This systematic review and meta-analysis synthesized evidence from 49 studies involving 3492 individuals with genetically or clinically confirmed Stickler syndrome. The analysis compared outcomes between those receiving prophylactic treatment for rhegmatogenous retinal detachment (RRD) and untreated individuals or eyes, though the comparator was not explicitly defined in all included studies.
The pooled prevalence of RRD in individuals with Stickler syndrome was 41.9% (95% CI, 33.78%-50.20%), and 26.1% (95% CI, 19.64%-33.13%) in eyes. Among those receiving prophylaxis, the RRD incidence was 8.7% in individuals (95% CI, 7.09%-10.48%) and 5.1% in eyes (95% CI, 4.02%-6.27%). Prophylaxis was associated with a 92% reduction in the odds of RRD (OR 0.08; 95% CI, 0.04%-0.17%). For surgical repair, the pooled final anatomic success rate was 85.5% (95% CI, 73.13%-94.74%), with combined scleral buckling and vitrectomy achieving 93.6% success (95% CI, 87.26%-97.98%). Safety and tolerability data were not reported.
Key limitations include high statistical heterogeneity (I² = 86.3% for individual prevalence, 82.1% for eye prevalence, 83.9% for surgical outcomes) and moderate to low certainty of evidence. The evidence certainty was moderate for patient-level prophylaxis and surgical outcomes but low for eye-level prophylaxis. The analysis is based on observational data, and the specific prophylactic protocols varied across studies.
For clinical practice, these findings support the potential role of prophylaxis in reducing RRD risk in Stickler syndrome, but the high heterogeneity and observational nature of the evidence preclude definitive conclusions. The surgical success rates, particularly for combined procedures, provide context for managing RRD when it occurs. Decisions should consider individual patient factors and the limitations of the available evidence.
View Original Abstract ↓
TOPIC: Stickler syndrome is an inherited connective tissue disorder with severe ocular manifestations. It is the leading syndromic cause of rhegmatogenous retinal detachment (RRD) particularly in the pediatric population.
CLINICAL RELEVANCE: To review the prevalence, prophylactic efficacy, and surgical outcomes of RRD in Stickler syndrome.
METHODS: Our protocol was registered on International Prospective Register of Systematic Reviews (PROSPERO) (CRD420251070425). We searched 6 databases and ClinicalTrials.gov from inception to June 2025. Studies reporting RRD-specific data in genetically or clinically confirmed Stickler syndrome were included. The primary outcome was RRD prevalence. Secondary outcomes included prophylactic efficacy and final surgical repair success. Meta-analysis was performed using the random-effects model, with assessment of heterogeneity and publication bias. Risk of bias was assessed using the Joanna Briggs Institute the Newcastle-Ottawa Scale tools. Evidence certainty was assessed using the (Grading of Recommendations Assessment, Development, and Evaluation) framework.
RESULTS: A total of 49 studies involving 3492 individuals were included. Thirty-one studies reported the prevalence of RRD in individuals, with a pooled estimate of 41.9% (95% confidence interval [CI], 33.78%-50.20%; I = 86.3%), whereas 23 studies reported prevalence in eyes, with a pooled estimate of 26.1% (95% CI, 19.64%-33.13%; I = 82.1%), with higher rates in type 1 Stickler syndrome. Twelve studies of prophylactically treated individuals showed an RRD incidence of 8.7% (95% CI, 7.09%-10.48%; I = 0.0%), and 15 studies of prophylactically treated eyes showed an incidence of 5.1% (95% CI, 4.02%-6.27%; I = 23.5%). Prophylaxis reduced the odds of RRD by 92% (odds ratio, 0.08; 95% CI, 0.04%-0.17%), with moderate-certainty evidence in patients (I = 76.9%) and low-certainty evidence in eyes (I = 83.5%). Fifteen studies reported surgical outcomes, with a pooled final anatomic success rate of 85.5% (95% CI, 73.13%-94.74%; I = 83.9%), supported by moderate-certainty evidence, and the highest success of 93.6% (95% CI, 87.26%-97.98%; I = 0.0%) was observed in eyes treated with combined scleral buckling and vitrectomy. Overall, most included studies were of acceptable methodologic quality.
CONCLUSIONS: Rhegmatogenous retinal detachment is highly prevalent in Stickler syndrome. Prophylaxis significantly reduces this risk, whereas surgery remains effective. These findings support early surveillance and prophylaxis and larger prospective trials comparing prophylactic and surgical techniques.
FINANCIAL DISCLOSURE(S): The authors have no proprietary or commercial interest in any materials discussed in this article.
