PIE POST (EURETINA 2018 VIENNA) - DAY 3

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23 SEP 2018 PIE Ma ga zine’s D aily C ong re s s New s on the P o s t e rio r S e gment

HIGHLIGHTS Effectiveness pg05 vs Cost in DR

New technology in DR in 3 . . .

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treatment

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Genetics play an important role in retinal disease

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The agony of choosing treatment options in retinal hemmorhage!

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Coming Soon

New Technology for

Diabetic Retinopathy

by Brooke Herron

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The third morning of the 18th EURETINA Congress featured an informational symposium on new technologies in diabetic retinopathy (DR). From screening and imaging to new anti-vascular endothelial growth factor (VEGF) therapies, there is much happening in the world of DR that will benefit patients and doctors, while ideally preserving vision and preventing unneeded blindness.

Screening and Tele-screening

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e know that access and availability screening for DR is vital to preserve vision. For example, because two-field digital imaging is offered to all people with diabetes in England, now – for the first time in five decades – DR is no longer the leading cause of certified blindness in people aged 16 to 64 in England and Wales.

That’s great, right? Definitely, for people with diabetes in England. But what about in other countries where this type of screening is costprohibitive?

“This [in England] is based on human graders – so they are expensive,” explained Andrzej Grzybowski, MD, PhD, Department of Ophthalmology, University of Warmia and Mazury in Olsztyn, Poland. “So, it’s difficult to put these systems in other parts of the world.”

And though human graders are the current gold standard, recent advances in the field of artificial intelligence (AI) and machine learning (ML) have encouraged the innovation of automated systems for retinal images for DR.

Dr. Grzybowski noted several of these systems in his presentation. The IDx-DR (IDx Technologies, Inc., Coralville, IA, USA) which was recently approved by the US Food and Drug Administration (FDA), is Cont. on Page 3 >>

HOTSHOT

“Mozart” observes a symposium about 3D visualization.

Full report, page 14

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////////Science for a better life

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23 September 2018 | Vienna, Austria

Will old age stop us seeing our grandkids?

80 80 %

of visually impaired % people are over the age of 50

of all visual impairment can be prevented or cured

CanWeLiveBetter.com Source 1: GBVI – Global Disaggregation of Numbers for Gender and Age. IAPB Vision Atlas, 2017 Source 2: Vision Impairment and Blindness. World Health Organization, 2017 L.AT.MKT.09.2018.8551 September 2018

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grading has been taken as absolute proof – which is reliable but never 100% accurate.”

“The future will be based on multitechnology approach and customized DR screening,” he concluded.

Ultra-wide field imaging in diabetic retinopathy Dr. Andrzej Grzybowski

based on two components, and combines classical, deliberately designed image analysis with a deep-learning convolutional neural network aspect. In addition, it’s designed to work with a specific nonmydriatic fundus camera from Topcon (Tokyo, Japan). The Retmarker DR software , an innovative Diabetic Retinopathy (DR) progression biomarker software, developed in partnership with a leading research institute - AIBILI (Association for Biomedical Research and Innovation in Light and Image, Coimbra, Portugal is being used for a few years now. It’s able to compare previous images and look for disease progression and can calculate the rate at which microaneurysms disappear and form.

Eyeart (Eyenuk Inc., CA, USA) is commercially available in the U.S. and Canada and is a small, portable, relatively inexpensive fundus camera with automatic grading that may help reach the most impoverished and remote communities in the future. One of the oldest systems is Retinalyze (RetinaLyze System A/S, Hellerup, Denmark, was revamped in 2007 to take into account progress in modern IT science and ML. And finally, and more experimentally, there’s a promising new algorithm in collaboration with Google. “It’s similar to IDx-DR, with the result on a scale of 0-1 corresponding to likelihood of a given DR classification, and it allows for high sensitivity and specificity,” he said. “It’s very promising, but it’s not commercially available yet.”

So which one should be used? Well, it’s actually a bit difficult to determine that.

“There are many differences in comparing current systems head-to-head,” said Dr. Grzybowski. “There are different grading methods used, a lack of common validation image set, there’s different performance depending on image quality, and human

According to Dr. Francesco Bandello, professor and chairman at the Department of Ophthalmology University Vita-Salute, Scientific Institute San Raffaele, Milan, Italy, fluorescein angiography (FA) is fundamental for screening, diagnosis, monitoring and treatment of DR. This is because good visualization of the retina is needed to assess non-perfused areas, vascular leakage, microvascular abnormalities and neovascularization (NV).

Dr. Bandello explained that there are different systems to achieve these images. The gold standard, he says, is the 7 Standard Field (7SF). It has an extended field (75°) over the standard fundus camera (30°) and there’s no contact. However, it requires highly skilled operators, patient collaboration, the far periphery is not explored. Another imaging system is the Spectralis Ultra-Widefield Lens (Heidelberg Engineering, Heidelberg, Germany). Its field extends further (105°) than 7SF, but it still cannot provide images of the far periphery.

