Prevalence and associations of intraretinal hyperreflective foci in age-related macular degeneration: the Beijing Eye Study.

To assess the prevalence and associations of external limiting membrane (ELM) defects on optical coherence tomographic (OCT) images in a general population, affected by age-related macular degeneration (AMD) or free of any retinal disease. Using OCT images, we assessed the ELM defect presence in participants of the population-based Beijing Eye Study. The study population consisted of 712 (44.2%) eyes with early AMD, 295 (18.3%) eyes with intermediate AMD, 12 (0.7%) eyes with geographic atrophy and 592 (36.7%) eyes without signs of AMD. ELM defect prevalence increased from 6/592 (1.0%; 95% CI: 0.0, 2.0) in the normal group to 57/712 (8.0%; 95% CI: 6.0, 10.0), 117/295 (39.7%; 95% CI: 34.2, 45.2) and 11/12 (91.7%; 95% CI: 73.7, 100) in the group with early AMD stage, intermediate AMD and late AMD stage, respectively. Higher ELM defect prevalence was spatially associated with higher prevalence of ellipsoid zone (EZ) defects (OR: 929; 95% CI: 291-2964; p < 0.001). In multivariable analysis, higher ELM defect prevalence correlated with higher AMD stage (OR: 2.22; 95% CI: 1.33, 3.71; p = 0.002), higher prevalence of intraretinal hyperreflective foci (iHRFs) superior to the EZ/ELM (OR: 29.7; 95% CI: 8.69-102; p < 0.001), lower prevalence of iHRFs beneath the EZ/ELM (OR: 0.11; 95% CI: 0.04, 0.35; p < 0.001) and higher prevalence of localized interdigitation zone thinnings (IZTs) (OR: 5.66; 95% CI: 3.14, 10.2; p < 0.001). The spatial correlation between ELM defects and EZ defects, the associations of both defect types with a higher occurrence of iHRFs superior to the ELM, the association between an absence of ELM defects and a higher prevalence of iHRFs located inferior to the ELM, and the association between a higher ELM defect prevalence and higher IZT prevalence may suggest the ELM/EZ may act as a barrier for RPE cells migrating into the retina.

Intraretinal Retinal Pigment Epithelium Cells in Age-Related Macular Degeneration

Characteristics and Spatial Distribution of Structural Features in Age-Related Macular Degeneration: A MACUSTAR Study Report

To assess associations of macular drusen in a general population, affected by age-related macular degeneration (AMD) or free of any retinal disease. Participants of the population-based cross-sectional Beijing Eye Study underwent optical coherence tomography. Macular volume scans were assessed for macular drusen. The study included 870 eyes (870 participants) (age: 64.7 ± 9.9 years; range: 50-91 years), randomly selected within the groups of early AMD (n = 356 (40.9%) eyes), intermediate AMD (n = 201; 23.1%), late AMD (n = 6; 0.7%) and within eyes without AMD (n = 307; 35.3%). In multivariable analysis, higher drusen count was associated (r2 = 25) with older age (beta: 0.08; p = 0.048), higher serum concentration of cholesterol (beta: 0.10; p = 0.008), shorter axial length (beta: -0.09; p = 0.03), thicker subfoveal choroidal thickness (beta: 0.08; p = 0.04), higher prevalences of macular hyperpigmentations (beta: 0.13; p < 0.001), hyperreflective foci (HRFs) (beta: 0.12; p = 0.004) and reticular pseudodrusen (beta: 0.27; p < 0.001), and a lower prevalence of a visible Henle's layer (beta: -0.15; p < 0.001). Larger drusen size was associated with shorter axial length (beta: -0.08; p = 0.03), thicker subfoveal choroidal thickness (beta: 0.18; p < 0.001), higher prevalences of macular hypopigmentations (beta: 0.14; p < 0.001) and HRFs (beta: 0.31; p < 0.001), and lower prevalences of a visible Henle's layer (beta: -0.19; p < 0.001) and of reticular pseudodrusen (beta: -0.09; p = 0.02). In this population-based study on Chinese, higher macular drusen count was associated with shorter axial length, thicker subfoveal choroidal thickness, higher prevalences of macular hyperpigmentations, HRFs and reticular pseudodrusen and lower prevalence of a visible Henle's layer. These findings may be clinically helpful and etiologically interesting.

