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Background: Diabetes is a leading cause of end-stage renal disease (ESRD). The purpose of this study is to assess the risk factors for renal replacement therapy (RRT) in the Early Treatment Diabetic Retinopathy Study (ETDRS)., Methods: We examined demographic, clinical, and laboratory characteristics of the 2226 subjects with complete laboratory data enrolled in the ETDRS. The primary renal variable evaluated was the time to development of renal replacement therapy, defined as the need for dialysis or transplantation. Multivariable Cox proportional hazards regression was used to assess risk factors for type 1 and type 2 diabetes separately., Results: The 5-year estimated incidence of RRT in the entire ETDRS population was 10.2% and 9.8% for patients with type 1 and type 2 diabetes, respectively. Of those patients with complete data, 127 of 934 (14%) of patients with type 1 diabetes, and 150 of 1292 (12%) patients with type 2 diabetes required RRT during the study. Baseline risk factors common to type 1 and type 2 diabetes included elevated total cholesterol, and serum creatinine; and low serum albumin and anemia. Other risk factors significant in type 1 diabetes included body mass index (BMI), shorter duration of diabetes, elevated hemoglobin A(1c) (HbA(1c)), elevated systolic blood pressure, and the development of proliferative diabetic retinopathy. Risk factors significant in type 2 diabetes, but not type 1 diabetes, included younger age, proteinuria, and elevated triglycerides., Conclusion: In this study, major modifiable risk factors such as hypertension, dyslipidemia, and hyperglycemia were found to be predictive of RRT. Other predictors were markers of vascular pathology and inflammation, proteinuria, hypoalbuminemia, and increased serum creatinine. Controlled clinical trials with treatment strategies that improve serum lipid levels, systemic blood pressure, glycemic control, and markers of inflammation may be important in furthering our knowledge on the pathogenesis of diabetic complications such as nephropathy and ESRD.

Objective: To estimate the potential public health impact of the findings of the Age-Related Eye Disease Study (AREDS) on reducing the number of persons developing advanced age-related macular degeneration (AMD) during the next 5 years in the United States., Methods: The AREDS clinical trial provides estimates of AMD progression rates and of reduction in risk of developing advanced AMD when a high-dose nutritional supplement of antioxidants and zinc is used. These results are applied to estimates of the US population at risk, to estimate the number of people who would potentially avoid advanced AMD during 5 years if those at risk were to take a supplement such as that used in AREDS., Results: An estimated 8 million persons at least 55 years old in the United States have monocular or binocular intermediate AMD or monocular advanced AMD. They are considered to be at high risk for advanced AMD and are those for whom the AREDS formulation should be considered. Of these people, 1.3 million would develop advanced AMD if no treatment were given to reduce their risk. If all of these people at risk received supplements such as those used in AREDS, more than 300,000 (95% confidence interval, 158,000-487,000) of them would avoid advanced AMD and any associated vision loss during the next 5 years., Conclusion: If people at high risk for advanced AMD received supplements such as those suggested by AREDS results, the potential impact on public health in the United States would be considerable during the next 5 years.

Purpose: To describe a regression of retinal hard exudates in 2 patients with diabetic maculopathy, and to report immunohistologic findings reflecting lipid deposition in the retina., Design: Two interventional case reports., Methods: Two patients with exudative diabetic maculopathy were treated to normalize serum lipids. Histologic examination and immunohistochemistry of each patient's eyes were performed to assess the localization of apolipoprotein B and cholesteryl ester, both of which are principal components of low-density lipoprotein., Results: Both patients showed a dramatic regression of retinal hard exudates after correction of dyslipidemia. Histopathology revealed diffuse lipids and cholesteryl ester in the retina. Apolipoprotein B and macrophages were colocalized in the perivascular space., Conclusions: The regression of hard exudates was most likely due to the aggressive lipid lowering in both patients. The novel histopathologic findings of hard exudate and diabetic maculopathy are similar to the pathologic changes observed in larger atherosclerotic lesions, except that they occur in the intraretinal perivascular space.

