Prevalence and predictors of myopic macular degeneration among Asian adults: pooled analysis from the Asian Eye Epidemiology Consortium.

AIMS: To determine the prevalence and predictors of myopic macular degeneration (MMD) in a consortium of Asian studies. METHODS: Individual-level data from 19 885 participants from four population-based studies, and 1379 highly myopic participants (defined as axial length (AL) >26.0 mm) from three clinic-based/school-based studies of the Asian Eye Epidemiology Consortium were pooled. MMD was graded from fundus photographs following the meta-analysis for pathologic myopia classification and defined as the presence of diffuse choroidal atrophy, patchy chorioretinal atrophy, macular atrophy, with or without 'plus' lesion (lacquer crack, choroidal neovascularisation or Fuchs' spot). Area under the curve (AUC) evaluation for predictors was performed for the population-based studies. RESULTS: The prevalence of MMD was 0.4%, 0.5%, 1.5% and 5.2% among Asians in rural India, Beijing, Russia and Singapore, respectively. In the population-based studies, older age (per year; OR=1.13), female (OR=2.0), spherical equivalent (SE; per negative diopter; OR=1.7), longer AL (per mm; OR=3.1) and lower education (OR=1.9) were associated with MMD after multivariable adjustment (all p<0.001). Similarly, in the clinic-based/school-based studies, older age (OR=1.07; p<0.001), female (OR=2.1; p<0.001), longer AL (OR=2.1; p<0.001) and lower education (OR=1.7; p=0.005) were associated with MMD after multivariable adjustment. SE had the highest AUC of 0.92, followed by AL (AUC=0.87). The combination of SE, age, education and gender had a marginally higher AUC (0.94). CONCLUSION: In this pooled analysis of multiple Asian studies, older age, female, lower education, greater myopia severity and longer AL were risk factors of MMD, and myopic SE was the strongest single predictor of MMD.

The In Vivo Correlation between Retinal Pigment Epithelium Thickness and Quantitative Fundus Autofluorescence in a White Population.

PURPOSE: To investigate the influence of age on the thickness of the retinal pigment epithelium (RPE)/Bruch's membrane (BM) complex and the quantitative autofluorescence (qAF) and to study the possible correlation existing between these 2 parameters in a healthy White population. DESIGN: Cross-sectional, observational study. PARTICIPANTS: Healthy White volunteers aged 18 to 65 years. METHODS: All subjects underwent spectral domain OCT (SD-OCT) and qAF imaging with the Heidelberg HRA-Spectralis (Heidelberg Engineering, Heidelberg, Germany). Spectral domain OCT images were analyzed using the in-built graph-based automatic segmentation algorithm for single retinal layer identification to assess RPE/BM complex thickness in vivo. The thickness values of both inner and outer rings of the Early Treatment Diabetic Retinopathy Study (ETDRS) grid, generated by the software using the "RPE" segmentation, were averaged to obtain a single RPE/BM complex thickness value in each eye. Quantitative autofluorescence images were also evaluated using a dedicated software. The qAF values of 8 subfields forming a ring centered onto the fovea were collected and averaged to obtain a single qAF value (qAF8) in each eye. The correlation among the RPE/BM complex thickness, the qAF value, and the age of the subjects was investigated. MAIN OUTCOME MEASURES: The in vivo correlation between RPE/BM complex thickness and qAF. RESULTS: A total of 105 eyes from 105 subjects (mean age, 42.1 ± 13.9 years; range, 18-65) were included in the analysis. The mean RPE/BM complex thickness significantly increased with age (r = 0.33, P = 0.0006). The values of qAF also positively increased with age (P < 0.0001). A significant correlation was found between qAF and RPE/BM complex thickness (r = 0.27, P = 0.004). After adjusting for age, iris color, and gender, the correlation remained significant only for subjects aged less than 40 years (P = 0.009). CONCLUSIONS: BM complex thickness was significantly co/BM complex thickness increased with age in a healthy White population. A similar increase was found for qAF values. After adjusting for age and iris color, qAF and RPE/BM complex thickness were still correlated in subjects aged less than 40 years. The RPE/BM complex thickness could reflect the lipofuscin/melanolipofuscin accumulation in normal subjects, adding great interest in RPE cell biology.