“The more common and practical is the Optos Ultra-Widefield (UWFA) Imaging system,” said Dr. Bandello. “You’re able to see 200° of the fundus and it’s the best solution for evaluating the periphery – only the extreme periphery is not visible.”

He noted a 2012 study by Wessel et al. that compared the 7SF with Optos UWFA (Optos Inc., MA, USA). The authors found that the UWFA disclosed 3.2 times more total retina surface, 3.9 times more non-

Dr. Francesco Bandello

perfusion, 1.9 times more NV and 3.8 times more laser panretinal photocoagulation (PRP) treated area.

“UWFA is going to revolutionize DR in multiple aspects . . . in diagnosis, staging, management and therapy,” said. Dr. Bandello.

New molecules for intravitreal therapies Worldwide, the incidence of blindness has been reduced since the introduction of antiVEGF. According to Dr. Anat Loewenstein, professor and director of the Department of Ophthalmology at the Tel Aviv Medical Center, Israel, if new molecules or antiVEGFs become available it could be reduced further. She says ideally, there would be longer acting treatment that mandate less injections that maintain visual acuity (VA) over time.

“We need a better visual acuity outcome,” said. Dr. Loewenstein. “And there are many drugs in the pipeline.”

Emerging treatments include next generation anti-VEGF agents, drugs targeting different pathways and gene therapy. One such anti-VEGF agent is brolucizumab. Results from the HAWK and HARRIER studies show that brolucizumab met the primary endpoint of noninferiority in change in BCVA from baseline to week 48. And more than half of brolucizumab patients were maintained a q12w dosing interval immediately following loading phase through week 48. In addition, significantly fewer patients on brolucizumab had disease activity at headto-head assessment.

Conbercept is a “lesser line” anti-VEGF from China for non-neovascular AMD. “It’s approved in China and it currently being evaluated by the FDA,” she explained. “It blocks all VEGF-A isoforms (VEGF-B, -C, and PGF and it has the longest half-life of any anti-VEGF (~7d).”

“But the most exciting drug is faricimab,” said Dr. Loewenstein. This is a novel bispecific antibody that simultaneously binds VEGF and angiopoietin 2 designed for intravitreal use.

“It’s engineered for efficacy, duration with the eye and fast systemic clearance.”

“I think we do have hope for giving our patients better VA with less injections,” she concluded.

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23 September 2018 | Vienna, Austria

Intraocular Foreign Bodies

and How to Remove Them

Medusa turned onlookers to stone...ironic that eyes were depicted in mythology as a weapon of destruction, when in real life they are too prone to destruction.

by Hazlin Hassan

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everal speakers from the Egyptian Vitreoretinal Society (EGVRS) shared some insights on the thorny issue of surgically removing foreign bodies from the eye at the 18th EURETINA Congress yesterday.

Surgeons need to be prepared for surprises, otherwise there is a risk of losing the patient or the eye. “Intraocular foreign bodies may reach 20-40% in industrialized areas,” said Professor Mahmoud Soliman of the Department of Ophthalmology, Cairo University, Egypt. Patients were predominantly males aged between 18-40 years old.

The most common foreign bodies (FB) tended to be metals, such as iron, steel, copper, lead, alloys, followed by stone and sand, glass and sometimes

organic materials. Most injuries occurred through hammering, and sometimes due to machinery, car accidents, sports, domestic and lastly blast injuries.

Prof. Soliman presented an example of one of his patients who had a nail in the eye. The size of the intraocular foreign body (IOFB) would determine the amount of ocular damage, while the nature of it would determine the reaction of the ocular tissues, he said. IOFBs should be suspected in all cases presenting with ocular trauma particularly with unexplained uveitis, he cautioned.

Prompt examination and dilation should take place due to the risk of cataract or vitreous hemorrhage. CT scans are also reliable. MRIs are contraindicated in metallic

IOFBs. The main objectives were optimum wound closure, to restore the architecture of the eye, removal of the IOFB, and to prevent infection. The standard treatment is vitrectomy and removal of the IOFB, according to Prof. Soliman. Results depend on the size of the IOFB, site of impact, infection and the timing of intervention.

Dr. Wael Soliman, from the Department of Ophthalmology of Assiut University, Egypt, shared on anterior chamber (AC) exit of IOFBs, using tools such as forceps and magnets. Advantages of AC exit of IOFBs include avoiding difficulties of large FBs removal through sclerotomies, he said.

This means avoiding enlarging of sclerotomies. However, there are disadvantages, including the possibility of enlarging corneal wounds and a risk of astigmatism.

Disadvantages of direct removal through sclerotomies include getting stuck at the port, getting entangled in the ciliary body, IOFB slipping back into the vitreous cavity during attempted removal, and a risk of the globe collapsing due to the enlarged sclerotomy.

Professor Mostafa Nabih from Cairo University, Egypt, shared his experiences using hybrid vitrectomies for IOFBs. He said they were a step forward as they were sutureless, involved shorter operation times, and proved more efficient.