Objectives: To evaluate the long-term natural history and effects of laser photocoagulation treatment in patients with diabetic retinopathy., Design: Follow-up study of the 214 surviving patients enrolled originally at the Johns Hopkins Clinical Center for the Early Treatment Diabetic Retinopathy Study (ETDRS), which was a clinical trial designed to evaluate the role of laser photocoagulation and aspirin treatment in patients with diabetic retinopathy., Methods: Early Treatment Diabetic Retinopathy Study patients enrolled in the Johns Hopkins Clinical Center had complete eye examinations, including best-corrected visual acuity measurements, fundus photographs, and medical questionnaires throughout the 7-year study. They had the same examinations at the final long-term follow-up visit at the National Eye Institute, National Institutes of Health, 13 to 19.5 years after the initial laser photocoagulation (median, 16.7 years)., Main Outcome Measures: The major outcomes were mortality and the rates of moderate and severe vision loss. The secondary outcomes were progression of diabetic retinopathy and need for other eye surgery., Results: Of the 214 patients who were alive at the end of the original ETDRS in 1989, 130 (61%) were deceased at the time of the re-examination. Of the 84 who were alive, 71 (85%) were examined at their long-term follow-up visit at the National Institutes of Health. At the long-term follow-up examination, 42% had visual acuity of 20/20 or better, and 84% had visual acuity of 20/40 or better in the better eye. Compared with baseline, 20% of patients had moderate vision loss (loss of 3 lines or more vision) in the better eye at follow-up. Only one patient had visual acuity of 20/200 bilaterally. He had visual acuity loss secondary to age-related macular degeneration. No patient had severe vision loss (worse than 5/200). All the initially untreated eyes of patients who had severe nonproliferative diabetic retinopathy or worse by the time of the ETDRS closeout visit of the original study received scatter photocoagulation treatment. Focal photocoagulation was performed in 43% bilaterally and 22% unilaterally. Cataract surgery was performed in 31% of the patients, vitrectomy in 17%, and glaucoma surgery in one patient., Conclusions: As previously reported, the mortality rate of patients with diabetic retinopathy is much higher than that of the general population. For those who survived, aggressive follow-up, with treatment when indicated, seems to be associated with maintenance of good long-term visual acuity for most patients. The need for laser scatter photocoagulation with long-term follow-up seems to be high.

Purpose: To develop consensus regarding clinical disease severity classification systems for diabetic retinopathy and diabetic macular edema that can be used around the world, and to improve communication and coordination of care among physicians who care for patients with diabetes., Design: Report regarding the development of clinical diabetic retinopathy disease severity scales., Participants: A group of 31 individuals from 16 countries, representing comprehensive ophthalmology, retina subspecialties, endocrinology, and epidemiology., Methods: An initial clinical classification system, based on the Early Treatment Diabetic Retinopathy Study and the Wisconsin Epidemiologic Study of Diabetic Retinopathy publications, was circulated to the group in advance of a workshop. Each member reviewed this using e-mail, and a modified Delphi system was used to stratify responses. At a later workshop, separate systems for diabetic retinopathy and macular edema were developed. These were then reevaluated by group members, and the modified Delphi system was again used to measure degrees of agreement., Main Outcome Measures: Consensus regarding specific classification systems was achieved., Results: A five-stage disease severity classification for diabetic retinopathy includes three stages of low risk, a fourth stage of severe nonproliferative retinopathy, and a fifth stage of proliferative retinopathy. Diabetic macular edema is classified as apparently present or apparently absent. If training and equipment allow the screener to make a valid decision, macular edema is further categorized as a function of its distance from the central macula., Conclusions: There seems to be a genuine need for consistent international clinical classification systems for diabetic retinopathy and diabetic macular edema that are supported with solid evidence. The proposed clinical classification systems provide a means of appropriately categorizing diabetic retinopathy and macular edema. It is hoped that these systems will be valuable in improving both screening of individuals with diabetes and communication and discussion among individuals caring for these patients.

Oxidative damage to the retina has been proposed as a risk factor for age-related macular degeneration (AMD). Dietary or supplemental antioxidants may play a protective role. The Age-Related Eye Disease Study (AREDS), a randomized, multicenter, placebo-controlled clinical trial designed to test the effect of pharmacologic doses of antioxidants and zinc on the incidence and progression of AMD, reported a beneficial effect of high-dose supplements, taken for approximately 6 years, in delaying the progression of intermediate AMD to advanced AMD. AREDS and subsequent research on dietary intake or supplement use have not indicated a protective role of antioxidant or zinc intake or supplement use in the incidence or prevalence of early AMD. Numbers of cases were insufficient to investigate effects on late AMD. Persons with intermediate AMD and without contraindications should consider using antioxidant and zinc supplements. There is no evidence to date that earlier use conveys benefit.