Exploring Factors Underlying Ethnic Difference in Age-related Macular Degeneration Prevalence.

AIMS: To assess contributions of dietary and genetic factors to ethnic differences in AMD prevalence. DESIGN: Population-based analytical study. METHODS: In the Blue Mountains Eye Study, Australia (European ancestry n = 2826) and Multi-Ethnic Cohort Study, Singapore (Asian ancestry, n = 1900), AMD was assessed from retinal photographs. Patterns of dietary composition and scores of the Alternative Healthy Eating Index were computed using food frequency questionnaire data. Genetic susceptibility to AMD was determined using either single nucleotide polymorphisms (SNPs) of the complement factor H and age-related maculopathy susceptibility 2 genes, or combined odds-weighted genetic risk scores of 24 AMD-associated SNPs. Associations of AMD with ethnicity, diet, and genetics were assessed using logistic regression. Six potential mediators covering genetic, diet and lifestyle factors were assessed for their contributions to AMD risk difference between the two samples using mediation analyses. RESULTS: Age-standardized prevalence of any (early or late) AMD was higher in the European (16%) compared to Asian samples (9%, p < .01). Mean AMD-related genetic risk scores were also higher in European (33.3 ± 4.4) than Asian (Chinese) samples (31.7 ± 3.7, p < .001). In a model simultaneously adjusting for age, ethnicity, genetic susceptibility and Alternative Healthy Eating Index scores, only age and genetic susceptibility were significantly associated with AMD. Genetic risk scores contributed 19% of AMD risk difference between the two samples while intake of polyunsaturated fatty acids contributed 7.2%. CONCLUSION: Genetic susceptibility to AMD was higher in European compared to Chinese samples and explained more of the AMD risk difference between the two samples than the dietary factors investigated.

Dietary Saturated Fatty Acid Intake and Early Age-Related Macular Degeneration in a Japanese Population.

Purpose: To assess the association of dietary saturated fatty acid (SFA) intake with the presence of early AMD in a Japanese population. Methods: The population-based Tsuruoka Metabolomics Cohort Study enrolled general population individuals aged 35 to 74 years from among participants in annual health check-up programs that included fundus photographs in Tsuruoka, Japan. A total of 4010 individuals participated in the baseline survey. After excluding nonresponders to a dietary survey and participants with suboptimal fundus image quality, 3988 participants (median age, 62.4 years) were included in this cross-sectional analysis. Dietary intake was assessed by a validated food frequency questionnaire. Fatty acids intake was adjusted for total energy intake by the residuals method. The association between fatty acid intake and presence of early AMD was assessed by logistic regression models. Results: Median daily SFA intake was 11.3 g (interquartile range, 9.6, 13.0 g). After adjustments for potential confounding factors, participants in the highest quartile of SFA intake were less likely to have early AMD, compared with the lowest quartile (odds ratio, 0.71; 95% confidence interval: 0.52-0.96). A significant trend for decreased risk of early AMD with increasing SFA intake was noted (P = 0.011). There was no significant association between poly-unsaturated fatty acid (PUFA) including n3-PUFA intake and early AMD. Conclusions: We found that increased SFA intake was associated with reduced risk of early AMD in a Japanese population with low SFA intake. Adequate fatty acid intake may be required to maintain retinal homeostasis and prevent AMD.

Rare Genetic Variants in Jewish Patients Suffering from Age-Related Macular Degeneration.

