Vitamin Supplements and Eye Disease
Can vitamin supplements help protect against cataracts and/or age-related macular degeneration? Read the results from the latest studies in this easy-to-navigate collection of recent MEDLINE abstracts compiled by the editors at Medscape.
Lyle BJ, Mares-Perlman JA, et al
Am J Epidemiol. 1999;149:801-9
The relation of antioxidant nutrients to the incidence of nuclear cataracts was investigated in a cohort of adults aged 43-84 years in the Beaver Dam Eye Study (Beaver Dam, Wisconsin). Nuclear opacity was assessed on a five-point ordinal scale using lens photographs taken at baseline (1988-1990) and at follow-up (1993-1995). Of the 1,354 persons eligible, 246 developed a nuclear cataract (level 4 or 5 opacity) in at least one eye. Antioxidant intakes were assessed using a food frequency questionnaire administered at baseline for time points corresponding to intake during the year preceding baseline and 10 years before baseline (the distant past). Lutein-zeaxanthin was the only carotenoid, out of five examined, that was associated with nuclear cataracts. Persons in the highest quintile of lutein intake in the distant past were half as likely to have an incident cataract as persons in the lowest quintile of intake (95% confidence interval 0.3-0.8). In the overall group, nuclear cataracts were not significantly related to intake of vitamin C or vitamin E. However, vitamins C and E were inversely associated with opacities in persons who had some other risk factors for cataracts. While results of this short term follow-up study are consistent with a possible protective influence of lutein and vitamins E and C on the development of nuclear cataracts, the evidence in the present study provides weak support for these associations.
Leske MC, Chylack LT Jr, He Q, et al
Ophthalmology 1998;105:831-6
Objective: The association of antioxidant nutrients and risk of nuclear opacification was evaluated in the Longitudinal Study of Cataract.
Design: Nutritional data were collected at baseline on the 764 participants, which included assessment of dietary intake, use of vitamin supplements, and plasma levels of vitamin E. Ophthalmologic and other data were collected at baseline and at yearly follow-up visits, including lens photographs, which were graded using the Lens Opacities Classification System III protocol.
Main Outcome Measures: Analyses examined whether the nutritional factors at baseline were related to increases in nuclear opacification at follow-up. The MULCOX2 approach, an extension of the Cox regression model, was used. Results are presented as relative risks (RRs) and 95% confidence intervals.
Intervention: Intervention was not applicable.
Results: The risk of nuclear opacification at follow-up was decreased in regular users of multivitamin supplements (RR = 0.69; 0.48-0.99), vitamin E supplements (RR = 0.43; 0.19-0.99), and in persons with higher plasma levels of vitamin E (RR = 0.58; 0.36-0.94).
Conclusions: In regular users of multivitamin supplements, the risk of nuclear opacification was reduced by one third; in regular users of vitamin E supplements and persons with higher plasma levels of vitamin E, the risk was reduced by approximately half. These results are similar to those obtained in our earlier case-control study. Because these data are based on observational studies only, the results are suggestive but inconclusive. The possible effect of nutritional supplements on the lens requires confirmation by ongoing clinical trials.
Christen WG, Ajani UA, Glynn RJ, et al
Am J Epidemiol. 1999;149:476-84
In a prospective cohort study, the authors examined whether self-selection for antioxidant vitamin supplement use affects the incidence of age-related maculopathy. The study population consisted of 21,120 US male physician participants in the Physicians' Health Study I who did not have a diagnosis of age-related maculopathy at baseline (1982). During an average of 12.5 person-years of follow-up, a total of 279 incident cases of age-related maculopathy with vision loss to 20/30 or worse were confirmed by medical record review. In multivariate analysis, as compared with nonusers of supplements, persons who used vitamin E supplements had a possible but nonsignificant 13% reduced risk of age-related maculopathy (relative risk = 0.87, 95 percent confidence interval (CI) 0.53-1.43), while users of multivitamins had a possible but nonsignificant 10% reduced risk (relative risk = 0.90, 95% CI 0.68-1.19). Users of vitamin C supplements had a relative risk of 1.03 (95% CI 0.71-1.50). These observational data suggest that among persons who self-select for supplemental use of antioxidant vitamin C or E or multivitamins, large reductions in the risk of age-related maculopathy are unlikely. Randomized trial data are accumulating to enable reliable detection of the existence of more plausible small-to-moderate benefits of these agents alone and in combination on age-related maculopathy.
