival injection with TA compared to patients who did not. No patient who received subconjunctival TA developed CME, while intravitreal bevacizumab had no significant effect on macular thickness. The study also found a significantly higher IOP in patients who received a TA injection, with six patients in the TA group recording an IOP higher than 25mmHg compared to none in the non-TA-treated group. Fifteen patients (7.1%) had an IOP increase of more than 5mmHg in the TA group, compared to one patient in the other treatment arms. “A single subconjunctival TA injection effectively prevents the development of CME after cataract surgery in diabetic patients. However, the risk of developing CME should be carefully weighed against the risk of developing an increased IOP,” concluded Dr Wielders. Rudy MMA Nuijts: rudy.nuijts@mumc.nl Laura Wielders: laura.wielders@mumc.nl Dr Oliver Findl discussed the details of the PREMED study with Dr Rudy Nuijts in an Eye Contact interview, http://player.escrs.org/

Rudy MMA Nuijts MD, PhD EUROTIMES | DECEMBER 2017/JANUARY 2018

SPECIAL FOCUS: CATARACT & REFRACTIVE

HIGH-RISK EYES Dr Boris Malyugin highlights strategies for tackling small pupils. Dermot McGrath reports

erforming cataract surgery on an eye with a small pupil remains technically challenging, but with the right tools and a clear strategy, the surgery can usually be completed successfully with little risk of complications, said Boris Malyugin MD, PhD, in his Binkhorst Medal Lecture at the XXXV Congress of the ESCRS in Lisbon. In a wide-ranging lecture that focused on the challenge of cataract surgery in high-risk eyes, Dr Malyugin, Professor of Ophthalmology and Deputy Director General at the S. Fyodorov Eye Microsurgery Federal State Institution in Moscow, Russia, paid tribute to predecessors such as Cornelius Binkhorst, whose work was instrumental in the development of intraocular lenses, and Svyatoslav Fyodorov, who designed the “Sputnik” pupil-fixated IOL. Turning to the question of high-risk eyes in cataract surgery, Dr Malyugin said that surgeons dealt with such cases every day. “The definition of high-risk eyes is very broad. Patients with local and/or systemic comorbidity, abnormal eye global anatomy, compromised capsules, increased lens hardness, zonular weakness and small pupils all come into this category,” he said. Small pupils pose a significant challenge even for skilled and experienced surgeons, and should not be taken lightly. “Poor mydriasis is not purely a geometrical issue and a question of accessing the lens – it is a lot more complex than that. A small pupil is an indicator of underlying pathologies within the eye, and is usually associated with systemic or local comorbidities, including but not limited to pseudoexfoliation syndrome, zonular weakness, blood-aqueous barrier disruption, and intraocular pressure spikes,” he said. Small pupils are also associated with an increased risk of complications such as iris trauma, capsular rupture, vitreous loss, inflammation, incomplete evacuation of the cortical material, and difficulties with placing and aligning the IOL in the bag, he added. “It was shown that every millimetre of pupil constriction increases our complication rate by 10%,” said Dr Malyugin. For many years, the standard pharmacological approach to small pupils was to use topical mydriatic agents, said Dr Malyugin, while more recently phenylephrine injections into the anterior chamber have become popular. While these compounds serve well for many patients, the pharmacological EUROTIMES | DECEMBER 2017/JANUARY 2018

Courtesy of S. Fyodorov Eye Microsurgery Complex Federal State Institution, Moscow, Russia

approach does not work all the time and may lead to unwanted ocular and systemic side-effects. Alternative strategies will be required to complete the surgery successfully in such cases, he said. If the intracameral injection does not provide sufficient mydriasis, one strategy is to proceed with viscodilation, posterior synechiolysis and pupilstretching techniques, if appropriate, said Dr Malyugin. Dissecting posterior synechiae will invariably improve mydriasis, and surgeons may also consider using mechanical expansion devices such as iris hoo`ks or pupil rings. Phacoemulsification is manageable in small pupils for an experienced surgeon, said Dr Malyugin. “By decreasing fluidic parameters, using phaco chop technique, by holding the instruments at the very centre of the anterior chamber using appropriate viscoelastic it is possible to avoid iris damage and complete surgery even with a constricted pupil of 4mm or even sometimes less in diameter,” he said. Iris hooks are effective at stretching the pupil, but they do have some significant drawbacks, said Dr Malyugin. “Iris hooks require multiple incisions and tend to overextend the pupil more than necessary. This can lead to damage to the iris tissue and to postoperative complications such as atonic pupil,” he said. “My personal preference,” Dr Malyugin said, “are the capsule hooks because they allow the surgeon not only to expand the pupil but also to stabilise the capsular bag in patients with compromised zonules.” Early in his surgical career, it was the frustration of working with firstgeneration pupil expansion rings that prompted Dr Malyugin to try to improve on those initial designs.

“These early expansion rings were not easy to work with and they could lead to complications with the surgery,” he said. This provided the initial inspiration for the Malyugin Ring (MicroSurgical Technology), a pupil expansion ring that would be easier to inject and position within the eye and that could be implanted with minimal trauma and removed through micro-incision. The Malyugin Ring consists of a presterilised single-use holder containing the ring and inserter and comes in two sizes: 6.25mm and 7.0mm. The secondgeneration version of the ring became available last year, said Dr Malyugin. Made from 5-0 polypropylene and implanted through a 2.0mm incision, the new ring is more flexible and gentler to the iris, and comes with a redesigned inserter that can easily fit through a 2mm clear corneal incision. “I still use the older versions of the ring for irises that are very fibrotic. In these cases I need a bit more force to expand the pupil. However, specifically for cases of intraoperative floppy iris syndrome (IFIS) the new ring works very well indeed,” he said. The Malyugin Ring can be inserted through regular incisions, as well as through the smaller microincisions used in MICS with a wound-assisted technique of insertion and removal. The device also works well in femtosecond-assisted cataract surgery, he said. These advantages and solid clinical results from the first trials of the device spurred phenomenal demand for the Malyugin Ring, with more than 1 million of the devices used in cataract patients since its introduction a decade ago. Boris Malyugin: boris.malyugin@gmail.com

SPECIAL FOCUS: CATARACT & REFRACTIVE

IOL POWER CALCULATION Ray tracing method offers several potential advantages. Leigh Spielberg MD reports

sing a ray tracing approach for IOL power calculation offers several important potential advantages over conventional approaches, reported Nino Hirnschall MD, PhD, Vienna Institute for Research in Ocular Surgery, Austria, at the XXXV Congress of the ESCRS in Lisbon, Portugal. “There are two potential advantages of a ray tracing-based IOL power calculation. First, more individual IOL power calculation is possible, for example in eyes with irregular cornea or those eyes who have previously undergone refractive surgery. Second, because it is a purely physical approach, no empirical ‘optimisation’ is required,” said Dr Hirnschall, referring to formula adjustments required for each surgeon. He presented the results of a study comparing the spherical equivalent outcomes of ray tracing-based IOL power calculation, using exact IOL design information, with the outcomes of a triple-optimised Haigis formula. The prospective study of 49 eyes of 49 patients used the IOLMaster 700 individualised eye model data, a physical lens position predictor and exact CT Asphina 409 MP IOL design information. “Ray tracing offers more detailed information of the cornea, as well as anatomical data instead of estimated lens position, both of which lead to a better refractive outcome,” said Dr Hirnschall. A potential limitation of the method is that exact IOL design information is needed Ray tracing resulted in a 2.5% increase in outcomes within 0.5D and 0.75D of target refraction, and a 10% increase in those coming within 1.00D. Prediction errors larger than 1.00D away from target refraction were lower in the ray tracing group (n=2) than in the Haigis group (n=13). “This shows promise not only for outcome performance, but also for surgeon and patient education, as well as management of patient expectations,” he concluded. Ray tracing involves calculating the path of a single “ray” of light passing through an optical system. In this case, retrospective ray tracing-based IOL power calculation was performed using retinal image quality metric (RIQM) criteria in an iterative procedure, and retinal image simulations were performed. In the ray tracing-based method, IOL selection is based on predicted visual acuity and a neuronal weighted RIQM. It involves ssOCT-based biometry and keratometry, using anterior and posterior corneal surfaces, corneal thickness, axial length, anterior chamber depth and white-to-white distance. Nino Hirnschall: nino. hirnschall@gmail.com

...more individual IOL power calculation is possible, for example in eyes with irregular cornea Nino Hirnschall MD, PhD

EUROTIMES | DECEMBER 2017/JANUARY 2018

22nd ESCRS Winter Meeting In conjunction with the Serbian Society of Cataract and Refractive Surgeons

9 – 11 February 2018 Sava Centar, Belgrade, Serbia Main Symposia Friday 9 February

Saturday 10 February

Traumatic Cataract: A Never Ending Story

Correction of Astigmatism in Cataract Surgery

Chairpersons: S. Barisic SERBIA B. Malyugin RUSSIA

Chairpersons: N. Reus THE NETHERLANDS F. Ribeiro PORTUGAL

Saturday 10 February

Sunday 11 February

Combined Cataract Surgery

Keep Calm: Stress Management During Cataract Surgery

17.00 – 18.30

11.30 – 13.00

Chairpersons: B. Djurovic SERBIA R. Nuijts THE NETHERLANDS

16.30 – 18.00

09.00 – 10.30

Organised by the Young Ophthalmologists Committee Chairpersons: V. Diakonis GREECE O. Findl AUSTRIA

Programme, Registration and Hotels available online

www.escrs.org

/ESCRS @ESCRSOfficial ESCRS

Other Highlights Friday 9 February

Saturday 10 February

 Basic Optics Course

 Cataract Surgery Didactic Course Part 2

 Cataract Surgery Didactic Course Part 1

 Cornea Didactic Course

 ESCRS/EuCornea Cornea Day



 Moderated Poster Session

 Refractive Surgery Didactic Course Part 1

 Refractive Surgery Didactic Course Part 2

Near Live Surgery Session

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

NEW

ESONT (European Society of Ophthalmic Nurses and Technicians) Saturday 10 February

Didactic Programme including:   

Biometry Infection Control OCT

 

Visual Acuity Visual Fields

Sunday 11 February  Serbian Society Symposium Developing Cataract and Refractive Surgery in a Developing Country

23 Surgical Skills

Training Courses



Book early to avoid disappointment

SPECIAL FOCUS: CATARACT & REFRACTIVE

NUCLEUS MANAGEMENT FOR

MSICS

Everything you ever wanted to know about manual small incision cataract surgery (MSICS) Part 3 â&#x20AC;&#x201C; Complications. Dr Soosan Jacob reports In the final part of this three-part series on MSICS, we will discuss complications and their management.

