Transition from film to digital fundus photography in the Longitudinal Studies of the Ocular Complications of AIDS.

PURPOSE: To describe the transition to digital imaging and assess any impact on ocular disease classification. METHODS: Film and digital images, acquired by certified photographers, were evaluated independently according to standard procedures for the following: image quality, presence of cytomegalovirus retinitis lesions, and their extent and proximity from disk and macula. Intergrader agreement within the digital medium was also assessed. RESULTS: Among the 15 eyes with cytomegalovirus retinitis, the mean difference between film and digital images for linear distance of lesion edge to disk was 0.02 disk diameters, for distance to center of macula was -0.04 disk diameters, and area covered by cytomegalovirus retinitis was 0.95 disk area. There was no statistically significant difference in distance and area measurements between media. Intergrader agreement in measurements of digital images was excellent for distance and area estimated. CONCLUSION: Our results suggest that digital grading of cytomegalovirus retinitis in Longitudinal Studies of the Ocular Complications of AIDS is comparable with that from film regarding disease classification, measurements, and reproducibility. These findings provide support for continuity of grading data, despite the necessary transition in imaging media.

Imaging of diabetic retinopathy and diabetic macular edema.

Imaging of the retinal complications of diabetes mellitus is rapidly changing from the emergence of new technology such as optical coherence tomography. In particular, the characterization of diabetic macular edema is much easier for the clinician and there are new, more sensitive clinical research end points. However, our understanding of structure-functional relationships remains suboptimal and the classification of macular edema by optical coherence tomography continues to evolve. The classification of diabetic retinopathy severity continues to rely upon fundus photography, although the transition from film to digital photography presents both challenges and advantages.

Mosaics versus Early Treatment Diabetic Retinopathy seven standard fields for evaluation of diabetic retinopathy severity.

PURPOSE: To compare agreement between mosaicked and seven field photographs for classification of the diabetic retinopathy (DR) severity. METHODS: Mosaic digital (MosD) images were compared with seven field stereo film (7FF) and stereo digital (7FD) photographs from a 152-eye cohort with full-spectrum Early Treatment of Diabetic Retinopathy severity levels for agreement on severity level, DR presence with ascending severity thresholds, DR index lesion presence, and classification repeatability. RESULTS: There was a substantial agreement classifying the Early Treatment Diabetic Retinopathy Study DR severity level between MosD and 7FF (kunweighted = 0.59, klinear weighted = 0.83), MosD and 7FD (κ = 0.62, κ weighted = 0.86), and 7FD and 7FF (κ = 0.62, κ weighted = 0.86) images. Marginal homogeneity analyses found no significant difference between MosD and 7FF (P = 0.44, Bhapkar's test). Kappa between MosD and 7FF ranged from 0.75 to 0.91 for the presence or absence of DR at 8 ascending severity thresholds. Repeatability among readers using MosD images was similar to repeatability among those using 7FF or 7FD. Repeatability among readers using MosD and 7FF images at various severity thresholds was similar. Kappa between MosD and 7FF grading for identifying DR lesions ranged from 0.61 to 1.00. CONCLUSION: Mosaic images are generally comparable with standard seven-field photographs for classifying DR severity.

Evaluation of the age-related eye disease study clinical lens grading system AREDS report No. 31.

PURPOSE: To examine the grading (interrater) reliability of the Age-Related Eye Disease Study (AREDS) Clinical Lens Grading System (ARLNS). DESIGN: Evaluation of diagnostic test or technology. PARTICIPANTS: One hundred fifty volunteers (284 eyes). METHODS: Participants with lens opacities of varying severity were independently graded at the slit lamp for cataract severity by 2 examiners (retinal or anterior segment specialists) using the ARLNS, which employs 3 standard photographs of increasing severity for classifying each of the 3 major types of opacity. Lens photographs were taken and graded at a reading center using the more detailed AREDS System for Classifying Cataracts from photographs. MAIN OUTCOME MEASURES: The Pearson correlation, weighted-kappa, and limits-of-agreement statistics were used to assess the interrater agreement of the gradings. RESULTS: Examinations were performed on 284 lenses (150 participants). Tests of interrater reliability between pairs of clinicians showed substantial agreement between clinicians for cortical and posterior subcapsular opacities and moderate agreement for nuclear opacities. A similar pattern and strength of agreement was present when comparing scores of retinal versus anterior segment specialists. Interrater agreement between clinical and reading center gradings was not as great as inter-clinician agreement. CONCLUSIONS: Interrater agreements were in the moderate to substantial range for the clinical assessment of lens opacities. Inherent differences in cataract classification systems that rely on slit lamp vs photographic assessments of lens opacities may explain some of the disagreement noted between slit lamp and photographic gradings. Given the interrater reliability statistics for clinicians and the simplicity of the grading procedure, ARLNS is presented for use in studies requiring a simple, inexpensive method for detecting the presence and severity of the major types of lens opacities. FINANCIAL DISCLOSURE(S): The authors have no proprietary or commercial interest in any of the materials discussed in this article.

