PIE POST (EURETINA 2022 Edition) Issue 1

Kicking it Off in Style at EURETINA 2022

by Matt Herman

The lights were up and the auditorium was packed for the opening ceremony of the 22nd EURETINA Congress (EURETINA 2022) on a beautiful September afternoon in Hamburg, Germany. Doctors, industry and press trickled in and filled seats all the way up to the opening remarks. The anticipation was palpable as attendees waited for the official opening of the four-day long event at the Congress Center Hamburg.

But all was quiet as the lights went down for Dr. Alistair Laidlaw, the current president of EURETINA, as he made his opening remarks about the past, present and future of the congress. With over 5,000 attendees, Dr. Laidlaw noted that this year’s event is a far cry from 22 years ago, which welcomed 230 delegates in the meeting’s first iteration.

Dreaming impossible dreams with diabetic retinopathy

With the pleasantries out of the way, it was time for the main event. The crowd erupted with electric applause as Dr. Laidlaw affectionately introduced a titan of the retinal world, 2022 EURETINA Lecture honoree, Dr. Sobha Sivaprasad.

Editor-in-chief of the prestigious Eye journal and recipient of over 18 million euros in grants, Dr. Sivaprasad is one of the most eminent and published researchers of the last few decades in the retinal world. Her EURETINA 2022 lecture was titled Steps to Achieving the Impossible in the Clinical Management of Diabetic Cont. on Page 3 >>

Retinopathy, and the buzz died down to quiet admiration as she launched into an analysis of the future of managing diabetic retinopathy.

Subdivide and conquer

Dr. Sivaprasad began by laying out three challenges in diabetic retinopathy research that need to be tackled: Preventing diabetic retinal disease (DRD), finding disruptive innovations and laying out steps to find such innovations.

One key factor Dr. Sivaprasad highlighted in accelerating research into DRD is the implementation of a system categorizing the disease’s progress into stages. In Group A, patients are little affected by their disease and still enjoy a high quality of life. Group B patients are already starting to see the onset of symptoms, and Group C patients have advanced forms of DRD with significant comorbidities. Part of the problem, Dr. Sivaprasad opined, is that most treatments focus on the more advanced patients in Group C, and she called for more attention to earlier stages in order to gain a step on DRD.

She then went over a series of steps for improving outcomes, starting with Group A. She stressed the importance of biomarkers early on, and emphasized controlling hyperglycemia and other risk factors. For Groups B and C, it is important to recognize adaptive changes in the retina, especially neuronal changes and microvascular changes. And for Group C, she stressed the need for neuroprotective agents, and highlighted the importance of predictive imaging going forward.

In the end, much can be done to usher in a new era for DRD according to Dr. Sivaprasad. Research foci can be

rebalanced,urgently needed prevention trials should be launched, and novel clinical endpoints must be validated.

Setting therapeutic targets for retinal neuronal changes will be key for disease management. Dr. Sivaprasad also put forth one critical avenue of research that will be a game changer for DRD –restoring the vascularization of the nonperfused area. “The ambition,” she said, “is to see a world without vision loss from diabetic disease.”

Awards ceremony, a bellwether for progress

Raucous applause for Dr. Sivaprasad’s lecture faded into the closing portion of the afternoon’s program, an awards ceremony for 2022 EURETINA Retinal Medicine Clinical Research Grant (RMCR) recipients and Film Award winners.

Three outstanding films were honored with EURETINA’s film awards. Third prize went to Dr. Adel Al-Akeely of Saudia Arabia for Subretinal Lavage for Persistent Subretinal Fluid after RRD Repair; 2nd prize was given to Dr. Piergiacomo Grassi of the United Kingdom for his film on removal of traumatic suprachoroidal dislocation of the crystalline lens, and 1st prize went home with Dr. Gagan

Bhatia of India for The Black Nucleus: An Anterior Segment Pearl or a VR Surgeon’s Nightmare?

