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BACKGROUND: omega-3 (n-3) Long-chain polyunsaturated fatty acids (LCPUFAs) affect processes implicated in vascular and neural retinal pathogenesis and thus may influence the risk of developing age-related macular degeneration (AMD). OBJECTIVE: We investigated whether omega-3 LCPUFA intake was associated with a reduced likelihood of developing central geographic atrophy (CGA) and neovascular (NV) AMD. DESIGN: We undertook a nested cohort study within a multicenter phase 3 clinical trial, the Age-Related Eye Disease Study (AREDS), to study progression to advanced AMD in 1837 persons at moderate-to-high risk of this condition. The AREDS was designed to assess the clinical course, prognosis, risk factors, and nutrient-based treatments of AMD and ran from November 1992 to December 2005. We obtained baseline data on omega-3 LCPUFA intake with a validated food-frequency questionnaire. Trained fundus graders ascertained AMD status from annual stereoscopic color photographs by using standardized methods at a single reading center across a 12-y period. We applied multivariable repeated-measures logistic regression with the incorporation of generalized estimating equation methods, because this permitted determination of progression to outcome at each visit. RESULTS: Participants who reported the highest omega-3 LCPUFA intake (median: 0.11% of total energy intake) were 30% less likely than their peers to develop CGA and NV AMD. The respective odds ratios were 0.65 (95% CI: 0.45, 0.92; P

Purpose: To evaluate whether dietary intake of luteiin/zeaxanthin and B vitamins is associated with cataract prevalence and incidence., Design: Clinic-based, baseline cross-sectional and prospective cohort study designs., Participants: Three thousand one hundred fifteen patients (6129 eyes) enrolled in the Age-Related Eye Disease Study 55 to 80 years of age followed up for mean of 9.6 years., Methods: Participants completed baseline food frequency questionnaires. Baseline and annual lens photographs were graded centrally. Multivariate models controlling for previously identified risk factors for cataracts tested for the association of cataracts with reported dietary intake, using the lowest quintile as reference., Main Outcome Measures: Cataract surgery, cataract status (type and severity) at baseline, and development of cataracts., Results: At baseline, increased dietary riboflavin and B12 were associated inversely with nuclear and cortical lens opacities. In comparisons of persons with and without cataract, persons with the highest riboflavin intake versus those with the lowest intake had the following associations: mild nuclear cataract: odds ratio (OR), 0.78; 95% confidence interval (CI), 0.63-0.97; moderate nuclear cataract: OR, 0.62; 95% CI, 0.43-0.90; and mild cortical cataract: OR, 0.80; 95% CI, 0.65-0.99. For B12, the results were: mild nuclear cataract: OR, 0.78; 95% CI, 0.63-0.96; moderate nuclear cataract: OR, 0.62; 95% CI, 0.43-0.88; and mild cortical cataract: OR, 0.77; 95% CI, 0.63-0.95. Highest dietary B6 intake was associated with a decreased risk of moderate nuclear lens opacity developing compared with the lowest quintile (OR, 0.67; 95% CI, 0.45-0.99). Highest dietary intake levels of niacin and B12 were associated with a decreased risk of development of mild nuclear or mild cortical cataracts in participants not taking Centrum (Pfizer, New York, NY) multivitamins. For participants taking multivitamins during the study, the highest intake of dietary folate was associated with an increased risk of mild posterior subcapsular lens opacity development. No statistically significant associations were found between lutein plus zeaxanthin intake and presence at baseline or development of nuclear or cortical lens opacity outcomes., Conclusions: These findings are consistent with earlier studies suggesting that dietary intake of B vitamins may affect the occurrence of age-related lens opacities. Further investigations are warranted., (Copyright © 2015 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To investigate whether the 2-year change in lens opacity severity on the Age-Related Eye Disease Study (AREDS) lens grading scale predicts progression to cataract surgery or loss of visual acuity by 5 years., Design: Prospective cohort study within a randomized clinical trial of oral supplements., Participants: The AREDS participants whose eyes were phakic at baseline and free of late age-related macular degeneration throughout the study., Methods: Baseline and annual lens photographs of AREDS participants (n = 3466/4757; 73%) were graded for severity of cataracts using the AREDS system for classifying cataracts from photographs. Clinical examinations conducted semiannually collected data on cataract surgery and visual acuity. Association of the change in lens opacities at 2 years with these outcomes at 5 years was analyzed with adjusted Cox proportional hazard models., Main Outcome Measurements: Progression of lens opacities on stereoscopic lens photographs at 2 years, cataract surgery, and visual acuity loss of 2 lines or more at 5 years., Results: The adjusted hazard ratios (HRs) for association of progression to cataract surgery at 5 years were: nuclear cataract increase of 1.0 unit or more compared with less than 1.0-unit change at 2 years, 2.77 (95% confidence interval [CI], 2.07-3.70; P < 0.001); cortical cataract increase of 5% or more in lens opacity in the central 5 mm of the lens compared with less than 5% increase at 2 years, 1.91 (95% CI, 1.27-2.87; P = 0.002); and posterior subcapsular cataract increase of 5% or more versus less than 5% in the central 5 mm of the lens, 8.25 (95% CI, 5.55-12.29; P < 0.001). Similarly, HRs of vision loss of 2 lines or more at 5 years for this degree of lens changes at 2 years were the following: nuclear, 1.83 (95% CI, 1.49-2.25; P < 0.001); cortical, 1.13 (95% CI, 0.78-1.65; P = 0.519); and posterior subcapsular cataract, 3.05 (95% CI, 1.79-5.19; P < 0.001)., Conclusions: Two-year changes in severity of lens opacities on the AREDS lens grading scale are predictive of long-term clinically relevant outcomes, making them potential surrogate end points in follow-up studies., (Copyright © 2015 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Importance: Providing long-term follow-up of the natural history of age-related macular degeneration (AMD) and associated risk factors will facilitate future epidemiologic studies and clinical trials., Objective: To describe 10-year progression rates to intermediate or advanced AMD., Design, Setting, and Participants: We observed the Age-Related Eye Disease Study (AREDS) participants for an additional 5 years after a randomized clinical trial of antioxidant vitamins and minerals was completed. Observation occurred at 11 clinical sites of medical retinal practices from academic institutions and community medical centers. Participants aged 55 to 80 years with no AMD or AMD of varying severity (n = 4757) were followed up in the AREDS trial for a median duration of 6.5 years. When the trial ended, 3549 of the 4203 surviving participants were followed for 5 additional years., Exposure: Treatment with antioxidant vitamins and minerals., Main Outcomes and Measures: Development of varying stages of AMD and changes in visual acuity. The rates of progression to large drusen and advanced AMD (neovascular AMD or central geographic atrophy) were evaluated using annual fundus photographs assessed centrally. Best-corrected visual acuity was measured at annual study visits., Results: The risk of progression to advanced AMD increased with increasing age (P = .01) and severity of drusen. Women (P = .005) and current smokers (P < .001) were at increased risk of neovascular AMD. In the oldest participants with the most severe AMD status at baseline, the risks of developing neovascular AMD and central geographic atrophy by 10 years were 48.1% and 26.0%, respectively. Similarly, rates of progression to large drusen increased with increasing severity of drusen at baseline, with 70.9% of participants with bilateral medium drusen progressing to large drusen and 13.8% to advanced AMD in 10 years. Median visual acuity at 10 years in eyes that had large drusen at baseline but never developed advanced AMD was 20/25; eyes that developed advanced AMD had a median visual acuity of 20/200., Conclusions and Relevance: The natural history of AMD demonstrates relentless loss of vision in persons who developed advanced AMD. These progression data and the risk factor analyses may be helpful to investigators conducting research in clinic populations.

