Updates for addressing challenges: novel strategies in the medical management of glaucoma

November 12, 2007

Glaucoma remains a leading cause of blindness worldwide despite advances in prevention and treatment. An estimated 6 million people have developed blindness due to glaucoma, and clinicians share the blame, according to L. Jay Katz, MD, director of the glaucoma service, Wills Eye Institute, Philadelphia.

Glaucoma remains a leading cause of blindness worldwide despite advances in prevention and treatment. An estimated 6 million people have developed blindness due to glaucoma, and clinicians share the blame, according to L. Jay Katz, MD, director of the glaucoma service, Wills Eye, Philadelphia.

While societal problems with access to healthcare as well as patient nonadherence to therapy contribute to the development of blindness from glaucoma, physicians err by providing inadequate therapy.

"There's a very delicate balance between overtreating and treating appropriately," Dr. Katz said, speaking at a continuing medical education symposium held at the New Orleans Marriott at the Convention Center Monday morning. He cited a surveillance study of data from 395 patients with primary open-angle glaucoma in six managed-care plans showing that IOP was inadequately controlled at many visits and that there was no change in therapy during half of the visits at which the IOP was ≥30 mm/Hg. While there could be many reasons for this, lack of physician aggressiveness in treating elevated IOP is likely one of the factors involved.

Setting and adjusting a target IOP is one of the fundamentals of glaucoma therapy, but emerging considerations that seem in influence IOP control include daily fluctuation, intervisit fluctuation, and body position, Dr. Katz said. Several studies have linked fluctuation over time to visual field progression, although others do not support this finding. Researchers will continue to investigate this potential risk factor and how clinicians might incorporate their findings into patient management.

Lowering IOP is the only proven method for treating glaucoma, said Louis B. Cantor, MD, Jay C. and Lucile L. Kahn professor of glaucoma research and education, Indiana University School of Medicine, Indianapolis. However, it addresses only one component of a complex disease.

"Hopefully we will have multifactorial therapy for this multifactorial disease in the future," Dr. Cantor said.

Initial therapy may consist of medications, laser, or surgery, although medically therapy is typically the first choice for most patients. The goals should be to achieve the lowest IOP on monotherapy, obtain a high response rate, maintain consistent IOP lowering, and obtain patient compliance and adherence.

Monotherapy is preferred because it improves patient compliance, is more economical, has no added side effects from additional therapeutic approaches, and reduces cumulative exposure to preservatives, Dr. Cantor said. Monotherapy has limitations, however, such as reduced effectiveness over time, and studies have shown that many patients will need adjunctive therapy to lower their IOP. However, clinicians should consider switching medications within the prostaglandin class before adding a second or third, he added.

A number of medications are appropriate as adjunctive agents to prostaglandins for lowering IOP. They include ocular beta-blockers, selective alpha-adrenergic agonists, and topical carbonic anhydrase inhibitors. Among the alpha-adrenergic agents, brimonidine 0.2% (Alphagan P, Allergan) has proven long-term control over 3 years and may have a neuroprotective role, suggested Robert D. Fechtner, MD. Dr. Fechtner is professor of ophthalmology and director, glaucoma division, at the Institute of Glaucoma and Visual Science, New Jersey Medical School, University of Medicine & Dentistry of New Jersey, Newark.

Few well-designed studies have been performed on additivity to prostaglandins, and in reality every patient will respond differently to an additional agent. Although drugs in all three classes can further reduce IOP levels, in general there is limited efficacy with adding multiple agents, Dr. Fechtner said. Other concerns include the risk of a washout effect when patients take the second medication too soon after the first, increased exposure to preservatives, and decreased adherence. Among the thousands of possible combinations of glaucoma therapy, the most rational approach may be to use a prostaglandin plus a topical beta-blocker, he continued.

Fixed combination products are another choice for adjunctive therapy, according to Michael Motolko, MD, FRCSC, FACS, professor of ophthalmology, University of Western Ontario, Ivey Eye Institute, London, Ontario. Fixed combination products can enhance compliance through fewer refills, lower costs, fewer drops to instill, and less ocular surface damage due to the cumulative effect of preservatives, Dr. Motolko said.

Studies have shown that fixed combinations typically result in greater IOP reductions than monotherapy with either agent and in some instances cause fewer side effects. For instance, one study showed that patients experienced less burning when timolol was added to dorzolamide. In another study, rates of allergic conjunctivitis were about 50% lower in patients treated with fixed brimonidine/timolol than with brimonidine monotherapy.

"The landscape has changed, and we now can think of adding a new weapon to our armamentarium of glaucoma therapies, and that is the fixed combination drug," Dr. Motolko said.

This continuing medical education activity was jointly sponsored by the New York Eye and Ear Infirmary and cme²:, a wholly owned subsidiary of Advanstar Communications Inc., publisher of Ophthalmology Times, and was supported through an unrestricted educational grant from Allergan.