Patient selection for GA therapy
Dr. Mammo discussed this evolution and how to choose patients who would best benefit from GA therapy.
(Image credit: AdobeStock/Noize)
Clinicians’ attitudes toward geography atrophy (GA) and treatment have been changing in the short term, as reflected by Danny A. Mammo, MD, from the Cole Eye Institute, Cleveland Clinic, Cleveland. He discussed this evolution and how to choose patients who would best benefit from GA therapy at the OSN New York 2024 conference November 8-10, New York.
The ideal candidate, he pointed out, should demonstrate an understanding of the disease process. “My ideal patient understands what it is like to lose vision from GA either from personal experience in the fellow eye or from family members or friends,” he commented.
The ideal patient also understands that treatment is not a one-off, but requires transportation for many clinic visits which may mean a strong commitment from either only the patient or also multiple family members.
Finally, Mammo said that he must be convinced that the patient likely has GA secondary to age-related macular degeneration (AMD).
Previously without treatments for GA, deciphering a cause for GA other than AMD may have been mostly an academic exercise. However, now with treatments, Mammo urges clinicians to take a more careful approach to taking into account multiple different causes of GA.
Some scenarios
Mammo discussed cases of GA development following resorption of large pigment epithelial detachments (PEDs). A longitudinal study1 investigated the GA growth rate in patients with reabsorbed drusenoid or serous PEDs. The patients had a dramatic visual reduction and GA occurred in place of the PED, the investigators reported. They found that these lesions had a slower growth rate and a smaller area of onset compared to rates previously reported. The visual acuity did not change significantly following reabsorption, which led to the conclusion that “these patients may not benefit from current treatments.”
Mammo suggested possible mechanisms of the GA in PED resorption: subclinical choroidal neovascular membranes in PED involution, retinal pigment epithelial (RPE) atrophy from prolonged displacement from the choriocapillaris leading to RPE dysfunction, or culmination of the active process of removal of drusen constituents from the PED, such as complement mediated, microglia, or activated Muller cells.
Another scenario is GA development in non-neovascular AMD. Dr. Mammo cited a retrospective study2 of eyes with at least 6 months of follow-up before GA developed. The investigators reported ultimately that different underlying mechanisms may lead to GA. The varying presentation included that drusen collapse occurred before GA in about two-thirds of eyes. Before GA developed, drusen with and without overlying vitelliform deposits were seen with subretinal drusenoid deposits were seen and, in some cases, vitelliform deposits without drusen were seen.
When considering diseases other than AMD, pattern dystrophy results from mutations in the PRPH2 gene and can mimic AMD, as can mitochondrial inherited diabetes and deafness, and Stargardt’s disease. Other inherited retinal diseases that may or may not benefit from anti-complement therapy can mimic AMD as well.
He advised physicians to be critical in their approach to GA, not only in clinic but also with industry partners. Considerations include asking patients about their age of diagnosis, family history, and paying close attention to findings on ultra widefield fundus photography and fundus autofluorescence.
References
Peng ET, Adrean SD. Geographic atrophy after reabsorption of pigment epithelial detachment (GARPED) study. BMC Ophthalmol. 2023;23:242.
Spaide RF. Pathways to geographic atrophy in nonneovascular age-related macular degeneration. Retina. 2024;44:1655-1665; doi: 10.1097/IAE.0000000000004242.