Importance: The Age-Related Eye Disease Study (AREDS) formulation for the treatment of age-related macular degeneration (AMD) contains vitamin C, vitamin E, beta carotene, and zinc with copper. The Age-Related Eye Disease Study 2 (AREDS2) assessed the value of substituting lutein/zeaxanthin in the AREDS formulation because of the demonstrated risk for lung cancer from beta carotene in smokers and former smokers and because lutein and zeaxanthin are important components in the retina., Objective: To further examine the effect of lutein/zeaxanthin supplementation on progression to late AMD., Design, Setting, Participants: The Age-Related Eye Disease Study 2 is a multicenter, double-masked randomized trial of 4203 participants, aged 50 to 85 years, at risk for developing late AMD; 66% of patients had bilateral large drusen and 34% had large drusen and late AMD in 1 eye., Interventions: In addition to taking the original or a variation of the AREDS supplement, participants were randomly assigned in a factorial design to 1 of the following 4 groups: placebo; lutein/zeaxanthin, 10 mg/2 mg; omega-3 long-chain polyunsaturated fatty 3 acids, 1.0 g; or the combination., Main Outcomes and Measure: S Documented development of late AMD by central, masked grading of annual retinal photographs or by treatment history. RESULTS In exploratory analysis of lutein/zeaxanthin vs no lutein/zeaxanthin, the hazard ratio of the development of late AMD was 0.90 (95% CI, 0.82-0.99; P = .04). Exploratory analyses of direct comparison of lutein/zeaxanthin vs beta carotene showed hazard ratios of 0.82 (95% CI, 0.69-0.96; P = .02) for development of late AMD, 0.78 (95% CI, 0.64-0.94; P = .01) for development of neovascular AMD, and 0.94 (95% CI, 0.70-1.26; P = .67) for development of central geographic atrophy. In analyses restricted to eyes with bilateral large drusen at baseline, the direct comparison of lutein/zeaxanthin vs beta carotene showed hazard ratios of 0.76 (95% CI, 0.61-0.96; P = .02) for progression to late AMD, 0.65 (95% CI, 0.49-0.85; P = .002) for neovascular AMD, and 0.98 (95% CI, 0.69-1.39; P = .91) for central geographic atrophy., Conclusion and Relevance: The totality of evidence on beneficial and adverse effects from AREDS2 and other studies suggests that lutein/zeaxanthin could be more appropriate than beta carotene in the AREDS-type supplements., Trial Registration: clinicaltrials.gov Identifier: NCT00345176.

Objective: To describe the long-term effects (10 years) of the Age-Related Eye Disease Study (AREDS) formulation of high-dose antioxidants and zinc supplement on progression of age-related macular degeneration (AMD)., Design: Multicenter, randomized, controlled, clinical trial followed by an epidemiologic follow-up study., Participants: We enrolled 4757 participants with varying severity of AMD in the clinical trial; 3549 surviving participants consented to the follow-up study., Methods: Participants were randomly assigned to antioxidants C, E, and β-carotene and/or zinc versus placebo during the clinical trial. For participants with intermediate or advanced AMD in 1 eye, the AREDS formulation delayed the progression to advanced AMD. Participants were then enrolled in a follow-up study. Eye examinations were conducted with annual fundus photographs and best-corrected visual acuity assessments. Medical histories and mortality were obtained for safety monitoring. Repeated measures logistic regression was used in the primary analyses., Main Outcome Measures: Photographic assessment of progression to, or history of treatment for, advanced AMD (neovascular [NV] or central geographic atrophy [CGA]), and moderate visual acuity loss from baseline (≥15 letters)., Results: Comparison of the participants originally assigned to placebo in AREDS categories 3 and 4 at baseline with those originally assigned to AREDS formulation at 10 years demonstrated a significant (P<0.001) odds reduction in the risk of developing advanced AMD or the development of NV AMD (odds ratio [OR], 0.66, 95% confidence interval [CI], 0.53-0.83 and OR, 0.60; 95% CI, 0.47-0. 78, respectively). No significant reduction (P = 0.93) was seen for the CGA (OR, 1.02; 95% CI, 0.71-1.45). A significant reduction (P = 0.002) for the development of moderate vision loss was seen (OR 0.71; 95% CI, 0.57-0.88). No adverse effects were associated with the AREDS formulation. Mortality was reduced in participants assigned to zinc, especially death from circulatory diseases., Conclusions: Five years after the clinical trial ended, the beneficial effects of the AREDS formulation persisted for development of NV AMD but not for CGA. These results are consistent with the original recommendations that persons with intermediate or advanced AMD in 1 eye should consider taking the AREDS formulation., Financial Disclosure(s): The authors have no proprietary or commercial interest in any of the materials discussed in this article., (Copyright © 2013 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Purpose: To investigate the long-term incidence of age-related cataract and cataract surgery in the Age-Related Eye Disease Study (AREDS) cohort., Methods: Baseline and annual lens photographs of participants, aged 55-80 years, were graded centrally for nuclear, cortical, and posterior subcapsular (PSC) lens opacities using the AREDS System for Classifying Cataracts. Progression from a baseline status of no or mild lens opacity to at least moderate severity was analyzed and cumulative incidence estimated rates were calculated for each lens opacity type and cataract surgery stratified by age, sex, race, age-related macular degeneration category, multivitamin (Centrum) use and history of diabetes., Results: The ten-year cumulative incidence was 43.6% for any cataract, 23.1% for nuclear cataract, 22.0% for cortical cataract, 13.1% for PSC cataract, and 26.8% for cataract surgery. The 5- and 10-year incidence rates of all cataract types and cataract surgery were significantly higher with increasing age. Females had a higher incidence of any, nuclear and cortical cataract and cataract surgery (p = 0.02-0.05). Incidence of cortical cataract was higher in non-white participants (p = 0.001)., Conclusions: These results are largely consistent with the results of previous observational studies. Long-term incidence rates of type-specific cataract can be useful in designing clinical studies of age-related cataract.

Objective: To investigate potential risk factors associated with incident nuclear, cortical, and posterior subcapsular (PSC) cataracts and cataract surgery in participants in the Age-Related Eye Disease Study (AREDS)., Design: Clinic-based prospective cohort study., Participants: Persons (n = 4425) 55 to 80 years of age enrolled in a controlled clinical trial of antioxidant vitamins and minerals, AREDS, for age-related macular degeneration and cataract., Methods: Lens photographs were graded centrally for nuclear, cortical, and PSC opacities using the AREDS system for classifying cataracts. Type-specific incident cataracts were defined as an increase in cataract grade from none or mild at baseline to a grade of moderate at follow-up, also with a grade of at least moderate at the final visit, or cataract surgery. Cox regression analyses were used to assess baseline risk factors associated with type-specific opacities and cataract surgery., Main Outcome Measures: Moderate cataract was defined as a grade of 4.0 or more for nuclear opacity, 10% or more involvement within the full visible lens for cortical opacity, and 5% or more involvement of the central 5-mm circle of the lens for PSC opacity. These were graded on baseline and annual lens photographs., Results: A clinic-based cohort of 4425 persons 55 to 80 years of age at baseline was followed up for an average of 9.8±2.4 years. The following associations were found: increasing age with increased risk of all types of cataract and cataract surgery; males with increased risk of PSC and decreased risk of cortical cataracts; nonwhite persons with increased risk of cortical cataract; hyperopia with decreased risk of PSC, nuclear cataract, and cataract surgery; Centrum (Wyeth Consumer Healthcare, Madison, NJ) use with decreased risk of nuclear cataract; diabetes with increased risk of cortical, PSC cataract, and cataract surgery; higher educational level with decreased risk of cortical cataract; and smoking with increased risk of cortical cataract and cataract surgery. Estrogen replacement therapy in female participants increased the risk of cataract surgery., Conclusions: These findings largely are consistent with the results of previous studies, providing further evidence for possible modifiable risk factors for age-related cataract., Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article., (Copyright © 2011 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Background: The Italian-American Clinical Trial of Nutritional Supplements and Age-Related Cataract was designed to assess the impact of a multivitamin-mineral supplement on age-related cataract. Trial results showed evidence of a beneficial effect of the supplement on all types of cataract combined, opposite effects on two of the three types of cataract (beneficial for nuclear opacities and harmful for posterior sub-capsular opacities) and no statistically significant effect on cortical opacities. No treatment recommendations were made. A post-trial survey was conducted on 817 surviving elderly participants to assess their satisfaction, their understanding of treatment assignment to supplement or placebo and the success of masking., Methods: Trial results were communicated by letter and the level of satisfaction and of understanding of the results was assessed by a questionnaire. Participants were offered the option of being unmasked: a second questionnaire was administered to this subset to assess their understanding of the randomisation process and the success of masking., Results: 610 participants (74.7%) responded to the survey:94.6% thought the description of the results was "very clear" or "quite clear", 5.4% "not clear" or "do not know"; 89.8% considered the results "very interesting" or "quite interesting", 10.2% "not interesting" or "do not know"; 60.3% expressed "satisfaction", 17.2% "both satisfaction and concern", 2.6% "concern", 19.9% "indifference" or "do not know".480 participants (78.7%) accepted the offer to be unmasked to their treatment assignment: 395 (82.3%) recalled/understood the possibility of assignment to vitamins or placebo, 85 (17.7%) did not. 68 participants (17.2%) thought they had taken vitamins (79.4% were correct; p = 0.0006), 47 (11.9%) thought they had taken placebo (59.6% were correct; p = 0.46) and 280 (70.9%) declared they did not know., Conclusions: The results were made difficult to explain to study participants by the qualitatively different effect of treatment on the two most visually significant types of cataract. Although the study did not lead to a recommendation to use the dietary supplement, the vast majority of participants reported satisfaction after they received the results but almost 20% of the participants expressed some concern. Masking to treatment assignment was successful in the majority of participants.

