PIE POST @EURETINA 2023, Issue 2

EURETINA The 23rd

Congress

Opens in Historic Amsterdam

The 23rd Congress of the European Society of Retina Specialists (EURETINA 2023) opened in the Netherlands, on Thursday at the RAI Amsterdam convention center, located only a short distance from the famous canals, museums and bustling center of the historic capital.

The Congress is taking place in hybrid mode, with content available for streaming during and after the event.

Thousands of delegates are attending this year’s live meeting held at the sprawling center in the Zuidas business district, with an exciting array of lectures and surgical skills training courses lined up daily until Sunday October 8, as well as the EURETINA exhibition featuring over 60 companies

by Hazlin Hassan

showcasing the latest in retina technologies and innovations.

EURETINA Lecture on OncoVR subspecialty

Delegates at yesterday’s opening ceremony had the privilege to hear this year’s EURETINA Lecture by Professor Bertil Damato, consultant ocular oncologist at St. Erik Eye Hospital, Stockholm, Sweden, and Moorfields Eye Hospital, London, United Kingdom.

“It’s very hard to find someone who doesn’t speak extraordinarily highly of him,”

EURETINA president Alistair Laidlaw said in introducing Prof. Damato. A highly-decorated professional, Prof. Damato provides expert,

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Congratulations to candidates who passed the inaugural FEBOS-EURETINA (Subspecialty) Exam for retina specialists, to set the standard of knowledge and clinical acumen, and harmonize patient care across Europe.

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industry-leading treatment in adult ocular oncology including ocular naevi, ocular melanoma and ocular carcinoma alongside ocular metastasis and conjunctival melanosis.

Prof. Damato is responsible for various innovations in modern ophthalmology, including being the first to formulate the concept of ‘toxic tumor syndrome’ after radiotherapy of uveal melanoma and to treat this condition by surgical removal or laser ablation of the offending tumor. He was also the first to perform trans-palpebral proton beam radiotherapy of uveal melanoma, thereby preventing ocular morbidity from keratinization of the superior palpebral conjunctiva.

Prof. Damato has also developed ‘MOLES’, an algorithm to distinguish benign naevi from malignant melanomas at the back of the eye. Speaking on the topic of OncoVR – A New Subspecialty?. Prof. Damato explained that onco-VR surgery can be divided into two sub-types of ‘biopsy’ and ‘treatment’. The former can be split into prognostic and diagnostic while the latter can be primary or secondary.

Biopsy techniques can also be separated into two types, one of which is the ‘maximalist’ where the surgeon carries out a total vitrectomy, retinopexy, and gas tamponade which could result in ocular morbidity.

However, Prof. Damato is in favor of the ‘minimalist’ technique, with no vitrectomy, retinopexy, or gas tamponade, where the operation is short and safe for the patient.

He also shared tips on how to carry out biopsies and prevent complications such as hemorrhage and seeding.

He also touched on how to treat retinal detachment after exoresection and toxic tumor syndrome. “Is there scope for an oncoVR subspecialty?

Of course I am going to say yes, because an oncoVR surgeon has the specialist knowledge and experience to obtain larger tumor samples with smaller biopsy procedures, avoid endoresection complications, such as local reccurences, intraocular

hemorrhage and gas embolism,” he explained. An oncoVR surgeon is also capable of successfully performing complex salvage procedures unique to ocular oncology, he added.

Inaugural August Deutman Awards

Last but not least, the August Deutman Awards were also handed out at the end of the opening ceremony to honor the contributions of Prof. August F. Deutman, MD, a highly-esteemed Dutch medical retina and vitreoretinal surgeon who was co-founder and the first president of EURETINA from 2001 to 2003. Prof. Deutman, who personally presented the awards, had co-founded EURETINA after seeing a need and opportunity for a new organization to help the members of the ophthalmology profession keep up to date with developments in the field of retina which was starting to take off at the time with the advent of revolutionary anti-VEGF treatments.

The EURETINA was established in 1999 to promote the sharing of knowledge among European vitreoretinal and macula specialists. Its annual congresses are the highlight of the Society’s annual activity, and since the 1st EURETINA Congress in 2001, participation has expanded rapidly from 211 to over 5,000 in recent years.

It aims to promote the exchange of knowledge and encourage critical discussion of new research and techniques between vitreoretinal and macula specialists worldwide. EURETINA actively promotes new diagnostic developments, advances in

vitreoretinal surgery, the development and application of new drugs, and changes in macular degeneration treatment. The Society is particularly committed to educating young vitreoretinal surgeons and encouraging the pursuit of its subspecialty among newly qualified ophthalmologists.

The winners of the inaugural awards are:

Best Free Paper

Paolo Lanzetta, University of Udine, Italy

Intravitreal aflibercept 8mg injection in patients with neovascular age-related macular degeneration: 60week results from the Phase 3 PULSAR trial.

