September 2007
Volume 48, Issue 9
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Clinical and Epidemiologic Research  |   September 2007
Retinopathy in Persons without Diabetes: The Los Angeles Latino Eye Study
Author Affiliations
  • Jennifer R. Chao
    From the Doheny Eye Institute and the Department of Ophthalmology, and the
  • Mei-Ying Lai
    Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California; and the
  • Stanley P. Azen
    Department of Preventive Medicine, Keck School of Medicine, University of Southern California, Los Angeles, California; and the
  • Ronald Klein
    Department of Ophthalmology and Visual Sciences, University of Wisconsin, School of Medicine and Public Health, Madison, Wisconsin.
  • Rohit Varma
    From the Doheny Eye Institute and the Department of Ophthalmology, and the
Investigative Ophthalmology & Visual Science September 2007, Vol.48, 4019-4025. doi:10.1167/iovs.07-0206
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      Jennifer R. Chao, Mei-Ying Lai, Stanley P. Azen, Ronald Klein, Rohit Varma, the Los Angeles Latino Eye Study Group; Retinopathy in Persons without Diabetes: The Los Angeles Latino Eye Study. Invest. Ophthalmol. Vis. Sci. 2007;48(9):4019-4025. doi: 10.1167/iovs.07-0206.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

purpose. To assess the prevalence of retinopathy and its relationship to sociodemographic and clinical characteristics in a population-based cohort of adult Latinos without diabetes mellitus.

methods. This was a population-based, cross-sectional study comprising 6357 Latinos, 40 years of age and older, from six census tracts in La Puente, Los Angeles, California. An interviewer-administered questionnaire assessed sociodemographic factors and medical history. Color fundus photographs were taken and graded in a masked manner according to a modified Airlie House Classification Grading System. Participants underwent a physical examination that included height, weight, blood pressure, random serum glucose, and glycosylated hemoglobin measurements. Univariate and multivariate logistic regression analyses were used to assess associations between sociodemographic and clinical characteristics and retinopathy in persons without diabetes.

results. The prevalence of retinopathy among individuals without diabetes in the Los Angeles Latino Eye Study (LALES) population was 6.6% (95% confidence interval 5.9%–7.4%). Stepwise logistic regression indicated that stage II hypertension (World Health Organization 2003 Guidelines), male gender, current smoking status, and obesity (body mass index ≥ 30 kg/m2) were associated with retinopathy (odds ratio = 4.3, 1.6, 1.4, and 1.3, respectively). No statistically significant associations with retinopathy were present for Native American ancestry; country of origin; health insurance status; history of cardiovascular disease; or history of aspirin, oral contraceptive, or hormone replacement therapy.

conclusions. The data suggest that the prevalence of retinopathy in nondiabetic individuals among Latinos of primarily Mexican ancestry is significant. Independent risk indicators for retinopathy in the study population are hypertension, male gender, current smoking status, and obesity.

