Roy C. Milton

Reduced Mortality among Children in Southern India Receiving a Small Weekly Dose of Vitamin A

Abstract Background. Clinical vitamin A deficiency affects millions of children worldwide, and subclinical deficiency is even more common. Supplemental vitamin A has been reported to reduce mortality among these children, but the results have been questioned. Methods. We conducted a randomized, controlled, masked clinical trial for one year in southern India involving 15,419 preschool-age children who received either 8.7 μmol (8333 IU) of vitamin A and 46 μmol (20 mg) of vitamin E (the treated group) or vitamin E alone (the control group). Vitamin supplements were delivered weekly by community health volunteers who also recorded mortality and morbidity. Weekly contact was made with at least 88 percent of the children in both study groups. The base-line characteristics of the children were similar and documented a high prevalence of vitamin A deficiency and undernutrition. Results. One hundred twenty-five deaths occurred, of which 117 were not accidental. The risk of death in the group treated with vitamin...

Impaired vision and hip fracture. The Framingham Study.

Falls affect a large proportion of the elderly and can result in a variety of injuries, including hip fractures. Several studies have suggested that visual impairment contributes to falls, but studies have not used standardized definitions of visual impairment and have not examined injurious falls or fractures. We looked at the risk of hip fracture associated with visual impairment in those members of the Framingham Study Cohort who took part in the Framingham Eye Study in 1973–75. Of 2,633 subjects followed for 10 years after the eye exam, 110 sustained hip fractures. The fracture rates in those with moderately impaired (20/30 to 20/80) vision (8.5%) and poor (20/100 or worse) vision (11.3%) were higher than in those with good (20/25 or better) vision (3.0%). After adjustment for age, sex, weight, alcohol consumption, and (in women) estrogen use, the relative risk of fracture in those with moderate impairment was 1.54 (95% CI = 0.95–2.49), while for those with poor vision, the relative risk was 2.17 (95% CI = 1.24–3.80). Of note, those with moderately impaired vision in one eye and good vision in the other had a higher risk of fracture (relative risk = 1.94) than those with a similar degree of binocular impairment (relative risk = 2.11). Poor vision in one or both eyes was linked to an elevated fracture risk. This suggests that good stereoscopic vision may be necessary to prevent falls. The risk of fracture with poor and moderately impaired vision combined was increased in women (relative risk = 1.96, 95% CI = 1.23–3.11) but not in men (relative risk = 0.79, 95% CI = 0.23–2.72). 17.5% (17/97) of women with poor vision in at least one eye sustained a hip fracture during the 10 years of the study. Cataracts were the most common cause of fracture‐related visual impairment, but neither cataracts nor other common eye diseases had an independent effect on fracture risk after adjustment for visual acuity. In sum, visual impairment is an important risk factor for hip fracture, especially among elderly women.

THE RELATIONSHIP OF DIETARY OMEGA-3 LONG-CHAIN POLYUNSATURATED FATTY ACID INTAKE WITH INCIDENT AGE-RELATED MACULAR DEGENERATION: AREDS REPORT NO. 23

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.

Risk of Advanced Age-Related Macular Degeneration after Cataract Surgery in the Age-Related Eye Disease Study: AREDS Report 25

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.

Plasma Cofactors of Platelet Function: Correlation with Diabetic Retinopathy and Hemoglobins Ala-c: Studies in Diabetic Patients and Normal Persons

We studied 29 diabetic patients (eight without and 21 with retinopathy) and 29 matched control subjects for hemoglobins Ala-c and plasma levels of fibrinogen, von Willebrand factor, and factor VIII/von Willebrand factor antigen. Hemoglobins Ala-c were elevated in all diabetic patients, regardless of retinopathy (P less than 0.001); fibrinogen was elevated only in those with retinopathy (P less than 0.001); and plasma von Willebrand factor was clearly elevated in those with proliferative retinopathy and minimally, if at all, elevated in those with background or no retinopathy. Plasma from five diabetic patients with proliferative retinopathy and five control subjects was tested for its ability to enhance the ADP-induced platelet aggregation of normal or von Willebrand platelet-rich plasma; no differences were found. We conclude that elevated levels of fibrinogen and von Willebrand factor, both recognized plasma cofactors of platelet function, are associated with proliferative diabetic retinopathy. A plasma factor that enhances ADP-induced platelet aggregation could not be found in diabetic plasma, and we doubt that increased von Willebrand factor is responsible for its finding by others.