Best e-Poster

Lourdes Vidal-Oliver, FOM

Valencia, Spain

Macular changes in patients with light silicone oil tamponade after macula-off retinal detachment surgery.

Best Video

Apoorva Ayachit, M M Joshi Eye Institute, India

Trials and tribulations in complex pediatric vitreoretinal detachments.

Top Scoring EBO-EURETINA

Exam Candidate 2023

Fernando Jose Huelin

Alcubierre, Spain

Retinal Detachment and Macular Holes

Face-to-face with evidence-based medicine

by Matt Herman

Day 1 of EURETINA opened up with a volley of vitreoretinal goodness. The target? Retinal detachment and macular holes, where a new injection of evidence-based approaches is changing everything.

The shuffle of feet and din of ophthalmic conversation is everywhere at RAI Amsterdam Convention Centre as Day 1 of the 23rd EURETINA Congress (EURETINA 2023) kicked off in style. And not a second was wasted in the Grand Auditorium, where audiences were treated to a marquee opening EURETINA Session, entitled Vitreoretinal Surgery I: Seeking the ground truth – evidencebased medicine approaches in retinal detachment and macular holes.

Learning from failure with PVS

After a pair of introductory talks from co-chair Prof. Pertile (Italy) and honorable guest Prof. John Norrie (United Kingdom), it was straight to the heart of the matter with Dr. Friederike Schaub (Germany). In her turn at the podium, she shared data from the PRIVENT trial1 on proliferative vitreoretinopathy (PVR).

The trial examined the preventative power of intravitreal 5-fluorouracil and heparin in PVR, and the results were… negative (!). “Unfortunately the interim analysis showed that there was no benefit for the trial patients that received [5-fluorouracil and heparin] in comparison to the placebo group,” she lamented after presenting the results.

The value of the trial, however, lies elsewhere. “We are at the beginning of the search for a solution to the PVR problem.” she said. “But it’s important to talk about and publish such negative results because we can all learn from them,” she concluded.

Dr. Schaub mentioned many such takeaways – but there was one that stood out. “I think the main reason [for the failure] was that we could not predict high risk eyes for PVR with laser flare photometry,” Dr. Schaub concluded. “We need to reconsider our knowledge about laser flare photometry.”

RRD and a BEAVRS data dam

Prof. David Yorston’s innovative use of data from EURETINA and the British and Eire Association of Vitreoretinal Surgeons (BEAVR) to test a tricky hypothesis on early intervention in off-macula rhegmatagenous retinal detachments (RRD) was up next.

“The obvious way to test this [maculaoff RRD] would be an RCT [randomized controlled trial], but it would be difficult to get regulatory approval to randomize patients to either immediate surgery or deliberately delayed surgery,” he noted.

This previously insurmountable obstacle is now eminently surmountable in the modern world of large databases – without risking patients’ sight. According to Dr. Yorston’s findings, the probability of regaining 6/12 or better vision improves if surgery is performed within 72 hours, with the probability of snatching back 1.3 logMAR or more reduced for every additional day of waiting.

Not (?!) taking macular holes lying down

Patients hate the face-down position still mandated during recovery from macular hole surgery. And in the final talks of the session, Profs. Varun Chaudhary (Canada) and David Steel (United Kingdom) gave some (mostly) good news on this front.

In his systematic review and metaanalysis, Prof. Chaudhary found that the face-down position had little to no effect on macular hole closure rate, with only a slight benefit to visual acuity. Great news for most macular hole patients dreading their postoperative staring match with the floor.

But not all of them, according to Prof. Steel. Though his meta-analysis mostly agreed with Prof. Chaudhary’s, there was one caveat in Prof. Steel’s individual participant data (IPD)-based meta-analysis. With macular holes greater than 400 microns, he found benefits to closure and visual acuity, though they plateaued at five days.

This slight deviation in results notwithstanding, there was one important takeaway for Prof. Chaudhary. “We need to look at the combination of clinical expertise, research evidence, and patient values and preferences. And these should be an important part of the consent process when we talk about positioning to our patients.”

Reference

1. Schaub F, Schiller P, Hoerster R, et al; PRIVENT Study Group (2022). Intravitreal 5-Fluorouracil and Heparin to Prevent Proliferative Vitreoretinopathy: Results from a Randomized Clinical Trial. Ophthalmology. 129(10): 1129–1141.

Precision Medicine Approach Needed in Diabetic Macular Edema

by Hazlin Hassan

Precision medicine is needed in the management of DME amid a myriad of challenges including many patients not responding well to treatment, experts at the 23rd EURETINA Congress (EURETINA 2023) in Amsterdam, Netherlands said on Thursday. A large proportion of patients do not respond well to anti-VEGF agents and there is a lack of evidence-based and universally accepted treatment regimen. Identifying which patients will not respond to anti-VEGF agents and determining the optimal administration interval are among the major challenges when it comes to managing this disease.