PURPOSE: To identify rare genetic variants in early age-related macular degeneration (AMD) utilizing whole-exome sequencing (WES). METHODS: Eight non-related early-AMD families of different Jewish ethnicities were ascertained. Initial mutation screening (phase-1) included common complement factor-H (CFH) p.Y402H; and age relatedmaculopathy susceptibility 2 (ARMS2) p.A69S; and rare variants complement factor-I (CFI) p.V412M; and hemicentin1 (HMCN1) c.4163delC identified previously in our population. Four families, whose initial screening for the aforementioned variants was negative, underwent WES (phase-2). Bioinformatics filtering was based on functionality (from a panel of 234 genes with proven or presumed association to AMD); predicted severity; and frequency (rare variants with minor allele frequency <1%). When applicable, further screening for specific rare variants was carried out on additional cases of similar ethnicities and phenotypes (phase-3). RESULTS: Phase-1 identified three families carrying CFI p.V412M mutation. WES analysis detected probable disease-related variants in three out of the remaining families. These included: a family with a variant in PLEKHA1 gene p.S177N; a family with previously reported variant p.R1210C in CFH gene; and two families with the C3 p.R735W variant. CONCLUSIONS: Rare, high-penetrance variants have a profound contribution to early-AMD pathogenesis. Utilization of WES in genetic research of multifactorial diseases as AMD, allows a thorough comprehensive analysis with the identification of previously unreported rare variants.

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.

Analysis of genetic polymorphisms for age-related macular degeneration (AMD) in Chinese Tujia ethnic minority group.

BACKGROUND: Age-related macular degeneration (AMD) can cause vision loss or blindness in elderly. The associations between single nucleotide polymorphism (SNP) and AMD in Chinese Tujia ethnic minority group are still unclear. METHODS: A total of 2122 Tujia volunteers were recruited and 197 of them were diagnosed with AMD (either dry or wet type).Then the blood specimens of these 197 AMD patients and 404 controls from the remaining 1925 normal Tujia volunteers were collected to detect the frequencies of 39 chosen SNPs. The Bonferroni method was used to correct the P values from the Fisher's exact test. RESULTS: The mean age of the 197 AMD patients(113 males and 84 females) was 68.4197 years old. No significant differences in allelic and genotypic frequencies were found for all the 39 SNPs between the patients and controls. However, weak correlations between 10 SNPs (CFH rs1329428 TT genotype, CFH rs3753394 CC genotype and T allele, CFH rs1410996 AA genotype, CFH rs800292 AA genotype, CFH rs800292 A allele, VEGF rs833061 TT genotype and C allele, VEGF rs2010963 CG genotype, VEGFR2 rs1531289 TT genotype, ARMS2 rs10490924 TT genotype, KCTD10 rs238104 GC genotype, rs1531289 T allele and ARMS2 rs10490924 T allele) and AMD were shown. CONCLUSIONS: The effects of 39 SNPs have found no associations with the morbidity of AMD in Chinese Tujia ethnic minority group.

The association between complement factor H rs1061170 polymorphism and age-related macular degeneration: a comprehensive meta-analysis stratified by stage of disease and ethnicity.

PURPOSE: The strength of association between complement factor H (CFH) rs1061170 polymorphism and age-related macular degeneration (AMD) differs between AMD subtypes and ethnicities. The main aim was to provide a systematic review and an updated meta-analysis stratified by stage of disease and ethnicity. METHODS: A literature search in the PubMed-Medline, EMBASE and Web of Science databases was conducted to identify epidemiological studies, published before September 2017, that included at least twp comparison groups (a control group with no signs of AMD and a case group of AMD patients). Genotype distribution, phenotype of the cases, ethnicity, mean age and gender ratio were collected. Odds ratios (ORs) and 95%CIs were estimated under the allelic, homozygous and heterozygous models. Sensitivity and subgroup analyses, by AMD subtype and ethnicity, were performed. RESULTS: The meta-analysis included data of 27 418 AMD patients and 32 843 controls from 76 studies. In Caucasians, the rs1061170 showed a significant association with early AMD (OR: 1.44; 95%CI 1.27-1.63), dry AMD (OR: 2.90; 95%CI 1.89-4.47) and wet AMD (OR: 2.46; 95%CI 2.15-2.83), under an allelic model. In Asians, the rs1061170 showed a significant association with advanced AMD (OR: 2.09; 95%CI 1.67-2.60), especially wet AMD (OR: 2.24; 95%CI 1.81-2.77). CONCLUSION: Our work provides a more comprehensive meta-analysis of studies investigating the effect of the CFH rs1061170 polymorphism on AMD risk. These findings not only improve the assessment of disease risk associated with the polymorphism, but also constitute a scientific background to be translated into clinical practice for AMD prevention.

