Association of age-related macular degeneration with complement activation products, smoking, and single nucleotide polymorphisms in South Carolinians of European and African descent.

Purpose: Smoking and the incidence of age-related macular degeneration (AMD) have been linked to an overactive complement system. Here, we examined in a retrospective cohort study whether AMD-associated single nucleotide polymorphisms (SNPs), smoking, ethnicity, and disease status are correlated with blood complement levels. Methods: Population: The study involved 91 AMD patients and 133 controls, which included 73% Americans of European descent (EUR) and 27% Americans of African descent (AFR) in South Carolina. Readouts: Participants were genotyped for 10 SNPs and systemic levels of complement factor H (CFH) activity, and the complement activation products C3a, C5a, and Bb were assessed. Main Outcome Measures: Univariate and multivariable logistic regression models were used to examine associations between AMD status and distinct readouts. Results: AMD affects EUR individuals more than AFRs. EUR but not AFR AMD subjects revealed higher levels of Factors C3a and Bb. In all subjects, a 10-unit increase in C3a levels was associated with an approximately 10% increase in the odds of being AMD-positive, and C3a and Bb were associated with smoking. While CFH activity levels were not correlated with AMD, a significant interaction was evident between patient age and CFH activity. Finally, EURs had lower odds of AMD with enhanced copies of rs1536304 (VEGFA) and higher odds with more copy numbers of rs3766404 (CFH). Conclusions: Our results support previous studies of systemic complement components being potential biomarkers for AMD, but they suggest that smoking and disease do not synergistically affect complement levels. We also suggest a novel susceptibility and protective haplotypes in the South Carolinian AMD population. Our studies indicate that augmented complement activation associated with advanced AMD could be attributed to a decrease in CFH activity in younger patients.

Circulating levels of mannose-binding lectin (MBL) in age-related macular degeneration / Níveis circulantes da lectina ligadora de manose (MBL) na degeneração macular relacionada à idade

ABSTRACT Purpose: To assess whether the serum levels of mannose-binding lectin of the lectin complement pathway are associated with age-related macular degeneration. Methods: Patients with age-related macular degeneration and age-matched controls underwent full ophthalmologic examination and optical coherence tomography. Using a time-resolved immunofluorometric assay, blood samples were evaluated to determine the serum mannose-binding lectin levels. Results: A total of 136 individuals were evaluated, including 68 patients with age-related macular degeneration (34 exudative and 34 nonexudative) and 68 age-matched controls. The median mannose-binding lectin level was 608 ng/mL (range, 30-3,415 ng/mL) in patients with age-related macular degeneration and 739 ng/mL (range, 30-6,039 ng/mL) in controls, with no difference between the groups. Additionally, the median mannose-binding lectin level was 476 ng/mL (range, 30-3,415 ng/mL) in exudative cases and 692 ng/mL (range, 30-2,587 ng/mL) in nonexudative cases. Conclusions: Serum mannose-binding lectin levels were not associated with age-related macular degeneration or with the exudative and nonexudative forms of the disease.

RESUMO Objetivos: Avaliar se as concentrações séricas da lectina ligante de manose da via das lectinas do sistema complemento estão associadas à degeneração macular relacionada à idade. Métodos: Pacientes com degeneração macular relacionada à idade a controles pareados realizaram exame oftalmológico completo e imagens de tomografia de coerência óptica. As concentrações de lectina ligante de manose foram aferidas em amostras de sangue pelo método "time-resolved Immunofluorometric assay". Resultados: Um total de 136 indivíduos foram avaliados incluindo 68 com degeneração macular relacionada à idade (34 exsudativa e 34 não-exsudativa) e 68 controles. Concentrações medianas de lectina ligante de ma-nose foram 608 ng/mL (30-3,415 ng/mL) nos casos e 739 ng/mL (30-6,039 ng/mL) nos controles, não havendo diferença entre os grupos. Comparando degeneração macular relacionada a idade exsudativa (mediana de lectina ligante de manose 476 ng/mL; 30-3,415 ng/mL) e não-exsudativa (692 ng/mL; 30-2,587 ng/mL) também não apresentaram diferença. Conclusões: Concentrações séricas de lectina ligante de manose não estão relacionadas à degeneração macular relacionada a idade ou às formas exsudativa e não-exsudativa.

Ethnic Differences in the Association Between Age-Related Macular Degeneration and Vision-Specific Functioning.

