We found the level of photoreceptor thinning above drusen determined by an intraeye comparison (i.e., thickness above drusen compared to thickness at adjacent drusen-free area) was similar to the values reported by others who compared photoreceptor layer thickness over drusen to matched normal populations.
25–28,34,35,37 This suggested, intraeye comparisons are appropriate for drusen quantification and may be useful during clinical assessment when individual variations in retinal thickness due to ethnicity, age, patient history, or other ocular pathologies could obscure drusen-associated changes.
52,53 Furthermore, when we compared the total retinal thickness of drusen-free areas to a matched normal population, it was significantly reduced, indicating that the retinal architecture of drusen-free areas in AMD patients also is abnormal. Sadigh et al.
25 found thinning in normal areas adjacent to drusen in only 10% of their patient cohort, highlighting that thickening (20%) or no change (70%) in thickness occurred more frequently. This discrepancy may be due to differences in quantification as Sadigh et al.
25 measured changes in photoreceptor layer thickness, while this study quantified total retinal thickness. As the overall macular thickness of our patient cohort was mostly within normal limits, thinning seen in drusen-free areas did not cause significant changes throughout the posterior pole. Thus, thinning of drusen-free areas may be due to nearby drusen accumulation rather than generalized retinal dysfunction. Alternatively, since our patient cohort only had early to intermediate AMD, such changes may not yet have been detectable. No consistent trend in total macular thickness has been shown for early AMD, signifying that this measurement may not be ideal for quantifying the initial retinal changes in AMD.
23,36–38 Overall, our data suggested that, although retinal thinning clearly occurs above drusen in comparison with adjacent drusen-free areas of the same eye, these drusen-free areas are themselves significantly thinner than matching retinal areas in the normal population.
Total retinal thinning of drusen and drusen-free areas compared to the normal population was most profound beyond the parafovea (>1250 μm). Functional and anatomical losses observed in AMD patients also have been reported beyond the parafovea and in the peripheral retina, suggesting rod photoreceptors are mostly lost in early disease.
39–41,54,55 This is supported by studies using adaptive optics scanning laser ophthalmoscopy, which show normal cone density above drusen and in drusen-free areas of AMD eyes.
56–58 Although RPE/PR thinning may be attributed to rod degeneration, abnormal cone adaptation, sensitivity, and multifocal electroretinograms in early AMD suggest remaining cones still may be dysfunctional.