Identification of novel pathogenic ABCA4 variants in a Han Chinese family with Stargardt disease.

Stargardt disease (STGD1, OMIM 248200) is a common hereditary juvenile or early adult onset macular degeneration. It ultimately leads to progressive central vision loss. Here, we sought to identify gene mutations associated with STGD1 in a three-generation Han Chinese pedigree by whole exome sequencing and Sanger sequencing. Two novel potentially pathogenic variants in a compound heterozygous state, c.3607G>T (p.(Gly1203Trp)) and c.6722T>C (p.(Leu2241Pro)), in the ATP binding cassette subfamily A member 4 gene (ABCA4) were identified as contributing to the family's STGD1 phenotype. These variants may impact the ABCA4 protein structure and reduce the retinal-activated ATPase activity, leading to abnormal all-trans retinal accumulation in photoreceptor outer segments and in retinal pigment epithelium cells. The present study broadens the mutational spectrum of the ABCA4 responsible for STGD1. A combination of whole exome sequencing and Sanger sequencing is likely to be a time-saving and cost-efficient approach to screen pathogenic variants in genetic disorders caused by sizable genes, as well as avoiding misdiagnosis. These results perhaps refine genetic counseling and ABCA4-targetted treatments for families affected by STGD1.

Observational study of clinical characteristics of dome-shaped macula in Chinese Han with high myopia at Zhongshan Ophthalmic Centre.

PURPOSE: To evaluate the prevalence of dome-shaped macula (DSM) in highly myopic eyes among Chinese Han and to detect the correlation with myopic maculopathy and macular complications. METHODS: A total of 736 Chinese Han patients (1384 eyes) with high myopia (refractive error≤6.0 diopters or axial length ≥26.5 mm) are reviewed based on information entered into a high-myopia database at Zhongshan Ophthalmic Centre. Subfoveal choroidal thickness (SFCT) and parafoveal choroidal thickness (PFCT) are measured. The prevalence of DSM in patients with myopic maculopathy is categorised from C0 to C4. Clinical features, including macular complications, SFCT and PFCT, are compared between myopic eyes with and without DSM. RESULTS: Among the 1384 eyes, 149 (10.77%) show DSM. In highly myopic eyes without macular complications, the best corrected visual acuity is significantly worse in patients with DSM (p=0.002), and the ratio between subfoveal and parafoveal choroidal thickness (S/PCT) is significantly elevated in patients with DSM (p=0.021). The proportion of foveal schisis (17.24% vs 62.86%) is much lower in eyes with DSM compared with those without DSM. However, the proportions of extrafoveal schisis (39.66% vs 5.37%), foveal serous retinal detachment (SRD) (5.17% vs 0) and epiretinal membrane (ERM) (24.14% vs 10.74%) are much higher in eyes with DSM. The proportion of DSM was lower in C0 and C1, but higher proportion of DSM was found in C3 and C4. CONCLUSIONS: DSM is found in 10.77% of highly myopic eyes among Chinese Han. DSM might be a protective mechanism for foveal schisis and a risk factor for extrafoveal schisis, SRD and ERM.

Variants in the ABCA4 gene in a Brazilian population with Stargardt disease.