Dr. Mohamed Tarek Moustafa, Lecturer of Ophthalmology at Minia University, Egypt, demonstrated the ‘Cowboy Loop’ for IOFB removal. Techniques for removal depend on the shape of the IOFB, nature of the FB and the state of the lens, he said.

In closing, Dr. Mahmoud Soliman concluded the session by talking about the prognosis for ‘Siderosis Bulbi,’ a serious complication of retained metallic IOFBs. Ferric ions are deposited in epithelial cells causing interruption of cellular activity and cell damage. If the cataract and foreign body are removed, vision can slowly recover, he emphasized.

Prof. Mahmoud Soliman

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Efficacy and Finance Issues Raised in Treating

Diabetic Retinopathy

by John Butcher

T

he clash of efficacy and finances were brought to the fore on the third day of the 18th EURETINA Congress in Vienna yesterday (September 22).

During a morning session at the event, Dr. Sobha Sivaprasad, a professor at Moorfields Eye Hospital in London, presented a study comparing the effectiveness of two treatments for proliferative diabetic retinopathy (PDR), while fellow speaker Dr. Neil Bressler, a professor of ophthalmology at John Hopkins University in the United States, talked about the effect of treatment cost on policymaker decisions.

Dr. Sivaprasad presented the findings of the CLARITY study, which compared the efficacy of aflibercept versus panretinal photocoagulation. The study’s primary aim was to determine if visual acuity at 52 weeks in patients with active PDR treated with aflibercept is non-inferior to those treated with panretinal photocoagulation, she said.

The study also had secondary objectives, she added, which included determining the potential benefits of aflibercept therapy in terms of peripheral

Dr. Sobha Sivaprasad

vision, low luminance vision, contrast sensitivity, incident macular edema and incident vitreous hemorrhage.

Funded by the National Institute for Health Research, the largest national clinical research funder in Europe, the study included 232 active PDR patients, balanced between each of the treatments.

The study found mean change in visual acuity from baseline to week 52 with aflibercept therapy was superior to panretinal photocoagulation, she said. In addition, there was less chance of incident vitreous hemorrhage or new onset diabetic macula edema (DME) with aflibercept therapy.

Panretinal coagulation was rarely required for non-regression with aflibercept, she continued, and a mean of just 1.4 aflibercept injections were required during the 40-week post loading phase.

There were no new safety concerns with aflibercept, she said, and patients preferred aflibercept therapy over panretinal photocoagulation.

The results were positive for aflibercept, however the study period was only one year which meant the long term sustainability of treatment with the drug could not be translated from it, she added.

The effectiveness of treatment alone is not enough though, Dr. Bressler told the congress, as policymakers and payers want cost effectiveness.

Comparing treatments for proliferative diabetic retinopahy on cost alone, panretinal photocoagulation at a cost of $345 in the US in 2016, compared to

ranibizumab at a cost of $1,916 per dose plus $103 for the injection procedure, shows a clear winner in terms of price, he said.

“For costs you don’t need any sort of complex analysis to figure out which costs more,” he said, but policymakers are interested in cost-effectiveness.

Typically, they consider treatment costs using a cost-effectiveness ratio, which measures price against effectiveness, on which high ratios are considered bad and low ratios good.

There is no “explicit threshold” for how much policymakers will pay for a treatment, said Dr. Bressler, but in developed countries generally less than $50,000 per quality adjusted life year (QALY), a generic measure of disease burden including quality and quantity of life lived, is considered good value, and in excess of $250,000 per QALY is considered too expensive. Anything between these costs becomes a “judgement call” for policymakers, he added.

Dr. Neil Bressler

Studying the cost-effectiveness of panretinal photocoagulation compared to ranibizumab suggests that for individuals with proliferative diabetic retinopathy and vision impairing diabetic macular edema, ranibizumab may be a cost-effective therapy when treating the better-seeing eye ($55,568/QALY), he said.

For people with proliferative diabetic retinopahy but without diabetic macular edema, ranibizumab is unlikely to be cost effective ($662,978/QALY), he added.

The results highlight the challenges when safety and efficacy results, which are important to patients and physicians providing their treatment, are at odds with cost-effectiveness results which are the focus of many payers and policymakers.

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23 September 2018 | Vienna, Austria

Artificial Intelligence and Virtual Reality, Soon Realities in Ophthalmology

Virtual reality: quickly becoming better than the post-it note alternative.

by John Butcher

O

phthalmologists introduced cutting edge technology and treatment developments on the final day of the 18th EURETINA Congress in Vienna yesterday (September 22).

Artificial intelligence (AI) and virtual reality (VR) will soon be realities that could transform the industry, the audience was told. And new optical developments could have a major impact on the study of Alzheimer’s disease.

Dr. Peter Maloca, an ophthalmologist from Moorfields Eye Hospital in London, introduced trials of virtual reality technology that allow users to walk through the human eye. OCT scans provide framed data, he said, but ophthalmologists should bear in mind that the problem may not be within that frame.