OUND CONSTRUCTION:

Buttonholing, wound gape and excessive astigmatism can occur secondary to dissecting a shallow tunnel (<50% scleral depth) or by not following the curve of the globe while dissecting. A buttonholed tunnel is not self-sealing and does not yield a stable anterior chamber (AC) for subsequent manoeuvres. Too deep a tunnel (>75% depth) can lead to premature entry. Unintentionally going full scleral thickness (100%) can cause uveal show, haemorrhage, scleral disinsertion and ciliary prolapse. Initiating and maintaining appropriate depth (50-75% scleral thickness) is therefore important. The globe is curved, and its curvature should be followed in forward and sideward dissection. The blade should be angled to follow the curvature forwards and the lateral edge of the blade should be tilted downwards slightly to match the sideward contour of the globe. The tunnel must be initiated on one side and continued over to the other side while maintaining the same plane. Starting

dissection at either end to try and meet in the middle can lead to inadvertent dissection in different planes with ensuing bridge of undissected tissue. Deep and superficial tunnels are managed by either reinitiating the dissection at the right plane or by creating a new tunnel at a different site. Reinitiating at a different plane should be done carefully to avoid a free tongue of scleral tissue that can compromise tunnel integrity. Premature entry can occur with deep dissection or if the crescent dissector is not angled more anteriorly at the limbus to follow the steeper corneal curvature. This leads to loss of valvular effect and iris prolapse with consequent iris chafing. Premature entry can also lead to iridodialysis, haemorrhage or, rarely, Descemetâ&#x20AC;&#x2122;s detachment. Suturing at the end of surgery is a must to avoid a leaking wound, hyphema and ectatic cicatrix. Too anterior a corneal entry leads to excessively long tunnel and difficulty in manoeuvring instruments. Ideal length of the tunnel is 2mm on the scleral aspect and 1.5mm on the corneal aspect. Significant against-the-rule astigmatism can arise from MSICS incisions unless care is taken. Remaining within the astigmatic neutral funnel and avoiding incisions too close to the limbus, shallow tunnels, large tunnels and straight tunnels can prevent this. Excessive wound distortion while expressing the nucleus or while inserting

the IOL can also cause wound gape and subsequent astigmatism. Holding the tunnel with forceps while dissecting can lead to loss of tunnel integrity. Gaping or leaking incisions require sutures.

NUCLEUS DELIVERY: The anterior capsular opening needs to be large enough to allow the nucleus delivery into AC. With a rhexis, it is important to make relaxing incisions before attempting to bring large, hard nuclei out. Failure to do this can cause zonulodialysis and damage to the entire bag. Excessive hydrodissection and hydrodelineation carry the risk of a capsular blow-out just as in phacoemulsification. Gentle, multiquadrant hydrodissection with intermittent decompression should be done. Softer nuclei can be hydroprolapsed, but attempting this with large, bulky nuclei through an intact rhexis can cause capsular blow-out. Repeated attempts to bring the nucleus into the AC, even with relaxing incisions, may cause capsular tear runaround, vitreous loss and nucleus drop. A small pupil hinders nucleus delivery. MSICS may therefore be better avoided in small rigid pupils and in cases of zonulodialysis or zonular weakness, especially by beginners. Difficulty may also be encountered while dialling the nucleus out of the bag. Repeated attempts without adequate viscoelastic protecting the corneal endothelium can result in corneal oedema and striate keratopathy. Once the nucleus is in the AC and ready to be expressed out, corneal endothelial protection should again be ascertained by injecting viscoelastic both above and below the nucleus.

NUCELUS EXPRESSION:

A long straight tunnel can leak and may require sutures

EUROTIMES | DECEMBER 2017/JANUARY 2018

A good internal corneal valve allows cortex aspiration without iris prolapse

Nucleus expression may become impossible if the tunnel length is inadequate. In this case, the tunnel has to be extended to either side with a keratome or needs to be

SPECIAL FOCUS: CATARACT & REFRACTIVE single piece or three-piece acrylic IOLs may be injected through an enlarged side port for in-the-bag IOL implantation if the rhexis is intact.

POST-OPERATIVE COMPLICATIONS:

A poorly constructed internal corneal valve leaks and allows iris to prolapse out

A leaking tunnel should be sutured and cortex aspiration done through a separate paracentesis in a formed AC

converted into an extracapsular incision by cutting either end of the incision. The width of the internal incision should be larger than the external incision in order to allow the nucleus to mould and exit out. Few undissected scleral fibres anywhere in the tunnel or premature entry with iris plugging the tunnel can also obstruct nuclear expression. In either case, the tunnel should be made complete and extended if required. An inferior iridodialysis with intracameral bleeding and hyphema can occur while attempting to deliver the nucleus with a vectis if the vectis is accidentally inserted under the iris instead of above it. This needs to be repaired through a Hoffman pocket using a double-armed 10-0 prolene suture. In case of a superior iridodialysis, the iris root can be sutured to the inner scleral

lip of the MSICS tunnel. Techniques like phaco-sandwich and phaco-fracture can cause collateral damage to the iris and endothelium because of the greater manipulations required within the AC.

CORTEX ASPIRATION: Attempting to aspirate cortex through the tunnel leads to shallowing of the AC, forward movement of posterior capsule and increased risk of posterior capsular rent. A separate side port should therefore be used for manoeuvres requiring a formed AC such as rhexis and cortex aspiration. Sub-tunnel cortex can be easily approached this way. Dialling the IOL within the bag can help dislodge residual small stubborn cortex. Single-piece or three-piece PMMA IOLs are implanted through the tunnel. Foldable

A leaking wound can cause a shallow AC and predispose to endophthalmitis. Severe against-the-rule astigmatism from wound gape may require opening the conjunctiva and suturing the incision. Increased iris manipulation can cause iritis and cystoid macular oedema. Corneal oedema, striate keratopathy and even corneal decompensation can arise from rough manipulations of the nucleus and instruments within the AC. 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 the live surgery

BIOMECHANICS MEETS TOMOGRAPHY H EY C O R VI S ST I just took a look at the tomography. These values call for caution. I don’t think I would operate.

H I P E N TAC AM The biomechanics looks good, though. The cornea is very stable. I don’t see any problem with operating.

O. K . TO G E TH E R N O W Tomography and corneal biomechanics together make the decision easier: Surgery could be an option.

Corvis® ST meets Pentacam®: Combined measurement results for a safe decision on surgery Benefit from the combination of biomechanical data from the Corvis® ST and tomographic data from the Pentacam®. Provide surgical care to more patients safely!

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Eurotimes ESCRS-Motiv Biomechanics 178x130 e 11.17.indd 1

14:18:422018 EUROTIMES | DECEMBER24.11.2017 2017/JANUARY

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Pentacam

TMS Placido

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12 ADVERTISING FEATURE

1.25

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0.25

ADVERTISING FEATURE

SPECIAL FOCUS: CATARACT & REFRACTIVE

JCRS SYMPOSIUM

Controversies

in Anterior

Segment

Surgery Monday April 16, 2018 1:00–2:30 pm

JCRS HIGHLIGHTS VOL: 43 ISSUE: 9 MONTH: SEPTEMBER 2017

LONG-TERM ADVERSE EFFECTS WITH PHAKIC IOL An ongoing concern with phakic IOLs involves long-term effects on endothelial cell loss. An international group of researchers assessed adverse device effects and annualised endothelial cell loss rate for up to 10 years after implantation of the Acrysof L-series Cachet phakic intraocular lens. The non-randomised study evaluated 638 patients (1,087 eyes) from previous clinical trials. This showed a persistent endothelial cell density decrease in some eyes that was larger than the annual rate expected with ageing. The mean central endothelial cell density change from baseline was -9.6% and -11.0% at six and seven years, respectively. Endothelial cell loss resulted in explantation in 3.1% of all eyes with the lens. Patients had no permanent vision loss. The most common adverse effects were peripheral iris adhesions in 5.2% of cases, corneal endothelial cell loss in 3.9% and IOL explantation in 3.4%. T Kohnen et al., JCRS, “Long-term safety follow-up of an anterior chamber angle-supported phakic intraocular lens”, Volume 43, Issue 9, p1163–1170.

HOW MANY POST-OPERATIVE VISITS ARE APPROPRIATE?

Moderators:

Nick Mamalis, MD Sathish Srinivasan, MD

Presbyopia-Correcting IOLs Surgical Correction of Aphakia in a 60-Year-Old Treating Inflammation After Intraocular Surgery

During the ASCRS Annual Meeting Washington, DC, USA

Many patients undergoing uncomplicated cataract surgery may not require a planned postoperative visit, a new study suggests. Investigators followed 1,249 patients seen during a one-year period. One group of patients (without comorbidity) had no planned postoperative visit, while a second group had a planned postoperative visit. Nine percent of patients initiated a postoperative contact, of whom 26% also had a scheduled visit. The reasons for the patient-initiated contacts were visual disturbance, redness and/or chafing, pain and anxiety. An evaluation of all medical records two years postoperatively found no reports of missed adverse events. The researchers conclude that it was possible to refrain from planned postoperative visits for patients having uncomplicated cataract surgery. I Westborg et al. JCRS, “Optimizing number of postoperative visits after cataract surgery: Safety perspective”, Volume 43, Issue 9, p1184–1189.

KERATOCONUS INNOVATIONS The ever-increasing popularity of laser refractive surgery makes the detection of corneal abnormalities extremely relevant. The accurate diagnosis of clinical or subclinical keratoconus is critical. Corneal topography is the primary diagnostic tool for keratoconus detection, and pachymetry data and corneal aberrations are also commonly used. However, corneal topography is not infallible. Therefore, complementary techniques should be used. These include corneal pachymetry to characterise the corneal thinning and aberrometry to characterise degradation of the corneal optics. Scheimpflug systems offer the possibility of obtaining topographic, pachymetric and aberrometric information simultaneously. OCT technology allows an accurate pachymetric characterisation. A Martínez-Abad et al., JCRS, “New perspectives on the detection and progression of keratoconus”, Volume 43, Issue 9, p1213–1227.

THOMAS KOHNEN European editor of JCRS

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EUROTIMES | DECEMBER 2017/JANUARY 2018

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CORNEA

SAFER TREATMENT Orphan drug enters phase III clinical development.

phase III clinical trial is now under way investigating the efficacy and safety of the orphan drug polyhexamethylene biguanide (PHMB) 0.08% ophthalmic solution (SIFI) as topical monotherapy for Acanthamoeba keratitis (AK). The study is being conducted by the Orphan Drug for Acanthamoeba Keratitis (ODAK) project, a European Commission-funded FP7 project led by the Italian-based pharmaceutical company SIFI. It has a randomised, quadruple-masked design and is comparing PHMB 0.08% plus placebo to current conventional care with PHMB 0.02% plus propamidine. Recruitment opened at Moorfields Eye Hospital, London, UK, on 8 August, 2017. Other participating centres are located in Southampton and Manchester in the UK, Milan and Venice in Italy, and Katowice, Poland. The study aims to randomise a total of 130 patients to treatment. John Dart MD, MA, Consultant Ophthalmologist at Moorfields Eye Hospital and Professor at the UCL Institute of Ophthalmology, is coordinating Principal Investigator for the phase III trial. “The trial is running smoothly. Just six weeks since its launch at our centre, six eligible patients have already agreed to enter,” he told EuroTimes. Patients with suspected AK will need to travel to one of the participating centres to enter the trial, explained Parwez Hossain MD, PhD, Consultant Ophthalmologist, Southampton General Hospital, who is the investigator at the Southampton centre. “Our early experience suggests, however, that more than 70% of patients with suspected AK will be found eligible for enrolment,” he commented.

