The ingenuity of pharmaceutical researchers continues to amaze in their bility to devise inventive solutions and improve upon our current arsenal of ophthalmic medications, devices,and delivery systems.
In this article, we will take a brief look at some of these new developments within various ophthalmic disciplines.
An emerging trend in glaucoma medications is combination agents. Some combinations in phase III development include Pfizer's Xalcom (latanoprost and timolol), Alcon's Extravan (travoprost and timolol), and Allergan's Combigan (brimonidine tartrate and timolol) and Lumigan (bimatoprost) with timolol. For these combination agents, the FDA requires that each component contributes to the efficacy of the eye drop, ensuring that a combination confers greater efficacy than either of the individual components.
Overall, it seems the advent of these combination medications is a winning situation for patients with glaucoma, potentially aiding with better compliance and consistency in dosing and medication use.
One mechanistic approach that has potential applicability for the treatment of glaucoma is that of rho kinase inhibitors. Rho kinase is an enzyme that is present in trabecular meshwork and ciliary muscle tissues. When treatment with a rho kinase inhibitor is applied, an increase in aqueous outflow and a decrease in IOP result. This effect has been observed in a rabbit model, inducing decreases from 4.3 to 5.3 mm Hg after 90 minutes.2 As the human clinical efficacy and safety profiles of such agents are researched, this evidence will determine the potential success of such agents, depending on how they perform relative to currently available standards of treatment such as latanoprost and timolol.
Further, neuroprotective agents may garner more attention as a potential form of therapy in coming years, mainly borrowed from treatments originally developed for other neurologic disorders such as Parkinson's disease or multiple sclerosis. For example, memantine (Namenda, Forest Pharmaceuticals), which is currently available for the treatment of Parkinson's disease, is being investigated in phase III glaucoma trials. Namenda acts as an N-methyl-D-asparate (NMDA) antagonist by binding to glutamate receptors on nerve cells, protecting the cells from excess calcium, and reducing cell toxicity.3 Glatiramer acetate (Copaxone, Teva Pharmaceuticals), currently used to treat multiple sclerosis, is also being investigated as a neuroprotective agent in patients with glaucoma, as are nitric oxide inhibitors.
Dry eye The more recently approved agents for dry eye include over-the-counter ophthalmic solutions Soothe (Alimera) and Systane (Alcon Laboratories). Soothe, approved in 2003, has a novel lipid restorative (Restoryl) that rapidly rebuilds the lipid layer, enhancing tissue lubrication and reducing tear evaporation. Systane has been shown to relieve both the signs and symptoms of dry eye.4 It works via a pH-dependent polymerization mechanism, in which the HP-guar and borate components of the eyedrop are induced to cross-link when instilled in the eye, forming a protective shield over the ocular surface.
Cyclosporine (Restasis, Allergan) for the treatment of severe dry eye remains the only prescription option. The product is becoming more widely accepted as practitioners continue to gain experience with its use and become more adept at identifying the patients for whom it provides the most benefit.