Purpose: To develop a computerized method of visual acuity testing for clinical research as an alternative to the standard Early Treatment for Diabetic Retinopathy Study (ETDRS) testing protocol, and to evaluate its test-retest reliability and concordance with standard ETDRS testing., Design: Test-retest reliability study., Methods: Multicenter setting of a study population of 265 patients at three clinical sites. Visual acuity was measured with both the electronic visual acuity testing algorithm (E-ETDRS) and standard ETDRS protocol (S-ETDRS) twice on one eye of each patient. E-ETDRS testing was conducted using the electronic visual acuity tester (EVA), which utilizes a programmed Palm (Palm, Inc, Santa Clara, California, USA) hand-held device communicating with a personal computer and 17-inch monitor at a test distance of 3 meters., Results: For the E-ETDRS protocol, test-retest reliability was high (r = 0.99; with 89% and 98% of retests within 0.1 logMAR and 0.2 logMAR of initial tests, respectively) and comparable with that of S-ETDRS testing (r = 0.99; with 87% and 98% of retests within 0.1 logMAR and 0.2 logMAR of initial test, respectively). The E-ETDRS and S-ETDRS scores were highly correlated (r = 0.96 for initial tests and r = 0.97 for repeat tests). Based on estimates of 95% confidence intervals, a change in visual acuity of 0.2 logMAR (10 letters) from a baseline level is unlikely to be related to measurement variability using either the E-ETDRS or the S-ETDRS visual acuity testing protocol., Conclusions: The E-ETDRS protocol has high test-retest reliability and good concordance with S-ETDRS testing. The computerized method has advantages over the S-ETDRS testing in electronically capturing the data for each tested letter, requiring only a single distance for testing from 20/12 to 20/800, potentially reducing testing time, and potentially decreasing technician-related bias.

Objective: To assess the visual results after surgical lens removal in patients with diabetic retinopathy., Design: A multicenter randomized clinical trial designed to assess the effect of photocoagulation and aspirin in patients with mild to severe nonproliferative or early proliferative diabetic retinopathy and/or macular edema., Participants: Of the 3711 patients enrolled in the Early Treatment Diabetic Retinopathy Study, lens surgery was performed on 205 patients (270 eyes) during follow-up that ranged from 4 to 9 years., Outcome Measurements: Visual acuity, macular edema status, and degree of diabetic retinopathy. In addition, risk factors associated with lens extraction and with poor postoperative visual acuity (worse than 20/100) were assessed., Results: The risk of lens extraction increased with increasing age, female sex, and baseline proteinuria. Ocular variables associated with increased risk of lens surgery included poor baseline visual acuity and vitrectomy performed during the course of the study. At 1 year after lens surgery, visual acuity improvement of 2 or more lines from preoperative levels occurred in 64.3% of the operated-on eyes assigned to early photocoagulation and 59.3% of eyes assigned to deferral of photocoagulation. In eyes assigned to early photocoagulation, 46% of eyes achieved visual acuity better than 20/40; 73%, better than 20/100; and 8%, 5/200 or worse at 1 year after surgery. Visual acuity results for eyes assigned to deferral of laser photocoagulation at 1 year were not as favorable; 36% achieved visual acuity better than 20/40; 55%, better than 20/100; and 17%, 5/200 or worse at 1 year after surgery. Evaluation of 1-year postoperative visual acuities for all eyes with mild to moderate nonproliferative diabetic retinopathy at the annual visit before lens surgery showed that 53% were better than 20/40; 90%, better than 20/100; and 1%, 5/200 or worse. However, for eyes with severe nonproliferative or worse retinopathy at the annual visit before lens surgery, only 25% were better than 20/40; 42%, better than 20/100; and 22%, 5/200 or worse at 1 year after lens surgery. There was little change in visual acuity between 1 and 2 years postoperatively. Increased severity of retinopathy and poor visual acuity before surgery were associated with visual acuity of worse than 20/100 at 1 year after surgery. Lens surgery was associated with a borderline statistically significant increased risk of progression of diabetic retinopathy in the adjusted analyses (P = .03). No statistically significant long-term increased risk of macular edema was documented after lens surgery., Conclusions: Visual acuity results after lens surgery in patients in the Early Treatment Diabetic Retinopathy Study were better than published results for similar patients. This may be because of more intensive photocoagulation for lesions of diabetic retinopathy in the Early Treatment Diabetic Retinopathy Study than in previously reported studies. Although patients with severe nonproliferative retinopathy or worse before lens surgery had poorer visual results, visual improvement was seen in 55% of these patients at 1-year follow-up. The main causes of poor visual results in eyes after lens surgery were complications of proliferative retinopathy and/or macular edema.

