New Horizons in the Treatment of Corneal Endothelial Dysfunction

The treatment of corneal endothelial dysfunction has experienced a revolutionary change in the past decades with the emergence of endothelial keratoplasty techniques: descemet stripping automated endothelial keratoplasty (DSAEK) and descemet membrane endothelial keratoplasty (DMEK). Recently, new treatments such as cultivated endothelial cell therapy, Rho-kinase inhibitors (ROCK inhibitors), bioengineered grafts, and gene therapy have been described. These techniques represent new lines of treatment for endothelial dysfunction. Their advantages are to help address the shortage of quality endothelial tissue, decrease the complications associated with tissue rejection, and reduce the burden of postoperative care following transplantation. Although further randomized clinical trials are required to validate these findings and prove the long-term efficacy of the treatments, the positive outcomes in preliminary clinical studies are a stepping stone to a promising future. Our aim is to review the latest available alternatives and advancements to endothelial corneal transplant.

Pharmaceutical treatment of primary open angle glaucoma

Background: Glaucoma is a progressive, irreversible optic neuropathy that results in serious vision loss and blindness. This review aimed to summarize key concepts of primary open angle glaucoma (POAG) pharmaceutical treatment trials over the last decade. Methods: We searched PubMed/MEDLINE and clinicaltrials.gov from January 1, 2010, to August 31, 2020, using the key words “POAG” and “Ocular topical therapeutics”. This search yielded 77 and 120 papers, respectively. Results: Thirty-three records were compatible with our inclusion criteria. Pharmaceutical treatment is a common intervention in POAG for lowering IOP. Prostaglandin (PG) analogues are most commonly recommended as initial medical therapy, which are administrated either as a monotherapy or in combination with other IOP-lowering classes of medications. Alternative therapies, such as ?-blockers, ?-2 adrenergic receptor agonists, and topical carbonic anhydrase inhibitors, have been used in combination or as a monotherapy. Rho-kinase inhibitors, such as netarsudil 0.02%, AR-13324 0.02%, and ripasudil are new IOP-lowering medications. Despite IOP reduction, there is a significant number of patients with POAG that may experience disease progression, and the risk of blindness over the long term is considerable. Conclusions: Clinical trials have indicated that pharmaceutical treatment of POAG is effective and safe. In addition, the new novel Rho-kinase inhibitors have shown significant IOP reduction. The new fixed combinations have also yielded significant reductions in IOP. POAG is a cause of irreversible vision loss, if not diagnosed and treated early. The condition is likely to progress in a significant number of patients, with a considerable risk of blindness in the long-term. How to cite this article: Al-Namaeh M. Pharmaceutical treatment of primary open angle glaucoma. Med Hypothesis Discov Innov Optom. 2021 Spring; 2(1): 8-17. DOI: https://doi.org/10.51329/mehdioptometry120

Anti-fibrotic activity of a rho-kinase inhibitor restores outflow function and intraocular pressure homeostasis

Glucocorticoids are widely used as an ophthalmic medication. A common, sight-threatening adverse event of glucocorticoid usage is ocular hypertension, caused by dysfunction of the conventional outflow pathway. We report that netarsudil, a rho-kinase inhibitor, decreased glucocorticoid-induced ocular hypertension in patients whose intraocular pressures were poorly controlled by standard medications. Mechanistic studies in our established mouse model of glucocorticoid-induced ocular hypertension show that netarsudil both prevented and reduced intraocular pressure elevation. Further, netarsudil attenuated characteristic steroid-induced pathologies as assessed by quantification of outflow function and tissue stiffness, and morphological and immunohistochemical indicators of tissue fibrosis. Thus, rho-kinase inhibitors act directly on conventional outflow cells to prevent or attenuate fibrotic disease processes in glucocorticoid-induced ocular hypertension in an immune-privileged environment. Moreover, these data motivate the need for a randomized prospective clinical study to determine whether netarsudil is indeed superior to first-line anti-glaucoma drugs in lowering steroid-induced ocular hypertension.

Neovascular Macular Degeneration: A Review of Etiology, Risk Factors, and Recent Advances in Research and Therapy

Neovascular age-related macular degeneration (exudative or wet AMD) is a prevalent, progressive retinal degenerative macular disease that is characterized by neovascularization of the choroid, mainly affecting the elderly population causing gradual vision impairment. Risk factors such as age, race, genetics, iris color, smoking, drinking, BMI, and diet all play a part in nvAMD’s progression, with anti-vascular endothelial growth factor (anti-VEGF) therapy being the mainstay of treatment. Current therapeutic advancements slow the progression of the disease but do not cure or reverse its course. Newer therapies such as gene therapies, Rho-kinase inhibitors, and levodopa offer potential new targets for treatment.