Macular Degeneration: Clemons TE

SanGiovanni JP, Chew EY, Agrón E, Clemons TE, Ferris FL, Gensler G, Lindblad AS, Milton RC, Seddon JM, Klein R, Sperduto RD, Anonymous00450. · National Eye Institute, Bethesda, Maryland, USA. · Arch Ophthalmol. · Pubmed #18779490 No free full text.

Abstract: OBJECTIVE: To examine the association of dietary omega-3 long-chain polyunsaturated fatty acid and fish intake with incident neovascular age-related macular degeneration (AMD) and central geographic atrophy (CGA). METHODS: Multicenter clinic-based prospective cohort study from a clinical trial including Age-Related Eye Disease Study (AREDS) participants with bilateral drusen at enrollment. Main outcome measures were incident neovascular AMD and CGA, ascertained from annual stereoscopic color fundus photographs (median follow-up, 6.3 years). We estimated nutrient and food intake from a validated food frequency questionnaire (FFQ) at baseline, with intake of docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), combined EPA and DHA, and fish as primary exposures. RESULTS: After controlling for known covariates, we observed a reduced likelihood of progression from bilateral drusen to CGA among people who reported the highest levels of EPA (odds ratio [OR], 0.44; 95% confidence interval [CI], 0.23-0.87) and EPA+DHA (OR, 0.45; 95% CI, 0.23-0.90) consumption. Levels of DHA were associated with CGA in age-, sex-, and calorie-adjusted models (OR, 0.51; 95% CI, 0.26-1.00); however, this statistical relationship did not persist in multivariable models. CONCLUSIONS: Dietary lipid intake is a modifiable factor that may influence the likelihood of developing sight-threatening forms of AMD. Our findings suggest that dietary omega-3 long-chain polyunsaturated fatty acid intake is associated with a decreased risk of progression from bilateral drusen to CGA.

Clemons TE, Milton RC, Klein R, Seddon JM, Ferris FL, Anonymous00135. · The EMMES Corporation, Rockville, Maryland 20850-1707, USA. · Ophthalmology. · Pubmed #15808240 links to  free full text

Abstract: PURPOSE: To describe the association of demographic, behavioral, medical, and nonretinal ocular factors with the incidence of neovascular age-related macular degeneration (AMD) and central geographic atrophy (CGA) in the Age-Related Eye Disease Study (AREDS), a randomized trial of antioxidants and zinc supplementation prophylaxis for development of advanced AMD. DESIGN: Clinic-based prospective cohort study. PARTICIPANTS: Of individuals with early or intermediate AMD at baseline with a median follow-up of 6.3 years, 788 were at risk of developing advanced AMD in one eye (the fellow eye had advanced AMD), and 2506 were at risk in both eyes. METHODS: The incidence of neovascular AMD and CGA was assessed from stereoscopic color fundus photographs taken at baseline and at annual visits beginning at year 2. MAIN OUTCOME MEASURES: Neovascular AMD was defined as photocoagulation for choroidal neovascularization, or photographic documentation at the reading center of any of the following: nondrusenoid retinal pigment epithelial detachment, serous or hemorrhagic retinal detachment, hemorrhage under the retina or the retinal pigment epithelium, and subretinal fibrosis. Central geographic atrophy was defined as geographic atrophy involving the center of the macula. RESULTS: In multivariable models, in persons at risk of advanced AMD in both eyes, while controlling for age, gender, and AREDS treatment group, the following variables were statistically significantly associated with the incidence of neovascular AMD: race (odds ratio [OR], white vs. black, 6.77; 95% confidence interval [CI], 1.24-36.9) and larger amount smoked (OR, >10 vs. < or =10 pack-years [a pack-year is an average of 1 pack of cigarette smoked per day for a year], 1.55; 95% CI, 1.15-2.09). The following were statistically significantly associated with the incidence of CGA: less education (OR, high school graduate or less vs. college graduate, 1.75; 95% CI, 1.10-2.78), greater body mass index (BMI) (OR, obese vs. nonobese, 1.93; 95% CI, 1.25-2.65), larger amount smoked (OR, >10 pack-years vs. < or =10 pack-years, 1.82; 95% CI, 1.25-2.65), and antacid use (OR, 0.29; 95% CI, 0.09-0.91). In persons at risk of developing advanced AMD in one eye, the incidence of neovascular AMD was associated with diabetes (OR, 1.88; 95% CI, 1.07-3.31), and the incidence of CGA was associated with use of antiinflammatory medications (OR, 0.22; 95% CI, 0.08-0.59). CONCLUSIONS: Results suggest that, among persons with early or intermediate AMD, smoking and BMI are modifiable factors associated with progression to advanced AMD, and suggest other associations (e.g., use of antacids and antiinflammatory medications) that warrant further study. This article contains additional online-only material available at http://www.ophsource.org/periodicals/ophtha. .