The Natural History of Gyrate Atrophy of the Choroid and Retina

Twenty-nine Finnish patients (8-80 years old during follow-up) with hyperornithinemia and gyrate atrophy (HOGA) were followed 2 to 31 years to determine when and how rapidly visual acuities and visual functions were affected by the disease. Considerable variability was observed both in the age at which visual acuities began to decrease and the age at which visual acuities reached 20/200. Acuities in phakic eyes tended to decrease from 20/30 to 20/200 in ten years or less, while aphakic eyes exhibited generally slower loss of vision. Without benefit of cataract surgery, the percentage of eyes with acuity 20/200 or worse would have been 37% at age 30 and 64% at age 40, but through surgery actually performed was 20% at age 40. Constriction of visual fields with age was marked and correlated well with diminution in dark adaptation.

Computer Evaluation of the Multivariate Normal Integral

A method is described for the evaluation by computer of the multivariate normal integral, for arbitrary mean vector, covariance matrix, and region of integration. Evaluation is by means of a modification of a multidimensional adaptive Simpsons quadrature with error control, applied to the iterated integral. Examples are given for integrals of up to six dimensions.

A randomized, double-masked, placebo-controlled clinical trial of multivitamin supplementation for age-related lens opacities. Clinical trial of nutritional supplements and age-related cataract report no. 3.

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.

Studies of aqueous humour dynamics in man. VI. Effect of age upon parameters of intraocular pressure in normal human eyes.

Abstract Parameters of aqueous dynamics have been evaluated for both eyes of each member of a group of young normal volunteers and of a group of old normal volunteers. In the old volunteers, the observed lower total facility is comprised of a lower true facility of outflow and a lower pseudofacility. The reduced outflow facility is partly counterbalanced by a lower aqueous flow. Also, in the older eyes, ocular rigidity is higher. Mean episcleral venous pressure is the same for the two groups. The major effect of age seen in this study is alteration of the function of the outflow pathways of the eye, with simultaneous, partially counter-balancing, decrease of aqueous production associated with decreased pseudofacility.

Dietary Compound Score and Risk of Age-Related Macular Degeneration in the Age-Related Eye Disease Study

PURPOSE Because foods provide many nutrients that may interact to modify risk for multifactorial diseases such as age-related macular degeneration (AMD), we sought to develop a composite scoring system to summarize the combined effect of multiple dietary nutrients on AMD risk. This has not been done previously. DESIGN Cross-sectional study. PARTICIPANTS From the 4003 participants in the Age-Related Eye Disease Study (AREDS), there were 7,934 eyes included in this study. METHODS Considering dietary intakes of vitamins C and E, zinc, lutein/zeaxanthin, docosahexaenoic acid, eicosapentaenoic acid, and low-dietary glycemic index (dGI) from AREDS baseline information, we assigned each nutrient a percentile rank score then summed them into a compound score for each participant. Using eye as the unit of analysis, we evaluated the association between the compound score and risk of prevalent AMD. Validation, fitness, and performance of the model were evaluated using bootstrapping techniques, adjusted quasi-likelihood under the independence model criterion, and the c-index, respectively. MAIN OUTCOME MEASURES Stereoscopic fundus photographs of the macula were taken and graded at baseline using the AREDS protocol and AMD Classification System. RESULTS Our results showed that higher compound scores were associated with lower risk for early AMD, indicated by drusen, and advanced AMD. Validation analyses indicated that these relationships are robust (the average 50-time bootstrapping per quartile odds ratios = 0.727, 0.827, and 0.753, respectively, for drusen, and 0.616, 0.536, and 0.572, respectively, for advanced AMD). Model selection analyses suggested that the compound score should be included, but that measures of dietary beta-carotene should not be included. CONCLUSIONS We found that consuming diets that provide low dGI and higher intakes of these nutrients were associated with the greatest reduction in risk for prevalent drusen and advanced AMD, whereas dietary beta-carotene did not affect these relationships. These findings warrant further prospective studies. FINANCIAL DISCLOSURE(S) Proprietary or commercial disclosure may be found after the references.