Retinal haemodynamics in individuals with well-controlled type 1 diabetes.

AIMS/HYPOTHESIS: Abnormalities in retinal haemodynamics have been reported in patients with type 1 diabetes in advance of clinical retinopathy. These abnormalities could therefore be useful as early markers or surrogate endpoints for studying the microangiopathy. Since the DCCT, the increased focus on good glycaemic control is changing the natural history of diabetic retinopathy. Based on this, the aim of this study was to investigate whether patients with type 1 diabetes treated entirely or mostly in the post-DCCT era and tested in the absence of confounding factors show retinal haemodynamic abnormalities. METHODS: We measured retinal haemodynamics by laser Doppler flowmetry in 33 type 1 diabetic individuals with no or minimal retinopathy (age 30+/-7 years, duration of diabetes 8.8+/-4.6 years, 9% showing microaneurysms), and 31 age- and sex-matched non-diabetic controls. The study participants were not taking vasoactive medications, and blood glucose at the time of haemodynamic measurements was required to be between 3.8 and 11.1 mmol/l. RESULTS: HbA1c was 7.5+/-1.2% and blood glucose 7.7+/-2.8 mmol/l in these type 1 diabetic individuals, indicating relatively good glycaemic control. Retinal blood speed, arterial diameter and blood flow were not different between the diabetic individuals and the matched controls. CONCLUSIONS/INTERPRETATION: Type 1 diabetic patients with no or minimal retinopathy who maintain relatively good glycaemic control do not show abnormalities of the retinal circulation at steady state, even after several years of diabetes. In such patients it may be necessary to test the vascular response to challenges to uncover any subtle abnormalities of the retinal vessels.

Proteomic analysis of human meibomian gland secretions.

BACKGROUND/AIM: Human tears contain hundreds of proteins that may exert a significant influence on tear film stability, ocular surface integrity, and visual function. The authors hypothesise that many of these proteins originate from the meibomian gland. This study's aim was to begin to develop the proteomic methodology to permit the testing of their hypothesis. METHODS: Meibomian gland secretions were collected from the lower eyelids of adult volunteers and placed in a chloroform-methanol mixture. Samples were partitioned in a biphasic system and non-lipid phase materials were reduced, alkylated, and trypsin digested to obtain peptides for protein identification. This peptide mixture was separated by micro-capillary reverse phase chromatography and the effluent examined by nano-electrospray MS and data dependent MS/MS. SEQUEST software was used to identify proteins from the MS/MS spectra. RESULTS: The methodological approach to date has permitted the identification of more than 90 proteins in human meibomian gland secretions. Proteins include the alpha2-macroglobulin receptor, IgA alpha chain, farnesoid X activated receptor, interferon regulatory factor 3, lacritin precursor, lactotransferrin, lipocalin 1, lysozyme C precursor, potential phospholipid transporting ATPase IK, seven transmembrane helix receptor (also termed somatostatin receptor type 4), testes development related NYD-SP21 (also termed high affinity IgE receptor beta subunit), and TrkC tyrosine kinase. CONCLUSIONS: These findings indicate that the meibomian gland secretes a number of proteins into the tear film. It is quite possible that these proteins contribute to the dynamics of the tear film in both health and disease.

Hormone replacement therapy and dry eye syndrome.

CONTEXT: Postmenopausal hormone replacement therapy (HRT) use is common in the United States. Some research suggests that estrogen may have detrimental effects on the tear film and could influence the development of dry eye syndrome, but few data are available on this relationship. OBJECTIVE: To determine the relationship of HRT and dry eye syndrome. DESIGN, SETTING, AND PARTICIPANTS: The Women's Health Study, a large cohort study in which 25 665 postmenopausal women provided information about use of HRT at baseline (1992), 12, and 36 months and dry eye syndrome at 48 months. MAIN OUTCOME MEASURES: (1) Clinically diagnosed dry eye syndrome, as reported by participants; (2) severe symptoms (both ocular dryness and irritation either constantly or often); and (3) either clinically diagnosed dry eye syndrome or severe symptoms, compared between women who used HRT vs those who did not. RESULTS: For the combined end point of either clinically diagnosed dry eye syndrome or severe symptoms, the multivariable-adjusted odds ratios were 1.69 (95% confidence interval [CI], 1.49-1.91) for estrogen use alone and 1.29 (95% CI, 1.13-1.48) for estrogen plus progesterone/progestin use compared with no HRT use. Each 3-year increase in the duration of HRT use was associated with a significant 15% (95% CI, 11%-19%) elevation in risk of clinically diagnosed dry eye syndrome or severe symptoms. Results were similar for the combined end point of clinically diagnosed dry eye syndrome and severe symptoms. CONCLUSIONS: These data suggest that women who use HRT, particularly estrogen alone, are at increased risk of dry eye syndrome. Physicians caring for women who are taking or considering HRT should be apprised of this potential complication.