To assess the prevalence and associations of the detectability of the three-layer sign (TLS) in a general population, including individuals with age-related macular degeneration (AMD) or without any retinal disease. Using OCT images running horizontally through the foveola of participants of the population-based Beijing Eye Study, we assessed the TLS detectability. We defined the TLS as the visibility of the ellipsoid zone (EZ), interdigitation zone and retinal pigment epithelium (RPE)/Bruch's membrane line as separate units in the foveola on optical coherence tomographic (OCT) images. The study included 1566 eyes (age: 65.3 ± 9.8 years; axial length: 23.01 ± 0.93 mm; range: 19.90 mm-28.93 mm), randomly selected within each group of normal eyes (n = 592; 37.8%), eyes with early AMD (n = 700; 44.7%), intermediate AMD (n = 267; 17.0%), and late AMD (n = 7; 0.4%). In the normal group, TLS prevalence decreased with older age (OR: 0.93; p < 0.001), declining from 217/265 (81.9%) in the 50-59 years age group to 57/126 (45.2%) in individuals aged 70+ years. In the whole study cohort, TLS prevalence decreased (p < 0.001) from 389/592 (65.7%) in the normal group to 334/700 (47.7%), 66/267 (24.7%) and 0/7 (0%) in early AMD, intermediate AMD and late AMD, respectively. In multivariable analysis, higher TLS prevalence was associated with younger age (OR: 0.92; p < 0.001), female sex (OR: 1.65; p < 0.001), lower AMD stage (OR: 0.51; p < 0.001), better best-corrected visual acuity (OR: 0.42; p = 0.03), and lower prevalence of a flat retinal pigment epithelium elevation (OR: 0.68; p = 0.04). The foveal TLS may be taken as a qualitative sign of the intactness of the deep layers of the fovea, with its prevalence decreasing with older age, higher AMD stage and worse best-corrected visual acuity.

To investigate the incidence of late age-related macular degeneration (AMD) over 3 years and risk factors for the development of late AMD in Korean patients having reticular pseudodrusen (RPD). Clinical records of Korean RPD patients with no late AMD at first examination and completion of 3 years of regular follow-up were retrospectively reviewed. All patients underwent complete ocular examinations, including multimodal imaging. Reticular pseudodrusen were classified as a separate lesion different from other early AMD lesions, and RPD were not considered a sign of early AMD. Risk factors for the development of late AMD were assessed. One hundred and ninety-two RPD eyes of 104 patients were included in this study. Mean age of patients was 69.4 ± 8.9 years, and other early AMD lesions were accompanied in 152 eyes (79.2%) at baseline. During 3 years, late AMD occurred in 30 eyes (15.6%); geographic atrophy in 24 eyes (12.5%); and neovascular AMD in 6 eyes (3.1%). Eyes having early AMD at baseline revealed significantly higher incidence for late AMD than those eyes having no early AMD at baseline (18.4% vs. 5%, P = 0.048). Late AMD occurred in 5 eyes (38.5%) from 13 fellow RPD eyes of unilateral late AMD at baseline. In logistic regression analysis, thin choroidal thickness, diffuse distribution of RPD, and the presence of late AMD on fellow eye at baseline were significant risk factors for developing late AMD in RPD eyes. Reticular pseudodrusen eyes revealed various progression rates to late AMD according to AMD status of both eyes. More frequent monitoring should be considered for patients with RPD at risk of progression to late AMD.

AimTo assess the impact of early and late age-related macular degeneration (AMD) on vision-specific functioning in Singapore Malays.MethodsAMD was assessed from fundus photographs. The following endpoints were considered for (a)...

Purpose To assess foveal microstructural changes influencing retinal sensitivity (RS) and fixation stability using microperimeter MP-1 in intermediate age-related macular degeneration (AMD).Methods In this cross-sectional study, 22 eyes of 22 patients (mean age: 75 ± 9.02 years) with intermediate AMD were enrolled. Retinal sensitivity and bivariate contour ellipse area (BCEA) were obtained by microperimetry MP-1 (Humphrey 10-2 68-loci grid) under mesopic conditions. Drusen type, drusenoid pigment epithelial detachment, hyperreflective foci (HF), integrity of external limiting membrane (ELM), inner ellipsoid zone (ISel), RPE/Bruch’s membrane complex (RPE/B) and subfoveal choroidal thickness were analyzed in the foveal region and compared with RS and BCEA. Spearman’s rank correlation coefficient was used to evaluate the relationship between variables. Logistic regression analysis was also used to assess morphological predictor influencing RS or BCEA.ResultsRS was strongly and inversely related with the presence of HF (r = −0.66, P = 0.001), integrity of ELM (r = −0.70, P < 0.001), ellipsoid zone (r = −0.45, P = 0.03). Instead, BCEA is positively related to the ellipsoid zone integrity (r = 0.45, P = 0.03). Logistic regression analysis confirmed that disruption of ISel influenced fixation stability (ExpB: 9.69, P = 0.04) but not RS. Instead, the presence of HF and disruption of ELM predicted RS reduction (ExpB: 0.55, P = 0.02 and ExpB: 0.29, P = 0.04, respectively).ConclusionsThe integrity of ELM and the presence of HF are both predictors of RS. The ELM status may be considered a new biomarker of retinal function together with HF. Instead, the integrity of ISel band seems to be a more selective predictor of BCEA than RS.