Two awardees of 2022 RMCR grants were honored. The first was Dr. Claudia Farinha of Portugal, for her study entitled Diet, Lifestyle, Systemic Medication and Genetics: Can the Risk for AMD be Modulated? (AMD_LifeGene). The second grant went to Dr. Suzanne Yzer of the Netherlands and her study on

Risk of Posterior Staphyloma in Highly Myopic Europeans: From Epidemiology to Anatomy and Back.

The presenter, Prof. Dr. Reinier Schlingemann, noted that the awarding of these grants and the EURETINA 2022 Lecture to women represents a seismic shift in the landscape of retinal medicine. The days of old when men dominated the field are over, and Prof. Dr. Schlingemann praised the women all around the world who are finally being recognized for their massive contributions to the fight against retinal disease.

With diseases like diabetic retinopathy on the rise, all hands the world over are needed on deck to stem the rising tide of sight-stealing diseases. And because of the work of incredible doctors like those showcased at the EURETINA 2022 opening ceremony, it certainly seems like sufferers of retinal disease have more than a fighting chance.

“The ambition, is to see a world without vision loss from diabetic disease.”

— Dr. Sobha Sivaprasad

The Ins and Outs of Diagnosing and Treating AMD

by Hazlin Hassan

Age-related macular degeneration (AMD) is the leading cause of severe, permanent vision loss in people over age 60. While there is no cure for it (yet), leading experts around the world discussed the latest in treatment regiments and a potential cure in the works for geographic atrophy, or latestage dry AMD, on the first day of the 22nd EURETINA Congress (EURETINA 2022) in Hamburg, Germany on Thursday.

Treat-and-extend from the start?

Treatment-naive patients with neovascular age-related macular degeneration (nAMD) may be treated with a treat-and-extend regimen (T&E) from the start with good functional outcomes, said Prof. Dr. Martin Zinkernagel from the Department of Ophthalmology, University of Bern, Inselspital, Germany.

This approach could reduce the treatment burden in some patients. The risk of undertreatment seems to be small as extension is only after two initial injections, and is done in two-week increments, he explained. He said that data from trials showed that a direct extension without the loading phase was possible in 42 (51%) of the patients.

Two (5%) of these patients had signs of activity with shortening of intervals after the third injection. Fifteen percent (15%) never had a reduction of the interval during treatment.

abnormalities identifies visual distortions caused by, but not limited to, conversion from dry to wet AMD. The ForeseeHome monitoring program (Notal Vision, Tel Aviv, Israel) is an early warning system to help patients detect wet AMD earlier while at home, in between eye appointments.

The PHP test is performed by the patient, she said. A home OCT allows doctors to safely extend retreatment intervals, she said, adding that patients showed excellent compliance in the real world.

New treatment on the horizon?

Dry AMD is a major public health concern and developing treatment options for the condition is challenging. Various treatment approaches are currently being investigated for dry AMD, the leading cause of visual disability in the industrialized world, said Dr. Kourous Rezaei of Illinois Retina Associates and Rush University Medical Center, USA.

Among the challenges of designing studies are that the etiology of AMD is not well-known and may be multifactorial. Disease progression is slow, and can be variable among patients.

“There is a mini loading phase of two injections and careful extension by two weeks. Optical coherence tomography angiography (OCT-A) monitoring is necessary. It potentially saves one antiVEGF injection in some patients, and longer durability anti-VEGF drugs in the future may be especially suited for such a treatment-extended regimen from the start,” concluded Prof. Dr.

Zinkernagel

Home monitoring in the era of long duration treatments for AMD

A new digital health model has been devised for remote patient monitoring, according to Prof. Anat Loewenstein, professor and director of the Department of Ophthalmology, Tel Aviv Medical Center, Israel. “Long duration treatments for AMD demand novel diagnostics methods,’’ she said. “We evaluated a new digital health model for remote patient monitoring.”

The preferential hyperacuity perimetry (PHP) test for detecting visual

An advanced form of dry AMD, geographic atrophy (GA) can have a devastating impact on vision. In the GATHER 1 Phase 2 and 3 trials evaluating the safety and efficacy of Zimura (avacincaptad pegol, IVERIC bio, NJ, USA) for the treatment of GA, 18-month safety data showed that it was generally well-tolerated after 18 months of administration.