Grading diabetic retinopathy severity from compressed digital retinal images compared with uncompressed images and film.

PURPOSE: To compare research grading of diabetic retinopathy (DR) severity level from compressed digital images versus uncompressed images and film. METHODS: Compressed (JPEG2000, 37:1) digital images (C) were compared with uncompressed digital (U) and film (F) stereoscopic photographs from a 152-eye cohort with full-spectrum Early Treatment Diabetic Retinopathy Study severity levels for agreement on severity level, DR presence with ascending severity threshold, presence of DR index lesions, and repeatability of grading. RESULTS: Classification of Early Treatment Diabetic Retinopathy Study severity levels from C images agreed substantially with results from F images (κ = 0.60, κ(w) [linear weighted] = 0.86) and uncompressed digital images (κ = 0.76, κ(w) = 0.92). For agreement of uncompressed digital versus F images, κ = 0.62 and κ(w) = 0.86. Distribution of Early Treatment Diabetic Retinopathy Study levels was not significantly different between C and F images (P = 0.09, Bhapkar's test for marginal homogeneity). For presence/absence of DR at 8 ascending severity thresholds, agreement between C and F was "almost perfect" (κ ≥ 0.8). Agreement on severity level between readers with C images was at least as good as that with uncompressed digital image or F. Repeatability of severity threshold grading between readers was similar using C or F images. For identifying individual DR lesions, agreement between C and F ranged from "moderate" to "perfect." Agreement of grading venous beading from C was slightly lower than from F. CONCLUSION: Full Early Treatment Diabetic Retinopathy Study scale DR severity level grading using C images is comparable to that using U images or film.

Calibration of fundus images using spectral domain optical coherence tomography.

BACKGROUND AND OBJECTIVE: Measurements performed on fundus images using current software are not accurate. Accurate measurements can be obtained only by calibrating a fundus camera using measurements between fixed retinal landmarks, such as the dimensions of the optic nerve, or by relying on a calibrated model eye provided by a reading center. However, calibrated spectral domain OCT (SD-OCT) could offer a convenient alternative method for the calibration of any fundus image. PATIENTS AND METHODS: The ability to measure exact distances on SD-OCT fundus images was tested by measuring the distance between the center of the fovea and the optic nerve. Calibrated SD-OCT scans measuring 6 X 6 X 2 mm centered on the fovea and the optic nerve were analyzed in 50 healthy right eyes. The foveal center was identified using cross-sectional SD-OCT images, and the center of the optic nerve was identified manually. The SD-OCT scans were registered to each other, and the distances between the center of the optic nerve and fovea were calculated. The overlay of these SD-OCT fundus images on photographic fundus images was performed. RESULTS: Any image of the fundus could be calibrated by overlaying the SD-OCT fundus image, and the measurements were consistent with previously defined calibration methods. The mean distance between the center of the fovea and the center of the optic nerve was 4.32 +/-0.32 mm. The line from the center of the optic nerve to the foveal center had a mean declination of 7.67 +/- 3.88 degrees. Mean horizontal displacement and vertical displacement were 4.27 +/- 0.29 mm and 0.58 +/- 0.29 mm, respectively. CONCLUSIONS: The overlay of the SD-OCT fundus image provides a convenient method for calibrating any image of the fundus. This approach should provide a uniform standard when comparing images from different devices and from different reading centers.

