Latanoprost 50micrograms/ml / Netarsudil 200micrograms/ml eye drops

The social impact of glaucoma is worth of note: primary open-angle glaucoma (POAG) is one of the leading causes of irreversible blindness worldwide, affecting some 68.56 million people with overall prevalence of 2.4%. Since one of the main risk factors for the development of POAG is the increase of intraocular pressure (IOP) causing retinal ganglion cells death, the medical treatment of POAG consists in the use of drugs endowed with neuroprotective effect and able to reduce IOP. These drugs include beta-blockers, prostaglandin analogues, carbonic anhydrase inhibitors, alpha or cholinergic agonists and rho kinase inhibitors. However, not all the patients respond to the same extent to the therapy in terms of efficacy and safety. Genetics and genome wide association studies have highlighted the occurrence of mutations and polymorphisms influencing the predisposition to develop POAG and its phenotype, as well as affecting the response to pharmacological treatment. The present systematic review and meta-analysis aims at identifying genetic variants and at verifying whether these can influence the responsiveness of patients to therapy for efficacy and safety. It follows the most updated Preferred Reporting Items for Systematic reviews and Meta-Analyses 2020 recommendations. The literature search was conducted consulting the most relevant scientific databases, i.e. PubMed/MEDLINE, Scopus, Web of Science and Public Health Genomics and Precision Health Knowledge Base up to June 14th, 2023. The search retrieved 1026 total records, among which eight met the eligibility criteria for inclusion in the analysis. The results demonstrated that the most investigated pharmacogenetic associations concern latanoprost and timolol, and that efficacy was studied more in depth than safety. Moreover, the heterogeneity of design and paucity of studies prompt further investigation in randomized clinical trials. In fact, adequately powered and designed pharmacogenetic association studies are needed to provide body of evidence with good certainty for a more appropriate use of medical therapy in POAG.PROSPERO registration: CRD42023434867.

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Background/Objectives: Rho-associated coiled-coil-containing protein kinase inhibitors (ROCKis) have now become known as modulators of corneal endothelial wound repair and cell survival. However, evidence remains fragmented across laboratory and clinical reports. We performed a systematic review to synthesize preclinical and clinical data on ROCKis in corneal disease, assess their efficacy and safety, and identify research gaps. Methods: We searched PubMed, Web of Science, Scopus, and Google Scholar (until May 2025) for English-language original studies evaluating ROCKis in corneal models or patients. Inclusion criteria encompassed in vitro, ex vivo, in vivo, and clinical trials reporting functional outcomes (endothelial cell density, wound closure, visual acuity). Results: Thirty-one studies met criteria: 14 preclinical studies and 17 clinical studies. Preclinical models (rabbit, porcine, human explants) uniformly showed ROCKis (Y-27632, Ripasudil, Netarsudil, H-1152) accelerate corneal endothelial cell proliferation, migration, and restoration of a hexagonal monolayer with improved barrier and pump function over days to weeks. In 17 clinical investigations, topical Ripasudil or Netarsudil and cultured cell injections achieved significant corneal thinning, endothelial cell density and central corneal thickness changes, and visual acuity improvements (≥2 lines) with minimal adverse events. Overall bias was moderate in non-randomized studies and low in the RCTs. Conclusions: ROCKis demonstrate consistent pro-regenerative effects on corneal endothelium in multiple models and show promising clinical efficacy in Fuchs endothelial dystrophy and pseudophakic endothelial failure. Future work should explore novel delivery systems and larger controlled trials to optimize dosing, safety, and long-term outcomes.

Abstract licence: CC BY

Background/Objectives: Primary open-angle glaucoma (POAG) is an anterior optic neuropathy that can lead to irreversible vision loss if untreated. Prostaglandin analogues are the first-line treatment, but new drug classes, such as rho kinase (ROCK) inhibitors, are being explored. This review evaluates the efficacy and safety of ROCK inhibitors in treating POAG based on completed trials, comparing results with available natural history data and identifying areas for further research. Methods: A systematic database search was conducted in Ovid MEDLINE and Ovid Embase on 5 April 2022 using the following keywords: 'glaucoma', 'rho kinase inhibitor', 'rho-kinase inhibitor', 'rock inhibitor', 'ripasudil', 'netarsudil', and 'fasudil'. Abstracts were screened for relevant studies and results summarized in tables. Results: The analysis of trials conducted for ROCK inhibitors reveals that they are a safe and efficacious drug to treat POAG, demonstrating non-inferiority to existing medical treatments. Comparison of data to natural history studies was inconclusive due to the lack of natural history studies and their limitations. The results showed ROCK inhibitors to be effective when combined with existing medical treatments. However, questions remain regarding the optimal dosage, patient selection, and cost-effectiveness. Outcome measures for future trials should be expanded to include additional methods of monitoring disease progression as well as patient quality-of-life. Conclusions: ROCK inhibitors have emerged with a favorable safety profile, efficaciously attenuating intraocular pressure. To elucidate their long-term therapeutic value and safety comprehensively, further independent, large-scale, prospective randomized controlled trials are warranted. Such studies are pivotal to augment our understanding of this emergent medication class.

