Age-related Macular Degeneration Grading Research Articles

Early Age-Related Macular Degeneration, Cognitive Function, and Dementia

To describe the association of cognitive function and dementia with early age-related macular degeneration (AMD) in older individuals. This population-based study included 2,088 persons aged 69 to 97 years who participated in the Cardiovascular Health Study. The AMD was assessed from retinal photographs based on a modified Wisconsin AMD grading system. Cognitive function was assessed using the Digit Symbol Substitution Test (DSST) and the Modified Mini-Mental State Examination. Participants were also evaluated for dementia using detailed neuropsychological testing. After controlling for age, sex, race, and study center, persons with low DSST scores (lowest quartile of scores, < or =30) were more likely to have early AMD (odds ratio, 1.38; 95% confidence interval, 1.03-1.85) than were persons with higher DSST scores. In analyses further controlling for education, systolic blood pressure, total cholesterol level, diabetes mellitus, smoking status, and apolipoprotein E genotype, this association was stronger (odds ratio, 2.00; 95% confidence interval, 1.29-3.10). There was no association of low Modified Mini-Mental State Examination scores, dementia, or Alzheimer disease with early AMD. In this older population, cognitive impairment may share common age-related pathogenesis and risk factors with early AMD.

Education, socio-economic status and age-related macular degeneration in Asians: the Singapore Malay Eye Study

Background/aims:Low socio-economic status is increasingly being identified as a risk marker for chronic diseases, but few studies have investigated the link between socio-economic factors and age-related macular degeneration (AMD). The...

Pigment Epithelium-Derived Factor Gene Met72Thr Polymorphism Is Associated With Increased Risk of Wet Age-related Macular Degeneration

To investigate the Met72Thr (T/C) polymorphism (rs1136287) of pigment epithelium-derived factor (PEDF) gene exon 3 in unrelated Taiwan Chinese patients with late age-related macular degeneration (AMD) and control subjects without AMD. Retrospective case-control study. We enrolled 190 unrelated Taiwan Chinese patients with late AMD and 90 age- and gender-matched control subjects. Grading of late AMD was classified based on a standardized set of diagnostic criteria established by the International Age-Related Maculopathy Epidemiologic Study. Late AMD was classified as either atrophic (dry, grade 4) or neovascular (wet, grade 5). Atrophic AMD refers to dry late-stage AMD without neovascularization, and wet AMD refers to neovascular AMD. Genomic deoxyribonucleic acid was prepared from peripheral blood obtained from all AMD patients and control subjects. Polymerase chain reaction analysis was used to analyze this polymorphism. Of the 190 participants with late AMD, atrophic AMD was diagnosed in 104 patients and wet AMD was diagnosed in 86 patients. The genotype distribution of the Met72Thr (T/C) variant of PEDF was TT (homozygous T), TC (heterozygous), and CC (homozygous C). The T allele was found significantly more frequently in wet AMD patients than in controls (50% vs 31%; P =.0005). The allele frequencies in atrophic AMD (30%) and controls (31%) did not differ significantly (all P = .87). The homozygous T genotype was more prevalent in wet AMD than in controls (26/86 [30%] vs nine/90 [10%]; odds ratio, 3.9; all P = .0015). The homozygous T genotype in atrophic AMD patients (8%) and controls (10%) did not differ significantly (all P = .75). Our data suggest that the PEDF Met72Thr T allele may be a risk factor for wet AMD in the Taiwan Chinese population. PEDF may play a role in the pathogenesis of wet AMD.

Peripheral Reticular Pigmentary Change Is Associated with Complement Factor H Polymorphism (Y402H) in Age-Related Macular Degeneration

To examine phenotypes of age-related macular degeneration (AMD) patients with the complement factor H (CFH) variant (Y402H, C allele at rs1061170). Clinic-based case series study. The data set contained a total of 956 unrelated cases of AMD. Age-related macular degeneration phenotypes of 796 carriers of the CFH Y402H variant were compared with the AMD phenotypes of 160 noncarriers. Presence or absence of 34 phenotypic features. Of the 34 features analyzed, only peripheral reticular pigmentary change (PRPC) was associated with this CFH variant (P = 0.0006). The proportion of AMD cases with PRPC correlated with the number of CFH risk C alleles in a dose-response fashion. The CFH Y402H polymorphism is associated with PRPC, suggesting that AMD changes are not limited to the macula. Current AMD grading methods assess only the macula and should consider incorporating peripheral retinal changes. Phenotypes that suggest a high-risk genotype may prove valuable for diagnostic, therapeutic, and research purposes.