Virtual reality would allow them to “walk in the eye with one hundred images per second,” he said, instead of looking at small part of the eye. As well as benefitting ophthalmologists, his studies had found using the technology could foster greater patient engagement, he added.

There are limits to the use of virtual reality, he continued, including high and expensive hardware requirements, latency in image movement and heavy headsets, but they would be solved soon. The benefits, he concluded, were enhanced understanding and potentially more accurate work. The next step in

the development of virtual reality for ophthalmology, according to Dr. Maloca, is to integrate it with AI. Dr. Pearse Keane, a consultant at Moorfields Eye Hospital, spoke about a partnership between Moorfields Eye Hospital and the AI company DeepMind, both based in London, that began in 2016.

The first paper from that collaboration was published recently by Nature Medicine magazine, he added. AI will be “transformative” he told the audience and ophthalmology is likely to be the first branch of medicine to be fundamentally changed by it.

The Moorfields-DeepMind collaboration involved creating two neural networks, he said. The first was trained with manually delineated OCT scan features so it could highlight pathology on the images.

The second network was trained to diagnose those images and recommend referrals.

The first network segments 15 different features from the scans,

Dr. Pearse Keane

intraretinal fluid, choroid and outer layers and fold over artefact among them, while the second network is able to recognize more than fifty retinal diseases.

“The Moorfields-DeepMind system is calibrated to make referrals based on standard practice in the UK, but could be recalibrated to other health systems,” explained Dr. Keane. It is capable of providing multi classifications if more than one problem is detected in an eye. In trials at Moorfields, where the networks system was tested against eight specialists, the AI system was found to perform as good or better, he told the audience. “The next steps for the AI system include enhanced training in its use and prospective clinical trials,” Dr. Keane concluded.

At the same session Dr. Tunde Peto, head of the ophthalmic image reading centre at Moorfields Eye Hospital, introduced the latest information on retinal vascular biomarkers for Alzheimer’s disease, a disease that will affect one in three of people born today within their lifetime. The retina is the window to the brain, she told the audience, with retinal markers offering clues to how Alzheimer’s disease develops and possibly how it might be treated.

“Treating the disease if urgent, given the ‘incoming tide’ of neurogenic diseases, particularly Alzheimer’s will affect one in three of people born today,” Dr. Peto said.

Recent studies have concentrated on the periphery of the eye she said, where they have identified drusen deposits in people suffering with Alzheimer’s as well as other abnormalities. Research is being done, but more is needed, involving large cohorts to tackle what is becoming an urgent problem.

Dr. Peter Maloca

Dr. Tunde Peto

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Experts Focus on Diabetes Epidemic

by John Butcher

M

edical experts focused on the growing problem of diabetes on the third day of the 18th EURETINA Congress in Vienna yesterday (September 22). Urbanization and lifestyle changes have led to a surge in the disease worldwide they said, and in turn an increase in many associated eye problems.

Dr. Coen Stehouwer, a professor of internal medicine at Maastrict University in the Netherlands, described the size of the problem. There has been a progressive worldwide increase in both type 1 and type 2 diabetes [to 400 million people in 2018], he told the audience. Dr. Stehouwer called it a “severe” disease that significantly reduces quality of life and leads to a shorter life, on average by ten years, according to data from Sweden. If risk factors, such as blood pressure and glycaemia levels, are controlled its impact and progression can be reduced or put it into remission, he said.

“Losing weight is also a substantial factor in putting diabetes into remission if it is at an early stage,” he added.

Diabetes mellitus is one of the most common chronic diseases in Europe, said Dr. Robert Finger, a professor of ophthalmic epidemiology and neuro-retinal imaging at the University of Bonn in Germany. With an estimated 66 million suffering from it across the continent in 2017, that number is estimated to rise to 81 million in 2045.

Diabetic eye disease is among the leading causes of vision loss among working age adults, especially due to proliferative diabetic retinopathy, he added.

By 2050 the number of people with diabetic eye disease is expected to increase by 34 percent to 8.6 million people within the European Union, he said,

with around one third of these requiring close monitoring and/or treatment due to advanced disease stages.

Dr. Mario Nubile, from the department of medicine and aging science, at the University of Chieti, in Pescara, Italy, spoke on the impact of diabetes on the ocular surface and the rise in disease risk this causes. “Virtually any component of the ocular surface can be affected by diabetic complications,” he told the audience.

People with diabetes are at risk of a range of eye problems, including diabetic retinopathy, cataract, glaucoma and ocular surface diseases.

Between 50% and 70% of diabetic patients suffer some form of diabetic keratopathy during the course of the disease, he said. Also, the duration of diabetes mellitus and poor glycemic control are factors in its [diabetic keratopathy] development.

Dry eye syndrome was common among diabetic patients, he added.

Symptoms including an itching sensation, stinging or burning, a gritty sensation, sensitivity to light, excessive tearing and burry vision are common.

