This review provides a comprehensive update on emerging ROCK inhibitors as an innovative treatment option for lowering intraocular pressure (IOP) in glaucoma and aims to describe the structure, mechanism of action, pharmaceutical characteristics, desirable ocular effects, including side effects for each agent. A literature review was conducted using PubMed, Scopus, clinicaltrials.gov, ARVO journals, Cochrane library and Selleckchem. Databases were searched using “investigational Rho kinase inhibitors,” and “glaucoma” as keywords. In addition to this building block strategy, successive fractions were employed to further refine the results. Of the several ROCK inhibitors discovered, only two drugs are currently approved for glaucoma treatment; Netarsudil in the USA and Ripasudil in Japan and China. We identified and reviewed 15 agents currently in laboratory or clinical trials. These agents lower IOP mainly by decreasing outflow resistance through pharmacologic relaxation of the trabecular meshwork (TM) cells and reducing episcleral venous pressure. They have an optimistic safety profile; however, conjunctival hyperemia, conjunctival hemorrhage, pain on instillation, and corneal verticillata are common. Other properties such as neuroprotection (enhancing optic nerve blood flow and promoting axonal regeneration), anti-fibrotic activity, and endothelial cell proliferation may improve the visual prognosis and surgical outcomes in glaucoma. In addition, these agents have the potential to work synergistically with other topical glaucoma medications.
Purpose To establish optical coherence tomography (OCT)/angiography (OCTA) parameter ranges for healthy eyes (HE) and glaucomatous eyes (GE) for a North Texas based population; to develop a machine learning (ML) tool and to identify the most accurate diagnostic parameters for clinical glaucoma diagnosis. Patients and Methods In this retrospective cross-sectional study, we included 1371 eligible eyes, 462 HE and 909 GE (377 ocular hypertension, 160 mild, 156 moderate, 216 severe), from 735 subjects. Demographic data and full OCTA parameters were collected. A Kruskal–Wallis test was used to produce the normative database. Models were trained to solve a two-class problem (HE vs GE) and four-class problem (HE vs mild vs moderate vs severe GE). A rigorous nested, stratified, group, 5×10 fold cross-validation strategy was applied to partition the data. Six ML algorithms were compared using classical and deep learning approaches. Over 2500 ML models were optimized using random search, with performance compared using mean validation accuracy. Final performance was reported on held-out test data using accuracy and F1 score. Decision trees and feature importance were produced for the final model. Results We found differences across glaucoma severities for age, gender, hypertension, Black and Asian race, and all OCTA parameters, except foveal avascular zone area and perimeter ( p <0.05). The XGBoost algorithm achieved the highest test performance for both the two-class (F1 score 83.8%; accuracy 83.9%; standard deviation 0.03%) and four-class (F1 score 62.4%; accuracy 71.3%; standard deviation 0.013%) problem. A set of interpretable decision trees provided the most important predictors of the final model; inferior temporal and inferior hemisphere vessel density and peripapillary retinal nerve fiber layer thickness were identified as key diagnostic parameters. Conclusion This study established a normative database for our North Texas based population and created ML tools utilizing OCT/A that may aid clinicians in glaucoma management.
Immune checkpoint inhibitors are increasingly being used for the treatment of several malignancies. In rare cases, patients develop disabling ophthalmic side effects such as dry eyes, episcleritis, keratitis, uveitis, inflammatory orbitopathy, myasthenia gravis, macular edema, and serous retinal detachment. We present a case of acute bilateral anterior uveitis, prolonged hypotony, and cataracts following the use of dual therapy ipilimumab and nivolumab. Physicians should be aware of these immune-mediated ocular adverse events and should have a management plan to deal with these side effects that range from mild to vision threatening.
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