Complications of Age-Related Macular Degeneration Prevention Trial (CAPT)
The Complications of Age-Related Macular Degeneration Prevention Trial (CAPT) was a multi-centered randomized clinical trial to evaluate whether prophylactic low intensity laser treatment to the retina can prevent the complications of the advanced stage of Age-Related Macular Degeneration (AMD), a stage that usually causes severe irreversible vision loss. CAPT was conducted in 23 clinical centers and in three resource centers and is funded by the National Eye Institute. The CPOB serves as both the CAPT Coordinating Center and the Fundus Photograph Reading Center.
What is AMD and Why is CAPT Important?
The macula is the part of the retina that is responsible for central visual functioning. AMD is the leading cause of irreversible blindness among people over age 50 in the United States and other Western countries. Approximately 230,000 Americans are believed to be legally blind due to AMD and approximately 1.7 million people in the U.S. have 1 or both eyes affected by the late stage of the disease. In the US alone, the direct cost of illness associated with AMD is conservatively estimated at $10 billion annually. Because the incidence of AMD rises sharply with age, these numbers will multiply as the American population over the age of 65 increases.
A treatment that can prevent the progression of AMD would have tremendous impact. According to one estimate, an intervention that reduced the risk of developing CNV by 30% in eyes of people most at risk could halve the rate of bilateral blindness from AMD and would have a major public health benefit by yielding substantial savings in expenditures devoted to treating advanced AMD and addressing the disability it causes.
Approximately 90% of people with AMD have the early or intermediate stage of the disease, characterized by yellowish deposits (drusen) under the macula. These stages of AMD are associated with good visual acuity, but problems exist with night vision, contrast sensitivity (the ability to discern subtle degrees of grayness) and the need for bright light for reading. Most AMD-related blindness is attributable to choroidal neovascularization (CNV), which occurs when new, abnormal blood vessels develop in the macula. Most risk factors for developing advanced AMD cannot be modified. Unfortunately, the treatments for advanced AMD are effective only in selected cases, the benefit is modest, and the need for multiple treatments is high.
One risk factor for advanced AMD is the existence of many large drusen in the macula. Since the 1970's, clinicians have reported that laser photocoagulation causes drusen to disappear. However, studies of the effects of laser treatment on preventing vision loss from advanced AMD have shown inconsistent results and have been based on relatively small numbers. The aim of the CAPT study is to provide a comprehensive evaluation of laser treatment for patients with two eyes at high risk for vision loss from AMD.
CAPT Study Design
CAPT enrollment opened May 1, 1999 and closed March 31, 2001, with a total of 1052 participants aged 50 and older enrolled. All patients had many large drusen in both eyes. One eye was randomly assigned to laser treatment and the other eye to observation. At 12 months, treated eyes that still had many drusen were given additional laser treatment. Follow-up continued until June 2006 when all of the patients were followed for five years and approximately half of the patients were followed for six years.
All patients were followed via study visits and telephone calls. Study visit procedures included established tests of visual function conducted by examiners masked to the treatment assignment of each eye, an examination by a CAPT ophthalmologist, and photographs of the retina of each eye that are assessed by masked graders in a centralized photograph Reading Center located at the CPOB. The photographs provide a clinical picture of the severity of AMD.
CAPT’s primary outcome measure was change in visual acuity. Secondary outcomes include the incidence of complications of AMD, changes in other measures of visual functioning and vision-related quality of life.
Description of the CAPT Intervention (Figure 1: Treatment Summary, PDF, 209KB)
All patients were treated immediately after randomization and again at 12 months if there had not been sufficient resolution of drusen.
Initial treatment consisted of 60 barely visible burns in a grid pattern within an annulus between 1500 and 2500 microns from the center of the macula (the fovea). Fifteen burns were applied per quadrant (Figure 1: Treatment Summary, PDF, 209KB).
Treatment at 12 months
Additional treatment was performed at 12 months if 10 or more large drusen remained in the treated eye within 1500 microns of the foveal center. During re-treatment, 30 burns were administered in the 1000 to 2000 microns annulus centered on the fovea, and drusen were treated directly. If all drusen within the annulus could be treated with less than 30 burns, the remainder of the burns was applied evenly within the treatment annulus, avoiding retinal vessels and any previous burns.
In November 2006, the CAPT Research Team reported the final study results. After 5 to 6 years of follow-up on each participant, CAPT researchers concluded that the CAPT treatment did NOT have either a beneficial or harmful effect on visual acuity. At 5 years, 20.5% of treated eyes and 20.5% of observed eyes lost at least three lines of vision compared to baseline. In addition, the CAPT treatment did not reduce or increase the risk of developing “wet” age-related macular degeneration or the risk of the advanced form of “dry” AMD (called geographic atrophy). Cumulative 5-year incidence rates for choroidal neovascularization were 13.3 for both treated and observed eyes. For geographic atrophy, cumulative 5-year incidence rates were 7.4 and 7.8%, respectively for treated and observed eyes. In summary, the CAPT treatment had no effect on either visual acuity or delaying the development of advanced AMD. To read the complete results, click here.
CPOB’s Role in CAPT
For more information on the CAPT study, please contact Ellen Peskin.