Sustained supplementation and monitored response with differing carotenoid formulations in early age-related macular degeneration.

PURPOSE: To compare the impact of sustained supplementation using different macular carotenoid formulations on macular pigment (MP) and visual function in early age-related macular degeneration (AMD). PATIENTS AND METHODS: Sixty-seven subjects with early AMD were randomly assigned to: Group 1 (20 mg per day lutein (L), 0.86 mg per day zeaxanthin (Z); Ultra Lutein), Group 2 (10 mg per day meso-zeaxanthin (MZ), 10 mg per day L, 2 mg per day Z; Macushield; Macuhealth), Group 3 (17 mg per day MZ, 3 mg per day L, 2 mg per day Z). MP was measured using customised heterochromatic flicker photometry and visual function was assessed by measuring contrast sensitivity (CS) and best-corrected visual acuity (BCVA). AMD was graded using the Wisconsin Age-Related Maculopathy Grading System (AREDS 11-step severity scale). RESULTS: At 3 years, a significant increase in MP from baseline was observed in all groups at each eccentricity (P<0.05), except at 1.75° in Group 1 (P=0.160). Between 24 and 36 months, significant increases in MP at each eccentricity were seen in Group 3 (P<0.05 for all), and at 0.50° in Group 2 (P<0.05), whereas no significant increases were seen in Group 1 (P>0.05 for all). At 36 months, compared with baseline, the following significant improvements (P<0.05) in CS were observed: Group 2-1.2, 6, and 9.6 cycles per degree (c.p.d.); Group 1-15.15 c.p.d.; and Group 3-6, 9.6, and 15.15 c.p.d. No significant changes in BCVA, or progression to advanced AMD, were observed. CONCLUSION: In early AMD, MP can be augmented with a variety of supplements, although the inclusion of MZ may confer benefits in terms of panprofile augmentation and in terms of CS enhancement.

Variation associated with measurement of retinal vessel diameters at different points in the pulse cycle.

BACKGROUND/AIMS: To assess the variability in retinal vessel measurements at different points in the pulse cycle. METHODS: A healthy white male aged 19 years had 30 digitised images taken at three distinct points in the pulse cycle over a one hour period. A pulse synchronised ear clip trigger device was used to capture images at the desired point in the pulse cycle. Two trained graders measured the retinal vessel diameter of one large arteriole, one large venule, one small arteriole, and one small venule 10 times in each of these 30 images. RESULTS: Within an image, variability was similar between graders, pulse point, and vessel type. Across images taken at the same point in the pulse period, the change from the minimum to maximum measurement was between 6% and 17% for arterioles and between 2% and 11% for venules. In addition, measurements of small vessels had greater changes than large vessels and no point in the pulse period was more variable than another. Ignoring pulse cycle increased variability across images in the large venule, but not in the other vessel types. Mixed effect models were fit for each of the vessel types to determine the greatest source of variability. Controlling for pulse point and grader, the largest source of variability for all four vessels measured was across images, accounting for more than 50% of the total variability. CONCLUSION: Measurements of large retinal venules is generally less variable than measurements of other retinal vessels. After controlling for pulse point and grader, the largest source of variation is across images. Understanding the components of variability in measuring retinal vessels is important as these techniques are applied in epidemiological studies.

The epidemiology of retinal vein occlusion: the Beaver Dam Eye Study.

PURPOSE: To describe the prevalence and the 5-year incidence of retinal central and branch vein occlusion and associated risk factors. METHODS: The Beaver Dam Eye Study (n = 4,926) is a population-based study in which retinal vein occlusions were detected at baseline (1988-1990) and at a 5-year follow-up examination (1993-1995) by grading of 30 degrees color fundus photographs. RESULTS: The prevalence and 5-year incidence of retinal branch vein occlusion were each 0.6%. The prevalence of retinal central vein occlusion was 0.1%, and the 5-year incidence was 0.2%. While adjusting for age, the prevalence of branch vein occlusion was associated with hypertension (odds ratio [OR] 5.42, 95% confidence interval [CI] 2.18, 13.47), diabetes mellitus (OR 2.43, 95% CI 1.04, 5.70), pulse pressure (OR 1.24 for 10 mm Hg, 95% CI 1.03, 1.48), ocular perfusion pressure (OR 2.09 for 10 mm Hg, 95% CI 1.45, 3.01), arteriovenous nicking (OR 16.75, 95% CI 7.33, 38.24), and focal arteriolar narrowing (OR 22.86, 95% CI 8.43, 62.03). The age-adjusted incidence of retinal branch vein occlusion was associated with current smoking (OR 4.43 95%, CI 1.53, 12.84) compared with nonsmokers and to focal arteriolar narrowing (OR 5.24, 95% CI 1.97, 13.94) at baseline. While controlling for age, the incidence of branch vein occlusion was not associated with serum lipid levels, body mass index, white blood cell count, alcohol consumption, aspirin use, glaucoma, intraocular pressure, or ocular hypertension. CONCLUSIONS: Retinal vein occlusion is infrequent in the population. These data suggest a strong association between retinal branch vein occlusion and retinal arteriolar changes. Data from larger populations are needed to further assess associations between risk factors and the incidence of retinal vein occlusions.