ADDRESSING A THERAPEUTIC NEED The development of PHMB 0.08% as topical monotherapy for AK aims to provide better, safer treatment for this severe, sight-threatening infection. AK is a significant cause of unilateral visual loss in contact lens wearers. Earlier diagnosis portends a better outcome, but even with early diagnosis, AK management involves many months of treatment, often more than one year, with no guarantee of resolution. Additionally, current treatment regimens are quite toxic to the ocular surface,” said Dr Hossain. EUROTIMES | DECEMBER 2017/JANUARY 2018

Cheryl Guttman Krader reports

Courtesy of Parwez Hossain MD, PhD

Acanthamoeba keratitis presenting with ring abscess

“Currently, PHMB 0.02% is the most effective treatment for AK, but findings from preclinical studies and a human phase I volunteer study indicate that PHMB 0.08% monotherapy has low toxicity and is well tolerated. The ODAK study will establish whether PHMB monotherapy with this new formulation and higher concentration will can shorten the treatment time whilst causing less ocular surface toxicity than combination therapy with two drugs,” he explained.

PRACTICAL PROTOCOL The phase III study is also evaluating concomitant anti-inflammatory treatment and management of patients with comorbid bacterial infection. “Inflammatory complications of AK mandate the use of corticosteroid drops and oral non-steroidal anti-inflammatory drugs (NSAIDs) in up to 75% of patients. The risk-benefit of anti-inflammatory treatment has been controversial, but we reported in a retrospective study that it was not associated with worse outcomes when initiated after starting anti-amoebic therapy,” said Dr Dart. All ODAK investigators will use the same topical corticosteroid with the same oral NSAID for anti-inflammatory therapy, but the dosing can be adjusted according to patient response. Anti-inflammatory treatment can only be introduced after

three weeks of anti-amoebic therapy in patients not using any anti-inflammatory medications at study entry, and there are additional criteria about managing patients on existing anti-inflammatory treatment. “Standardising the anti-inflammatory therapy will reduce the variables we have to control for when analysing the outcomes and results in a coherent and simpler treatment protocol,” Dr Dart said. The inclusion of patients with bacterial co-infection in the trial recognises its presence in up to 20% of patients with AK. Antibiotic treatment for patients with active bacterial co-infection is also standardised. “We wanted this to be a real-world trial. Excluding individuals with bacterial co-infection would have left out a substantial group of AK patients for whom our results would be meaningless. Our overall treatment protocol is complex, but if it is effective, this study will give substantial guidance to clinicians worldwide regarding how to manage AK and provide a gold standard against which the results of modifications to treatment can be measured,” Dr Dart said. For more information about the trial please contact: odak-office@odak-project.eu. John Dart: j.dart@ucl.ac.uk Parwez Hossain: P.N.Hossain@soton.ac.uk

Corn

C o r n

DALK RESULTS PROVE SAFE

RETINA

European Society of Cornea and Ocular Surface Disease Specialists

DALK procedure provides stable long-term visual and refractive outcomes. Dermot McGrath reports

eep anterior lamellar keratoplasty (DALK) provides safe and stable long-term visual and refractive outcomes, with reduced rates of endothelial cell loss and a lower risk of graft rejection compared to penetrating keratoplasty (PK), Vincent Borderie MD told delegates attending the 8th EuCornea Congress in Lisbon. “DALK decreases the long-term endothelial cell loss, which results in a significant increase in long-term graft survival. There is also a lower incidence of glaucoma with DALK compared to PK, so I think the take-home message is that DALK is really a safer procedure than PK,” he said. Dr Borderie, in practice at the Quinze-Vingts Hospital in Paris, France, said that many surgeons hesitate before making the transition to DALK for corneal stromal disorders. “There is a learning curve with DALK. It is a difficult technique to master, it is time-consuming and it can be stressful for the surgeon,” he said. Despite these hurdles, improvements in DALK techniques over the past decade, as well as greater surgical familiarity with that particular approach, are resulting in a greatly reduced conversion rate to PK procedures, said Dr Borderie. While a variety of different DALK techniques are available, including dry dissection, hydrodissection, “big bubble”, air needle and cannula DALK, Dr Borderie said that in his experience the best results are obtained using Dr Anwar’s “big bubble” technique to treat bare Descemet’s membrane. When the big bubble approach is not feasible, manual dissection of the stroma is still a viable option, said Dr Borderie. “The most interesting development in this respect in recent years involves the use of intraoperative OCT, which allows the surgeon to control the depth of dissection and assessment of bare Descemet’s membrane,” he said. One of the key advantages of DALK is that it removes the central corneal stroma while leaving host corneal endothelium and Descemet’s membrane intact, said Dr Borderie. This results in less endothelial cell loss and ultimately a reduced risk of immune rejection. In one prospective study of 690 consecutive keratoplasties (448 PKs and 242 lamellar keratoplasties) for stromal disorders carried out between 1993 and 2013 by one surgeon, the graft survival was 93% for lamellar procedures and around 75% for PK after 240 months, said Dr Borderie. Another retrospective study by Dr Borderie of 142 consecutive DALK cases compared to 142 PK cases found an average five-year postoperative endothelial cell loss of 22.3% in the DALK group and -50.1% in the PK group. The longterm, model-predicted graft survival and endothelial densities were higher after DALK than after PK, he said. While DALK graft failures still occur due to infection and trauma, new technologies such as femtosecond-assisted DALK should help in the near future to reduce the failure rate even further, he concluded.

www.eucornea.org

Vincent Borderie: vincent.borderie@upmc.fr EUROTIMES | DECEMBER 2017/JANUARY 2018

th EURETINA

Winter Meeting

16–17 February 2018 InterContinental Hotel Budapest, Hungary In partnership with the Hungarian Society of Ophthalmology, this will be the first meeting hosted by EURETINA in Eastern Europe.

6 Clinical Sessions including: ∙ AMD ∙ Clinical Cases ∙ Diabetic Retinopathy

∙ Imaging ∙ Uveitis/Inflammation ∙ Vitreoretinal Surgery

All Delegate Registration €50 (Limited capacity) Exhibition & Sponsorship Opportunities Available

www.euretina.org

RETINA

GUT FLORA AND AMD Research explores link between gut bacteria and AMD. Dermot McGrath reports

he composition of the gut microbiome may have an impact on the development of age-related macular degeneration (AMD), thereby opening up potential new avenues of research and therapeutic strategies, according to Swiss researcher Martin S Zinkernagel MD, PhD. “We know that diet has an impact on the gut microbiome, which may constitute a link between nutrition and the development of AMD. The impact of specific bacterial species on the development of experimental choroidal neovascularisation is currently being investigated. Future treatments for AMD may well target the composition of the gut microbiome,” he told the 17th EURETINA Congress in Barcelona. The intestinal microbiome forms a complex ecosystem of up to 100 trillion microbes per individual, with the human body containing roughly as many bacteria as human cells, said Dr Zinkernagel, Bern University Hospital, Switzerland. “To date, more than 10,000 bacteria species have been identified in the gut, and there are approximately 100 times more genes in the gut microbiome than human genes, so there are a vast number of organisms residing there,” he said. The intestinal gut flora plays a major role in the degradation and digestion of nutrition and is a fundamental component of human physiology. Changes in the microbiome can trigger changes in human cellular activities and contribute to the development of metabolic diseases such as diabetes or atherosclerosis, said Dr Zinkernagel.

MULTIFACTORIAL DISEASE He noted that AMD is a multifactorial disease in which nutrition and genetics are known to play a role, although very few studies have specifically targeted the gut microbiome as a potential contributory factor to the progression of the disease. He said that one recent study, however, showed that highfat diets exacerbate choroidal neovascularisation in a mouse model by increasing the relative abundance of the phylum Firmicutes in the gut microbiome. To explore this link further, Dr Zinkernagel initiated a pilot study of 12 patients with neovascular AMD and 11 age-matched controls without AMD to establish whether the compositional and functional diversity of the intestinal microbiome is associated with neovascular AMD. After sequencing the intestinal metagenomes of both sets of patients, the results showed an enrichment of certain microbial genera, namely oscillibacter, anaerotruncus, eubacterium ventriosum and ruminococcus torques in AMD patients versus bacteroides eggerthii in controls. The next step for Dr Zinkernagel and his research team is to validate these results in a larger study. He concluded that the findings may ultimately open a significant field of research and therapeutic development if the observations lead to opportunities for beneficial modification of the microbiome to alter the course of the retinal pathology. Martin S Zinkernagel: martin.zinkernagel@insel.ch EUROTIMES | DECEMBER 2017/JANUARY 2018

RETINA

MODERN GENE THERAPY Genetic mutations in the retina can be addressed by gene therapy, while robotic systems promise new surgery techniques. Dermot McGrath reports

Courtesy of Robert MacLaren MD, PhD

Gene therapy using optical coherence tomography

ene therapy for inherited retinal diseases is currently being validated in several clinical trials, paving the way for a potential paradigm shift in the treatment of previously incurable eye diseases, according to Dominik Fischer MD, PhD. In a broad overview of the history and rationale for gene therapy, Dr Fischer told delegates attending the 17th EURETINA Congress in Barcelona that the retina, with its different cell populations, is an ideal target for gene replacement. “The retina is really quite uniquely susceptible to genetic mutations. A lot can go wrong genetically speaking, and there are a whole host of mechanisms that can be targeted by genetic mutations and can lead to blindness. These genetic mutations can potentially be addressed by gene therapy, and this is why it deserves interest,” he said. Gene therapy can work well in retinal disease stages where there is still photoreceptor function, said Dr Fischer, but it is less likely to deliver any benefit in late-stage retinal diseases where neither photoreceptor nor RPE cells are available to be transduced by gene therapy. In these cases, replacement strategies such as electronic implants or stem cell therapy are more likely to prove beneficial, he said. The history of gene therapy stems back to the 1940s and 1950s, when researchers came to realise that it is actually the EUROTIMES | DECEMBER 2017/JANUARY 2018