Purpose: To examine the grading (interrater) reliability of the Age-Related Eye Disease Study (AREDS) Clinical Lens Grading System (ARLNS)., Design: Evaluation of diagnostic test or technology., Participants: One hundred fifty volunteers (284 eyes)., Methods: Participants with lens opacities of varying severity were independently graded at the slit lamp for cataract severity by 2 examiners (retinal or anterior segment specialists) using the ARLNS, which employs 3 standard photographs of increasing severity for classifying each of the 3 major types of opacity. Lens photographs were taken and graded at a reading center using the more detailed AREDS System for Classifying Cataracts from photographs., Main Outcome Measures: The Pearson correlation, weighted-kappa, and limits-of-agreement statistics were used to assess the interrater agreement of the gradings., Results: Examinations were performed on 284 lenses (150 participants). Tests of interrater reliability between pairs of clinicians showed substantial agreement between clinicians for cortical and posterior subcapsular opacities and moderate agreement for nuclear opacities. A similar pattern and strength of agreement was present when comparing scores of retinal versus anterior segment specialists. Interrater agreement between clinical and reading center gradings was not as great as inter-clinician agreement., Conclusions: Interrater agreements were in the moderate to substantial range for the clinical assessment of lens opacities. Inherent differences in cataract classification systems that rely on slit lamp vs photographic assessments of lens opacities may explain some of the disagreement noted between slit lamp and photographic gradings. Given the interrater reliability statistics for clinicians and the simplicity of the grading procedure, ARLNS is presented for use in studies requiring a simple, inexpensive method for detecting the presence and severity of the major types of lens opacities., Financial Disclosure(s): The authors have no proprietary or commercial interest in any of the materials discussed in this article., (Copyright © 2010 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)

Objective: To compare US population prevalence estimates for myopia in 1971-1972 and 1999-2004., Methods: The 1971-1972 National Health and Nutrition Examination Survey provided the earliest nationally representative estimates for US myopia prevalence; myopia was diagnosed by an algorithm using either lensometry, pinhole visual acuity, and presenting visual acuity (for presenting visual acuity > or =20/40) or retinoscopy (for presenting visual acuity < or =20/50). Using a similar method for diagnosing myopia, we examined data from the 1999-2004 National Health and Nutrition Examination Survey to determine whether myopia prevalence had changed during the 30 years between the 2 surveys., Results: Using the 1971-1972 method, the estimated prevalence of myopia in persons aged 12 to 54 years was significantly higher in 1999-2004 than in 1971-1972 (41.6% vs 25.0%, respectively; P < .001). Prevalence estimates were higher in 1999-2004 than in 1971-1972 for black individuals (33.5% vs 13.0%, respectively; P < .001) and white individuals (43.0% vs 26.3%, respectively; P < .001) and for all levels of myopia severity (>-2.0 diopters [D]: 17.5% vs 13.4%, respectively [P < .001]; < or =-2.0 to >-7.9 D: 22.4% vs 11.4%, respectively [P < .001]; < or =-7.9 D: 1.6% vs 0.2%, respectively [P < .001])., Conclusions: When using similar methods for each period, the prevalence of myopia in the United States appears to be substantially higher in 1999-2004 than 30 years earlier. Identifying modifiable risk factors for myopia could lead to the development of cost-effective interventional strategies.

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.

The use of multivitamin-mineral supplements has become increasingly common, but whether the use of such supplements improves micronutrient status remains still unclear. The objective of this report is to investigate how a long-term vitamin-mineral supplementation following the US Recommended Daily Intake (RDI) affected the plasma levels of selected nutrients in a subset (No. = 407) of participants in the Italian-American Clinical Trial of Nutritional Supplements and Age-related Cataract (CTNS). The CTNS was a double-blind, single centre, controlled clinical trial of 1020 participants aged 55-75 years randomized to a daily tablet of Centrum(R) or placebo. A representative sample of 40% of the 1020 subjects, whom plasma level of selected vitamins was determined at the baseline, was retested throughout the treatment period that averaged 9.0 +/- 2.4 years. Participants assigned to Centrum(R) showed a significant increase (p < 0.005) in mean/median plasma levels of vitamin E, beta-carotene, folate, and vitamin B12, and an improved riboflavin status when compared with participants assigned to placebo. Differences concerning vitamin C were statistically less relevant and those concerning vitamin A were at a borderline level. In the treated group the effect of supplementation on plasma levels of vitamins A, E, and C, and on the glutathione reductase activation coefficient was significantly higher in participants with lower nutritional status at baseline.

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.

Objective: To evaluate the effect of a multivitamin/mineral supplement on development or progression of age-related lens opacities., Design: Randomized, double-masked, single center, placebo-controlled clinical trial., Participants: One thousand twenty participants, 55 to 75 years old and with early or no cataract, were randomly assigned to a daily tablet of a multivitamin/mineral formulation or a placebo., Methods: Baseline and annual lens photographs were graded for severity of lens opacities according to a modification of the Age-Related Eye Disease Study system for classifying cataracts., Main Outcome Measures: The primary outcome was a prespecified increase from baseline in nuclear, cortical, or posterior subcapsular cataract (PSC) opacity grades or cataract surgery. Secondary outcomes included an increase in type-specific opacity grades, cataract surgery, and visual acuity (VA) loss from baseline > or =15 letters., Results: Participants were observed for an average of 9.0+/-2.4 years. There was a decrease in total lens events in participants assigned to the multivitamin/mineral formulation compared with those assigned to the placebo (hazard ratio [HR], 0.82; 95% confidence interval [CI], 0.68-0.98; P = 0.03). Nuclear events were significantly less common (HR, 0.66; 95% CI, 0.50-0.88; P = 0.004) and PSC events significantly more common (HR, 2.00; 95% CI, 1.35-2.98; P<0.001) in participants taking the multivitamin/mineral formulation than in those assigned to the placebo. No statistically significant treatment effects were seen for cortical opacities, moderate VA loss, or cataract surgery., Conclusions: Lens events were less common in participants who took the multivitamin/mineral formulation, but treatment had opposite effects on the development or progression of nuclear and PSC opacities, the 2 most visually important opacity subtypes.