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Purpose: Netarsudil is a Rho kinase inhibitor and the first new class of clinically useful ocular hypotensive agents. In this study, we conducted a systematic literature review and meta-analysis to summarize and synthesize the available evidence on the efficacy and safety of fixed-dose combination (FDC) therapy with netarsudil/latanoprost in patients with glaucoma.Methods: We identified relevant studies in PubMed, Ovid Medline, Embase, and Cochrane Central until April 2021. The quality of the studies and the level of evidence were assessed using the Risk of Bias tool. Efficacy was measured as the mean difference in reducing intraocular pressure (IOP), and safety was assessed by the risk of conjunctival hyperemia (CH) due to FDC therapy, netarsudil monotherapy, or latanoprost monotherapy.Results: Four studies met the predefined eligibility criteria and were included in the meta-analysis. The mean difference in the reduction in IOP after 2 weeks and 4 to 6 weeks of drug administration was -2.41 mmHg (95% confidence interval [CI], -2.95 to -1.87) and -1.77 mmHg (95% CI, -2.31 to -1.87), respectively, in patients receiving FDC therapy versus those receiving latanoprost monotherapy. On the other hand, latanoprost monotherapy had a greater effect in reducing IOP than netarsudil monotherapy after 4 to 6 weeks of administration (mean difference, 0.95 mmHg; 95% CI, 0.43 to 1.47). The risk of CH was significantly higher with both FDC therapy and netarsudil monotherapy compared to latanoprost monotherapy in week 12, where the relative ratio was 3.01 (95% CI, 1.95 to 4.66) and 2.33 (95% CI, 1.54 to 3.54), each.Conclusions: Netarsudil/latanoprost FDC therapy has a significantly greater effect on reducing IOP than latanoprost alone. The symptoms of CH were mostly mild, and only a few glaucoma patients discontinued the medication owing to CH in earlier clinical trials. Therefore, it would be beneficial to consider the administration of netarsudil/latanoprost FDC therapy in patients with glaucoma.

Abstract licence: CC BY-NC 4.0

ObjectiveAs monotherapy is insufficient for some patients, the existing fixed-dose combination (FDC) requires two or more daily administrations with declining adherence. The present study compared the efficacy and safety of netarsudil/latanoprost FDC with monotherapy of its individual components in patients with glaucoma.MethodsA systematic literature search was performed for studies comparing netarsudil/latanoprost fixed-dose combination (FDC) vs. monotherapy in patients with glaucoma. The primary endpoints included intraocular pressure (IOP), intraocular pressure reduction percentage (IOPR%) and adverse events (AEs).ResultsThree randomized controlled trial studies (RCTs) involving 1,692 patients (FDC: 556, netarsudil: 577, latanoprost: 559) were included in this meta-analysis. FDC was more effective than netarsudil, with significantly lower diurnal IOP over three time points (8:00 a.m., 10:00 a.m., 4:00 p.m.), mean diurnal IOP (MD = −2.36 [−3.08, −1.63], P < 0.00001) and higher IOPR% (MD = 9.60 [7.86, 11.33], P < 0.00001). When comparing FDC with latanoprost, both mean diurnal IOP (MD = −1.64 [−2.05, −1.23], P < 0.00001) and diurnal IOP across 3 time points were significantly lower with FDC than with latanoprost, while FDC induced significantly higher IOPR% (MD = 6.09 [4.40, 7.77], P < 0.00001). Incidence of total AEs was similar between netarsudil and FDC, but higher with FDC than with latanoprost.ConclusionNetarsudil/latanoprost FDC appears to be superior to netarsudil or latanoprost alone, with better ocular hypotensive effects. However, there are concerns that netarsudil/latanoprost FDC was associated with a significantly higher incidence of AEs specifically compared with latanoprost.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=311956.

Abstract licence: CC BY 4.0