Are there advantages in implanting a yellow IOL to reduce the risk of AMD?

Outer retinal band integrity strongly predicts late age-related macular degeneration (AMD). However, it is often assessed subjectively as "continuity" using inconsistent definitions. Alternatively, "curvature" of the outer retinal bands is a quantitative metric that strongly correlates with AMD biomarkers and can screen for intermediate AMD. We evaluated the prognostic ability of retinal pigment epithelium (RPE) and ellipsoid zone (EZ) curvature for late AMD against outer retinal band continuity, pigmentary abnormalities, reticular pseudodrusen, and drusen volume. Consecutive patients with intermediate AMD who progressed to late AMD (n = 17) or remained stable (n = 42) were recruited. RPE and EZ curvature were quantified as a ratio of their lengths over Bruch's membrane using the sinuosity method of assessing river curvature, where a ratio of ∼1 indicates no outer retinal pathology. RPE, EZ, and Bruch's membrane were manually segmented and their lengths automatically extracted. The primary outcomes were outer retinal sinuosity and the odds ratio of predicting late AMD. Mean follow-up time for progressors and nonprogressors was 4.4 and 3.6 years. RPE sinuosity was strongly associated with pigmentary abnormalities (P = 0.001) and drusen volume (P = 0.004) but not reticular pseudodrusen (P = 0.28). RPE sinuosity >1.03 was the strongest predictor of late AMD developing within 5 years (15 [2.9-75]) and across the study period (25 [2.3-282]). Drusen volume >0.03 mm3 was the strongest predictor of progression within 2 years (33 [2.5-426]), and RPD could not independently predict progression within any time frame. RPE curvature is a promising, quantitative outer retinal biomarker that can prognosticate late AMD and potentially enhance prognostic models.

Aim: To explore the association of use versus no use and the influence of pack-year use of smokeless tobacco with that of early and late age-related macular degeneration (AMD) in rural and urban south Indian population. We hypothesized that the use and pack-years of use would be significantly associated with both early and late AMD. We therefore sought to examine subjects who gave a history of using smokeless tobacco and we quantified the usage as pack-years, to examine the association with that of early and late AMD.Materials and methods: This was part of Sankara Nethralaya: Rural–Urban Age-related Macular degeneration study (SN-RAM study), which was conducted between 2007 and 2010. Subjects aged 60 years or older or those turning 60 in the present calendar year, with a history of using smokeless tobacco were noted along with duration and number of packs used per day. Smokeless tobacco was defined as chewed-tobacco (loose leaves) and/or snuff (finely chopped tobacco). Subjects underwent detailed ophthalmic evaluation including cataract grading using the Lens Opacities Classification System (LOCS III), 45° 4-field stereoscopic fundus photography and AMD evaluation. Pack-years of smokeless tobacco use was stratified as <15, 15–34 and ≥35 years; the association of tobacco use and pack-years of use with that of early and late AMD was examined. A p value of < 0.05 was considered statistically significant.Results: The number of smokeless tobacco users was significantly higher in rural (n = 767) than in urban groups (n = 281), p < 0.001. Of the 1048 users, 238 subjects (23%) provided details regarding quantification of use. There were no significant differences in the pack-years between rural and urban areas, p = 0.756 or that between AMD and no AMD, p = 0.562. Use of smokeless tobacco compared with no use was significantly associated with late AMD, OR= 3.178, 95%CI: 1.095, 9.227, p = 0.033, when adjusted for age, gender, rural-urban differences, presence of diabetes, socioeconomic status, systolic and diastolic blood pressure, total cholesterol, low-density and high-density lipoprotein levels. The association was not significant for early AMD, p = 0.582. The pack-years of use did not show a statistically significant association with early or late AMD. Furthermore, out of the 1048 subjects, 547 reported as using areca nut. Of which, 415 (75.8%) subjects had no AMD, 119 (21.7%) showed evidence of early AMD and 13 (2.4%) had late AMD. There was no significant association between the use of areca nut and early AMD, (X2 (1, N = 930) = 2.345, p = 0.126) or with that of late AMD (X2 (1, N = 761) = 0.075, p = 0.785).Conclusions: Smokeless tobacco use compared with no use, is associated with late AMD, regardless of the pack-years of use. Tobacco use is a modifiable risk factor. Efforts to reduce or stop the use of smokeless tobacco is indicated in an effort to prevent vision loss with respect to late AMD.