DNA that transports information that is useful and necessary for cells to have a physiological potential, said Dr Fischer. Later on, in the 1960s, investigators discovered that virus particles are very efficient in bringing DNA into cells. In ocular gene therapy as applied today, engineered viral vectors are used to bring specifically designed DNA into retinal cells that bring therapeutic benefit. In a separate presentation focused on the present challenges and future directions of gene therapy surgery, Professor Robert MacLaren FRCOphth, FRCS, said that robotic systems are likely to transform the way gene therapy is delivered into the eye. “The robot system that we have been using (developed by Preceyes BV) represents a great advance in gene therapy to deliver the adeno-associated viral vector containing the replacement gene. The advantage is that the movements are extremely still and precise and under the full control of the surgeon. This allows us to potentially deliver the injection over a much longer period rather than over a few seconds with manual injection,” he said. Prof MacLaren said that refinement of surgical technique represents the next key challenge for gene therapy. “I would say that the basic science has now been done in terms of gene therapy in the retina, but what we need to focus on now is the surgical technique of delivering the virus to make sure we get the same effects in humans that we have seen in the

basic science models so far,” he said. To inject the virus, the patient’s retina is first detached and then the virus is injected directly into the subretinal space. There is very little margin for error with injection, said Prof MacLaren. “If we don’t get the subretinal injection right, we get reflux, intravitreal leakage and an inflammatory response,” he said. The introduction of OCT microscopy into gene therapy surgery has greatly helped reduce the risk of over-stretching the retina, inducing inflammation and reducing the therapeutic effect, said Prof MacLaren. “This type of tech was not available even two years ago and this really has revolutionised the surgery to ensure that there is not too much stretching of the retina,” he said. While doubts have been expressed in some quarters about the long-term effectiveness of gene therapy treatment, Prof MacLaren said that the therapy has been shown to be effective up to at least a decade after surgery based on a single injection of the viral vector. “The evidence we have so far from the human trials supports what we have seen in all the animal models, which is that if done correctly in the correct dose with all the cells transduced in a retina that is not irreversibly damaged, then the gene therapy treatment will be permanent,” he said. Dominik Fischer: Dominik.Fischer@merton.ox.ac.uk Robert MacLaren: enquiries@eye.ox.ac.uk

18TH EURETINA

CONGRESS

VIENNA 20-23 SEPTEMBER

2018 www.euretina.org

RETINA

EARLY RESULTS Anti-VEGF monotherapy insufficient for all DME patients. Dermot McGrath reports

nly a minority of diabetic macular oedema (DME) patients that show limited initial visual improvement with anti-VEGF therapy can be expected to develop a clinically significant visual response with continued intensive anti-VEGF treatment and monitoring over the following one-to-three years, according to Anat Loewenstein MD, PhD. “For patients with a suboptimal visual response after the first three intravitreal anti-VEGF injections it may be appropriate to consider adjustments to the treatment regimen, as we know there is a very good chance that these patients will not derive any benefit from ranibizumab injections over the long term,” she told delegates attending the 17th EURETINA Congress in Barcelona. Dr Loewenstein, Professor of Ophthalmology and Deputy dean of the medical school at the Sackler Faculty of Medicine, Tel Aviv University, Israel, presented results on behalf of the EARLY (Early Anti-VEGF Response and Long-term efficacY) programme, a series of post-hoc analyses of data from the Diabetic Retinopathy Clinical Research Network’s (DRCR.net) Protocol I study of ranibizumab plus laser in DME. EARLY was initiated to explore the relationship between early and long-term anatomic and visual acuity responses to anti-VEGF therapy. Dr Loewenstein’s presentation focused on the strength of

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the association between visual acuity outcome after three monthly anti-VEGF intravitreal injections and visual acuity outcomes at one and three years, with particular emphasis on non-responders to treatment. The visit schedule for the first year of treatment was every four weeks, with years two and three depending on the treatment group. In the ranibizumab-treated groups, the visit schedule could be extended up to a maximum of 16 weeks, said Dr Loewenstein. At each visit, a decision was taken on retreatment based on an assessment of the timing of visit, visual acuity, central retinal thickness, laser treatment history, failure or futility criteria and investigator discretion. While the visual acuity results overall were excellent at five years, there was a subpopulation of patients who were not responsive to treatment, defined as patients who showed less than five letters’ improvement at 12 weeks (39.7%) compared to two other cohorts: five-to-nine letter improvement (23.2%), and more than 10 letters’ improvement (37.1%). The investigators also looked at anatomical parameters and identified 35% of patients that had less than 20% improvement in central retinal thickness (CRT) at week 12 after three Ranibizumab injections. Post-hoc analysis of the non-responder group found that eyes with less than a five-letter gain after three injections showed limited additional improvement for the study duration of three years. “After one year, one-in-four of these patients will move to the group showing more than two lines’ improvement, and after three years one-in-three of them will move to the same group. However, 50% of them will remain in the non-responder category. This means that if we just continue to inject anti-VEGF as per Protocol I, we inject without giving these patients a chance to improve,” she said. Similar results were also achieved when the investigators looked at the OCT parameters, said Dr Loewenstein. “Those eyes with less than 20% CRT improvement at 12 weeks were found to have less chance of obtaining good visual acuity. Their mean visual acuity at three years was lower than that of the patients who had more than 20% reduction in CRT at three months,” she said. A further sub-analysis of the eyes in Protocol I also looked at the duration of the oedema and the impact, if any, it may have on long-term visual acuity in patients with DME. “One-third of study eyes showed persistent oedema over the first year. Among eyes with the most persistent oedema at week 52, the oedema tended to persist over the second year in three-quarters of them, and this had a very important impact on the visual acuity,” she said. Patients with the greatest duration of oedema at week 52 had worse average vision improvement over the study duration. Eyes with the most persistent oedema gained significantly fewer letters at week 52, and their poorer visual acuity persisted at weeks 104 and 156. Anat Loewenstein: Anat Loewenstein MD, PhD anatl@tlvmc.gov.il

One-third of study eyes showed persistent oedema over the first year

RETINA

NEW LENSES FOR AMD Many types of telescopic and non-telescopic implants are now available for eyes with macular disease. Roibeard Ó hÉineacháin reports

atients with age-related macular degeneration (AMD) are now being treated with a range of intraocular lenses, but all have their specific limitations and potential complications, a recent review indicates. “We really need further independent clinical studies with longer follow-up data prior to the routine use of these implants,” said lead author Andrzej Grzybowski MD, PhD, MBA, University of Warmia and Mazury, Olsztyn, and Foundation for Ophthalmology Development, Poznan, Poland, whose study appeared in Graefes Archives of Clinical and Experimental Ophthalmology.

INTRAOCULAR TELESCOPES Dr Grzybowski and colleagues reviewed the literature for prospective and retrospective studies of implantable devices in the treatment of various stages of AMD. They found seven types of IOLs recommended for AMD: an implantable miniature telescope called the IOL-VIP System, the Lipshitz macular implant, the sulcus-implanted Lipshitz macular implant, the LMI-SI, the Fresnel Prism Intraocular Lens, the iolAMD and the Scharioth Macula Lens. He noted that telescope implants magnify the image projected on the retina and/ or skew the image away from the central scotoma. The most common designs are based on the Galilean telescope, consisting of two lenses with high positive and negative power, respectively. The implantable miniature telescope (IMT) enlarges patient’s central 20-24° field of view by up to three-fold. It is composed of a 4.4mm telescope with a PMMA base that sits in the capsular bag.

The Lipshitz implantable miniature telescope (IMT) following implantation in the eye

The IOL-VIP System consists of two IOLs, a high minus-power biconcave IOL in the capsular bag and a high plus-power biconvex IOL in the anterior chamber. The two PMMA lenses together provide a 1.3-fold magnification and shift the enlarged image towards the preferred retinal locus. The iolAMD is another double-implant system, but in this case the high pluspower lens is implanted in the sulcus. The high plus-power IOL has a hyper-asphericoptic that is slightly de-centred. The lenses provide a 1.2-fold magnification. Meanwhile, the Lipshitz macular implant (LMI), and sulcus-implanted Lipshitz macular implant (LMI-SI, now marketed as the Orilens, OptoLight) is based on a reflecting telescope, and combines a primary concave mirror and a secondary convex mirror within a normal IOL configuration. In addition to providing a 2.5-fold magnification, the LSI implants also provide normal unmagnified peripheral vision. There are also two lenses that operate on entirely different principles. These include the Fresnel Prism Intraocular Lens, which provides no magnification but instead displaces the retinal image to a healthy part of the retina. And finally, there is the add-on bifocal Scharioth Macula Lens (A45 SML, Medicontur), designed to provide near vision to the pseudophakic AMD patients while preserving normal peripheral vision.

RESULTS GENERALLY GOOD To date, the best researched is the IMT. In the two-year, prospective, 28-centre IMT-002 pivotal study, 90% of 217 patients achieved an improvement of two or more lines of ETDRS.

Central visual field projection

The Lipshitz implantable miniature telescope (IMT)

The most common complications for the IMT were corneal oedema iris damage/prolapse and capsular rupture. No complications were reported in the small series published regarding the IOL-VIP and the Scharioth macular lens. All patients with the LMI and LMI-SI had slight glare and a small proportion experienced difficulties with neuroadaptation. One patient who underwent monocular implantation of the iolAMD had diplopia. Dr Grzybowski noted that the implants differ in terms of the incision size required. The IMT requires a 10.0mm incision. The LMI LMI-SI and the IOLVIP require a 7.0mm incision, whereas the hydrophobic acrylic IOL AMD and the Scharioth lens can be injected with a standard injector system through a 3.0mm incision. He added that none of the lens-based telescopic implants are suitable for pseudophakic patients because they require implantation in the capsular bag. In contrast, the sulcus-implanted Scharioth lens and the LMI-SI can be implanted either at the same time as the conventional IOL or any time thereafter. Another important consideration is the amount of training and neuroadaptation required. For example, the IOL-VIP requires two weeks of preoperative training and three months of postoperative training, and some authors report that patients require three-to-six months of training after IMT implantation. “Much of the success will depend on the commitment and dedication of the patient towards these visual rehabilitation,” he added. For more details please see A Grzybowski et al. Graefes Arch Clin Exp Ophthalmol 255 (9), 1687-1696. 2017 Jul 24. Andrzej Grzybowski: ae.grzybowski@gmail.com EUROTIMES | DECEMBER 2017/JANUARY 2018

RETINA

OPHTHALMOLOGICA VOL: 238 ISSUE: 5

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PRE-OP SD-OCT CAN PREDICT VITREOLYSIS OUTCOMES Spectral domain optical coherence tomography (SD-OCT) can confirm the therapeutic morphological effect of ocriplasmin injections. In a series of 40 patients in a retrospective study who received intravitreal ocriplasmin, 13 of these 40 benefited from treatment. Statistical analysis revealed that higher baseline foveal thickness (p = 0.018) and non-tractional epiretinal membranes (p = 0.05) resulted in a worse outcome. Eyes with treatment success gained nine letters, compared to a gain of only one line in treatment failures. However, the researchers found no correlation between pre-injection SD-OCT findings and visual outcomes. C Wertheimer et al, “Impact of Preinjection Spectral Domain Optical Coherence Tomography Findings in the Use of Intravitreal Ocriplasmin in a Clinical Setting”, Ophthalmologica 2017, Volume 238, Issue 5.