Purpose: To describe the causes of and risk factors for persistent severe visual loss occurring in the Early Treatment Diabetic Retinopathy Study (ETDRS)., Methods: The ETDRS was a randomized clinical trial investigating photocoagulation and aspirin in 3,711 persons with mild to severe nonproliferative or early proliferative diabetic retinopathy. Severe visual loss, defined as best-corrected visual acuity of less than 5/200 on at least two consecutive 4-month follow-up visits, developed in 257 eyes (219 persons). Of these 257 eyes, 149 (127 persons) did not recover to 5/200 or better at any visit (persistent severe visual loss). Ocular characteristics of these eyes were compared with those of eyes with severe visual loss that improved to 5/200 or better at any subsequent visit. Characteristics of patients with severe visual loss that did and did not improve and those without severe visual loss were also compared., Results: Severe visual loss that persisted developed in 149 eyes of 127 persons. In order of decreasing frequency, reasons recorded for persistent visual loss included vitreous or preretinal hemorrhage, macular edema or macular pigmentary changes related to macular edema, macular or retinal detachment, and neovascular glaucoma. Compared with all patients without persistent severe visual loss, patients with persistent severe visual loss had higher mean levels of hemoglobin A1c (10.4% vs 9.7%; P = .001) and higher levels of cholesterol (244.1 vs 228.5 mg/dl; P = .0081) at baseline. Otherwise, patients with persistent severe visual loss were similar to patients with severe visual loss that improved and to those without severe visual loss., Conclusions: Persistent severe visual loss was an infrequent occurrence in the ETDRS. Its leading cause was vitreous or preretinal hemorrhage, followed by macular edema or macular pigmentary changes related to macular edema and retinal detachment. The low frequency of persistent severe visual loss in the ETDRS is most likely related to the nearly universal intervention with scatter photocoagulation (either before or soon after high-risk proliferative diabetic retinopathy developed) and the intervention with vitreous surgery when clinically indicated.

Purpose: To identify risk factors for the development of high-risk proliferative diabetic retinopathy (PDR) and for the development of severe visual loss or vitrectomy (SVLV) in eyes assigned to deferral of photocoagulation in the Early Treatment Diabetic Retinopathy Study (ETDRS)., Methods: Multivariable Cox models were constructed to evaluate the strength and statistical significance of baseline risk factors for development of high-risk PDR and of SVLV., Results: The baseline characteristics identified as risk factors for high-risk PDR were increased severity of retinopathy, decreased visual acuity (or increased extent of macular edema), higher glycosylated hemoglobin, history of diabetic neuropathy, lower hematocrit, elevated triglycerides, lower serum albumin, and persons with mild to moderate nonproliferative retinopathy, younger age (or type 1 diabetes). The predominant risk factor for development of SVLV was the prior development of high-risk PDR. The only other clearly significant factor was decreased visual acuity at baseline. In the eyes that developed SVLV before high-risk proliferative retinopathy was observed, baseline risk factors were decreased visual acuity (or increased extent of macular edema), older age (or type 2 diabetes), and female gender., Conclusions: These analyses supported the view that the retinopathy-inhibiting effect of better glycemic control extends across all ages, both diabetes types, and all stages of retinopathy up to and including the severe nonproliferative and early proliferative stages and the possibility that reducing elevated blood lipids and treating anemia slow the progression of retinopathy.