Retinal emboli and stroke: the Beaver Dam Eye Study.

OBJECTIVE: To describe the prevalence at baseline and the 5-year incidence of retinal emboli, associated risk factors, and the relationship of retinal emboli at baseline to stroke and ischemic heart disease mortality. METHODS: The Beaver Dam Eye Study is a large (N = 4926) population-based study of persons aged 43 to 86 years at the baseline examination. Retinal emboli were detected at baseline (1988-1990) and at a 5-year follow-up (1993-1995) by grading of stereoscopic 30 degrees color fundus photographs using standardized protocols. Cause-specific mortality was determined from death certificates. RESULTS: The prevalence of retinal arteriolar emboli was 1.3%, and the 5-year incidence was 0.9%. After adjustments were made for age and sex, the prevalence of retinal emboli was associated with higher pulse pressure, hypertension, diabetes mellitus, past and current smoking, cardiovascular disease, and the presence of retinopathy. After adjustments were made for age and sex, the incidence of retinal emboli was associated with past and current smoking and a history of coronary artery bypass surgery. After age, sex, and systemic factors were controlled for, people with retinal emboli had a significantly higher hazard of dying with a mention of stroke on the death certificate (hazard ratio = 2.61, 95% confidence interval = 1.12-6.08) than those without retinal emboli. CONCLUSIONS: Persons with retinal emboli are at an increased risk of stroke-related death. Data also show an association of smoking, hypertension, and cardiovascular disease with the prevalence of retinal emboli. CLINICAL RELEVANCE: Data from this population-based study suggest that after discovery of retinal emboli in the asymptomatic patient, referral for possible medical intervention to control hypertension, if present, may be beneficial.

Alcohol consumption and the 5-year incidence of age-related maculopathy: the Beaver Dam eye study.

OBJECTIVE: This study evaluated alcohol consumption as a risk factor for incidence of age-related maculopathy (ARM). DESIGN: Persons aged 43 to 86 years in 1988 in Beaver Dam, Wisconsin, were examined from 1988 through 1990 and 1993 through 1995, n = 3684. The presence and severity of ARM at both examinations were determined from gradings of stereoscopic fundus photographs using the Wisconsin Age-related Maculopathy Classification System. Alcohol consumption was determined by self-report. RESULTS: Men drinking at least 78 g/week of alcohol from beer had a higher 5-year age-adjusted incidence of early ARM (10.6%) than did men who did not drink beer (6.9%), but the test for trend was only borderline significant (P = 0.08). However, incidence of soft indistinct drusen (P = 0.01), increased drusen area (P < 0.01), and confluent drusen (P = 0.02) are all associated with beer drinking in men. Increased retinal pigment and retinal pigment epithelial depigmentation are not associated with beer drinking in men or women nor are any lesions associated with total alcohol consumption or consumption from liquor or wine in either men or women. CONCLUSIONS: Except for an association of beer drinking with retinal drusen in men, consumption of alcoholic beverages is not likely to be an important risk factor for incidence of ARM.

The five-year incidence and progression of age-related maculopathy: the Beaver Dam Eye Study.

