Efficacy and safety of different regimens for primary open-angle glaucoma or ocular hypertension: a systematic review and network meta-analysis

Purpose To assess the efficacy and safety of different regimens, including monotherapy and double therapy, for primary open-angle glaucoma (POAG) or ocular hypertension. Methods We searched PubMed, EMBASE and clinicaltrials.gov for studies that fit our inclusion criteria in this network meta-analysis. Randomized controlled trials that report data on efficacy and safety of medications for POAG or ocular hypertension are included. Data on intra-ocular pressure (IOP) lowering effect and incidence of adverse events including hyperaemia and ocular discomfort were extracted and used in mixed-comparison analysis. Results This study includes 72 randomized trials. Data were available on 12 medical treatments of POAG or ocular hypertension. Of 66 possible comparisons of outcome efficacy, 15 treatments were compared directly. Compared to prostaglandin analogues (PGA), beta-blockers (BB) showed relatively weaker ability to lower IOP, followed by α2-adrenergic agonists (AA) and carbonic anhydrase inhibitors (CAI). For dual therapy, regimens composed of a combination of PGA with another treatment demonstrated more powerful IOP lowering efficacy, while the combination of two non-PGA drugs had lower efficacy in controlling IOP than PGA alone. There was no statistical significance in combinations that did not include PGA on efficacy of IOP control. In terms of tolerance, PGA alone leads to more severe hyperaemia than any other monotherapy regimen, while BBs have the lowest effect on the incidence of hyperaemia. Most dual therapy regimens containing PGA also lead to serious hyperaemia, with the exception of PGA + AA. Compared to regimens containing PGA, those with BB are less likely to cause hyperaemia. Conclusion Our network meta-analysis showed that PGAs provide best IOP lowering effect among all the monotherapy regimen. Combination of PGA and other category of drugs leads to better IOP decrease. Combination of BB and another non-PGA drug may have less ocular side-effects than PGA alone.