Retinal microvascular lesions such as retinopathy (including microaneurysms, retinal hemorrhages, and hard exudates), focal arteriolar narrowing, and arteriovenous nicking have been reported in persons without diabetes in large population-based studies. 1 2 3 4 5 6 7 The prevalence of retinopathy in nondiabetic populations has been far greater than the 0.8% originally reported by the Framingham Eye Study, ranging instead from 7.8% to 9.8% in more recent reports. 2 4 8 9 10 11 Significant associations have been made between the presence of systemic disease and cardiovascular risk factors and the presence of retinal lesions and microvascular changes. Hypertension is the most widely reported risk factor of retinopathy in the nondiabetic population. 1 2 4 9 Other associated risk factors include high serum glucose levels, dyslipidemia, metabolic syndrome (hypertension, hyperglycemia, central obesity, and dyslipidemia), carotid artery intima–media thickening, and a history of coronary heart disease and stroke. 3 9 12 13  
Studies have been undertaken to investigate factors contributing to incident retinopathy as well, including blood glucose, hypertension, age, and abdominal obesity. 5 14 15 Separately, others have associated the presence of retinopathy in persons without diabetes with an increased incidence of stroke and stroke-related mortality, decreased renal function, hypertension, and diabetes. 16 17 18 19 20 Together, these findings support the theory that cardiovascular risk factors are significant in the development of nondiabetic retinopathy, and that retinopathy may, in turn, be an independent predictive marker of cardiovascular, cerebrovascular, and other diseases. 
Only one report of nondiabetic retinopathy in adult Latinos has been published to date 21 This study of adult Latinos living in Arizona reported a higher prevalence of nondiabetic retinopathy than that in other population-based studies and also reported a lack of association between hypertension and retinopathy in its population. The Los Angeles Latino Eye Study (LALES) is a large, population-based survey designed to evaluate the prevalence of ocular disease in adult Latinos from six census tracts in La Puente, California. One of its primary goals is to obtain an accurate estimate of the prevalence of disease that is generalizable to Mexican-Americans in the United States. 22 The purpose of our study was to assess the prevalence and relationship of retinopathy to sociodemographic and clinical characteristics in our population-based cohort of adult Latinos in Los Angeles without diabetes. 
Subjects and Methods
Design
The LALES design, methods, and baseline data have been described in detail elsewhere. 22 In brief, it was a 5-year, population-based, cross-sectional study designed to characterize visual impairment and prevalence of eye disease in Latinos. The study population consisted of self-identified Latinos, 40 years of age or older, living in one of six census tracts in the city of La Puente, Los Angeles, California. A total of 7789 eligible participants were identified, and 6142 participants completed the interview and in-clinic examination. All study procedures adhered to the tenets of the Declaration of Helsinki for research involving human subjects. Written proper consent was obtained from all study participants before data collection, and approval for conducting the study was obtained from the Los Angeles County/University of Southern California Medical Center Institutional Review Board. 
Clinical Procedures
Participants underwent interviews, ophthalmic examinations, and brief physical examinations. 22 Interview questions included inquiries regarding sociodemographic factors such as age, gender, country of birth, degree of acculturation, Native American ancestry, and possession of health insurance. Medical history queries included a history of atherosclerotic disease/myocardial infarction or stroke; use of aspirin, oral contraceptives, or hormone replacement therapy; and history of alcohol and tobacco use. During the ophthalmic examination, visual acuity was measured with the revised Early Treatment of Diabetic Retinopathy Study (ETDRS) charts 1, 2, and 3, and Lea symbol charts were used for the illiterate participants. Fundus photography was performed (TRC 50EX Retinal Camera; Topcon Corp. of America, Paramus, NJ, with Ektachrome 100 film; Eastman-Kodak, Rochester, NY). Three color fundus photographs were taken in all participants without diabetes: stereo fundus 30° photographs centered on the disc (Diabetic Retinopathy Study [DRS] standard field 1) and macula (DRS standard field 2) and a nonstereo photograph temporal to, but including the fovea (DRS standard field 3). 23 Additional fundus photographs were taken if any lesions were found outside these fields. The physical examination included weight, height, and blood pressure measurements. Participants removed excess clothing and shoes, and weight measurements were recorded to the nearest 0.1 kg and height to the nearest 0.5 cm. Blood pressure was measured with participants seated with both feet flat on the floor and after they had been quiet for at least 5 minutes. Their right arms were bared, supported, and positioned at heart level, and measurements were taken using a sphygmomanometer (Random Zero; Hawksley & Sons Ltd., West Sussex, UK) with a Baum cuff of appropriate size. Twenty minutes later, the blood pressure measurement was repeated. Random blood glucose and glycosylated hemoglobin were measured (B-Glucose Analyzer; Hemocue Inc., Lake Forest, CA, and the DCA 2000+ System; Bayer Corp., Tarrytown, NY, respectively). Other clinical procedures are described in detail elsewhere. 22  
Definition of Diabetes Mellitus
Participants were categorized into three groups: no diabetes, questionable diabetes, and definite diabetes. They were identified as being without diabetes mellitus if they had all the following: (1) no history of diabetes; (2) a hemoglobin A1c level less than 6.5%; and (3) random blood glucose less than 200 mg/dL. Participants who had all the following were considered to have questionable diabetes: (1) no history of diabetes; (2) hemoglobin A1c level of between 6.5% and 6.9%; and (3) random blood glucose less than 200 mg/dL. As described elsewhere, 24 participants were considered to have definite diabetes if they had any one of the following: (1) history of diabetes with treatment by oral hypoglycemic medications, insulin, or diet alone; (2) hemoglobin A1c of 7.0% or higher; or (3) random blood glucose of 200mg/dL or higher. 
Definition and Grading of Nondiabetic Retinopathy
Fundus photographs were used to determine the presence of retinopathy. Participants were defined as having retinopathy if any one of the following lesions were present in either eye: retinal microaneurysms, blot hemorrhages, cotton-wool spots, hard exudates, intraretinal microvascular abnormalities, venous beading, new retinal vessels, preretinal or vitreous hemorrhages, or macular edema. Graders identified lesions as “definite” if they were at least 90% certain the lesion was present and as “questionable” if they could make the determination with only 50% to 89% certainty. Retinopathy from an otherwise identifiable etiology including artery and vein occlusions, macroaneurysms, retinal cholesterol emboli, and epiretinal membranes were marked separately. Grading was performed at the Ocular Epidemiology Grading Center at the University of Wisconsin, Madison, Wisconsin, and the graders were masked to the diabetic status of the participants. 
Other Definitions