The LOC387715 Gene, Smoking, Body Mass Index, Environmental Associations with Advanced Age-Related Macular Degeneration

Background and Aims: Age-related macular degeneration (AMD) is the leading cause of blindness in the Western World. It is now evident that both genetic and environmental factors contribute to disease susceptibility. We tested the hypotheses that (a) a common coding SNP in the LOC387715 gene is associated with advanced AMD (geographic atrophy or choroidal neovascularization), and (b) that modifiable environmental exposures alter AMD susceptibility associated with this SNP. Methods: A case-control association analysis was performed on participants (530 advanced AMD cases and 280 controls) ascertained as part of the multi-center Age-Related Eye Disease Study. AMD status was determined by the reading center from fundus photographs using the AREDS AMD grading categorization. Environmental risk factor exposure data was collected from participants whose DNA was also genotyped for the LOC387715 gene SNP rs10490924. Multivariate logistic regression analyses were performed. Results and Conclusions: The number of risk alleles at the LOC387715 SNP was associated with advanced AMD, with odds ratios (OR) = 3.0 (95% confidence interval (CI) 2.1–4.3) for the GT heterozygous genotype and OR = 12.1 (5.6–26.5) for the homozygous TT risk genotype, after controlling for demographic and behavioral risk factors. The LOC387715 SNP was associated with both forms of advanced AMD. Current cigarette smoking and body mass index were independently related to AMD, controlling for genotype. However, there was no statistical interaction between LOC387715 genotype and smoking with regard to advanced AMD development.

Exposure to Chlamydia pneumoniae Infection and Progression of Age-related Macular Degeneration

Recent studies have found an association between exposure to Chlamydia pneumoniae infection and risk of age-related macular degeneration (AMD). To assess a potential risk of AMD progression posed by exposure to C. pneumoniae, the authors reexamined Australian residents in 2001-2002 who were aged 51-89 years with early AMD at baseline (1992-1995). Examination included macular photography and an enzyme-linked immunosorbent assay to determine antibody titers to the elementary bodies from C. pneumoniae AR39. AMD progression was assessed quantitatively, using both coarse and fine progression steps following an international classification for AMD grading, and also qualitatively, by side-by-side comparison of baseline and follow-up macular photographs. Serologic data were available for 246 of 254 (97%) subjects. AMD progression was associated with a higher antibody titer. After adjustment for age, smoking, family history of AMD, history of cardiovascular diseases, and source study, the subjects in the upper tertiles of antibody titers were 2.1 (95% confidence interval: 0.92, 4.69), 2.6 (95% confidence interval: 1.24, 5.41), and 3.0 (95% confidence interval: 1.46, 6.37) times more at risk of progression than those in the lowest tertile, using three definitions of progression, respectively. The fact that seroreactivity to C. pneumoniae was independently associated with the risk of AMD progression suggests that C. pneumoniae infection may be an additional risk factor for AMD progression.

Decreased Thickness and Integrity of the Macular Elastic Layer of Bruch's Membrane Correspond to the Distribution of Lesions Associated with Age-Related Macular Degeneration

Age-related macular degeneration (AMD) is a leading cause of blindness in the elderly. In its severest form, choroidal neovessels breach the macular Bruch's membrane, an extracellular matrix compartment comprised of elastin and collagen laminae, and grow into the retina. We sought to determine whether structural properties of the elastic lamina (EL) correspond to the region of the macula that is predilected toward degeneration in AMD. Morphometric assessment of the macular and extramacular regions of 121 human donor eyes, with and without AMD, revealed a statistically significant difference in both the integrity (P < 0.0001) and thickness (P < 0.0001) of the EL between the macular and extramacular regions in donors of all ages. The EL was three to six times thinner and two to five times less abundant in the macula than in the periphery. The integrity of the macular EL was significantly lower in donors with early-stage AMD (P = 0.028), active choroidal neovascularization (P = 0.020), and disciform scars (P = 0.003), as compared to unaffected, age-matched controls. EL thickness was significantly lower only in individuals with disciform scars (P = 0.008). The largest gaps in macular EL integrity were significantly larger in all categories of AMD (each P < 0.0001), as compared to controls. EL integrity, thickness, and gap length in donors with geographic atrophy did not differ from those of controls. These structural properties of the macular EL correspond spatially to the distribution of macular lesions associated with AMD and may help to explain why the macula is more susceptible to degenerative events that occur in this disease.