MORPHOLOGICAL RESPONSE TO ANTI-VEGF MOST PRONOUNCED IN FIRST TWO WEEKS New research suggests that the greatest proportion of the morphological effects on the retina induced by intravitreal antivascular endothelial growth factor (anti-VEGF) injections in eyes with neovascular age-related macular degeneration (AMD) occurs within the first week after the injection. The prospective study involved 50 patients with active choroidal neovascularisation secondary to AMD. Twenty-two patients received bevacizumab, 15 received ranibizumab and 13 received aflibercept. Spectraldomain optical coherence tomography showed that mean central retinal thickness was 391.22µm at baseline, but was reduced by 26.15µm (p<0.001) after one week, by 12.54µm (p<0.001) after two weeks, but by only 3.52µm (p=0.09) after three weeks. Mean intraretinal layer thickness changed significantly only between baseline and week one (p<0.001). P Enders et al, “Early Changes of Retinal Morphology in Therapy of Neovascular Age-Related Macular Degeneration with Three Commonly Used Anti-VEGF Agents”, Ophthalmologica 2017, Volume 238, Issue 5.

AUTOLOGOUS BLOOD CONCENTRATE EFFECTIVE IN REFRACTORY MACULAR HOLE Re-vitrectomy with autologous platelet concentrate (APC) and gas is a very effective treatment in persistent macular hole after vitrectomy with ILM peeling and gas. The retrospective study of 75 eyes whose MH did not resolve following vitrectomy with ILM peeling and gas and underwent re-vitrectomy with gas and APC or whole blood. Closure rate after revitrectomy was 85.2% (52/61) in the APC group and 7.1% (1/14) in the WB group. Purtskhvanidze K et al, “Persistent Full-Thickness Idiopathic Macular Hole: Anatomical and Functional Outcome of Revitrectomy with Autologous Platelet Concentrate or Autologous Whole Blood”, Ophthalmologica 2017, Volume 238, Issue 5.

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

EUROTIMES | DECEMBER 2017/JANUARY 2018

GLAUCOMA

DRUG-DELIVERY SYSTEMS Researchers debate the future of glaucoma medical therapy with sustained release technology. Roibeard Ó hÉineacháin reports

hich of the sustainedrelease drug-delivery approaches now being developed for the treatment of glaucoma will prove to be the most successful five years? An expert panel debated this question at the 7th World Glaucoma Congress in Helsinki, Finland. James Brandt MD, of the University of California, Davis, USA, argued in favour of extraocular approaches, noting that it is the safest and most reversible means of drug delivery. In two-thirds of patients receiving IOP-lowering medications, the indication is either ocular hypertension (OHT) or early glaucoma. While some compromise in safety may be acceptable in eyes with more advanced disease, safety is the priority in eyes with early disease, particularly when one considers the generally slow rate of progression that is typical of the disease, he said.

NEW EXTRAOCULAR DRUG-DELIVERY DEVICE Topical medications are an extraocular approach that should work in theory. However, research indicates that around half of patients do not adhere to their regimens and identifying these patients can be difficult. An extraocular sustainedrelease delivery system could address the problem without sacrificing safety. One extraocular device that is currently in an advanced stage of development is the bimatoprost ocular insert. The ring-shaped device consists of a polypropylene core coated with bimatoprost-impregnated silicone. It is designed for placement beneath the eyelids in the conjunctival fornix. It is not bioabsorbable but is replaced every six months by the patient’s physician. Phase II results with the ocular insert indicate that it is safe, lowers IOP predictably and is well tolerated. In a study published in 2017 (Brandt et al,

Ophthalmology, ePub in press) with 144 patient-years of data, patients had consistent lowering of IOP for up to 19 months of follow-up. An important potential advantage of the ocular insert as a drug-delivery platform is that it can be impregnated with multiple agents; an insert combining bimatoprost and timolol is already in development. “After all, half of the patients in the Ocular Hypertension Treatment Study needed two or more drugs to achieve the Study’s modest IOPlowering goal of 20%,” said Dr Brandt.

THE BEST OPTION? Ingeborg Stalmans MD, Catholic University KU Leuven, Belgium, maintained that an intracameral sustainedrelease approach is most likely to prove successful in the medical treatment of glaucoma because it delivers medication directly and reduces the amount entering systemic circulation. She noted that poor adherence is not the only problem in current medical treatments for glaucoma. Bio-availability is also an important issue. She noted that the volume of a typical eye drop is 20-to-50μl, but pre-corneal space can only hold around 7.0μl. The excess either rolls down the cheek or enters systemic circulation through the nasolacrimal duct. In fact, only 1-to-5μl is absorbed by the eye. “Alternative drug-delivery systems might achieve a longer lasting, highly localised delivery with more accurate concentrations and fewer side-effects than topical administration,” Dr Stalmans said. She noted that Allergan has developed a modified version of the intravitreal Ozurdex implant, which contains a slowrelease formulation of bimatoprost rather than dexamethasone, and is designed for intracameral injection. Like the Ozurdex implant, it is biodegradable and therefore does not need to be removed. In a dose-ranging study, the bimatoprost implant provided rapid, sustained IOP

Alternative drug-delivery systems might achieve a longer lasting, highly localised delivery with more accurate concentrations and fewer side-effects than topical administration Ingeborg Stalmans MD

lowering with an overall reduction from baseline ranging from 7.2mmHg to 9.5mmHg, depending on the dosage, for 16 weeks. In addition, a proportion of the eyes with the implant continued to have significant IOP reduction at two years. A phase III trial is now under way and is expected to be completed in 2018. Dr Stalmans noted that the injections should prove acceptable from a patient’s perspective. She cited a study showing that 75% of patients are willing to undergo subconjunctival injections every three months. That study also showed that 86% of patients surveyed were willing to accept higher costs, and that patients who do admit to non-adherence and those who were on multiple medications were the most willing to accept repeated injections and increased costs. With regard to safety, she pointed out that that intravitreal injections have been shown to carry only a very small risk of endophthalmitis and have now become routine in the treatment of retinal disease. “Humans are clumsy and forgetful, imprecise and unreliable. High-tech drug-delivery systems are not, and this is why I believe that medications delivered through a sustained-release platform may particularly the intracameral route may be the future of ophthalmology.

INTRAVITREAL MAY BE THE BEST OPTION Concluding the debate was Uday Kompella PhD, University of Colorado, Denver, USA, who argued that intravitreal drug-delivery has many theoretical advantages over both extraocular and intracameral approaches. He noted that, like intracameral approaches but unlike extraocular approaches, intravitreal approaches deliver 100% of the drug into the eye. In addition, unlike intracameral approaches, intravitreal drug delivery presents no danger to the cornea. He added that there are already wellestablished biodegradable and nonbiodegradable slow-release systems for drug delivery to the vitreous humour, including a non-biodegradable system that allows for fluocinolone acetate to be administered once every three years. James Brandt: jdbrandt@ucdavis.edu Ingeborg Stalmans: ingeborg.stalmans@med.kuleuven.be Uday Kompella: uday.kompella@ucdenver.edu EUROTIMES | DECEMBER 2017/JANUARY 2018

GLAUCOMA

MYOPIA AND GLAUCOMA Careful examination and avoidance of trabeculectomy prescribed for moderate-to-high myopes with glaucoma. Roibeard Ó hÉineacháin reports

he diagnosis and management of glaucoma in eyes with moderateto-high myopia brings many challenges. Three leading glaucoma specialists shared their views on the optimum approach to such cases in a series of presentations at the 7th World Glaucoma Congress in Helsinki, Finland. Eyes with moderate-to-high myopia have an increased risk for glaucoma, but myopia can also sometimes masquerade as glaucoma. However, careful examination can distinguish between the two pathologies and ensure good treatment decisions, said Tin Aung PhD, FRCSed FRCSOphth, Singapore National Eye Centre and the National University of Singapore. “A concurrent diagnosis of moderateto-high myopia does not fundamentally influence diagnosis and medical treatment,” he noted. He pointed out that in the Blue Mountain Eye Study, myopia of -6.D or more was associated with an increased risk of glaucoma and the higher the myopia the higher the risk. On the other hand, in eyes with myopia, a tilted disk or peripapillary atrophy (PPA) may mimic glaucomatous optic neuropathy. The key to glaucoma diagnosis in such cases is the detection of progression, because if there is progression, glaucoma is most likely the cause. He therefore recommended serial disc photography and added that research suggests that macular OCT measurements of the ganglion cell complex (GCC) and macular retinal ganglion cellinner plexiform layer (GCIPL) may provide better glaucoma detection than standard retinal nerve fibre layer measurements. Regarding functional measurements, he noted that tilted discs and PPA in myopic eyes can themselves cause visual field defects.

However, as with serial disc photography, progression detected by repeated visual field tests, will reveal if it is glaucoma. He added that whether a glaucoma patient is myopic or not, the aim of treatment will be the reduction of IOP. However, if surgery is indicated, minimally invasive glaucoma surgery may pose less risk of hypotony maculopathy in moderateto-high myopes than would trabeculectomy.

CAVEATS IN DIAGNOSIS Ki Ho Park MD, PhD, Seoul National University, agreed that a concurrent diagnosis of moderate-to-high myopia should not influence medical treatment of glaucoma. However, he stressed that there are many potential pitfalls in the diagnosis of glaucoma in such cases. “A diagnosis of glaucoma in moderateto-high myopia patients is challenging because it is difficult to differentiate between glaucomatous changes and myopic changes. Disk tilt, peripapillary atrophy, chorioretinal atrophy and eyeball elongation make it difficult to detect glaucomatous structural change,” he said. He noted that eyes with moderate-to-high myopia typically have a large optic nerve head and an elongated disk with shallow cupping and extensive PPA. However, RNFL defects are less common than in glaucoma and, when present, the loss of thickness is more diffuse and less localised than it is in glaucoma. Sometimes the elongation of the myopic eye causes a temporal convergence of the superotemporal and inferotemporal RNFL, creating pseudo-RNFL defects by Optical Coherence Tomography (OCT), so-called “red disease”. Regarding treatment, Dr Park cited several studies showing that neither

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EUROTIMES | DECEMBER 2017/JANUARY 2018

the presence nor degree of myopia appear to have any impact on the rate of progression. Therefore, a concurrent diagnosis of moderate-to-high myopia should not influence the estimation of the target IOP, he said. However, when surgery is indicated, trabeculectomy should be avoided, since myopia raises the risk for hypotony maculopathy, particularly in patients with other significant risk factors, such as young age, male gender and low scleral rigidity. Robert Chang MD, Stanford University, concurred with Dr Park regarding the avoidance of trabeculectomy in highly myopic eyes. He also reminded that the secondary Tubes vs Trabs study showed that tubes performed as well as trabeculectomy in terms of IOP reduction, but with a lower incidence of persistent hypotony. However, he took the position that a concurrent diagnosis of moderate-to-high myopia does influence both diagnosis and medical treatment. Dr Chang included several case examples illustrating the point of how high myopia can distort OCT results as well as affecting response to filtering surgery, both of which are well documented in the literature. “We also have to be wary of peripheral retinal changes as well as myopic degeneration changes in high myopes, so it’s a good idea to consult with your retinal surgeon. If it’s a straightforward case, you may also want to perform cataract surgery sooner for the marked visual improvement it can bring in very high myopes,” he added. Tin Aung: aung.tin@snec.com.sg Ki Ho Park : kihopark@snu.ac.kr David Chang: tmenzies@stanford.edu

JOHN HENAHAN

CLOSING DATE FRIDAY 30 MARCH 2018

PRIZE 2018

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GLAUCOMA

PERFUSION PRESSURE The link between blood flow and glaucoma remains controversial. Roibeard Ó hÉineacháin reports

here is a broad accumulation of data from epidemiological studies suggesting that reduced ocular perfusion pressure is associated with an increased risk of glaucoma and glaucoma progression, said Leopold Schmetterer PhD, Singapore Eye Research Institute, Singapore. However, the degree of association between the two conditions is still in question and complex, he told the 8th World Glaucoma Congress. Dr Schmetterer noted that ocular perfusion pressure is generally calculated by subtracting intraocular pressure, as a proxy for venous pressure, from brachial arterial blood pressure, as a proxy for ocular arterial blood pressure. The same type of calculation also provides an estimation of the systolic and diastolic ocular perfusion pressure. “There are many limitations to the way we calculate ocular perfusion pressure, and generally its relationship to ocular blood flow is relatively unclear,” Dr Schmetterer cautioned.

