Purpose
To assess the association between ocular factors and age-related macular degeneration (AMD) in Latinos.
Design
Population-based, cross-sectional study of 6357 self-identified Latinos aged 40 years and older.
Methods
Ophthalmic examination included subjective refraction, measurement of axial length, evaluation of iris color, Lens Opacities Classification System II (LOCS II) grading of cataracts, and stereoscopic macular photographs for AMD lesions. Generalized estimating equation analysis incorporated data from both eyes to estimate odds ratios (OR) adjusted for covariates.
Results
After controlling for confounders (age, gender, and smoking), prior cataract surgery was associated with advanced AMD (OR, 2.8; 95% CI, 1.01, 7.8), increased retinal pigment (OR, 1.6; 95% CI, 1.02, 1.5), and retinal pigment epithelial depigmentation (OR, 2.2; 95% CI, 1.1, 4.4). The presence of any lens opacity was associated with soft drusen (OR, 1.2; 95% CI, 1.002, 1.5). Longer axial length (per mm) was associated with decreased odds of soft drusen, increased retinal pigment, and geographic atrophy (GA) (ORs, 0.8 [95% CI, 0.7, 0.9], 0.8 [95% CI, 0.7, 0.9], 0.7 [95% CI, 0.5, 0.9], respectively). Myopia was inversely associated with soft drusen (OR, 0.8; 95% CI, 0.7, 0.99). Lighter-colored irises were associated with GA (OR, 5.0; 95% CI, 1.0, 25.3).
Conclusions
Cross-sectional associations of ocular factors such as cataract, cataract surgery, and refractive errors with early AMD lesions found in Latinos are consistent with those in non-Hispanic Whites. Additionally, prior cataract surgery was associated with advanced AMD.
Age-related macular degeneration (AMD) is the leading cause of irreversible blindness and visual impairment in the United States and other industrialized countries. Previous population-based studies among Caucasians have identified possible associations of various ocular factors with AMD. These include hyperopia with both early and advanced AMD; cataracts with early AMD; and iris color with both early and advanced AMD. Pooled data from the Blue Mountains and Beaver Dam eye studies found an association between cataract surgery and advanced AMD, as too did pooled data from the Salisbury Eye Evaluation Survey, Proyecto VER, and the Baltimore Eye Survey.
This paper aims to examine the association of various ocular risk factors with early and advanced AMD lesions among Latinos, primarily Mexican Americans living in La Puente, California, USA.
Methods
The Los Angeles Latino Eye Study (LALES) is a population-based, cross-sectional study of adult Latinos aged 40 years and older, living in 6 census tracts in the city of La Puente, California. This city was chosen because of its large, stable Latino population and its similar socioeconomic demographic profile to that of Latinos in the United States. The survey design and methods have been reported in detail elsewhere. Briefly, after written, informed consent was obtained, a detailed in-home interview was conducted to determine demographic factors, ocular and medical histories, various risk factors, and access to medical and ocular care. Trained ophthalmologists and technicians used standardized protocols in performing a comprehensive ocular examination, which included 30-degree stereoscopic color fundus photographs of Diabetic Retinopathy Study fields 1 and 2 and a modified field 3 on all participants.
Iris color was graded as blue, gray, hazel, or brown using the Iris Color Classification System, 1990. Lenses were examined at the slit lamp under maximum dilation with tropicamide 1% and phenylephrine 2.5%. The Lens Opacities Classification System II (LOCS II) was used to categorize lens opacities into 5 nuclear, 5 posterior subcapsular (PSC), and 7 cortical grades of increasing severity, according to photographic standards. Lens opacities were considered to be present if a LOCS II grade of 2 or more was present. Mixed cataract was defined as the presence of more than 1 type of lens opacity (nuclear, PSC, or cortical) with a LOCS score of ≥2 in any area. Reproducibility of LOCS II grading was measured by proportionally weighted kappa statistics for agreement by an independent replicate on 50 participants every 5 to 6 months. Results showed good inter-grader agreement for all opacity types (weighted κ = 0.7–0.8).
Visual acuity for each LALES participant was measured for each eye. Automated refraction was performed (using the Humphrey Autorefractor Model 599; Carl Zeiss Meditec, Dublin, California, USA), followed by subjective refraction using standardized protocols. Spherical refractive error was measured to the closest 0.25 diopters (D). Cylinder power was measured to the closest 0.25 D. The spherical equivalent (SE; sphere plus half cylinder) was used in all analyses as the measure of refractive error. Axial length was estimated using the average of 3 measurements obtained using an A-scan ultrasound (Ultrasonic A-SCAN pachymeter, Exton, Pennsylvania, USA).
