Luke Oh, MD
Columbia University, New York, NY
The “Non-neovascular AMD” section of ACRC 2024 started with three excellent talks moderated by Drs. Alexander Brucker and Srinivas Sadda. These presentations highlighted the importance of identifying structural and functional outcome measurements for dry AMD, a deep dive into whether complement is a satisfactory target for geographic atrophy (GA), and a review of the current state of drugs in development for GA. This was followed shortly afterwards by a riveting panel on “Controversies in GA management” moderated by Dr. Jason Slakter and featuring Drs. Philip Ferrone, Irene Barbazetto, Lee Jampol, and David Brown.
Dr. Eleanora Lad presented findings regarding potential biomarkers of disease progression both in early-intermediate AMD as well as in GA, and the importance of considering what are clinically relevant outcome measurements in trials. The cone-contrast test, dark adaptation, and microperimetry were found to be reliable measurements of functional decline in patients with early-intermediate AMD. With regards to GA, loss of visual acuity was more significant in better seeing eyes with smaller lesions and unifocal atrophy, which is the opposite that of the population being enrolled in current clinical trials. Future interests include identifying subgroups of GA that have high risk of rapid anatomical expansion and concomitant functional loss.
Dr. Demetrios Vavvas then provided his spirited opinions on complement factor as a target for GA and the limitations of current GA therapies. Like Dr. Lad, Dr. Vaavas emphasized the importance of function as the primary measure of treatment. The talk addressed the absence of clear functional benefit with current GA therapies and discussed studies that demonstrate complement levels and risk alleles did not correlate with GA. Additionally, studies involving Risuteganib, a synthetic peptide regulating integrin, as well as drugs targeting Fas signaling, were highlighted as they show early promise. Dr. Vavvas ended by noting that an improved understanding of the genetics and natural history of GA is needed.
Next, Dr. Peter Kaiser presented an update on alternative avenues for dry AMD treatment. His talk focused on 5 primary targets including reducing oxidative stress, reducing byproduct accumulation, visual cycle modulation, stem cells, and inflammation suppression.Mitochondrial dysfunction is a key feature of dry AMD and elamipretide is a promising medication that restores mitochondrial structure and has been shown to reduce ellipsoid zone (EZ) attenuation. Dr. Kaiser also mentioned that beta-amyloid is a shared interest for treatment of Alzheimer’s disease and dry AMD. Several new topical and oral medications are attempting to reduce its accumulation.
Also, drugs targeting the visual cycle, including those that have been used in trials for Stargardt disease, may have potential for disease modulation. Finally, stem cell approaches are still being explored with attempts being made to create scaffolds for polarization.
These talks were then followed by a highlight of the ACRC program, a panel discussing controversies in GA management. A series of GA cases were presented by Dr. Slakter to the panelists followed by a succession of questions covering which patients to treat, which eye to inject, and injection technique. With regards to who to treat, Drs. Ferrone, Barbazetto, and Brown agreed on the treatment of several cases with preserved central visual acuity and quickly progressive disease. Dr. Jampol did not feel there was a presented case that he would treat and warned of the importance of confirming that a patient truly has GA before offering treatment. All panelists emphasized the importance of discussing limitations and risks of the medication with patients before treatment. The panel agreed that they would treat the worse eye first to monitor for adverse reactions to the medication before treating the better seeing eye. Dr. Ferrone expressed that he treats eyes separated by 4-6 weeks while Dr. Brown noted that he routinely injects both eyes at the same visit although he starts off with one. All panelists were currently using pegcetacoplan with exception of Dr. Jampol who is using neither. As for injection technique, Drs. Ferrone and Brown use speculums for injection due to the viscosity of the medication and expressed lower threshold for AC paracentesis following injection.