Serum vitamin E levels negatively correlate with severity of age-related macular degeneration

Age-related macular degeneration (AMD) pathogenesis has been related to UV radiation and other factors that may promote increased oxidative damage to the retina. Patients with different AMD grading ( n=25) were compared with an age-matched group of AMD-free subjects ( n=15), both groups older than 60 years. A modification of the AMD grading system is proposed that allows patient grading and not single eye grading. AMD patients showed statistically significant lower serum levels of vitamin E and Zn than AMD-free subjects. Moreover, a negative correlation (Spearman's correlation coefficient r=−0.815, P<0.001) could be established between AMD grading of both the patients’ eyes and serum vitamin E levels. Sun exposure index (SEI) was also compared and found to be significantly higher in the AMD group. The results presented establish the importance of antioxidants in AMD, and set the basis for further studies on adjuvant therapies with antioxidants for AMD. Finally, the results also confirm the pathogenic role of UV radiation in AMD.

The Wisconsin age-related macular degeneration grading system: performance in an independent centre.

The Wisconsin age-related macular degeneration grading system: performance in an independent centre.

Seven year follow-up of age-related maculopathy in an elderly British population.

Despite age-related macular degeneration (AMD) being the commonest cause of blindness amongst the elderly in Western society, the incidence of new lesions is poorly documented and the natural history of existing disease remains ill understood. To document in an elderly population the incidence of new AMD lesions and the progression of pre-existing AMD over time. Baseline ophthalmic examinations were performed on a geographically defined random population sample of elderly people in 1982-4, and retinal photographs taken. The present study re-examined and re-photographed survivors after approximately 7 years using the same fundus camera. Photographs were randomly encoded, and independently graded for AMD features by two masked observers using the Wisconsin AMD grading system. Disagreements were resolved by review to reach a consensus. Eighty-two of the 88 participating survivors had photographs of gradable quality on both occasions in at least one eye. Mean age at follow-up was 87 years (range 84-97 years) and 70.7% of subjects were female. Paired photographs were available on 158 eyes, and showed important differences in drusen type, drusen area and characteristics of the retinal pigment epithelium (RPE) between initial and subsequent examinations. The 7 year incidence (and regression) of lesions was: drusen 30.6% (20.0%), RPE degeneration 54.5% (8.8%), increased pigment 11.6% (64.7%), subretinal haemorrhage 1.3%, subretinal scar/fibrin 1.3% and geographic study 1.3%. These unique population-based results provide new insight into the natural history of AMD in an elderly population.

The Wisconsin Age-related Macular Degeneration grading system: Performance in an independent centre

INTRODUCTION Age-related Macular Degeneration (AMD) is the commonest cause of blindness in developed nations. Despite this, the epidemiology of AMD is poorly understood. A need for the documentation of AMD prevalence and incidence at a population level has stimulated the development of a comprehensive, observer-based, photographic grading method for AMD in Wisconsin.AIM To independently assess the performance of the Wisconsin method by self-taught graders outside its centre of inception.METHOD The inter-observer variability and confidence limits for detection of change were assessed for two self-taught graders (ophthalmologists). Self teaching was achieved exclusively from documentation and photographs provided by the system developers in Wisconsin. 295 retinal photographs of elderly people were independently assessed for 13 features by each of the two graders.RESULTS Weighted and unweighted kappa statistics, % exact and one step apart agreement, and confidence limits for detection of change were calculated for the graded features on a ‘by eye’ basis, and where appropriate, on a ‘by retinal subfield’ basis. Levels of agreement for weighted kappa were moderate to substantial for most features. 95% and 90% confidence limits for significant change beyond measurement error were determined in terms of scale increments.CONCLUSION We conclude that the Wisconsin AMD grading system can be independently learnt from documentation and photographs alone, and that an acceptable level of performance is attainable by self-taught graders.