Clemons TE, Kurinij N, Sperduto RD, Anonymous00337. · AREDS Coordinating Center, The EMMES Corp., 401 N. Washington Street, Suite 700, Rockville, MD 20850-1707, USA. · Arch Ophthalmol. · Pubmed #15136320 links to  free full text

Abstract: OBJECTIVE: To assess the association of ocular disorders and high doses of antioxidants or zinc with mortality in the Age-Related Eye Disease Study (AREDS). METHODS: Baseline fundus and lens photographs were used to grade the macular and lens status of AREDS participants. Participants were randomly assigned to receive oral supplements of high-dose antioxidants, zinc, antioxidants plus zinc, or placebo. Risk of all-cause and cause-specific mortality was assessed using adjusted Cox proportional hazards models. RESULTS: During median follow-up of 6.5 years, 534 (11%) of 4753 AREDS participants died. In fully adjusted models, participants with advanced age-related macular degeneration (AMD) compared with participants with few, if any, drusen had increased mortality (relative risk [RR], 1.41; 95% confidence interval [CI], 1.08-1.86). Advanced AMD was associated with cardiovascular deaths. Compared with participants having good acuity in both eyes, those with visual acuity worse than 20/40 in 1 eye had increased mortality (RR, 1.36; 95% CI, 1.12-1.65). Nuclear opacity (RR, 1.40; 95% CI, 1.12-1.75) and cataract surgery (RR, 1.55; 95% CI, 1.18-2.05) were associated with increased all-cause mortality and with cancer deaths. Participants randomly assigned to receive zinc had lower mortality than those not taking zinc (RR, 0.73; 95% CI, 0.61-0.89). CONCLUSIONS: The decreased survival of AREDS participants with AMD and cataract suggests that these conditions may reflect systemic rather than only local processes. The improved survival in individuals randomly assigned to receive zinc requires further study.

Clemons TE, Chew EY, Bressler SB, McBee W, Anonymous00036. · AREDS Coordinating Center, The EMMES Corporation, 401 N Washington Street, Suite 700, Rockville, MD 20850-1707, USA. · Arch Ophthalmol. · Pubmed #12583787 links to  free full text

Abstract: OBJECTIVES: To describe the vision-targeted, health-related quality of life, measured with the National Eye Institute Visual Function Questionnaire (NEI-VFQ), in patients with age-related macular degeneration, cataract, or reduced visual acuity; to determine the relationship between the NEI-VFQ subscale scores and clinical measures of visual function; and to assess the internal consistency and reliability of the NEI-VFQ subscales. DESIGN: The 39-item NEI-VFQ was administered at the 5-year clinic visit to 4077 Age-Related Eye Disease Study participants. RESULTS: The subscales of the NEI-VFQ had moderate to high internal consistency (Cronbach's alpha = 0.58-0.91). The NEI-VFQ scores for participants with advanced age-related macular degeneration in 1 or both eyes, severe nuclear opacity, reduced visual acuity, or cataract surgery generally were lower than scores for disease-free participants (P<.001). CONCLUSION: These findings support the use of the NEI-VFQ as a measure of vision-targeted, health-related quality of life among patients with age-related macular degeneration, cataract, or reduced visual acuity.

SanGiovanni JP, Arking DE, Iyengar SK, Elashoff M, Clemons TE, Reed GF, Henning AK, Sivakumaran TA, Xu X, DeWan A, Agrón E, Rochtchina E, Sue CM, Wang JJ, Mitchell P, Hoh J, Francis PJ, Klein ML, Chew EY, Chakravarti A. · National Eye Institute (NEI)/National Institutes of Health (NIH), Bethesda, Maryland, United States of America. · PLoS One. · Pubmed #19434233 links to  free full text