PURPOSE: The aim of the study was to describe the incidence and progression of retinal drusen, retinal pigmentary abnormalities, and signs of late age-related maculopathy. POPULATION: A population of 3583 adults (range, 43-86 years of age at baseline) living in Beaver Dam, Wisconsin, was studied during a 5-year period. METHODS: Characteristics of drusen and other lesions typical of age-related maculopathy were determined by grading stereoscopic color fundus photographs using the Wisconsin Age-Related Maculopathy Grading System. RESULTS: There was a statistically significant increased incidence of age-related maculopathy lesions with age (P < 0.05). Individuals 75 years of age or older had a significantly (P < 0.01) higher 5-year incidence of the following characteristics than people 43 to 54 years of age: larger sized drusen (125-249 microm, 17.6% vs. 2.1%; > or = 250 microm, 6.5% vs. 0.2%), soft indistinct drusen (16.3% vs. 1.8%), retinal pigment abnormalities (12.9% vs. 0.9%), exudative macular degeneration (1.8% vs. 0%), and pure geographic atrophy (1.7% vs. 0%). After adjusting for age, the incidence of early age-related maculopathy was 2.2 times (95% confidence interval 1.6, 3.2) as likely in women 75 years of age or older compared with men this age. At follow-up, late age-related macular degeneration was more likely to develop in eyes with soft indistinct drusen (6.5% vs. 0.1%) or retinal pigmentary abnormalities (7.1% vs. 0.1%) at baseline than in eyes without these lesions. CONCLUSIONS: These population-based estimates document the high incidence of signs of age-related maculopathy in people 75 years of age or older, and in women compared with men that age. The findings demonstrate that the presence of soft drusen and pigmentary abnormalities significantly increases the risk for the development of geographic atrophy and exudative macular degeneration.

Retinal microaneurysm counts and 10-year progression of diabetic retinopathy.

OBJECTIVE: To determine the relationship of change in the number of retinal microaneurysms to the 10-year progression to significant retinopathy, proliferative retinopathy, and clinically significant macular edema. DESIGN: Population-based study of persons with younger- and older-onset diabetes with 10 years of follow-up. SETTING AND PATIENTS: Eleven-county area in southern Wisconsin, where 189 patients with diabetes who had only retinal microaneurysms in photographs at baseline participated in 4- and 10-year follow-up examinations. OUTCOME MEASURES: Ten-year incidence of moderate nonproliferative diabetic retinopathy or worse, proliferative retinopathy, or clinically significant macular edema as determined by masked grading of stereoscopic color fundus photographs of seven standard fields. RESULTS: The increase in the number of retinal microaneurysms and the ratio of the number of retinal microaneurysms at the 4-year follow-up to the number at baseline were positively associated with incidence of proliferative retinopathy or clinically significant macular edema at the 10-year follow-up. Proliferative retinopathy was approximately 4.6 times and clinically significant macular edema was approximately 9.1 times more likely to develop at 10-year follow-up in eyes in which the number of microaneurysms increased by 16 or more from baseline to the 4-year follow-up than in eyes with no increase. Proliferative retinopathy was 3.4 times and clinically significant macular edema was 6.7 times more likely to develop at 10-year follow-up in eyes that had ratios of 3 or greater of the number of retinal microaneurysms at the 4-year follow-up to the number at baseline than in eyes in which the ratios were smaller. These relationships remained after controlling for the level of glycosylated hemoglobin and type of diabetes. CONCLUSIONS: Microaneurysm counts using stereoscopic color fundus photographs are an early important measure of progression of retinopathy and may serve as a surrogate end point for severe change in some clinical trials.

The relationship of age-related maculopathy, cataract, and glaucoma to visual acuity.

PURPOSE: To investigate the relationship of age-related maculopathy, cataract, and glaucoma to visual acuity in the population-based Beaver Dam Eye Study. METHODS: A cross-sectional, population-based study was performed in people 43 through 86 years of age residing in Beaver Dam, Wisconsin, who were identified between 1987 and 1988 and examined (n = 4926) between 1988 and 1990. Of those who participated, 99.4% were white. Visual acuity was measured (n = 4886) using a modification of the Early Treatment Diabetic Retinopathy Study protocol. Stereoscopic color fundus photographs and slit lamp and retroillumination photographs of the lens were graded in a masked fashion using standardized protocols to determine the presence of age-related maculopathy and central cataract. RESULTS: Fifty-seven percent of those who were legally blind had late age-related maculopathy in both eyes. The frequency of visual acuity of 20/200 or worse was not significantly different in eyes with exudative macular degeneration (48%) than in eyes with pure geographic atrophy (42%). While controlling for other factors (age, central cataract, and glaucoma) in participants with both gradable age-related maculopathy and visual acuity measurable in at least one eye (n = 4716), investigators found that each of the early age-related maculopathy lesions was associated with a decrease in visual acuity of approximately two letters or fewer when compared to eyes without these lesions. Late age-related maculopathy was associated with a decrease of approximately seven lines of letters read correctly. CONCLUSION: These data demonstrate that exudative macular degeneration and pure geographic atrophy are the most important causes of legal blindness in this population and that early age-related maculopathy, central cataract, and glaucoma had a small effect on visual acuity.