Importance: Understanding the link between ethnicity and health is critical to making appropriate public policy decisions. Few population-level data are available about this connection, however, including the influence of ethnicity on the association between age-related macular degeneration (AMD) and vision-specific functioning (VSF). Objective: To identify the influence of ethnicity on VSF among Chinese, Malay, and Indian patients with AMD. Design, Setting, and Participants: This cross-sectional, population-based study relied on patients and their data from 3 population-based studies in 3 ethnic groups: Chinese, Malay and Indian. Of 10 033 Chinese, Malay, and Indian adults who participated in the study, 9962 (99.3%) who had gradable fundus images and Visual Function Index (VF-11) data available were included in the analyses for the present study. Uniocular presenting distance visual acuity was measured using the logMAR chart. Separate multiple linear regression models examined the association between AMD and VSF in the 3 ethnic groups, adjusting for age, sex, presenting visual acuity in the better-seeing eye, educational level, income, smoking status, hypertension, diabetes, cardiovascular disease, total cholesterol level, and other eye conditions. Data were collected between January 20, 2004, and December 19, 2011; data analysis was conducted between November 12, 2015, and December 28, 2016. Exposures: Age-related macular degeneration according to fundus photographs graded using a modified Wisconsin Age-Related Maculopathy Grading System. Main Outcomes and Measures: Rasch analysis was used to convert VF-11 questionnaire scores to estimated interval measures of VSF. Results: Of the 9962 participants, the mean (SD) age was 58.8 (10.4) years; 4909 (49.3%) were male; 590 (5.9%) had early AMD (241 Chinese, 161 Malays, and 188 Indians) and 60 (0.6%) had late AMD (25 Chinese, 21 Malays, and 14 Indians). In the adjusted models, compared with no AMD, early AMD was associated with a small reduction in VSF (2.9%; ß = -0.12; 95% CI, -0.23 to -0.00; P = .046) in the Chinese group but not in the Indian and Malay groups. Moreover, Chinese participants with late AMD had a clinically significant 19.1% loss of VSF (ß = -0.78; 95% CI, -1.13 to -0.43, P < .001). In the Malay group, those with late AMD had a 13.5% drop in VSF (ß = -0.49; 95% CI, -1.01 to 0.04; P = .07) compared with their counterparts without AMD. Similarly, late AMD was not associated with VSF in the Indian group. Conclusions and Relevance: Early and late AMD negatively affected VSF in Chinese but not in Indian and Malay participants. This finding suggests that there is an independent ethnic influence in the association of the disease with VSF in multiethnic Asian populations, thus warranting ethnicity-based strategies to delay the onset or progression of AMD.

Age-Related Macular Degeneration and Its Risk Factors in North Africans Living in Algeria and Italy.

PURPOSE: To determine the risk factors for age-related macular degeneration (AMD) in Algerians, and compare these data with those on North Africans living in Italy. METHODS: All patients over 55 years of age consulting one of the 23 involved Algerian ophthalmologists were invited to participate, and 1,183 patients were included. Data collection was standardized based on the Simplified Théa Risk Assessment Scale (STARS) questionnaire. A similar study was conducted in North Africans living in Italy (n = 1,011). Patients with only soft drusen and/or pigmentary abnormalities were classified as early AMD, and patients with geographic atrophy and/or neovascular AMD were classified as late AMD. RESULTS: In the final multivariate model, risk for early and/or late AMD was significantly increased with older age, family history of AMD, Black ethnicity, atherosclerosis, beer consumption, high fruit consumption, cataract surgery, myopia, and hyperopia. High consumption of green vegetables was associated with lower risk for both early and late AMD. In comparison with North Africans from Italy, Algerians generally had a healthier profile (younger, less obesity, smoking, and cardiovascular diseases, and higher consumption of fruits and vegetables) and a lower risk for AMD. CONCLUSION: This study documents risk factors for AMD in North-African populations for the first time.

Gender specific association of a complement component 3 polymorphism with polypoidal choroidal vasculopathy.