Smith W, Mitchell P, Webb K, et al
Ophthalmology 1999;106:761-7
Objective: To assess associations between the stages of age-related maculopathy (ARM) and dietary intake of carotene, vitamin C, retinol, and zinc.
Design: Cross-sectional, population-based study.
Participants: A total of 3654 subjects 49 years of age and older from a defined area, west of Sydney, Australia, participated. A total of 2900 participants (79.4%) completed accurate food records.
Intervention: Masked grading of stereoscopic macular photographs, detailed interviewer-administered questionnaire, and 145-item self-administered food frequency questionnaire.
Main Outcome Measures: Late ARM and early ARM were diagnosed from photographic grading.
Results: The authors found no statistically significant associations between ARM and dietary intake of either carotene, zinc, or vitamins A or C, either from diet or supplements or from the combined intake from diet and supplements. Multivariate-adjusted odds ratios (95% confidence interval) were calculated comparing highest to lowest dietary intake quintiles. For late ARM, the odds ratios were carotene, 0.7 (range, 0.3-2.0); vitamin A, 1.2 (range, 0.5-3.3); vitamin C, 1.3 (range, 0.5-3.4); and zinc, 1.0 (range, 0.4-2.8). For early ARM, the odds ratios were carotene, 0.7 (range, 0.4-1.1); vitamin A, 1.2 (range, 0.7-2.0); vitamin C, 0.9 (range, 0.5-1.4); and zinc, 0.8 (range, 0.5-1.3). No significant trends were apparent. Adjustment for energy intake also showed no associations between these antioxidants and ARM. Further, no associations were found between increasing intake of foods high in antioxidant vitamins and decreasing prevalence of either late or early ARM.
Conclusions: The authors found no associations between ARM and dietary antioxidants, either from diet alone or including supplements, or from selected foods, in the Blue Mountains Eye Study population.
Klein R, Klein BE, Jensen SC, et al
Ophthalmology 1997;104:7-21
Purpose: The aim of the study was to describe the incidence and progression of retinal drusen, retinal pigmentary abnormalities, and signs of late age-related maculopathy. Population: A population of 3583 adults (range, 43-86 years of age at baseline) living in Beaver Dam, Wisconsin, was studied during a 5-year period.
Methods: Characteristics of drusen and other lesions typical of age-related maculopathy were determined by grading stereoscopic color fundus photographs using the Wisconsin Age-Related Maculopathy Grading System.
Results: There was a statistically significant increased incidence of age-related maculopathy lesions with age (P < 0.05). Individuals 75 years of age or older had a significantly (P < 0.01) higher 5-year incidence of the following characteristics than people 43 to 54 years of age: larger sized drusen (125-249 microm, 17.6% vs. 2.1%; > or = 250 microm, 6.5% vs. 0.2%), soft indistinct drusen (16.3% vs. 1.8%), retinal pigment abnormalities (12.9% vs. 0.9%), exudative macular degeneration (1.8% vs. 0%), and pure geographic atrophy (1.7% vs. 0%). After adjusting for age, the incidence of early age-related maculopathy was 2.2 times (95% confidence interval 1.6, 3.2) as likely in women 75 years of age or older compared with men this age. At follow-up, late age-related macular degeneration was more likely to develop in eyes with soft indistinct drusen (6.5% vs. 0.1%) or retinal pigmentary abnormalities (7.1% vs. 0.1%) at baseline than in eyes without these lesions. Conclusions: These population-based estimates document the high incidence of signs of age-related maculopathy in people 75 years of age or older, and in women compared with men that age. The findings demonstrate that the presence of soft drusen and pigmentary abnormalities significantly increases the risk for the development of geographic atrophy and exudative macular degeneration.
