An evidence-based review of unoprostone isopropyl ophthalmic solution 0.15% for glaucoma: place in therapy

Abstract

Glaucoma is a progressive, neurodegenerative optic nerve disease that can cause significant visual morbidity and affects over 60 million people worldwide. The only known modifiable risk factor for glaucoma at this time is elevated intraocular pressure (IOP), which may be treated with medications, laser therapy, and/or incisional surgery. Topical ocular medications are commonly used as first-line therapy for glaucoma, although side effects may limit their use. Unoprostone is a novel 22-carbon ocular hypotensive agent that may be advantageous in treating some patients with open angle glaucoma or ocular hypertension. Unlike the 20-carbon prostanoids, such as latanoprost, that lower IOP primarily through an increase in uveoscleral outflow, unoprostone may lower IOP through increased aqueous outflow via the conventional trabecular meshwork pathway. Although not as efficacious as other prostanoids, unoprostone is effective for IOP reduction both as monotherapy and adjunctive therapy with timolol. Unoprostone has decreased affinity for the prostaglandin F2α receptor, which may explain its well tolerated ocular and systemic side effect profile compared with other prostanoids.

Keywords: Rescula®; glaucoma; medication; prostaglandin; unoprostone.

Figure 1

Molecular structure of unoprostone isopropyl and related molecules. Notes: Unoprostone isopropyl (A) is a 22-carbon derivative of docosahexanoic acid (D), a naturally occurring fatty acid found in the central nervous system and retina. Following ocular instillation, unoprostone is hydrolyzed by corneal esterases to its active form, unoprostone free acid (C). The 20-carbon prostanoids, such as latanoprost, are derived from the eicosanoid, prostaglandin F_2α (B).

Figure 2

Mean 12-hour diurnal IOP comparing unoprostone, timolol, and betaxolol monotherapy. Notes: Reprinted with permission from the American Journal of Ophthalmology, Volume 133/edition 1, Nordmann JP, Mertz B, Yannoulis NC, Schwenninger C, Kapik B, Shams N; for the Unoprostone Monotherapy Study Group-EU. A double-masked randomized comparison of the efficacy and safety of unoprostone with timolol and betaxolol in patients with primary open-angle glaucoma including pseudoexfoliation glaucoma or ocular hypertension. 6 month data, pages 1–100, Copyright 2002, with permission from Elsevier. Abbreviations: UIOS, unoprostone isopropyl ophthalmic solution; TMOS, timolol maleate ophthalmic solution; BHOS, betaxolol hydrochloride ophthalmic solution; IOP, intraocular pressure.

Figure 3

Change in diurnal IOP (percentage) with unoprostone, dorzolamide, and brimonidine as adjunctive therapy with timolol. Notes: Mean percentage changes in the 8 hour diurnal IOP from a timolol-treated baseline at week 12 were −12.3%, −12.5%, and −14.4% in the unoprostone, brimonidine, and dorzolamide groups, respectively. Reproduced from Unoprostone as adjunctive therapy to timolol: a double masked randomised study versus brimonidine and dorzolamide. Hommer A, Kapik B, Shams N; for the Unoprostone Adjunctive Therapy Study Group, Volume 87(5), pages 592–598, Copyright 2003, with permission from BMJ Publishing Group Ltd. Abbreviations: IOP, intraocular pressure; SD, standard deviation.