PIE POST (EURETINA 2022 Edition) Issue 3

EURETINA 2022 Gisbert Richard Keynote Lecture

Highlights Discussing Macular Surgery Safety with Patients

by Hazlin Hassan

Amacular hole is a rare eye condition that can blur the central vision, affecting everyday tasks like driving or reading. Usually linked to age-related changes, these holes occur when an opening forms in the macula.

who want to know more about the risks and the outcomes?

Prof. Catherine Creuzot-Garcher, MD, PhD, retinal surgeon, University Hospital, Dijon, France, who is this year’s recipient of the Gisbert Richard Keynote Lecture, provided some tips on how to broach macular surgery outcomes and complications with patients on Day 3 of the 22nd EURETINA Congress (EURETINA 2022) in Hamburg, Germany.

Some patients with macular holes may not require treatment right away but surgeons may recommend surgery if a macular hole is getting bigger, getting worse, or causing serious vision problems. What are the complications of macular surgery, if any, and what do you say to patients Cont. on Page 3 >>

The most difficult question to answer

“One of the most difficult things I fear is to answer a question raised by a patient. ‘Are you sure I can recover or keep my visual acuity or are you sure I do not face complications and I do not lose my vision or worse, my eye?’,” she told the audience.

The main challenges in macular diseases are to recover and keep good visual acuity, while decreasing the rate of complications. Patients may ask what their chances are to recover good visual acuity, or anatomic efficacy in idiopathic macular hole (IMH) surgery.

The chance to close macular holes is very high or is almost 90 to 100% of cases, Prof. Creuzot-Garcher noted. Surgery is increasingly more tailored, whether or not to use a longer-lasting internal template and whether a flap is needed or not. “So we have tailored surgery, reaching very good anatomical outcomes,” she shared.

Combined, instead of consecutive surgery

Patients who can recover 20/20 are generally younger patients, those with good visual acuity at presentation, short duration of symptoms, and integrity of ellipsoid zone. As for complications,

Prof. Creuzot-Garcher considers cataract as more of a mandatory side effect associated with macular surgery.

She proposes more combined surgery in macular surgery, having compared combined surgery versus consecutive surgery. “What we found was that we improved the visual acuity with both groups, that visual acuity recovery was obtained earlier with combined surgery compared to consecutive surgery.

It is also more cost effective to carry out combined surgery compared to consecutive surgery, with a Medicare study showing 17 to 20% per-patient cost saving to Medicare.

Consecutive surgeries cost around 4,676 euros while a combined surgery costs an estimated 2,436 euros.

Complications in macular surgery

Based on more than 150,000 procedures, the endophthalmitis rate after macular surgery was 0.25%. There is a temporary increased risk during the switch to transconjunctival vitrectomy.

Endophthalmitis can be prevented by sticking to recommended practice, that is oblique scleral incision, conjunctival displacement, vitreous incarceration, and the use of intracameral antibiotic (cefuroxime) in combined surgery.

The final complication is retinal detachment. The incidence of retinal detachment after macular surgery is 2.3%.

“In conclusion, microsurgery makes patients and retinal surgeons happy because we have both good efficacy and safety. And we have been able to tailor procedures to better identify good candidates for surgery with limited risk of complications,” emphasized. Prof. Creuzot-Garcher.

In ending her talk, Prof. Creuzot-Garcher noted further that collaborative studies are necessary to reach this goal.

Editor’s Note:

Prof. Dr. Gisbert Richard is the chairman and head of the Department of Ophthalmology at the University Medical Center Hamburg in Eppendorf, Germany. Author of more than 800 scientific papers, he is the co-founder and the first president of EURETINA (2001). Most of his research has been devoted to diagnostic and therapeutic improvements in diseases of the macula, the retina and the vitreous body. He developed fluorescein videoangiography (patent in 1985), which enabled for the first time the quantification of retinal and choriodal circulation and a better understanding of retinal dysfunction.

Prof. Catherine Creuzot-Garcher specializes in diabetic retinopathy and age-related macular edema. She has written 300 papers and 15 books. She is the head of the Department of Ophthalmology at the University Hospital Dijon, France. She is also president of the European Board of Ophthalmology, general secretary of the European Vision and Eye Reserach, president of the College of the University Ophthalmologists of France, and president of the French National University Council in Ophthalmology. She has been knighted with the Chevalier de la Legion d’Honneur for her work in ophthalmology.

Walking a Mile in the Shoes of a Diabetic Retinal Disease Patient at EURETINA 2022

by Matt Herman

Roles were reversed at a Day 3 morning symposium as superstar doctors presented the patient’s perspective on vitreoretinal injections like aflibercept.

It’s hump day here in Hamburg, and it was morning of the living dead here at the Congress Center Hamburg as the 22nd EURETINA Congress (EURETINA 2022) participants lumbered sleepily into the venue for a third day of retinal action.