VandenLangenberg GM, Mares-Perlman JA, Klein R, et al
Am J Epidemiol. 1998;148:204-14
Associations between antioxidants and zinc and the 5-year incidence of early, age-related maculopathy (ARM) were investigated in a population-based cohort of middle-aged and older adults participating in the Beaver Dam Eye Study in Beaver Dam, Wisconsin. A food-frequency questionnaire was administered at baseline (1988-1990) to collect dietary information for that time period and a period of time 10 years earlier (1978-1980) from a 50 percent random sample of persons participating in this study. The incidence of the specific lesions of larger drusen (>125 microns) and pigmentary abnormalities and the incidence of any ARM were assessed by masked grading of stereoscopic color fundus photographs in 1,709 persons who participated in 5-year follow-up eye examinations. Significant, but modest, inverse associations (p < 0.05) were observed between intakes of pro-vitamin A carotenoids and dietary vitamin E and the incidence of large drusen and between zinc and the incidence of pigmentary abnormalities. No significant inverse associations were found between antioxidant or zinc intake and the incidence of overall early ARM. If ARM, which is characterized by a broad spectrum of lesions, involves a number of different underlying pathophysiologic processes, then associations between specific antioxidants and the incidence of distinct macular lesions may be biologically important. However, because there were too few incident late ARM cases in this cohort, the authors were unable to assess whether antioxidant intake is associated with the progression of early ARM to late-stage macular degeneration. Clinical trials and longer-term prospective studies are needed to elucidate further the impact of antioxidants and zinc on the development and progression of ARM.
Control Clin Trials 1999;20:573-600
The Age-Related Eye Disease Study (AREDS) was initially conceived as a long-term multicenter, prospective study of the clinical course of age-related macular degeneration (AMD) and age-related cataract. Data on progression rates and risk factors from the study will increase understanding of the clinical course of both conditions, generate hypotheses about etiology, and aid in the design of clinical trials of potential interventions. In addition to collecting natural history data, AREDS includes a clinical trial of high-dose vitamin and mineral supplements for AMD and a clinical trial of high-dose vitamin supplements for cataract. The clinical trials were initiated largely because of the widespread public use in the United States of commercially available pharmacologic doses of vitamins and minerals to treat these two eye conditions and the absence of definitive studies on the safety and efficacy of their use. Important design issues for the clinical trials include: defining cataract and AMD, estimating event rates, determining the type and dosage of vitamins and minerals to be tested for each condition, and identifying the parameters necessary for monitoring safety and efficacy. This paper describes the AREDS design, including the study rationale and operational structure, and the approach adopted to combine, for two diseases, clinical trials with a natural history study.
J Nutr. 2000;130(5S Suppl):1516S-9S
The Age-Related Eye Disease Study includes a clinical trial of high dose antioxidant and zinc supplements for age-related macular degeneration and a clinical trial of high dose antioxidants for cataract. The clinical trials were initiated largely because of the widespread public use in the United States of commercially available pharmacological doses of vitamins and minerals to treat these two eye conditions and the absence of definitive studies on the safety and efficacy of their use. This report focuses on the clinical trial of zinc and the possibility that this elderly study cohort, who were randomly assigned in a factorial design to receive zinc, antioxidants and placebo, could be assessed for zinc effects other than those currently addressed by the trial.
Tikellis G, Robman LD, Harper CA, et al
Ophthalmic Epidemiol. 1999;6:181-94
Purposes: (1) To develop the methodology for the grading of macular one-frame stereoslides and to assess the reliability of the system. (2) To determine the prevalence of soft drusen (> 63 microm) and pigment abnormalities synonymous with age-related maculopathy (ARM) at baseline, in a clinical trial of volunteers aged between 55 and 80 years of age. (3) To ascertain the power of the study to detect the 4-year incidence and progression of ARM in vitamin E versus placebo treated participants, given the baseline prevalence.