Neovascular age-related macular degeneration (AMD) and polypoidal choroidal vasculopathy (PCV) are leading causes of irreversible blindness in developed countries. In this study, we investigated the associations of haplotype-tagging single nucleotide polymorphisms (SNPs) in the complement component 3 (C3) gene with both neovascular AMD and PCV, and potential epistatic effects on C3. Eight tagging SNPs in C3 were genotyped in 708 unrelated study subjects: 200 neovascular AMD patients, 233 PCV patients and 275 controls. Among the eight C3 SNPs, rs17030 was associated with PCV after adjusted for gender and SNP-gender interaction (P = 0.008, OR = 2.94; 95% CI: 1.32-6.52). Moreover, an interaction between rs17030 and gender was identified in PCV (P = 0.02). After stratification by gender, the rs17030 G allele was found to confer an increased risk for PCV in male (P = 0.010, OR = 1.56) but not in female. The haplotype AG defined by the major alleles of rs17030 and rs344555 was also associated with PCV in male (P = 0.010, OR = 0.64). In contrast to PCV, none of the eight SNPs was significantly associated with neovascular AMD. This study shows an association of C3 rs17030 with PCV in male, indicating that C3 may have an epistatic effect with gender in the pathogenesis of PCV.

A prospective study of treatment patterns and 1-year outcome of Asian age-related macular degeneration and polypoidal choroidal vasculopathy.

OBJECTIVE: To study the treatment patterns and visual outcome over one year in Asian patients with choroidal neovascular membrane secondary to age-related macular degeneration (AMD-CNV) and polypoidal choroidal vasculopathy (PCV). DESIGN: Prospective cohort, non-interventional study. METHODS: 132 treatment-naïve patients who received treatment for AMD-CNV and PCV were included. All patients underwent standardized examination procedures including retinal imaging at baseline and follow-up. AMD-CNV and PCV were defined on fundus fluorescein angiography and indocyanine green angiography at baseline. Patients were treated according to standard of care.We report the visual acuity (VA) and optical coherence tomography (OCT) measurements at baseline, month 3 and month 12 The factors influencing month 12 outcomes were analyzed. MAIN OUTCOME MEASURE: Type of treatment, number of Anti-vascular endothelial growth factor (VEGF) treatments, visual outcome over one year. RESULTS: Anti-VEGF monotherapy was the initial treatment in 89.1% of AMD-CNV, but only 15.1% of PCV. The mean number of anti-VEGF injections up to month 12 was 3.97 (4.51 AMD-CNV, 3.43 PCV, p = 0.021). Baseline OCT, month 3 OCT and month 3 VA were significant in determining continuation of treatment after month 3. At month 12, mean VA improved from 0.82 (∼20/132) at baseline to 0.68 (∼20/96) at month 12 (mean gain 6.5 ETDRS letters, p = 0.002). 34.2% of eyes (38/113 eyes) gained ≥15 ETDRS letters and 14.4% (16/113 eyes) lost ≥15 ETDRS letters. There were no significant differences in visual outcome between AMD-CNV and PCV (p = 0.51). Factors predictive of month 12 visual outcome were baseline VA, baseline OCT central macular thickness, month 3 VA and age. CONCLUSIONS: There is significant variation in treatment patterns in Asian eyes with exudative maculopathy. There is significant visual improvement in all treatment groups at one year. These data highlight the need for high quality clinical trial data to provide evidence-based management of Asian AMD.

Ethnic variation in early age-related macular degeneration lesions between white Australians and Singaporean Asians.

PURPOSE: We compared early age-related macular degeneration (AMD) lesion characteristics between white Australians and Singaporean Asians. METHODS: Participants of the Blue Mountains Eye Study (BMES; whites, n = 3508) and the Singapore Epidemiology of Eye Disease Study (SEED; Malay, n = 3280, Indian, n = 3400, and Chinese, n = 3353) underwent examinations, including retinal photography. The AMD lesions were assessed following the Wisconsin AMD grading protocol by the same photographic grader. Prevalence and characteristics of early AMD lesions were compared between the BMES and the SEED. The associations between ethnicity and early AMD lesion types were analyzed using logistic regression models adjusting for age, sex, smoking status, lipids, and genetic polymorphisms associated with AMD. RESULTS: After age-standardization to the BMES population, the prevalence of distinct soft drusen was significantly higher in Singaporeans compared to Australians (23.9%, 95% confidence interval [CI] 22.9-25.0 vs. 6.2%, 95% CI 5.3-7.0), with an adjusted odds ratio (OR) of 4.6 (95% CI 3.4-6.0). In contrast, the prevalence of indistinct soft or reticular drusen was significantly lower in Singaporeans compared to Australians (6.5%, 95% CI 5.9-7.1 vs. 8.3%, 95% CI 7.4-9.3, with nonsignificant adjusted OR of 1.2, 95% CI 0.8-1.7). Soft drusen of any type were present frequently at the inner and outer macula (within a zone ≥500 to <3000 µm radius from the foveal center) among Singaporeans, while among Australians soft drusen were present more frequently at the central macula (<500 µm radius). CONCLUSIONS: Singaporean Asians had a milder spectrum of early AMD lesions and lesion characteristics (predominantly distinct soft drusen and noncentral location) compared to white Australians.