Associations between Serum Vitamin D and Genetic Variants in Vitamin D Pathways and Age-Related Macular Degeneration in the European Eye Study

The Incidence and Progression of Age-Related Macular Degeneration over 15 Years: The Blue Mountains Eye Study

To assess the photoreceptor layer thickness and its associations with age-related macular degeneration (AMD). Participants of the population-based Beijing Eye Study without optic nerve or retinal diseases (except for early and intermediate AMD) were examined by optical coherence tomography of the macula. The study cohort was composed of 2426 participants (mean age: 62.8±9.1 years; range: 50-93 years), with 200 and 393 individuals affected by early AMD and intermediate AMD, respectively. In multivariable analysis, thickness of Henle's fibre layer, outer nuclear layer, external limiting membrane and myoid zone (HOEM) combined was not significantly associated with AMD prevalence (beta: 0.03; p=0.08) or AMD stage (beta: 0.04; p=0.06), after adjusting for younger age (beta: -0.09; p<0.001), shorter axial length (beta: -0.07; p<0.001), thicker ellipsoid zone (EZ) (beta: 0.19; p<0.001), thicker photoreceptor outer segment (POS) layer (beta: 0.12; p<0.001), thicker subfoveal choroid (beta: 0.11; p<0.001) and thinner retinal pigment epithelium/Bruch's membrane (RPE/BM) layer (beta: -0.17; p<0.001). Thicker EZ correlated with lower AMD prevalence (beta: -0.04; p=0.03) and lower AMD stage (beta: -0.02; p=0.02), with adjustment for older age (beta: 0.05; p=0.03), longer axial length (beta: 0.06; p=0.001), thicker HOEM (beta: 0.19; p<0.001) and thinner RPE/BM (beta: -0.31; p<0.001). Including only normal eyes and eyes with early AMD, EZ thickness was not significantly correlated with AMD prevalence (beta: -0.02; p=0.49). Thicker POS correlated with lower AMD prevalence (beta: -0.06; p<0.001) after adjusting for younger age (beta: -0.10; p<0.001), thicker HOEM (beta: 0.08; p<0.001) and thinner RPE/BM layer (beta: -0.62; p<0.001). If only normal eyes and eyes with early AMD were included, POS thickness was not significantly related to AMD prevalence (beta: -0.03; p=0.09). Thickness of HOEM, EZ and POS was not significantly associated with the prevalence of early AMD.

To assess cross-sectional and longitudinal associations between exposure to Chlamydia pneumoniae infection and age-related macular degeneration (AMD) in the nested case-control sample drawn from the Blue Mountains Eye Study (BMES) cohort. The BMES examined 3654 persons aged 49 to 97 years during 1992 through 1994 (BMES I survey). Survivors from this cohort (n = 2335; 75%) and 1174 persons who moved in this area or reached an eligible age were examined during 1997 through 2000 (BMES II survey, n = 3509). One hundred ninety-seven AMD cases and 433 control subjects matched for age, sex and smoking status, were drawn from the BMES II survey. Photographic macular grading followed the Wisconsin grading system. Plasma samples were analyzed with an enzyme-linked immunosorbent assay to determine antibody titers to the elementary bodies from C. pneumoniae AR39. Associations between seroreactivity to C. pneumoniae and prevalent and incident AMD were assessed by using logistic regression models. There were 159 early and 38 late AMD cases. Of them, 87 cases of early and 22 of late AMD developed between the baseline and follow-up examinations. After adjustment for age, gender, and smoking, no significant association was evident between C. pneumoniae antibody titer and any prevalent early or late AMD (OR 1.02, 95% CI 0.66-1.56 comparing upper with lower tertile of antibody titer). Findings were similar when early or late AMD was analyzed separately. Analysis confined to incident AMD also showed no significant association with the incidence of either early (OR 0.92, 95% CI 0.52-1.64) or late (OR 1.85, 95% CI 0.57-6.05) AMD. The results did not change after adjustment for family history of AMD and cardiovascular disease. In this nested case-control sample of an older Australian population we found no association between C. pneumoniae antibody titers and early AMD. The study has insufficient power to assess an association with late AMD.