Methods: The 1204 participants enrolled in the Vitamin E, Cataract, and Age-related Maculopathy Study (VECAT) had colour stereoslides of their fundus taken using the Nidek 3-DX mydriatic fundus camera. The stereoslides were graded by two masked graders according to the "International Classification System for ARM and AMD". Assessment of inter- and intra-observer reliability was carried out on a regular basis on 15% of randomly selected slides. Anticipated rates of incidence and progression were based on results reported by the Beaver Dam Eye Study and the Chesapeake Bay Waterman Study. Power estimations were determined using the "nQuery Advisor" software program. Analyses were carried out on the worse affected eye.
Results: Inter-observer reliability was moderate to substantial (Kappa 0.5-0.88) whilst intra-observer agreement was high (0.6-1.0). The prevalence of any soft drusen was 32%. Significant associations were found between soft large indistinct drusen, hypopigmentation, hyperpigmentation and age (p = 0.0001, 0.024 and 0.0001, respectively). The study has at least 87% power to detect an odds ratio equal to two for the progression of soft distinct, soft indistinct, hyperpigmentation and hypopigmentation.
Conclusions: The VECAT study methodology appears to be highly reliable and to have sufficient power to detect the differences in the four-year progression of soft distinct and indistinct drusen and pigment abnormalities between the treatment groups.
Garrett SK, McNeil JJ, Silagy C, et al
Ophthalmic Epidemiol. 1999;6:195-208
Cataract is the leading cause of blindness in the world today, while age-related macular degeneration is responsible for the majority of new cases of visual impairment in the Western world. There is a growing body of evidence suggesting a role for antioxidant therapy to prevent the progression of these conditions. A 4-year prospective, randomised, controlled trial of an antioxidant versus placebo in a population of healthy volunteers aged 55-80 years at enrolment is described. This paper outlines the primary aims of the Vitamin E, Cataract and Age-related Macular Degeneration (VECAT) Study, the methodology, and the recruitment rates. Additional data on the toxicity and non-ocular effects of vitamin E will also be collected. Standardised clinical grading of macular and lens features, and comparison of serial macular photographs and digital lens photographs will form the basis for assessment of primary study outcomes. Information collected in this study will assist in the assessment of the potential value of antioxidants in preventing the enormous burden imposed on developed communities by age-related eye disease. In addition, important data on prevalence and progression rates of cataract and macular degeneration will be collected.
Robman LD, Tikellis G, Garrett SK, et al
Aust N Z J Ophthalmol. 1999;27:410-6
Purpose: To describe the methodology of eye examination and the baseline eye characteristics of the Vitamin E, Cataract and Age-Related Maculopathy (VECAT) study participants.
Methods: A sample of volunteers from an urban area of Melbourne, Australia, were recruited to participate in a randomized, controlled trial investigating the effect of vitamin E on the development of cataract and age-related maculopathy Standardized eye examinations involved clinical assessment, which included Wilmer grading of the lens, digital photography of the lens with Nidek EAS-1000 lens camera and stereo photography of the macular area with the Nidek 3-DX fundus camera. All cases of ophthalmic findings were determined on the basis of pathology in the worse eye.
Results: Most eyes were free from abnormalities.The most frequent findings were cataract and age-related macular changes. Nuclear cataract (nuclear opacity grade >2) was present in 4.5%, cortical cataract (cortical opacity grade >2) in 14.3% and posterior subcapsular cataract in 3.0% of participants; in addition, coronary cataract was observed in 13.6%. Soft drusen larger than 125 pm were found in 11.4%, retinal pigment epithelium changes in 9.5%, epiretinal membrane in 6.6% and age-related macular degeneration in 0.5% of participants. SUMMARY: Due to the selection criteria, the majority of participants had clear or minor lens changes and/or minor retinal age-related changes. Precise instrumental documentation will allow an accurate assessment of the incidence and dynamics of these changes throughout 4 years of observation.