Hypertension was defined according to The Seventh Report of the Joint Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC7) criteria. The categories are normal, less than 120 mm Hg systolic blood pressure (SBP) and less than 80 mm Hg diastolic blood pressure (DBP); prehypertension, 120 to 139 mm Hg SBP or 80 to 89 mm Hg DBP; stage I hypertension, 140 to 159 mm Hg SBP or 90 to 99 mm Hg DBP; and stage II hypertension, ≥160 mm Hg SBP or ≥100 mm Hg DBP. 25 Definitions of sociodemographic factors are described in detail elsewhere. 26 Relevant to this study, alcohol use was defined as the following: nondrinker (less than 12 drinks in the past), ex-drinker (at least 12 drinks in the past with no alcoholic beverage use in the past year), partial drinker (fewer than 5 drinks of beer, wine, or hard liquor per day), and regular drinker (at least 5 drinks of beer, wine, or hard liquor per day). A participant was described as a nonsmoker (smoking no more than 100 cigarettes in the past), an ex-smoker (>100 cigarettes in the past and not currently smoking), or a current smoker (>100 cigarettes and smoking at the time of the questionnaire). Aspirin, oral contraceptives, and hormone replacement use was noted if participants reported taking the respective medications for at least the past 6 months. 
Statistical Analysis
Prevalence of nondiabetic retinopathy was calculated as the ratio of the number of participants without diabetes who have evidence of definite retinopathy in either eye to the total number of participants without diabetes. Univariate logistic regression was used to assess the association of sociodemographic and cardiovascular factors with retinopathy. Multiple logistic regression analyses with forward step-wise selection were used to evaluate the independent relationship of significant variables (using a P ≤ 0.5 criterion) with retinopathy. All confidence intervals (CIs) presented are 95%, and all analyses were conducted at a less than 0.05 significance level (Statistical Analysis System 8; SAS Institute Inc., Cary, NC). 
Results
Description of Study Cohort
Figure 1outlines our study cohort. Of the 7789 eligible participants identified in LALES, 6131 completed the interview and in-clinic examination. Those with definite diabetes (n = 1263) and questionable diabetes (n = 194) were excluded, and 4674 participants without diabetes remained. Of the latter group without diabetes, 4568 participants had gradable stereoscopic retinal photographs, and 4057 without retinopathy in either eye were excluded. In addition, participants with questionable retinopathy or retinopathy of otherwise identifiable causes (see the Methods section for definitions) were excluded. This resulted in 287 participants without diabetes but with evidence of definite retinopathy in either eye, not attributable to an otherwise identifiable retinal etiology (such as artery and vein occlusions, macroaneurysms, retinal cholesterol emboli, and epiretinal membranes). 
Prevalence and Characteristics of Retinopathy
The prevalence of retinopathy in our study was 6.6%, where the numerator was the number of participants with definite retinopathy (n = 287) and the denominator the number of participants without diabetes who had gradable fundus photographs, excluding those with questionable retinopathy and retinopathy of identifiable etiology (n = 4344). With the exclusion of participants with questionable diabetes, our prevalence should reflect retinopathy in only the nondiabetic population (i.e., nondiabetic retinopathy). This was supported by the findings that random blood glucose and hemoglobin A1c levels were not associated with retinopathy, as defined in our study, by univariate analysis (Table 1)
The prevalence of specific retinal lesions present in participants without diabetes is illustrated in Table 2 . The most common lesions were retinal microaneurysms (n = 257, 89.5%), followed by cotton wool spots (n = 27, 9.4%), intraretinal microvascular abnormalities (n = 9, 3.1%) and hard exudates (n = 9, 3.1%). In addition, of the 287 individuals with any retinopathy in either eye, 268 (93.4%) had retinal lesions in only one eye. Most of the retinal lesions including microaneurysms, cotton wool spots, intraretinal microvascular abnormalities, and hard exudates were more likely to be unilateral than bilateral. 
Association of Risk Indicators
Univariate associations of retinopathy and sociodemographic and lifestyle factors are presented in Table 3 . Male gender was a significant risk factor for retinopathy (odds ratio [OR] = 1.6, P = 0.0002). Lifestyle factors (e.g., history of smoking status and alcohol use) were significant risk factors by univariate analysis (OR = 1.5, P = 0.02 and OR = 1.5, P = 0.007, respectively). Overall, older age was not a significant risk factor for retinopathy; however, there was a significant trend across the five age groups by the Cochran-Armitage trend test (P = 0.08). We did not detect a statistically significant association of retinopathy with country of birth, acculturation status, Native American ancestry, or health insurance in our univariate analysis. 
The association of cardiovascular risk factors and presence of retinopathy in nondiabetic individuals by univariate analysis is presented in Table 4 . Hypertension, as defined by the World Health Organization 2003 Guidelines, was a significant risk factor for retinopathy. In our study, an individual with stage II hypertension was 4.5 times more likely to have retinopathy than were normotensive individuals (P < 0.0001). Body mass index at the level of clinical obesity (≥30 k/m2) was also a significant risk factor for retinopathy (OR = 1.3, P = 0.04). Waist-hip ratio was not a significant risk factor by univariate analysis (data not shown). In addition, a history of myocardial infarction and stroke did not appear to be associated risk factors, nor did the use of aspirin, oral contraceptives, or hormone replacement therapy. 
Table 5presents the results of the stepwise logistic regression analyses. The presence of retinopathy in nondiabetic individuals was independently associated with hypertension (primary risk indicator), male gender (secondary risk indicator), current smoking status (tertiary risk indicator), and elevated body mass index (quaternary). In the step-wise analyses, age and history of alcohol consumption were not independently associated with retinopathy. 
Discussion
This study describes the prevalence and risk factors associated with nondiabetic retinopathy in the LALES, a population-based study of eye disease in Latinos of primarily Mexican ancestry. Excluding participants with definite and questionable diabetes as well as those with known artery and vein occlusions, macroaneurysms, retinal cholesterol emboli, or epiretinal membranes, we found a 6.6% prevalence of retinopathy in persons without diabetes. Univariate analysis confirmed the lack of association between random blood glucose and hemoglobin A1c levels to retinopathy in this group. Our finding was similar to that previously reported in the Beaver Dam Eye Study, Cardiovascular Health Study, Blue Mountains Eye Study, Hoorn Study, and the Diabetes Prevention Program Research Group, which reported prevalences ranging from 7.8% to 9.8% in their nondiabetic populations. 2 4 9 10 11 Notably, our result differs from that of Proyecto VER which reported the prevalence of retinopathy in nondiabetic Mexican-American individuals to be significantly higher at 15%. 21 This discrepancy may have been due to the use of different fundus fields in the grading of retinopathy between our studies (DRS standard fields 1, 2, and 3 in our study and DRS fields 1, 2, and 4 in Proyecto VER). In addition, there may be differences in population characteristics independent of ethnicity. 