Abstract: BACKGROUND: Age-related macular degeneration (AMD), a chronic neurodegenerative and neovascular retinal disease, is the leading cause of blindness in elderly people of western European origin. While structural and functional alterations in mitochondria (mt) and their metabolites have been implicated in the pathogenesis of chronic neurodegenerative and vascular diseases, the relationship of inherited variants in the mitochondrial genome and mt haplogroup subtypes with advanced AMD has not been reported in large prospective cohorts. METHODOLOGY/PRINICIPAL FINDINGS: We examined the relationship of inherited mtDNA variants with advanced AMD in 1168 people using a three-stage design on samples from 12-year and 10-year prospective studies on the natural history of age-related eye disease. In Stage I we resequenced the entire genome in 99 elderly AMD-free controls and 215 people with advanced AMD from the 12-year study. A consistent association with AMD in 14 of 17 SNPs characterizing the mtDNA T haplogroup emerged. Further analysis revealed these associations were driven entirely by the T2 haplogroup, and characterized by two variants in Complex I genes (A11812G of MT-ND4 and A14233G of MT-ND6). We genotyped T haplogroups in an independent sample of 490 cases and 61 controls from the same study (Stage II) and in 56 cases and 246 controls from the 10-year study (Stage III). People in the T2 haplogroup were approximately 2.5 times more likely to have advanced AMD than their peers (odds ratio [OR] = 2.54, 95%CI 1.36-4.80, P<or=0.004) after considering the totality of evidence. Findings persisted after considering the impact of AMD-associated variants A69S and Y402H (OR = 5.19, 95%CI 1.19-22.69, P<or=0.029). CONCLUSION: Loci defining the mtDNA T2 haplogroup and Complex I are reasonable targets for novel functional analyses and therapeutic research in AMD.

SanGiovanni JP, Agrón E, Clemons TE, Chew EY. · No affiliation provided · Arch Ophthalmol. · Pubmed #19139352 No free full text.

This publication has no abstract.

Chew EY, Sperduto RD, Milton RC, Clemons TE, Gensler GR, Bressler SB, Klein R, Klein BE, Ferris FL. · National Eye Institute, Bethesda, Maryland, USA. · Ophthalmology. · Pubmed #19091420 No free full text.

Abstract: PURPOSE: To assess the risk of advanced age-related macular degeneration (AMD) developing after cataract surgery. DESIGN: Cohort study. PARTICIPANTS: Four thousand five hundred seventy-seven participants (8050 eyes) from a multicenter, controlled, randomized clinical trial, the Age-Related Eye Disease Study (AREDS). METHODS: Development of advanced AMD, either neovascular (NV) AMD or geographic atrophy (GA), was evaluated with annual fundus photographs, and history of cataract surgery was assessed every 6 months. Cox proportional hazard models with time-dependent covariates were conducted for NV AMD and GA separately. MAIN OUTCOME MEASURES: Neovascular AMD, GA, and central GA (CGA; involving the center of the macula). RESULTS: The Cox proportional hazards model of right eyes showed nonsignificant hazard ratios of 1.20 (95% confidence interval [CI], 0.82-1.75) for NV AMD, 0.80 (95% CI, 0.61-1.06) for GA, and 0.87 (95% CI, 0.64-1.18) for CGA. Similar results were obtained for left eyes: 1.07 (95% CI, 0.72-1.58) for NV AMD, 0.94 (95% CI, 0.71-1.25) for GA, and 0.86 (95% CI, 0.63-1.19) for CGA. For participants with advanced AMD in 1 eye (AREDS category 4), the hazard ratios for fellow eyes were 1.08 (95% CI, 0.65-1.72) for NV AMD and 0.98 (95% CI, 0.64-1.49) for CGA. CONCLUSIONS: The AREDS results showed no clear effect of cataract surgery on the risk of progression to advanced AMD. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.

Anonymous00220, SanGiovanni JP, Chew EY, Clemons TE, Ferris FL, Gensler G, Lindblad AS, Milton RC, Seddon JM, Sperduto RD. · The EMMES Corporation, 401 N Washington St, Ste 700, Rockville, MD 20850-1707, USA. · Arch Ophthalmol. · Pubmed #17846363 links to  free full text

Abstract: OBJECTIVE: To evaluate the relationship of dietary carotenoids, vitamin A, alpha-tocopherol, and vitamin C with prevalent age-related macular degeneration (AMD) in the Age-Related Eye Disease Study (AREDS). METHODS: Demographic, lifestyle, and medical characteristics were ascertained on 4519 AREDS participants aged 60 to 80 years at enrollment. Stereoscopic color fundus photographs were used to categorize participants into 4 AMD severity groups and a control group (participants with < 15 small drusen). Nutrient intake was estimated from a self-administered semiquantitative food frequency questionnaire at enrollment. Intake values were energy adjusted and classified by quintiles. The relationship between diet and AMD status was assessed using logistic regression analyses. RESULTS: Dietary lutein/zeaxanthin intake was inversely associated with neovascular AMD (odds ratio [OR], 0.65; 95% confidence interval [CI], 0.45-0.93), geographic atrophy (OR, 0.45; 95% CI, 0.24-0.86), and large or extensive intermediate drusen (OR, 0.73; 95% CI, 0.56-0.96), comparing the highest vs lowest quintiles of intake, after adjustment for total energy intake and nonnutrient-based covariates. Other nutrients were not independently related to AMD. CONCLUSION: Higher dietary intake of lutein/zeaxanthin was independently associated with decreased likelihood of having neovascular AMD, geographic atrophy, and large or extensive intermediate drusen.

