Johnathan Bailey
Maximilian Kong
Columbia University
Imaging
Saturday morning’s Contemporary Retinal Imaging session was moderated by Dr. Christina Weng and Dr. John Miller. This eye-opening session outlined many aspects of retinal imaging, including future advances for monitoring and managing age-related Macular Degeneration (AMD), diabetic retinopathy, and geographic atrophy.
Dr. Christina Weng of Baylor University opened with her talk, entitled “Home Monitoring for Age-related Macular Degeneration.” She introduced the FDA-approved home OCT as a means to optimize the way we manage AMD. As patients acquire daily OCT scans, the total volume for each day is mapped to fluid volume trajectory. Dr. Weng presented a newly-diagnosed wet AMD patient who received a single anti-VEGF injection and then was able to immediately extend to 12 weeks before fluid recurred, an interval that typically takes 44 weeks or longer to reach. The DRCR Retina Network Protocol AO is conducting a multi-center randomized clinical trial of 600 treatment-naive eyes with wet AMD from 80 sites. The patients will be randomized 1:1 into either a treat and extend or home OCT-guided treatment arm, and all eyes will receive faricimab. She hopes recruitment will be completed near the end of 2025.
Dr. Paolo Silva of Joslin Diabetes Center discussed “Ultrawide Field Imaging in Diabetic Retinopathy.” Dr. Silva began his talk by stating that current diabetes and eye treatments combined with telemedicine may reduce the incidence of diabetes-related blindness by as much as 95%. However, ungradable image rates can adversely impact telemedicine programs. The transition to UWFI combats this, as the ungradable image rate is reduced from 10% to 3% per patient while speeding up image evaluation and acquisition time. He then described DRCR Protocol AA, a prospective, observational longitudinal study which evaluated whether the detection of predominantly peripheral lesions (PPL) improves the ability to predict rates of retinopathy worsening over time beyond the risk associated with baseline ETDRS DRSS level. Eyes with FA-PPL had a 1.7-fold greater risk of disease worsening over 4 years and were consistent within DR severity subgroups. His research has shown that worse DRSS severity and the presence of PPL are strongly associated with increased nonperfusion. DR lesions identified in UWF-color or UWF-FA images, regardless of lesion location, carry a similar risk of disease worsening. His work suggests that identification of lesions throughout the entire retina is critically important to accurately stratify the risk for progression over time. He concluded that UWF-color and UWF-FA images may provide additional prognostic value in determining the risk of DRSS worsening, and that accurate classification of overall disease severity and progression can be improved by accounting for lesions predominantly outside the ETDRS fields.
Dr. Glenn Jaffe of Duke University presented on “Imaging Geographic Atrophy: Autofluorescence, OCT, Photos.” He opened by discussing his research comparing single drusen size on color fundus photography and spectral-domain OCT, noting that it was easier to diagnose drusen on OCT and identify non-drusen pathological features. The talk shifted to discuss geographic atrophy, which is imaged in a variety of different methods: color fundus photography, FA, FAF, NIR, OCT, and emerging AI approaches. For the clinic and clinical trials, his approach begins with en face imaging to obtain a global impression of the atrophy. He suggests using a B-scan to confirm the images depict geographic atrophy using consensus on atrophy meeting group (CAM) criteria: loss of outer retina, loss of RPE at least 250 microns, and loss of choroidal hypertransmission at least 250 microns. Area of GA can be measured on FAF and NIR, and OCT can assist in defining the boundaries. To conclude, he presented AI as a means to improve accuracy in the future, and he described high performance of some recent algorithms, but Dr. Jaffe suggests that additional validation is needed.
GA and IRD
The second session of MACULA 2025 focused on geographic atrophy (GA) and inherited retinal diseases and was moderated by Dr. Demetrios Vavvas, MD, PhD, Dr. Mandeep Singh, MD, PhD, and Dr. Stephen Tsang, MD, PhD.
