Macular Microaneurysms Are Associated With Chronic Kidney Disease and Deep Capillary Plexus Ischemia in Referable Diabetic Retinopathy.

Purpose: To identify retinal and systemic factors linked to macular microaneurysms (MAs) in referable diabetic retinopathy (refDR). Methods: Eighty-three eyes from 65 patients with refDR without diabetic macular edema underwent multiple 3 × 3-mm optical coherence tomography angiography (OCTA) scans. The scans were averaged, and OCTA metrics were calculated, including vessel length density in the deep capillary plexus (VLD-DCP). Ultra-widefield fluorescein angiography was used to extract macular MA count within a 3-mm circle centered on the fovea and the nonperfusion index (NPI) across the entire visible retina. Chronic kidney disease (CKD) was defined as an estimated glomerular filtration rate <60 mL/min/1.73 m² for at least 3 months. Linear mixed models were used to assess the relationships with MA count, and receiver operating characteristic curve analysis evaluated MA diagnostic performance for detecting CKD. Results: The median MA count was 6 (interquartile range, 2-12). In univariate analysis, macular MA count was significantly associated with CKD, NPI, and several OCTA parameters. In multivariable models adjusting for age, sex, CKD, NPI, and one OCTA parameter per model, CKD (P = 0.007-0.013) and VLD-DCP (P = 0.003) remained independently associated with MA count. A threshold of 14 macular MAs yielded the highest Youden index for CKD, with a sensitivity of 58.8%, a specificity of 86.4%, and an area under the curve of 0.755. Conclusions: CKD and reduced VLD-DCP were independently associated with higher macular MA count in refDR, suggesting that MA count may serve as a marker for systemic microvascular disease.