Progression of diabetic macular edema: correlation with blood retinal barrier permeability, retinal thickness, and retinal vessel diameter.

PURPOSE: To study the progression of diabetic macular edema (DME) in relation to baseline retinal thickness, retinal vascular leakage, and retinal trunk vessel diameters. METHODS: In this single-center study, 45 patients were enrolled with 62 eligible eyes defined as having DME of a grade less than clinically significant macular edema (CSME). From the start, the patients were included in a multicenter study exploring the effect of ruboxistaurin versus placebo for 3.4 years. Subsequently, the patients were followed up for a mean of 5.7 years by optical coherence tomography, fundus photography, and vitreous fluorometry. Baseline values in eyes that progressed to photocoagulation treatment were compared with values from eyes that did not reach this endpoint. RESULTS: In the 22 eyes of 18 patients in which CSME was diagnosed and treated, mean retinal vascular leakage at baseline was 5.6 (95% CI 4.2-7.6) nm/s, whereas eyes that did not progress to photocoagulation had a significantly lower mean leakage at baseline of 3.4 (95% CI 2.7-4.3) nm/s. No significant difference was found for measures of baseline retinal thickness or summarized retinal trunk vessel diameters. Eyes that progressed to photocoagulation treatment (mean delay to treatment, 3.6 years) had significantly higher foveal thicknesses than did nonprogressing eyes, from 18 months after study initiation. CONCLUSIONS: Progression to photocoagulation treatment for CSME was associated with higher retinal vascular leakage at baseline, whereas baseline retinal vessel diameters and retinal thickness were comparable in progressing and nonprogressing eyes. Baseline leakage was the strongest predictor of progression from non-CSME to photocoagulation for CSME.

Apolipoprotein e gene and age-related maculopathy in older individuals: the cardiovascular health study.

OBJECTIVE: To examine the association between the apolipoprotein E (APOE) gene and age-related maculopathy (ARM) in an older population. METHODS: Two thousand one hundred seventy persons 65 years and older sampled from 4 US communities had ARM signs assessed from retinal photographs using a modified Wisconsin Age-Related Maculopathy Grading System. DNA extracted from blood samples was analyzed for common APOE alleles. RESULTS: After controlling for age, sex, cigarette smoking, and other factors, white participants carrying the epsilon2 allele had an increased risk of late ARM (odds ratio, 2.53 [95% confidence interval, 1.08-5.90]) while carriers of the epsilon4 allele had a lower risk of late ARM (odds ratio, 0.69 [95% confidence interval, 0.19-2.50]). There were too few late ARM cases in African American individuals for analysis. CONCLUSION: APOE polymorphism is associated with late ARM in older white persons 65 years and older. Consistent with previous studies, the APOE epsilon2 allele is associated with a significant increased risk of late ARM development, whereas the epsilon4 allele may confer some protection.

Three-year incidence and cumulative prevalence of retinopathy: the atherosclerosis risk in communities study.

PURPOSE: To describe the three-year incidence and cumulative prevalence of retinopathy and its risk factors. DESIGN: Population-based, prospective cohort study in four US communities. METHODS: In the Atherosclerosis Risk in Communities (ARIC) Study, 981 participants had retinal photography of one randomly selected eye at the third examination (1993 to 1995) and three years later at the fourth examination (1996). Photographs were graded on both occasions for retinopathy signs (for example, microaneurysm, retinal hemorrhage, and/or cotton-wool spots). Incidence was defined as participants without retinopathy at the third examination who developed retinopathy at the fourth examination, and cumulative prevalence was defined to include incident retinopathy as well as participants who had retinopathy at both the third and fourth examinations. RESULTS: The three-year incidence and cumulative prevalence of any retinopathy in the whole cohort was 3.8% and 7.7%, respectively. In multivariable analysis, incident retinopathy was related to higher mean arterial blood pressure (odds ratio [OR] 1.5, 95% confidence interval [CI] 1.0 to 2.3, per standard deviation increase in risk factor levels), fasting serum glucose (OR 1.6, 95% CI 1.3 to 2.1), serum total cholesterol (OR 1.4, 95% CI 1.0, 2.0), and plasma fibrinogen (OR 1.4, 95% CI 1.1 to 1.9). Among persons without diabetes, the three-year incidence and cumulative prevalence of nondiabetic retinopathy was 2.9% and 4.3%, respectively. Incident nondiabetic retinopathy was related to higher mean arterial blood pressure (OR 1.4, 95% CI 0.9 to 2.3) and fasting serum glucose (OR 1.5, 95% CI 1.0 to 2.3). Among persons with diabetes, the three-year incidence and cumulative prevalence of diabetic retinopathy was 10.1% and 27.2%, respectively. CONCLUSIONS: Retinopathy signs occur frequently in middle-aged people, even in those without diabetes. Hypertension and hyperglycemia are risk factors for incident retinopathy.

