Association of HTRA1 rs11200638 with age-related macular degeneration (AMD) in Brazilian patients.

Age-related macular degeneration is a multifactorial disease that can lead to vision impairment in older individuals. Although the etiology of age-related macular degeneration remains unknown, risk factors include age, ethnicity, smoking, hypertension, obesity, and genetic factors. Two main loci have been identified through genome-wide association studies, on chromosomes 1 and 10. Among the variants located at the 10q26 region, rs11200638, located at the HTRA1 gene promoter, has been associated with age-related macular degeneration in several populations and is considered the main polymorphism. We conducted a replication case-control study to analyze the frequency and participation of rs11200638 in the etiology of age-related macular degeneration in a sample of patients and controls from the State of São Paulo, Brazil, through polymerase chain reaction and enzymatic digestion. The frequency of the A allele was 57.60% in patients with age-related macular degeneration and 36.45% in controls (p value < 1e-07), representing a 2.369-fold higher risk factor for the disease. Both the AA and AG genotypes were observed more frequently in the age-related macular degeneration group compared to the control group (p = 1.21e-07 and 0.0357, respectively). No statistically significant results were observed after stratification in dry versus wet types or advanced versus non-advanced forms. To our knowledge, this is the first time the association between rs11200638 and overall age-related macular degeneration has been reported in South America.

Incidence of Age-Related Macular Degeneration in a Multi-Ethnic United States Population: The Multi-Ethnic Study of Atherosclerosis.

PURPOSE: To describe the incidence of age-related macular degeneration (AMD) and associated risk factors in 4 racial/ethnic groups (white, black, Hispanic, and Chinese) residing in the United States. DESIGN: Prospective cohort study. PARTICIPANTS: A total of 3811 participants, aged 46 to 86 years, from the Multi-Ethnic Study of Atherosclerosis (MESA) cohort, with retinal data collected twice, on average, 8 years apart. METHODS: Fundus images, taken using a digital camera through dark-adapted pupils using a standard protocol and the same equipment at both study visits, were graded centrally for early and late AMD on the basis of drusen size, type and area, increased retinal pigment, retinal pigment epithelial depigmentation, neovascular lesions, and geographic atrophy using the modified Wisconsin Age-Related Maculopathy Grading System. Demographic, clinical, and laboratory measures were included in multivariable regression models to determine their impact on the variation in AMD incidence among racial/ethnic groups. MAIN OUTCOME MEASURES: Incident early and late AMD. RESULTS: The overall 8-year age- and sex-standardized incidence of early and late AMD were 4.1% and 2.3%, respectively, with incidence of early and late AMD highest in whites (5.3% and 4.1%, respectively), intermediate in Chinese (4.5% and 2.2%, respectively) and Hispanics (3.3% and 0.8%, respectively), and lowest in blacks (1.6% and 0.4%, respectively). By adjusting for age and sex, blacks had a 70% lower risk of developing early AMD than whites, and this decreased only slightly to a 67% lower risk after multivariable adjustment. By adjusting for age, sex, and race/ethnicity, hyperopia was associated with early AMD (odds ratio [OR], 1.51; 95% confidence interval [CI], 1.04-2.20), as was astigmatism (OR, 1.47; 95% CI, 1.00-2.16), but not myopia (P = 0.29). Age, race/ethnicity, current smoking, hyperopia, and AMD-susceptibility genotypes Complement Factor H (CFH) RS1061170 and Age Related Maculopathy Susceptibility 2 (ARMS2) RS3793917 were independently associated with incident early AMD in multivariable models for the combined sample. However, the only statistically significant factor consistently associated with incident early AMD across the 4 racial/ethnic groups was increasing age. Risk factors for late AMD were not assessed because of its low incidence, particularly across racial/ethnic groups. CONCLUSIONS: Variation in the incidence of early AMD exists among racial/ethnic groups in the United States and is not explained by the clinical, genetic, and environmental factors included in this study.

Incidence of Late-Stage Age-Related Macular Degeneration in American Whites: Systematic Review and Meta-analysis.

PURPOSE: To estimate incidence of age-related macular degeneration (AMD) by subtype in American whites aged ≥50 years. DESIGN: Systematic review and meta-analysis. SETTING: Prospective cohort studies of AMD incidence in populations of white European ancestry published in MEDLINE, EMBASE, and Web of Science. STUDY POPULATION: Fourteen publications in 10 populations that examined AMD incident cases were identified. OBSERVATION PROCEDURE: Data on age-sex-specific incidence of late AMD, geographic atrophy (GA) and neovascular AMD (NVAMD), year of recruitment, AMD grading method, and continent were extracted. MAIN OUTCOME MEASURE(S): Annual incidence of late AMD, GA, and NVAMD by age-sex in American whites aged ≥50 years from a Bayesian meta-analysis of incidence studies was compared with incidence extrapolated from published prevalence estimates. RESULTS: Incidence rates from the review agreed with those derived from prevalence, but the latter were based on more data, especially at older ages and by AMD subtypes. Annual incidence (estimated from prevalence) of late AMD in American whites was 3.5 per 1000 aged ≥50 years (95% credible interval 2.5, 4.7 per 1000), equivalent to 293 000 new cases in American whites per year (95% credible interval 207 000, 400 000). Incidence rates approximately quadrupled per decade in age. Annual incidence GA rates were 1.9 per 1000 aged ≥50 years, NVAMD rates were 1.8 per 1000. Late AMD incidence was 38% higher in women vs men (95% credible interval 6%, 82%). CONCLUSIONS: Estimating AMD incidence from prevalence allows better characterization at older ages and by AMD subtype where longitudinal data from incidence studies are limited.