SanGiovanni JP, Chew EY, Clemons TE, Davis MD, Ferris FL, Gensler GR, Kurinij N, Lindblad AS, Milton RC, Seddon JM, Sperduto RD, Anonymous00204. · AREDS Coordinating Center, The EMMES Corporation, 401 N. Washington Street, Rockville, MD 20850, USA. · Arch Ophthalmol. · Pubmed #17502507 links to  free full text

Abstract: OBJECTIVE: To evaluate the association of lipid intake with baseline severity of age-related macular degeneration (AMD) in the Age-Related Eye Disease Study (AREDS). METHODS: Age-Related Eye Disease Study participants aged 60 to 80 years at enrollment (N = 4519) provided estimates of habitual nutrient intake through a self-administered semiquantitative food frequency questionnaire. Stereoscopic color fundus photographs were used to categorize participants into 4 AMD severity groups and a control group (participants with <15 small drusen). RESULTS: Dietary total omega-3 long-chain polyunsaturated fatty acid (LCPUFA) intake was inversely associated with neovascular (NV) AMD (odds ratio [OR], 0.61; 95% confidence interval [CI], 0.41-0.90), as was docosahexaenoic acid, a retinal omega-3 LCPUFA (OR, 0.54; 95% CI, 0.36-0.80), comparing highest vs lowest quintile of intake, after adjustment for total energy intake and covariates. Higher fish consumption, both total and broiled/baked, was also inversely associated with NV AMD (OR, 0.61; 95% CI, 0.37-1.00 and OR, 0.65; 95% CI, 0.45-0.93, respectively). Dietary arachidonic acid was directly associated with NV AMD prevalence (OR, 1.54; 95% CI, 1.04-2.29). No statistically significant relationships existed for the other lipids or AMD groups. CONCLUSION: Higher intake of omega-3 LCPUFAs and fish was associated with decreased likelihood of having NV AMD.

Clemons TE, Rankin MW, McBee WL, Anonymous00029. · No affiliation provided · Arch Ophthalmol. · Pubmed #16606880 links to  free full text

Abstract: OBJECTIVE: To investigate potential associations between cognitive function and/or impairment and age-related macular degeneration (AMD) and visual impairment in the Age-Related Eye Disease Study (AREDS). METHODS: The AREDS is an 11-center natural history study of AMD and age-related cataract. The AREDS Cognitive Function Battery was administered to 2946 participants. The battery consists of 6 neuropsychological tests measuring performance in several cognitive domains. The Dunnett multiple comparison test was used to identify differences by AMD and visual acuity severity. The relationship with cognitive impairment was also assessed using logistic regression. RESULTS: Mean scores of instruments in the AREDS Cognitive Function Battery declined with increased macular abnormalities and reduced visual acuity. After adjustment for age, sex, race, education, smoking status, diabetes mellitus, hypertension, and depression, increased macular abnormalities (trend P value <.05) reduced mean cognitive function scores as measured by the Modified Mini-Mental State Examination and the Wechsler Logical Memory Scale. Reduced vision was found to be associated with reduced mean cognitive function scores as measured by the Modified Mini-Mental State Examination and letter and verbal fluency tasks. Persons with vision worse than 20/40 OU were more likely to be cognitively impaired (Modified Mini-Mental State Examination score <80) (odds ratio, 2.88 [95% confidence interval, 1.75-4.76]) compared with persons with visual acuity of 20/40 or better OU. CONCLUSION: These data suggest a possible association of advanced AMD and visual acuity with cognitive impairment in older persons.

