In Vivo Longitudinal Measurement of Cone Photoreceptor Density in Intermediate Age-Related Macular Degeneration

center dot PURPOSE: To evaluate cone photoreceptor density in clinically unremarkable retinal regions in patients with age-related macular degeneration (AMD) using adaptive optics scanning laser ophthalmoscopy (AOSLO).center dot DESIGN: Prospective case series with normal compari-son group.center dot METHODS: Ten eyes of 7 patients with intermedi-ate AMD were studied, including 4 with predominantly subretinal drusenoid deposits (SDD) and 3 without SDD. Macular regions with a clinical absence of AMD-associated lesions were identified by cone packing struc-ture on AOSLO and optical coherence tomography. Cone density was measured in 1174 clinically unremarkable re-gions within the central subfield (CSF), the inner (IR), and outer rings (OR) of the Early Treatment Diabetic Retinopathy Study grid over 39.6 +/- 3.3 months and com-pared with age-matched normal values obtained in 17 par-ticipants.center dot RESULTS: Cone density decreased at 98.3% of the ex-amined locations over time in the eyes with AMD. In the CSF, IR, and OR, cones declined by-255 +/- 135,-133 +/- 45, and-59 +/- 24 cones/degree2 /year, respectively, in eyes with SDD, and by-212 +/- 89,-83 +/- 37, and-27 +/- 18 cones/degree2 /year, respectively, in eyes without SDD. The percentage of retinal loci with cone density lower than normal ( Z score <-2) increased over the follow-up: from 42% at the baseline to 80% at the last visit in eyes with SDD and from 31% to 70% in eyes without SDD.center dot CONCLUSIONS: AOSLO revealed cone photoreceptor loss in regions that appear otherwise unremarkable clini-cally. These findings may help explain the loss of mesopic sensitivity reported in these areas in eyes with intermediate AMD. (Am J Ophthalmol 2023;248: 60-75.(c) 2022 Elsevier Inc. All rights reserved.)