Objective: To examine the association between cigarette smoking and the incidence of nuclear and non-nuclear lens opacities in members of the Framingham Eye Study Cohort., Participants and Methods: Eye examinations were conducted on surviving members of the Framingham Heart Study Cohort from 1973 to 1975 (Framingham Eye Study I) and again from 1986 to 1989 (Framingham Eye Study II). Smoking data, collected biennially since 1948 in the Heart Study, were used to examine the relationship between cigarette smoking and the incidence of lens opacities. Two thousand six hundred seventy-five persons were examined in the Framingham Eye Study I. Our analysis included 660 persons, aged 52 to 80 years, who were free of lens opacities at the first eye examination., Results: During the approximately 12.5 years between eye examinations, lens opacities developed in a total of 381 persons, with nuclear opacities constituting the most frequent type. In logistic regression analyses that controlled for age, sex, education, and diabetes, a significant positive association with increasing duration of smoking and number of cigarettes smoked daily was found for nuclear lens opacities, alone or in combination (test for trend, P < or = .002), but not for nonnuclear opacities (test for trend, P = .62). Among the heavier smokers (persons who smoked > or = 20 cigarettes per day according to 6 or more biennial Framingham Heart Study examinations), 77% were still smoking at the time of the first eye examination. Persons who smoked 20 or more cigarettes per day at the time of the first eye examination were at substantially increased risk for the development of nuclear opacities than nonsmokers (odds ratio, 2.84; 95% confidence interval, 1.46-5.51). There was no apparent excess risk for persons with nonnuclear lens opacities (odds ratio, 1.42; 95% confidence interval, 0.65-3.07)., Conclusion: This study provides further evidence that cigarette smokers have an increased risk of developing nuclear lens opacities. The risk was greatest for heavier smokers, who tended to be current smokers and who smoked more cigarettes and for a longer duration.

Objective: To evaluate the relationship between serum lipid levels, retinal hard exudate, and visual acuity in patients with diabetic retinopathy., Design: Observational data from the Early Treatment Diabetic Retinopathy Study., Participants: Of the 3711 patients enrolled in the Early Treatment Diabetic Retinopathy Study, the first 2709 enrolled had serum lipid levels measured., Main Outcome Measures: Baseline fasting serum lipid levels, best-corrected visual acuity, and assessment of retinal thickening and hard exudate from stereoscopic macular photographs., Results: Patients with elevated total serum cholesterol levels or serum low-density lipoprotein cholesterol levels at baseline were twice as likely to have retinal hard exudates as patients with normal levels. These patients were also at higher risk of developing hard exudate during the course of the study. The risk of losing visual acuity was associated with the extent of hard exudate even after adjusting for the extent of macular edema., Conclusions: These data demonstrate that elevated serum lipid levels are associated with an increased risk of retinal hard exudate in persons with diabetic retinopathy. Although retinal hard exudate usually accompanies diabetic macular edema, increasing amounts of exudate appear to be independently associated with an increased risk of visual impairment. Lowering elevated serum lipid levels has been shown to decrease the risk of cardiovascular morbidity. The observational data from the Early Treatment Diabetic Retinopathy Study suggest that lipid lowering may also decrease the risk of hard exudate formation and associated vision loss in patients with diabetic retinopathy. Preservation of vision may be an additional motivating factor for lowering serum lipid levels in persons with diabetic retinopathy and elevated serum lipid levels.

Objective: To test the hypothesis that digoxin, an inhibitor of Na(+)-K(+)-ATPase activity, accelerates the progression of diabetic retinopathy., Research Design and Methods: We compared the incidence and risk of retinopathy in 120 digoxin-taking vs. 867 non-digoxin-taking diabetic participants in the Wisconsin Epidemiologic Study of Diabetic Retinopathy (WESDR) and in 117 digoxin-taking vs. 1,883 non-digoxin-taking diabetic subjects in the Early Treatment Diabetic Retinopathy Study (ETDRS). In both studies, retinopathy was detected by grading stereoscopic color photographs using the modified Airlie House classification scheme, and a two-step difference in baseline retinopathy grade was considered significant., Results: After controlling for other risk factors, we found no statistically significant association with either 4-year incidence of retinopathy (WESDR) or progression of retinopathy (WESDR and ETDRS) in patients taking digoxin at baseline compared with those not taking digoxin., Conclusions: These data suggest that digoxin therapy does not adversely affect the course of diabetic retinopathy.