Purpose: The aim of this study was to analyze and report pathogenic variants in the ABCA4 gene in Brazilian patients with a clinical diagnosis of Stargardt disease. Methods: This retrospective study evaluated variants in the ABCA4 gene in Brazilian patients with Stargardt disease. The patients' visual acuity and age of symptom onset were obtained from previous medical records. The patients were classified according to the autofluorescence patterns. Results: Fifty patients aged between 10 and 65 years from 44 families were included in the study. Among these cases, the mean age of symptom onset was 14 years (range, 5-40 years). ABCA4 gene sequencing was conclusive in 40 patients (80%), negative in two patients (4%), and inconclusive in eight patients (16%). Four families carried homozygous pathogenic variants. Segregation analysis results were available for 23 families. One novel variant was found: p.Ala2084Pro. The most frequent pathogenic variant in this group was p.Arg602Trp (12/100 alleles). Based on the phenotypic characteristics assessed with fundus autofluorescence imaging, 12 patients were classified as having type I phenotype, 16 as having type II, and 18 patients as having type III. The cases classified as type III phenotype included patients who were homozygous for the p.Asn96Asp and p.Arg2030* variants. One patient with a type I phenotype carried the homozygous intronic variant c.3862+1G>A. Conclusions: Next-generation sequencing was effective for the molecular diagnosis of genetic diseases and specifically allowed a conclusive diagnosis in 80% (40/50) of the patients. As the ABCA4 gene does not show a preferential region for pathogenic variants, the diagnosis of Stargardt disease depends on broader analysis of the gene. The most common pathogenic variants in the ABCA4 gene described in the literature were also found in these Brazilian patients. Although some genotype-phenotype correlations were found, more studies regarding the progression of Stargardt disease will help increase our understanding of the pathogenicity of these gene variants.

Circulating levels of mannose-binding lectin (MBL) in age-related macular degeneration.

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.

Toll-Like Receptors and Age-Related Macular Degeneration.

Age-related macular degeneration (AMD) is the leading cause of central vision loss in the over 50s worldwide. Activation of the immune system has been implicated in disease progression, but while polymorphisms in genes associated with the immune system have been identified as risk factors for disease, the underlying pathways and mechanisms involved in disease progression remain incompletely characterised. Typically inflammatory responses are mediated by microbial infection; however, in chronic conditions, a form of 'sterile' inflammation exists whereby immune responses occur in areas of the body, in the absence of microbes; 'sterile' inflammation is likely to be central to AMD. In this case the innate immune response is triggered when alarm signals released by stressed cells or damaged tissue are identified by pattern recognition receptors (PRRs). Toll-like receptors (TLRs) are a family of membrane-spanning PRRs for which host-derived ligands have been identified; these include heat shock proteins, extracellular matrix breakdown products, mRNA from necrotic cells and modified lipids. Here we review the evidence for TLR involvement in the pathogenesis of AMD.

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.

VISUAL ACUITY IN PATIENTS WITH STARGARDT DISEASE AFTER AGE 40.

PURPOSE: To better define visual acuity loss in patients with Stargardt disease later in life. METHODS: The most recent best-corrected visual acuities in the better-seeing eye of 221 patients with Stargardt disease over 40 years of age were recorded. Also included were the age at subjective onset for symptoms and duration of symptoms. Juvenile onset was defined as onset before age 21; adult onset was defined as onset between 21 and 40 years; and late onset was defined as onset at age 41 or later. RESULTS: The median age of the patients with Stargardt disease was 53.1 years. Twenty-four patients (10.9%) had worse than 20/400 best-corrected visual acuity, and none had either light perception or no light perception vision. Whereas 17 of the 52 juvenile onset patients had best-corrected visual acuity worse than 20/400, only 4 of 80 adult-onset patients and 1 of 70 late-onset patients reached this level of acuity loss. CONCLUSION: Although many patients with Stargardt disease lose visual acuity to the 20/200 to 20/400 range, and some lose visual acuity beyond 20/400, none of these patients reached either light perception or no light perception. The numbers found in this study will be valuable in counseling patients with Stargardt disease and could have value in planning treatment trials.

Factors Associated with Age-Related Macular Degeneration in Chinese American Adults: The Chinese American Eye Study (CHES).