FLT1 genetic variation predisposes to neovascular AMD in ethnically diverse populations and alters systemic FLT1 expression.

PURPOSE: Current understanding of the genetic risk factors for age-related macular degeneration (AMD) is not sufficiently predictive of the clinical course. The VEGF pathway is a key therapeutic target for treatment of neovascular AMD; however, risk attributable to genetic variation within pathway genes is unclear. We sought to identify single nucleotide polymorphisms (SNPs) associated with AMD within the VEGF pathway. METHODS: Using a tagSNP, direct sequencing and meta-analysis approach within four ethnically diverse cohorts, we identified genetic risk present in FLT1, though not within other VEGF pathway genes KDR, VEGFA, or VASH1. We used ChIP and ELISA in functional analysis. RESULTS: The FLT1 SNPs rs9943922, rs9508034, rs2281827, rs7324510, and rs9513115 were significantly associated with increased risk of neovascular AMD. Each association was more significant after meta-analysis than in any one of the four cohorts. All associations were novel, within noncoding regions of FLT1 that do not tag for coding variants in linkage disequilibrium. Analysis of soluble FLT1 demonstrated higher expression in unaffected individuals homozygous for the FLT1 risk alleles rs9943922 (P = 0.0086) and rs7324510 (P = 0.0057). In silico analysis suggests that these variants change predicted splice sites and RNA secondary structure, and have been identified in other neovascular pathologies. These data were supported further by murine chromatin immunoprecipitation demonstrating that FLT1 is a target of Nr2e3, a nuclear receptor gene implicated in regulating an AMD pathway. CONCLUSIONS: Although exact variant functions are not known, these data demonstrate relevancy across ethnically diverse genetic backgrounds within our study and, therefore, hold potential for global efficacy.

Prevalence, racial variations, and risk factors of age-related macular degeneration in Singaporean Chinese, Indians, and Malays.

OBJECTIVE: To describe the prevalence and risk factors for age-related macular degeneration (AMD) in a multiethnic Asian cohort of Chinese, Malay, and Indian persons. DESIGN: Population-based cross-sectional study. PARTICIPANTS: A total of 10 033 persons (3280 Malay, 3400 Indian, and 3353 Chinese; response rate, 75%) 40 years of age or older residing in Singapore. METHODS: We performed comprehensive systemic and ocular examinations, retinal photography, and laboratory investigations for all participants. We graded early and late AMD signs from retinal photographs using the modified Wisconsin AMD grading scale. We calculated the age-standardized prevalence of AMD using the 2010 Singapore adult population and analyzed risk factors for AMD using logistic regression models. MAIN OUTCOME MEASURES: Early and late AMD. RESULTS: Of the 9799 participants with gradable photographs, 588 had early AMD and 60 had late AMD. The age-standardized prevalence was 5.1% (95% confidence interval [CI], 4.6-5.5) for early AMD and 0.5% (95% CI, 0.4-0.6) for late AMD. The prevalence of early AMD was similar between Chinese (5.7%) and Indian (4.5%; P = 0.27) persons and lower in Malays (3.5%; P = 0.002 compared with Chinese; P = 0.09 compared with Indians); in contrast, the prevalence for late AMD was similar across ethnic groups (Chinese, 0.6%; Indian, 0.3%; and Malay, 0.3%; P = 0.20). Risk factors for early AMD were older age (odds ratio [OR], 1.40 per 5-year increase in age; 95% CI, 1.33-1.47), male gender (OR, 1.81; 95% CI, 1.43-2.29), hypertension (OR, 1.28; 95% CI, 1.02-1.61), and hyperopic refraction (OR, 1.17 per 1-diopter increase in spherical equivalent; 95% CI, 1.11-1.24). Risk factors for late AMD include older age (OR, 1.87 per 5-year increase in age; 95% CI, 1.54-2.19), smoking more than 5 packs per week (OR, 3.63; 95% CI, 1.34-9.80), and presence of chronic kidney disease (OR, 2.17; 95% CI, 1.22-3.88). CONCLUSIONS: Early AMD is more common in Chinese and Indians than in Malays, but there were no racial variations in the prevalence of late AMD.