Objective: To assess whether the use of aspirin exacerbates the severity or duration of vitreous/preretinal hemorrhages in patients with diabetic retinopathy., Design: The Early Treatment Diabetic Retinopathy Study (ETDRS), a multicenter randomized clinical trial, was designed to assess the effect of photocoagulation and aspirin on 3711 patients with mild to severe nonproliferative or early proliferative diabetic retinopathy., Intervention: Patients were randomly assigned to either an aspirin (650 mg/d) or a placebo group. One eye of each patient was randomly assigned to early photocoagulation and the other to deferral of photocoagulation., Main Outcome Measures: The severity and duration of the vitreous/preretinal hemorrhages were determined from gradings of the annual, seven standard stereoscopic field, fundus photographs. Clinical examinations scheduled every 4 months also provided information on the presence and duration of hemorrhages., Results: Annual fundus photographs of eyes assigned to deferral of photocoagulation revealed vitreous/preretinal hemorrhages at some time during follow-up in 564 patients (30%) assigned to the placebo group and 585 patients (32%) assigned to the aspirin group (P = .48). Based on gradings of fundus photographs, there were no statistical differences in the severity of vitreous/preretinal hemorrhages (P = .11) or their rate of resolution (P = .86) between the groups. Clinical examination of eyes assigned to deferral of photocoagulation revealed 721 eyes (39%) assigned to the aspirin group and 689 (37%) assigned to the placebo group that had vitreous/preretinal hemorrhages during the course of the study (P = .30). Again, no statistically significant difference was found between the rates of resolution, as assessed clinically, between the two treatment groups (P = .43)., Conclusions: As previously reported, the use of aspirin did not increase the occurrence of vitreous/preretinal hemorrhages in patients enrolled in the ETDRS. The data presented in this report demonstrate that the severity and duration of these hemorrhages were not significantly affected by the use of aspirin and that there were no ocular contraindications to its use (650 mg/d) in persons with diabetes who require it for treatment of cardiovascular disease or for other medical indications.

Purpose: Accommodative amplitude in persons with diabetes was investigated using data collected as part of the Early Treatment Diabetic Retinopathy Study., Methods: Accommodative amplitude was measured at the baseline visit in 1,058 patients who had good visual acuity and who were less than 46 years old. Risk factors for low accommodative amplitude at baseline were evaluated using multivariable linear regression. Change in accommodative amplitude after photocoagulation was evaluated using paired t tests and repeated measures analysis of variance for the 578 patients who underwent follow-up measurements at the 4-month visit., Results: Accommodative amplitudes in Early Treatment Diabetic Retinopathy Study patients were lower than normal accommodative amplitudes. Older age (P < 0.001) and increased duration of diabetes (P < 0.01) were risk factors associated with low amplitudes of accommodation in the Early Treatment Diabetic Retinopathy Study. Full scatter photocoagulation was associated with an apparently transient additional reduction in accommodative amplitude; a one third diopter loss in accommodative amplitude was demonstrated only at the 4-month visit (P < 0.001)., Conclusion: This study demonstrates that diabetes and duration of diabetes, along with age, are important risk factors for reduced accommodative amplitude. These factors along with an apparently transient decrease in accommodative amplitude following scatter photocoagulation should be considered when assessing the accommodative needs of patients with diabetes and when discussing side effects of full scatter photocoagulation.

Diabetic retinopathy is the leading cause of blindness in young adults, ages 20-55. Without treatment 50% of those with proliferative diabetic retinopathy will be blind within 5 years. Over the last 2 decades the National Eye Institute has supported four different multicenter randomized clinical trials for diabetic retinopathy. Implementation of the results from these clinical trials can markedly reduce the risk of blindness.

