# Biomarkers of Preclinical Diabetic Retinopathy Detected by OCT Angiography—A Descriptive Review

## TL;DR

This review explores how OCTA can detect early microvascular changes in diabetic patients before retinopathy becomes visible, offering potential for early diagnosis.

## Contribution

The study synthesizes current evidence on OCTA biomarkers for preclinical diabetic retinopathy in both type 1 and type 2 diabetes.

## Key findings

- Early microvascular changes like reduced vessel density and FAZ enlargement are detectable by OCTA before clinical DR onset.
- Changes are most consistent in the deep capillary plexus, indicating its susceptibility to early diabetic damage.
- OCTA shows promise as a noninvasive tool for identifying preclinical diabetic retinopathy biomarkers.

## Abstract

Background: Diabetic retinopathy (DR) is a leading cause of vision loss worldwide. Microvascular changes precede clinically detectable DR, creating an opportunity for early diagnosis and intervention. Optical coherence tomography angiography (OCTA) enables noninvasive, quantitative assessments of retinal and choroidal microcirculation and has emerged as a promising tool for identifying early biomarkers of DR. The goal of this study was to review the literature on OCTA-derived biomarkers associated with preclinical diabetic retinopathy in patients with type 1 and type 2 diabetes mellitus. Methods: This descriptive literature review summarizes current evidence regarding OCTA-derived biomarkers associated with preclinical diabetic retinopathy in patients with type 1 and type 2 diabetes mellitus. A search of the PubMed/MEDLINE database was performed to identify original studies published between 2015 and 2025 evaluating OCTA parameters in diabetic patients without clinically detectable diabetic retinopathy. The findings were synthesized qualitatively due to methodological heterogeneity among studies in terms of OCTA devices, imaging protocols, and analyzed parameters. Results: The reviewed studies consistently reported early microvascular abnormalities detectable by OCTA prior to the development of clinically visible diabetic retinopathy. The most frequently described changes included reduced vessel density (VD) and perfusion parameters, enlargement and increased irregularity of the foveal avascular zone (FAZ), areas of capillary non-perfusion, and alterations in vascular network geometry and complexity. These changes were most consistently observed in the deep capillary plexus (DCP), suggesting that this vascular layer may be particularly susceptible to early diabetic microvascular damage. Conclusions: This review provides a comprehensive synthesis of OCTA-derived biomarkers associated with early retinal microvascular alterations in diabetic patients without clinically detectable diabetic retinopathy. By integrating findings from recent studies, the review highlights the potential role of OCTA in identifying preclinical microvascular changes and discusses current methodological challenges and future research directions.