Macular pigment spatial profiles in South Asian and white subjects.

PURPOSE: Variability in central macular pigment optical density (MPOD) has been reported among healthy individuals. These variations seem to be related to risk factors of AMD, such as female sex, smoking, and ethnicity. This study investigates variations in the spatial profiles of MPOD among ethnicities. METHODS: Using heterochromatic flicker photometry (HFP), MPOD was measured at seven retinal locations in 54 healthy, young South Asian and 19 white subjects of similar age. Macular pigment spatial profiles were classified as either typical exponential, atypical ring-like, or atypical central dip. RESULTS: Central MPOD was significantly greater in South Asian (0.56 ± 0.17) compared with white subjects (0.45 ± 0.18; P = 0.015). Integrated MPOD up to 1.8° (i.e., average MPOD [MPODav(0-1.8)]) was also significantly increased in South Asian (0.34 ± 0.09) compared to white subjects (0.27 ± 0.10; P = 0.003). Average MPOD(0-1.8) was significantly increased in all subjects presenting a ring-like profile (0.35 ± 0.08) or central dip profile (0.39 ± 0.09), compared with typical exponential profiles (0.28 ± 0.09; P < 0.0005). We found a statistically significant association between ethnicity and spatial profile type (P = 0.008), whereby an exponential profile was present in 79% of white compared with 41% of the South Asian subjects. CONCLUSIONS: Central MPOD, MPODav(0-1.8), and the prevalence of atypical spatial profiles were significantly increased in South Asian compared with white subjects. Atypical profiles resulted in increased integrated MPOD up to 1.8°, and may therefore offer enhanced macular protection from harmful blue light.

Australian optometric and ophthalmologic referral pathways for people with age-related macular degeneration, diabetic retinopathy and glaucoma.

BACKGROUND: This study investigated the referral pathways offered to patients with age-related macular degeneration (AMD), diabetic retinopathy (DR) or glaucoma (GL) by ophthalmologists and optometrists. METHODS: Australian ophthalmologists and optometrists were surveyed regarding referral decisions to other eye-care specialists (inter- or intra-professional), general medical practitioners (GPs), low vision rehabilitation (LVR) and support services. Thematic analysis and concept mapping were applied to highlight current and ideal referral pathways. RESULTS: The survey was completed by 155 optometrists and 50 ophthalmologists and deemed representative of their respective professions in Australia. Not surprisingly, the vast majority of the participating optometrists (97 to 99 per cent) referred to ophthalmologists regardless of the underlying condition. Clear differences (Chi-square: p < 0.05) were observed in the referral patterns of optometrists and ophthalmologists to GPs and support services. General medical practitioner services were almost exclusively used for patients with DR, while AMD triggered a significantly higher referral rate to low vision rehabilitation and support services than the other two disorders. CONCLUSION: While ophthalmologists predominantly referred patients with AMD, DR or GL to low vision rehabilitation services, optometrists' referrals were highly skewed toward ophthalmology. Referrals to other supporting services by the two groups were not greatly used. The perceived referral pathways by the two eye-care professionals suggested a unidirectional route, potentially highlighting the need for a more collaborative approach that facilitates optimal use of eye health care and allied services.

Is aspirin intake associated with early age-related macular degeneration? The Singapore Indian Eye Study.

BACKGROUND/AIMS: To examine the relationship between aspirin intake and early age-related macular degeneration (AMD) among an Asian population. METHODS: A population based cross sectional study of 3207 ethnic Indians aged 40 years or older residing in Singapore. AMD signs were graded from retinal images following the modified Wisconsin grading system. Information on aspirin intake was obtained from a standardised questionnaire. RESULTS: The prevalence of early AMD was 5.6%. Aspirin use was reported by 11.4% of participants. Early AMD signs were present among 10.9% of aspirin users and 4.9% of non-aspirin users (p<0.001). After adjusting for potential confounders, including age, smoking and previous cataract surgery, aspirin use was associated with early AMD (OR 1.50; 95% CI: 1.01 to 2.22). The association weakened and was not significant after additional adjustment for cardiovascular disease (OR 1.38; 95% CI 0.89 to 2.14). In stratified analysis, aspirin use was significantly associated with early AMD in participants with (adjusted OR 2.64, 95% CI 1.31 to 5.36) but not without (OR 0.73; 95% CI 0.36 to 1.51) a history of cardiovascular disease (interaction term, p=0.011). CONCLUSIONS: Aspirin intake overall was not associated with early AMD in this sample of Asian Indians, but in those with a history of cardiovascular disease the association between aspirin intake and early AMD might warrant further investigation.