But sluggishness was not on the menu at this morning’s symposium, entitled Durability Across Indications, as your correspondent squeezed himself between coffee-toting delegates in a packed-tothe-gills Hall 4 for a peek at the patient perspective in diabetic retinal diseases (DRDs).

The beast of treatment burden

Everyone loves a long, sharp needle to the eye every few weeks – or not. Treatment burden and interval decrease is the main goal of any anti-VEGF drug regimen, and according to Prof. Varun Chaudhary, this a key goal in optimizing outcomes for a DRD like nAMD.

Prof. Chaudhary presented two patients who were able to extend their treatment intervals (q) to as high as 12 weeks despite less-than-promising OCT scans. The second patient was particularly challenging, as she was spotty with compliance and not seeing immediate results.

But individualizing her treatment regimen and listening to her concerns paid dividends, and a patient who was ready to give up was brought back from the abyss of vision loss with aflibercept, showing the power of decreased burden of treatment.

When bad news is better than no news

Tough love and hard truths were the themes for Dr. Justus Garweg and his presentation on DME. Diabetes is a chronic disease, and treatment can only go so far as compliance allows.

He shared two patient cases – a working patient with a history of poor systemic diabetes management and a patient with delayed response. Both patients ended up returning to the clinic despite frustration with their treatment regimen, but why?

It might be a bitter pill to swallow, but it’s all about talking to the patient beforehand for Dr. Garweg. “After [some injections], you see some improvement… which is not impressive for the patient. But since he knew from the beginning he had a nonstatic edema… he said ok, you told me before. And after continuing for 5 months he saw a significant gain.”

Treat-and-extend to win with polypoidal choroidal vasculopathy

Moderator Prof. Gemmy Cheung of Singapore National Eye Centre (SNEC) was up next with two polypoidal choroid vasculopathy (PCV) patients of her own. Though the first patient was a big success with only minimal subretinal fluid at q16 after 6 injections, her second patient was more challenging. After a successful start with monotherapy and an extension to q6, compliance fell off and treatment

intervals needed to be carefully adjusted.

The lesson learned, she shared, was that although q16 is the goal, PCV treat-andextend regimen adjustments need to take not only what the eye gives, but also the constraints of the patient and their individual needs.

From clinical trials to the real world with RVO

Superstar retinal expert Dr. Sobha Sivaprasad closed things off with a deep dive on retinal vein occlusion (RVO) and aflibercept (Eylea; Bayer, Leverkusen, Germany).

Dr. Sivaprasad’s LEAVO trial demonstrated that aflibercept is an effective drug for RVO, but the question is whether excellent treat-and-extend results from clinical trials can be translated to the real world.

The cases she showcased indicated that the treat-and-extend does work with RVO. Moderators and audience members alike were abuzz about a patient who saw a gain from 30 letters to almost 80 letters after five injections over two years.

As the session concluded, it was clear that this is just the reality with anti-VEGF injections like aflibercept and new treatand-extend injection regimens; patient outcomes are improving, treatment burdens are decreasing and real world results are within grasp.

The Next Frontier in Fighting Retinal Diseases

by Hazlin Hassan

After a decade of using aflibercept (Eylea; Bayer, Leverkusen, Germany) to treat patients with exudative retinal disease, its maker is looking ahead to the potential role of novel anti-vascular endothelial growth factor (anti-VEGF) formulations, cell and gene therapies and home monitoring, and artificial intelligence (AI) to fight diseases in ophthalmology in the near future.

New innovations could have an impact on clinical practice and the lives of patients living with vision-threatening retinal disease. Bayer AG (Leverkusen, Germany) is exploring cell and gene therapies to treat the currently incurable, said Professor Francine Behar-Cohen of Paris Descartes University in France, during a session on Day 3 of the 22nd EURETINA Congress (EURETINA 2022) in Hamburg, Germany.

Such therapies could mean the reversal of severe diseases for the first time. “Novel pathways are currently under investigation as therapeutic targets for the treatment of retinal disease,” Prof. Behar-Cohen said.

With the first retinal gene therapy approved by the European Medicines

Agency (EMA) in 2018, and others currently in development, gene therapy and related approaches show great potential in the treatment of retinal disease. Bayer is involved in a collaboration investigating nextgeneration cell therapies for age-related macular degeneration (AMD) and inherited retinal diseases.

Preclinical and early-phase studies are also investigating cell therapies with promising results, indicating the potential of these therapies to rescue lost photoreceptors and restore damaged retinal tissue, thus preserving vision.

Bigger could be better after all

Aflibercept 2 mg is the standard of care in exudative retinal disease, offering patient benefits through proactive treatand-extend (T&E) dosing. After a decade of treating more than 20,000 patients from over 20 countries, there is now a hypothetical rationale for increasing the anti-VEGF dose.

