Relative risk of retinal detachment in COL2A1 compared to COL11A1 Stickler syndrome: an individual patient data meta-analysis

To compare the relative risk of retinal detachment between patients with COL2A1 and COL11A1 Stickler syndrome. It is unclear whether the rate of retinal detachment differs between COL2A1 and COL11A1 Stickler syndrome. Previous studies included too few patients to detect a difference between genotypes. Individual patient data meta-analysis of cohort studies, case-control studies, cross-sectional studies, case series, and case reports across the MEDLINE, Embase, Scopus, Web of Science Core Collection, and Web of Science Preprint Citation Index databases from 1991 to 2025. Articles providing eye examination results in subjects with genetically confirmed COL2A1 or COL11A1 Stickler syndrome were included. From the included articles, individual patient data on affected gene, age at last follow-up, and presence or absence of retinal detachment were extracted. Patients who had prophylactic retinopexy were excluded. A mixed effects logistic regression adjusted for clustering by article and by family was used to determine the relative risk of retinal detachment. Risk of bias was evaluated using the JBI Critical Appraisal Checklist for Case Series. The study was prospectively registered with PROSPERO (CRD42023428144). Overall certainty of evidence was evaluated with Grading of Recommendations Assessment, Development and Evaluation. Of the 1420 articles screened, 179 were eligible for inclusion and 141 provided individual patient data for a total of 673 patients from 430 families. Retinal detachment was present in 229 of 491 (47%) COL2A1 Stickler syndrome patients and in 51 of 182 (28%) COL11A1 Stickler syndrome patients. The relative risk of retinal detachment was 1.78 times higher in COL2A1 compared to COL11A1 Stickler syndrome (95% CI: 1.30-2.43 p < 0.001). The certainty of evidence was moderate. Our findings indicate a higher risk of retinal detachment in COL2A1 compared to COL11A1 Stickler syndrome, which may aid clinicians in determining individualized management plans for patients with Stickler syndrome. However, due to reporting biases inherent to the case series and case reports from which we obtained data, the overall certainty of evidence was rated as moderate and our analysis was limited to providing relative risk of retinal detachment, not absolute risk.