Body mass index and the incidence of visually significant age-related maculopathy in men.

BACKGROUND: Reports have suggested relationships of body weight with age-related maculopathy (ARM), particularly its nonneovascular (dry) forms, but results are inconsistent and prospective data are scarce. OBJECTIVE: To examine prospectively relationships of body mass index (BMI; calculated as weight in kilograms divided by the square of height in meters) with visually significant dry and neovascular ARM during an average of 14.5 years of follow-up. METHODS: Incident ARM was assessed by medical record confirmation of self-reported ARM among the 21 121 men participating in the Physicians' Health Study who (1) were followed up for at least 7 years, (2) were free of visually significant ARM at baseline, and (3) had information on BMI and cigarette smoking. We used proportional hazards regression models to estimate rate ratios (RRs) and 95% confidence intervals (CIs) for visually significant dry ARM (256 cases) and neovascular ARM (84 cases) within 4 categories of BMI: lean (< 22.0), normal (22.0-24.9), overweight (25.0-29.9), and obese (> or = 30.0). RESULTS: Adjusting for age, randomized aspirin and beta carotene assignments, and cigarette smoking, the incidence for visually significant dry ARM was lowest in men with a normal BMI. Compared with these men, the RRs (95% CIs) were as follows: 1.43 (1.01-2.04) for lean, 1.24 (0.93-1.66) for overweight, and 2.15 (1.35-3.45) for obese men. Although there was no significant relationship of BMI with the diagnosis of neovascular ARM, due to the small number of cases these analyses could not rule out an important relationship. CONCLUSIONS: Obesity is a risk factor for visually significant ARM in men, in particular for dry ARM. However, the relationship of BMI with dry ARM appears to be J-shaped, and the leanest individuals also appear to be at increased risk.

Age-related maculopathy in a randomized trial of low-dose aspirin among US physicians.

OBJECTIVE: To examine the development of age-related maculopathy (ARM) in a large-scale trial of low-dose aspirin treatment. METHODS: The Physicians' Health Study I was a randomized, double-masked, placebo-controlled trial of low-dose aspirin (325 mg every other day) and beta carotene (50 mg every other day) in the prevention of cardiovascular disease and cancer conducted among 22 071 US male physicians aged 40 to 84 years in 1982. A total of 21 216 participants did not report ARM at baseline, were followed up for at least 7 years, and are included in this analysis. MAIN OUTCOME MEASURES: Total ARM, defined as a self-report confirmed by medical record evidence of an initial diagnosis subsequent to randomization, and ARM with vision loss, defined as total ARM but with vision loss to 20/30 or worse attributable to ARM. RESULTS: Early termination of the randomized aspirin component of the Physicians' Health Study I, after an average of 60.2 months of treatment and follow-up due to a statistically extreme 44% reduced risk of first myocardial infarction, resulted in a far lower number of incident cases of ARM during the aspirin treatment period than would have accrued without early termination. Thus, during an average of 60.2 months of follow-up, a total of 117 cases of ARM were confirmed, including 57 cases responsible for vision loss to 20/30 or worse. There were 51 cases of ARM in the aspirin group and 66 in the placebo group (relative risk, 0.77; 95% confidence interval, 0.54-1.11). For ARM with vision loss, there were 25 cases in the aspirin group and 32 in the placebo group (relative risk, 0.78; 95% confidence interval, 0.46-1.32). CONCLUSIONS: These randomized trial data tend to exclude any large beneficial effect of 5 years of low-dose aspirin treatment on ARM. However, a smaller, but potentially important, beneficial effect cannot be ruled out and would require testing in randomized trials of adequate size and duration.

Aspirin use and risk of cataract in posttrial follow-up of Physicians' Health Study I.