Treatments for diabetes-related ocular

Dr. Mario Nubile

Dr. Morten la Cour

surface abnormalities include systemic therapies, artificial tears, antibiotics, bandage contact lenses, tarsorrhaphy and amniotic membrane transplantation, he said. New approaches include topical nerve growth factor (NGF), which promotes corneal nerve regeneration, he added.

Diabetic involvement on the ocular surface was a common issue he concluded, that could be worsened by surgery.

Dr. Morten la Cour, chairman of the ophthalmology department, Glostrup Hospital, Copenhagen University, Denmark, talked about those risks when performing cataract surgery on diabetic patients.

People with diabetes are five times more likely to develop cataracts than people without the condition, he said, with the risk increasing with age, poorer diabetes control and more severe retinopathy.

Performing cataract surgery however, was a risk to diabetic patients, he continued, and could potentially worsen diabetic retinopathy (or iris neovascularization) and diabetic macular edema.

The risk of persistent diabetic macular edema is significant after cataract surgery and increases with the severity of diabetic retinopathy, he said. Even in eyes with mild or no retinopathy there is an increased risk of persistent diabetic macular edema, he added.

Patients who do undergo surgery should also be monitored after the event because, according to studies, complications peak three to six months afterwards, he added.

Despite the complications, cataract extraction does result in improved vision in the majority of diabetics, however.

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Vincent Borderie, MD, PhD France - Moderator

Maria Cristina Savastano, MD Italy

Luca Di Antonio, MD, PhD Italy

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23 September 2018 | Vienna, Austria

Early Detection and Aflibercept to

Preserve Vision in Diabetic Eye Disease

by Brooke Herron

I

t’s proven that early detection of diabetic macular edema (DME) and diabetic retinopathy (DR) produces better results – and less chance of losing sight – for patients.

In a Bayer-sponsored symposium at the 18th EURETINA Congress entitled “Changing the course: disease modification with intensive early treatment for DME,” key thought leaders shared their insight into treatment to preserve vision in these patients.

According to a recent study, Americans rated losing their eyesight as having the greatest impact in daily life. This includes both near-sighted activities (like reading a newspaper) to far-sighted activities (like going down stairs). To avoid loss of sight, it’s imperative to identify and catch DME and DR in patients at an early stage.

“The importance of early screening for DR should not be underestimated,” said Dr. Neil M. Bressler, a professor of ophthalmology at John Hopkins University in the United States. “Timely detection and treatment of DR can prevent vision loss and blindness. Ideally, it needs to be diagnosed when visual acuity (VA) is still relatively good to obtain 20/25 or better VA outcomes.”

The multi-targeted MoA of aflibercept It’s known that both vascular endothelial growth factor (VEGF) and placental growth factor (PlGF) play a role in the pathology of diabetic eye disease; they both contribute to development of retinal vascular leakage and edema. This is where aflibercept can help: It’s specifically designed for highaffinity binding to both VEGF and PlGF. “Aflibercept has a greater binding affinity for VEGF-A than its native receptors,” said Dr. Ian Pierce, MB, ChB, BSc, FRCOPHTH, consultant ophthalmologist and vitreoretinal surgeon at the Spire Liverpool Hospital (Liverpool, United Kingdom).

“It inhibits VEGF-induced activation in vitro with greater potency than ranibizumab or bevacizumab – and unlike those two, aflibercept also inhibits the activity of PlGF.

Examine the evidence: Aflibercept in DME The efficacy of aflibercept in DME is supported by evidence from robust clinical trials like VIVID and VISTA (3 years). Both the VIVID and VISTA studies showed that rapid and increasing VA gains were achieved with early, intensive aflibercept treatment in year 1.

“At week 52, patients receiving aflibercept gained >10 letters on average from baseline,” said Prof. Edoardo Midena, Professor of Ophthalmology and Visual Sciences at the University of Padova, School of Medicine, and Chairman of the Department of Ophthalmology, Padova University Hospital, Padova, Italy. “These results were maintained over 148 weeks with continued active treatment,” he added.

Continued treatment is the key in managing the disease – and early, intensive treatment in year 1 allowed for a pronounced reduction in treatment burden thereafter. “You need to treat correctly in the loading phase. Don’t do one injection and stop because the patient has improved – use the loading phase,” he continued.

“When you treat with aflibercept for two to three years, you’re able to stabilize the situation and you protect the patient and improve his quality of life.”

Does it matter which anti-VEGF you use?

A recent study published in the New England Journal of Medicine says “yes.” The authors compared aflibercept, bevacizumab and ranibizumab in treating DME and found that overall, aflibercept was superior. In addition, EURETINA provides the following evidence-based treatment guidelines for DME: “The use of ranibizumab for patients with poorer baseline VA will most likely result in the same VA results after two years of aflibercept, but the effect will be reached slightly slower – therefore, treatment should be initiated with aflibercept, if available in these patients.”

“So does it matter which anti-VEGF you use? Yes,” agreed Dr. Bressler. “We’re confident that aflibercept is better.”

