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BACKGROUND AND OBJECTIVE To determine the prophylactic and therapeutic value of a single subthreshold 810-nanometer laser treatment in patients with high risk drusen as a manifestation of dry age-related macular degeneration in both eyes. PATIENTS AND METHODS The Prophylactic Treatment of Age-related Macular Degeneration study enrolled 1,278 eyes of 639 participants who were 50 years or older with at least 5 drusen 63 µm or more in diameter in each eye. Treatment consisted of the placement of an annular grid of 48 extrafoveal, subthreshold 810-nm diode laser applications centered at but sparing the foveola in one eye of each participant, with the fellow eye serving as a control. Development of choroidal neovascularization and change in best-corrected visual acuity were compared between treated and untreated eyes. RESULTS Subthreshold laser treatment did not decrease the incidence of choroidal neovascularization in treated versus untreated eyes. A modest visual acuity benefit in treated eyes was found at 24 months (1.5 letter difference; P = .04) and in the treated eyes of participants with a baseline visual acuity between 20/32 and 20/63 (4.0 letter difference; P = .0034). However, this treatment effect was not sustained at 3 years. CONCLUSION A single subthreshold 810-nanometer laser treatment to eyes of participants with bilateral high risk drusen is not an effective prophylactic strategy against choroidal neovascularization. [Ophthalmic Surg Lasers Imaging 2009;40:530-538.] AUTHORS From the UPMC Eye Center (TRF, PMB), University of Pittsburgh, Pittsburgh, Pennsylvania; the Shiley Eye Center (WRF), University of California–San Diego, La Jolla, California; and the W. K. Kellogg Eye Center (DCM), University of Michigan, Ann Arbor, Michigan. Accepted for publication December 19, 2008. Supported by Iridex Corporation, Mountain View, California, and the sources listed under the individual center descriptions found at the end of the article; the Eye and Ear Foundation of Pittsburgh, Pittsburgh, Pennsylvania; Research to Prevent Blindness, Inc., New York, New York; and unrestricted funds from several participating centers. Presented in part at the annual meeting of the American Academy of Ophthalmology, October 15-18, 2005, Chicago, Illinois, and the annual meeting of the Association for Research in Vision and Ophthalmology, April 30-May 4, 2006, Ft. Lauderdale, Florida. The authors thank photographic readers Cheryl Hiner, Columbia, MD, Rosemary J. Brothers, Madison, WI, and Linda Huang, MD, and Maria Palaiou, MS, Pittsburgh, PA; the Data and Safety Monitoring Committee voting members Donald J. D’Amico, MD, Mark W. Johnson, MD, J. Richard Landis, PhD, and nonvoting ex-officio member, Dr. Musch; and Giorgio Dorin for his contribution to the manuscript. The authors have no financial or proprietary interest in the materials presented herein. Address correspondence to Thomas R. Friberg, MS, MD, UPMC Eye Center, 203 Lothrop Street, Suite 824, Pittsburgh, PA 15213. doi: 10.3928/15428877-20091030-01

With the exception of panretinal laser photocoagulation, no therapy has been shown to modify the course of diabetic retinopathy. Success in developing new therapies for diabetic retinopathy will depend on how well the disease process is understood and on whether interventions can be identified that ameliorate or circumvent critical stages in the development of the disease. A model of the disease process is presented to serve as a frame-work on which pieces of the puzzle can be placed and new areas of potential interventional therapy can be conceptualized.

Objectives. —This report presents information on the effects of aspirin on mortality, the occurrence of cardiovascular events, and the incidence of kidney disease in the patients enrolled in the Early Treatment Diabetic Retinopathy Study (ETDRS). Study Design. —This multicenter, randomized clinical trial of aspirin vs placebo was sponsored by the National Eye Institute. Patients. —Patients (N=3711) were enrolled in 22 clinical centers between April 1980 and July 1985. Men and women between the ages of 18 and 70 years with a clinical diagnosis of diabetes mellitus were eligible. Approximately 30% of all patients were considered to have type I diabetes mellitus, 31% type II, and in 39% type I or II could not be determined definitely. Intervention. —Patients were randomly assigned to aspirin or placebo (two 325-mg tablets once per day). Main Outcome Measures. —Mortality from all causes was specified as the primary outcome measure for assessing the systemic effects of aspirin. Other outcome variables included cause-specific mortality and cardiovascular events. Results. —The estimate of relative risk for total mortality for aspirin-treated patients compared with placebo-treated patients for the entire study period was 0.91 (99% confidence interval, 0.75 to 1.11). Larger differences were noted for the occurrence of fatal and nonfatal myocardial infarction; the estimate of relative risk was 0.83 for the entire follow-up period (99% confidence interval, 0.66 to 1.04). Conclusions. —The effects of aspirin on any of the cardiovascular events considered in the ETDRS were not substantially different from the effects observed in other studies that included mainly nondiabetic persons. Furthermore, there was no evidence of harmful effects of aspirin. Aspirin has been recommended previously for persons at risk for cardiovascular disease. The ETDRS results support application of this recommendation to those persons with diabetes at increased risk of cardiovascular disease. (JAMA. 1992;268:1292-1300)

DIABETES arises through two etiologically distinct routes.1 Type I diabetes is the result of immunologically mediated destruction of the pancreatic beta cells, and usually requires replacement ther...

The relationship between HLA-DR phenotype, refractive error, and risk of both nonproliferative and proliferative diabetic retinopathy was studied among 227 insulin-dependent diabetics participating in a case-control study of diabetic retinopathy. In the absence of myopia, risk of both proliferative and nonproliferative diabetic retinopathy was increased for HLA-DR phenotypes 4/0, 3/0, and X/X (HLA susceptible) compared to HLA-DR phenotypes 3/4, 3/X, and 4/X (HLA nonsusceptible). Odds ratios equalled 11.8 and 7.4 respectively. In the presence of myopia this increased risk associated with HLA status was abolished. Myopia decreased the risk of proliferative and nonproliferative diabetic retinopathy among HLA-susceptible individuals, odds ratio equalled .09 and .09, but had no protective influence among HLA-nonsusceptible individuals.

It has been suggested that mast cells may play a role in the growth and maintenance of new blood vessels. Since capillary proliferation is an important component of diabetic retinopathy, we have examined 38 retinas from patients with all stages of this disease, looking for the presence of mast cells. No mast cells were observed in any of the retinal specimens, regardless of the degree or severity of diabetic retinopathy and in spite of the fact that mast cells were seen in the sclera of all 38 specimens. These results suggest that the presence of mast cells is not an obligatory requirement for all types of neovascularization.

While only a small proportion of adult-onset diabetic patients develop vision threatening retinopathy, this group makes up a major portion of those diabetics seeking ophthalmologic care. Fifty-three percent of patients having fundus photographs at the W.P. Beetham Eye Unit of the Joslin Clinic developed diabetes at the age of 20 or over, and almost 30% at the age of 40 or over. Twenty-two percent of all patients seen with proliferative retinopathy were in this latter group. Ten of 54 patients with proliferative retinopathy in the greater than or equal to 40 onset group were not taking insulin. The older onset patients who developed proliferative retinopathy did so after shorter durations of diabetes and with more visual disability than younger onset patients. Macular edema was more common in adult-onset patients, and its presence in a patient less than 50 years old was usually associated with proliferative or preproliferative retinopathy.