Keep learning. Stay relevant.

REDUCED OCULAR PERFUSION PRESSURE AS RISK FACTOR Most of the prevalence studies regarding glaucoma suggest that low ocular perfusion increases the risk of having the disease. Those studies include the Baltimore Eye Study, the Blue Mountain Eye study, the Singapore Malay Eye Study and the Los Angeles Latino Eye Study. One exception is the Beijing Eye study, which showed no link between the two conditions. Regarding incidence, Dr Schmetterer noted that the Barbados Eye Study showed a clear relationship between the nine-year incidence of glaucoma and low ocular perfusion pressure at baseline. In the Rotterdam Eye study, the relationship was less pronounced and only reached significance among participants receiving antihypertensive medication. In the Thessaloniki Eye study, low diastolic ocular perfusion pressure resulting from antihypertensive treatment was associated with increased cupping and a decreased optic disc rim area, even in eyes without glaucoma. In the Early Manifest Glaucoma Trial (EMGT), patients with low systolic ocular perfusion pressure (<125 mmHg) had a 1.39- and 1.42-fold higher risk of progression over the entire period of the trial, in a univariate and a multivariate analysis, respectively (p=0.038). Fluctuation of ocular perfusion pressure also appears to influence the risk of progression. In a retrospective study carried out in Korea, a 1.0mmHg increase in ocular perfusion pressure fluctuation was associated with 27.2% greater chance of glaucoma progression. Dr Schmetterer noted that the data are not unequivocal. A meta-analysis published in the American Journal of Ophthalmology indicates that both high and low blood pressure are associated with increased risk of open-angle glaucoma (Zhao et al, AJO 2014, 158:615-627). “If you pool together all the studies there is a relatively clear indication that both very low and very high blood pressure or perfusion pressure is associated with the disease,” he added.

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Leopold Schmetterer: leopold.schmetterer@meduniwien.ac.at EUROTIMES | DECEMBER 2017/JANUARY 2018

OCULAR

A FRIVOLOUS NECESSITY Practice Management

ESCRS

& Development

22–26 September 2018 Vienna, Austria

CALLING ALL MARKETERS!

WIN A €1000 BURSARY. ESCRS Practice Management and Development Marketing Case Study Competition Submission Deadline Monday 30 July 2018 For further details visit: www.escrs.org

Grow Your Practice

Manage Your Business

Social media can be a key tool for ophthalmologists. Aidan Hanratty reports

hat can one say about social media in 2017? Despite its ubiquity, it can still prove difficult to wield as a marketing tool. ESCRS social media manager Caroline Anderson addressed delegates at the XXXV Congress of the ESCRS in Lisbon at a special Practice Management and Development Programme with a view to explaining the pitfalls and benefits of social media for ophthalmologists. Her presentation began with a quote from Diana DeBrohun, a social media coach, which pointed out that even going back to the telephone in 1876, “tools for connecting with others have often been considered frivolous before being accepted as a necessity”. It’s a decade since Apple launched the era of the smartphone with the iPhone, and despite its naysayers social media has only grown since then. Today, it’s an essential part of any business strategy. Anderson honed in on some examples of how doctors can make themselves heard in a busy marketplace. One of these was Florian Kretz MD, who uses Facebook to communicate with patients and highlight work he’s doing, both professional and humanitarian. Her next example was a US-based Surgical Retina Fellow and blogger named Steven M Christiansen MD, who has successfully built his own brand under the moniker ‘Eye Steve’. His site covers new and interesting stories that he hopes will “educate, inform, and inspire all things eye”. Recent entries covered tips on how to view the solar eclipse safely in the US, as well as a breakdown of the story involving a woman who had reportedly lost 27 contact lenses in her eye. He also appeared on local news radio ahead of the eclipse, giving him more of an opportunity to expand his reach. Most interestingly for Anderson, Eye Steve once lightheartedly tweeted “The Richard Lindstrom, MD just added me on LinkedIn. Whoa. #starstruck”, showing the power of social media as a networking tool. “There are no boundaries, just opportunities,” said Anderson. What these doctors do best is provide good content, “the Yin to the Yang of social”. This may be news from conferences such as the ESCRS Congress, special offers at their clinic or even news about new members of staff. “People do business with and use the services of people they like and trust, so social media can help you connect and engage with these potential customers.” Ultimately, using social media is a marathon and not a sprint, as it takes time to build your network or following. Anderson pointed out that doctors wouldn’t use a machine in their practice if they were unfamiliar with it, so they shouldn’t use a social media platform to market their practice without a proper understanding of it how it works. There’s no time like the present, however: “The longer you wait to get on social media, the more behind the competition you will be.” Caroline Anderson: caroline.anderson@escrs.org

EUROTIMES | DECEMBER 2017/JANUARY 2018

OCULAR

EYE DISEASE LINKED TO GUT Certain eye pathologies can show links to rheumatoid and gastro diseases. Priscilla Lynch reports

phthalmologists need to be more aware of the links between certain eye pathologies and rheumatoid and gastroenterological conditions, and refer these patients to the relevant specialties, the Irish College of Ophthalmologists 2017 Annual Conference heard. Recurrent uveitis can indicate that a patient has an underlying autoimmune disease such as ankylosing spondylitis, while gut-related symptoms in eye patients can be indicative of inflammatory bowel disease (IBD), cautioned Doug Veale MD, Consultant Rheumatologist, St Vincent’s University Hospital, Dublin, who discussed managing inflammatory disease with biologic medications. He highlighted the link between uveitis and spondyloarthropathies (SpA) – anterior uveitis is the most common extra-articular manifestation of SpA. Prof Veale promoted the usefulness of DUET (Dublin Uveitis Evaluation Tool), an algorithm developed to assist earlier diagnosis of SpA by ophthalmologists in acute anterior uveitis. “It [DUET] is very simple and focuses on the presence or absence of inflammatory back pain. So, if patients have back pain that is worse in the morning time and gets better with exercise, that is the key,” Prof Veale told EuroTimes. Discussing the various biologics, he concluded that monoclonal antibodies seem to have a higher level of efficacy than the fusion proteins in treating uveitis and SpA, with promising new agents in the pipeline. Also speaking during the conference was Richard Farrell MD, Consultant Gastroenterologist, Connolly Hospital, Dublin, on the diagnosis and management of gut inflammation in ophthalmology patients. He recommended that doctors ask patients about symptoms outside their own disease areas, e.g. do eye patients have gut symptoms, etc. Suspect IBD symptoms in ophthalmology patients can include chronic diarrhoea, abdominal cramps, rectal bleeding, weight loss, anaemia and raised inflammatory markers (WBC, ESR, CRP). However, the majority of these patients will have IBS, haemorrhoids and gastroenteritis rather than underlying IBD, he explained. Ocular manifestations are more common in female gastroenterology patients, those with colitis and patients with other extra-intestinal manifestations, said Prof Farrell. Episcleritis, scleritis and anterior uveitis are the most common ocular manifestations of underlying IBD, and treatment of the underlying IBD can cure the eye pathology, he noted, adding that steroids and anti-TNF therapies are effective for chronic scleritis and uveitis. Prof Farrell also highlighted that IBD therapy can cause ocular pathology, including posterior subcapsular cataracts, glaucoma and opportunistic ophthalmic infections induced by systemic or topical steroids, optic neuropathy, nystagmus, ophthalmoplegia caused by cyclosporine and anti-TNF therapies, while methotrexate can build up in tears and cause conjunctival/corneal irritation.

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Richard Farrell: rfarrell@rcsi.ie Douglas Veale: douglas.veale@ucd.ie EUROTIMES | DECEMBER 2017/JANUARY 2018

PAEDIATRIC OPHTHALMOLOGY

OCT AND PAEDIATRICS OCT proves its mettle in paediatric ophthalmology. Dermot McGrath reports

ptical coherence tomography (OCT) is quickly becoming an increasingly valuable tool in paediatric ophthalmology, thanks to its noninvasive characteristics and the enhancement of image resolution and acquisition speeds, according to Araceli Trueba Lawand MD, PhD. “Fourier domain OCT technology, eye tracking and handheld devices have all aided in the clinical implementation of OCT in paediatric ophthalmology. Large amounts of research are being done in this field but not all have conclusive clinical implications as yet,” Dr Trueba Lawand told delegates attending the European Society of Ophthalmology (SOE) Congress in Barcelona. While OCT has the potential to play an important role in the monitoring of various ocular diseases in children, its scope is currently limited by the lack of normative OCT data needed to identify deviations from the normal range in younger populations, noted Dr Trueba Lawand. “We must know normality in order to detect abnormality in these patients.” “The lack of normative data limits longitudinal studies. One application where OCT may prove particularly useful in the future is in measuring macular ganglion cell layer-inner plexiform layer (GCL-IPL) thickness as an early marker of structural damage in children with optic pathway gliomas (OPGs), and a possible future surrogate of visual acuity and visual fields in young children.”