Anterior Segment Update

Yamane Double Needle Technique Sets the Standard

PIE Magazine’s Daily Congress News on the In order to address these challenges, Dr. Yamane, in cooperation with Geuder AG (Heidelberg, Germany), one of the leading manufacturers for ophthalmic surgical instruments, successfully designed a novel instrument which will enable surgeons to perform the technique.

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by Hazlin Hassan

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he new double needle technique for intrascleral haptic fixation by Dr. Shin Yamane introduces higher standards in intraocular lens (IOL) scleral fixation surgery, and eliminates the need for conjunctival incision, suture or glue.

When Dr. Yamane, Assistant Professor at the Department of Ophthalmology and Micro-Technology at Yokohama City University, Japan, created his technique, his aim was to minimize the sclerotomies created during IOL fixation.

After several attempts, he successfully developed a new surgical procedure (Flanged Intrascleral Intraocular Lens Fixation with Double Needle Technique) which can be done without conjunctival incisions, suture or glue. The technique allows the procedure to be performed in a minimally invasive way, and in a much shorter time. But he realized that surgeons may face several challenges while attempting the double needle technique, as tunneling in the sclera and sclerotomy entry may prove to be a challenge to reproduce.

There three key points which should be noted during the technique are: 1. Positional relationship of the wounds: it is appropriate for the wound where the IOL is inserted and the sclerotomy site where the 30-G needle is inserted, to be in positions that are separated by 90 degrees or less. By ensuring that the two sclerotomies remain 180 degrees apart, this makes it easier to insert the leading haptic into the 30-G needle.

2. Double-needle technique: If the leading haptic is pulled out together with the 30-G needle, the IOL will rotate

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in the counter clockwise direction. If insertion of the tip of the trailing haptic into a 30-G needle is attempted, the trailing haptic will touch the cornea.

Placing the haptic in the inner cavity of the 30-G needle resolves this issue and makes insertion easier.

Insertion angle: to reduce stress on the IOL haptic, the direction of the 30-G needle should be identical with that of the haptics. Each 30-G needle is inserted at an angle of 20 degrees with respect to the corneal limbus. And at 5 degrees with respect to the iris surface.

The ‘Yamane Double-Needle Stabilizer’ is aimed at standardizing the intricate measurements and angles needed to create reproducible sclerotomy entries and scleral tunnels. The tool helps surgeons simplify the identification of sclerotomy sites and provides control over the insertion angles when creating the sclera tunnels.

It incorporates two landmarks for ease of visualization of the sclerotomy sites, at 2mm from limbus and 180 degrees apart, eliminating the need for axis markers, calpers or ink.

It also enables surgeons to place an IOL precisely into an aphakic eye by scleral fixation only, without conjunctival incision or suture or glue. Designed with a ring shape and fixating teeth, the stabilizer provides excellent fixation of the eye when piercing it with the needles. The haptics are strongly attached to the sclera, preventing IOL dislocation in future.

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23 September 2018 | Vienna, Austria

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23 September 2018 | Vienna, Austria

The Future for Retinal Genetics

Dr. Caroline Klaver

Professor Robert MacLaren

by Hazlin Hassan

T

here are exciting developments in gene therapies and clinical practice for inherited eye diseases, leading genetics experts told a session at the 18th EURETINA Congress yesterday.

A European Medicines Agency panel on Friday recommended approval of Spark Therapeutics’ gene therapy for blindness, voretigene neparvovec, approved as Luxturna in the United States, said Bart LeRoy, associate professor of Ophthalmic Genetics and Visual Electrophysiology at Ghent University, Belgium.

Rare genetic disorders can cause vision loss and blindness. Antisense OligoNucleotides therapy is also being tried out, among others, in Ghent, he said. Several gene therapy trials are also underway. He pointed out that deep phenotyping is “absolutely essential in a world of rapid genotyping,” and that genotyping is an essential part of the workup of all patients.

There are several therapeutic strategies in the pipeline, besides voretigene neparvovec, as well as generic gene strategies for specific subsets of patients, he said.

Dr. Caroline Klaver, professor of Epidemiology and the Genetics of Eye Diseases, at Erasmus MC, Rotterdam talked about the genetic risk of age-related macular degeneration (AMD) and myopia.

She advocates practicing a healthy lifestyle including consuming plenty of fruits and vegetables rich in carotenoids,

lutein and zeaxanthin, fish and nuts (omega-3 fatty acids) supplements (i.e. vitamins, zinc), maintaining a normal weight, exercise, and avoiding smoking. All these would boost anti-inflammatory, antioxidative, and anti-angiogenic actions.

As for patients’ response to genetic testing for age-related macular degeneration, she said interest in testing was high, and a high genetic risk increased the incentive to improve the patient’s lifestyle. She also touched on whether Asians carried a higher risk or carried more risk genes for myopia compared to those with European ethnicity. “The end of the story is that no, they don’t. Actually there is a lot of overlap between these risk alleles,” she said.