Unresponsive patients and unpredictable results

Edoardo Midena, MD, PhD, professor and chairman of the Department of Ophthalmology, University of Padova, Italy, said there are “unrecognized” different pathophysiologic pathways with DME, during a session on Day 1 of the congress. There are also “unpredictable” treatment results with the current “so-called gold standard” of care, said Prof. Midena. “The realworld scenario and the worldwide data is showing that after the first year of treatment, an important proportion of patients treated with the gold standard approach are not really responding to the treatment,” he said. The DME personalized treatment needs a “precision medicine” integrated approach. “The pathophysiology of DME needs to be fully revisited.”

Liquid biopsies are not just for cancer anymore

Liquid biopsies offer the potential to improve on the knowledge of intraocular eye disease and the management of DME. Aqueous (AH) and vitreous (VH) humour could

prove valuable in efforts to study retinal conditions, as they are suitable fluids to study biomarkers for retinal disorders, said Giulia Midena, MD, from the University of Padova, Italy.

Liquid biopsies are non-invasive and samples can be collected repeatedly. They also provide considerably comprehensive information, and are more sensitive as biomarkers than that of tissue biopsy. Biochemical circulation biomarkers are biomarkers obtained by sampling biologic fluid. “Emerging technologies have opened up a new concept of ‘imaging biomarker’, which allows a better understanding of the main pathogenic process involved,” she explained. The exact quantification of intraocular biomarkers contributes to the precision medicine approach.

An AH liquid biopsy also seems to overcome the limitations of imaging biomarkers and clarifies the pathophysiology of DME, she concluded.

Seeing more with AI

Artificial Intelligence-based algorithms can help in the diagnosis and treatment of DME, said Marco

Lupidi, MD, associate professor of ophthalmology at Università Politecnica delle Marche, Italy. The algorithms are diagnostic tools that can identify different biomarkers that characterize DME, he explained. AIbased algorithms provide a reliable and reproducible assessment of the most relevant OCT biomarkers in DME.

The method may allow clinicians to routinely identify and quantify these parameters, offering an objective way of diagnosing and following DME eyes. “Current results encourage the integration of these AI-based approaches into clinical practice to help in the diagnosis and evaluation of the therapeutic response,” added Dr. Lupidi.

A study on the fully automated detection and quantification of macular fluid in OCT using deep learning showed that a method based on deep learning is able to detect and quantify intraretinal (IRF) and subretinal fluid (SRF), with optimal accuracy for patients with DME, neovascular agerelated macular degeneration (AMD), and retinal vein occlusion (RVO). Optimal accuracy for the detection and quantification of IRF for all 3 macular pathologies.

EURETINA’s Diabetic Retina-o-Rama Rundown

by Matt Herman

You can’t throw a rock down the road of modern posterior segment without hitting diabetic retinal issues. EURETINA 2023 wasted no time getting to it with some of the most recognizable names in the game.

around one such avenue –angiopoietin-2 (ANG2) inhibitors.

Roche’s VABYSMO (faricimab injection) targets both ANG2 and VEGF pathways, but the key takeaways from Prof. Schlingemann’s talk were mixed. After an analysis of the YOSEMITE and RHINE studies comparing faricimab to aflibercept, Prof. Schlingemann’s first conclusion was pointed.

“If you look at a clinical study, you always have to look at the primary outcomes. So does adding angiopoietin-2 add to efficacy compared to anti-VEGF? The answer is no. There was no superiority” he said flatly.

But Prof. Schlingemann was clear that this is not the end of the road for ANG2, or even for faricimab – far from it, in fact.

“Is there hope for faricimab? Yes, there is hope,” he continued. “I think that faricimab is very valuable as a second-line drug in nonresponders to anti-VEGF A.”

Vitreoretinal specialists the world over would be hard-pressed to find a more talked-about topic in retinal medicine than maladies related to diabetes. Maybe it’s because diabetes is on the march worldwide, and has been for decades. Maybe it’s due to the fact that treatment agents like anti-VEGFs make it one of the most valuable segments in ophthalmology – and all of medicine, for that matter.

Whatever the case may be, new inquiries into and knowledge about how diabetes affects the retina is more critical than ever. And the 23rd EURETINA Congress (EURETINA 2023) didn’t waste any time putting some of these issues center stage with EURETINA Session 2: Diabetic Retina bright and (sort of) early in the

Grand Auditorium of the RAI Amsterdam Convention Centre.

Beginning of the end for anti-VEGF?

From miracle cure to much maligned, anti-VEGF agents have had their fair share of twists and turns since their introduction over twenty years ago. Many in the retinal space, like session co-chair Prof. Reinier Schlingemann (The Netherlands), recognize both the potential and pitfalls of treating exudative disease with these powerful agents. But is it time yet to go beyond anti-VEGF?

