Fundus autofluorescence in neovascular age-related macular degeneration, a clinicopathologic correlation relevant to macular atrophy.

Abstract

PURPOSE\nMacular atrophy (MA) of retinal pigment epithelium (RPE) and photoreceptors leads to vision loss in neovascular age-related macular degeneration (nAMD) despite successful treatment with anti-angiogenic agents. To enhance understanding of MA, fortify the cellular basis of fundus autofluorescence (FAF) imaging, and inform management of nAMD, we performed histological analysis of an eye with multimodal clinical imaging and apparent prior exudation due to nAMD.\n\n\nDESIGN\nCase study and clinicopathologic correlation.\n\n\nSUBJECT\nA white woman in whom AMD findings of inactive subretinal fibrosis (right eye) were followed for 9 years using FAF and optical coherence tomography (OCT), with no detectable subretinal fluid or other recurrent exudation, and no intravitreal injections before death at age 90 years.\n\n\nMETHODS\nThe right eye was preserved 6.25 hours after death, post-fixed in osmium tannic acid paraphenylenediamine, and prepared for sub-micrometer epoxy resin sections (n=115), with 19 matched to clinical OCT B-scans.\n\n\nMAIN OUTCOME MEASURES\nLight microscopic morphology of a hyperautofluorescent (hyperFAF) area attributed to prior exudation ( floodplain hyperFAF), hypoautofluorescent (hypoFAF) spots of MA, and areas of unremarkable FAF.\n\n\nRESULTS\nFloodplain hyperFAF was visible throughout the 9 years follow-up, with several hypoFAF atrophic spots expanding within it over time. The hyperFAF pattern corresponded to outer retinal atrophy (ORA) on OCT and photoreceptor loss over dysmorphic yet continuous RPE in histology. The hypoFAF spots inside the floodplain corresponded to complete retinal pigment epithelium (RPE) and outer retinal atrophy (cRORA) on OCT and loss of both photoreceptors and RPE in histology. In contrast, areas of unremarkable FAF showed continuous RPE accompanied by full-length photoreceptors and a thick outer nuclear layer.\n\n\nCONCLUSION\nThis direct clinicopathologic correlation for FAF imaging is the first for nAMD. FAF is a projection image that involves optical signal modulation by photoreceptors as well as emission signal sources in RPE. HyperFAF attributed to an exudative floodplain signifies loss of photoreceptors over continuous RPE. HypoFAF in MA signifies loss of both cell layers. FAF imaging should be interpreted with the multilayer perspective provided by OCT for maximal value. Prevention of exudation in nAMD may preserve photoreceptors.