Dr Araceli Trueba Lawand performing OCT on a child

EUROTIMES | DECEMBER 2017/JANUARY 2018

OCT images of: A) A normal macula; B) Foveal hypoplasia (presence of the inner retinal layers posterior to the foveola, shallower or absent foveal pit, diminished outer nuclear layer widening, decreased photoreceptor outer segment lengthening, and overall thickening of the retina); C) Macular retinosquisis (separation of layers, mainly affecting inner nuclear layers); and D) Combined Hamartoma (a hyperreflective mass showing thickened and disorganised retinal tissue)

Some progress has already been made in obtaining normative values of retinal nerve fibre layer (RNFL) and macular parameters in children using spectral domain OCT, said Dr Trueba Lawand. She cited a recent study of Al-Haddad et al. in which RNFL and macular thickness measurements were performed in 108 children using the Cirrus OCT machine. The authors give extensive comparative data of previous studies in the literature, and their results were comparable to other studies using the same Cirrus OCT machine. There is, however, great variability among results between the different OCT machines. This must be considered when evaluating and comparing OCT measurements in children, as suggested by Dr Trueba Lawand. OCT has also proven useful in characterising the time course of normal foveal development in vivo in term infants and young children, said Dr Trueba Lawand. Studies by Lee et al. have successfully modelled the complex, non-linear developmental trajectories for each retinal layer in infants and young children and demonstrated that development continues until adolescence (Figure 3A). In another OCT-based study, Thomas et al. developed a structural grading system for foveal hypoplasia based on the stage at which foveal development was arrested. This helps to provide a prognostic indicator for visual acuity and is applicable in a range of disorders associated with foveal hypoplasia, she said (Figure 3B). More controversial is the possible role of the retina in amblyopia, noted Dr Trueba Lawand. While a study by

Al-Haddad et al. found no changes in the RNFL between amblyopic and normal eyes, qualitative and quantitative macular changes suggestive of foveal immaturity seem to persist into adulthood. OCT is also being used to characterise and monitor retinal dystrophies and dysplasias that present in early childhood, said Dr Trueba Lawand, and has also proven helpful in identifying the aetiology of infantile nystagmus syndrome, a heterogeneous group of disorders for which there are multiple causes with different prognoses (Figure 3C). In the field of oncology, OCT is useful in differentiating between various paediatric intraocular tumours through a systematic evaluation of tumour reflectivity, the degree of involvement of individual retinal layers, associated vitreoretinal interface abnormalities and the transition pattern between abnormal and normal retina, she said (Figure 3D). Another area where OCT may play a valuable role in the future is in evaluating risk factors for vision loss in paediatric idiopathic intracranial hypertension (IIH). A study by Gospe et al. showed that clinical observation of high papilloedema grade on presentation is predictive of poor visual outcomes, and that vision loss is associated not only with optic atrophy but also with photoreceptor damage. Initial OCT findings may permit better risk stratification and aid in determining how aggressively to treat idiopathic intracranial hypertension in these young patients, she concluded. Araceli Trueba Lawand: aratru@gmail.com

Courtesy of Araceli Trueba Lawand MD, PhD

PAEDIATRIC OPHTHALMOLOGY

HSV KERATITIS IN CHILDREN Aggressive treatment needed to fight amblyopia and recurrence. Cheryl Guttman Krader reports

erpes simplex virus (HSV) keratitis occurs less often in children than in adults, but the infection tends to be more severe in children and mandates aggressive treatment to reduce the risk for corneal opacity and irregular astigmatism leading to amblyopia and poor quality of vision, said Marc Labetoulle MD, PhD, at the 2017 WSPOS Paediatric Subspecialty Day meeting in Lisbon, Portugal. “Topical or systemic antiviral agents can be prescribed as curative treatment for HSV epithelial keratitis, but intravenous acyclovir is indicated in cases of necrotising stromal keratitis. Corticosteroids should not be given for either of those conditions, but a topical corticosteroid combined with oral acyclovir or valacylovir is recommended for treatment of non-necrotising stromal keratitis,” said Dr Labetoulle, Head, Department of Ophthalmology, Bicêtre Hospital, Le Kremlin-Bicêtre, France. Discussing topical antiviral treatment for HSV keratitis in children, Dr Labetoulle said that only trifluridine and acyclovir are authorised for paediatric use, at least in France. Topical ganciclovir is a reasonable choice, however, considering that at the dose given, potential systemic exposure is >500-fold lower than would occur with systemic ganciclovir treatment in children with cytomegalovirus retinitis. Regarding systemic antiviral treatment for HSV keratitis, there are no published data on use of acyclovir in children aged younger than two years, but it is commonly used in the paediatric age group for other indications, even at a high dose. Administration in children is facilitated with acyclovir syrup 200mg/5mL and acyclovir suspension 800mg/10 mL. Dr Labetoulle cautioned that sorbitol and glycerol contained in the suspension can cause diarrhoea, particularly in children aged younger than six years. There are no published data on use of oral valacylovir in children younger than 12 years of age or for oral famciclovir in patients younger than 18 years of age. “However, because valacylovir is converted to acyclovir after ingestion, there is no scientific reason that it should be contraindicated in kids, providing that renal function is monitored”, Dr Labetoulle said. The dosage for oral antiviral medications to treat HSV keratitis in children is controversial. Some authors recommend using the same dosage as in adults, whereas others recommend using half the adult dosage in children whose body weight is below 20 kg. Dr Labetoulle noted that the frequency of HSV keratitis recurrence is about two-fold higher in children than in adults. While no children were enrolled in the Herpetic Eye Disease Study that established the efficacy of oral acyclovir for reducing HSV keratitis recurrence, Dr Labetoulle suggested that for suppressive treatment in children, acyclovir could be given at half the recommended adult dosage. “Collaboration with a paediatrician is mandatory, however, when treating very young children,” he stressed.

WSPOS World Society of Paediatric Ophthalmology & Strabismus

s u B s p E C i A l tY d A Y

Friday 21 September 2018, Vienna, Austria

Preceding the 36th Congress of the ESCRS, 22 – 26 September 2018

Marc Labetoulle: marc.labetoulle@aphp.fr EUROTIMES | DECEMBER 2017/JANUARY 2018

OUTLOOK ON INDUSTRY

ZEISS AT LARA 829MP, the new EDoF (Extended Depth of Focus) intraocular lens from ZEISS. AT LARA EDoF IOL is designed to provide a high degree of spectacle independence and to induce less visual side-effects compared to multifocal IOLs, enabling excellent vision over a wide range of distances

CARL ZEISS MEDITEC CZM has a million reasons to smile. Sean Henahan reports

arl Zeiss Meditec celebrated one million reasons to smile at the XXXV Congress of the ESCRS in Lisbon recently. The company announced that more than one million small incision lenticule extraction (SMILE) procedures have been performed worldwide. SMILE is a minimally invasive corneal refractive procedure performed using the ZEISS VisuMax femtosecond laser. It is a flap-free approach in which a corneal lenticule is removed through a small incision. Purported advantages include improved corneal biomechanics, no concern about traumatic flap displacement, lower incidence of long-term dry eye, and less damage to corneal nerves. The SMILE procedure is now being performed in 65 countries by more than 1,300 surgeons in over 700 clinics around the world. The procedure received US FDA approval in 2016 for use in the reduction or elimination of up to -8.00 dioptres of myopia, with -0.50D or less cylinder and MRSE -8.25D in patients who are at least 22 years of age. The SMILE FDA approval and first commercial treatments in the US (March 2017) were important steps because SMILE is now available in every major LVC market around the world.

EUROTIMES | DECEMBER 2017/JANUARY 2018

“SMILE has been out for over 10 years now and there have been close to 500 peer-reviewed publications about the procedure in the literature. We have many long-term outcome studies, some with over seven years, that suggest good visual outcomes and stability for the treatment of myopia,” said Steven Schallhorn MD, Chief Medical Officer for Global Ophthalmic Devices at ZEISS, in an interview with EuroTimes. Dr Schallhorn noted those involved in the development of SMILE were able to take advantage of many lessons learned during the evolution of LASIK. SMILE was first performed in 2007 by Professor Walter Sekundo and represents the first major advancement in laser vision correction since the 1990s. The experience with LASIK taught the importance of understanding the reasonable capabilities of the procedure, and, equally important, careful patient selection, he emphasised. Several recent clinical studies, including some that were reported at the ESCRS Congress in Lisbon, concluded that SMILE was as safe, and as effective, as LASIK for the correction of myopia. Current research is looking at the role of SMILE for the treatment of astigmatism in the US, as well as hyperopia and presbyopia. Some unique applications were also presented. For example, Dr Soosan Jacob demonstrated a new technique to

treat limbal dermoids using SMILE during the Lisbon meeting.1 After SMILE was introduced by early adopters, this unique procedure is now available for the broad community of ophthalmologists. Anyone interested in performing SMILE must complete appropriate training courses and are encouraged to attend peer-to-peer meetings. Moreover, ZEISS provides clinical application support, helping doctors get through the learning curve of SMILE, with the goal of delivering superior visual outcomes. The company also offers marketing and practice development support, in which consultants offer suggestions on such things as improving patient communications.

AT LARA Dr Schallhorn was also enthusiastic about the AT LARA, ZEISS’ entry in the extended depth of focus (EDoF) intraocular lens field. “The AT LARA EDoF is a good fit for the lifestyle of many patients that we treat today. It reflects the need that active patients have for spectacle-free intermediate near vision, such as using a smartphone, tablet or computer, which is a different visual task than reading small print in a book. It’s easy to appreciate that this lifestyle trend will continue,” said Dr Schallhorn.

OUTLOOK ON INDUSTRY LARA is an acronym that lists the features of the EDoF lens. The initial ‘L’ refers to the light bridge optic design of the lens. “This refers to the unique optical design that provides an extended range of focus, a broad depth of focus. It is, of course, much different than a monofocal lens, and a significant improvement over the traditional bifocal lens,” said Dr Schallhorn. The first ‘A’ in the acronym stands for ‘aspheric’, as the optic of the IOL is optimised for neutral asphericity to improve the quality of vision. The ‘R’ refers to reduced visual sideeffects provided by the design of the lens. He explained that ZEISS engineers applied a specific manufacturing process for the lens. The patented smooth microphase technology allows it to produce transitional phase zones, which minimises light scatter. The final ‘A’ refers to the advanced chromatic optics of the IOL. “Chromatic aberration is an issue with all types of lenses, especially multifocal IOLs. The optical engineers at ZEISS designed the lens to minimise chromatic aberration for better contrast sensitivity,” he explained. The AT LARA also has a 360-degree sharp posterior edge to minimise posterior capsule opacification. It comes preloaded to improve workflow, so that efficiency and productivity go hand and hand with this lens, he added. “We have great confidence that this lens will deliver what the optical engineers have designed it to do; that is, provide a broad range of focus with few visual symptoms.” In addition to his duties at ZEISS, Dr Schallhorn continues to practise surgery. He trained as an F-14 naval fighter pilot and was TOPGUN instructor in the US Navy before earning his medical degree. He retired from the Navy in 2007, where he served as the Refractive Surgery Program Manager. He founded the US Department of Defence refractive surgery programme, which now includes more than 20 centres offering refractive surgery to active duty personnel.

A refractive lenticule and small incision of less than 6mm are created inside the intact cornea – all in one step

The lenticule is subsequently removed through this small incision, leaving the remainder of the superficial cornea intact

The removal of the lenticule changes the shape of the cornea, thereby achieving the desired refractive correction

Off-label use.