Although certain systemic risk factors for vascular disease including hypertension, male gender, current smoking status, and obesity were significantly and independently associated with nondiabetic retinopathy by univariate and stepwise multivariate logistic regression analysis, other factors, such as history of atherosclerotic disease, myocardial infarction, stroke, and history of aspirin, oral contraceptive, or hormone replacement therapy were not significantly associated. In contrast to the Proyecto VER finding, which showed a lack of association between hypertension status and retinopathy, 21 our finding that hypertension is significantly associated with retinopathy is consistent with that of several other studies. 1 2 4 10 Male gender was also significantly associated with prevalent retinopathy both by univariate and stepwise logistic regression analysis. The Beaver Dam Eye Study reported that after adjustment for age, men had a significantly higher prevalence of retinopathy than did women, 4 but the Hoorn study, which did not control for age, reported that gender was not a significant risk factor in prevalent retinopathy. 10 Notably, both subsequent incidence studies report no statistically significant male gender risk after adjustment for age. 5 15 Incident studies in our population may be needed to elucidate this association further. 
Prior studies have adjusted for smoking status in the multivariate analysis of risk factors of retinopathy, 1 13 but we found that current smoking status is itself independently associated with prevalent retinopathy in our population. The Hoorn Study of Incident Retinopathy showed that cigarette smokers and ex-smokers had higher but nonsignificant odds ratios compared with those of individuals who had never smoked. 5 10 It is possible that their inclusion of ex-smokers with current smokers diluted the significance of the difference in the comparison to current smokers. 
Although we did not find a significant association between older age and prevalent retinopathy, there was a significant trend across increasing age groups. This lack of significant association was consistent with findings from some studies of prevalent and incident retinopathy 5 10 15 ; however, the 5-year incidence study in the Blue Mountains Eye Study population reported a significant association with increasing age. 14 Notably, age was a significant risk factor for arteriolar narrowing and arteriovenous nicking. 15 Other factors thought to have an effect on retinal vasculature, such as aspirin, oral contraceptive, and hormone replacement use were investigated. In a recent study, regular aspirin use has been associated with wider retinal arteriolar diameter, 27 but we found no significant association with aspirin and retinopathy in our population. Further evaluation of the affects of age and medication on retinal microvasculature is warranted. 
One of the most clinically useful implications to arise from these population studies is the association of retinopathy with systemic diseases, including coronary heart disease, incident congestive heart failure, clinical stroke and stroke mortality, nephropathy, carotid artery thickening, and incident diabetes. 9 16 17 18 19 28 29 Of note, we did not find a significant association with patient-reported histories of atherosclerotic disease, myocardial infarction, or stroke, but objective measurements such as ultrasound determination of carotid artery intima–media thickening or medical chart documentation of disease may be needed to detect the subclinical or clinical cardiovascular disease in our population and its relationship to retinopathy. In addition, it will be useful to examine incident cardiovascular disease and its relationship to previously documented retinopathy. 
To characterize better the type of retinopathy observed in our study, we reported the frequency of specific retinal lesions and their laterality. The most common lesions were microaneurysms and retinal hemorrhages, and most were unilateral. This is consistent with the Beaver Dam Eye Study findings that when retinopathy was present, it was more likely to be bilateral (60.1%) in persons with known diabetes mellitus compared with those without diabetes (9.5%, P < 0.0001). 30 There is evidence that nondiabetic retinal lesions are more ephemeral than are diabetic retinal lesions. In the Blue Mountains Eye Study, although there was a 10% incidence of nondiabetic retinopathy over 5 years, there was also a 72% regression in baseline lesions. 14 Thus, given the cross-sectional nature of this report, it would be important to examine the progression and profile of our lesions in a follow-up incidence study. In addition, it would be useful to study the correlation between the incidence of retinopathy and the development of visual impairment, to identify visually significant and possibly treatable retinal lesions. 
A limitation to our study is the use of random blood glucose and hemoglobin A1c levels, rather than oral glucose tolerance testing, in determining the definition of diabetes. A recent study by the Diabetes Prevention Program used oral glucose tolerance testing to identify a 7.9% prevalence of retinopathy in participants with subdiabetic levels of glycemia. 11 It is likely that this subdiabetic cohort was included in our study population, although they were not specifically identified by oral glucose tolerance testing. However, as noted in prior studies, a hemoglobin A1c level of 7% or higher has good sensitivity and specificity when compared with results of oral glucose tolerance testing. 24 31 Definitions similar to ours were used by other large population-based studies, including the Beaver Dam Eye Study and Proyecto VER, allowing us to compare our findings accordingly. 4 21 Another limitation is the possible misclassification of subtle retinal lesions. Although we were careful to exclude retinal lesions of identifiable etiologies, including artery and vein occlusions, macroaneurysms, retinal cholesterol emboli, and epiretinal membranes, it is possible that graders could have missed small branched vein occlusions that appear clinically similar to nondiabetic retinopathy. Finally, because we graded our retinopathy based on the three retinal field photographs described earlier, we cannot exclude the possibility that there were lesions outside of these fields that were not included in our retinopathy classification. 
In conclusion, the results of this study demonstrate that the prevalence of retinopathy in nondiabetic participants in the LALES is similar to that reported by other large population-based studies. We report that hypertension, male gender, history of current smoking status, and greater body mass index are significantly associated with prevalent retinopathy. In addition, we elucidate the unilateral nature of retinal lesions found in nondiabetic retinopathy. Long-term follow-up studies are needed to determine the visual and systemic significance of nondiabetic retinopathy in the LALES population. 
Appendix 1
The Los Angeles Latino Eye Study Group
University of Southern California, Los Angeles, CA (study site): Rohit Varma, Sylvia H. Paz, LiVina Abbott, Stanley P. Azen, Lupe Cisneros, Elizabeth Corona, Carolina Cuestas, Denise R. Globe, Sora Hahn, Mei Lai, George Martinez, Susan Preston-Martin, Ronald E. Smith, Mina Torres, Natalia Uribe, Jennifer Wong, Joanne Wu, and Myrna Zuniga. 
Battelle Survey Research Center, St. Louis, MO: Sonia Chico, Lisa John, Michael Preciado, and Karen Tucker. 
Ocular Epidemiology Grading Center, University of Wisconsin, Madison, WI: Ronald Klein. 
 
