The positive correlation between the progressive photoreceptor damage and the increased macular leakage indicating the severity of diabetic retinopathy

AIM: To evaluate photoreceptor changes and their correlation with microvascular alterations in different stages of diabetic retinopathy (DR). METHODS: Thirty-two treatment-naïve DR patients (50 eyes) without clinically significant macular edema were graded into mild, moderate, and severe non-proliferative DR (NPDR) and proliferative DR (PDR). The macula was imaged using adaptive optics scanning laser ophthalmoscopy (AO-SLO) at five subsections. Mean/minimum photoreceptor density, cell regularity, dispersion, spacing, and dark areas were recorded. Central macular thickness (CMT) and macular leakage index (MLI) were measured. RESULTS: The percentage of dark areas increased gradually with DR severity: 1.86 ± 1.52 (mild NPDR), 3.32 ± 1.45 (moderate NPDR), 4.22 ± 2.11 (severe NPDR), and 5.92 ± 3.06 (PDR) (P = 0.007). MLI also progressively increased (P = 0.01): 0.31 ± 0.60%, 3.47 ± 4.70%, 6.92 ± 5.44%, and 8.98 ± 3.58%, respectively. MLI showed a positive correlation with the percentage of dark areas (r = 0.36, P = 0.01). No significant changes were observed in photoreceptor density, regularity, dispersion, spacing, CMT, or visual acuity. CONCLUSIONS: Dark areas observed by AO-SLO suggest photoreceptor abnormalities, indicating decreased waveguiding ability and localized dysfunction as DR progresses. The positive correlation between dark areas and macular vascular leakage implies early dysfunction of the retinal neurovascular unit (NVU) in DR, warranting further investigation.