(Stroke. 1997;28:63-66.)
© 1997 American Heart Association, Inc.
Articles |
Prevalence of Asymptomatic Retinal Emboli in an Australian Urban Community
the Departments of Ophthalmology (P.M., J.J.W., W.L.) and Public Health and Community Medicine (S.R.L.), University of Sydney, and the National Centre for Epidemiology and Population Health, Australian National University, Canberra (W.S.), Australia.
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Abstract |
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 Top Abstract IntroductionSubjects and MethodsResultsDiscussionReferences |
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Background and Purpose Because no population-based estimates are available for asymptomatic retinal emboli, we aimed to assess prevalence and associations of this sign in a defined older Australian urban population.
Methods A total of 3654 persons aged 49 years or older, representing 82% of residents in an urban area west of Sydney, underwent a detailed eye examination that included medical history, stereo retinal photography, and fasting blood tests including lipids. Retinal emboli were diagnosed clinically and from photographic grading and classified as cholesterol, platelet-fibrin, or calcific in type.
Results Asymptomatic retinal emboli were found in 51 participants (1.4%; 95% confidence interval [CI], 1.0% to 1.8%). The prevalence was 0.8% in persons aged <60 years, 1.4% for those aged 60 to 69 years, 2.1% for those aged 70 to 79 years, and 1.5% for those aged 80 years or older. Men had a significantly higher prevalence (2.2%) of retinal emboli than women (0.8%, P<.001) after adjustment for age (odds ratio [OR], 2.7; 95% CI, 1.5 to 4.8). Forty-one emboli (80%) were cholesterol type, 7 (14%) were platelet-fibrin, and 3 (6%) were calcific. Significant associations were found after age-sex adjustment, with hypertension (OR, 2.2; 95% CI, 1.2 to 3.8), a combined history of vascular disease (OR, 2.4; 95% CI, 1.3 to 4.4), past vascular surgery (OR, 3.5; 95% CI, 1.4 to 8.5), and current (OR, 2.2; 95% CI, 1.1 to 4.2) or any (OR, 2.6; 95% CI, 1.2 to 4.3) smoking history. These associations persisted after multivariate analysis. There were no significant associations with diabetes, obesity, or fasting blood test findings.
Conclusions This study provides accurate prevalence rates for asymptomatic retinal emboli in the elderly and confirms associations with hypertension, smoking, and vascular disease.
Key Words: embolism • epidemiology • retina
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Introduction |
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TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
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Retinal emboli are discrete or plaquelike opacities that can be seen ophthalmoscopically within the lumen of retinal arterioles. In a recent US case-control study of 70 consecutive men with asymptomatic retinal emboli and 21 control subjects, asymptomatic retinal cholesterol emboli were found to have significant associations with hypertension, smoking, and the presence of heterogeneous carotid plaques on ultrasound.1 Follow-up of these 70 men for a mean period of 3.4 years revealed a 10-fold increase in the annual rate of stroke in the case subjects compared with a second group of 70 matched control subjects without emboli or ocular ischemia.2 The stroke risk was independent of other vascular risk factors, and most stroke cases (71%) involved carotid territory on the same side as the embolus.
One of the earliest descriptions of emboli in the retinal circulation was given by Butler in 1927.3 In one patient he described a "bright embolus" just beyond the first fork of the inferior temporal arteriole, which persisted for 3 weeks. Witmer and Schmid4 also described cholesterol retinal artery embolism. Fisher5 observed emboli in transient monocular blindness, whereas Russell6 documented retinal emboli in cases of permanent monocular blindness from retinal artery occlusion. Hollenhorst7 proposed the significance of retinal emboli in 1961, reporting bright orange-yellow plaques at the bifurcation of retinal arterioles in 11% of 235 patients with carotid occlusive disease. He observed that these emboli were often transient and sometimes moved distally in the retinal vessels. Hollenhorst considered them an important sign of atherosclerosis and noted that they were frequently asymptomatic.
Retinal emboli may have a reflective (bright) or nonreflective (dull) appearance, may be single or multiple, and may be seen in one or both eyes.8 Reflective or crystalline emboli are seen to reflect light or glisten and are thought to be largely composed of cholesterol salts,9 whereas nonreflective or noncrystalline emboli5 may be composed of platelet-fibrin10 or calcified material.11 Emboli may persist in the retinal circulation for periods from days to years in some cases.8 Emboli are observed in more than half of branch12 and less than half of central retinal artery occlusion cases.13 Russell14 proposed that the most common reflective (cholesterol) emboli arise from ulcerating atheromatous internal or common carotid plaques, nonreflective (platelet-fibrin) emboli arise from mural thrombus in the carotid, and white (calcific) emboli originate from cardiac valvular structures. It is likely that platelet-fibrin emboli also arise from ulcerated carotid plaques.10
Although there have been a number of reports from clinic-based case series of both symptomatic and asymptomatic retinal emboli,8 9 15 there have been no reports estimating the prevalence of retinal emboli in a defined population. Knowledge of the age- and sex-specific prevalence of asymptomatic retinal emboli would be valuable in assessing the utility of retinal examination as a simple noninvasive means of detecting persons at increased risk of stroke or other vascular events. Our study aimed to (1) estimate the age- and sex-specific prevalence of asymptomatic retinal emboli in a representative older Australian population sample and (2) assess comorbidity and possible risk factors for asymptomatic retinal emboli.