“There was no Zimura-related inflammation, no Zimura-related discontinuation from the trial, no cases of endophthalmitis, and no Zimura-related adverse events,” said Dr. Rezaei.

“Through month 18, the reported incidence of CNV in the untreated fellow eye was 11 patients (3.8%) and in the study eye was 3 patients (2.7%) in the sham control group, 8 patients (11.9%) in the Zimura 2 mg group, and 13 patients (15.7%) in the Zimura 4 mg group,” he added.

The most frequently reported ocular adverse events were related to the injection procedure.

When a Plan Doesn’t Come Together

The Real World Efficacy Gap and Diabetic Macular Edema

Presenters at the 22nd EURETINA Congress (EURETINA 2022) in Hamburg, Germany, explained why exciting new breakthroughs in DME therapy sometimes don’t live up to their clinical trial promise.

It can be the ultimate buzzkill – a landmark new retinal treatment crushes its clinical trial benchmarks and zips through regulatory approval. Vitreoretinal clinicians and patients worldwide rejoice at a potent new partner for saving sight and battling baddies like diabetic macular edema (DME). Life is fine as the sun shines afresh on a dark and potentially sight-stealing condition.

But then doctors begin treatment and the letdown comes. Promising and seemingly iron-clad clinical trial results end up not carrying over into the real world. This is the reality of the efficacy gap, and doctors at a lunch symposium on Day 1 of EURETINA 2022 made headway in clarifying its origins.

Playing hooky, playing with fire

In the first presentation, Dr. Laurent Kodjikian of France laid out some of the known causes of this efficacy gap with DME in his presentation entitled Unmet Needs in the Treatment of DME.

One of the major roots of causes of the efficacy discrepancy, according to Dr. Kodjikian, lies in injection frequency and patient compliance. Missing injections will cause serious adverse effects in terms of visual acuity loss and progression of DME, and this leads to an efficacy gap.

Dr. Kodjikian then pointed to a variety of things that lead to loss of patient compliance in the real world. Frequent injections with anti-VEGF treatment mean more hospital visits. And with the average appointment taking 4.5 hours, many patients fall by the wayside and tank

by Matt Herman

results compared to efficacy in trials.

His research also found that 25% of patients are also lost to follow-up, which also undoubtedly both obscurs trial results and indicates future compliance issues in the real world. “We have to keep in mind that poor adherence to anti-VEGF treatment in the real world may lead to suboptimal outcomes and rewards,” he concluded.

Getting in early and considering the mechanism of action

Of course, laying all the blame at the feet of the patient is just plain unfair. To this end, Dr. Javier ZarranzVentura’s presentation – Translating the Mechanism of Action into Efficacy in Real-world Clinical Practice – dealt with how caregivers can better translate the mechanism of action of drugs like dexamethasone into real world results.

He first shared some data about Ozurdex (dexamethasone intravitreal implant), with existing research showing the drug undetectable about 6 months post-implantation. This makes time an important factor, Dr. Zarranz-Ventura said. “If you treat patients early, they always start their treatment with better reliability, they always get better with each treatment down the line, and they end up with better vision.”

With that he pointed out differences in patients who are treatment-naive or who have been previously treated for the disease. This is where the importance of the mechanism of action comes into play.

If drugs like dexamethasone or even for other eye conditions are still detectable, this changes efficacy in the real world versus in the heavily controlled

environment of a trial. Dr. ZarranzVentura concluded that this and many other pathways and pathophysiological variables factor into what to use as the first-line or second-line treatment. And this has a profound influence on realworld outcomes stacking up to RCT results.

The power of customization

All this culminated in Dr. Patricia Udaondo’s presentation – Individualizing Treatment in DME and International Guidelines – which tidily wrapped up the session. Patient compliance is an issue, and with the influence of differing mechanisms of action what can be done

It’s quite simple, according to Dr. Udaondo. “Trying to trick this complex disease with a single treatment or treating all the patients the same way is not the answer,” she stated.

