Retinal Thickness in Anxiety, Depression, and Substance Use Disorders: A Systematic Review and Meta-Analysis of Optical Coherence Tomography (OCT) Studies Highlighting Substantial Heterogeneity

BackgroundOptical coherence tomography (OCT) is increasingly used to investigate retinal structural changes across neurological and neuropsychiatric conditions. This systematic review and meta-analysis synthesises evidence examining retinal thickness in anxiety, depression, and substance use disorders (SUD) compared with healthy controls. MethodsA pre-registered systematic search (PROSPERO: CRD42024559542) of major databases following PRISMA guidelines was conducted. Case-control studies measuring retinal layer thickness via OCT in adults with DSM or ICD diagnosed anxiety, depression, or SUD were included. Multilevel random-effects models were used to calculate pooled standardised mean differences (SMD) and account for dependencies. ResultsThirty-three studies were included for narrative review, and 25 studies with 145 effect sizes were included for meta-analysis. The primary analysis, which pooled all disorders and effect sizes from available retinal thickness measures, found no significant differences between cases and controls (SMD = -0.20; 95% CI [-0.53, 0.14]; p = .244). Subgroup analyses for anxiety, depression, and SUD also yielded non-significant results (all p > .05). No specific retinal layer was consistently affected, and there was no evidence of an age x diagnosis interaction. Significant heterogeneity (Q = 756.57, p < .001) was present across analyses. ConclusionThis meta-analysis found no significant associations between retinal structural differences and anxiety, depression, or SUD. The field is characterised by high heterogeneity and publication bias, limiting the strength of evidence for the utility of OCT as a reliable biomarker for these conditions. Standardised, large-scale studies are needed with strict controls for confounding factors, including medication, disease stage and ocular parameters, alongside standardised OCT segmentation protocols. Article HighlightsO_LIFirst meta-analysis of OCT retinal thickness in anxiety, depression and SUD. C_LIO_LINo significant retinal thickness differences found between cases and healthy controls. C_LIO_LIAge and sex did not moderate the association between diagnosis and retinal thickness. C_LIO_LIHigh heterogeneity and publication bias limit utility of OCT as a neuropsychiatric biomarker. C_LIO_LIStandardised protocols are needed to clarify retinal changes in psychiatric research. C_LI