Prognostic value of retinal neurodegeneration markers for the progression of diabetic retinopathy: a systematic review and meta-analysis

Background In recent years, diabetes mellitus (DM) has emerged as a chronic disease with a steadily increasing prevalence. It is closely associated with lifestyle and metabolic factors, including poor lifestyle habits that contribute to systemic metabolic alterations. Among its vascular complications, diabetic retinopathy (DR) is one of the most serious, with a high incidence rate and recognized as the leading cause of preventable blindness in working-age adults. The major challenges associated with DR is predicting disease progression. The transition from non-proliferative DR to proliferative DR is highly heterogeneous among individuals. This variability poses a substantial dilemma in clinical practice, as it hinders the routine identification of high-risk patients who require periodic monitoring and early intervention. Methods This systematic review was conducted according to the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses and was registered in the International Prospective Register of Systematic Reviews (CRD420251082364). This study included only longitudinal, prospective, and retrospective cohort studies published in any language. Eligible studies were required to report baseline markers of retinal neurodegeneration and DR status at the follow-up visit. A scientific literature search was conducted using PubMed, Scopus, and Web of Science, with no restrictions on publication dates. Additionally, a gray literature search was conducted in databases such as Google Scholar, OpenGrey, and ARVO (The Association for Research in Vision and Ophthalmology). Results A total of 6,656 articles were retrieved from PubMed, Web of Science, and Scopus databases. After removing duplicates, 5,911 remained for title and abstract analyses. Of these, 33 studies were selected for full reading, of which 20 were excluded because they failed to meet the inclusion criteria, leaving 13 studies for systematic review. Conclusions This systematic review demonstrates that advanced imaging biomarkers obtained using OCT and OCTA are independent predictors of DR progression. Markers quantifying vascular perfusion failure, such as CC FD% and neural structural damage, particularly m-GCIPL thinning, were identified as the most robust predictors of disease progression. Future efforts should focus on standardizing protocols, validating promising biomarkers across diverse populations, establishing clinical cutoffs, and designing clinical trials to evaluate early interventions guided by these markers.