Different impact of high-density lipoprotein-related genetic variants on polypoidal choroidal vasculopathy and neovascular age-related macular degeneration in a Chinese Han population.

Neovascular age-related macular degeneration (nAMD) and polypoidal choroidal vasculopathy (PCV) are both major serosanguinous maculopathies among the Asian elderly. They are similar in phenotype. Genetic variants in high-density lipoprotein (HDL) pathway were discovered to be associated with AMD in two genome-wide association studies. In this study with a Chinese Han cohort, we investigated the impacts of these genetic variants on nAMD and PCV separately. The missense coding variants and previously identified variants at LIPC, ABCA1, CETP, LPL and FADS1 loci were genotyped in 157 nAMD patients, 250 PCV patients and 204 controls without any macular abnormality. The known variants in CFH, ARMS2 and near HTRA1 were also genotyped. Fasting serum cholesterol levels were determined. The variants in CFH, ARMS2 and near HTRA1 were strongly associated with both PCV (P < 10(-6), 10(-7) and 10(-7) respectively) and nAMD (P < 10(-6), 10(-16) and 10(-17) respectively). None of the studied HDL-related variants were significantly associated with nAMD. A missense variant in CETP, rs5882, was significantly associated with PCV (P = 2.73 × 10(-4)). The rs5882 GG genotype had a 3.53-fold (95% CI: 1.93-6.45) increased risk for PCV, and conferred a significantly lower serum HDL-cholesterol level for PCV patients than the AA genotype (P = 0.048). These results suggest the need to separate PCV from nAMD in association studies especially with Asian cohorts, and that the HDL pathway may involve in the pathogenesis of PCV and nAMD differently.

Vision health disparities in the United States by race/ethnicity, education, and economic status: findings from two nationally representative surveys.

PURPOSE: To assess vision health disparities in the United States by race/ethnicity, education, and economic status. DESIGN: Cross-sectional, nationally representative samples. METHODS: We used national survey data from the National Health and Nutrition Examination Survey (NHANES) and the National Health Interview Survey (NHIS). Main outcome measures included, from NHANES, age-related eye diseases (ie, age-related macular degeneration [AMD], cataract, diabetic retinopathy [DR], glaucoma) and from NHIS, eye care use (ie, eye doctor visits and cannot afford eyeglasses when needed) among those with self-reported visual impairment. The estimates were age- and sex-standardized to the 2000 US Census population. Linear trends in the estimates were assessed by weighted least squares regression. RESULTS: Non-Hispanic whites had a higher prevalence of AMD and cataract surgery than non-Hispanic blacks, but a lower prevalence of DR and glaucoma (all P < .001 in NHANES 2005-2008). From 1999 to 2008, individuals with less education (ie, high school) and lower income (poverty income ratio [PIR] <1.00 vs ≥ 4.00) were consistently less likely to have had an eye care visit in the past 12 months compared with their counterparts (all P < .05). During this period, inability to afford needed eyeglasses increased among non-Hispanic whites and Hispanics (trend P = .004 and P = .007; respectively), those with high school education (trend P = .036), and those with PIR 1.00-1.99 (trend P < .001). CONCLUSIONS: Observed vision health disparities suggest a need for educational and innovative interventions among socioeconomically disadvantaged groups.

Five-year incidence of age-related macular degeneration: the Beijing Eye Study.