Intake of zinc and antioxidant micronutrients and early age-related maculopathy lesions.

BACKGROUND: Macular degeneration, the end stage of age-related maculopathy (ARM), is the leading cause of legal blindness worldwide, and few modifiable risk factors are known. The high concentration of carotenoids in the macula, plus evidence linking oxidative stress to ARM and carotenoids to antioxidation, generated the hypothesis that higher antioxidant intakes can prevent ARM. Results of observational and intervention studies have been inconsistent. OBJECTIVE: To evaluate associations between intakes of zinc and antioxidant micronutrients and early ARM. METHODS: Between 1993 and 1995, ARM was assessed in 398 Boston-area women aged 53-74 y using the Wisconsin Age-related Maculopathy System of grading retinal fundus photographs. The women were a subset of the Nurses' Health Study cohort. Micronutrient intake was assessed by semi-quantitative food frequency questionnaires administered four times between 1980 and the baseline eye examinations. RESULTS: After multivariate adjustment for potential confounders, 1980 energy-adjusted intakes of alpha-carotene, beta-carotene, lycopene, total retinol, total vitamin A, and total vitamin E were significantly inversely related to the prevalence of pigmentary abnormalities (PA). Furthermore, increasing frequency of consuming foods high in alpha-or beta-carotene was associated with lower odds of PA; compared to women consuming these foods < 5 times/wk, odds ratios (95% CI) were 0.7 (0.3-1.6) for 5-6 times/wk, 0.6 (0.2-1.3) for 7-9.5 times/wk, and 0.3 (0.1-0.7)for > or =10 times/wk. Lutein/zeaxanthin intakes and more recent intakes of most carotenoids were unrelated to PA, and intakes of zinc and antioxidant micronutrients were unrelated to having large or intermediate drusen alone.

Age-related macular degeneration and risk for stroke.

BACKGROUND: Age-related macular degeneration (AMD) affects 7 million persons 40 years of age and older in the United States. Risk factors for the disease are similar to those for stroke. OBJECTIVE: To determine what relationship, if any, exists between AMD and incident clinical stroke. DESIGN: Prospective cohort study. SETTING: The population-based Atherosclerosis Risk in Communities Study, which was conducted in Minnesota, Maryland, Mississippi, and North Carolina. PATIENTS: 10 405 persons between 49 and 73 years of age who had no history of stroke or coronary heart disease. MEASUREMENTS: Participants had retinal photographs taken between 1993 and 1995. A standardized protocol was used to evaluate the photographs for the presence of drusen and other signs of AMD. Incident stroke events were identified and validated by reviewing case records. RESULTS: There were 498 early-stage and 10 late-stage cases of AMD in the cohort (n = 508). Over a 10-year period, 241 persons had an incident stroke event. After adjusting for age, sex, ethnicity, and site, the authors found that persons with early-stage AMD had a higher cumulative incidence of stroke than those without the disease (4.08% vs. 2.14%). The presence of early-stage AMD was associated with a higher adjusted risk for stroke (hazard ratio, 1.87 [95% CI, 1.21 to 2.88]). Further adjustment for systolic blood pressure, diabetes, cigarette smoking, and use of antihypertensive medications did not substantially alter this association (hazard ratio, 1.85 [CI, 1.19 to 2.87]). The authors found that the association between early-stage AMD and stroke varied by study site and patient ethnicity. Multivariable-adjusted hazard ratios were 3.15 and 1.07 in samples of white patients in Minnesota and Maryland, respectively; 3.77 in a sample of African-American patients in Mississippi; and 0.33 in a sample of mostly white patients (91%) in North Carolina. No site included sufficient numbers of both African-American and white patients to determine whether ethnicity contributed to the observed differences by study site. LIMITATIONS: There were few cases of late-stage AMD, and the cohort assembly method prohibited full understanding of variation by ethnicity and site. CONCLUSION: Middle-aged persons with signs of early-stage AMD have a higher risk for stroke independent of traditional stroke risk factors.