BACKGROUND: In Physicians' Health Study I, randomized trial results indicated no major beneficial effect of 5 years of low-dose aspirin treatment on total cataract (relative risk [RR], 0.94; 95% confidence interval [CI], 0.79-1.13) or cataract extraction (RR, 0.81; 95% CI, 0.65-1.01) during the period of treatment. OBJECTIVE: To examine the effect of assigned aspirin treatment and posttrial, self-selected aspirin use on the risk of age-related cataract over the 15 years of follow-up of Physicians' Health Study I. METHODS: Participants were 20 968 US male physicians enrolled in Physicians' Health Study I who did not report cataract at baseline. At 7 years, after termination of the randomized aspirin component of the trial, self-selected aspirin use was computed from annual questionnaires. The main outcome measures were 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: During a median of 14.9 years of follow-up, there were 2081 cataracts and 1198 cataract extractions. Overall, the age- and beta carotene-adjusted RR of cataract in men assigned to aspirin compared with those assigned to placebo was 1.09 (95% CI, 1.00-1.18). For cataract extraction, the RR was 1.09 (95% CI, 0.98-1.22). During a median posttrial follow-up of 7.9 years, a total of 1225 incident cataracts and 635 cataract extractions were documented. The multivariate RR of cataract in men who reported using aspirin frequently (>/=180 days per year) at 7 years compared with nonusers (0-13 days per year) was 1.20 (95% CI, 1.03-1.40). For cataract extraction, the multivariate RR was 1.22 (95% CI, 0.98-1.51). Results for diagnosis and extraction of cataract subtypes were similar. CONCLUSIONS: Analyses based on randomized aspirin assignment indicated no long-term benefit of 5 years of low-dose aspirin treatment on total cataract or cataract extraction. Posttrial, observational data also indicated no decreased risk of cataract in aspirin users and suggested a small increased risk of cataract in aspirin users. Further randomized trial data to investigate the effect of longer term treatment with low-dose aspirin are being collected as part of the ongoing Women's Health Study, a randomized trial of low-dose aspirin and vitamin E among 39 876 apparently healthy, postmenopausal US female health professionals.

Efficacy and tolerability outcomes after punctal occlusion with silicone plugs in dry eye syndrome.

PURPOSE: Silicone punctal plugs are widely used to conserve moisture in tear-deficient eyes. We studied the efficacy and tolerability of punctal plugs in symptom reduction and improvement of ocular surface disease parameters in dry eye syndrome. METHODS: We reviewed the records of 50 consecutive patients with dry eye syndrome who were symptomatic despite maximally tolerable lubricant therapy and had bilateral lower punctal plug insertion. After plug insertion, all patients (41 women and nine men) had 6 months or more of follow-up. The subjects ranged in age from 22 to 57 years (mean, 30 years). We recorded subjective and objective improvement of ocular surface disease, frequency of lubricant use, need for upper punctal occlusion, and occurrence of complications after plug insertion. We determined plug retention rates using Kaplan-Meier analyses and assessed associated factors using Cox proportional hazards models. RESULTS: Six months after initial plug placement, 43 of 50 patients (86%) were symptom free, 28 of them (56%) with plugs alone, and 38 patients (76%) had stopped using lubricants on a daily basis. Spontaneous loss of plugs was common, especially in the initial 3 months of follow-up. Considering all plugs, the estimated probability of plug retention was 63% after 6 months of follow-up. Puncta refitted after initial plug loss were twice as likely to lose the replacement plug (P =.02). Upper punctal plugs showed a 4.3-fold higher risk of loss compared with plugs inserted in lower puncta (P <.0001). CONCLUSIONS: There is both a reduced dependency on artificial lubricants and relief of symptoms of dry eye after punctal plugs. However, spontaneous plug loss occurs in a substantial minority of patients. Patient education and close follow-up, particularly in the first 3 months, is recommended to detect plug loss and ensure adequate control of the disease.

A prospective study of blood pressure and risk of cataract in men.