Purpose: To describe use of serial lens examinations to assign cataract phenotype in the Age-Related Eye Disease Study (AREDS)., Design: Cohort study., Methods: Lens photographs were graded annually using the AREDS system for classifying cataracts. Nuclear grades (0.9 to 6.1) were assigned using standard photographs. Percentage of pupillary involvement was used to assign cortical and posterior subcapsular grades. Cutpoints were established for the presence or absence of each type of opacity (absent<4.0 for nuclear, <10% for cortical, and <5% of central 5 mm for posterior subcapsular). An algorithm weighted for grades at the last three examinations was used to assign cataract phenotype. Separately, cataract phenotype was assigned as grade predicted at final visit by linear regression of serial grades. Results from the two approaches were compared and final person phenotypes were established. These person cataract phenotype assignments were compared with phenotype assignments based on the last serial grade alone., Results: Four thousand six hundred and twenty-eight AREDS participants aged 55 to 80 years at baseline had median follow-up of 10.6 years. Person phenotype assignments agreed for the two approaches in 4,557 (98.5%) participants after some algorithmic adjudication. Phenotypes were no cataract (n=1,418), nuclear (n=1,287), cortical (n=1,396), posterior subcapsular (n=541), cataract surgery and no specific opacity type (n=335), and questionable (n=426). Phenotype assignments based on serial grades and on last examination alone were in good agreement., Conclusions: Serial lens photographs obtained over a 10-year period were used to provide a robust assignment of cataract phenotype. Well-characterized cataract phenotypes are of importance as genetic studies of the AREDS cohort are considered.

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.

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.

Purpose: To evaluate the effect of the multivitamin Centrum on the development and progression of age-related lens opacities., Design: Clinic-based prospective cohort study., Participants: Four thousand five hundred ninety individuals with at least one natural lens and photographic follow-up (median, 6.3 years) were assessed for development or progression of lens opacities., Main Outcome Measures: Progression of "any" lens opacity or type-specific opacity was ascertained from lens photographs taken at baseline and at annual visits beginning at year 2., Methods: The Age-Related Eye Disease Study (AREDS) showed no statistically significant effect of a high-dose antioxidant formulation on progression of lens opacities. Centrum also was provided to approximately two thirds of the study participants. Because Centrum use was elective, a logistic regression model of baseline characteristics was used to generate a propensity score for Centrum use. Repeated-measures logistic regression, adjusted for propensity score and other covariates, was used to evaluate associations of Centrum use and lens opacity., Results: Centrum use, adjusted for propensity score and other covariates, was associated with a reduction in "any" lens opacity progression (odds ratio [OR] = 0.84, 95% confidence interval [CI] = 0.72-0.98, P = 0.025). Results for individual lens opacity types suggested that Centrum use was protective for nuclear opacity events (OR = 0.75, 95% CI = 0.61-0.91, P = 0.004)., Conclusion: Observational data from the AREDS and other studies suggest that use of a multivitamin may delay the progression of lens opacities. A National Eye Institute-sponsored clinical trial scheduled for completion in 2007 will provide additional data on Centrum use and cataract development.

Context: The prevalence of visual impairment in the US public has not been surveyed nationally in several decades., Objective: To estimate the number of US individuals aged 12 years or older who have impaired distance vision due to uncorrected refractive error., Design, Setting, and Participants: The National Health and Nutrition Examination Survey (NHANES), using a multistage probability sampling design, included a vision evaluation in a mobile examination center. Visual acuity data were obtained from 13,265 of 14,203 participants (93.4%) who visited the mobile examination center in 1999-2002. Visual impairment was defined as presenting distance visual acuity of 20/50 or worse in the better-seeing eye. Visual impairment due to uncorrected refractive error was defined as (presenting) visual impairment that improved, aided by automated refraction results, to 20/40 or better in the better-seeing eye., Main Outcome Measures: Presenting distance visual acuity (measured with usual corrective lenses, if any) and distance visual acuity after automated refraction., Results: Overall, 1190 study participants had visual impairment (weighted prevalence, 6.4%; 95% confidence interval [CI], 6.0%-6.8%), and of these, 83.3% could achieve good visual acuity with correction (95% CI, 80.9%-85.8%). Extrapolating these findings to the general US population, approximately 14 million individuals aged 12 years or older have visual impairment (defined as distance visual acuity of 20/50 or worse), and of these, more than 11 million individuals could have their vision improved to 20/40 or better with refractive correction., Conclusions: Visual impairment due to uncorrected refractive error is a common condition in the United States. Providing appropriate refractive correction to those individuals whose vision can be improved is an important public health endeavor with implications for safety and quality of life.

Purpose: To investigate the association at baseline between plasma levels of selected vitamins and the presence and type of cataract in the participants in The Italian-American Trial of Nutritional Supplements and Age-related Cataract., Methods: At baseline, the participants (1020, 710 with "early cataract" and 310 with "no cataract," 55-75 years of age) received an ocular examination, photographic lens grading, and measurement of plasma levels of vitamins A, C, E, beta-carotene, and of red blood cell glutathione reductase activity., Results: In multiple logistic models adjusted for potential confounders, high vitamin C levels were associated with a protective effect on nuclear (N) [OR: 0.54; 95% CI: 0.30, 0.97] and posterior subcapsular (PSC) cataract (OR: 0.37; 95% CI: 0.15, 0.93). High vitamin E levels were associated with increased prevalence of cortical cataract (C) (OR: 1.99; 95% CI: 1.02-3.90), PSC (OR: 3.27; 95% CI: 1.34, 7.96) and of any cataract (OR: 1.86; 95% CI: 1.08, 3.18)., Conclusions: In agreement with some earlier studies, we found higher plasma levels of vitamin C to be associated with reduced prevalence of N and PSC cataracts. The finding of an increased prevalence of some types of cataract with higher levels of vitamin E was unexpected, has not been previously reported, and could be due to unadjusted confounding.

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.

Purpose: To investigate possible associations between sequence changes in the galactokinase gene (GALK1) and age-related cataract in a European population., Methods: Persons without lens opacities and persons with clinically significant age-related cataract were selected from those participating in the Collaborative Italian-American Clinical Trial of Nutritional Supplements and Age-Related Cataract or from those attending the Section of Ophthalmology of the University of Parma for cataract surgery. Type and severity of the opacities were assessed by slit-lamp and retro-illumination lens photographs. Mutations in GALK1 were identified by PCR amplification of individual exons and flanking sequences and sequencing using fluorescent terminator technology in an ABI 377 Prism or 3100 automated DNA sequencer., Results: DNA samples were obtained from 115 individuals with clear lenses and from 185 individuals with cataract (106 with any nuclear, 88 with any cortical, and 25 with any posterior sub capsular cataract). 157 of the 185 patients with cataract (85%) were age-matched with a control within an age range of plus or minus 1 year. SNPs causing amino acid changes in the galactokinase protein were identified in exon 4; I184M, 1/115 control versus 0/185 cataractous individuals, p=0.38, exon 6; G274D, 0/115 control versus 1/185 cataractous individuals, p>0.99, and exon 7; V338A, 0/115 control versus 1/185 cataractous individuals, p>0.99. Thus, there were no significant differences in the distribution of sequence alterations resulting in amino acid changes between control and cataractous individuals. Eighty samples showed a C to T transition 43 bases into intron 7 (46 cataracts and 34 controls). Testing the distribution of the intron 7 findings showed Hardy-Weinberg equilibrium for both cases (p=0.73) and controls (p=0.51). There was no difference in C/T distribution between cases and controls (p=0.27)., Conclusions: In this northern Italian population age-related cataract does not appear to be associated with GALK1 alleles. Since this is due to a lack of sequence changes in both affected and control individuals, this study cannot rule out the possibility of an association in other populations.

