Clinical Challenge

Ophthaproblem

Sanjay Sharma, MD, MSC, MBA, FRCSC Gaurav K. Shah, MD

A 64-year-old man presents complaining of mild visual changes in his right eye. His visual acuity is recorded at 6/9 in this eye. He is otherwise healthy.

The patient should consider having which of the following?

1. Vitamin supplementation
2. Thermal laser photocoagulation
3. Photodynamic therapy with verteporfin for injection
4. No treatment

Answer to Ophthaproblem

1. Vitamin supplementation

The macula is the central portion of the retina. At the centre of the macula is the fovea. Although the fovea is only 0.5 mm in diameter, it is responsible for the ability to read, drive, and recognize fine detail, including facial features.

Age-related macular degeneration (AMD) is now the leading cause of visual loss in North America among patients older than 50. Although no population-based studies have been conducted in Canada, the Beaver Dam study conducted in the United States revealed that nearly 2% of all patients evaluated had evidence of “late” AMD, as did 7.8% of patients older than 75.1 The 5-year incidence of late AMD in that study was 1%.2 From data provided by this and other studies, we can estimate that more than 700 000 Canadians have some form of age-related maculopathy and more than 100 000 have “wet” AMD.

Patients with AMD have a great reduction in the quality of their lives. In fact, we were recently able to demonstrate that patients blind due to macular degeneration had a 60% reduction in the quality of their lives.3

Age-related maculopathy is a degenerative disease of the deep retinal layers, including the retinal pigment epithelium. The disease can be classified as either dry or wet. Patients with wet AMD have either choroidal neovascularization, where new blood vessels grow under the retina or retinal pigment epithelium, or detachment of the pigment epithelium (by serous fluid or blood). Retinal angiography is used for patients with wet AMD to determine whether a new blood vessel is causing leakage and whether it is treatable by either thermal laser photocoagulation or photodynamic therapy.

While thermal laser therapy4 and photodynamic therapy5 have been proven beneficial for patients with wet AMD, until recently no treatment had been available for dry AMD.

The Age-Related Eye Disease Study (AREDS), a prospective, randomized, double-masked clinical trial sponsored by the United States National Eye Institute,6 sought to determine the efficacy of vitamin supplementation in preventing the progression of macular degeneration. In the AREDS, patients with dry macular degeneration were randomly assigned to antioxidants (500 mg of vitamin C, 400 IU of vitamin E, and 15 mg of -carotene), zinc (80 mg of zinc as zinc oxide and 2 mg of copper), both, or placebo. Patients were followed for 7 years for development of either a three-line visual loss or an AMD event (essentially development of wet AMD). Patients were classified into one of three groups depending on severity of disease:

• group 1: essentially disease-free;
• group 2: early AMD, as evidenced by many small drusen, single intermediate drusen, or pigment abnormalities;
• group 3: intermediate AMD, as evidenced by larger drusen or geographic atrophy away from the centre of the macula; or
• group 4: no advanced AMD in the study eye but wet AMD in the other eye, or loss of vision in the other eye secondary to AMD. These patients were deemed to be at higher risk of developing the two study end points.

Vitamin supplementation was found to reduce risk of developing advanced AMD in groups 3 and 4 (odds ratio [OR] for antioxidants plus zinc 0.66, 99% confidence interval [CI] 0.47 to 0.91; OR for zinc 0.71, 99% CI 0.52 to 0.99; OR for antioxidants 0.76, 99% CI 0.55 to 1.05).6 The combination of antioxidants and zinc also resulted in a reduction in moderate visual loss (OR 0.73, 99% CI 0.54 to 0.99).6 No statistically significant adverse effects were noted with any of the formulations.The AREDS study showed no benefit of high-dose vitamin supplementation for treatment of cataracts.7

Management

This patient was referred to an ophthalmologist on a nonurgent basis. He was noted to have advanced but dry AMD in both eyes, as evidenced by the confluence of numerous large drusen and pigmentary changes (Figure 1).

Dr Sharma is an Associate Professor in the Department of Ophthalmology and an Assistant Professor in the Department of Epidemiology at Queen’s University in Kingston, Ont, and is Director of the Cost-Effective Ocular Health Policy Unit at the Hotel Dieu Hospital. Dr Shah is an Assistant Professor of Ophthalmology at Washington University and a retinal specialist at the Barnes Eye Institute in St Louis, Mo.

Figure 1. Advanced dry age-related macular degeneration