Efficacy, effectiveness, and safety of rho-kinase inhibitors in uveitic glaucoma and ocular hypertension secondary to uveitis: a systematic review and meta-analysis

PURPOSE: To evaluate the efficacy, effectiveness, and safety of Rho-kinase (ROCK) inhibitors in the management of uveitic glaucoma (UG) and ocular hypertension secondary to uveitis (OHT-SU) through a systematic review and meta-analysis. METHODS: We systematically searched PubMed, EMBASE, Virtual Health Library, and medRxiv databases until October 29, 2024, for studies evaluating UG or OHT-SU patients treated with ROCK inhibitors. Eligible designs included case series with over 10 patients, cross-sectional studies, cohort studies, and randomized controlled trials. Risk of bias was assessed using the CLARITY tools and validated metrics such as those developed by Hoy et al., Hassan Murad et al., and the RoB-2 tool. A pressure (IOP) reduction meta-analysis at different follow-up points was conducted using R software. The study was registered in PROSPERO with the CRD42024618812 number. RESULTS: Eleven studies (383 participants, 256 eyes) were analyzed. Some studies reported outcomes per eye, whereas others reported outcomes only per patient; thus, the number of eyes reflects only explicitly reported data. Based on the risk of bias assessment, two studies had a low risk of bias, four raised some concerns, and five were at high risk of bias. Pooled mean age was 64.2 ± 15.2 years (from 10 studies reporting age); sex distribution (50.5% male, 49.5% female, from 7 studies reporting gender). ROCK inhibitors achieved a statistically significant reduction in IOP at 3 months (mean difference: -9.32 mmHg, 95% CI: -17.02 to -1.62). These effects were sustained at 12 months (-7.92 mmHg, 95% CI: -10.28 to -5.56). Combination therapy enhanced pressure control. The most common adverse event was conjunctival hyperemia, with a pooled prevalence of 6% (95% CI: 3%-15%), followed by ocular pain and blurred vision. Importantly, no major safety differences were found between ripasudil and netarsudil. Additionally, ROCK inhibitors also improved surgical outcomes in UG patients. CONCLUSION: ROCK inhibitors demonstrate significant and sustained IOP-lowering effects in UG and OHT-SU with a favorable safety profile. Their additive effect with conventional treatments and potential benefits in surgical outcomes highlight their role as promising therapeutic agents. Further clinical trials are needed to compare different ROCK inhibitors and assess their long-term safety and effectiveness in different populations.