OBJECTIVE: To assess associations between age-related macular degeneration (AMD) and multiple factors comprising a conceptual model of AMD risk in a population of Chinese Americans, and to draw comparisons with a similar risk assessment of a Latino population. DESIGN: A cross-sectional population-based study. PARTICIPANTS: We enrolled 4582 Chinese Americans aged ≥50 residing in Monterey Park, California. METHODS: Participants completed a comprehensive eye examination, including stereoscopic fundus photography and ocular biometric measurements. Fundus images were graded using a modified version of the Wisconsin Age-Related Maculopathy Grading System. MAIN OUTCOMES AND MEASURES: Odds ratios for factors significantly modifying the risk of AMD and its related retinal lesions. RESULTS: Of the eligible participants, 4172 (72%) had fundus photographs gradable for AMD. Early AMD was present in 375 eyes (4.6%), and late AMD was present in 17 (0.2%). Shorter axial length, male sex, older age, and family history of AMD were identified as independent risk factors for prevalent AMD and its characteristic retinal lesions using a conceptual model of potential AMD risk factors. Of 4 AMD risk factors identified for Latinos, 3 (older age, male sex, shorter axial length) overlapped with those identified for Chinese Americans, with an association similar in magnitude and direction. Lower levels of education were a risk factor specific to Latinos. Based on a multivariable logistic regression model, the predicted probability of early AMD was 31% lower among Chinese Americans relative to Latinos (95% confidence interval [CI], 17%-43%). Chinese Americans also had statistically significantly lower odds of any AMD and 2 types of early retinal lesions symptomatic of AMD. CONCLUSIONS: Factors associated with prevalent AMD are similar for Chinese Americans and Latinos. Chinese Americans who were older, were male, had a family history of AMD, and had a shorter axial length were at an increased risk for AMD compared with those without these risk factors. We observed a significantly lower predicted prevalence of AMD among Chinese Americans compared with Latinos, even after controlling for all relevant covariates, suggesting that additional genetic or lifestyle differences may play an important role in determining AMD risk.

ERG and OCT findings of a patient with a clinical diagnosis of occult macular dystrophy in a patient of Ashkenazi Jewish descent associated with a novel mutation in the gene encoding RP1L1.

A 57-year-old man with a past medical history of diabetes presented for consultation with a several year history of slowly progressive vision loss in both eyes, which continued to deteriorate over 7 years of follow-up. Multimodal imaging was performed and was significant for the following: on spectral domain optical coherence tomography, a gap lesion was present in the ellipsoid layer, beneath the umbo, as well as subtle macular changes on auto fluorescence imaging. Multifocal electroretinography was performed and was abnormal, and a clinical diagnosis of occult macular dystrophy was made. The patient was subsequently evaluated with genetic testing that revealed a novel p.P73S:c 217C>T nonsense mutation within the retinitis pigmentosa 1-like-1 (RP1L1) gene. The clinical significance of the identified variation will require further investigation.

Physical Activity and Age-related Macular Degeneration: A Systematic Literature Review and Meta-analysis.

PURPOSE: To better understand the association, in a white population, of physical activity and age-related macular degeneration (AMD)-the main cause of irreversible severe vision loss in developed countries-given the suggestion that a healthy lifestyle may assist in delaying the onset and progression of AMD. DESIGN: Systematic review and meta-analysis. METHODS: Medline, EMBASE, and Google Scholar were systematically searched for studies up to May 2015. Reference lists of published articles were hand searched and study authors were contacted to provide additional data. Those in the lowest category of activity in each study were compared with all other participants to assess the association between physical activity and both early and late AMD using random-effects meta-analysis. RESULTS: Nine studies (subject age range 30-97 years) were included in the meta-analysis. Physical activity was found to have a protective association with both early AMD (8 studies, n = 38 112, odds ratio (OR) 0.92, 95% confidence interval [CI] 0.86-0.98) and late AMD (7 studies, n = 28 854, OR 0.59, 95% CI 0.49-0.72). CONCLUSIONS: Physical activity is associated with lower odds of early and late AMD in white populations. These findings have important implications, reinforcing the public health message of staying active throughout life. However, further longitudinal studies are required to confirm and further characterize a protective effect of physical activity on the onset and/or progression of AMD.

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.