A modified Wisconsin age-related maculopathy grading system was used to grade individual age-related macular degeneration lesions by masked graders at the Wisconsin Ocular Epidemiology Grading Center. A more detailed description about all grading procedures and definitions has been presented elsewhere. Early AMD was defined as the absence of signs of advanced AMD and the presence of 1) soft indistinct or reticular drusen or 2) hard distinct or soft distinct drusen with pigmentary abnormalities (retinal pigment epithelium [RPE] depigmentation or increased retinal pigment). Advanced AMD was defined as the presence of 1) geographic atrophy (GA) or 2) exudative AMD. Signs of exudative AMD were retinal pigment epithelial detachment or serous detachment of the sensory retina, subretinal or sub-RPE hemorrhages, and subretinal fibrous scars. Geographic atrophy was defined as a circular discrete area (of at least 175 μm in diameter) of retinal depigmentation with visible choroidal vessels, in the absence of exudative AMD.
Data and Statistical Analyses
Data were entered into an automated database using Microsoft Office Access 1998, with internal automated quality control checks. The Statistical Analysis System (version 8; SAS Institute Inc, Cary, North Carolina, USA) was used for tabulations and statistical analyses. All odds ratios (OR) were age- and sex-adjusted and all confidence intervals presented are 95%. Inter- and intra-grader agreement was assessed using the quadratic weighted kappa statistic on a random subset of 30 eyes. There was moderate to excellent inter- and intra-observer agreement (κ = 0.8–1.0 for early AMD, exudative AMD, and geographic atrophy and κ = 0.4–0.9 for individual early AMD lesions). Logistic regression was performed using each AMD lesion as a dependent variable. Generalized estimating equation (GEE) analyses were performed to assess associations of ocular variables with AMD.
Results
Of the 7789 eligible self-identified Latinos, 6870 individuals (88%) completed an in-home interview and 6357 (82%) participated in a clinical examination. A total of 5875 participants with complete clinical examination, biometry, and refractive status were included in the analyses. The mean age of participants was 54.6 years (SD ± 10.7) and 58.4% were female. Cataract was present in 986 participants (16.8%) and 193 or 3.3% had previously had cataract surgery ( Table 1 ). After adjusting for age, sex, and history of smoking, there was a statistically significant association of any of the 3 types of lens opacity combined with soft indistinct drusen. Prior cataract surgery increased the odds of increased retinal pigment, RPE depigmentation, and advanced AMD ( Table 2 ).
| No AMD (N=10 681) | Early AMD (N=664) | Soft Indistinct Drusen (N=421) | Increased Retinal Pigment (N=381) | RPE Depigmentation (N=153) | Any Advanced AMD (N=36) | Geographic Atrophy (N=13) | Exudative AMD (N=23) | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Characteristic | N | % | N | % | N | % | N | % | N | % | N | % | N | % | N | % |
| Cataract | ||||||||||||||||
| Any cataract | 1394 | 13.1 | 127 | 19.1 | 105 | 26.8 | 65 | 17.1 | 27 | 17.6 | 13 | 36.1 | 5 | 38.5 | 8 | 34.8 |
