Topical Rho kinase inhibitors as a perioperative adjunct in fuchs endothelial corneal dystrophy: a systematic review and meta-analysis

Abstract Background Fuchs endothelial corneal dystrophy (FECD) is the leading indication for corneal transplantation worldwide. Intraocular surgery in FECD affected eyes carries a heightened risk of endothelial cell loss and postoperative corneal decompensation. Topical Rho-associated protein kinase (ROCK) inhibitors, such as Ripasudil, have emerged as a potential strategy for perioperative endothelial preservation and regeneration. This systematic review and meta-analysis evaluates the efficacy and safety of topical ROCK inhibitors administered perioperatively in FECD undergoing intraocular surgery. Methods PubMed, Embase, and Cochrane CENTRAL were searched from inception to May 2026. Eligible studies were controlled studies of topical ROCK inhibitors in FECD undergoing intraocular surgery, including phacoemulsification, Descemet stripping, and endothelial keratoplasty. Risk of bias was assessed using the RoB 2.0 and ROBINS-I tools. Random-effects meta-analyses were performed for best-corrected visual acuity (BCVA) and central corneal thickness (CCT); remaining outcomes were synthesised narratively, and certainty of evidence was assessed using GRADE. Results Four studies were included, comprising 100 patients and 131 eyes: three randomised controlled trials and one non-randomised comparative study. Pooled analysis demonstrated a non-significant standardised mean difference in BCVA favouring ripasudil (− 0.80; 95% CI − 2.26 to 0.66; p = 0.144; I² = 67.5%) and a non-significant mean difference in CCT (− 34.21 μm; 95% CI − 148.40 to 79.99; p = 0.326; I² = 84.7%). Endothelial cell density was preserved or increased in ripasudil-treated eyes across all studies reporting it, though differing measurement methods precluded pooling. In one trial of advanced-stage disease, corneal decompensation occurred in 43% of control eyes versus none in the ripasudil group. Adverse events were infrequent, predominantly transient conjunctival hyperaemia. Conclusions In this meta-analysis, pooled analyses of visual acuity and central corneal thickness did not demonstrate statistically significant differences favouring topical ROCK inhibitors, and the overall certainty of evidence was low to very low. A consistent direction of effect favouring ripasudil was observed across included studies, and a reduction in corneal decompensation was reported in one trial of advanced-stage disease; however, these findings should be interpreted with caution given the small evidence base and the heterogeneity of surgical contexts and disease severity across included studies. Adequately powered randomised trials, are required before clinical recommendations can be made. Clinical trial number Not applicable. Systematic review registration PROSPERO CRD420261405168.