Retinal microvascular abnormalities and MRI-defined subclinical cerebral infarction: the Atherosclerosis Risk in Communities Study.

BACKGROUND AND PURPOSE: Retinal microvascular abnormalities reflect cumulative small vessel damage from elevated blood pressure and may reflect subclinical cerebral microvascular changes. We examined their associations with MRI-defined cerebral infarcts. METHODS: Population-based, cross-sectional study of 1684 persons 55 to 74 years of age without a history of clinical stroke, sampled from 2 US southeastern communities. Retinal photographs were obtained and graded for presence of retinal microvascular abnormalities, including arteriovenous nicking, focal arteriolar narrowing, retinal hemorrhages, soft exudates and microaneurysms. Photographs were also digitized, and retinal vessel diameters were measured and summarized as the arteriole-to-venule ratio (AVR). Cerebral MRI scans were graded for presence of cerebral infarct, defined as a lesion > or =3 mm diameter in a vascular distribution with typical imaging characteristics. RESULTS: There were a total of 183 MRI cerebral infarcts. After adjustment for age, gender, race, 6-year mean arterial blood pressure, diabetes, and other stroke risk factors, cerebral infarcts were associated with retinal microvascular abnormalities, with odds ratios 1.90 (95% CI, 1.25 to 2.88) for arteriovenous nicking, 1.89 (95% CI, 1.22 to 2.92) for focal arteriolar narrowing, 2.95 (95% CI, 1.30 to 6.71) for blot hemorrhages, 2.08 (95% CI, 0.69, 6.31) for soft exudates, 3.17 (95% CI, 1.05 to 9.64) for microaneurysms, and 1.74 (95% CI, 0.95 to 3.21) for smallest compared with largest AVR. In stratified analyses, these associations were only present in persons with hypertension. CONCLUSIONS: Retinal microvascular abnormalities are associated with MRI-defined subclinical cerebral infarcts independent of stroke risk factors. These data suggest that retinal photography may be useful for studying subclinical cerebrovascular disease in population-based studies.

Dietary glycemic index and carbohydrate in relation to early age-related macular degeneration.

BACKGROUND: Several dietary factors have been linked to age-related maculopathy (ARM), the early form of age-related macular degeneration, and there is reason to think that dietary carbohydrate may play a role in the development of ARM. OBJECTIVE: The purpose of the present study was to examine the relation between dietary carbohydrate quality, as measured by dietary glycemic index (GI) or total carbohydrate intake, and ARM. DESIGN: From the Nurses' Health Study, 1036 eyes from 526 Boston-area participants without a previous ARM diagnosis were included in the present study. The presence and degree of ARM were classified by the Age-Related Eye Diseases Study system. Long-term dietary information was based on data from an average of 4 food-frequency questionnaires collected over a 10-y period before the assessment of ARM. With eyes as the unit of analysis, we used a generalized estimating approach to logistic regression to estimate the odds ratios for ARM in a manner that accounted for the lack of independence between the 2 eyes from the same subject. RESULTS: After multivariate adjustment, dietary GI was related to ARM (specifically to retinal pigmentary abnormalities), whereas total carbohydrate intake was not. The odds ratio for ARM being in the highest tertile of dietary GI (> or =77.0) versus the lowest (<74.6) was 2.71 (95% CI: 1.24, 5.93; P for trend = 0.01). Neither dietary GI nor total carbohydrate intake was related to drusen. CONCLUSION: Our results suggest that dietary GI may be an independent risk factor for ARM.

Retinal arteriolar narrowing, hypertension, and subsequent risk of diabetes mellitus.