Can vitamin supplements help protect against cataracts and/or age-related macular degeneration? Read the results from the latest studies in this easy-to-navigate collection of recent MEDLINE abstracts compiled by the editors at Medscape.
Lyle BJ, Mares-Perlman JA, et al
Am J Epidemiol. 1999;149:801-9
The relation of antioxidant nutrients to the incidence of nuclear cataracts was investigated in a cohort of adults aged 43-84 years in the Beaver Dam Eye Study (Beaver Dam, Wisconsin). Nuclear opacity was assessed on a five-point ordinal scale using lens photographs taken at baseline (1988-1990) and at follow-up (1993-1995). Of the 1,354 persons eligible, 246 developed a nuclear cataract (level 4 or 5 opacity) in at least one eye. Antioxidant intakes were assessed using a food frequency questionnaire administered at baseline for time points corresponding to intake during the year preceding baseline and 10 years before baseline (the distant past). Lutein-zeaxanthin was the only carotenoid, out of five examined, that was associated with nuclear cataracts. Persons in the highest quintile of lutein intake in the distant past were half as likely to have an incident cataract as persons in the lowest quintile of intake (95% confidence interval 0.3-0.8). In the overall group, nuclear cataracts were not significantly related to intake of vitamin C or vitamin E. However, vitamins C and E were inversely associated with opacities in persons who had some other risk factors for cataracts. While results of this short term follow-up study are consistent with a possible protective influence of lutein and vitamins E and C on the development of nuclear cataracts, the evidence in the present study provides weak support for these associations.
Leske MC, Chylack LT Jr, He Q, et al
Ophthalmology 1998;105:831-6
Objective: The association of antioxidant nutrients and risk of nuclear opacification was evaluated in the Longitudinal Study of Cataract.
Design: Nutritional data were collected at baseline on the 764 participants, which included assessment of dietary intake, use of vitamin supplements, and plasma levels of vitamin E. Ophthalmologic and other data were collected at baseline and at yearly follow-up visits, including lens photographs, which were graded using the Lens Opacities Classification System III protocol.
Main Outcome Measures: Analyses examined whether the nutritional factors at baseline were related to increases in nuclear opacification at follow-up. The MULCOX2 approach, an extension of the Cox regression model, was used. Results are presented as relative risks (RRs) and 95% confidence intervals.
Intervention: Intervention was not applicable.
Results: The risk of nuclear opacification at follow-up was decreased in regular users of multivitamin supplements (RR = 0.69; 0.48-0.99), vitamin E supplements (RR = 0.43; 0.19-0.99), and in persons with higher plasma levels of vitamin E (RR = 0.58; 0.36-0.94).
Conclusions: In regular users of multivitamin supplements, the risk of nuclear opacification was reduced by one third; in regular users of vitamin E supplements and persons with higher plasma levels of vitamin E, the risk was reduced by approximately half. These results are similar to those obtained in our earlier case-control study. Because these data are based on observational studies only, the results are suggestive but inconclusive. The possible effect of nutritional supplements on the lens requires confirmation by ongoing clinical trials.
Christen WG, Ajani UA, Glynn RJ, et al
Am J Epidemiol. 1999;149:476-84
In a prospective cohort study, the authors examined whether self-selection for antioxidant vitamin supplement use affects the incidence of age-related maculopathy. The study population consisted of 21,120 US male physician participants in the Physicians' Health Study I who did not have a diagnosis of age-related maculopathy at baseline (1982). During an average of 12.5 person-years of follow-up, a total of 279 incident cases of age-related maculopathy with vision loss to 20/30 or worse were confirmed by medical record review. In multivariate analysis, as compared with nonusers of supplements, persons who used vitamin E supplements had a possible but nonsignificant 13% reduced risk of age-related maculopathy (relative risk = 0.87, 95 percent confidence interval (CI) 0.53-1.43), while users of multivitamins had a possible but nonsignificant 10% reduced risk (relative risk = 0.90, 95% CI 0.68-1.19). Users of vitamin C supplements had a relative risk of 1.03 (95% CI 0.71-1.50). These observational data suggest that among persons who self-select for supplemental use of antioxidant vitamin C or E or multivitamins, large reductions in the risk of age-related maculopathy are unlikely. Randomized trial data are accumulating to enable reliable detection of the existence of more plausible small-to-moderate benefits of these agents alone and in combination on age-related maculopathy.
