From microaneurysm to retinal capillary macroaneurysm: Optical coherence tomographic evidence of aneurysmal evolution in diabetic retinopathy

Purpose: To present a proof-of-concept case series documenting the novel in-vivo progression of retinal microaneurysms (MAs) into retinal capillary macroaneurysms (RCMAs) in diabetic retinopathy (DR) using serial optical coherence tomography (OCT). Observations: We longitudinally followed four treatment-naïve DR eyes. Over 9 to 30 months, serial OCT clearly captured the enlargement of pre-existing MAs into distinct RCMAs, characterized by a marked increase in wall reflectivity and significant morphological remodelling. This conversion consistently coincided with a notable exacerbation of localized diabetic macular edema (DME) and increased hyperreflective intraretinal dots (HRIDs), indicative of increased inflammation and leakage. The MAs originated in both inner and middle retinal layers. Conclusions and importance: Our series presents the first in vivo, multi-case demonstration of MAs dynamically enlarging into RCMAs, a clinically significant and aggressive form of diabetic microvascular disease. This transformation is consistently associated with worsening CME and increased HRIDs, marking RCMAs as a more exudative and potentially treatment-resistant subset of DME. Emerging evidence, supported by our observations, suggests that many RCMAs may arise at interconnecting vertical channels between the superficial and deep capillary plexuses, where mixed arterial-venous flow and focal pressure gradients predispose to outpouching. These findings challenge current uniform therapeutic approaches, underscoring the importance of serial-OCTs in detecting and characterizing this evolution. Early OCT-based identification could enable more tailored interventions, reducing the risk of severe vision loss. Future research should further clarify systemic and local drivers of this progression, refine OCT biomarkers, and assess whether aggressive or multimodal therapy targeting RCMAs improves patient outcomes.