Age-related macular degeneration in ethnically diverse Australia: Melbourne Collaborative Cohort Study.

PURPOSE: To determine and compare the prevalence of age-related macular degeneration (AMD) in older Australians of Anglo-Celtic and Southern European origin. METHODS: A total of 21,132 participants of the Melbourne Collaborative Cohort Study, aged 47-86 years, were assessed for AMD in 2003-2007 with non-mydriatic fundus photography. Of these, 14% were born in Southern Europe (Greece, Italy or Malta), with the remaining 86% of Anglo-Celtic origin, born in Australia, the United Kingdom or New Zealand. RESULTS: Overall, 2694 participants (12.7%) had early stages of AMD, defined as either one or more drusen ≥ 125 µm (with or without pigmentary abnormalities) or one or more drusen 63-124 µm with pigmentary abnormalities in a 6000-µm diameter grading grid, in the absence of late AMD in either eye. A total of 122 participants (0.6%) had late AMD, defined as either geographic atrophy or neovascular AMD. In logistic regression analysis, adjusted for age, sex, smoking, education and physical activity, Southern Europeans compared to Anglo-Celts had a higher prevalence of the early stages of AMD (odds ratio, OR, 1.15, 95% confidence interval, CI, 1.00-1.34), and lower prevalence of late AMD (OR 0.36, 95% CI 0.17-0.78). CONCLUSIONS: Australians of Southern European origin have a higher prevalence of the early stages of AMD and lower prevalence of late AMD compared to those of Anglo-Celtic origin. Although AMD prevalence in the older age group(s) of Southern Europeans could be underestimated due to disparity in participation rates, it is likely that both lifestyle and genetic factors play their parts in differential AMD prevalence in these ethnic groups.

Drusen and photoreceptor abnormalities in African-Americans with intermediate non-neovascular age-related macular degeneration.

PURPOSE/AIM: To investigate the relationship of drusen and photoreceptor abnormalities in African-American (AA) patients with intermediate non-neovascular age-related macular degeneration (AMD). MATERIALS AND METHODS: AA patients with intermediate AMD (n = 11; age 52-77 years) were studied with spectral-domain optical coherence tomography. Macular location and characteristics of large drusen (≥125 µm) were determined. Thickness of photoreceptor laminae was quantified overlying drusen and in other macular regions. A patient with advanced AMD (age 87) was included to illustrate the disease spectrum. RESULTS: In this AA patient cohort, the spectrum of changes known to occur in AMD, including large drusen, sub-retinal drusenoid deposits and geographic atrophy, were identified. In intermediate AMD eyes (n = 17), there were 183 large drusen, the majority of which were pericentral in location. Overlying the drusen there was significant thinning of the photoreceptor outer nuclear layer (termed ONL(+)) as well as the inner and outer segments (IS + OS). The reductions in IS + OS thickness were directly related to ONL(+) thickness. In a fraction (∼8%) of paradrusen locations with normal lamination sampled within ∼280 µm of peak drusen height, ONL(+) was significantly thickened compared to age and retinal-location-matched normal values. Topographical maps of the macula confirmed ONL thickening in regions neighboring and distant to large drusen. CONCLUSIONS: We confirm there is a pericentral distribution of drusen across AA-AMD maculae rather than the central localization in Caucasian AMD. Reductions in the photoreceptor laminae overlying drusen are evident. ONL(+) thickening in some macular areas of AA-AMD eyes may be an early phenotypic marker for photoreceptor stress.

Association of sequence variation in the CX3CR1 gene with geographic atrophy age-related macular degeneration in a Greek population.