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EUROTIMES | DECEMBER 2017/JANUARY 2018

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VISUAL OPTICS It’s often good to get back to the fundamentals. The Handbook of Visual Optics, Volume 1: Fundamentals and Eye Optics (CRC Press), edited by Pablo Artal, “offers an authoritative overview of encyclopaedic knowledge in the field of physiologic optics”. This is very much a text PUBLICATION of basic optical science, in HANDBOOK OF VISUAL OPTICS, the sense that its focus is the VOLUMES 1 AND 2 structure and function of the EDITOR eye, rather than its pathology. It PABLO ARTAL integrates knowledge not only from medicine and biology, but PUBLISHED BY CRC PRESS also physics, psychology and engineering. For example, Chapter 9: Instrumentation for Adaptive Optics (AO), first covers the principles of AO and then goes on to describe wavefront sensors and correctors to give the reader an in-depth look at how AO works. I personally found the chapter on the retina to be fascinating. A sub-chapter entitled “Retinal Compression is Similar to Video Compression” explains how, in highluminance situations, retinal circuits act as filters that pass only certain kinds of information and block other kinds. On the other hand, in scotopic conditions, retinal processing is expansive, meaning that signals converge to active the system despite low rates of stimulation by incoming photons. The Handbook is very readable, despite the complicated material. It is most appropriate for researchers in visual optics and those involved in the design and testing of ophthalmic and optometric instrumentation. Trainees seeking a deeper understanding of the eye’s physiological optical system would also benefit from reading this text.

BOOK

REVIEWS

INSTRUMENTATION AND VISION CORRECTION Once we understand how the visual system works and how to measure its function, we can move on to the correction of its flaws. The 2nd volume of this tandem, entitled Instrumentation and Vision Correction (also edited by Pablo Artal), describes the concepts underlying the ways we can improve vision. Its three parts are “Part I: Ophthalmic Instrumentation;” “Part II: Vision Correction,” and “Part III: The Impact of the Eye’s Optics on Vision”. Most relevant to the practising ophthalmologist is Part II, which includes chapters on accommodating and adjustable intraocular lenses. Whereas Volume 1 is particularly relevant for researchers and engineers, Volume 2 is more appropriate for ophthalmologists, particularly surgeons who specialise in cataract and refractive procedures and who are interested in staying on the cutting edge. Readers can get a 15% discount off the price of these books from Wisepress.com using the discount code on the ESCRS Education Portal at education.escrs.org

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ATTEND THE LARGEST U. S. MEETING DEDICATED EXCLUSIVELY TO THE NEEDS OF THE ANTERIOR SEGMENT PR ACTICE.

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ADDITIONAL PROGRAMS ASCRS REFRACTIVE DAY • APRIL 13 ASCRS GLAUCOMA DAY • APRIL 13

TIER ONE RATES DEADLINE WEDNESDAY, JANUARY 24

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TECHNICIANS & NURSES PROGRAM • APRIL 14–16

Programming will be held in the Walter E. Washington Convention Center.

ASOA WORKSHOPS • APRIL 13 T&N TECH TALKS • APRIL 13

RANDOM THOUGHTS

MEDICINAL CANNABIS Should cannabis be used to treat glaucoma? Aidan Hanratty reports

n October 2017, Canadian investment firm LCG Capital signed an option with AAA Trichomes to acquire an interest in a new cannabis processing facility to be built in Quebec. Canadians who have been authorised by their healthcare practitioner are allowed purchase or produce limited amounts of cannabis for their own medical purposes. At present there are 69 producers licensed by Health Canada, and following investments in Australia and South Africa, LGC are hoping to make inroads into this growing market. Several states worldwide have decriminalised cannabis use for medical reasons, but without defining clearly what conditions warrant its use. Health Canada, for example, lists the potential therapeutic uses for dozens of conditions, among them anorexia nervosa, multiple sclerosis and fibromyalgia. Studies, survey data and conclusions are presented, but in

most cases the list points out that concrete evidence is lacking and that further research is required. Since the 1970s it has been suggested that cannabis use can help treat glaucoma. This has been disputed for almost as long, however. In short, smoking marijuana has proven to be effective for lowering intra-ocular pressure (IOP), a key element in glaucoma treatment. Its effects last for just three-to-four hours, and patients need a 24-hour reduction in pressure, so one would have to be smoking six-to-eight times per day. In a study carried out to observe the effects of cannabis on IOP, researchers noted that seven of nine participants lost any beneficial effect of the drug due to tolerance. Furthermore, smoking can have negative effects, such as dizziness, sleepiness, distortion of perception and anxiety. “Synthetic analogues of cannabinoid with more potency and longer duration of action, sensible utilisation of novel drug delivery systems namely nanoparticle approaches, and combination of

cannabinoids with other conventional drugs to control glaucoma could be alternative solutions,” write the authors of a detailed paper entitled The arguments for and against cannabinoids application in glaucomatous retinopathy. In another study, entitled Cannabinoids and glaucoma, researchers pointed out the difficulties of attempting to administer cannabis via eye drops. “After instillation of an eye drop of any medication, loss of the instilled solution via the lacrimal drainage system and poor drug penetration results in only <5% of an applied dose reaching the intraocular tissues,” the authors write. As well as this, natural cannabinoid extracts “are highly lipophilic and have low aqueous solubility”, making effective application even more difficult. While cannabis in fact has proven effective as an appetite stimulant, a spasticity relief and pain relief for a variety of conditions, it remains the case that more traditional remedies such as eye drops or surgery, based on current research, may continue to be appropriate for the treatment of glaucoma.

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INDUSTRY NEWS

INDUSTRY

NEWS

DIGITAL ADVANCE

Take control of your future. Belong to something powerful. Join us. www.escrs.org

EUROTIMES | DECEMBER 2017/JANUARY 2018

During the 2017 American Academy of Ophthalmology’s (AAO) Annual Meeting in New Orleans, ZEISS presented new technologies advancing the digitalisation of eye care, including VERACITY™ Surgical, a cloud-based cataract surgery planning platform. ZEISS also presented new diagnostic technologies for retina and glaucoma to help eye doctors more effectively and efficiently advance patient care: CLARUS™ 500, the first fundus imaging system combining True Color with exceptional clarity within an ultra-widefield view; and HFA3 SITA Faster, which reduces visual field testing time by more than 50%. “Digital technology is fundamentally changing our world and has a major impact in healthcare,” says Dr Ludwin Monz, President and CEO of Carl Zeiss Meditec. “ZEISS is constantly addressing future-forward trends, such as digitalisation, which is reshaping how medicine is practised today, to give doctors innovative solutions to help patients,” he said. www.zeiss.com

FDA CLEARANCE

NEW ADDITION

Topcon Medical Systems has announced that its PASCAL® Synthesis TwinStar™ laser, (combined 577Nm and 638Nm) has received FDA 510(k) clearance. (K170409) “The Synthesis TwinStar further expands the PASCAL line of laser photocoagulators offering the ability to treat retinal disorders with a 577Nm yellow wavelength or with a 638Nm red wavelength,” said a spokeswoman. ““The yellow module allows doctors to treat with a single spot as well as with a variety of patterns and four spot sizes. The yellow module can also be used with the optional Endpoint Management software for sub-threshold procedures. The red wavelength, ideal for targeting choroidal vessels in the neovascular membrane, is for single spot treatments and has two different spot sizes,” she said. www.topcon.com

Katena Products has purchased Rhein Medical Inc. Founded nearly 30 years ago, Rhein Medical is focused on the anterior segment surgical business. “The acquisition of the Rhein Medical line is an important addition to Katena’s product portfolio. The combination of these two renowned brands will bring internal synergies as well as offering physicians a more complete resource for handheld instrumentation,” said Mark Fletcher, CEO of Katena Products. Rhein Medical President John Bee said: “Having dedicated ourselves to producing the finest quality instruments possible, we are confident that our legacy of quality will continue under Katena.” www.katena.com

CALENDAR

↙

LAST CALL

2018 JANUARY Basic Science Course in Ophthalmology

8 January – 2 February New York, USA http://columbiaeye.org/education/ the-basic-science-course

9th International Course on Ophthalmic and Oculoplastic Reconstruction and Trauma Surgery

10–12 January Vienna, Austria http://www.ophthalmictrainings.com/workshops

Annual Conference on Ocular Microsurgery

10–13 January 2018 Eilat, Israel www.eyemeetingeilat.com/en/

The 22nd ESCRS Winter Meeting will take place in Belgrade

FEBRUARY

22nd ESCRS Winter Meeting 9–11 February Belgrade, Serbia www.escrs.org

2nd International Swept Source OCT & Angiography Conference 16–17 February Paris, France https://www.issoct.com/

8th EURETINA Winter Meeting 16–17 February Budapest, Hungary www.euretina.org

MARCH

14th ISOPT Clinical: The International Symposium on Ocular Pharmacology & Therapeutics 1–3 March Tel Aviv, Israel https://www.isoptclinical.com/

MARCH

32nd International Congress of the Hellenic Society of Intraocular Implant and Refractive Surgery 1–4 March Athens, Greece www.hsioirs.org/index.php/en/

Frankfurt Retina Meeting 2018

24–25 March Mainz, Germany www.eckardt-frankfurt.de

APRIL

2018 ASCRS•ASOA Annual Meeting

13–17 April Washington DC, USA http://annualmeeting.ascrs.org/

4th ESASO Anterior Segment Academy

26–28 April Milan, Italy www.esasoasa2018.org

MAY

NEW 15th Congress of the South-East European Ophthalmological Society 31 May – 2 June Szeged, Hungary http://www.seeos.eu

The 32nd International Congress of the Hellenic Society of Intraocular Implant and Refractive Surgery will take place in Athens

EUROTIMES | DECEMBER 2017/JANUARY 2018

CALENDAR

JUNE

NEW World Congress on Clinical, Pediatric and Neuro Ophthalmology

4–5 June Osaka, Japan https://neuro.ophthalmologyconferences.com

31st International Congress of German Ophthalmic Surgeons

14–16 June Nuremberg, Germany http://www.doc-nuernberg.de/index-e.php

3rd World Eye Bank Symposium

15 June Barcelona, Spain http://www.gaeba.org/events/ 3rd-world-eye-bank-symposium-gaeba/

WOC 2018

16–19 June Barcelona, Spain www.icoph.org

The 2018 EURETINA, EuCornea and ESCRS Congresses will take place in Vienna

SEPTEMBER

OCTOBER

SEPTEMBER

18th EURETINA Congress

NEW Ophthalmic Imaging: from Theory to Current Practice

2018 WSPOS Subspecialty Day

20–23 September Vienna, Austria www.euretina.org

21 September Vienna, Austria www.wspos.org

36th Congress of the ESCRS

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

22–26 September Vienna, Austria www.escrs.org

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9th EuCornea Congress

12 October Paris, France http://www.vuexplorer.com/en/congres 27–30 October Chicago, USA https://www.aao.org/

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