Retinal Microvascular Biomarkers of Exercise and Physical Fitness: A Systematic Review with Narrative Synthesis

Background: Retinal microvascular assessment has emerged as a promising non-invasive approach for evaluating vascular health. Recent advances in retinal imaging technologies have enabled detailed characterization of retinal vascular structure and function, raising interest in their potential role as biomarkers of exercise-related vascular adaptation. This systematic review with narrative synthesis aimed to summarize current evidence regarding the relationship between exercise, physical fitness, and retinal microvascular biomarkers. Methods: A systematic literature search was conducted in PubMed, Scopus, and Web of Science for studies published from January 2021 to June 2026, followed by a supplementary update search to identify eligible publications available through 31 July 2026. Search terms combined retinal microvascular assessment techniques with terms related to exercise, physical activity, physical fitness, and exercise training. Following screening and eligibility assessment, 42 publications were included in the final qualitative synthesis, comprising 20 publications identified through the initial search and 22 additional publications identified through the supplementary update search. Several publications represented complementary analyses of the same or overlapping study cohorts and were therefore not considered independent replications. Results: The included studies comprised observational studies and exercise intervention trials involving healthy individuals and clinical populations. Retinal biomarkers assessed included vessel diameters, arteriovenous ratio (AVR), vessel density, perfusion density, foveal avascular zone (FAZ), retinal oxygen extraction, wall-to-lumen ratio (WLR), and choriocapillaris perfusion parameters. Several studies reported measurable acute and chronic retinal vascular responses to exercise, although the direction, magnitude, and clinical meaning of these changes varied according to population, exercise modality, imaging technique, and biomarker. Observational studies generally reported associations between higher physical activity or cardiorespiratory fitness and a more favorable retinal vascular profile, but causal interpretation remains limited. Conclusions: Retinal microvascular biomarkers appear sensitive to acute physiological stress and may reflect selected adaptations associated with longer-term exercise exposure. However, retinal responses are heterogeneous and biomarker-specific, and their biological and clinical significance remains incompletely established. Methodological heterogeneity, overlapping study cohorts, and the limited number of adequately powered randomized and longitudinal studies constrain causal interpretation and generalizability. Retinal vascular measures should therefore currently be regarded as candidate biomarkers and research tools rather than validated surrogate outcomes or routine clinical measures.