Robert MacLaren, professor of ophthalmology, University of Oxford and honorary consultant vitreoretinal surgeon at Oxford University Hospital, Moorfields Eye Hospital and Manchester Royal Eye Hospital, touched on gene therapy for retinitis pigmentosa. Xirius is a Phase I and II gene therapy clinical trial for X-linked retinitis pigmentosa (XLRP), an inherited genetic disease that results in progressive retinal degeneration, which eventually leads to blindness. The disease is caused by a defect in a certain gene located on the X-chromosome, and affects men and women differently.

There are currently no effective treatments available for XLRP. This clinical trial will investigate the safety, tolerability and efficacy of a retinal gene therapy with

an adeno-associated viral (AAV) vector encoding the defective gene Retinitis Pigmentosa GTPase Regulater (RPGR).

Conclusions for the Xirius trial revealed that all 18 patients in six cohorts have been treated in the escalation phase of the Xirius trial. There is early proof of concept with durable dose related improvements seen as early as month 1. Proof of concept provides researchers with the basis to move into the expansion phase this year. Mild steroidresponsive sub-retinal information has been observed in cohorts 4-5 (no vitritis).

Sustained efficacy signal is also seen in 3/3 patients in cohort 3 and 2/6 patients in cohorts 4 and 5.

Dr. Stanislao Rizzo, chair of the Department of Ophthalmology, University of Florence, Italy, delivered a presentation on the Argus II retinal implant for retinitis pigmentosa. Data showed that 76% of patients would undergo the procedure again while only 24% said they would not.

Those who replied in the negative said they had expected more, even though they had received an explanation on the limits and benefits of the system. The incidence of device failure as of June 2018 was only 2 out of 506 implants. He concluded that the results are very encouraging in the majority of patients. Subjects report using Argus II in their daily lives and that it had a positive impact on their well-being. The implant can reliably withstand long-term implantation in a significant number of subjects with an acceptable safety profile, he added.

Mozart Says

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Oh,

the Agony!

by Brooke Herron

W

ithout a doubt, Mozart was a legendary composer. But even with his genius, we have to wonder . . . did Mozart ever agonize over any parts of his masterpieces? Did he ever question whether what key the music should be in, or perhaps what instruments should play which piece?

As an ophthalmologist – and even with his superior intelligence – Mozart would undoubtably be faced with some difficult choices. As many posterior segment diseases remain challenging to treat – some even without a standardization of care – he likely would have agonized over treatment options (like the rest of us mere mortals).

One condition that causes treatment decision agony is subretinal macular hemorrhage. Dr. Carl Ardnt, MD, PhD, professor of ophthalmology, Université de Reims Champagne-Ardenne, Reims, France, discussed this conundrum in his presentation, titled: “Agony of Choice.”

Currently there are multiple treatment options available to manage subretinal hemorrhage, this includes: pneumatic displacement, intravitreal or subretinal recombinant tissue plasminogen activator injection (subretinal rt-PA), intravitreal anti-VEGF drugs, retinal pigment epithelial patch, macular translocation and/or a combination of these therapies. That’s a lot of choices.

Of those, Dr. Ardnt says there are two combinations that work best. The first is vitrectomy with subretinal rt-PA, fluid air exchange with anti-VEGF (in cases of AMD) – this combination produces the greatest visual acuity improvement (VA). For the best final VA, he recommends intravitreal

injections of gas, subretinal rt-PA and anti-VEGF. He then presented several cases to explain his recommendations, some of which are included below.

The first case involved a 56-year-old patient with VA of counting fingers (CF), a history of branch vein occlusion – and she was taking an oral anticoagulant for vein occlusion. “Here, we chose to do the vitrectomy with fluid gas exchange and subretinal rt-PA,” said Dr. Ardnt. “Visual acuity is going up after three months . . . the patient went up to 0.8 which is quite good.” He added oral anticoagulants were suspended and that there’s a better outcome in non-AMD eyes with subretinal hemorrhage.

Another case included a patient with AMD with VA of CF who was treated with vitrectomy, gas, subretinal rt-PA and antiVEGF. “This patient did surprisingly well – they started with CF and VA continuously improved,” said Dr. Arndt. “At each visit, we also re-injected anti-VEGF.” So, should ophthalmologists perform surgery every time? Or just inject into the vitreous? Dr. Arndt says not all the time – it can go very badly.

In the final case, the patient was treated with vitrectomy, subretinal rtPA, gas and anti-VEGF. “At month 1, we had a hemorrhage. At month 2 we had retinal detachment – and the nightmare isn’t finished – then we had recurring hemorrhage under silicone,” he said. “These procedures don’t go well every time.”

Dr. Arndt says that the STAR study will hopefully determine the best line of treatment, provide a clearer understanding of these hemorrhages and answer questions like “is rt-PA really necessary, or is vitrectomy gas enough?”

Dr. Alireza Mirshahi also discussed this “agony of choice” when treating macular hemorrhages. Among the various therapy options, his presentation focused on anti-VEGF as monotherapy. To determine treatment, he says that classification is key.

