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Purpose: To investigate the potential locally mediated neuroprotective effect of the glucagon‐like peptide 1 receptor agonist, semaglutide, in the mouse retina, including an assessment of the underlying mechanisms of action. Methods: The study was conducted using surgically isolated retinas from female C57BL/6jRj mice as ex vivo model system. Retinas were exposed to different concentrations (10–100 nM) of semaglutide for different exposure durations (2–48 h). Retinal explant viability was assessed employing the lactate dehydrogenase release assay. The number of retinal ganglion cells (RGCs) was quantified employing immunohistochemistry. The acute and intermediate effect of semaglutide on the ex vivo retinal glucose metabolism under euglycemic conditions was assessed through metabolic mapping employing [U‐13C]glucose, followed by relative analyte quantification employing gas chromatography–mass spectrometry. The influence of semaglutide on the retinal mitochondrial function was assessed by employing the Seahorse assay on isolated retinal mitochondria. Results: Semaglutide exerted no effect on the retinal explant or RGC viability. Semaglutide may acutely potentiate the retinal ex vivo glucose metabolism/mitochondrial function indicated by statistically significant glucose hypermetabolism (increased 13C‐enrichment) of certain tricarboxylic acid intermediates (citrate and α‐ketoglutarate) relative to the control. Results on the effect of semaglutide on the mitochondrial function/oxygen consumption rate are not yet available. Conclusions: Under the experimental conditions, semaglutide did not influence the retinal explant or RGC‐specific viability. Semaglutide may acutely potentiate the retinal ex vivo glucose metabolism by enhancing the mitochondrial function. Additional studies are needed for clarification.

Purpose: To compare the efficacy and safety of rho kinase inhibitor (ROKi) with placebo or other glaucoma medication in people diagnosed with open‐angle glaucoma (OAG), primary open‐angle glaucoma (POAG) or ocular hypertension (OHT). Methods: We searched CENTRAL, MEDLINE, Embase, PubMed, LILACS, ClinicalTrials and ICTRP for randomized clinical trials and controlled clinical trials with no restrictions of type, year, and publication status. Two review authors independently screened, extracted data, and evaluated risk of bias. Results: We included 17 trials (4953 participants) evaluating the efficacy and safety of marketed ROKI‐based drugs; netarsudil and ripasudil. Trial duration varied from 24 h to 12 months. The intraocular pressure (IOP) lowering effect of netarsudil may be superior to placebo (mean difference (MD) 3.11 mmHg 95% CI 2.59–3.62; low‐certainty evidence), but inferior to latanoprost (MD 0.97 mmHg 95% CI 0.67–1.27; moderate‐certainty) and timolol (MD 0.66 95% CI 0.41–0.91; low‐certainty). Combining netarsudil and latanoprost probably further reduces IOP compared with either netarsudil (MD 2.66 mmHg 95% CI 2.35–2.98; moderate‐certainty) or latanoprost (MD 1.64 mmHg 95% CI 1.11–2.16; moderate‐certainty). Combining ripasudil and timolol may probably reduce IOP compared with timolol monotherapy (MD 0.75 mmHg 95% CI 0.21–1.29; moderate‐certainty). The certainty of evidence reporting ocular adverse events (AEs) was very low or low. However, compared to timolol, netarsudil (21 additional ocular AEs per 100‐person‐months 95% CI 14–27; moderate‐certainty) and combination therapy with ripasudil/timolol (35 additional ocular AEs per 100 person‐months 95% CI 25–45; moderate‐certainty) probably lead to more ocular AEs. ROKi was not associated with any particular serious AEs. Conclusions: The current evidence suggests that in people diagnosed with OHT or (P)OAG, the hypotensive effect of netarsudil may be inferior to latanoprost and slightly inferior to timolol. Combining netarsudil and latanoprost probably further reduces IOP compared with monotherapy. However, differences are small and may not be clinically significant. Netarsudil as mono‐ or combination therapy may result in more ocular AEs, but the evidence on AEs is limited.