Objective: Diabetic retinopathy, which leads to macular edema and retinal neovascularization, is the leading cause of blindness among working-age Americans. Previous research has demonstrated significant cost savings associated with detection of eye disease in Americans with type I diabetes. However, detection and treatment of eye disease among those with type II diabetes was previously thought not to be cost-saving. Our purpose was to estimate the current and potential federal savings resulting from the screening and treatment of retinopathy in patients with type II diabetes, based on recently available data concerning efficacy of treating both macular edema and neovascularization along with new data on federal budgetary costs of blindness., Research Design and Methods: We used computer modeling, incorporating data from population-based epidemiological studies and multicenter clinical trials. Monte Carlo simulation was used, combined with sensitivity analysis and present value analysis of cost savings., Results: Screening and treatment for eye disease in patients with type II diabetes generates annual savings of $247.9 million to the federal budget and 53,986 person-years of sight, even at current suboptimal (60%) levels of care. If all patients with type II diabetes receive recommended care, the predicted net savings (discounted at 5%) exceeds $472.1 million and 94,304 person-years of sight. Nearly all savings are associated with detection and treatment of diabetic macular edema. Enrolling each additional person with type II diabetes into currently recommended ophthalmological care results in an average net savings of $975/person, even if all costs of care are borne by the federal government., Conclusions: Our analysis indicates that prevention programs aimed at improving eye care for patients with diabetes not only reduce needless vision loss but also will provide a financial return on the investment of public funds.

Ten Sloan letters were used in the visual acuity charts developed for use in the Early Treatment Diabetic Retinopathy Study. We used the data from the 3,710 Early Treatment Diabetic Retinopathy Study subjects to investigate the relative difficulty of the ten Sloan letters and to evaluate whether the position of a letter on a line affected its relative difficulty. In general, our findings were consistent with those of the previous study. The four letters with curved contours (C, O, S, and D) were more difficult to discern at threshold than the six letters (Z, N, H, V, R, and K) composed of straight lines. Our data demonstrate that under these test conditions, letters at the end of a line are more likely to be read incorrectly than letters at the beginning of the line. This finding indicates that these data are probably not useful for evaluating possible crowding phenomena.

Panretinal photocoagulation could prevent most blindness from proliferative disease--if risk is identified early. This makes it essential that primary physicians include annual ophthalmologic evaluation in the management of patients at risk. Meanwhile, studies are under way on promising medical approaches, including intensive insulin regimens, aldose reductase blockers, and angiogenesis inhibitors.

Objective: To review the natural history and treatment indications for diabetic retinopathy., Research Design and Methods: Studies of the natural history of diabetic retinopathy and major clinical trials sponsored by the National Eye Institute were reviewed., Results: Diabetic retinopathy remains a leading cause of vision disability in the U.S. Vision loss results from the consequences of proliferative retinopathy or macular edema. Photocoagulation has been demonstrated to be an effective treatment for these complications of diabetes., Conclusions: All people with diabetes should be evaluated regularly to determine whether they would benefit from photocoagulation. As a referral guideline, any person with type I diabetes of > 5 yr duration and all people with type II diabetes or any retinopathy should be referred to an ophthalmologist.

Background: The Early Treatment Diabetic Retinopathy Study (ETDRS) enrolled 3711 patients with mild-to-severe nonproliferative or early proliferative diabetic retinopathy in both eyes. Patients were randomly assigned to aspirin 650 mg/day or placebo. One eye of each patient was assigned randomly to early photocoagulation and the other to deferral of photocoagulation. Follow-up examinations were scheduled at least every 4 months, and photocoagulation was initiated in eyes assigned to deferral as soon as high-risk proliferative retinopathy was detected. Aspirin was not found to have an effect on retinopathy progression or rates of vitreous hemorrhage. The risk of a combined end point, severe visual loss or vitrectomy, was low in eyes assigned to deferral (6% at 5 years) and was reduced by early photocoagulation (4% at 5 years). Vitrectomy was carried out in 208 patients during the 9 years of the study. This report presents baseline and previtrectomy characteristics and visual outcome in these patients., Methods: Information collected at baseline and during follow-up as part of the ETDRS protocol was supplemented by review of clinic charts for visual acuity and ocular status immediately before vitrectomy., Results: Vitrectomy was performed in 208 (5.6%) of the 3711 patients (243 eyes) enrolled in the ETDRS. The 5-year vitrectomy rates for eyes grouped by their initial photocoagulation assignment were as follows: 2.1% in the early full scatter photocoagulation group, 2.5% in the early mild scatter group, and 4.0% in the deferral group. The 5-year rates of vitrectomy (in one or both eyes) were 5.4% in patients assigned to aspirin and 5.2% in patients assigned to a placebo. The indications for vitrectomy were either vitreous hemorrhage (53.9%) or retinal detachment with or without vitreous hemorrhage (46.1%). Before vitrectomy, visual acuity was 5/200 or worse in 66.7% of eyes and better than 20/100 in 6.2%. One year after vitrectomy, the visual acuity was 20/100 or better in 47.6% of eyes, including 24.0% with visual acuity of 20/40 or better., Conclusions: With frequent follow-up examinations and timely scatter (panretinal) photocoagulation, the 5-year cumulative rate of pars plana vitrectomy in ETDRS patients was 5.3%. Aspirin use did not influence the rate of vitrectomy.

