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

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).

Prospective case series with normal comparison group.

Ten eyes of 7 patients with intermediate 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 structure on AOSLO and optical coherence tomography. Cone density was measured in 1174 clinically unremarkable regions 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 compared with age-matched normal values obtained in 17 participants.

Cone density decreased at 98.3% of the examined 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.

AOSLO revealed cone photoreceptor loss in regions that appear otherwise unremarkable clinically. These findings may help explain the loss of mesopic sensitivity reported in these areas in eyes with intermediate AMD.