Abnormal Thickening as well as Thinning of the Photoreceptor Layer in Intermediate Age-Related Macular Degeneration

PURPOSE. To investigate the relationship between photoreceptor layers overlying and adjacent to large drusen in intermediate nonneovascular AMD. METHODS. Patients with AMD (n = 41; aged 53-83 years) and elderly control subjects without eye disease (n = 10; aged 51-79 years) were studied with spectral-domain optical coherence tomography. Characteristics of large drusen (>= 125 mu m) were measured and the thickness of photoreceptor laminae overlying drusen and in retinal regions neighboring the drusen were quantified. RESULTS. There were 750 large drusen in 63 intermediate AMD eyes studied. The width of the drusen sampled averaged 352 mu m (SD = 153) and the height averaged 78 mu m (SD = 31). There was significant reduction of the photoreceptor outer nuclear layer (ONL) thickness overlying 92% of the drusen. The thickness of the layer corresponding to photoreceptor inner and outer segments above drusen was also reduced, and the reduction was proportional to ONL thickness. In a substantial fraction (similar to 20%) of normally laminated paradrusen locations sampled within similar to 300 mu m of peak drusen height, ONL thickness was significantly increased compared with age and retinal location-matched normal values. Topographical analyses of the macula showed ONL thickening occurring in paradrusen regions as well as retinal locations distant from drusen. CONCLUSIONS. Reductions in the photoreceptor laminae overlying drusen were detectable and this is consistent with histological studies revealing neuronal degeneration in AMD. ONL thickening in some macular areas of AMD eyes has not been previously reported and may be an early phenotypic marker for photoreceptor stress, as it has been speculated to be in hereditary retinal degenerations. (Invest Ophthalmol Vis Sci. 2013;54:1603-1612) DOI:10.1167/iovs.12-11286