William G. Christen

Association of visual impairment with mobility and physical function.

To examine the association of distant vision and physical function in the population of older adults.

Primary pars plana vitrectomy versus scleral buckle surgery for the treatment of pseudophakic retinal detachment: a randomized clinical trial.

Objective: To compare the anatomical and functional outcome of scleral buckle (SB) surgery with that of pars plana vitrectomy (PPV) alone in the treatment of primary rhegmatogenous pseudophakic retinal detachment (RD). Methods: In this prospective, randomized clinical trial, 150 eyes of 150 patients with pseudophakic RD and proliferative vitreoretinopathy (PVR) stage B or less were randomized to SB surgery (75 eyes) or primary PPV (75 eyes). SB surgery involved break localization, cryotherapy, placement of a circumferential 240 style 2.5-mm solid silicone band, combined with a local buckle when indicated, and transscleral drainage of subretinal fluid. PPV included extensive vitreous removal, perfluoro-n-octane injection or endodrainage of subretinal fluid to flatten the retina, cryopexy treatment of breaks, and fluid/air exchange with injection of 20% SF6. Postoperative follow-up was 1 year. Break diagnosis, operating time, intraoperative and postoperative complications, retinal reattachment rate for single as well as multiple surgeries, axial length changes, and best-corrected visual acuity at 1 year after surgery were the main outcome measures. Results: The number of eyes that were diagnosed with additional breaks interoperatively was higher in the PPV group (P = 0.004, &khgr;2 test). Mean operating time was significantly less (P = 0.0001, t-test) in the PPV group. With a single surgery, the retina was reattached in 62 eyes (83%) in the SB surgery group and in 71 eyes (94%) in the PPV group (P = 0.037, Fisher exact test). With subsequent surgeries, final anatomical reattachment was achieved in 71 cases in the SB surgery group and in 74 cases in the PPV group (P = 0.37, Fisher exact test). Mean axial length change at 1 year was 0.95 mm in the SB surgery group and 0.1 mm in the PPV group (P = 0.0001, t-test). Mean final best-corrected visual acuity (logMAR) was 0.40 in the SB surgery group and 0.33 in the PPV group (P = 0.26, t-test). Conclusions: Primary PPV offers potential advantages over SB surgery in the treatment of pseudophakic RD, including less operating time, accurate diagnosis of breaks, higher reattachment rate with a single surgery, and no postoperative axial length changes. Retinal reattachment rate with multiple surgeries and final visual acuity at 1 year were similar for SB surgery and PPV.

Functional Blindness and Visual Impairment in Older Adults from Three Communities

PURPOSE The purpose of this study is to examine the association of sociodemographic factors with functional blindness and visual impairment in an aged population. METHODS Three population-based cohorts (East Boston, MA; New Haven, CT; and Iowa and Washington Counties, IA) of persons aged 71 years and older were screened for bilateral functional near and distant vision during an in-home interview in 1988. RESULTS Screening was completed by 5335 participants. The prevalence of functional blindness increased with age, from 1% at age 71 to 74 years to 17% in those 90 years of age and older. Functional visual impairment increased from 7% at age 71 to 74 years to 39% in those 90 years of age and older. In multivariate analyses, residence in a nursing home, older age, glaucoma, insulin-requiring diabetes at baseline, East Boston site, history of cataract, and lower 1982 income were independent and significantly associated with both functional blindness and visual impairment. Age and nursing home residence were significantly (P < 0.05) more strongly associated with blindness (odds ratios 4.8 and 6.1, respectively) than they were with visual impairment. CONCLUSION Functional blindness and visual impairment are quite prevalent among the oldest old and the institutionalized. The number of affected individuals will increase as the population ages and life expectancy increases. Although visual problems are associated with aging, nursing home residence, health problems, and socioeconomic conditions, they may be readily remediable and may lead to immediate improvements in quality of life.

Folic Acid, Pyridoxine, and Cyanocobalamin Combination Treatment and Age-Related Macular Degeneration in Women: The Women's Antioxidant and Folic Acid Cardiovascular Study

BACKGROUND Observational epidemiologic studies indicate a direct association between homocysteine concentration in the blood and the risk of age-related macular degeneration (AMD), but randomized trial data to examine the effect of therapy to lower homocysteine levels in AMD are lacking. Our objective was to examine the incidence of AMD in a trial of combined folic acid, pyridoxine hydrochloride (vitamin B(6)), and cyanocobalamin (vitamin B(12)) therapy. METHODS We conducted a randomized, double-blind, placebo-controlled trial including 5442 female health care professionals 40 years or older with preexisting cardiovascular disease or 3 or more cardiovascular disease risk factors. A total of 5205 of these women did not have a diagnosis of AMD at baseline and were included in this analysis. Participants were randomly assigned to receive a combination of folic acid (2.5 mg/d), pyridoxine hydrochloride (50 mg/d), and cyanocobalamin (1 mg/d) or placebo. Our main outcome measures included total AMD, defined as a self-report documented by medical record evidence of an initial diagnosis after randomization, and visually significant AMD, defined as confirmed incident AMD with visual acuity of 20/30 or worse attributable to this condition. RESULTS After an average of 7.3 years of treatment and follow-up, there were 55 cases of AMD in the combination treatment group and 82 in the placebo group (relative risk, 0.66; 95% confidence interval, 0.47-0.93 [P = .02]). For visually significant AMD, there were 26 cases in the combination treatment group and 44 in the placebo group (relative risk, 0.59; 95% confidence interval, 0.36-0.95 [P = .03]). CONCLUSIONS These randomized trial data from a large cohort of women at high risk of cardiovascular disease indicate that daily supplementation with folic acid, pyridoxine, and cyanocobalamin may reduce the risk of AMD.