PURPOSE: Cataract is the leading cause of blindness worldwide. Blood pressure has been identified as a risk factor in some, but not all, previous studies. We aimed to test prospectively the hypothesis that high blood pressure increases risk of age-related cataract. METHODS: Participants in the Physicians' Health Study of 22,071 men aged 40 to 84 years in 1982 completed annual questionnaires that provided medical history including self-reported blood pressure, treatment for hypertension, and cataract. Over 12 years, 1392 cataracts were confirmed by medical record review among 17,762 physicians with complete data and no reported cataract at baseline. We used proportional hazards regression models to examine relations of systolic blood pressure (SBP), diastolic blood pressure (DBP), hypertension, as well as antihypertensive medications with cataract, after control for potential confounding factors. RESULTS: In models adjusting for age and randomized treatment assignment, there was a significant relationship of SBP, but not DBP, hypertension, or antihypertensive medications (each p > or = 0.23) with incident cataract. Estimates were attenuated after adjusting for multiple potential confounders, although the relationship of SBP with incident cataract remained significant. The multivariate adjusted rate ratio (95% confidence interval) of cataract for SBP > or = 150 versus < 120 mm Hg was 1.31 (1.04-1.66), p for trend = 0.04. For DBP > or = 90 versus < 70 mm Hg, the estimate was 1.11 (0.84-1.45), p for trend = 0.33. CONCLUSIONS: Overall, these data suggest that the relationship of blood pressure with cataract is not strong, and is subject to confounding by other risk factors. The modest magnitude of the association with SBP and lack of significant relationships with DBP and hypertension may suggest a non-causal relationship of blood pressure with cataract.

Relations of body fat distribution and height with cataract in men.

BACKGROUND: Cataract is the leading cause of blindness worldwide. Body mass index (BMI; in kg/m(2)) is a risk factor for cataract, but other anthropometric measurements may also be important. OBJECTIVE: We tested relations of alternative measures of body size, including height and waist-to-hip ratio (WHR), as well as BMI, with cataract. DESIGN: This was a prospective follow-up study. We analyzed data from 20271 participants in the Physicians' Health Study who did not have cataract at baseline and for whom there was complete information on weight, height, and other risk factors. For analyses concerning WHR, we excluded 3121 additional men for whom we did not have these measurements, assessed at the ninth year of follow-up. The main outcome measures were incident cataract and cataract surgery. RESULTS: Among the 17150 men for whom there were complete data, we confirmed an incident cataract in 1727 during an average of 14 y of follow-up. In proportional hazards regression models that adjusted for many known or suspected risk factors, higher BMI [rate ratio (RR) = 1.25 for >/=27.8 compared with <22, P: for trend = 0. 03], height (RR = 1.23 for >/=184 cm compared with

Baseline self-reported cataract and subsequent mortality in Physicians' Health Study I.

PURPOSE: To examine whether a reported history of cataract, a possible marker of aging, is associated with future mortality. METHODS: Participants were 18,669 of the 22,071 U.S. male physicians enrolled in the Physicians' Health Study I who had complete information at study entry, including self-report of presence or absence of baseline cataract. Participants were without a previous history of myocardial infarction, stroke, transient cerebral ischemia, or cancer (except non-melanoma skin cancer). Reported deaths were confirmed by an End Points Committee of physicians. RESULTS: A total of 581 participants reported a personal history of cataract at baseline. During an average of 12.4 years of follow-up, there were 1,514 deaths including 496 due to cardiovascular (CV) and 1,018 due to non-CV causes. After adjustment for differences in age, men who reported cataract at baseline had a non-significant 9% increased risk of death from any cause compared to men who did not report cataract (RR, 1.09; 95% CI, 0.91-1.30). The RRs were 1.03 (95% CI, 0.75-1.41) for CV death and 1.12 (95% CI, 0.90-1.40) for non-CV death. Adjustment for other risk factors had little effect on these estimates. Similar results were obtained in analyses conducted separately among those with and without self-reported diabetes at baseline. CONCLUSIONS: These results from a population of generally healthy physicians indicate that a report of a history of cataract is not associated with any material increase in mortality after adjustment for differences in age between men with and without cataract. Additional investigation of this cohort is in progress to determine whether incident age-related cataracts as well as their subtypes, confirmed by medical record review, are associated with increased mortality.

Smoking cessation and risk of age-related cataract in men.