Significant amounts of scarce resources are devoted to medical research, but there have been few attempts to assess whether the benefits to society of these investments exceed the costs. A method for undertaking such an assessment has been developed and applied retrospectively to the Diabetic Retinopathy Study, a major clinical trial funded by the National Eye Institute from 1972-1981. It was estimated that the trial, which cost $10.5 million, generated a net saving of $2816 million to society ($231 million when the costs of lost production are excluded) (1982 prices) and a gain to patients of 279,000 vision years. This approach could be applied prospectively in considering priorities for medical research, in conjunction with traditional criteria such as the scientific merit of the proposal and the capabilities of the investigators. The key factors affecting the economic returns from medical research are the prevalence, incidence and economic burden of the disease in question, the costs and effectiveness of the medical intervention concerned, the likely impact of the clinical trial on clinical practice and the likely timespan of benefits from knowledge obtained during the trial.

The Early Treatment Diabetic Retinopathy Study, a randomized clinical trial supported by the National Eye Institute, was designed to assess the effect of photocoagulation and aspirin in 3711 patients with mild to severe nonproliferative or early proliferative diabetic retinopathy. Although the primary goal of the study was to evaluate the effect of photocoagulation and aspirin on diabetic retinopathy, the study also provided an opportunity to evaluate the effects of aspirin on the development of cataract. No evidence showed that aspirin use reduced the risk of development of cataract requiring extraction (4.1% vs 4.3% in patients assigned to aspirin or placebo treatment, respectively; Mantel-Cox P = .77; relative risk, 1.05; 99% confidence interval, 0.73 to 1.51). Aspirin use also did not reduce the risk of less extensive but visually significant lens opacities developing (29.6% vs 28.3%; Mantel-Cox P = .76; relative risk, 0.99; 99% confidence interval, 0.85 to 1.15). Early Treatment Diabetic Retinopathy Study results do not support the hypothesis that aspirin (at a dose of 650 mg/d) reduces the risk of cataract development in this diabetic population.

Diabetic macular edema is the leading cause of decreased vision from diabetic retinopathy. This decreased vision is caused by an increase in extracellular fluid within the retina distorting the retinal architecture and frequently taking on a pattern of cystoid macular edema. This fluid accumulates within the retina because of the breakdown of the barriers within the retinal blood vessels and possibly the pigment epithelium. Diabetic macular edema tends to be a chronic disorder. Although spontaneous recovery is not an uncommon occurrence, over one-half of diabetics with macular edema will lose two or more lines of visual acuity within two years. The most promising treatment for diabetic macular edema has been photocoagulation. It is recommended that in all patients with diabetic macular edema attempts be made to normalize elevated blood glucose, decrease elevated blood pressure, and improve cardiac or renal status. Reduction of serum lipids by diet or pharmacologic means is an unproven treatment at this time. The Early Treatment Diabetic Retinopathy Study hopefully will provide more definitive information as to whether photocoagulation is effective in various subgroups of patients with diabetic macular edema.

Age-related macular degeneration (AMD) is one of the four most common causes of blindness in the United States. Retinal manifestations of AMD can be categorized as either atrophic or neovascular/exudative. To the best of our knowledge, the proportion of patients legally blind due to the neovascular/exudative manifestations of this disease has not been previously reported. Data from two studies, the Framingham Eye Study and a large case-control study, demonstrate that the vast majority of patients with legal blindness due to AMD have the neovascular/exudative form of the disease. Seventy-nine percent of eyes legally blind due to AMD in the Framingham population and 90% of eyes legally blind due to AMD in the case-control study had neovascular/exudative retinopathy. This is in spite of the fact that neovascular/exudative retinopathy is a relatively infrequent complication of AMD.