Figure 1.
 
Profile of the study cohort. *Participants with definite diabetes (n = 1263) and questionable diabetes (n = 194). †Retinopathy from an otherwise identifiable retinal etiology, including artery and vein occlusions, macroaneurysms, retinal cholesterol emboli, and epiretinal membranes, are marked separately.
Figure 1.
 
Profile of the study cohort. *Participants with definite diabetes (n = 1263) and questionable diabetes (n = 194). †Retinopathy from an otherwise identifiable retinal etiology, including artery and vein occlusions, macroaneurysms, retinal cholesterol emboli, and epiretinal membranes, are marked separately.
Table 1.
 
Association between Glycemic Indices and Retinopathy in Persons without Diabetes
Table 1.
 
Association between Glycemic Indices and Retinopathy in Persons without Diabetes
Risk Indicator No Retinopathy (n = 4057) Retinopathy (n = 287) Odds Ratio (95% CI) P
Random blood glucose (<200 mg/dL) 0.52
 ≤33% Tertile 1270 (92.8%) 98 (7.2%) 1.0
 34%–65% Tertile 1351 (93.5%) 94 (6.5%) 1.1 (0.8–1.4)
 ≥66% Tertile 1414 (93.9%) 92 (6.1%) 1.2 (0.9–1.6)
HbA1c (<7.0) 0.76
 ≤33% Tertile 1086 (93.0%) 82 (7.0%) 1.0
 34%–65% Tertile 1380 (93.7%) 93 (6.3%) 1.0 (0.7–1.3)
 ≥66% Tertile 1571 (93.5%) 110 (6.5%) 1.1 (0.8–1.5)
Table 2.
 
Prevalence of Clinical Characteristics of Retinopathy in Persons without Diabetes
Table 2.
 
