Purpose: To utilize high resolution AOSLO to evaluate differences in cone density, reflectivity and regularity in eyes with and without diabetes (DM) and across a range of diabetic retinopathy (DR) severity.
Methods: Cone mosaics at the fovea and 4 macular quadrants (1x1.2° area, mean+SD eccentricity = 4.2±0.4°) were imaged using AOSLO (2.5µm resolution). Contrast of aligned and averaged images was automatically standardized based on the 8-bit histogram. Cone counting was performed semi-automatically using ImageJ and manual correction by 2 independent graders masked to clinical data. Count differences >20% were adjudicated. Parameters including density, nearest neighbor (NN) and Voronoi tile measurements were calculated as well as mean reflectivity of each Voronoi tile.
Results: Forty eyes of 40 subjects were assessed. For subjects, mean±SD age was 44±12yrs, 57% (N=12) were male, 78% (31) had DM, DM duration was 22±14yrs and 32% (10) had no DR, 19% (6) mild nonproliferative DR (NPDR), 29% (9) moderate NPDR, 10% (3) severe NPDR and 10% (3) PDR. No consistent relationship for DM or DR was seen with absolute cone density, NN measurements, or reflectivity. However, the reflectivity regularity index (RI) (Voronoi tile reflectivity mean/SD) decreased in all 5 macular regions with increasing DR severity and this decrease was statistically significant in the inferior regions of the macula (No DR: 4.6±0.9, mild NPDR: 4.5±0.8, moderate NPDR: 4.5±0.7, severe NPDR: 4.2±0.9, PDR: 3.8±0.9, p<0.05). A significantly lower NN RI (NN mean/SD) was seen in macular quadrants in eyes with DM as compared with no DM (4.7±1.0 vs. 5.4±1.5, p<0.04). Increasing age correlated with a decrease in mean cone density (<35y: 11,567±2,848, 35-50y: 10,933±2,403, 50+y: 10,023±2,219 cones/mm2, p<0.05) as well as an increase in reflectivity RI (4.1±0.9, 4.3±0.8, 4.8±0.8, respectively, p=0.002) in all regions.
Conclusions: Although absolute cone density does not appear to change substantially in diabetes, decreases in regularity of cone spacing and reflectivity regularity are associated with presence of DM and increasing DR severity, respectively. If future studies demonstrate that these properties correlate with functional or metabolic alterations of the retinal photoreceptors, these assessments may provide novel predictors of visual or anatomic outcomes in the diabetic eye.