BACKGROUND: Microvascular disease and hypertension have been linked with risk of diabetes mellitus. We examined the association of retinal arteriolar narrowing, a marker of chronic hypertension, with incident diabetes. METHODS: Prospective cohort study of 3251 nondiabetic persons aged 43 to 86 years living in Wisconsin. The diameters of retinal vessels were measured from baseline retinal photographs of participants. Retinal measurements were summarized as the retinal arteriole-to-venule ratio, with smaller ratios indicating narrower arteriolar diameters. Incident diabetes cases were ascertained at the 5-year and 10-year follow-up examinations. RESULTS: There were 249 incident diabetes cases. Participants with narrower retinal arteriolar diameters had a higher incidence of diabetes (cumulative incidences of 5.1%, 7.0%, 9.2%, and 11.7%, comparing decreasing quartiles of arteriole-to-venule ratio). After controlling for baseline casual blood glucose level, glycosylated hemoglobin level, body mass index, and other risk factors, retinal arteriolar narrowing was significantly associated with risk of incident diabetes (multivariable-adjusted relative risk, 1.53; 95% confidence interval, 1.03-2.27; comparing smallest to largest arteriole-to-venule ratio quartiles). Participants with both hypertension and retinal arteriolar narrowing had a 3-fold higher risk of incident diabetes (multivariable-adjusted relative risk, 3.41; 95% confidence interval, 1.66-6.98) than normotensive participants without arteriolar narrowing. CONCLUSIONS: Retinal arteriolar narrowing is related to risk of incident diabetes. These data suggest a possible link between systemic arteriolar narrowing associated with hypertension and diabetes development.

Retinal vessel diameters and incident open-angle glaucoma and optic disc changes: the Rotterdam study.

PURPOSE: It remains unclear whether reduced retinal blood flow and smaller arterioles, reported to exist in patients with open-angle glaucoma (OAG), are a cause or a consequence of ganglion cell loss. We examined whether baseline retinal vessel diameters were related to incident (i)OAG or incident optic disc changes in a population-based sample. METHODS: In the prospective population-based Rotterdam Study, baseline diameters of retinal arterioles and venules (1990-1993) were measured in digitized images of 3469 persons (aged 55 years and older) at risk for OAG. The follow-up examinations took place from 1997 to 1999. iOAG was based on the presence of incident glaucomatous visual field loss and/or incident glaucomatous optic neuropathy. Changes in neuroretinal rim, cup area, or vertical cup-to-disc ratio were calculated with a semiautomated image analyzer in 2782 persons. RESULTS: After a mean follow-up time of 6.5 years, 74 participants had iOAG. At baseline, the mean arteriolar diameter was 147.5 +/- 14.2 microm (SD) and the venular, 222.9 +/- 20.0 microm. Neither arteriolar diameters (odds ratio [OR] per SD decrease: 0.82; 95% confidence interval [CI]: 0.66-1.03) nor venular ones (OR per SD increase: 1.20; 95% CI: 0.95-1.53) were significantly related to iOAG. Baseline retinal vessel diameters did not predict changes in the optic disc. Additional adjustment for cardiovascular risk factors did not alter these results. CONCLUSIONS: The data show that baseline retinal vessel diameters did not influence the risk of iOAG or incident optic disc changes. These data provide no evidence for a retinal vascular role in the pathogenesis of OAG.

Estrogen replacement therapy and retinal vascular caliber.

OBJECTIVE: It is unclear if estrogen replacement therapy (ERT) has an effect on the retinal circulation. In the current study, we examine the association of ERT, female reproductive factors, and retinal vascular caliber. DESIGN: Population-based cross-sectional study. PARTICIPANTS: Women participants aged 43 to 84 years living in Beaver Dam, Wisconsin. METHODS: Retinal photographs of participants taken at the baseline examination were digitized, and the diameters of arterioles and venules were measured using a well-established technique. Estrogen replacement therapy and female reproductive factors were ascertained by interview. MAIN OUTCOME MEASURES: Retinal arteriolar and venular diameters. RESULTS: Of the 2469 women participants with data for analysis, 10.5% were current users of ERT and 7.4% were past users. After adjusting for age, blood pressure (BP), body mass index, smoking, and other factors, women who were current users of ERT had narrower retinal arteriolar and venular diameters than those who were past users or never used, with mean arteriolar diameters of 167.6 microm for current users, 170.8 microm for past users, and 170.9 microm for those who never used (P = 0.009) and mean venular diameters of 239.9 microm for current users, 244.0 microm for past users, and 243.9 microm for those who never used (P = 0.02). There was a significant trend of increasing narrowing for both arterioles (P trend, 0.01) and venules (P trend, 0.007) with increasing duration of ERT. Associations were somewhat stronger in younger women and women without a history of hypertension and cigarette smoking. Female reproductive factors (e.g., age of menarche and pregnancy) were not associated with retinal vessel diameters. CONCLUSIONS: Estrogen replacement therapy is associated with narrower retinal vessel diameters, independent of BP and other vascular factors.