Prevalence of Clinical Characteristics of Retinopathy in Persons without Diabetes
Clinical Characteristic All (n = 287) Unilateral (n = 268) Bilateral (n = 19)
Microaneurysms 257 (89.5%) 240 (83.6%) 17 (5.9%)
Retinal hemorrhages 2 (0.7%) 2 (0.3%) 0
Hard exudates 9 (3.1%) 8 (2.8%) 1 (0.4%)
Cotton wool spots 27 (9.4%) 27 (9.4%) 0
Venous loops 6 (2.1%) 6 (0.1%) 0
Intraretinal microvascular abnormalities 9 (3.1%) 8 (2.8%) 1 (0.4%)
Venous beading 0 0 0
New vessels on optic disc 0 0 0
New retinal vessels (neovascularization elsewhere) 0 0 0
Preretinal/vitreous hemorrhage 0 0 0
Any macular edema 3 (1.0%) 1 (0.4%) 2 (0.4%)
Clinically significant macular edema (CSME) 1 (0.3%) 0 1 (0.4%)
Table 3.
 
Univariate Associations between Sociodemographic Characteristics and Retinopathy among LALES Participants
Table 3.
 
Univariate Associations between Sociodemographic Characteristics and Retinopathy among LALES Participants
Risk Indicator No Retinopathy (n = 4057) Retinopathy (n = 287) Odds Ratio (95% CI) P
Age (y) 0.18
 40–49 1808 (94.1%) 113 (5.9%) 1.0
 50–59 1201 (93.3%) 86 (6.7%) 1.1 (0.9–1.5)
 60–69 688 (92.8%) 53 (7.2%) 1.2 (0.9–1.7)
 70–79 291 (91.8%) 26 (8.2%) 1.4 (0.9–2.2)
 80+ 69 (88.5%) 9 (11.5%) 2.1 (1.0–4.3)
Gender 0.0002
 Female 2421 (94.6%) 139 (5.4%) 1.0
 Male 1636 (91.7%) 148 (8.3%) 1.6 (1.2–2.0)
Country of birth 0.25
 United States 872 (92.6%) 70 (7.4%) 1.0
 Other 3185 (93.6%) 217 (6.4%) 1.2 (0.9–1.6)
Acculturation score 0.82
 Low (<2.3) 937 (93.2%) 68 (6.8%) 1.0
 High (≥2.3) 3120 (93.4%) 219 (6.6%) 1.0 (0.8–1.4)
Native American ancestry 0.43
 Yes 197 (94.7%) 11 (5.3%) 1.0
 No 3860 (93.3%) 276 (6.7%) 0.8 (0.4–1.5)
Health insurance 0.09
 Yes 2551 (92.9%) 195 (7.1%) 1.0
 No 1500 (94.2%) 92 (5.8%) 1.2 (1.0–1.6)
Smoking status 0.02
 Non-/ex-smoker 3489 (93.8%) 232 (6.5%) 1.0
 Current smoker 555 (91.1%) 54 (8.2%) 1.5 (1.1–2.0)
Alcohol use 0.007
 Non/partial/ex 3509 (93.8%) 232 (6.2%) 1.0
 Regular/heavy 534 (90.8%) 54 (9.2%) 1.5 (1.1–2.1)
Table 4.
 
Univariate Associations between Cardiovascular Risk Factors and Retinopathy among LALES Participants
Table 4.
 
Univariate Associations between Cardiovascular Risk Factors and Retinopathy among LALES Participants
Risk Indicator No Retinopathy (n = 4057) Retinopathy (n = 287) Odds Ratio (95% CI) P
Hypertension (JNC7 Classification) <0.0001
 Normotension/low (SBP<120; DBP<80) 1888 (95.3%) 93 (4.7%) 1.0
 Prehypertension (SBP 120–139 or DBP 80–89) 4808 (92.4%) 116 (7.6%) 1.7 (1.3–2.2)
 Stage I (SBP 140–159 or DBP 90–99) 596 (93.3%) 43 (6.7%) 1.5 (1.0–2.1)
 Stage II (SBP ≥160 or DBP ≥100) 159 (82.0%) 35 (18.0%) 4.5 (2.9–6.8)
Body mass index (kg/m2) 0.04
 <30 kg/m2 2128 (94.2%) 131 (5.8%) 1.0
 ≥30 kg/m2 1893 (92.6%) 151 (7.4%) 1.3 (1.0–1.7)
History of atherosclerotic disease or MI 0.32
 No 3842 (93.5%) 266 (6.5%) 1.0
 Yes 213 (91.8%) 19 (8.2%) 1.3 (0.8–2.1)
History of stroke 0.30
 No 3966 (93.5%) 278 (6.5%) 1.0
 Yes 89 (90.8%) 9 (9.2%) 1.4 (0.7–2.9)
Aspirin use 0.93
 No 2091 (93.5%) 146 (6.5%) 1.0
 Yes 224 (93.3%) 16 (6.7%) 1.0 (0.6–1.7)
Oral contraceptives* 0.09
 No 946 (93.7%) 64 (6.3%) 1.0
 Yes 423 (95.9%) 48 (4.1%) 0.6 (0.4–1.1)
Hormone replacement therapy* 0.09
 No 1107 (94.9%) 60 (5.1%) 1.0
 Yes 262 (92.2%) 22 (7.8%) 1.5 (0.9–2.6)
Table 5.
 