PURPOSE: To examine the incidence of age-related macular degeneration (AMD) and its associated factors in an adult Chinese population. DESIGN: Population-based study. PARTICIPANTS: The Beijing Eye Study, which included 4439 subjects (age ≥ 40 years) in 2001, was repeated in 2006 with 3251 (73.2%) subjects participating. METHODS: Fundus photographs were graded using the International Age-related Maculopathy Epidemiological Study Group grading system. MAIN OUTCOME MEASURES: Incidence of AMD. RESULTS: Gradable slides were available on 3049 (93.9%) subjects who participated in the survey of 2001 and again in 2006. The incidence of early, late, and neovascular AMD per eye was 2.6% (95% confidence interval [CI], 2.2-3.0), 0.1% (95% CI, 0.00-0.2), and 0.1% (95% CI, 0.00-0.2), respectively. The incidence of early, late, and neovascular AMD per person was 4.2 ± 0.4% (95% CI, 3.5-5.0), 0.1 ± 0.1% (95% CI, 0.0-0.2), and 0.1 ± 0.1% (95% CI, 0.0-0.2), respectively. By multivariate analysis, incident early AMD was associated significantly with greater age at baseline (P = 0.01; odds ratio [OR], 1.03; 95% CI, 1.01-1.06), smaller optic disc size (P = 0.007; OR, 0.50; 95% CI, 0.30-0.83), smaller scleral spur distance (P = 0.04; OR, 0.59; 95% CI, 0.36-0.98), and hyperopic refractive error (P = 0.057; OR, 1.15; 95% CI, 1.00-1.33), with the latter being significant only marginally. It was not associated with the systemic parameters of gender, body height, body mass index, region of habitation, level of education, profession, smoking, arterial blood pressure, diabetes mellitus, fasting blood concentrations of glucose, triglycerides, high-density or low-density lipoproteins; or the ocular parameters of intraocular pressure, retinal arterial and vein diameters, retinal microvascular abnormalities, amount of nuclear cataract, cortical cataract or subcapsular cataract, pseudophakia, glaucoma, nonglaucomatous optic neuropathy, retinal vein occlusions, size of the beta zone of parapapillary atrophy, or progression of the zone of atrophy during the follow-up from 2001 to 2006. CONCLUSIONS: Hyperopia, short interscleral spur distance, and small optic disc size were, beside older age, the main factors associated with incident early AMD. This may point to a small globe size, potentially in relation to a firmly attached vitreous, playing a role in early incident AMD. FINANCIAL DISCLOSURE(S): The authors have no proprietary or commercial interest in any of the materials discussed in this article.

Association of macular pigment optical density with risk factors for wet age-related macular degeneration in the Indian population.

PURPOSE: To investigate macular pigment optical density (MPOD) in patients with and without wet age-related macular degeneration (AMD) and to elucidate the association between MPOD and the risk factors for AMD in an Indian population. METHODS: Thirty-three subjects with wet AMD and 29 controls above 50 years old underwent MPOD measurement with the 'Macular Densitometer'. The subjects were also tested for their smoking history, lifetime ultraviolet (UV) exposure, dietary intake of carotenoids, and body mass index (BMI). RESULTS: Smokers had a higher risk for AMD than the non-smokers (P=0.032) and a lower MPOD level than non-smokers (mean (95% CI)) (0.16 (0.09-0.23) vs 0.28 (0.22-0.34), adjusted P=0.026). Subjects with lowest UV exposure had higher MPOD than those with the highest (0.46 (0.38-0.54) vs 0.17 (0.01-0.33), P=0.01). MPOD was significantly lower among those with the lowest quartile of dietary intake of carotenoids (0.14 (0.08-0.21) vs 0.25 (0.13-0.36), P=0.012). Smoking, obesity, and UV index showed an inverse association with the MPOD. Low MPOD, smoking, and UV exposure had 5.11 (1.73-15.08), 3.54 (1.08-11.57), and 5.24 (1.06-25.96) odds for AMD, respectively, whereas higher dietary intake of carotenoids showed a protective effect for AMD. CONCLUSION: We found an inverse association between wet AMD and MPOD. Among the established risk factors of wet AMD, we found an inverse association of smoking, UV index, and obesity with MPOD, whereas a positive association was found between dietary intake of carotenoids and MPOD.

Validity of self-reported eye disease and treatment in a population-based study: the Los Angeles Latino Eye Study.