CONTEXT: Although cigarette smoking has been shown to be a risk factor for age-related cataract, data are inconclusive on the risk of cataract in individuals who quit smoking. OBJECTIVE: To examine the association between smoking cessation and incidence of age-related cataract. DESIGN: Prospective cohort study conducted from 1982 through 1997, with an average follow-up of 13.6 years. SETTING AND PARTICIPANTS: A total of 20,907 US male physicians participating in the Physicians' Health Study I who did not have a diagnosis of age-related cataract at baseline and had reported their level of smoking at baseline. MAIN OUTCOME MEASURES: Incident age-related cataract defined as self-report confirmed by medical record review, diagnosed after study randomization and responsible for vision loss to 20/30 or worse, and surgical extraction of incident age-related cataract, in relation to smoking status and years since quitting smoking. RESULTS: At baseline, 11% were current smokers, 39% were past smokers, and 50% were never smokers. Average reported cumulative dose of smoking at baseline was approximately 2-fold greater in current than in past smokers (35.8 vs 20.5 pack-years). Two thousand seventy-four incident cases of age-related cataract and 1193 cataract extractions were confirmed during follow-up. Compared with current smokers, multivariate relative risks (RRs) of cataract in past smokers who quit smoking fewer than 10 years, 10 to fewer than 20 years, and 20 or more years before the study were 0.79 (95% confidence interval [CI], 0.64-0.98), 0.73 (95% CI, 0.61-0.88), and 0.74 (95% CI, 0.63-0.87), respectively, after adjustment for other risk factors for cataract and age at smoking inception. The RR for never smokers was 0.64 (95% CI, 0.54-0.76). The reduced risk in past smokers was principally due to a lower total cumulative dose (RR of cataract for increase of 10 pack-years of smoking, 1.07; 95% CI, 1.04-1.10). A benefit of stopping smoking independent of cumulative dose was suggested in some analyses. Results for cataract extraction were similar. CONCLUSION: These prospective data indicate that while some smoking-related damage to the lens may be reversible, smoking cessation reduces the risk of cataract primarily by limiting total dose-related damage to the lens. JAMA. 2000;284:713-716

Demographic predictors of eye care utilization among women.

BACKGROUND: Visual impairment may be preventable or treatable with timely intervention. Differences in the use of eye care services may play a role in fostering the racial and socioeconomic gap in the burden of visual impairment in the United States. OBJECTIVE: The objective of this study was to examine the frequency of eye examinations in women and how this varies with age, race, marital status, geographic region, profession, education, and income. SUBJECTS AND METHODS: We used logistic regression models to examine data obtained by mailed questionnaires from 39,876 female health professionals participating in the Women's Health Study. RESULTS: Most women (83%) had an eye examination within the past 2 years. The likelihood of having an eye examination in the past 2 years increased with age (odds ratio [OR] = 2.59 for age > or =75 years versus those <50 years; P [trend] <0.0001), higher education (OR = 1.27 for master's degree versus licensed nurse training; P [trend] = 0.0004), and higher household income (OR = 1.85 for > or =$100,000 versus <$10,000; P [trend] <0.0001). Women from the south were less likely to have had an eye examination than those from the west (OR = 0.92; P = 0.03). Compared with whites, Asian/Pacific Islanders were less likely (OR = 0.76; P = 0.02) and blacks more likely (OR = 1.27; P = 0.02) to have had an eye examination within 2 years. CONCLUSIONS: Age, education, income, race/ethnicity, and region of residence were independent predictors of having had an eye examination in the past 2 years. Known medical and ocular problems appeared to explain the association with age but not the other findings, although the clinical significance of these associations was not determined in the present study. Additional research on determinants of eye care-seeking behavior could help in devising new strategies to encourage preventive behaviors, especially among groups at higher risk of visual impairment.

A randomized, 12-year primary-prevention trial of beta carotene supplementation for nonmelanoma skin cancer in the physician's health study.

CONTEXT: Although basic research provides plausible mechanisms for benefits of beta carotene supplementation on nonmelanoma skin cancer (NMSC) primarily consisting of basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), observational studies are inconsistent. Randomized trial data are limited to 1 trial of secondary prevention that showed no effect of beta carotene on the incidence of NMSC after 5 years. OBJECTIVE: To test whether supplementation with beta carotene reduces the risk for development of a first NMSC, including BCC and SCC. DESIGN: Randomized, double-blind, placebo-controlled trial with 12 years of beta carotene supplementation and follow-up. SETTING: Physicians' Health Study in the United States. PARTICIPANTS: Apparently healthy male physicians aged 40 to 84 years in 1982 (N = 22 071). INTERVENTION: Beta carotene, 50 mg, on alternate days. MAIN OUTCOME MEASURE: Relative risk (RR) and 95% confidence interval (CI) for a first NMSC, BCC, and SCC. RESULTS: After adjusting for age and randomized aspirin assignment, there was no effect of beta carotene on the incidence of a first NMSC (RR, 0.98; 95% CI, 0.92-1.05), BCC (RR, 0.99; 95% CI, 0.92-1.06), or SCC (RR, 0.97; 95% CI, 0.84-1.13). There was also no significant evidence of beneficial or harmful effects of beta carotene on NMSC by smoking status (current, past, or never). CONCLUSION: This large-scale, randomized, primary prevention trial among apparently healthy well-nourished men indicates that an average of 12 years of supplementation with beta carotene does not affect the development of a first NMSC, including BCC and SCC.