Objective: To examine the development of age-related cataract in a trial of beta carotene supplementation in men., Design: Randomized, double-masked, placebo-controlled trial., Methods: Male US physicians aged 40 to 84 years (n = 22 071) were randomly assigned to receive either beta carotene (50 mg on alternate days) or placebo for 12 years., Main Outcome Measures: Age-related cataract and extraction of age-related cataract, defined as an incident, age-related lens opacity, responsible for a reduction in best-corrected visual acuity to 20/30 or worse, based on self-report confirmed by medical record review., Results: There was no difference between the beta carotene and placebo groups in the overall incidence of cataract (998 cases vs 1017 cases; relative risk [RR], 1.00; 95% confidence interval [CI], 0.91-1.09) or cataract extraction (584 vs 593; RR, 1.00; 95% CI, 0.89-1.12). In subgroup analyses, the effect of beta carotene supplementation appeared to be modified by smoking status at baseline (P =.02). Among current smokers, there were 108 cases of cataract in the beta carotene group and 133 in the placebo group (RR, 0.74; 95% CI, 0.57-0.95). Among current nonsmokers, there was no significant difference in the number of cases in the 2 treatment groups (884 vs 881; RR, 1.03; 95% CI, 0.94-1.13). The results for cataract extraction appeared to be similarly modified by baseline smoking status (P =.05)., Conclusions: Randomized trial data from a large population of healthy men indicate no overall benefit or harm of 12 years of beta carotene supplementation on cataract or cataract extraction. However, among current smokers at baseline, beta carotene appeared to attenuate their excess risk of cataract by about one fourth.

Objective: To investigate whether serum lipid/lipoprotein levels are independent risk factors for nuclear, cortical, or posterior subcapsular (PSC) cataracts., Design: Case-control study nested in a cohort study., Participants and Methods: Eye examinations were conducted on surviving members of the Framingham Offspring Heart Study cohort from 1989 to 1991 (Framingham Offspring Eye Study) to determine cataract case-control status. Data from the Framingham Offspring Heart Study, including fasting serum total cholesterol, high-density lipoprotein cholesterol, and triglyceride measurements collected first in 1971, again approximately 8 years later, and approximately every 4 years thereafter were used to examine associations between lipid levels (mean levels across examinations and slope of measurements over time) and the presence of specific cataract types. The multistage analyses included 1869 persons aged 45 years and older., Main Outcome Measures: A standardized grading system was used to grade cortical, nuclear, and PSC cataracts., Results: The median age of participants was 55 years; 49% were males. In multivariable logistic regression models adjusted for potential confounders, fasting hypertriglyceridemia (>/=250 mg/dl) was associated with an increased risk of PSC cataract in men (P = 0.02). High-density lipoprotein cholesterol levels

Objective: To evaluate the relationship between intake of total and specific types of fat and risk for advanced age-related macular degeneration (AMD), the leading cause of irreversible blindness in adults., Design: A multicenter eye disease case-control study., Setting: Five US clinical ophthalmology centers., Patients: Case subjects included 349 individuals (age range, 55-80 years) with the advanced, neovascular stage of AMD diagnosed within 1 year of their enrollment into the study who resided near a participating clinical center. Control subjects included 504 individuals without AMD but with other ocular diseases. Controls were from the same geographic areas as cases and were frequency-matched to cases by age and sex., Main Outcome Measures: Relative risk for AMD according to level of fat intake, controlling for cigarette smoking and other risk factors., Results: Higher vegetable fat consumption was associated with an elevated risk for AMD. After adjusting for age, sex, education, cigarette smoking, and other risk factors, the odds ratio (OR) was 2.22 (95% confidence interval [CI], 1.32-3.74) for persons in the highest vs those in the lowest quintiles of intake (P for trend,.007). The risk for AMD was also significantly elevated for the highest vs lowest quintiles of intake of monounsaturated (OR, 1.71) and polyunsaturated (OR, 1.86) fats (Ps for trend,.03 and.03, respectively). Higher consumption of linoleic acid was also associated with a higher risk for AMD (P for trend,.02). Higher intake of omega-3 fatty acids was associated with a lower risk for AMD among individuals consuming diets low in linoleic acid, an omega-6 fatty acid (P for trend,.05; P for continuous variable,.03). Similarly, higher frequency of fish intake tended to reduce risk for AMD when the diet was low in linoleic acid (P for trend,.05). Conversely, neither omega-3 fatty acids nor fish intake were related to risk for AMD among people with high levels of linoleic acid intake., Conclusion: Higher intake of specific types of fat--including vegetable, monounsaturated, and polyunsaturated fats and linoleic acid--rather than total fat intake may be associated with a greater risk for advanced AMD. Diets high in omega-3 fatty acids and fish were inversely associated with risk for AMD when intake of linoleic acid was low.

Purpose: To assess the prevalence of refractive errors and vision impairment in school-age children in Shunyi District, northeast of Beijing, the Peoples Republic of China., Methods: Random selection of village-based clusters was used to identify a sample of children 5 to 15 years of age. Resident registration books were used to enumerate eligible children in the selected villages and identify their current school. Ophthalmic examinations were conducted in 132 schools on children from 29 clusters during May 1988 to July 1998, including visual acuity measurements, cycloplegic retinoscopy, cycloplegic autorefraction, ocular motility evaluation, and examination of the external eye, anterior segment, media, and fundus. Independent replicate measurements of all children with reduced vision and a sample of those with normal vision were done for quality assurance monitoring in three schools., Results: A total of 6,134 children from 4,338 households were enumerated, and 5,884 children (95.9%) were examined. The prevalence of uncorrected, presenting, and best visual acuity 0.5 (20/40) or worse in at least one eye was 12.8%, 10.9%, and 1.8%, respectively; 0.4% had best visual acuity 0.5 or worse in both eyes. Refractive error was the cause in 89.5% of the 1,236 eyes with reduced vision, amblyopia in 5%, other causes in 1.5%, with unexplained causes in the remaining 4%. Myopia -0.5 diopter or less in either eye was essentially absent in 5-year-old children, but increased to 36.7% in males and 55.0% in females by age 15. Over this same age range, hyperopia 2 diopters or greater decreased from 8.8% in males and 19.6% in females to less than 2% in both. Females had a significantly higher risk of both myopia and hyperopia., Conclusions: Reduced vision because of myopia is an important public health problem in school-age children in Shunyi District. More than 9% of children could benefit from prescription glasses. Further studies are needed to determine whether the upward trend in the prevalence of myopia continues far beyond age 15 and whether the development of myopia is changing for more recent birth cohorts.

Purpose: To assess the prevalence of refractive errors and vision impairment in school-age children in a suburban area (La Florida) of Santiago, Chile., Methods: Random selection of geographically defined clusters was used to identify a representative sample of children 5 to 15 years of age. Children in the 26 selected clusters were enumerated through a door-to-door survey and invited to report to a community health clinic for examination. Visual acuity measurements, cycloplegic retinoscopy, cycloplegic autorefraction, ocular motility evaluation, and examination of the external eye, anterior segment, media, and fundus were done from April through August 1998. Independent replicate examinations of all children with reduced vision and a sample of those with normal vision were done for quality assurance monitoring in six clusters., Results: A total of 6,998 children from 3,830 households were enumerated, and 5,303 children (75.8%) were examined. The prevalence of uncorrected, presenting, and best visual acuity 0.50 (20/40) or worse in at least one eye was 15.8%, 14.7%, and 7.4%, respectively; 3.3% had best visual acuity 0.50 or worse in both eyes. Refractive error was the cause in 56.3% of the 1,285 eyes with reduced vision, amblyopia in 6.5%, other causes in 4.3%, with unexplained causes in the remaining 32.9%. Myopia -0.50 diopter or less in either eye was present in 3.4% of 5-year-old children, increasing to 19.4% in males and 14.7% in females by age 15. Over this same age range, hyperopia 2.00 diopters or greater decreased from 22.7% to 7.1% in males and from 26.3% to 8.9% in females. Females had a significantly higher risk of hyperopia than males., Conclusions: Refractive error, associated primarily with myopia, is a major cause of reduced vision in school-age children in La Florida. More than 7% of children could benefit from the provision of proper spectacles. Efforts are needed to make existing programs that provide free spectacles for school children more effective. Further studies are needed to determine whether the upward trend in myopia continues far beyond 15 years of age.

