The eye-mind connection: a systematic review of retinal biomarkers and ocular signatures in major psychiatric disorders.

Abstract

<h4>Background</h4>Psychiatric disorders such as schizophrenia, bipolar disorder, major depression, and dementia are increasingly associated with specific ocular and retinal abnormalities. These associations may reflect shared neurovascular, inflammatory, and neurodegenerative mechanisms, yet findings remain scattered and understudied. This systematic review synthesizes existing evidence on ocular and retinal pathologies across major psychiatric conditions, highlighting common retinal biomarkers that may inform future screening strategies.<h4>Methods</h4>Following PRISMA 2020 guidelines, a systematic search of PubMed, Scopus, Web of Science, and Embase was conducted. Meta-analysis was initially planned but deemed infeasible due to significant methodological and reporting heterogeneity among eligible studies. Therefore, a structured qualitative synthesis was performed, supported by visual mapping of cross-disorder associations.<h4>Results</h4>Seventeen studies met inclusion criteria, covering major psychiatric conditions including schizophrenia, bipolar disorder, depression, and dementia. Across these disorders, approximately three-quarters of schizophrenia studies (≈75%) reported retinal nerve fiber layer (RNFL) thinning, and two-thirds of dementia studies (≈67%) showed retinal vascular abnormalities or RNFL loss. Glaucoma and dry eye syndrome were the most frequently observed in mood disorders, whereas microvascular dropout was reported in optical coherence tomography angiography (OCT-A) analyses of depression and bipolar disorder. The heatmap visualization highlighted overlapping neuro-ophthalmic signatures, and retinal biomarker analysis identified RNFL thinning and microvascular dropout as potential shared indicators of disease burden.<h4>Conclusion</h4>This review emphasizes the emerging evidence for retinal biomarkers as accessible correlates of neuropsychiatric pathology. Although quantitative synthesis was not feasible, the qualitative patterns highlight the need for large-scale, prospective, and biomarker-validation studies integrating ophthalmology and psychiatry. These findings underscore the clinical potential of the brain-retina axis in mental health diagnostics.