PURPOSE: To examine the validity of self-reported eye disease, including cataract, age-related macular degeneration (AMD), glaucoma, and diabetic retinopathy (DR), and self-reported surgical treatment for cataract and DR in the Los Angeles Latino Eye Study (LALES). DESIGN: Population-based, cross-sectional study. PARTICIPANTS: A total of 6357 Latinos aged 40+ years from the LALES. METHODS: Participants underwent a detailed interview, including survey questions about ocular health, diagnoses, and timing of last eye examination, and a standardized clinical examination. Self-report was compared with examination to determine sensitivity and specificity by length of time since last eye examination. Stepwise logistic regression was used to determine factors associated with inaccurate self-report. MAIN OUTCOME MEASURES: Sensitivity and specificity were calculated for 4 self-reported eye diseases (cataract, AMD, glaucoma, and DR) and for surgical treatment of cataract and DR. Odds ratios (ORs) were determined for factors associated with inaccurate self-report underestimating eye disease and treatment. RESULTS: For each disease, sensitivity and specificity in those who reported their last eye examination as <1 year ago were 36.8% and 92.5% for cataract, 37.7% and 96.3% for glaucoma, 5.1% and 98.9% for AMD, and 25.7% and 94.2% for DR, respectively. Self-report was less accurate with increasing time since last eye examination. Inaccurate self-report was independently associated with better visual acuity (OR, 2.4), <2 comorbidities (OR, 1.7), last eye examination/visit 1 to 5 years ago and ≥ 5 years ago (OR, 2.3 and 4.9, respectively), and less education (OR, 1.3 for 7-12 years and 1.7 for <7 years). Of 88 participants surgically treated for cataract who reported an eye examination <1 year ago, sensitivity and specificity of self-reported surgical history were 90.9% and 99.9%, respectively. Of the 31 participants treated for DR (laser/surgery) and reporting an eye examination <1 year ago, sensitivity and specificity of self-reported surgical history were 19.4% and 99.6%, respectively. CONCLUSIONS: Among Latinos, self-reporting of eye disease and surgical history provides a significant underestimate of the disease burden. This may lead to significant misclassification in vision research if self-report alone is used to identify persons with eye disease.

Asian age-related macular degeneration phenotyping study: rationale, design and protocol of a prospective cohort study.

BACKGROUND: Current knowledge of the phenotypic characteristics (e.g. clinical features, risk factors, natural history and treatment response) of age-related macular degeneration (AMD) in Asians remains limited. This report summarizes the rationale and study design of a prospective observational study of Asian neovascular AMD, including polypoidal choroidovasculopathy variant. DESIGN: The Asian AMD phenotyping study is a prospective, observational clinical study of Asian patients with neovascular AMD or polypoidal choroidovasculopathy in three tertiary eye centres in Singapore. PARTICIPANTS: The study aims to recruit 500 consecutive patients from the retinal clinics of three tertiary eye centres in Singapore. METHODS: Standardized examination procedures include interviews, a comprehensive eye examination, digital photography of the retina, fundus fluorescein and indocyanine green angiography and spectral domain optical coherence tomography using a standardized protocol. Blood samples were collected for biochemical analyses and stored for genetic and proteomic studies. MAIN OUTCOME MEASURES: The aim of the study was to build a comprehensive database of clinical, angiographic, functional and natural history data of Asian AMD over a 12-month follow-up period. RESULTS: This article discusses the methodology and design of this prospective multi-centred study. CONCLUSION: This study will provide in-depth longitudinal data of the evolution of clinical features, risk factors, natural history and treatment pattern and response of Asian AMD and polypoidal choroidovasculopathy, allowing unique insights into pathogenesis and the design of new treatment strategies.

Complement factor H genetic variant and age-related macular degeneration: effect size, modifiers and relationship to disease subtype.

BACKGROUND: Variation in the complement factor H gene (CFH) is associated with risk of late age-related macular degeneration (AMD). Previous studies have been case-control studies in populations of European ancestry with little differentiation in AMD subtype, and insufficient power to confirm or refute effect modification by smoking. METHODS: To precisely quantify the association of the single nucleotide polymorphism (SNP rs1061170, 'Y402H') with risk of AMD among studies with differing study designs, participant ancestry and AMD grade and to investigate effect modification by smoking, we report two unpublished genetic association studies (n = 2759) combined with data from 24 published studies (26 studies, 26,494 individuals, including 14,174 cases of AMD) of European ancestry, 10 of which provided individual-level data used to test gene-smoking interaction; and 16 published studies from non-European ancestry. RESULTS: In individuals of European ancestry, there was a significant association between Y402H and late-AMD with a per-allele odds ratio (OR) of 2.27 [95% confidence interval (CI) 2.10-2.45; P = 1.1 x 10(-161)]. There was no evidence of effect modification by smoking (P = 0.75). The frequency of Y402H varied by ancestral origin and the association with AMD in non-Europeans was less clear, limited by paucity of studies. CONCLUSION: The Y402H variant confers a 2-fold higher risk of late-AMD per copy in individuals of European descent. This was stable to stratification by study design and AMD classification and not modified by smoking. The lack of association in non-Europeans requires further verification. These findings are of direct relevance for disease prediction. New research is needed to ascertain if differences in circulating levels, expression or activity of factor H protein explain the genetic association.