Purpose: To examine whether high intraocular pressure (greater than or equal to 25 mm Hg) or a history of treatment for glaucoma is associated with decreased survival and, if so, how such ocular markers might be explained., Methods: Eye examinations, including applanation tonometry, were conducted on members of the Framingham Eye Study cohort from February 1, 1973, to February 1, 1975. Participants who reported a history of treatment for glaucoma were identified. Survival data, including information on the date of death, were available from the time of the Eye Study through March 31, 1990., Results: Of the 1,764 persons under the age of 70 years at the baseline eye examination, 1,421 persons had low intraocular pressure (< or =20 mm Hg), 264 persons had medium intraocular pressure levels (20 to 24 mm Hg), and 79 persons had high intraocular pressure (> or =25 mm Hg) or history of glaucoma treatment. During the follow-up period, 29%, 30%, and 47% died in the groups with low, medium, and high intraocular pressure (or history of glaucoma treatment), respectively. In an age-and-sex adjusted Cox proportional hazards analysis, the death rate ratio for the group with medium intraocular pressure relative to the group with low intraocular pressure was 1.04. The corresponding death rate ratio for the group with high intraocular pressure was 1.56 with a 95% confidence interval of 1.11 to 2.19 (P < .001). After adjustment for age, sex, hypertension, diabetes, cigarette smoking, and body mass index, a positive relationship remained, but at a borderline level of significance (P = .075)., Conclusions: High intraocular pressure or the presence of glaucoma is a marker for decreased life expectancy in the Framingham Eye Study cohort. The relationship is present even after adjustment for risk factors known to be associated with higher mortality such as age, sex, hypertension, diabetes, cigarette smoking, and body mass index. Special attention to the general health status of patients with high intraocular pressure or glaucoma seems warranted.

Objective: To describe the clinical course of affected and unaffected eyes in patients with idiopathic macular holes., Patients: Prospective study of patients with macular holes enrolled in the Eye Disease Case-Control Study., Main Outcome Measures: The best-corrected visual acuity at follow-up was compared with that at baseline. Changes in the macular holes, including increases in size or spontaneous regression, were assessed. The rates of development of new macular holes in fellow unaffected eyes were estimated., Results: Of the 198 patients examined at baseline, 28 (14.1%) died before reevaluation. Of those who survived, 122 (71.8%) had a follow-up examination. Approximately 34% (34.4%) of all eyes with macular holes had an increase in the size of the macular hole. Forty-five percent of eyes had a decrease in visual acuity of 2 or more lines and 27.8%, of 3 or more lines; 40.9% remained stable, with a gain or loss of fewer than 2 lines. The rate of development of a new macular hole during follow-up in fellow eyes that were unaffected at baseline was 4.3% for 3 or fewer years of follow-up, 6.5% for 4 to 5 years of follow-up, and 7.1% for 6 or more years of follow-up. Spontaneous regression of the macular hole occurred in 3 (8.6%) of 35 patients with a follow-up interval of 6 or more years, whereas no regression occurred in patients with a shorter follow-up., Conclusions: The visual acuity of 45.0% of eyes with macular holes deteriorated by 2 or more lines during follow-up. The rate of development of macular holes in unaffected fellow eyes was low.

Purpose: To examine whether low-dose aspirin (325 mg on alternate days) reduces the risk of age-related cataract and subtypes. This report extends previous findings, including both subtypes and additional newly identified incident cases since the earlier report., Methods: All 20,979 participants in the Physicians' Health Study, a randomized trial of aspirin and beta-carotene among U.S. male physicians age 40-84 in 1982, who did not report cataract at baseline were included. Average follow-up was five years. The main outcome measure was incident, age-related cataract responsible for a reduction in best-corrected visual acuity to 20/30 or worse, based on self-report confirmed by medical record review., Results: 501 age-related cataracts were diagnosed during follow-up, including 416 with nuclear sclerosis and 212 with a posterior subcapsular component; 318 cataracts progressed to surgical extraction. Overall, there were 245 cataracts in the aspirin group and 256 in the placebo group (relative risk [RR], 0.94; 95% confidence interval [CI], 0.79 to 1.13; P = 0.52). Cataract extractions were 19% less frequent in the aspirin than in the placebo group (RR, 0.81; 95% CI, 0.65 to 1.01; P = 0.06). In subgroup analyses of subtypes, aspirin takers had a lower risk of posterior subcapsular cataract (RR, 0.74; 95% CI, 0.57 to 0.98; P = 0.03) but not nuclear sclerosis (RR, 0.96; 95% CI, 0.79 to 1.16; P = 0.65) cataract., Conclusions: Overall, these randomized trial data tend to exclude a large benefit of five years of low-dose aspirin therapy on cataract development and extraction. The data are compatible with a modest benefit on cataract extraction for this duration of aspirin therapy. Subgroup analyses raise the possibility of a modest, but potentially important, protective effect of aspirin on posterior subcapsular cataract, a particularly disabling subtype.

Objective: The purpose of the study was to determine whether body mass index (BMI) is an independent risk factor for the development of nuclear, cortical, or posterior subcapsular lens opacities., Design: A cohort study., Participants and Methods: Eye examinations were conducted on surviving members of the Framingham Heart Study Cohort from 1973 to 1975 (Framingham Eye Study I) and again from 1986 to 1989 (Framingham Eye Study II). Data from the Framingham Heart Study, including weight measurements collected biennially from 1948, were used to examine associations between BMI (mean BMI across examinations, slope of BMI over time, and fluctuations in BMI) and the development of lens opacities. This analysis included 714 individuals, aged 52-80 years, who were free of lens opacities at the first eye examination., Main Outcome Measures: Development of nuclear, cortical, and posterior subcapsular lens opacities., Results: A total of 444 persons developed lens opacities during the approximately 13 years between eye examinations. In logistic regression analyses that controlled for age, sex, education, diabetes, and smoking, the risk of developing cortical opacity increased with higher BMI at the time of the first eye examination (P = 0.002). Risk of cortical opacities also increased, at a borderline level of significance, with higher average BMI (P = 0.09) across examinations and increasing BMI levels over time (P = 0.10). There was a strong association between increasing BMI over time and the development of posterior subcapsular lens opacities (P = 0.002). No associations were found for nuclear lens opacities., Conclusions: Although the mechanism explaining the association is unclear, these findings suggest that BMI, a potentially modifiable characteristic, is associated with the development of cortical and posterior subcapsular lens opacities.

Objective: Possible risk factors for hemiretinal vein occlusion were identified and compared with risk factor profiles for central and branch retinal vein occlusion., Design: The design was a multicenter case-control study., Methods: The authors identified 79 patients with hemiretinal vein occlusion (HRVO), 258 patients with central retinal vein occlusion (CRVO), 270 patients with branch retinal vein occlusion (BRVO), and 1142 control subjects at 5 clinical centers. Risk factor data were obtained through interviews, clinical examinations, and laboratory analyses of blood specimens., Results: Systemic hypertension and history of diabetes mellitus were associated with increased risk of HRVO. Risk of CRVO increased with history of diabetes, systemic hypertension, and higher erythrocyte sedimentation rate (females only); risk of CRVO decreased with increasing amounts of physical activity and increasing amounts of alcohol consumption. Systemic hypertension, higher body mass index, and higher alpha2-globulin levels were associated with increased risk of BRVO, whereas higher high-density lipoprotein levels and increasing levels of alcohol consumption were associated with decreased risk of BRVO. Glaucoma history was associated with all three types of retinal vein occlusion., Conclusion: Patients presenting with retinal vein occlusion should be evaluated for cardiovascular disease, diabetes, and glaucoma.

