Associations Between Capillary Diameter, Capillary Density, and Microaneurysms in Diabetic Retinopathy: A High-Resolution Confocal Microscopy Study

Purpose: To use high-resolution histology to define the associations between microaneurysms, capillary diameter and capillary density alterations in diabetic retinopathy (DR). Methods: Quantitative comparisons of microaneurysm number, capillary density and capillary diameter were performed between eight human donor eyes with nonproliferative DR and six age- and eccentricity-matched normal donor eyes after retinal vascular perfusion labelling. The parafovea, 3-mm, 6-mm, and 9-mm retinal eccentricities were analyzed and associations between microvascular alterations defined. Results: Mean capillary density was reduced in all retina regions in the DR group (P = 0.013). Microaneurysms occurred in all retina regions in the DR group, but the association between decreased capillary density and microaneurysm number was only significant in the 3-mm (P = 0.040) and 6-mm (P = 0.007) eccentricities. The mean capillary diameter of the DR group (8.9 ? 0.53 ?m) was greater than the control group (7.60 ? 0.40 ?m; P = 0.033). There was no association between capillary diameter increase and capillary density decrease (P = 0.257) and capillary diameter increase and microaneurysm number (P = 0.147) in the DR group. Within the parafovea of the DR group, capillary density was significantly reduced, and capillary diameter was significantly increased in the deep capillary plexus compared with the superficial and intermediate plexuses (all P < 0.05). Conclusions: In DR, capillary density reduction occurs across multiple retina eccentricities with a predilection for the deep capillary plexus. The association between microaneurysm number and capillary density is specific to retina eccentricity. Capillary diameter increase may be an early biomarker of DR. These findings may refine the application of optical coherence tomography angiography techniques for the management of DR.