High levels of plasma C-reactive protein and future risk of age-related cataract.

PURPOSE: Chronic intraocular inflammation, with or without systemic inflammation, is associated with increased risk of cataract. Whether systemic inflammation alone is associated with cataract is unknown. This study examined the association between plasma C-reactive protein (CRP), a marker of systemic inflammation, and risk of cataract. METHODS: In the Physicians' Health Study, we recently analyzed plasma CRP levels in baseline blood specimens from 543 men who later developed cardiovascular disease, and 543 who did not. These data provided a cost-efficient means to explore whether baseline plasma CRP is associated with future risk of age-related cataract. After excluding 252 men with prior diagnosis of cataract or missing data, we followed the remaining 834 men defined by baseline CRP level for 11 years for incident cataract. We used proportional hazards regression models, stratified by cardiovascular disease status. RESULTS: Baseline CRP was significantly higher among men who later developed cataract than levels among those who remained free of cataract, P = 0.02 (median 1.53 versus 1.23 mg/L). In a multivariable model adjusted for cardiovascular disease, randomized aspirin and beta carotene assignments, age, diabetes, cigarette smoking, alcohol consumption, body mass index, exercise, and parental history of myocardial infarction, the levels of CRP remained significantly associated with development of cataract (P = 0.001); but the association was less significant in a model using log CRP levels (P = 0.038). In exploratory analyses of a threshold effect, the excess risk was significant only among men with levels at or above the 97.5th centile (6.17 mg/L); compared to those with lower levels, the relative risk in these men was 3.00 (95% confidence interval, 1.53 to 5.91; P = 0.002). Relative risks associated with CRP levels at or above versus below the 85th, 90th, and 95th percentiles were not significant (relative risks 1.29, 1.50, and 1.77, respectively). CONCLUSIONS: Overall, our results suggest that elevated levels of CRP are associated with future risk of cataract in these apparently healthy men. This early report raises the possibility that systemic inflammation may play a role in the pathogenesis of age-related cataract.

Corneal transplantation in young children with congenital hereditary endothelial dystrophy. Multicenter Pediatric Keratoplasty Study.

PURPOSE: To describe the surgical success rate and visual results of penetrating keratoplasty in a series of young children with congenital hereditary endothelial dystrophy and to summarize the current literature on outcomes of keratoplasty for congenital hereditary endothelial dystrophy, with particular attention to the timing of surgery. METHODS: The authors conducted a retrospective study of children aged 12 years and younger who underwent penetrating keratoplasty between 1975 and 1994 at four participating eye centers, and who were followed for at least 6 months postoperatively. For this report, 21 corneal transplants performed in 16 eyes of nine patients with congenital hereditary endothelial dystrophy were studied. Patients' median age at the time of first keratoplasty was 40 months (range, 3 months to 10 years). RESULTS: During a mean follow-up period of over 70 months (range, 6 to 240 months), 11 (69%) of 16 eyes retained full graft clarity. The 2-year survival rate of first grafts was 71% (95% confidence interval, 47% to 95%). Postoperative visual acuity improvement of 1 or more Snellen lines was seen in five of 10 eyes in which the patients were old enough for accurate assessment of visual acuity; however, just four of these 10 eyes attained a visual acuity of 20/200 or better. CONCLUSIONS: Penetrating keratoplasty for congenital hereditary endothelial dystrophy in children has a reasonable chance of surgical success when performed at a young age; however, the prognosis for improved visual acuity in children appears to be more guarded. Decisions on the timing of surgical intervention for congenital hereditary endothelial dystrophy should be made on a case-by-case basis. Although the threat of irreversible amblyopia in untreated eyes and good surgical success rates even among very young children argue for the consideration of relatively early surgical intervention in the most severely affected cases, there is evidence to support delaying surgery in some cases.

Prospective cohort study of antioxidant vitamin supplement use and the risk of age-related maculopathy.

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.

Low-dose aspirin and risk of cataract and subtypes in a randomized trial of U.S. physicians.

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.