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Subjects and Methods |
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TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
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Study Population
The Blue Mountains Eye Study is a population-based survey of vision and common eye diseases in an urban elderly population (aged 49 years and older) comprising two postal code areas in the Blue Mountains region west of Sydney, Australia. This geographically well-defined area has a stable and homogenous population, which is representative of the state of New South Wales in measures of socioeconomic status. Details of the survey method and procedures have been previously described.16 In summary, of 4433 eligible persons, 3654 (82.4%) were examined during a 2-year period. Among those 779 nonparticipants, 501 (11.3% of 4433) refused to participate; of this 501, 353 (8.0% of 4433) permitted a brief interview.
Procedures
The study was approved by the Western Sydney Area Health Service Human Ethics Committee, and written informed consent was obtained from all participants. At the clinic, a detailed demographic and medical history was taken, including a history of diabetes, hypertension, vascular events (angina, acute myocardial infarct, or stroke), and smoking. Hypertension was defined as systolic blood pressure 
160 mm Hg, diastolic blood pressure 95 mm Hg, or current use of antihypertensive medications.
Seated blood pressure, height, and weight were measured. All subjects examined underwent a detailed eye examination, including subjective refraction. Stereo retinal photographs (30°) were taken of Diabetic Retinopathy Study fields 1 (disc) and 2 (macula), as well as nonstereo photographs of fields 3 (temporal), 4, and 5 (upper and lower temporal vascular arcades) and nasal to the optic disc.17 Subjects were asked to return for fasting blood tests; 88% of participants complied with this request. Diabetes was defined as fasting blood glucose 7.8 mmol/L, use of medication for diabetes, or physician diagnosis of diabetes.
Gradable retinal photographs of at least one eye were available for 3583 of the 3654 participants (98.1%). The photographs were read in a masked manner by one of two trained graders, with high reproducibility.16 All photographic fields of each eye were examined by the graders to detect retinal emboli, which were classified as definite or questionable. All cases of emboli were adjudicated by the primary author, and only definite embolic lesions were included in the analysis. There were no cases detected clinically that were not also detected during photographic grading. The embolus type was classified as (1) cholesterol, if it had a reflective, glistening, yellowish, sharp-edged appearance; (2) fibrin-platelet, if the embolus was dull white-gray and amorphous, sometimes with an irregular border; or (3) calcific, if it appeared as a large, bright white chunk. Fibrin-platelet emboli were clearly distinguished from prominent arteriolar sheathing, which can have a similar appearance. Embolus size was assessed using grading circles developed for assessment of age-related maculopathy lesions18 by Dr Ronald Klein, Madison, Wisconsin.
Statistical Analysis
Statistical Analysis System (SAS Institute Inc) was used for statistical analyses, including the Mantel-Haenszel test, 
2 statistic, and logistic regression analyses. In logistic regressions, age was used as a continuous variable.
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Results |
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TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
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Emboli were present in one or both eyes of 51 participants (prevalence, 1.4%; 95% confidence interval [CI], 1.0% to 1.8%). None had presented with a retinal artery occlusion or transient monocular blindness, and hence all were considered asymptomatic. Retinal emboli were found in 0.8% of persons aged <60 years, 1.4% of those aged 60 to 69 years, 2.1% of those aged 70 to 79 years, and 1.5% of those aged
80 years (2 trend, 3.9; P<.05). The prevalence was significantly higher in men (2.2%) than in women (0.8%) (odds ratio, 2.7; 95% CI, 1.5 to 4.8) after adjustment for age in a logistic regression. Overall, 67% of emboli were found in men. The Figure
shows the prevalence of retinal emboli by age and sex.
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Emboli were single in 45 persons (88%) and multiple in 6 (12%), with both eyes involved in 2. Five persons had two emboli and 1 person had three. Emboli were found more frequently along the course of an artery (69%) than at a bifurcation (31%). Cholesterol emboli made up the majority (41 cases, 80%). Platelet-fibrin emboli were found in 7 subjects (14%) and calcific emboli in 3 (6%). Smaller emboli were most frequent, with 43% measuring 
63 µm, 27% 64 to 125 µm, and 30% >125 µm.