The association of glycemia and cause-specific mortality in a diabetic population.

BACKGROUND: The purpose of this study was to investigate the association of glycemia with cause-specific mortality in a diabetic population. METHODS: The study was a cohort design based in a primary care setting. Participants were all younger-onset diabetic persons (conditions diagnosed when they were younger than 30 years old and taking insulin, N = 1210) and a random sample of older-onset diabetic persons (conditions diagnosed when they were 30 years or older, N = 1780). Glycosylated hemoglobin levels were obtained at baseline examinations in 1980 to 1982 in which 996 younger-onset and 1370 older-onset persons participated. Median follow-up was 10 years in younger-onset and 8.3 years in older-onset persons; four younger-onset and two older-onset persons were unavailable for follow-up. The main outcome measure was cause-specific mortality as determined from death certificates. RESULTS: In the younger-onset group after controlling for other risk factors in proportional hazards models and considering underlying cause of death, glycosylated hemoglobin was significantly associated with mortality from diabetes (hazard ratio [HR] for a 1% change in glycosylated hemoglobin, 1.25; 95% confidence interval [CI], 1.13 to 1.38) and ischemic heart disease (HR, 1.18; 95% CI, 1.00 to 1.40). In the older-onset group, glycosylated hemoglobin was significantly associated with mortality from diabetes (HR, 1.32; 95% CI, 1.21 to 1.43), ischemic heart disease (HR, 1.10; 95% CI, 1.04 to 1.17), and stroke (HR, 1.17; 95% CI, 1.05 to 1.30), but not cancer (HR, 0.99; 95% CI, 0.88 to 1.10). Results for any mention of specific causes of death were similar. CONCLUSION: These results suggest possible benefit to the control of glycemia with respect to death due to vascular disease and diabetes.

Retinopathy in African Americans and whites with insulin-dependent diabetes mellitus.

BACKGROUND: The development and progression of diabetic retinopathy in African Americans with insulin-dependent diabetes mellitus is not known. METHODS: Two hundred subjects with insulin-dependent diabetes mellitus with duration of diabetes 16 years or less at first visit were studied; 58 were African Americans and 142 were whites. All had gradable stereoscopic color fundus photographs (seven standard fields) from at least two visits (mean time between first and second visit was 4.1 years). Subjects with hemoglobinopathy or proliferative retinopathy or subjects who had evidence of treatment for proliferative retinopathy at first visit were excluded. Masked grading of photographs was conducted using the modified Airlie House classification scheme. RESULTS: African Americans were older, heavier, had higher systolic blood pressure (all P < .05), and marginally higher hemoglobin A1 (HbA1) values (P = .06) than the whites at first visit. African Americans had a lower rate of two steps or more progression from preexistent retinopathy (19%) than whites (43%). Progression to proliferative retinopathy or treatment was similar by race. Multivariate analysis predicting development oe progression of retinopathy, while controlling for length of follow-up, found higher HbA1 (odds ratio [OR] = 2.15), longer duration of insulin-dependent diabetes mellitus (OR = 1.69), higher serum creatinine concentration (OR = 1.59), and white race (OR = 2.62) to be independent risk factors. CONCLUSIONS: These data suggest a previously unsuspected reduction in the adjusted risk for development and progression of retinopathy in African Americans. The reason for this apparently reduced risk are not known.

Migraine headache and its association with open-angle glaucoma: the Beaver Dam Eye Study.

PURPOSE: To investigate the relationship of a history of migraine headache to open-angle glaucoma. METHODS: In an epidemiologic study of age-related eye disease, subjects were asked if they had migraine headaches. The diagnosis of glaucoma was based on visual field, intraocular pressure, cup/disc ratio, and history. RESULTS: Those younger than 65 years were significantly more likely to report a history of migraine (P = 0.001) as were women (P < 0.001). There was no difference in the frequency of open-angle glaucoma between those with and those without migraine headache (P = 0.87). Multivariate analyses did not alter the conclusion. CONCLUSION: In this population-based study there is no evidence of a relationship between open-angle glaucoma and migraine headache.

Detection of drusen and early signs of age-related maculopathy using a nonmydriatic camera and a standard fundus camera.