Smith W, Mitchell P, Webb K, et al
Ophthalmology 1999;106:761-7
Objective: To assess associations between the stages of age-related maculopathy (ARM) and dietary intake of carotene, vitamin C, retinol, and zinc.
Design: Cross-sectional, population-based study.
Participants: A total of 3654 subjects 49 years of age and older from a defined area, west of Sydney, Australia, participated. A total of 2900 participants (79.4%) completed accurate food records.
Intervention: Masked grading of stereoscopic macular photographs, detailed interviewer-administered questionnaire, and 145-item self-administered food frequency questionnaire.
Main Outcome Measures: Late ARM and early ARM were diagnosed from photographic grading.
Results: The authors found no statistically significant associations between ARM and dietary intake of either carotene, zinc, or vitamins A or C, either from diet or supplements or from the combined intake from diet and supplements. Multivariate-adjusted odds ratios (95% confidence interval) were calculated comparing highest to lowest dietary intake quintiles. For late ARM, the odds ratios were carotene, 0.7 (range, 0.3-2.0); vitamin A, 1.2 (range, 0.5-3.3); vitamin C, 1.3 (range, 0.5-3.4); and zinc, 1.0 (range, 0.4-2.8). For early ARM, the odds ratios were carotene, 0.7 (range, 0.4-1.1); vitamin A, 1.2 (range, 0.7-2.0); vitamin C, 0.9 (range, 0.5-1.4); and zinc, 0.8 (range, 0.5-1.3). No significant trends were apparent. Adjustment for energy intake also showed no associations between these antioxidants and ARM. Further, no associations were found between increasing intake of foods high in antioxidant vitamins and decreasing prevalence of either late or early ARM.
Conclusions: The authors found no associations between ARM and dietary antioxidants, either from diet alone or including supplements, or from selected foods, in the Blue Mountains Eye Study population.
Klein R, Klein BE, Jensen SC, et al
Ophthalmology 1997;104:7-21
Purpose: The aim of the study was to describe the incidence and progression of retinal drusen, retinal pigmentary abnormalities, and signs of late age-related maculopathy. Population: A population of 3583 adults (range, 43-86 years of age at baseline) living in Beaver Dam, Wisconsin, was studied during a 5-year period.
Methods: Characteristics of drusen and other lesions typical of age-related maculopathy were determined by grading stereoscopic color fundus photographs using the Wisconsin Age-Related Maculopathy Grading System.
Results: There was a statistically significant increased incidence of age-related maculopathy lesions with age (P < 0.05). Individuals 75 years of age or older had a significantly (P < 0.01) higher 5-year incidence of the following characteristics than people 43 to 54 years of age: larger sized drusen (125-249 microm, 17.6% vs. 2.1%; > or = 250 microm, 6.5% vs. 0.2%), soft indistinct drusen (16.3% vs. 1.8%), retinal pigment abnormalities (12.9% vs. 0.9%), exudative macular degeneration (1.8% vs. 0%), and pure geographic atrophy (1.7% vs. 0%). After adjusting for age, the incidence of early age-related maculopathy was 2.2 times (95% confidence interval 1.6, 3.2) as likely in women 75 years of age or older compared with men this age. At follow-up, late age-related macular degeneration was more likely to develop in eyes with soft indistinct drusen (6.5% vs. 0.1%) or retinal pigmentary abnormalities (7.1% vs. 0.1%) at baseline than in eyes without these lesions. Conclusions: These population-based estimates document the high incidence of signs of age-related maculopathy in people 75 years of age or older, and in women compared with men that age. The findings demonstrate that the presence of soft drusen and pigmentary abnormalities significantly increases the risk for the development of geographic atrophy and exudative macular degeneration.