Purpose: To assess intra- and interobserver reproducibility of the Age-Related Eye Disease Study (AREDS) system for grading lens opacities and to provide data on its capacity to reliably detect changes in lens status., Methods: Independent and replicate grading of 40 sets of lens photographs (one slit-lamp and two retroillumination photographs) were performed by three experienced observers. Patients were participants in the Collaborative Italian-American Clinical Trial of Nutritional Supplements which is testing the effect of a mineral-multivitamin supplement on age-related cataract (CTNS). Scatterplots and intraclass correlation were used to assess measurement error., Results: Analysis revealed good intra- and interobserver reproducibility of the system. Greatest intraobserver measurement error showed 100% of pairs within 10% areal difference for cortical cataract, 97.5% within 15% areal difference for posterior subcapsular cataract, and 100% within 1 density unit difference for nuclear opacity. Greatest interobserver measurement error showed 95% of pairs within 10% areal difference for cortical cataract, 97.5% within 15% areal difference for posterior subcapsular cataract, and 97.5% within 1.5 density unit difference for nuclear opacity., Conclusions: The AREDS lens opacities grading system appears to be sufficiently reliable to detect changes of at least 10% areal involvement for cortical, 15% areal involvement for posterior subcapsular, and 1.0 units for nuclear opacities. It therefore seems sufficiently sensitive to adequately monitor progression of lens opacities in a longitudinal study of patients with early cataract. Its applicability in a population with advanced or complex mixed opacities must await further testing.

Objective: To examine the association between cigarette smoking and the incidence of nuclear and non-nuclear lens opacities in members of the Framingham Eye Study Cohort., Participants and Methods: Eye examinations were conducted on surviving members of the Framingham Heart Study Cohort from 1973 to 1975 (Framingham Eye Study I) and again from 1986 to 1989 (Framingham Eye Study II). Smoking data, collected biennially since 1948 in the Heart Study, were used to examine the relationship between cigarette smoking and the incidence of lens opacities. Two thousand six hundred seventy-five persons were examined in the Framingham Eye Study I. Our analysis included 660 persons, aged 52 to 80 years, who were free of lens opacities at the first eye examination., Results: During the approximately 12.5 years between eye examinations, lens opacities developed in a total of 381 persons, with nuclear opacities constituting the most frequent type. In logistic regression analyses that controlled for age, sex, education, and diabetes, a significant positive association with increasing duration of smoking and number of cigarettes smoked daily was found for nuclear lens opacities, alone or in combination (test for trend, P < or = .002), but not for nonnuclear opacities (test for trend, P = .62). Among the heavier smokers (persons who smoked > or = 20 cigarettes per day according to 6 or more biennial Framingham Heart Study examinations), 77% were still smoking at the time of the first eye examination. Persons who smoked 20 or more cigarettes per day at the time of the first eye examination were at substantially increased risk for the development of nuclear opacities than nonsmokers (odds ratio, 2.84; 95% confidence interval, 1.46-5.51). There was no apparent excess risk for persons with nonnuclear lens opacities (odds ratio, 1.42; 95% confidence interval, 0.65-3.07)., Conclusion: This study provides further evidence that cigarette smokers have an increased risk of developing nuclear lens opacities. The risk was greatest for heavier smokers, who tended to be current smokers and who smoked more cigarettes and for a longer duration.

Purpose: To examine the distribution of cortical opacities across the lens in the Italian-American Natural History Study of Age-Related Cataract and to study the association between an index of sunlight exposure and the location of cortical cataract within the lens., Methods: Lens photographs of one eye of 731 persons with cortical opacities (503 with pure and 228 with mixed types of opacity) were included in the analysis. A radial grid superimposed on the photographs was used to assess presence, location, and severity of wedge-shaped cortical opacities., Results: Both the prevalence and the extent of cortical opacities were highest in the inferior-nasal quadrant and lowest in the superior-nasal quadrant of the lens. In polychotomous logistic regression, persons with the greatest excess areal involvement in the inferior half of the lens were more likely to have high exposure to sunlight, as measured by a sunlight index, than persons with excess involvement in the superior half of the lens (odds ratio, 1.73; 95% confidence interval 1.03, 2.93). Excess areal involvement of the inferior lens also was associated with the pure type of cortical cataract and with the total extent of the opacity., Conclusions: Age-related cortical opacities occur more frequently inferiorly than superiorly and, to a lesser extent, nasally than temporally. Possibly higher exposure of these lens segments to sunlight may explain this preferential location of cortical opacities.

Purpose: To investigate possible associations between the gene number and allelic forms of glutathione S-transferase M1 (GSTM1) and the occurrence of nucleic and cortical age-related cataracts., Methods: Patients with cortical cataract, nuclear cataract, mixed and cortical cataract, and no cataract were sytematically selected from subjects evaluated in the Italian-American Study of the Natural History of Age-Related Cataract. The patients were typed for the A, B, and null alleles of GSTM1 using a variation of the amplification refractory mutation system., Results: Forty-nine percent of patients (50/102) with cortical cataracts, 45% (13/29) with nuclear cataracts, 51% (36/71) with mixed nuclear and cortical cataracts, and 50% of controls (49/98) were homozygous for the null GSTM1 allele. Twenty-five percent of patients (26/102) with cortical cataracts, 24% (7/29) with nuclear cataracts, 31% with mixed nuclear and cortical cataracts, and 27% of controls (26/98) displayed only the A allele for GSTM1. Twenty-four percent of patients (24/102) with cortical cataract, 24% (7/29) with nuclear cataracts, 14% (10/71) with mixed nuclear and cortical cataract, and 18% of controls showed only the B allele for GSTM1. Two percent of patients (2/102) with cortical cataracts, 7% (2/29) with nuclear cataracts, 4% (3/71) with mixed nuclear and cortical cataracts, and 5% of controls (5/98) showed both A and B alleles for GSTM1., Conclusions: No associations between the GSTM1 alleles, including the null allele, and cataracts were detected in this study.

The purpose of this study was to characterize the clinical course of myopia in a selected pediatric population. The computerized records of a health maintenance organization provided longitudinal data on 501 children aged 5 to 15 years. We examined the influence of age at diagnosis, gender, race, and initial refraction on progression of myopia. Mean follow-up was 34 months, with 75% of children having follow-up longer than 16 months. The mean rate of myopic progression was greater for children whose myopia was diagnosed at a younger age (5-7 years, -0.56 diopters/year versus 11-15 years, -0.28 diopters/year; p < 0.0001). Children with more than one diopter of myopia at first diagnosis progressed faster than children with less than or equal to one diopter of myopia (mean rate -0.48 diopter/year versus -0.41 diopter/year; p = 0.05). Cumulative event rate curves suggest a gender effect in the prepuberty years of 8 to 10, with myopia progressing faster in girls than boys (p = 0.003). Progression of myopia did not differ between white and non-white children. More rapidly progression of myopia is associated with younger age at initial diagnosis and greater severity of initial myopic refraction.

There has been increasing use of high-dosage zinc supplementation in the population, in particular as a potential treatment for age-related macular degeneration. We examined the relationship between fasting serum zinc and serum lipid levels in 778 adults, aged 22 to 80 years, who were control subjects in a multicenter, clinic-based case-control study. The samples were taken during 1987 to 1990, a time when vitamin/mineral supplementation was becoming increasingly common. We found that higher serum zinc levels, most notably those above the highest quintile, were associated with higher levels of total serum cholesterol, low-density-lipoprotein cholesterol, and triglycerides. No significant trend was noted for high-density-lipoprotein cholesterol. Previous studies demonstrated that high-dosage zinc supplements raise serum zinc levels. The possibility that use of such supplements can adversely affect serum lipid profiles suggests that chronic ingestion of such supplements should not be done without adequate medical supervision.

