Comparative effectiveness and safety of sulfur hexafluoride versus octafluoropropane tamponade in pars plana vitrectomy for idiopathic full-thickness macular hole: a systematic review and meta-analysis

Abstract

Introduction: Idiopathic full-thickness macular hole (FTMH) significantly impairs central vision, affecting quality of life. Pars plana vitrectomy (PPV) with internal limiting membrane peeling and gas tamponades such as sulfur hexafluoride (SF6) and octafluoropropane (C3F8) is the standard surgical treatment. Current evidence on the comparative effectiveness and safety of SF6 versus C3F8 remains inconclusive, prompting clinical uncertainty. This systematic review and meta-analysis aimed to compare the anatomical, the visual outcomes, and safety profiles of SF6 and C3F8 as gas tamponades in PPV for idiopathic FTMH. Methods: A systematic search of MEDLINE, Embase, and Cochrane CENTRAL databases was conducted for randomized controlled trials (RCTs) and observational cohort studies published between January 2000 and April 2025. Included studies evaluated adult patients with idiopathic FTMH treated by PPV and gas tamponade using SF6 or C3F8. Studies were selected based on clearly differentiated outcomes between gases, exclusion of non-idiopathic cases, and English full-text availability. Our primary outcome was the anatomical FTMH closure rate. Secondary outcomes included bestcorrected visual acuity (BCVA) improvements and incidence of postoperative complications/adverse events. Data on these outcomes was extracted independently by two reviewers. Risk of bias (RoB) was assessed using the RoB 2 tool for RCTs and ROBINS-I for observational studies. Meta-analyses were performed using random-effects models as appropriate. Certainty of evidence was evaluated using GRADE. Results: Six studies (4 RCTs, 2 cohort studies; total 580 participants) were included. Anatomical closure rates were comparable for C3F8 (88.1%) and SF6 (86.0%; RR 1.03, 95% CI 0.96–1.11). No significant differences were observed in BCVA at 3 months (MD - 0.09 LogMAR, 95% CI -0.27–0.08), BCVA at final follow-up (MD -0.05 LogMAR, 95% CI - 0.15–0.06), or change from baseline BCVA at final follow-up (MD 0.04 LogMAR, 95% CI - 0.06–0.14). Rates of primary open-angle glaucoma (RD 0.00, 95% CI -0.02–0.02), ocular hypertension (RD -0.00, 95% CI -0.02–0.02), new-onset cataract formation (RR 1.02, 95% CI 0.85–1.22), and subsequent cataract surgery (RR 1.11, 95% CI 0.82–1.49) showed no significant differences. Sensitivity analyses excluding high-risk studies did not materially alter the results. Conclusion: This systematic review found no significant differences between SF6 and C3F8 gas tamponades regarding anatomical closure, BCVA improvement, or postoperative complications in PPV for idiopathic FTMH. The overall certainty of evidence ranged from very low to moderate. As neither gas tamponade demonstrated superiority, clinical decisions should consider patient preferences, surgeon expertise, and specific clinical circumstances. Further high-quality studies with standardized protocols are warranted to enhance the certainty of current findings.