VandenLangenberg GM, Mares-Perlman JA, Klein R, et al
Am J Epidemiol. 1998;148:204-14
Associations between antioxidants and zinc and the 5-year incidence of early, age-related maculopathy (ARM) were investigated in a population-based cohort of middle-aged and older adults participating in the Beaver Dam Eye Study in Beaver Dam, Wisconsin. A food-frequency questionnaire was administered at baseline (1988-1990) to collect dietary information for that time period and a period of time 10 years earlier (1978-1980) from a 50 percent random sample of persons participating in this study. The incidence of the specific lesions of larger drusen (>125 microns) and pigmentary abnormalities and the incidence of any ARM were assessed by masked grading of stereoscopic color fundus photographs in 1,709 persons who participated in 5-year follow-up eye examinations. Significant, but modest, inverse associations (p < 0.05) were observed between intakes of pro-vitamin A carotenoids and dietary vitamin E and the incidence of large drusen and between zinc and the incidence of pigmentary abnormalities. No significant inverse associations were found between antioxidant or zinc intake and the incidence of overall early ARM. If ARM, which is characterized by a broad spectrum of lesions, involves a number of different underlying pathophysiologic processes, then associations between specific antioxidants and the incidence of distinct macular lesions may be biologically important. However, because there were too few incident late ARM cases in this cohort, the authors were unable to assess whether antioxidant intake is associated with the progression of early ARM to late-stage macular degeneration. Clinical trials and longer-term prospective studies are needed to elucidate further the impact of antioxidants and zinc on the development and progression of ARM.
Control Clin Trials 1999;20:573-600
The Age-Related Eye Disease Study (AREDS) was initially conceived as a long-term multicenter, prospective study of the clinical course of age-related macular degeneration (AMD) and age-related cataract. Data on progression rates and risk factors from the study will increase understanding of the clinical course of both conditions, generate hypotheses about etiology, and aid in the design of clinical trials of potential interventions. In addition to collecting natural history data, AREDS includes a clinical trial of high-dose vitamin and mineral supplements for AMD and a clinical trial of high-dose vitamin supplements for cataract. The clinical trials were initiated largely because of the widespread public use in the United States of commercially available pharmacologic doses of vitamins and minerals to treat these two eye conditions and the absence of definitive studies on the safety and efficacy of their use. Important design issues for the clinical trials include: defining cataract and AMD, estimating event rates, determining the type and dosage of vitamins and minerals to be tested for each condition, and identifying the parameters necessary for monitoring safety and efficacy. This paper describes the AREDS design, including the study rationale and operational structure, and the approach adopted to combine, for two diseases, clinical trials with a natural history study.
J Nutr. 2000;130(5S Suppl):1516S-9S
The Age-Related Eye Disease Study includes a clinical trial of high dose antioxidant and zinc supplements for age-related macular degeneration and a clinical trial of high dose antioxidants for cataract. The clinical trials were initiated largely because of the widespread public use in the United States of commercially available pharmacological doses of vitamins and minerals to treat these two eye conditions and the absence of definitive studies on the safety and efficacy of their use. This report focuses on the clinical trial of zinc and the possibility that this elderly study cohort, who were randomly assigned in a factorial design to receive zinc, antioxidants and placebo, could be assessed for zinc effects other than those currently addressed by the trial.
Tikellis G, Robman LD, Harper CA, et al
Ophthalmic Epidemiol. 1999;6:181-94
Purposes: (1) To develop the methodology for the grading of macular one-frame stereoslides and to assess the reliability of the system. (2) To determine the prevalence of soft drusen (> 63 microm) and pigment abnormalities synonymous with age-related maculopathy (ARM) at baseline, in a clinical trial of volunteers aged between 55 and 80 years of age. (3) To ascertain the power of the study to detect the 4-year incidence and progression of ARM in vitamin E versus placebo treated participants, given the baseline prevalence.