| Nuclear sclerosis | 617 | 5.8 | 68 | 10.2 | 58 | 14.8 | 37 | 9.7 | 17 | 11.1 | 13 | 36.1 | 5 | 38.5 | 8 | 34.8 |
| Posterior subcapsular | 141 | 1.3 | 17 | 2.6 | 15 | 2.3 | 9 | 2.4 | 1 | 0.7 | 3 | 8.3 | 0 | 0.0 | 3 | 13.0 |
| Cortical cataract | 1018 | 9.5 | 92 | 13.9 | 74 | 18.9 | 49 | 12.9 | 20 | 13.1 | 7 | 19.4 | 1 | 7.7 | 6 | 26.1 |
| Mixed | 350 | 3.3 | 46 | 6.9 | 40 | 10.2 | 28 | 7.3 | 11 | 7.2 | 8 | 22.2 | 1 | 7.7 | 7 | 30.4 |
| Cataract surgery | 216 | 2.0 | 43 | 6.5 | 39 | 9.3 | 25 | 6.6 | 14 | 9.2 | 11 | 30.6 | 4 | 30.8 | 7 | 30.4 |
| Refractive error | ||||||||||||||||
| emetropia (−0.5 to 0.5) | 5163 | 48.3 | 261 | 39.3 | 154 | 37.1 | 151 | 39.6 | 63 | 41.2 | 7 | 19.4 | 3 | 23.1 | 4 | 17.4 |
| hyperopia mild (+0.5 to +3) | 3004 | 28.1 | 230 | 34.6 | 138 | 5.1 | 141 | 37.0 | 44 | 28.8 | 19 | 52.8 | 7 | 53.8 | 12 | 52.2 |
| hyperopia mod/high (>+3) | 389 | 3.6 | 31 | 4.7 | 21 | 33.3 | 15 | 3.9 | 9 | 5.9 | 2 | 5.6 | 0 | 0.0 | 2 | 8.7 |
| myopia mild (−0.5 to −3) | 1714 | 16.0 | 120 | 18.1 | 85 | 20.5 | 59 | 15.5 | 30 | 19.6 | 6 | 16.7 | 3 | 23.1 | 3 | 13.0 |
| myopia mod/high (<−3) | 379 | 3.5 | 15 | 2.3 | 17 | 4.1 | 10 | 2.6 | 4 | 2.6 | 0 | 0.0 | 0 | 0.0 | 0 | 0.0 |
| Iris color | ||||||||||||||||
| lighter (gray/blue/green) | 3715 | 34.7 | 207 | 31.1 | 135 | 32.4 | 127 | 33.3 | 57 | 37.3 | 21 | 58.3 | 10 | 77 | 11 | 47.8 |
| tan/brown | 6952 | 65.1 | 451 | 67.9 | 282 | 67.6 | 249 | 65.4 | 93 | 60.8 | 13 | 36.1 | 3 | 23.1 | 10 | 43.5 |
| Soft Indistinct Drusen | Increased Retinal Pigment | RPE Depigmentation | Any Advanced AMD | Geographic Atrophy | Exudative AMD | |
|---|---|---|---|---|---|---|
| Characteristic | OR (95% CI) a | OR (95% CI) a | OR (95% CI) a | OR (95%CI) a | OR (95% CI) a | OR (95% CI) a |
| Cataract | ||||||
| Absent | 1 | 1 | 1 | 1 | 1 | 1 |
| Present | 1.2 (1.002, 1.5) | 0.8 (0.5, 1.0) | 0.8 (0.5, 1.4) | 0.5 (0.2, 1.1) | 0.8 (0.2, 3.5) | 0.7 (0.2, 1.7) |
| Nuclear sclerosis | ||||||
| Absent | 1 | 1 | 1 | 1 | 1 | 1 |
| Present | 1.2 (0.95, 1.6) | 1.0 (0.6, 1.3) | 1.3 (0.7, 2.4) | 1.9 (0.7, 4.9) | 2.2 (0.5, 10.2) | 1.7 (0.6, 4.5) |
| Posterior subcapsular | ||||||
| Absent | 1 | 1 | 1 | 1 | 1 | 1 |
| Present | 0.9 (0.6, 1.5) | 1.1 (0.5, 2.5) | 0.3 (0.0, 2.2) | 1.5 (0.5, 4.7) | 0.3 (0.0, 3.8) | 2.7 (0.8, 9.4 ) |
| Cortical | ||||||
| Absent | 1 | 1 | 1 | 1 | 1 | 1 |
| Present | 1.1 (0.9, 1.4) | 0.9 (0.6, 1.3) | 0.9 (0.5, 1.7) | 0.5 (0.2, 1.6) | 0.2 (0.0, 1.8) | 0.9 (0.3, 2.6) |
| Mixed | ||||||
| Absent | 1 | 1 | 1 | 1 | 1 | 1 |
| Present | 1.0 (0.8, 1.5) | 1.4 (0.9, 2.3) | 1.5 (0.7, 3.3) | 1.3 (0.4, 4.6) | 0.3 (0.0, 4.3) | 2.8 (0.92, 8.5) |
| Cataract surgery | ||||||
| None | 1 | 1 | 1 | 1 | 1 | 1 |
| Yes | 1.0 (0.7, 1.4) | 1.6 (1.02, 2.6) | 2.2 (1.1, 4.4) | 2.8 (1.01, 7.8) | 2.6 (0.4, 14.7) | 2.8 (0.8, 9.6) |
a Odds ratios (OR) adjusted for age, sex, and smoking. Odds ratios in bold are statistically significant.
Table 3 presents the odds of having early and advanced AMD by refractive error and axial length after adjusting for age, sex, and history of smoking. Myopia was protective for soft drusen, but not advanced AMD. Similarly, there was a protective association of longer axial length per 1 mm with soft indistinct drusen and increased retinal pigment and GA.
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