OBJECTIVE--To evaluate the relationships between dietary intake of carotenoids and vitamins A, C, and E and the risk of neovascular age-related macular degeneration (AMD), the leading cause of irreversible blindness among adults. DESIGN--The multicenter Eye Disease Case-Control Study. SETTING--Five ophthalmology centers in the United States. PATIENTS--A total of 356 case subjects who were diagnosed with the advanced stage of AMD within 1 year prior to their enrollment, aged 55 to 80 years, and residing near a participating clinical center. The 520 control subjects were from the same geographic areas as case subjects, had other ocular diseases, and were frequency-matched to cases according to age and sex. MAIN OUTCOME MEASURES--The relative risk for AMD was estimated according to dietary indicators of antioxidant status, controlling for smoking and other risk factors, by using multiple logistic-regression analyses. RESULTS--A higher dietary intake of carotenoids was associated with a lower risk for AMD. Adjusting for other risk factors for AMD, we found that those in the highest quintile of carotenoid intake had a 43% lower risk for AMD compared with those in the lowest quintile (odds ratio, 0.57; 95% confidence interval, 0.35 to 0.92; P for trend = .02). Among the specific carotenoids, lutein and zeaxanthin, which are primarily obtained from dark green, leafy vegetables, were most strongly associated with a reduced risk for AMD (P for trend = .001). Several food items rich in carotenoids were inversely associated with AMD. In particular, a higher frequency of intake of spinach or collard greens was associated with a substantially lower risk for AMD (P for trend < .001). The intake of preformed vitamin A (retinol) was not appreciably related to AMD. Neither vitamin E nor total vitamin C consumption was associated with a statistically significant reduced risk for AMD, although a possibly lower risk for AMD was suggested among those with higher intake of vitamin C, particularly from foods. CONCLUSION--Increasing the consumption of foods rich in certain carotenoids, in particular dark green, leafy vegetables, may decrease the risk of developing advanced or exudative AMD, the most visually disabling form of macular degeneration among older people. These findings support the need for further studies of this relationship.

Cataracts develop in the lens of the eye which is responsible for focusing incoming light onto the retina. Early in life the lens is transparent, and incoming light encounters no difficulty in its passage through the eye. With aging, the lens becomes less clear, incoming light is scattered to an increasing degree, and if loss of lens clarity is severe enough, vision is affected. When clouding of the lens impairs vision, a clinically significant cataract is present. Currently there is no medical treatment for age-related cataract. The only treatment is surgical removal of the affected lens when vision is sufficiently impaired. A major goal of past and on-going epidemiologic studies is the identification of risk factors for cataract, so that strategies for the prevention of cataract can be developed.

To explore the existence of a dose-response relationship between sunlight exposure and risk of age-related cataracts, we analyzed data collected from 1008 patients with cataracts and 469 control subjects enrolled in the Italian-American Case-Control Study of Age-Related Cataracts. Fourteen variables related to sunlight exposure history were included in the questionnaire administered to the study participants. A sunlight index was constructed and its relationship to the presence of cataracts was modeled by logistic regression. After adjustments for potential confounding variables and for age and sex, a significant dose-response effect (P = 0.01) was detected between the sunlight exposure index and the presence of pure cortical cataracts. With the exception of corticonuclear cataracts, all the other mixed types of opacity also showed a dose-response association with the sunlight index. These data support the hypothesis that sunlight exposure is a risk factor in the development of cortical cataracts, and demonstrate the existence of a dose-response relationship in this association.

Purpose: To compare the relationship between logMAR visual acuity (VA) and cataract severity and between contrast sensitivity (CS) and cataract severity in pure types of age-related lens opacities., Methods: Analysis included patients followed in the ongoing Italian-American Study of the Natural History of Age-Related Cataract. Lens opacities were classified and graded according to the Lens Opacities Classification System II (LOCS II). Visual acuity was measured with the Early Treatment Diabetic Retinopathy Study Chart. Contrast sensitivity was measured with the Pelli-Robson chart., Results: Data from 1,076 eyes were used for the analysis (366 clear lenses; 550, 124, and 36 eyes with cortical, nuclear and posterior subcapsular cataract, respectively). In age-adjusted analyses, increasing severity of all three cataract types was associated with progressively higher logMAR VA, which translates into poorer acuity, and lower CS scores. For both VA and CS, the effect of increasing severity was greatest for nuclear and least for cortical opacities. After adjusting for age and VA, CS scores were no longer associated with cataract type and severity, with the exception of advanced cortical opacities., Conclusions: Increased cataract severity, as determined by LOCS II grading, is strongly associated with both VA and CS scores. Contrast sensitivity scores obtained from testing at low spatial frequency do not seem to offer additional information over standard VA testing in early cortical and posterior subcapsular opacities nor in nuclear cataracts.

Background: Recent reports have suggested that a secondary effect of radial keratotomy may be a reduction in intraocular pressure (IOP) levels., Methods: In an effort to study the relationship of radial keratotomy to IOP, we compared the mean IOP from the baseline and follow-up visits during 1 year after surgery of operated versus nonoperated eyes of patients enrolled in the Prospective Evaluation of Radial Keratotomy (PERK) study. To investigate if radial keratotomy had more of an effect on eyes with higher baseline IOPs, the same analysis was performed on a subset (134 patients) who had a baseline IOP of 15 mm Hg or greater., Results: The average baseline IOP for both operated eyes and nonoperated eyes was 14.6 mm Hg. There was no significant difference in mean IOP between operated and nonoperated eyes across all time points (p = .18). Although mean IOP changed over time, it did not clinically differ in operated versus nonoperated eyes at any time point. These findings were similar in the analysis of eyes with higher baseline IOP (15 mm Hg or greater)., Conclusion: We conclude that the radial keratotomy performed in the PERK study had no effect on IOP within 1 year after surgery.

Objective: To determine whether the vitamin/mineral supplements used in two cancer intervention trials affected the risk of developing age-related cataracts., Design: Two randomized, double-masked trials with a duration of 5 to 6 years and end-of-trial eye examinations., Setting: Rural communes in Linxian, China., Participants: In trial 1, 2141 participants aged 45 to 74 years, and, in trial 2, 3249 participants aged 45 to 74 years., Interventions: Multivitamin/mineral supplement or matching placebo in trial 1; factorial design to test the effect of four different vitamin/mineral combinations in trial 2 (retinol/zinc, riboflavin/niacin, ascorbic acid/molybdenum, and selenium/alpha-tocopherol/beta carotene)., Main Outcome Measures: Prevalence of nuclear, cortical, and posterior subcapsular cataracts in treatment groups at end of trials., Results: In the first trial, there was a statistically significant 36% reduction in the prevalence of nuclear cataract for persons aged 65 to 74 years who received the supplements. In the second trial, the prevalence of nuclear cataract was significantly lower in persons receiving riboflavin/niacin compared with persons not receiving these vitamins. Again, persons in the oldest group, 65 to 74 years, benefited the most (44% reduction in prevalence). No treatment effect was noted for cortical cataract in either trial. Although the number of posterior subcapsular cataracts was very small, there was a statistically significant deleterious effect of treatment with riboflavin/niacin., Conclusions: Findings from the two trials suggest that vitamin/mineral supplements may decrease the risk of nuclear cataract. Additional research is needed in less nutritionally deprived populations before these findings can be translated into general nutritional recommendations.

Purpose: The study was designed to evaluate the relative anatomic position of the crossing vessels at the site of occlusion in eyes with branch retinal vein occlusion (BRVO)., Methods: Fundus photographs of 106 eyes (104 patients) with recent BRVO from the Eye Disease Case-Control Study were used to examine the relative position of artery and vein at occluded crossings. Three separate comparison groups were formed by identifying corresponding arteriovenous crossings for each occluded crossing in: (1) the ipsilateral but opposite vessel arcade within eyes affected by BRVO; (2) the same quadrant in unaffected eyes of BRVO patients; and (3) the same quadrant in eyes of patients without BRVO, matched by age, sex, and race with the BRVO patients., Results: The site of obstruction of the branch vein was an arteriovenous crossing in all affected eyes. In 99% of eyes with BRVO, the artery was located anterior to the vein at the obstructed site. In the three comparison groups, the artery was anterior to the vein in 62%, 61%, and 54% of the crossings, respectively, yielding statistically significant differences for each group of control crossings compared with BRVO crossings (P < 0.001)., Conclusion: Finding the vein to be consistently between the more rigid artery and the retina at almost all arteriovenous crossings affected by BRVO suggests a possible role for mechanical obstruction in the pathogenesis of BRVO.