Stepwise Logistic Regression Analysis of Clinical Predictors for Retinopathy in LALES Participants
Table 5.
 
Stepwise Logistic Regression Analysis of Clinical Predictors for Retinopathy in LALES Participants
Risk Indicator Odds Ratio 95% CI P
Hypertension (WHO 2003 Guidelines) <0.0001
 Normotensive/low (SBP<120 and DBP <80) 1.0
 Prehypertension (SBP 120–129 or DBP 80–89) 1.6 (1.2–2.1)
 Stage I (SBP 140–159 or DBP 90–99) 1.4 (1.0–2.0)
 Stage II (SBP ≥160 or DBP ≥100) 4.3 (2.8–6.6)
Gender 0.0006
 Female 1.0
 Male 1.6 (1.2–2.0)
Smoking status 0.028
 Non- and ex-smoker 1.0
 Current smoker 1.4 (1.0–2.0)
Body mass index (kg/m2) 0.045
 <30 kg/m2 1.0
 ≥30 kg/m2 1.3 (1.0–1.7)
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Figure 1.
 
Profile of the study cohort. *Participants with definite diabetes (n = 1263) and questionable diabetes (n = 194). †Retinopathy from an otherwise identifiable retinal etiology, including artery and vein occlusions, macroaneurysms, retinal cholesterol emboli, and epiretinal membranes, are marked separately.
Figure 1.
 
Profile of the study cohort. *Participants with definite diabetes (n = 1263) and questionable diabetes (n = 194). †Retinopathy from an otherwise identifiable retinal etiology, including artery and vein occlusions, macroaneurysms, retinal cholesterol emboli, and epiretinal membranes, are marked separately.
Table 1.
 
Association between Glycemic Indices and Retinopathy in Persons without Diabetes
Table 1.
 
Association between Glycemic Indices and Retinopathy in Persons without Diabetes
Risk Indicator No Retinopathy (n = 4057) Retinopathy (n = 287) Odds Ratio (95% CI) P
Random blood glucose (<200 mg/dL) 0.52
 ≤33% Tertile 1270 (92.8%) 98 (7.2%) 1.0
 34%–65% Tertile 1351 (93.5%) 94 (6.5%) 1.1 (0.8–1.4)
 ≥66% Tertile 1414 (93.9%) 92 (6.1%) 1.2 (0.9–1.6)
HbA1c (<7.0) 0.76
 ≤33% Tertile 1086 (93.0%) 82 (7.0%) 1.0
 34%–65% Tertile 1380 (93.7%) 93 (6.3%) 1.0 (0.7–1.3)
 ≥66% Tertile 1571 (93.5%) 110 (6.5%) 1.1 (0.8–1.5)
Table 2.
 
Prevalence of Clinical Characteristics of Retinopathy in Persons without Diabetes
Table 2.
 
Prevalence of Clinical Characteristics of Retinopathy in Persons without Diabetes
Clinical Characteristic All (n = 287) Unilateral (n = 268) Bilateral (n = 19)
Microaneurysms 257 (89.5%) 240 (83.6%) 17 (5.9%)
Retinal hemorrhages 2 (0.7%) 2 (0.3%) 0
Hard exudates 9 (3.1%) 8 (2.8%) 1 (0.4%)
Cotton wool spots 27 (9.4%) 27 (9.4%) 0
Venous loops 6 (2.1%) 6 (0.1%) 0
Intraretinal microvascular abnormalities 9 (3.1%) 8 (2.8%) 1 (0.4%)
Venous beading 0 0 0
New vessels on optic disc 0 0 0
New retinal vessels (neovascularization elsewhere) 0 0 0
Preretinal/vitreous hemorrhage 0 0 0
Any macular edema 3 (1.0%) 1 (0.4%) 2 (0.4%)
Clinically significant macular edema (CSME) 1 (0.3%) 0 1 (0.4%)
Table 3.
 
Univariate Associations between Sociodemographic Characteristics and Retinopathy among LALES Participants
Table 3.
 
