Recent advances in pharmacotherapy of glaucoma

Abstract

Glaucoma is a slow progressive degeneration of the retinal ganglion cells (RGCs) and the optic nerve axons, leading to irreversible blindness if left undiagnosed and untreated. Although increased intraocular pressure is a major risk factor of glaucoma, other factors include increased glutamate levels, alterations in nitric oxide (NO) metabolism, vascular alterations and oxidative damage caused by reactive oxygen species. Glaucoma is the second leading cause of blindness globally, accounting for 12.3% of the total blindness. Glaucoma has been broadly classified as primary or secondary open-angle or angle-closure glaucoma. The primary goal in management of glaucoma is to prevent the risk factor, especially elevated intraocular pressure (IOP), using medications, laser therapy or conventional surgery. The first-line treatment of glaucoma usually begins with the use of a topical selective or nonselective blocker or a prostaglandin analog. Second-line drugs of choice include alpha-agonists and topical carbonic anhydrase inhibitors. Cholinergic agonists are considered third-line treatment options. When a single therapy is not sufficient to lower the IOP, a combination therapy is indicated. To enhance the patient compliance, drug delivery systems like electronic devices, ocular inserts, tansdermal and mechanical drug delivery systems have been developed. Use of viscoelastic agents in ophthalmic formulations, emulsions and soluble ophthalmic drug inserts (SODI) enhance patience compliance and ocular drug delivery in patients in long-term glaucoma therapy. For patients who do not respond to antiglaucoma medications, laser trabeculoplasty and incisional surgery are recommended. Several nutrients and botanicals hold promise for the treatment of glaucoma, but most studies are preliminary, and larger, controlled studies are required. Future directions for the development of a novel therapy glaucoma may target glutamate inhibition, NMDA receptor blockade, exogenously applied neurotrophins, open channel blockers, antioxidants, protease inhibitors and gene therapy.

Nucleotides in the Eye: Focus on Functional Aspects and Therapeutic Perspectives

“…Disruption of this equilibrium results in raised IOP, which is an important risk factor in the pathogenesis of glaucoma, a multifactorial optic neuropathy characterized by damage to the optic nerve head and irreversible field of vision loss (Friedman et al, 2004). For this reason, most glaucoma drug treatments involve lowering IOP, either by decreasing the production of aqueous humor or by improving its outflow (Gupta et al, 2008).…”

Diadenosine tetraphosphate as a potential therapeutic nucleotide to treat glaucoma

“…Most glaucoma pharmaceutical treatments involve lowering IOP, either by decreasing the production aqueous humour or by improving its outflow, thereby reducing damage of the optic nerve. [2]. Some families of compounds are currently used to induce such IOP reduction, and more are emerging as promising substances to treat this disorder [3].…”

A Comparative Study on the Safety and Efficacy of Topical Bimatoprost With Timolol Maleate in Glaucoma Patients

“…It lowers IOP in both normotensive and in chronic open angle glaucoma patients. (6,7,8) It reduces IOP by 20-33%, on an average. Early trials demonstrated that it is more effective in lowering IOP as compared to epinephrine and pilocarpine.…”

“…Timolol is the US-FDA's gold standard drug for glaucoma therapy, against which all new medications must be compared prior to approval. (8) Bimatoprost, is a synthetic prostamide analog that was approved for use in US in 2001. (8,9) It lowers IOP by a dual mechanism: primarily by increasing pressure dependent (presumed trabecular meshwork) outflow, but also by increasing pressure-independent (Presumed uveoscleral) outflow.…”