Efficacy and safety of stem cell therapy for dry eye syndrome in Sjögren's syndrome: a systematic review and meta-analysis.

Background: Stem cell therapy holds considerable potential for treating dry eye syndrome, though it has yet to receive clinical approval. Aim: This paper systematically quantifies the efficacy and safety of stem cell-based therapies in dry eye syndrome caused by Sjögren's syndrome, aiming to provide information for dry eye treatment efforts. Methods: This systematic review collected literature published prior to 16 January 2026 in PubMed, Embase, and the Cochrane Library concerning stem cell therapy for Sjögren's syndrome-induced dry eye disease. Efficacy outcomes comprised: OSDI scores, along with changes in NIKBUT first, Oxford score, and Schirmer test results. Safety outcomes comprised commonly reported adverse events. Continuous outcomes were expressed as mean difference (MD), while dichotomous outcomes used single-group rates, both presented with 95% CI. All data analyses were conducted using Review Manager 5.4 software, adhering to the PRISMA guidelines. Results: This meta-analysis included five studies involving 114 patients with dry eye syndrome. Results demonstrated that stem cell therapy significantly altered the OSDI score compared to pre-treatment levels: -15.10 (95% CI: -18.65, -11.56; P < 0.00001). NIKBUT first scores increased significantly by 3.26 points post-treatment (95% CI: 2.17, 4.34; P < 0.00001). The Oxford score showed a change of -0.20 (95% CI: -0.85, 0.45; P = 0.55) post-treatment. The Schirmer test score exhibited an overall change of 3.87 (95% CI: 1.93, 5.81; P < 0.0001). Specifically, the MD at 2 weeks, 4 months, and 12 months was 8.76 (95% CI: 0.58, 16.94; P < 0.04), 3.52 (95% CI: 1.66, 5.38; P < 0.002), and 5.10 (95% CI: 0.24, 9.96; P < 0.04), respectively. The incidence of injection pain at 4 weeks was 14% (95% CI: -11%, 39%, P = 0.28). Ocular discomfort occurred in 16% of subjects at 4 weeks (95% CI: -4%, 35%, P = 0.11). Periorbital oedema occurred in 14% of subjects at 4 weeks (95% CI: -11%, 39%, P = 0.28). Blurred vision and periorbital paresthesia occurred at treatment with rates of 21% (95% CI: -7%, 50%, P = 0.14) and 15% (95% CI: -4%, 35%, P = 0.12), respectively. Conclusion: This meta-analysis indicates that stem cell therapy effectively reduces OSDI scores, increase Schirmer test scores, and enhances tear film stability in dry eye syndrome caused by Sjögren's syndrome. However, the increased incidence of adverse events in the short term suggests that benefits and risks must be carefully weighed prior to clinical application, with rigorous monitoring and close follow-up required throughout treatment. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/view/CRD420261287054, identifier CRD420261287054.