Methods for evaluation of retinal microvascular abnormalities associated with hypertension/sclerosis in the Atherosclerosis Risk in Communities Study.

OBJECTIVE: To develop protocols to photograph and evaluate retinal vascular abnormalities in the Atherosclerosis Risk in Communities (ARIC) Study; to test reproducibility of the grading system; and to explore the relationship of these microvascular changes with blood pressure. DESIGN: Population-based, cross-sectional study. PARTICIPANTS: Among 4 examination centers, 11,114 participants (48-73 years of age) at their third triennial examination, after excluding persons with diabetes from this analysis. METHODS: One eye of each participant was photographed by technicians with nonmydriatic fundus cameras. Reading center graders evaluated focal arteriolar narrowing, arteriovenous (AV) nicking, and retinopathy by examining slides on a light box and measured diameters of all vessels in a zone surrounding the optic disc on enhanced digitized images. To gauge generalized narrowing, vessel diameters were combined into central arteriolar and venular equivalents with formulas adjusting for branching, and the ratio of equivalents (A/V ratio) was calculated. MAIN OUTCOME MEASURES: Retinal vascular abnormalities, mean arteriolar blood pressure (MABP). RESULTS: Among 11,114 participants, photographs were obtained of 99%, with quality sufficient to perform retinal evaluations in 81%. In the 9040 subjects with usable photographs, A/V ratio (lower values indicate generalized arteriolar narrowing) ranged from 0.57 to 1.22 (median = 0.84, interquartile range = 0.10), focal arteriolar narrowing was found in 7%, AV nicking in 6%, and retinopathy in 4%. Because of attrition of subjects and limitation of methods, prevalence of abnormality was likely underestimated. Controlling for gender, race, age, and smoking status, these retinal changes were associated with higher blood pressure. For every 10-mmHg increase in MABP, A/V ratio decreased by 0.02 unit (P < 0.0001), focal arteriolar narrowing had an odds ratio (OR) of 2.00 (95% confidence interval [CI] = 1.87-2.14), AV nicking had an OR of 1.25 (95% CI = 1.16-1.34), and retinopathy had an OR of 1.25 (95% CI = 1.15-1.37). For any degree of generalized narrowing, individuals with focal narrowing had MABP approximately 8 mmHg higher than those without (P < 0.0001). Masked replicate assessment of a sample found the following reproducibility: for A/V ratio, correlation coefficient = 0.79 and median absolute difference = 0.03; for focal arteriolar narrowing, kappa = 0.45; for AV nicking, kappa = 0.61; and for retinopathy, kappa = 0.89. CONCLUSION: Protocols have been developed for nonmydriatic fundus photography and for evaluation of retinal vascular abnormalities. Several microvascular changes were significantly associated with higher blood pressure; follow-up will show whether these are predictive of later cerebrovascular or cardiovascular disease independently of other known risk factors.

Retinal arteriolar diameters and elevated blood pressure: the Atherosclerosis Risk in Communities Study.

Narrowing and other changes in retinal arterioles may reflect damage due to hypertension, which may predict stroke and other cardiovascular diseases independently of blood pressure level. Newly developed quantitative methods of assessing retinal narrowing are used to determine whether this sign is related only to current blood pressure or whether it also independently reflects the effects of previous blood pressure. Retinal photography was performed at the third examination of Atherosclerosis Risk in Communities (ARIC) Study in 1993-1995, and results are presented for the 9,300 nondiabetic participants aged 50-71 years. Generalized narrowing of smaller arterioles was strongly and monotonically related to current blood pressure in men and women, whether they were taking antihypertensive medications or not, and, independent of current blood pressure, was consistently and monotonically related to blood pressure levels measured 3 and 6 years before the retinal assessment. Arteriovenous nicking was also independently related to both current and previous blood pressures. The patterns of association suggested that these signs reflect both transient and persisting structural effects of elevated blood pressure, in agreement with the scant pathologic literature available. The findings suggest that retinal assessment may be useful for research on the microvascular contributions to clinical cardiovascular diseases.

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.

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.

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.