Clinician versus reading center assessment of cytomegalovirus retinitis lesion size.

PURPOSE: To compare clinician and fundus photograph reading center assessments of the cytomegalovirus (CMV) retinitis area and change in the CMV retinitis area over time, and to investigate how these assessments correlate with the visual field (VF) of eyes with CMV retinitis. DESIGN: Analysis of pooled data from 2 multicenter randomized clinical trials and 1 prospective multicenter epidemiologic study. PARTICIPANTS: Ninety-five eyes of 79 patients. At baseline, each eye had CMV retinitis restricted to zone 1 and/or zone 2 (approximately the photographable postequatorial retina), as assessed by the evaluating clinician. METHODS: Comparison of CMV retinitis area, change in area over time as assessed by clinicians and a fundus photograph reading center, and correlation of these assessments with VF measurement. MAIN OUTCOME MEASURES: Cytomegalovirus retinitis area, change in CMV retinitis area over time, and VF score. RESULTS: Baseline assessments of the mean retinitis area were, by clinicians, 12.8% of the total retinal area and, by the reading center, 6.3% of the total retinal area (P<0.001). There was a positive correlation between clinician and reading center assessments of retinitis area at baseline (rho = 0.77 and P<0.0001 by Pearson correlation and rho = 0.54 and P<0.001 by concordance). Both clinician and reading center size measures correlated negatively with VF (Spearman correlation rhos = -0.38 and -0.52, respectively; P<0.001 each). Mean changes in area over a 3-month interval were, by clinicians, +1.2% and, by the reading center, +1.1% (P = 0.68). Regression analysis showed a positive concordance (rho = 0.42, P<0.001). Change in VF over a 3-month interval did not correlate with change in retinitis area as assessed by clinicians or the reading center. CONCLUSIONS: Awareness of the similarities and differences between clinician and reading center assessments of CMV retinitis area should permit clinicians to apply research data to clinical practice more effectively. Clinician assessment of retinitis area correlates negatively with VF, a clinically meaningful visual outcome in patients with CMV retinitis.

Cardiovascular risk factors for retinal vein occlusion and arteriolar emboli: the Atherosclerosis Risk in Communities & Cardiovascular Health studies.

