Abstract
Purpose :
Interpretation of GA trial outcomes and patient selection for recently approved complement inhibitors would benefit from new data about subcellular, cellular, and tissue-level contributors to FAF signal. We investigated 2 eyes of 1 woman with bilateral multifocal GA and thick choroids, with in vivo multimodal imaging followed by histology.
Methods :
In 6 clinic visits in 5 years, both eyes were imaged using optical coherence tomography (OCT), near infrared reflectance (NIR; Spectralis), plus 55° color and green FAF (Topcon). Best corrected visual acuity (OD, OS) was 20/80, 20/40 at presentation and 20/400, 20/100 at the last visit. Six years later, after patient death at age 93 years, eyes were recovered 5 hours postmortem and opened for preservation. OS was imaged ex vivo and prepared for high-resolution epoxy resin histology linked to OCT B-scans (PMID 37306417; 26255578). FAF intensities at 100, 500, and 1000 µm on either side of long atrophy borders was measured with ImageJ.
Results :
Bilateral multifocal GA exhibited appearance, growth, and coalescence of atrophic spots associated with drusen, mostly calcified, best seen in color and FAF, and less so in NIR due to thick choroid. Histology of OS revealed dilated veins especially nasally, attenuated choriocapillaris, multiple calcified drusen with thick basal laminar deposit (BLamD), and a layer of stage 1 subretinal drusenoid deposit. Four FAF stages of drusen-driven atrophy (PMID 33217617) were apparent. In the outer junctional zone, FAF signal was highest at 100 µm, corresponding to thin and continuous RPE over thick BLamD and short or absent outer segments. In the inner junctional zone, a mottled low signal at 100 µm and negligible signal at 500-1000 µm corresponded to dissociated RPE and absent RPE, respectively. Strong hyperFAF within atrophy corresponded to islands of RPE and photoreceptors between expanding atrophic spots started at drusen.
Conclusions :
In this eye, a hyperFAF border and stages 2-3 of drusen-driven atrophy corresponds to thin continuous RPE and loss of overlying outer segments that normally absorb incoming light. Thickened RPE in some locations increase the pathlength of light through fluorophores. Ongoing studies will quantify the relative contribution of RPE- and photoreceptor-specific modulators of FAF.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.