Dietary Carotenoids, Vitamins C and E, and Risk of Cataract in Women: A Prospective Study

OBJECTIVE To examine in prospective data the relation between dietary intake of carotenoids and vitamins C and E and the risk of cataract in women. DESIGN Dietary intake was assessed at baseline in 39,876 female health professionals by using a detailed food frequency questionnaire. A total of 35,551 women provided detailed information on antioxidant nutrient intake from food and supplements and were free of a diagnosis of cataract. The main outcome measure was cataract, defined as an incident, age-related lens opacity responsible for a reduction in best-corrected visual acuity in the worse eye to 20/30 or worse based on self-report confirmed by medical record review. RESULTS A total of 2031 cases of incident cataract were confirmed during a mean of 10 years of follow-up. Comparing women in the extreme quintiles, the multivariate relative risk of cataract was 0.82 (95% confidence interval, 0.71-0.95; test for trend, P = .04) for lutein/zeaxanthin and 0.86 (95% confidence interval, 0.74-1.00; test for trend, P = .03) for vitamin E from food and supplements. CONCLUSION In these prospective observational data from a large cohort of female health professionals, higher dietary intakes of lutein/zeaxanthin and vitamin E from food and supplements were associated with significantly decreased risks of cataract.

Mycophenolate Mofetil after Methotrexate Failure or Intolerance in the Treatment of Scleritis and Uveitis

PURPOSE To evaluate the outcomes of treatment with mycophenolate mofetil in patients with scleritis and uveitis refractory to or intolerant of methotrexate. DESIGN Retrospective noncomparative case series. PARTICIPANTS Eighty-five patients with scleritis and/or uveitis who failed with or did not tolerate methotrexate and were subsequently treated with mycophenolate mofetil between 1998 and 2006. METHODS We reviewed medical records of patients who were treated with mycophenolate mofetil after methotrexate intolerance or failure at one tertiary uveitis referral practice. We recorded dose and duration of methotrexate and mycophenolate mofetil therapy, inflammation grade, Snellen visual acuity (VA), use of other immunomodulatory therapy, and adverse events. Multivariate logistic regression was used to identify factors associated with inflammation control. MAIN OUTCOME MEASURES Control of inflammation, steroid-sparing effect, VA, and adverse effects were assessed. RESULTS Inflammation was controlled with mycophenolate mofetil in 47 patients (55%), with 5 achieving durable remission off all medication. In multivariate logistic regression analysis that adjusted for gender and age, the odds of inflammation control were lower for patients with scleritis (odds ratio [OR], 0.19; 95% confidence interval [CI], 0.04-0.93; P = 0.04) than for patients without scleritis. Among patients without scleritis, the odds of inflammation control were lower for patients with juvenile idiopathic arthritis (JIA)-associated uveitis (OR, 0.14; CI, 0.02-0.81, P = 0.03) compared to patients without JIA-associated uveitis. Eight of the 11 patients (73%) who were taking concomitant prednisone were able to taper their dose to <10 mg daily. Visual acuity declined in a greater percentage of patients who were unresponsive to mycophenolate mofetil (29%) compared with that of patients who responded to mycophenolate mofetil (9%). Side effects requiring discontinuation of mycophenolate mofetil occurred in 18 patients (21%). CONCLUSIONS Mycophenolate mofetil was effective in controlling inflammation in approximately half of the patients who had previously failed with or did not tolerate methotrexate. The odds of inflammation control were less in patients with the diagnoses of scleritis and JIA.

Genome-wide association analysis identifies TXNRD2, ATXN2 and FOXC1 as susceptibility loci for primary open-angle glaucoma

Primary open-angle glaucoma (POAG) is a leading cause of blindness worldwide. To identify new susceptibility loci, we performed meta-analysis on genome-wide association study (GWAS) results from eight independent studies from the United States (3,853 cases and 33,480 controls) and investigated the most significantly associated SNPs in two Australian studies (1,252 cases and 2,592 controls), three European studies (875 cases and 4,107 controls) and a Singaporean Chinese study (1,037 cases and 2,543 controls). A meta-analysis of the top SNPs identified three new associated loci: rs35934224[T] in TXNRD2 (odds ratio (OR) = 0.78, P = 4.05 × 10−11) encoding a mitochondrial protein required for redox homeostasis; rs7137828[T] in ATXN2 (OR = 1.17, P = 8.73 × 10−10); and rs2745572[A] upstream of FOXC1 (OR = 1.17, P = 1.76 × 10−10). Using RT-PCR and immunohistochemistry, we show TXNRD2 and ATXN2 expression in retinal ganglion cells and the optic nerve head. These results identify new pathways underlying POAG susceptibility and suggest new targets for preventative therapies.