OBJECTIVE: To examine the associations of retinal vein occlusion and arteriolar emboli with cardiovascular disease. DESIGN: Population-based cross-sectional study. PARTICIPANTS: Pooled from the Atherosclerosis Risk in Communities Study (n = 12,642; mean age, 60 years) and the Cardiovascular Health Study (n = 2824; mean age, 79 years). METHODS: Retinal vein occlusion and arteriolar emboli were identified from a single nonmydriatic retinal photograph using a standardized protocol. Photographs were also graded for arteriovenous nicking and focal arteriolar narrowing. All participants had a comprehensive systemic evaluation, including standardized carotid ultrasonography. MAIN OUTCOME MEASURES: Retinal vein occlusion and arteriolar emboli. RESULTS: Prevalences of retinal vein occlusion and arteriolar emboli were 0.3% (n = 39 cases) and 0.2% (n = 34 cases), respectively. After adjusting for age, retinal vein occlusion was associated with hypertension (odds ratio [OR], 2.96; 95% confidence interval [CI], 1.43-6.14), systolic blood pressure (BP) (OR, 4.12; 95% CI, 1.40-12.16; highest quartile vs. lowest), diastolic BP (OR, 2.64; 95% CI, 1.07-6.46; highest quartile vs. lowest), carotid artery plaque (OR, 5.62; 95% CI, 2.60-12.16), body mass index (OR, 3.88; 95% CI, 1.23-12.18; highest quartile vs. lowest), plasma fibrinogen (OR, 3.29; 95% CI, 1.08-10.02; highest quartile vs. lowest), arteriovenous nicking (OR, 4.09; 95% CI, 2.00-8.36), and focal arteriolar narrowing (OR, 5.17; 95% CI, 2.59-10.29). After adjusting for age, retinal arteriolar emboli were associated with hypertension (OR, 3.14; 95% CI, 1.44-6.84), systolic BP (OR, 3.46; 95% CI, 1.13-10.65; highest quartile vs. lowest), prevalent coronary heart disease (OR, 2.33; 95% CI, 1.01-5.42), carotid artery plaque (OR, 4.62; 95% CI, 1.85-11.57), plasma lipoprotein (a) (OR, 3.69; 95% CI, 1.20-11.41; highest quartile vs. lowest), plasma fibrinogen (OR, 3.09; 95% CI, 0.98-9.76; highest quartile vs. lowest), and current cigarette smoking (OR, 3.08; 95% CI, 1.47-6.47). Approximately a quarter of participants with retinal vein occlusion and arteriolar emboli had evidence of carotid artery plaque as defined from ultrasound. CONCLUSIONS: Retinal vein occlusion and retinal arteriolar emboli are associated with carotid artery disease, hypertension, and other cardiovascular risk factors.

The Age-Related Eye Disease Study severity scale for age-related macular degeneration: AREDS Report No. 17.

OBJECTIVE: To develop a fundus photographic severity scale for age-related macular degeneration (AMD). METHODS: In the Age-Related Eye Disease Study, stereoscopic color fundus photographs were taken at baseline, at the 2-year follow-up visit, and annually thereafter. Photographs were graded for drusen characteristics (size, type, area), pigmentary abnormalities (increased pigment, depigmentation, geographic atrophy), and presence of abnormalities characteristic of neovascular AMD (retinal pigment epithelial detachment, serous or hemorrhagic sensory retinal detachment, subretinal or sub-retinal pigment epithelial hemorrhage, subretinal fibrous tissue). Advanced AMD was defined as presence of 1 or more neovascular AMD abnormalities, photocoagulation for AMD, or geographic atrophy involving the center of the macula. We explored associations among right eyes of 3212 participants between severity of drusen characteristics and pigmentary abnormalities at baseline and development of advanced AMD within 5 years of follow-up. RESULTS: A 9-step severity scale that combines a 6-step drusen area scale with a 5-step pigmentary abnormality scale was developed, on which the 5-year risk of advanced AMD increased progressively from less than 1% in step 1 to about 50% in step 9. Among the 334 eyes that had at least a 3-step progression on the scale between the baseline and 5-year visits, almost half showed stepwise progression through intervening severity levels at intervening visits. Replicate gradings showed agreement within 1 step on the scale in 87% of eyes. CONCLUSIONS: The scale provides convenient risk categories and has acceptable reproducibility. Progression along it may prove to be useful as a surrogate for progression to advanced AMD.

Medication use and retinal vessel diameters.

PURPOSE: To study the influence of different medications on retinal vessel diameters. DESIGN: Cross-sectional study. METHODS: Retinal photographs in the Beaver Dam Eye Study (n = 4926, aged 43 to 84 years) were digitized, and the diameters of retinal vessels were measured. Participants' current medications were recorded at the examination. RESULTS: There were few significant associations between medication use and retinal vessel diameters. After adjusting for age, blood pressure, and other factors, participants who were using topical beta-blocker eyedrops had narrower retinal arteriolar (P = .05) and venular (P = .006) diameters than nonusers. Systemic beta-blocker was not associated with retinal vessel diameter size. CONCLUSION: We found few associations between current medication use and retinal vessel diameter. Retinal vessels were narrowed in those taking antiglaucoma medications, most strikingly in those prescribed topical beta-blockers, although such a relationship could not be established among those using systemic beta-blockers.