In his leadoff presentation, Prof. Schlingemann centered his talk, Beyond VEGF in Diabetic Retinopathy,

And this ability alone, compared to faricimab’s similar results to aflibercept at q8 and q16 in the YOSEMITE and RHINE studies, means that there is much more work to do to make a definitive declaration about other therapeutic targets like ANG2.

“If you look at a clinical study, you always have to look at the primary outcomes. So does adding angiopoietin-2 add to efficacy compared to anti-VEGF?

The answer is no. There was no superiority”

Prof. Reinier Schlingemann

New updates from retinal research valhalla

The Diabetic Retinopathy Clinical

Research Network (DRCR.net) studies are legendary in posterior segment, and Dr. Jennifer Sun from the United States was on hand to give some updates.

Her talk summarized an effort by DRCR.net to standardize the categorizations of responses to antiVEGF in diabetic retinopathy patients as ‘strong’ and ‘weak’.

“One of the major questions that’s arisen in the field is how we can better predict which eyes respond well to treatment and which ones won’t,” Dr. Sun began. “Addressing this question has really been limited by the lack of agreement on the definitions of treatment response.”

Enter DRCR.net, whose work focused on phenotyping the disease into strong and weak responders based on central subfield thickness (CST) and visual acuity (VA). “We fit equations to estimate the change in vision and central subfield thickness at 24 weeks as a continuous function,” she explained.

Those above the line determined by this function were considered as

‘strong responders’ and those under as ‘weak. “These are more precise than the three baseline categories shown before,” she continued, referring to previous methodologies setting static ranges as response subtypes.

In the end, the uses for such a classification are many. Dr. Sun indicated that these phenotypes could be used to drive research on potential new therapeutic targets. In the near term, future DRCR pharmacogenetic studies, training artificial intelligence to predict treatment response, and work in predictive biomarkers will all make use of these continuous functiondefined response categories.

DIAMONDS are forever

Retinal laser is starting to find its way into more and more clinics, and Prof. Noemi Lois (United Kingdom) shared results from the DIAMONDS study comparing subthreshold micropulse laser (SML) to standard laser (SL) for the treatment of diabetic macular edema (DME) in patients with central subfield thickness (CST) values of less than 400 microns.

The trial was designed to detect equivalence in the two treatments, but Prof. Lois also noted that it was also able to detect non-inferiority and superiority. Best corrected visual acuity was the primary endpoint, but a variety of secondary endpoints including CST, cost per quality of life year (QALY) and number of laser treatments received.

In the end, DIAMONDS showed SML and SL to be equivalent for the primary endpoint. But significant differences were found in cost (GBP897.83 for SML vs. 1,125.66 for SL), making SML an effective and cheaper option for DME treatment in patients with CST of less than 400 microns.

The return of DRIL?

The venerable Prof. Edoardo Midena (Italy) needs no introduction to the vast majority of the retinal world, and his long-standing fixation on biomarkers for retinal disease shouldn’t, either. The topic of his talk was the controversial disorganization of retinal

inner layers (DRIL), and their use as a biomarker.

Prof. Midena’s talk centered around potentially new revelations about DRIL based on retinal OCT imaging, and most importantly, a novel approach using liquid biopsy in human eyes. The presence of DRIL has been correlated with visual acuity loss, but there are still doubts about how useful it is. “We need to identify the biological counterpart of the OCT signs we are currently seeing on our examinations,” he stated generally.

Though his work on DRIL did not provide a definitive verdict, it did yield tantalizing prospects. “DRIL remains a controversial issue. We have not solved the story. But the liquid biopsy approach… has shown that it’s correlated more to Müller cell dysfunction more than other components in the retina,” Prof. Midena concluded. And this, either through the findings themselves or its landmark use of liquid biopsy, could open up the door to a new world of possibilities.

Systemic risk roundup

Dr. Mathus Rehak (Germany) was up last with his review of the literature on systemic risk factors and their influence on the efficacy of DME treatment. For Dr. Rehak, it’s clear that morphological, mostly OCT-based ocular parameters are insufficient in predicting visual acuity in sufferers of the disease.

This, when combined with the wellestablished correlation between systemic factors and the development of these diseases, makes systemic factors a promising area of research for predicting visual acuity responses to treatment, according to Dr. Rehak.

Amongst all of the published work, there is one avenue that is already yielding results. “We have some signals that renal parameters might influence the final prognosis for visual acuity in our patients,” he asserted. But this is only the beginning. “We still need further, larger prospective studies to explain the role of single systemic parameters,” Dr. Rehak concluded.

Prof. Reinier Schlingemann (The Netherlands)

Prof. Noemi Lois (United Kingdom)