Visual outcome in herpes simplex virus and varicella zoster virus uveitis: A clinical evaluation and comparison

PURPOSE To compare clinical characteristics and outcomes in patients with uveitis caused by herpes simplex virus (HSV) and varicella zoster virus (VZV). DESIGN Retrospective comparative study. PARTICIPANTS Forty patients with HSV uveitis and 24 patients with VZV uveitis. METHODS A retrospective study of 40 patients with HSV and 24 patients with VZV uveitis was performed. The patients were followed between May 1987 and September 1999 (median follow-up time, 46 months). The diagnosis of HSV uveitis was made clinically and serologically, and the diagnosis of VZV uveitis was made clinically. MAIN OUTCOME MEASURES Clinical presentation of the disease, ocular complications, visual acuity, surgical and medical treatments needed. RESULTS Both populations were comparable for gender and age at disease onset. The course of the disease tended to be remitting and recurrent in HSV patients and chronic in VZV patients (P = 0.046). The most frequent ocular complication in both groups was secondary glaucoma (54% HSV, 38% VZV). Twenty-five percent of VZV patients developed posterior pole complications (cystoid macular edema, epiretinal membrane, papillitis, retinal fibrosis, and detachment) compared with 8% of HSV patients (P = 0.069). Treatment modalities selected were generally similar in the two groups, although periocular and systemic steroids were required more frequently in HSV patients (60% versus 25%; P = 0.01). Surgical procedures were required with similar frequency in both populations. The percentage of eyes that were legally blind at end of follow-up was also comparable (HSV, 20%; VZV, 21%). The visual outcome was similar in the studied populations. CONCLUSIONS This study represents the only direct comparison of HSV and VZV uveitis patients reported in the literature. HSV patients were more likely to be treated with periocular and systemic steroids, and VZV patients were more likely to develop posterior pole complications (a finding of borderline significance). Other parameters evaluated in this study were not statistically different in the two patient groups.

Age-Related Cataract in a Randomized Trial of Vitamins E and C in Men

OBJECTIVE To test whether supplementation with alternate-day vitamin E or daily vitamin C affects the incidence of age-related cataract in a large cohort of men. METHODS In a randomized, double-masked, placebo-controlled trial, 11,545 apparently healthy US male physicians 50 years or older without a diagnosis of cataract at baseline were randomly assigned to receive 400 IU of vitamin E or placebo on alternate days and 500 mg of vitamin C or placebo daily. MAIN OUTCOME MEASURE Incident cataract responsible for a reduction in best-corrected visual acuity to 20/30 or worse based on self-report confirmed by medical record review. APPLICATION TO CLINICAL PRACTICE Long-term use of vitamin E and C supplements has no appreciable effect on cataract. RESULTS After 8 years of treatment and follow-up, 1174 incident cataracts were confirmed. There were 579 cataracts in the vitamin E-treated group and 595 in the vitamin E placebo group (hazard ratio, 0.99; 95% confidence interval, 0.88-1.11). For vitamin C, there were 593 cataracts in the treated group and 581 in the placebo group (hazard ratio, 1.02; 95% confidence interval, 0.91-1.14). CONCLUSION Long-term alternate-day use of 400 IU of vitamin E and daily use of 500 mg of vitamin C had no notable beneficial or harmful effect on the risk of cataract. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00270647.

Elevated Levels of Interleukin 6 in the Vitreous Fluid of Patients with Pars Planitis and Posterior Uveitis: The Massachusetts Eye & Ear Experience and Review of Previous Studies

Introduction: Although the exact mechanisms that lead to uveitis are not entirely known, the role of cytokines in the pathogenesis of this disease has been shown to be important. Prior studies described the presence of an array of cytokines in the intraocular fluid of patients with uveitis. Review of these studies indicate that Interleukin-6 (IL-6) is present, and animal data suggest the important role of IL-6 in the regulation of ophthalmologic immune responses. Purpose: We investigated whether IL-6, TNF-alpha, IL-1 alpha, beta, IL-2 are present in the vitreous of patients with active intermediate and posterior uveitis. Methods: Vitreous specimens were collected from 23 eyes of patients with active intermediate and posterior uveitis who underwent diagnostic or therapeutic vitrectomies. TNF-alpha, IL-1 alpha and beta, IL-2 and IL-6 were measured by enzyme-linked immunosorbent assay. Eight vitreous fluid samples from eye bank eyes were used as control. Results: IL-6 was higher in the vitreous of patients with uveitis compared to control samples (p = 0.0119). No TNF-alpha, IL-2, IL1-alpha or beta was detected. The levels of IL-6 did not correlate with a specific clinical diagnosis, but patients with pars planitis and panuveitis had the highest levels (p = 0.58) Conclusions: IL-6 is elevated in the vitreous of patients with active intermediate and posterior uveitis.