Spatial Dissociation of Subretinal Drusenoid Deposits and Impaired Scotopic and Mesopic Sensitivity in AMD

Abstract

Purpose: Subretinal drusenoid deposits (SDD) first appear in the rod-rich perifovea and can extend to the cone-rich fovea. To refine the spatial relationship of visual dysfunction with SDD burden, we determined the topography of mesopic and scotopic light sensitivity in participants with non-neovascular AMD with and without SDD.

Methods: Thirty-three subjects were classified into three groups: normal (n = 9), AMD-Drusen (with drusen and without SDD; n = 12), and AMD-SDD (predominantly SDD; n = 12). Mesopic and scotopic microperimetry were performed using 68 targets within the Early Treatment Diabetic Retinopathy Study grid, including points at 1.7° from the foveal center (rod:cone ratio, 0.35). Age-adjusted linear regression was used to compare mesopic and scotopic light sensitivities across groups.

Results: Across the entire Early Treatment Diabetic Retinopathy Study grid and within individual subfields, the three groups differed significantly for mesopic and scotopic light sensitivities (all P < 0.05). The AMD-SDD group exhibited significantly decreased mesopic and scotopic sensitivity versus both the normal and the AMD-Drusen groups (all P < 0.05), while AMD-Drusen and normal eyes did not significantly differ (all P > 0.05). The lowest relative sensitivities were recorded for scotopic light levels, especially in the central subfield, in the AMD-SDD group.

Conclusions: SDD-associated decrements in rod-mediated vision can be detected close to the foveola, and these deficits are proportionately worse than functional loss in the rod-rich perifovea. This finding suggests that factors other than the previously hypothesized direct cytotoxicity to photoreceptors and local transport barrier limitations may negatively impact vision. Larger prospective studies are required to confirm these observations.

Figure 1.

Macular light sensitivity was assessed in subfields of the ETDRS grid. Shown are the central subfield, inner ring, and outer ring of this grid, with the 68 test points indicated. Mean values for rods/mm², cones/mm², and rod:cone ratio at subfield test points, as determined by histology in older eyes with normal maculae, are 15,787, 49,042, and 0.35 for the four points in the central subfield, 49,663, 19,563, and 2.7 for 12 points in the inner ring, and 79,895, 12,054, and 6.9 for 52 points in the outer ring, respectively.

Figure 2.

Representative multimodal retinal images of subjects in three diagnostic groups. Left column, eye in the normal group; middle column, eye in the AMD–Drusen group; right column, eye in the AMD–SDD group. Deposit distribution is typical of AMD cases, i.e., abundant drusen in the central subfield (middle column) and abundant SDD in the perifovea and sparing the fovea (right column). Top row, color fundus photograph; second row, near infrared (NIR) reflectance image. Green arrow lines indicate where spectral domain (SD) OCT were taken. Third row, SD-OCT B-scan taken along the corresponding green arrow line in NIR image; bottom row, magnified (×5) SD-OCT image within the white box in corresponding SD-OCT B-scan. Red arrowheads highlight four drusen. Green arrowheads highlight five SDD. ONL, outer nuclear layer; ELM, external limiting membrane; EZ, ellipsoid zone; RPE–BL–BrM, retinal pigment epithelium–basal lamina–Bruch's membrane. Scale bars in SD-OCT: 200 µm.

Figure 3.

Map of median mesopic and scotopic light sensitivity measured in the three subject groups. Each dot indicates the 68 microperimetry target locations, within the subfields of the ETDRS. As evidenced by the shift to dark colors, the lowest sensitivities were recorded for AMD–SDD at both mesopic and scotopic light levels. Further within the scotopic maps, the lowest sensitivities were recorded within the central subfield.

Figure 4.

Sensitivity in the AMD–SDD group is worse than eyes in the AMD–Drusen, even in the central subfield, where rods are sparse. All P values were obtained from pairwise comparisons between subjects in different groups and were adjusted for age.