Univariate Associations between Sociodemographic Characteristics and Retinopathy among LALES Participants
Risk Indicator No Retinopathy (n = 4057) Retinopathy (n = 287) Odds Ratio (95% CI) P
Age (y) 0.18
 40–49 1808 (94.1%) 113 (5.9%) 1.0
 50–59 1201 (93.3%) 86 (6.7%) 1.1 (0.9–1.5)
 60–69 688 (92.8%) 53 (7.2%) 1.2 (0.9–1.7)
 70–79 291 (91.8%) 26 (8.2%) 1.4 (0.9–2.2)
 80+ 69 (88.5%) 9 (11.5%) 2.1 (1.0–4.3)
Gender 0.0002
 Female 2421 (94.6%) 139 (5.4%) 1.0
 Male 1636 (91.7%) 148 (8.3%) 1.6 (1.2–2.0)
Country of birth 0.25
 United States 872 (92.6%) 70 (7.4%) 1.0
 Other 3185 (93.6%) 217 (6.4%) 1.2 (0.9–1.6)
Acculturation score 0.82
 Low (<2.3) 937 (93.2%) 68 (6.8%) 1.0
 High (≥2.3) 3120 (93.4%) 219 (6.6%) 1.0 (0.8–1.4)
Native American ancestry 0.43
 Yes 197 (94.7%) 11 (5.3%) 1.0
 No 3860 (93.3%) 276 (6.7%) 0.8 (0.4–1.5)
Health insurance 0.09
 Yes 2551 (92.9%) 195 (7.1%) 1.0
 No 1500 (94.2%) 92 (5.8%) 1.2 (1.0–1.6)
Smoking status 0.02
 Non-/ex-smoker 3489 (93.8%) 232 (6.5%) 1.0
 Current smoker 555 (91.1%) 54 (8.2%) 1.5 (1.1–2.0)
Alcohol use 0.007
 Non/partial/ex 3509 (93.8%) 232 (6.2%) 1.0
 Regular/heavy 534 (90.8%) 54 (9.2%) 1.5 (1.1–2.1)
Table 4.
 
Univariate Associations between Cardiovascular Risk Factors and Retinopathy among LALES Participants
Table 4.
 
Univariate Associations between Cardiovascular Risk Factors and Retinopathy among LALES Participants
Risk Indicator No Retinopathy (n = 4057) Retinopathy (n = 287) Odds Ratio (95% CI) P
Hypertension (JNC7 Classification) <0.0001
 Normotension/low (SBP<120; DBP<80) 1888 (95.3%) 93 (4.7%) 1.0
 Prehypertension (SBP 120–139 or DBP 80–89) 4808 (92.4%) 116 (7.6%) 1.7 (1.3–2.2)
 Stage I (SBP 140–159 or DBP 90–99) 596 (93.3%) 43 (6.7%) 1.5 (1.0–2.1)
 Stage II (SBP ≥160 or DBP ≥100) 159 (82.0%) 35 (18.0%) 4.5 (2.9–6.8)
Body mass index (kg/m2) 0.04
 <30 kg/m2 2128 (94.2%) 131 (5.8%) 1.0
 ≥30 kg/m2 1893 (92.6%) 151 (7.4%) 1.3 (1.0–1.7)
History of atherosclerotic disease or MI 0.32
 No 3842 (93.5%) 266 (6.5%) 1.0
 Yes 213 (91.8%) 19 (8.2%) 1.3 (0.8–2.1)
History of stroke 0.30
 No 3966 (93.5%) 278 (6.5%) 1.0
 Yes 89 (90.8%) 9 (9.2%) 1.4 (0.7–2.9)
Aspirin use 0.93
 No 2091 (93.5%) 146 (6.5%) 1.0
 Yes 224 (93.3%) 16 (6.7%) 1.0 (0.6–1.7)
Oral contraceptives* 0.09
 No 946 (93.7%) 64 (6.3%) 1.0
 Yes 423 (95.9%) 48 (4.1%) 0.6 (0.4–1.1)
Hormone replacement therapy* 0.09
 No 1107 (94.9%) 60 (5.1%) 1.0
 Yes 262 (92.2%) 22 (7.8%) 1.5 (0.9–2.6)
Table 5.
 
Stepwise Logistic Regression Analysis of Clinical Predictors for Retinopathy in LALES Participants
Table 5.
 
Stepwise Logistic Regression Analysis of Clinical Predictors for Retinopathy in LALES Participants
Risk Indicator Odds Ratio 95% CI P
Hypertension (WHO 2003 Guidelines) <0.0001
 Normotensive/low (SBP<120 and DBP <80) 1.0
 Prehypertension (SBP 120–129 or DBP 80–89) 1.6 (1.2–2.1)
 Stage I (SBP 140–159 or DBP 90–99) 1.4 (1.0–2.0)
 Stage II (SBP ≥160 or DBP ≥100) 4.3 (2.8–6.6)
Gender 0.0006
 Female 1.0
 Male 1.6 (1.2–2.0)
Smoking status 0.028
 Non- and ex-smoker 1.0
 Current smoker 1.4 (1.0–2.0)
Body mass index (kg/m2) 0.045
 <30 kg/m2 1.0
 ≥30 kg/m2 1.3 (1.0–1.7)
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