Demetrios Vavvas, MD, PhD, opened the session with a talk titled “Treating GA, Including Photobiomodulation: Benefits and Risks.” He outlined the limited efficacy and evidence supporting current treatments for GA and summarized research on complement inhibitors, dietary supplements, and photobiomodulation. Dr. Vavvas emphasized that the evidence supporting these treatment modalities remains weak. He questioned the FDA’s approval of pegcetacoplan, citing the lack of functional improvements in vision and study limitations, including significant loss to follow up and failure to disclose baseline risk between study groups. He also expressed caution regarding the recommendation of AREDS supplements for GA, noting that evidence stems from post-hoc analyses of lesion size progression rather than studies directly investigating functional benefits. Similarly, he critiqued photobiomodulation, which despite showing positive trends in post-hoc analyses, failed to demonstrate significant functional benefits and had fairly small sample sizes.
Mandeep Singh, MD, PhD followed with a presentation titled “Clinical Trials for Inherited Retinal Diseases.” He noted that, since the approval of Luxturna for RPE65-related retinitis pigmentosa (RP), no additional gene therapies for inherited retinal diseases have been approved. Dr. Singh suggested that the FDA’s longstanding requirement for gene therapy treatments to demonstrate a 7 dB improvement in functional endpoints, originally extrapolated from glaucoma trials, poses a potentially insurmountable challenge for investigators. He highlighted gene therapy trials for X-linked RP, including XIRIUS, LUMEOS, and SKYLINE, emphasizing the severity of X-linked forms of RP and the urgent need for effective treatments. Dr. Singh also discussed newer approaches, such as the BRILLIANCE trial in Leber congenital amaurosis, the first ophthalmology trial to apply CRISPR technology to living patients, and the ILLUMINATE trial, which uses antisense oligonucleotides to modify protein synthesis in the same condition. He explored the potential of repurposing existing drugs, such as the Oral Metformin for ABCA4 Retinopathy trial, to leverage their established safety profiles for accelerated approval. Dr. Singh concluded by discussing gene-agnostic treatments, which offer hope to the 30-50% of inherited retinal disease patients whose causative genes remain unidentified. Strategies in this category include neuroprotection, exemplified by the NAC-ATTACK trial for RP, optogenetics, as seen in the RESTORE trial with MCO-010, and stem cell therapies.
Jason Comander, MD, PhD delivered the final talk of the session, titled “Vitamin Supplements for GA or RP: Vitamin A? Not Today.” He concurred with Dr. Vavvas that evidence supporting nutritional supplementation for retinal diseases is often insufficient, using the now-redacted recommendation for vitamin A supplementation in RP as an example. However, as highlighted by Dr. Singh, progress in inherited retinal disease is slow, leaving dietary supplementation and lifestyle modification among the few actionable recommendations available outside of clinical trial enrollment. For RP, Dr. Comander strongly advised avoiding vitamin E, including AREDS formulations. He also endorsed the potential benefits of wearing sunglasses outdoors, DHA supplementation, regular exercise, and maintaining a healthy diet. In Stargardt disease, he emphasized the importance of avoiding vitamin A supplementation, including AREDS1 supplements, and supported the benefits of outdoor sunglasses use and smoking cessation. For patients with intermediate and advanced AMD, Dr. Comander endorsed the use of AREDS2 supplements, adherence to the Mediterranean diet, increased fish consumption, and smoking cessation as effective lifestyle modifications.
During the discussion, Dr. Neil Bressler, MD and Dr. Lee Jampol, MD echoed the caution regarding photobiomodulation for AMD and GA. Dr. Bressler urged the audience to wait for further peer-reviewed literature based on data from new commercially available photobiomodulation devices. Dr. Fernando Arevalo, MD, PhD added that retina specialists in Latin America, where such devices are also in use, share a similarly skeptical outlook. Dr. Vavvas commended the skepticism regarding photobiomodulation, but expressed concern that similar issues exist with anticomplement therapies. The session provided a critical appraisal of current and emerging treatments for geographic atrophy and inherited retinal diseases.
Read All Atlantic Coast Retina Club / Macula 2025 Articles:
Mystery Cases 1 & 2
Mystery Cases 3 & 4
Mystery Cases 5 & 6
Mystery Cases 7, 8, 9
Imaging, GA, and IRDs
Keynote Lectures
DR and DME
Choroidal Neovascularization
Retinal Vascular Diseases
Ocular Oncology
Special Topics & Women in Retina