According to Dr. Mirshahi, the rationale for using anti-VEGF monotherapy is that it’s a causative treatment (inactivation of CNV); it’s minimally invasive, it’s broadly available; its efficacy is independent of postoperative position; it has a very high level of safety; as well as an acceptable level off efficacy.

“Patients with subretinal bleeding in a centrally scarred, peripherally active CNV (with the FLATCAPS classification of F0 P1) are the most suitable for anti-VEGF monotherapy,” he explained. “To goal is to preserve the visual field.”

He notes several studies that support his claims with the evidence stating that results depend on the following: size of the hemorrhage, duration of symptoms and central foveal thickness. Similar results were shown in hemorrhages secondary to PCV. “Anti-VEGF monotherapy is safe and effective in macular hemorrhages, particularly if classified F0 P1,” he concluded. “Classification is key in the decision-making process.” And as long as comparative studies are not available, he gives the following advice: primum non nocere (Latin for “First, do no harm.”)

It’s clear that the agony of choice remains and there are no guidelines for best or first line treatment. This means, for now, ophthalmologists must use their instincts and rely on studies and real-world experience to create their Mozart-approved musical (or surgical) masterpieces.

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23 September 2018 | Vienna, Austria

New Technologies for

VR Surgeries

by Hazlin Hassan Dr. David Chow

N

ew technologies can be used for better outcomes and to create new possibilities in every vitreoretinal surgery, an Alcon Surgical Retina Symposium at the 18th EURETINA Congress heard yesterday.

Moderated by Professor Ramin Tadayoni, from Paris, France, the session discussed the latest cutting edge tools by Alcon, including the NGENUITY 3D Visualization System.

Using the NGENUITY, integrated with the CONSTELLATION Vision System through DATAFUSION software, has shown to be essential in real case scenarios, as all the parameters are displayed on the screen, explained Dr. Khalid Al-Sabti, CEO of the Kuwait Specialized Eye Centre. “This is very important because it will help you to make split-second decisions if you need to alter some of your parameters,” he said.

He showed two cases in which NGENUITY was used, one of which was a straightforward retinal detachment and vitrectomy, where he used the latest cutters to get as close as possible to the retina. If surgeons were not using digital displays, they would not be able to tell the cut-rate they were using, he explained.

“Having a digital overlay gives you accurate information as to what is your cut rate,” he added.

The second case he highlighted was a little more complicated – that of vein occlusion and macular edema (ME).

Some 10 to 15 years ago, the only available option was to use laser but this was extremely difficult and may sometimes have unfavorable outcomes. Today, by

using NGENUITY, with its features such as enhanced depth perception, color filters and magnification, the surgery can be done with a much better outcome than it would have many years ago, said Dr AlSabti. Three-months postoperatively, the normal blood flow was established in the patient. “What used to be a very difficult and unpredictable surgery has become a successful surgery in selected patients,” he said.

Dr. David Chow, Assistant Professor from The University of Toronto, St Michaels Hospital and Toronto Retina Institute, Canada, shared tips on how to apply scientific methods to better use the NGENUITY to maximize its powerful tools during surgeries. He noted that statistics from a survey showed that only 8% of NGENUITY owners always used it, while some 48% sometimes did, and 44% never did.

Some surgeons may take a while to get used to operating the tool effectively, such as maximizing their view on the system, properly focusing the system, properly white balancing the system and so on. With NGENUITY’s greater depth of field compared to microscopes, he said that older surgeons had a bigger advantage using the tool. Magnification is 48% higher with NGENUITY, he added.

He recommended that the camera aperture be kept at 30% and TV at 1.2m as this maximizes the visual capabilities of the NGENUITY. If surgeons need more light, they should turn up the light pipe power and not open the camera aperture, which is a common mistake. For macular work,

he advised surgeons to maximize lateral and depth resolution, whereas for global vitrectomy work, he suggested to maximize the depth of field.

The quality of the cutter which you use can also make a difference in surgery. Dr. Carl Claes, from St. Augustines Hospital, Antwerp, Belgium, talked about Beveled 27G probes and shared 3D videos demonstrating how it could improve surgery results. Vitrectome shape is crucial to define how close you can get to the retina without the risk of damaging retinal tissue, he said.

He said he enjoyed using the Advanced ULTRAVIT 10k Beveled Tip Probe Cutters as they can be used as a pair of scissors, and did an excellent job of trimming fibrotic tissues. He also briefly talked about the new SHARKSKIN ILM Forceps, which he said had a very good grip, thanks to its unique design on the tip.

Dr. Stanislao Rizzo, Chair of the Department of Ophthalmology, University of Florence, Italy, showed how his operating room had improved since the installation of NGENUITY. The new equipment proved to be an advantage for scrub nurses and assistants who were able to watch exactly what he was doing. He also noted that no surgeons reported neck and backache at the end of surgery in 185 operations, each lasting 60 minutes or less.

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