“Increasing the initial molar dose of an anti-VEGF agent may offer a longer

duration of VEGF suppression and therefore a reduced treatment burden,” said Professor Paolo Lanzetta of University of Udine in Italy.

Proactive T&E with aflibercept 2 mg can achieve meaningful vision gains with a reduction in treatment burden across indications. The efficacy, durability and safety profile of aflibercept 2 mg is supported by extensive data from clinical trials and real-world studies.

Phase 3 studies of aflibercept 8 mg in nAMD and DME are ongoing, with the aim to improve on treatment outcomes seen with aflibercept 2 mg, the current standard of care.

Next level unlocked

Technological innovations such as home monitoring and AI have the potential to optimize treatment outcomes for patients with exudative retinal disease, according to Professor Varun Chaudhary of McMaster University in Canada. This is achieved by facilitating early diagnosis, reducing treatment burden, aiding disease monitoring and predicting treatment response, he said.

“AI can detect numerous exudative retinal diseases on optical coherence tomography (OCT) at the same level as a retina specialist, which may facilitate early diagnosis,” noted Prof. Chaudhary.

Home monitoring may provide more autonomy to patients and thus may increase adherence, while increased monitoring may allow more timely and consistent patient care thereby improving visual outcomes. It may also help offset the projected growth in demand for ophthalmological care.

“Ongoing initiatives supported by Bayer are striving to advance clinical knowledge and create a network of worldwide expertise, optimizing care and helping patients to see a better life,” said Professor Nicole Eter (University of Munster, Germany) in wrapping up the session.

Preclinical and clinical studies of cell and gene therapies show great potential in the treatment of retinal degeneration by restoring damaged retinal tissue to improve visual function, which Bayer is investing significantly in.

The Injection Insurrection

When to Think Beyond Anti-VEGFs

Anti-VEGF is the gold standard in treating many retinal diseases, but it is not a panacea.

Despite what Hollywood would have us believe, practicing medicine is a rather conservative business. In most cases, treating serious retinal illness is a far cry from the heart-pounding, adrenaline-soaked adventures so popular on the big screen. Anti-vascular endothelial growth factor (anti-VEGF) injections have long been old reliable for many retinal diseases, and there is a bevy of research backing that status up.

But the pathology of retinal diseases is complex, and sometimes old habits need to die hard. On Day 3 of the 22nd EURETINA Congress (EURETINA 2022) at the Singapore Society of Ophthalmology session, top doctors gathered to review instances where antiVEGF injections are not a one-size-fits-all treatment option.

When things are not what they seem

Sometimes retinal diseases are masters of disguise, throwing out red herrings that could lead to costly mistakes. Although this kind of masquerading is normally seen with uveitis, Dr. Alesandro Invernizzi from University of Milan, highlighted some retinal cases where pumping the brakes on anti-VEGF can be critical.

Dr. Invernizzi pointed to pseudocysts and things like macular telangiectasia, acquired vitelliform lesions, domeshaped maculopathy, and inflammatory choroidal neovascularization (CNV) as times when it is best to put the anti-VEGF needle down. In such cases, multimodal imaging, thorough clinical examination

and customized treatment regimens must be looked to instead.

Extra complexity with chronic CS

It’s not all fun and games when central serous chorioretinopathy (CSC) gets chronic, and especially not when you throw vascularization into the mix, which can happen in 36% of all chronic or complex CSC cases.

by Matt Herman

Dr. Camiel J.F. Boon of the Netherlands found that in cases with CNV, anti-VEGF response can fall flat. This could be because CNV in these cases is relatively inactive, with the CSC providing the subretinal fluid instead. Fortunately, our old friend photodynamic therapy (PDT) can answer the call, as either primary PDT or a tag-team of PDT and an anti-VEGF were found to be effective in treating suck tricky cases.

Problematic polyps

Last up on the docket was Dr. Kelvin Teo of Singapore National Eye Centre (SNEC) and his discussion of alternative options for polypoidal choroidal vasculopathy (PCV). Though Dr. Boon touched on this in the previous presentation, Dr. Teo took it upon himself to go deeper.

As a subtype of nAMD, anti-VEGFs would seem to be the logical go-to here, but there are cases where this can be a mistake. One such case is when the polyps become sight-threatening or cause other complications.

Doctors need to reach deeper into their arsenal in such cases. He pointed to a case of submacular hemorrhage that developed 8 weeks after an initial 12week extension with anti-VEGFs, and in this case adding PDT did the trick nicely.

In another case with a submacular hemorrhage, pneumatic displacement seemed to be the go, but a stubborn polypoidal lesion remained. In this case, the lesion was treated with focal laser, and that was that.

Of course, doctors shouldn’t be so quick to toss anti-VEGFs aside in many cases. Treatment regimens are complex, and a simple adjustment when PDT is not an option is always worth a try.