The trick, of course, is seeing that different patients have different needs. Compliance may be an issue with some, and so treatments like Ozurdex (Allergan, an AbbVie company) that require significantly fewer injections may fit them. Other patients appear at earlier or later stages in the progression of the disease, while others still have already proven unresponsive to treatments like anti-VEGF.

The key is considering all of these factors and more. And if this is done, the prospects for patients with DME are bright indeed.

Syndromic and Vascular Retinal Disease in Childhood

by Hazlin Hassan

While there is still no cure for retinal dystrophies, a heterogeneous group of hereditary diseases that cause progressive and severe loss of vision, researchers around the world are attempting to find ways to treat these, including gene therapy.

A pioneering new gene therapy treatment may help to save the sight of patients with Leber’s congenital amaurosis (LCA), a mutation in the RPE65 gene, that causes retinal dystrophy and affects 1 in 40,000 newborns.

The voretigene neparvovec (Luxturna™; Spark Therapeutics, PA, USA) gene therapy is administered through an injection under the retina, and restores the ability to make normal protein like that in a healthy eye. Dr. Robert Henderson, pediatric ophthalmologist and vitreoretinal surgeon at the UCLGreat Ormond Street Institute of Child Health, United Kingdom, shared during the first day of the 22nd EURETINA Congress (EURETINA 2022) in Hamburg, Germany on Thursday, that 11 patients had been treated, involving 21 eyes.

Dr. Henderson shared videos of one of the

patients, a 3-year-old boy who behaved like a typical RPE65 patient and was looking for the sun or spotlights, as his light-sensitive cells in his retina were not working properly, before he was treated. Post-treatment, the boy was seen being active and cycling during a dimly-lit “typical British winter’s evening.”

Despite the fact that the boy had bilateral subfoveal atrophy secondary to therapy, the parents are still happy that his visual behaviors have improved and feel that it has been a benefit, said Dr. Henderson. Evidence suggests that younger children receiving this treatment could see better results than older patients. Nearly half of patients developed subretinal deposits.

Pediatric retinovascular disease

Dr. Henderson also discussed several clinical features of pediatric retinovascular disease.

Two-thirds of patients with Coats’ disease, a rare eye disorder involving abnormal development of blood vessels in the retina, will present before the age of 10, with 70% being males. Treatment

modalities include laser to areas of non-perfusion and direct to aneurysmal vessels, intravitreal avastin, and steroids.

Incontinentia pigmenti is a congenital multi-system disorder, which in the eye presents as a vasoproliferative disorder of the retina that can cause total retinal detachment and blindness. Other systems affected are skin, central nervous system (CNS), teeth and hair. The most common ocular features are peripheral avascular retina with abnormal vessel proliferation which can lead to retinal folds, total retinal detachment and blindness. Other rarer ocular findings are strabismus, congenital cataract and microphthalmos. A total of 62% will present with dental abnormalities such as hypodontia and microdontia, 25% with neurological complications such as epilepsy.

Pediatric syndromic retinal detachment

Pediatric syndromic retinal detachment (RD) and persistent fetal vasculature (PFV) involves very challenging surgeries, said Dr. Fanny Nerinckx, senior vitreoretinal surgeon at the Ophthalmology Department at Ghent University Hospital, Belgium. Her advice is that surgeons must identify underlying vitreoretinal pathology, define their surgical strategy, and consider sequential bilateral surgery.

They must also think about specific instruments to use, and the patient’s postoperative care.

Amblyopia treatment is also mandatory to achieve a good visual outcome.

In cases of pediatric syndromic RD, she noted that 30% of pediatric RDs are traumatic.

“If there is no trauma, 50% are associated with ocular conditions,” said Dr. Nerinckx.

“Careful examination is needed,” she emphasized.

For PFV, she suggests first ruling out retinoblastoma. Surgery should be done in six to eight weeks, with follow-ups after to check for refractive changes, as well as amblyopia treatment.

Surgical complications may include iatrogenic retinal tears, hemorrhage when cutting stalk, and secondary glaucoma.