PURPOSE: The study was designed to compare the severity of age-related maculopathy as graded from photographs taken using three different techniques. METHODS: Two methods of nonstereoscopic 45 degrees retinal photography of the macula (through a nonpharmacologically dilated pupil and through a pharmacologically dilated pupil) were compared with results from standard 30 degrees stereoscopic photographs in 112 subjects. Corresponding photographic fields were graded by a masked grader for the presence of any drusen, soft drusen, retinal pigment epithelial degeneration, increased retinal pigmentation, and early and late age-related maculopathy. RESULTS: Exact agreement between gradings of the 45 degrees photographs taken through nonpharmacologically dilated pupils and 30 degrees photographs taken through dilated pupils was 75% for any drusen, 72% for soft drusen, 72% for retinal pigment epithelial degeneration, 74% for increased retinal pigment, 85% for pure geographic atrophy, and 89% for exudative macular degeneration. The kappa scores varied from 0.33 for geographic atrophy to 0.60 for exudative macular degeneration. Slightly higher rates of agreement between gradings were found after dilation. CONCLUSION: These data suggest that 45 degrees nonstereoscopic fundus photographs, when graded according to a standard classification scheme, should be considered for detection of age-related maculopathy in situations where the pupils cannot be pharmacologically dilated and retinal specialists are not available to examine the fundus.

A pilot study of glaucoma visual field screening in diabetes.

Because people with diabetes may be at increased risk of glaucoma, we performed a pilot study using automated visual field testing for screening them. One hundred and seventy-six diabetic persons who had participated in the Wisconsin Epidemiologic Study of Diabetic Retinopathy were tested with the Armaly-Drance screening pattern on the Humphrey Visual Field Analyzer. Individuals with moderate diabetic retinopathy or worse tended to have lower sensitivity of the central visual field and missed more points than those with no or only mild retinopathy. People with a history of glaucoma had slightly less sensitivity and missed more points than controls. These preliminary findings suggest that although people with diabetes and glaucoma may more frequently have visual field defects than people with diabetes but no glaucoma, a larger study is needed. This pilot study shows that such a study would be feasible and should be designed to indicate the sensitivity, specificity, and cost-benefit ratio of a screening program so as to assess the utility of the screening visual field test for finding glaucoma amongst people with diabetes.

The relationship of retinal microaneurysm counts to the 4-year progression of diabetic retinopathy.

The relationship of retinal microaneurysms to the progression of diabetic retinopathy over a 4-year period was examined in a population-based sample of diabetic persons. The number of microaneurysms in color stereoscopic fundus photographs of seven standard fields was counted in the eyes of diabetic persons (n = 236) who had only microaneurysms in photographs at the baseline examination. If only one eye was involved (n = 121), the mean number of microaneurysms was 2.3; with bilateral involvement (n = 115), the mean was 9.3 in the more involved eye. The number of microaneurysms at the baseline examination was positively associated with significant progression of retinopathy. This relationship remained after controlling for the level of glycosylated hemoglobin. These data suggest that the number of microaneurysms at baseline is an important predictor of progression of diabetic retinopathy. Microaneurysm counts may prove to be a useful early end point in clinical trials.

Are seven standard photographic fields necessary for classification of diabetic retinopathy?

Stereoscopic fundus photography of seven fields has become standard procedure for detecting diabetic retinopathy. However, the question has arisen as to whether adequate detection of retinopathy can be achieved with fewer fields. This question was investigated in a population-based study of 2694 diabetic persons. Retinopathy levels derived from the detailed grading of all seven fields were compared with those derived from combinations of two, three or four fields, the data for these being selected from the grading of the full seven fields. For eight retinopathy levels, the rate of agreement with seven fields ranges from 80% for two fields to 91% for four fields. For four retinopathy levels, agreement increases to 85 to 95%. The rate of agreement also varies with the specific retinopathy level, with level 65 being especially sensitive to the number of fields. The sensitivity of two to four fields compared to seven fields for detecting any retinopathy varies from 87 to 95%. For detecting proliferative retinopathy, sensitivity varies from 74 to 90%, and for Diabetic Retinopathy Study high-risk characteristics, it varies from 81 to 91%. Analysis of two groups of 50 eyes in which the combinations of fields were graded independently shows a small but nonsignificant effect of field overlap. These results indicate that in some situations, fewer fields may be adequate.

Does the severity of diabetic retinopathy predict pregnancy outcome?