Ferris FL, Davis MD, Clemons TE, Lee LY, Chew EY, Lindblad AS, Milton RC, Bressler SB, Klein R, Anonymous00307. · AREDS Coordinating Center, The EMMES Corporation, Rockville, MD 20850-1707, USA. · Arch Ophthalmol. · Pubmed #16286620 links to  free full text

Abstract: OBJECTIVE: To develop a simplified clinical scale defining risk categories for development of advanced age-related macular degeneration (AMD). METHODS: Following development of a detailed scale for individual eyes based on gradings of fundus photographs in the Age-Related Eye Disease Study, rates of progression to advanced AMD were assessed in cross-tabulations of presence or absence in each eye of 2 easily identified retinal abnormalities, drusen and pigment abnormalities. Large drusen and any pigment changes were particularly predictive of developing advanced AMD. RESULTS: The scoring system developed for patients assigns to each eye 1 risk factor for the presence of 1 or more large (> or = 125 microm, width of a large vein at disc margin) drusen and 1 risk factor for the presence of any pigment abnormality. Risk factors are summed across both eyes, yielding a 5-step scale (0-4) on which the approximate 5-year risk of developing advanced AMD in at least one eye increases in this easily remembered sequence: 0 factors, 0.5%; 1 factor, 3%; 2 factors, 12%; 3 factors, 25%; and 4 factors, 50%. For persons with no large drusen, presence of intermediate drusen in both eyes is counted as 1 risk factor. CONCLUSION: This simplified scale provides convenient risk categories for development of advanced AMD that can be determined by clinical examination or by less demanding photographic procedures than used in the Age-Related Eye Disease Study.

Lindblad AS, Clemons TE. · AREDA Coordinating Center, The EMMES Corporation, 401 N. Washington Street, Ste. 700, Rockville, MD 20850-1707, USA. · Arch Ophthalmol. · Pubmed #16157800 links to  free full text

Abstract: OBJECTIVE: To describe the ability of the National Eye Institute Visual Function Questionnaire (NEI-VFQ) to detect meaningful change over time (responsiveness) to the primary Age-Related Eye Disease Study outcomes. METHODS: The 25-item NEI-VFQ plus appendix was administered at 2 visits at 1- to 4-year intervals to 4119 participants in the Age-Related Eye Disease Study. Events evaluated were progression to advanced age-related macular degeneration (AMD), visual acuity (VA) loss of at least 15 letters, and lens opacity progression. Responsiveness was measured by the t statistic, effect size (ES), responsiveness statistic, and area under the receiver operating characteristic curve. Variance components were used to estimate the contributions of events to variability of the NEI-VFQ score. RESULTS: Overall NEI-VFQ score was responsive to AMD progression (t = 14.0; P< .001; ES = 0.81) and VA (t = 16.2; P< .001; ES = 0.74). Mean changes ranged from 11 to 25 points for the subscales of general vision, near and distance activities, social functioning, mental health, role difficulties, dependency, and driving. The NEI-VFQ was unresponsive to lens opacity progression, although when the event occurred in the eye with the best vision at the first administration, the lens opacity ES was moderate for the color vision (ES = 0.62) and driving subscales (ES = 0.66). Progression to advanced AMD and VA loss contributed significantly to the variation in the mean difference in overall VFQ score. CONCLUSIONS: Changes in the NEI-VFQ overall and subscale scores of 10 points or more are associated with clinically significant changes in vision and AMD. This finding may assist the design of interventional studies of AMD and VA loss that include the NEI-VFQ as an outcome measure.

Rankin MW, Clemons TE, McBee WL. · The EMMES Corporation, Rockville, MD 20850, USA. · Ophthalmic Epidemiol. · Pubmed #16033748 links to  free full text

Abstract: PURPOSE: To determine whether the AREDS Telephone Battery can be substituted for the In-Clinic Cognitive Function Battery to assess cognitive function, so that participants could still provide follow-up information without having to come to the clinic. METHODS: Correlation analysis was performed on scores of the following in-clinic and telephone administrations: 1) Modified Mini-Mental State Examination (3MS), conducted in person vs. Telephone Interview Cognitive Status (TICS-M); 2) Wechsler Memory Scale-III (WMS-III), Logical Memory I and II; 3) Digits Backwards (a sub-test of the WMS-R); 4) Verbal Fluency; and 5) Letter Fluency (F,A,S). RESULTS: A total of 1,738 AREDS participants completed an In-Clinic Battery and a Telephone Battery within twelve months. Significant positive correlations were found for all tests, ranging from rho = 0.89 between the 3MS and TICS-M scores (95% CI; 0.88 - 0.90), to rho = 0.71 for Letter Fluency (95% CI; 0.68 - 0.74). CONCLUSION: The linear relationships between the In-Clinic Battery and Telephone Battery scores support the hypothesis that the Telephone Battery is an appropriate substitute for participants who are unable to complete an in-clinic assessment of cognitive function.