Limited medical therapy drives impetus for product development

By Cheryl Guttman Krader

Recent innovations have addressed some limitations of medical treatment for glaucoma, but unmet needs remain, said Sunita Radhakrishnan, MD.

Discussing the current status of medical therapy for glaucoma, Dr. Radhakrishnan cited newer formulations that are more ocular surface friendly and the first beta blocker-free, fixed combination as useful advances. Items on her “medical therapy wish list” included products with better drug delivery systems and options acting via alternate mechanisms of action. 

Sunita Radhakrishnan, MD, presented her "medical therapy wish list" for glaucoma.

“Until we have a surgical procedure that delivers the effectiveness of a filter with the safety of microinvasive glaucoma surgery and maintains its benefits over the long-term, medical therapy is here to stay,” said Dr. Radhakrishnan, in private practice at Glaucoma Center of San Francisco.

Progress for safety, adherence

The potential for chronically used topical medications to damage the ocular surface is an often-ignored issue. However, it is an important concern that underscores the value of medications that limit preservative-related toxicity.

“We know from patient reports and many studies that ocular surface disease is highly prevalent among glaucoma patients being treated with medical therapy,” Dr. Radhakrishnan said. “We also know that the preservative benzalkonium chloride (BAK) contributes to the disruption of the ocular surface.”

Currently, there are two branded products formulated with non-BAK preservatives, brimonidine tartrate 0.1% and 0.15% with Purite (Alphagan P, Allergan/Actavis) and travoprost 0.004% with sofZia (Travatan Z, Alcon Laboratories). In addition, there are three preservative-free options: tafluprost 0.0015% (Zioptan, Merck), single-use dorzolamide HCl 2%/timolol maleate 0.5% (Cosopt PF, Akorn), and single-use timolol maleate 0.5% (Timoptic in Ocudose, Bausch + Lomb).

For patients whose IOP cannot be controlled on a single medication, use of a fixed-combination product offers the opportunity to reduce preservative exposure with an added convenience option that can enable compliance and avoid drop washout. Recently, the fixed-combination category was expanded by the addition of the brinzolamide 1%/brimonidine 0.2% combination (Simbrinza Suspension, Alcon), the only beta-blocker-free, fixed-combination.

Dr. Radhakrishnan noted that relative to its individual components, the brinzolamide/brimonidine fixed-combination has a similar side-effect profile and greater IOP-lowering efficacy. The magnitude of IOP reduction provided by the brinzolamide/brimonidine fixed-combination is about the same as that provided by monotherapy with a prostaglandin.

Future developments

Several companies are working to develop novel technology for delivering medication to the eye. Such systems will be a welcome advance considering the problems patients encounter using the existing eye drop bottle.

“Topical medications for glaucoma need to be used every day for many years, and many patients have difficulty getting their drops into the eye,” said Dr. Radhakrishnan.

“These issues are the impetus for the development of alternative drug-delivery systems that can facilitate topical administration or provide sustained drug delivery."

As another advantage, better drug-delivery systems could allow for treatment regimens using a lower dose of the active medication that could minimize side effects without compromising IOP-lowering efficacy. The 0.01% formulation of bimatoprost (Lumigan 0.01%, Allergan/Actavis) offers a good illustration of that concept. 

Reformulated with a higher concentration of BAK, which improves drug delivery through the cornea, bimatoprost 0.01% has the same IOP-lowering effect as its predecessor, bimatoprost 0.03%, but is associated with a lower rate of conjunctival hyperemia.

Dr. Radhakrishnan noted that although the concentration of BAK in bimatoprost 0.01% is fourfold higher than that found in bimatoprost 0.03%, it is similar to the concentration of BAK found in branded and generic formulations of latanoprost.

The availability of a medication providing a different mechanism of action than existing options would also be a welcome addition for patients, Dr. Radhakrishnan said. Today’s most commonly used, IOP-lowering drugs either act as aqueous suppressants (beta-blockers, alpha agonists, and carbonic anhydrase inhibitors) or increase uveoscleral outflow (prostaglandin analogues, alpha agonists).

Increasing trabecular outflow is another mechanism for lowering IOP, but it is only provided by pilocarpine, which has limited use because of its side effects. However, agents acting as rho kinase inhibitors may augment the group of trabecular outflow medications in the future.

Dr. Radhakrishnan added that because IOP-lowering alone is not enough to stop glaucoma progression for some patients, it is also encouraging to hear that there is interest in developing neuroprotective agents for glaucoma.