The authors sought to determine whether the severity of diabetic retinopathy is a predictor of subsequent pregnancy outcome. One hundred and seventy-nine pregnant diabetic women were evaluated in their first trimester of pregnancy. Stereoscopic color photographs of the ocular fundus were taken and graded by the Fundus Photography Reading Center. Thirty-nine women had no retinopathy, while 28 had proliferative retinopathy in the worse eye. The women's history and hospital delivery room charts were reviewed with regard to pregnancy outcome. Thirty-three pregnancies terminated with an adverse outcome. A logistic regression analysis was used to evaluate significant predictors of pregnancy outcome. Of maternal age, duration of diabetes, glycosylated hemoglobin, proteinuria, cigarette smoking status, and severity of diabetic retinopathy, only the last variable significantly predicted an adverse outcome. These data suggest that the severity of retinopathy should be considered when counseling a pregnant diabetic woman.

An alternative method of grading diabetic retinopathy.

The purpose of this report is to present a system for grading the severity of diabetic retinopathy that is a rapid, relatively inexpensive, and standardized alternative to the more detailed Early Treatment Diabetic Retinopathy Study (ETDRS) system; present data on its reproducibility; and compare it to the detailed ETDRS grading system. The alternative system was used to grade fundus photographs obtained during a large prevalence study, the Wisconsin Epidemiologic Study of Diabetic Retinopathy (WESDR). The alternative method involved grading seven stereoscopic standard fields as a whole, and assigning a level of severity for the eye according to the greatest degree of retinopathy using a modified Airlie House Classification scheme. Using an eight-level classification system of increasing severity of retinopathy, there was 78.3% exact agreement between the alternative and ETDRS systems. A grader regraded all 503 disagreements, and was in exact agreement 49.3% of the time with the alternative system, 35.7% of the time with the detailed system, and 15.0% with neither the alternative or detailed systems. Interobserver agreement for the alternative system was 78.5%; intraobserver agreement over a 9 month to 1 year period was 90.0% for grader 1 and 84.0% for grader 2. The alternative system of grading, when used by experienced graders, is a reproducible method for objectively determining retinopathy status in epidemiologic studies.

Quantitation of optic disc cupping.

In population-based studies and in clinical practice a reliable, objective measure of optic disc cupping is needed. This measure is of special importance when following patients with diagnosed or suspected glaucoma. We have developed a new system using stereoscopic fundus photographs for quantitating optic disc cupping from these photographs. Measurements of the cup are based on cup contour. For this system, measurements of longest and shortest cup and longest and shortest disc diameters by two observers were highly correlated, with correlation coefficients of 0.88, 0.88, 0.77, and 0.82, respectively. Mean cup to disc ratios for long and short disc diameters were within 0.04 (n = 330) between the two observers. The measurements show a high degree of inter- and intra-observer reliability, and are inexpensive in time and materials to perform. This method is well suited to population-based studies.

Diabetic retinopathy as detected using ophthalmoscopy, a nonmydriatic camera and a standard fundus camera.

The study was performed to evaluate whether the severity of diabetic retinopathy as assessed by three alternative methods was concordant with the severity of retinopathy as determined from 30 degrees stereoscopic photographs. The three methods were direct ophthalmoscopy through an undilated pupil, nonstereoscopic 45 degrees retinal photography through a pharmacologically undilated pupil and nonstereoscopic 45 degrees photography through a dilated pupil. A single 45 degrees photograph centered between the disc and fovea was taken and direct ophthalmoscopy was performed on 99 persons prior to pharmacological dilation of the pupil. After dilation, another 45 degrees photograph was taken of the same field, as well as 30 degrees stereoscopic color photographs of DRS fields 1, 2 and 4 (modified). Corresponding photographic fields were graded by masked, trained graders for the severity of retinopathy and for the presence of specified diabetic lesions using the Modified Airlie House Classification scheme. For three levels of severity of retinopathy (none, nonproliferative or proliferative) exact agreement between direct ophthalmoscopy and grading of retinopathy from stereoscopic photographs taken with the standard 30 degrees camera was 54.3% (n = 94). For four levels of severity of retinopathy (none, microaneurysms only, all other nonproliferative retinopathy and proliferative retinopathy), exact agreement between gradings of retinopathy of the 45 degrees photographs taken through undilated pupils and 30 degrees photographs taken through dilated pupils was 82.5% (n = 63); and for 45 degrees photographs and 30 degrees photographs taken through dilated pupils it was 86.5% (n = 74). These data suggest that 45 degrees nonstereoscopic fundus photographs, when graded according to a standard classification scheme, provide reasonably reliable photographic representation of the severity of retinopathy when broad overall categories are used.