Longitudinal Optical Coherence Tomography Angiography Assessment of Retinal Microvascular Changes in Patients Receiving Oral Isotretinoin

Objective: To determine whether oral isotretinoin therapy is associated with longitudinal changes in retinal structure and microvasculature measured by optical coherence tomography angiography (OCTA).Methods: This prospective, longitudinal, bilateral-eye study was conducted at an anonymized Erzincan Binali Yıldırım University Mengücek Gazi Training and Research Hospital between 01 June 2021 and 01 June 2022.Fifty-four patients receiving oral isotretinoin for acne were enrolled; of these, 34 patients (68 eyes) completed baseline, month 1, month 3, and month 6 visits, forming the complete-case sample.All quantitative optical coherence tomography (OCT)/OCTA examinations were performed on the Nidek retinopathy study (RS)-3000 advance platform after topical tropicamide-induced dilation.Acquisitions were repeated until the image-quality index was at least 0.70; scans that did not reach this threshold or had clinically relevant artifacts were excluded.Longitudinal change was analyzed with patientclustered Gaussian generalized estimating equations, adjusted for eye laterality, age, and sex.Time was modeled categorically.Endpointlevel multiplicity was controlled using the Benjamini-Hochberg false-discovery rate (FDR) procedure, and pairwise contrasts were assessed using the Holm procedure and a global FDR correction.Results: The analytic dataset included 34 patients, 68 eyes, and 272 eye-time observations.Mean age was 20.71 ± 3.33 years; 22 patients (64.7%) were women and 12 (35.3%)were men.No OCT or OCTA endpoint showed an FDR-confirmed time effect; no significant change was detected in any parameter.The lowest omnibus time-effect P value was observed for inner-nasal Early Treatment Diabetic Retinopathy Study 9 (ETDRS9) perfusion (Wald χ 2 = 9.786, df = 3, p = 0.0205), but this finding did not survive FDR adjustment (q = 0.5284).The smallest pairwise contrast was the inner-temporal ETDRS9 perfusion between months 6 and 1 (difference = 1.338,SE = 0.532, p = 0.0119), which was not significant after the within-endpoint Holm correction (p = 0.0715) or the global FDR correction (q = 0.5934).Patient-averaged models, non-parametric repeated-measures tests, and time-by-eye interaction models were consistent with the primary analysis.Conclusion: Over 6 months of oral isotretinoin therapy, no retinal structural or OCTA microvascular parameters exhibited changes that remained significant after correction for multiple testing.Small nominal fluctuations should be interpreted as exploratory signals rather than confirmatory evidence of retinal microvascular toxicity.