acuity, but this endpoint would take many years to assess. To shorten the time period, other surrogate endpoints have been developed to assess efficacy of drugs in trials involving dry AMD.

Some trials have evaluated the change in drusen area by fundus photography, while others aim to determine a drug’s effects on the growth of GA, since GA is a feature of dry AMD that directly correlates with the loss of photoreceptors and RPE. Although there is uncertainty surrounding the best molecular pathway to target for the treatment of dry AMD, several different strategies have evolved. The utilization and development of novel imaging modalities combined with the results of clinical trials will translate new insights into future study design and appropriate clinical endpoints.

Risk Reduction in Dry AMD

AREDS

The most significant trial on modulation of risk of AMD and nutrition was the AREDS clinical trial [17]. Patients were enrolled in the AREDS clinical trial if they had extensive small drusen, intermediate drusen, large drusen, noncentral GA, or pigment abnormalities in one or both eyes, or advanced AMD or vision loss due to AMD in one eye. The 3640 participants in the trial were randomly assigned to receive either:

(1) antioxidants (vitamin C, 500 mg; vitamin E, 400 IU; and beta-carotene, 15 mg); (2) zinc, 80 mg, as zinc oxide and copper, 2 mg, as cupric oxide; (3) antioxidants plus zinc; or (4) placebo. The primary outcome measures were photographic documentation of progression to or treatment for advanced AMD or at least moderate visual acuity loss from baseline (³15 letters). Those participants with extensive small drusen, nonextensive intermediate size drusen, or pigment abnormalities had only a 1.3% fiveyear probability of progression to advanced AMD [17]. Upon exclusion of these participants, it was determined that those receiving zinc and antioxidants plus zinc significantly reduced the odds of developing advanced AMD in the higher-risk group. There was a statisti-

cally significant reduction in the rates of moderate visual acuity loss in those participants receiving antioxidants plus zinc [17]. The study concluded therefore that patients with extensive intermediate size drusen, at least one large druse, noncentral GA in one or both eyes, or advanced AMD or vision loss due to AMD in one eye, and without contraindications such as smoking should consider supplementation with antioxidants plus zinc. The effect of supplementation with lutein, zeaxanthine, and omega-3 fatty acids is under investigation in the AREDS 2 trial.

Pearl

AREDS – Vitamin and Antioxidant

Composition

•Vitamin C 500 mg

•Vitamin E 400 International Units (IU)

•Beta-carotene 15 milligrams (mg)

•Zinc 80 milligrams (mg)

•Copper 2 milligrams (mg)

Laser/CAPT

Drusen, as risk factors for progression of AMD, have been the target of laser therapy. Gass first reported on the disappearance of drusen adjacent to sites of laser photocoagulation. He proposed that laser may promote improved approximation of RPE to Bruch’s membrane thereby preventing visual loss in the area of drusen. Gass also commented on the possible complications including stimulation of CNV and RPE atrophy at the site of laser [18].

There are several speculations about the mechanism of laser-induced drusen regression and visual acuity stabilization. Photocoagulation may decrease drusen debris production by damaging overlying RPE. Alternatively, it may stimulate RPE metabolic and phagocytic activity clearing debris. Animal models have shown than laser induces an increased number of choriocapillaris endothelial cell processes and choroidal pericyte