Associations of retinal emboli with vascular risk factors are given in the Table. Hypertension was more prevalent in persons with (57%) than in those without (38%) emboli and remained a significant predictor of retinal emboli after adjustment for age and sex. History of angina, myocardial infarct, or stroke was more frequent in persons with retinal emboli, but these differences were not significant after adjustment. A combined history of any vascular disease (hypertension, angina, myocardial infarct, or stroke) was significantly more frequent in persons with emboli (67%) than in those without (44%) after adjustment for age and sex. Current or past smokers also had a significantly increased risk of emboli. A history of past vascular surgery (coronary, lower limb, or carotid) was more frequent among persons with retinal emboli (12%) than without emboli (2.8%), significant after age and sex adjustment. No significant relationships were found with body mass index or fasting blood tests including hematocrit level, platelet count, and levels of serum total cholesterol, triglycerides, HDL cholesterol, glucose, creatinine, or plasma fibrinogen. The magnitude of these associations was similar for cholesterol emboli only.
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Adjusting separately for the two factors most strongly associated with retinal emboli (either a history of past vascular surgery or current smoking) did not substantially affect the odds for any vascular disease, hypertension, past vascular surgery, or smoking. There was insufficient power for all factors to be included in a multivariate model at the same time.
In this population, isolated microaneurysms and hemorrhages were also detected during the grading of retinal photographs in 12% of persons without diabetes. These nondiabetic retinopathy lesions were found in 18% of persons with retinal emboli compared with 12% in those without emboli.
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Discussion |
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TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
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There have been no previous reports of the prevalence of retinal emboli from a large population-based sample. This information may be valuable, considering the recent prospective finding of a 10-fold increase in stroke rate in asymptomatic retinal embolus case subjects compared with matched control subjects2 and an earlier study indicating a fourfold to fivefold increased risk.19 Data on the prevalence of asymptomatic retinal emboli could assist in identifying at-risk individuals who might benefit from carotid imaging, increased surveillance of vascular risk factors, or risk factor intervention.
It is of interest that the prevalence of asymptomatic retinal emboli found in this study (1.4% for all emboli and 1.1% for cholesterol emboli only) is close to that for asymptomatic retinal cholesterol emboli in male veterans attending an eye clinic in Albuquerque, New Mexico (0.8%; 70/9000).1 The predominance of cholesterol (80%) to platelet-fibrin or calcific emboli found in this study is similar to that observed in a previous clinic series (76%).8
The predominance of retinal emboli cases in men (67%) found in our study is also very close to that found in clinic studies, including those in London (67%)15 and Sydney (66%).8 This male proportion matches that for retinal artery occlusion12 13 20 21 and the higher incidence rate of stroke among males.22 23 It also supports a common role for retinal emboli in both retinal artery occlusion and stroke.2 19
The associations with vascular disease may be underestimates because of the decreased survival of patients with retinal emboli24 and of patients with vascular disease, resulting in a survivor cohort effect. For example, those who die from stroke may have all had preceding retinal emboli, and those who survive their mild stroke may be less likely to have retinal emboli. Alternatively, those with retinal emboli may die quickly before they can develop a diagnosable vascular disease.
When either smoking or hypertension were included as covariates in an age-sex adjusted model assessing associations between retinal emboli and each vascular outcome, the odds ratios did not change substantially. This suggests that the association between retinal emboli and vascular outcomes is independent of both smoking and hypertension.
Approximately 35% of persons aged 60 years in this population had seen an ophthalmologist within the last 2 years. Eye doctors could use this opportunity to screen for retinal emboli during routine eye examinations. Referral for investigation of vascular status of those found with emboli will not waste resources in most cases and may reduce future vascular events with appropriate intervention. However, the optimal management of patients in whom asymptomatic retinal emboli are observed has not yet been determined.25 In one study, 18% of case subjects with asymptomatic emboli had internal or common carotid stenosis of >75%, with the stenosis worse on the side of the embolus in 70%.8 This suggests that carotid imaging may be a worthwhile investigation for some persons found with emboli.
An important limitation of any study examining embolus prevalence is the lack of reliable data documenting the average duration of emboli in the retinal circulation. In view of the known evanescent nature of some emboli,7 8 it is possible that in many persons, emboli from ulcerated atherosclerotic plaques may recur frequently. It is also likely that the reported prevalence is an underestimate.
Five-year follow-up of this cohort is at present being planned and will identify incident stroke and other vascular events. This will enable assessment of the association between the presence of asymptomatic retinal emboli and incident vascular disease.
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Acknowledgments |
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This study was supported by the Australian Department of Health and Human Services and the Save Sight Institute, University of Sydney (Australia).
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Footnotes |
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Reprint requests to Paul Mitchell, MD, FRACO, FRACS, FRCOphth, Department of Ophthalmology, University of Sydney, Hawkesbury Rd, Westmead, NSW, Australia, 2145.
Received June 3, 1996; revision received October 3, 1996; accepted October 3, 1996.
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References |
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