Some of the top names in retina, from Dr. Judy Kim (USA) to Prof. Gemmy Cheung (Singapore), gave updates on the latest developments in neovascular age-related macular degeneration at the AAO 2024 Subspecialty Day in Chicago.
State of the art developments in neovascular age-related macular degeneration (nAMD) were on the docket during the retina portion of the Subspecialty Day at the 128th Annual Meeting of the American Academy of Ophthalmology (AAO 2024).
Leaders in the field took the stage to deliver bite-sized updates from across the nAMD landscape, including imaging, potential correlations between anti-VEGF and atrophy formation, polypoidal nAMD, fibrosis and more.
The present and future of nAMD imaging
Dr. Judy Kim took the microphone first to talk about the present state of imaging in nAMD—and lay out where we might be going.
One of the most important steps forward in imaging, said Dr. Kim, has been the move from a fluorescein angiogram-based classification to one more in tune with modern methods.
“In the era of OCT and anti-VEGF, millennials have never been taught—and we often don’t use—classification based on angiograms because we have non-invasive, in vivo biopsies of the retina in normal and diseased states,” she said. “Recently, OCT-based macular neovascularization has been developed.”
This OCT-based classification system includes Type 1, or occult, macular neovascularization (MNV), Type 2 (classic), Type 3 (retinal angiomatous proliferative) and polypoidal choroidal vasculopathy (PCV).
Dr. Kim then described the system she and other members of the Asia Pacific Ocular Imaging Society PCV Workgroup have laid out for PCV.
The workgroup has formulated three OCT-based criteria for the disease that they believe have high predictive value, specificity and sensitivity for PCV: sub-retinal pigment epithelium (RPE) ring-like lesions, enface OCT-complex RPE elevations and sharp-peaked pigment epithelial detachment (PED).1
According to Dr. Kim, however, the near future promises even more advancements. The advent of widely-available OCT angiography portends a shift towards multimodal imaging in understanding nAMD.
Home-based OCT and artificial intelligence also promise to change the way that practitioners diagnose and treat nAMD in its various forms, and she concluded her talk by summarizing what’s next with these new developments.
“I believe that multimodal imaging, combined with artificial intelligence, will help us to determine therapeutic response,” she said. “This will become more and more important as we move to durable therapies, and telemedicine will also play a bigger role as we move towards personalized treatment in nAMD.”
Anti-VEGF and atrophy?
One of the hotter topics of the anti-VEGF era has been a potential—and highly controversial—connection between the use of anti-VEGF and the development of atrophy in the macula and beyond.
Dr. Barbara Blodi (USA) next presented her recently published paper, featuring a post-hoc analysis of atrophy in the Phase III MARINA study on ranibizumab.2
According to Dr. Blodi, MARINA gives researchers a unique opportunity to investigate the connection between atrophy and anti-VEGF, as it was the last clinical trial with a sham arm.
“Previous publications (on the topic) are missing something,” Dr. Blodi said. “The question of whether the atrophy is part of its natural history or a treatment effect could not be answered in these papers due to the lack of a control group.”
In the study, Dr. Blodi found a significant increase in macular atrophy in the ranibizumab arm over the sham arm. Atrophy started as early as three months, and at 24 months, was detectable in 36.8% and 40.4% for ranibizumab 0.3 and 0.5 mg, respectively, versus 21.0% in the sham arm.
Another interesting finding of the study was that the absence of fibrosis was the only variable found that could be associated with increased macular atrophy. “Atrophy may be undetectable under these areas of fibrosis, but this doesn’t explain why atrophy develops faster,” she said.
As for take-home clinicians, Dr. Blodi was unequivocal in her recommendations as researchers continue to explore this connection. “We need to monitor eyes for the development of atrophy,” she said. “We need anti-VEGF medication, but if fluid has resolved or remains stable, we should definitely consider less frequent dosing.”
Key takeaway round-up
Here are some of the other key takeaways from this session’s remaining presentations:
In his talk titled, Impact of Disease Activity Criteria on Dosing Interval in Patients With Neovascular AMD, Dr. Marco Zarbin discussed how durability data in modern anti-VEGF Phase III pivotal trials can be skewed by trial-specific definitions of disease activity.
Dr. Zarbin cited data from a recent real-world study at Moorfields Eye Hospital (London, UK), where patients were given faricimab 6 mg, extended according to disease activity criteria from modern pivotal Phase III anti-VEGF studies: TENAYA/LUCERNE (faricimab), HAWK/HARRIER (brolucizumab) and PULSAR (aflibercept 8 mg).
In the study, 94% of patients were extended at week 16 in Moorfields clinical practice, with 78% being extended according to the TENAYA/LUCERNE criteria, 76% with the HAWK/HARRIER data, and 100% with the PULSAR data.
“Depending on the disease activity criteria used, you get different durability,” Dr. Zarbin said. “The point I’m trying to make is that depending on these criteria, the same drug can give different estimates.”
Dr. Usha Chakravarthy (United Kingdom) delivered a talk on Biomarkers of Fibrosis in Treated Neovascular AMD.
According to Dr. Chakravarthy, there has never been a better time to standardize the identification and quantification of fibrosis, especially in the context of clinical trial endpoints for nAMD.
Agreement amongst experts can be highly variable, she said, regardless of imaging modality—and this can lead to problems.
“There are impediments now to establishing accurate prevalence and incidence, and this includes a lack of precise definitions by imaging modality, suboptimal images, and assessment reported at variable timepoints,” she said. “We must address all of this as we progress towards therapies that may prevent or delay the onset of fibrosis.”
Prof. Gemmy Cheung concluded the session with a round-up of treatment modalities for PCV.
She discussed some of the latest research on both monotherapy with individual anti-VEGF agents like aflibercept 2 mg and 8 mg, brolucizumab and faricimab—as well as combination therapy that brings in photodynamic therapy.
“The simple message is that anti-VEGF therapy works in a majority of patients,” Prof. Cheung said. “Yet there remains a great deal of heterogeneity, and in some cases, even if we use combination therapy, we can’t close the polyps—and that remains an area of unmet need.”
Her final takeaway point was that understanding the interaction between the branching neovascular network and polypoidal lesion could be a potential treatment target that reduces long-term recurrence.
Ultimately, Prof. Cheung’s findings echoed a theme shared by all of the day’s presentations: nAMD detection, treatment and screening has never been in a better place—and the outlook for new advancements in the diagnosis and management of the disease is similarly bright.
Editor’s Note: Reporting for this story took place during the 128th Annual Meeting of the American Academy of Ophthalmology (AAO 2024) from 18-21 October in Chicago, Illinois, USA.
References
- Cheung CMG, Lai TYY, Teo K, et al. Polypoidal Choroidal Vasculopathy: Consensus Nomenclature and Non-Indocyanine Green Angiograph Diagnostic Criteria from the Asia-Pacific Ocular Imaging Society PCV Workgroup. Ophthalmology. 2021;128(3):443-452.
- Blodi BA, Domalpally A, Corkery E, et al. Prevalence of Macular Atrophy in the MARINA Study of Ranibizumab versus Sham for Neovascular Age-Related Macular Degeneration. Ophthalmol Retina. 2023;7(8):661-671.
- Bhatia B, Sim SY, Chalkiadaki E, et al. Impact of Disease Activity Criteria on Extending Injection Intervals in Real-World Patients with Neovascular Age-related Macular Degeneration: A Moorfields Analysis. Invest Ophthalmol Vis Sci. 2024;65(7):4902.