Methods: The 1204 participants enrolled in the Vitamin E, Cataract, and Age-related Maculopathy Study (VECAT) had colour stereoslides of their fundus taken using the Nidek 3-DX mydriatic fundus camera. The stereoslides were graded by two masked graders according to the "International Classification System for ARM and AMD". Assessment of inter- and intra-observer reliability was carried out on a regular basis on 15% of randomly selected slides. Anticipated rates of incidence and progression were based on results reported by the Beaver Dam Eye Study and the Chesapeake Bay Waterman Study. Power estimations were determined using the "nQuery Advisor" software program. Analyses were carried out on the worse affected eye.
Results: Inter-observer reliability was moderate to substantial (Kappa 0.5-0.88) whilst intra-observer agreement was high (0.6-1.0). The prevalence of any soft drusen was 32%. Significant associations were found between soft large indistinct drusen, hypopigmentation, hyperpigmentation and age (p = 0.0001, 0.024 and 0.0001, respectively). The study has at least 87% power to detect an odds ratio equal to two for the progression of soft distinct, soft indistinct, hyperpigmentation and hypopigmentation.
Conclusions: The VECAT study methodology appears to be highly reliable and to have sufficient power to detect the differences in the four-year progression of soft distinct and indistinct drusen and pigment abnormalities between the treatment groups.
Garrett SK, McNeil JJ, Silagy C, et al
Ophthalmic Epidemiol. 1999;6:195-208
Cataract is the leading cause of blindness in the world today, while age-related macular degeneration is responsible for the majority of new cases of visual impairment in the Western world. There is a growing body of evidence suggesting a role for antioxidant therapy to prevent the progression of these conditions. A 4-year prospective, randomised, controlled trial of an antioxidant versus placebo in a population of healthy volunteers aged 55-80 years at enrolment is described. This paper outlines the primary aims of the Vitamin E, Cataract and Age-related Macular Degeneration (VECAT) Study, the methodology, and the recruitment rates. Additional data on the toxicity and non-ocular effects of vitamin E will also be collected. Standardised clinical grading of macular and lens features, and comparison of serial macular photographs and digital lens photographs will form the basis for assessment of primary study outcomes. Information collected in this study will assist in the assessment of the potential value of antioxidants in preventing the enormous burden imposed on developed communities by age-related eye disease. In addition, important data on prevalence and progression rates of cataract and macular degeneration will be collected.
Robman LD, Tikellis G, Garrett SK, et al
Aust N Z J Ophthalmol. 1999;27:410-6
Purpose: To describe the methodology of eye examination and the baseline eye characteristics of the Vitamin E, Cataract and Age-Related Maculopathy (VECAT) study participants.
Methods: A sample of volunteers from an urban area of Melbourne, Australia, were recruited to participate in a randomized, controlled trial investigating the effect of vitamin E on the development of cataract and age-related maculopathy Standardized eye examinations involved clinical assessment, which included Wilmer grading of the lens, digital photography of the lens with Nidek EAS-1000 lens camera and stereo photography of the macular area with the Nidek 3-DX fundus camera. All cases of ophthalmic findings were determined on the basis of pathology in the worse eye.
Results: Most eyes were free from abnormalities.The most frequent findings were cataract and age-related macular changes. Nuclear cataract (nuclear opacity grade >2) was present in 4.5%, cortical cataract (cortical opacity grade >2) in 14.3% and posterior subcapsular cataract in 3.0% of participants; in addition, coronary cataract was observed in 13.6%. Soft drusen larger than 125 pm were found in 11.4%, retinal pigment epithelium changes in 9.5%, epiretinal membrane in 6.6% and age-related macular degeneration in 0.5% of participants. SUMMARY: Due to the selection criteria, the majority of participants had clear or minor lens changes and/or minor retinal age-related changes. Precise instrumental documentation will allow an accurate assessment of the incidence and dynamics of these changes throughout 4 years of observation.