PURPOSE: To explore the association of two single nucleotide polymorphisms (SNPs) in the CX3CR1 gene with grades of age-related macular degeneration (AMD) in a population-based setting. METHODS: The Thessaloniki Eye study is a cross-sectional population-based epidemiologic study of chronic eye diseases in Thessaloniki, Greece. A total of 371 subjects were included and classified according to their AMD status. Subjects with AMD Grades 0-1 (n = 188) were compared to those with AMD Grades 2-3 (n = 138), to those with AMD Grade 4 (geographic atrophy) (n = 20) and to those with AMD Grade 5 (neovascular AMD) (n = 25) with regard to the presence of CX3CR1 polymorphisms (V249I and T280M). Polychotomous logistic regression analysis adjusted for age, gender, and smoking was conducted and the log-additive allelic model was preferred. RESULTS: Participants with AMD Grade 4 were approximately three times more likely to carry the VI249 and nine times more likely to carry the II249 alleles, compared to those with AMD Grades 0-1, whereas those with AMD Grades 2-3 or Grade 5 did not differ. The T280M polymorphism was not associated with either AMD Grades 2-3 or AMD Grades 4 or 5. CONCLUSION: In this Greek population, after adjusting for known risk factors, increased risk of geographic atrophy (GA) AMD among the carriers of the V249I polymorphism in the CX3CR1 gene was found. Our study failed to reveal any association with the T280M polymorphism reported in previous studies. Additional studies in different ethnic populations using standardized methodology are needed in order to confirm this association.

Clinical characteristics of reticular pseudodrusen in Korean patients.

PURPOSE: To clarify the clinical characteristics of reticular pseudodrusen in Korean patients. DESIGN: Retrospective, observational, consecutive case series. METHODS: A total of 255 eyes of 130 patients diagnosed with reticular pseudodrusen were evaluated. Reticular pseudodrusen were diagnosed by characteristic fundus findings using ophthalmoscopy, color fundus photography with blue-channel examination, near-infrared photography, red-free photography, autofluorescence imaging, fluorescein angiography, indocyanine green angiography, and spectral-domain optical coherence tomography. Age-related macular degeneration (AMD) was determined by the International Classification and Grading System. RESULTS: The mean age was 72.6 ± 9.0 years (range, 43 to 92 years). Most reticular pseudodrusen patients had bilateral disease (97.7%), with a female preponderance (86.2%). All 3 patients who showed unilateral reticular pseudodrusen had neovascular AMD in the eye with no reticular pseudodrusen. AMD was found in 183 eyes (71.8 %), among which early AMD was found in 115 eyes (45.1%), geographic atrophy was found in 41 eyes (16.1%), and neovascular AMD was found in 27 eyes (10.6%). The mean age of patients with AMD and with no AMD was 73.7 ± 9.2 years (range, 58 to 92 years) and 69.9 ± 11.7 years (range, 43 to 90 years), respectively, and there was a statistical difference between these 2 groups (P < .05). Classic choroidal neovascularization was found in 13 eyes (48.1%), and occult choroidal neovascularization was found in 14 eyes (51.9%) in the neovascular AMD group. CONCLUSIONS: Reticular pseudodrusen occurs in Koreans, and clinical manifestations of reticular pseudodrusen in Koreans did not differ significantly from those described in white persons. However, our study demonstrated a higher rate of bilaterality compared with those previously reported, and geographic atrophy was found to be associated more commonly with reticular pseudodrusen than with neovascular AMD. Ethnical differences may be associated with these findings, and further studies are required.

Racial differences in age-related macular degeneration rates in the United States: a longitudinal analysis of a managed care network.

PURPOSE: To compare the incidence, prevalence, and hazard of nonexudative and exudative age-related macular degeneration (AMD) among different races throughout the United States. DESIGN: Retrospective longitudinal cohort study. METHODS: Billing records of all encounters for 2 259 061 beneficiaries aged ≥40 enrolled in a large, national US managed care network from 2001 through 2007 were reviewed and the incidence and prevalence of nonexudative and exudative AMD were determined and stratified by race. Cox regression analyses determined the hazard of nonexudative and exudative AMD for each race, with adjustment for confounders. RESULTS: During the study, 113 234 individuals (5.0%) were diagnosed with nonexudative and 17 181 (0.76%) with exudative AMD. After adjustment for confounders, blacks had a significantly reduced hazard of nonexudative (hazard ratio [HR]=0.75, 95% confidence interval [CI]: 0.71-0.79) and exudative AMD (HR=0.70, 95% CI: 0.59-0.83) at age 60 and a reduced hazard of nonexudative (HR=0.56, 95% CI: 0.52-0.60) and exudative AMD (HR=0.45, 95% CI: 0.37-0.54) at age 80 relative to whites. Similar comparisons for Latinos demonstrated an 18% reduced hazard for nonexudative AMD at age 80 (HR=0.82, 95% CI: 0.76-0.88) relative to whites. Asian Americans showed a 28% increased hazard for nonexudative AMD at age 60 (HR=1.28, 95% CI: 1.20-1.36) but a 46% decreased hazard for exudative AMD at age 80 (HR=0.54, 95% CI: 0.40-0.73). CONCLUSIONS: Racial minorities, including Latinos and Asian Americans, do not appear to have similar risks of developing nonexudative and exudative AMD as whites. Additional studies using other sources should be conducted to determine the generalizability of this study's findings to other groups.