Nattokinase atherothrombotic prevention study: A randomized controlled trial.

BACKGROUND: Described to be antithrombotic and antihypertensive, nattokinase is consumed for putative cardiovascular benefit. However, no large-scale, long-term cardiovascular study has been conducted with nattokinase supplementation. OBJECTIVE: To determine the effect of nattokinase on subclinical atherosclerosis progression and atherothrombotic biomarkers. METHODS: In this double-blinded trial, 265 individuals of median age 65.3 years, without clinical evidence of cardiovascular disease (CVD) were randomized to oral nattokinase 2,000 fibrinolytic units or matching placebo. Primary outcome was rate of change in subclinical atherosclerosis measured by serial carotid ultrasound every 6 months as carotid artery intima-media thickness (CIMT) and carotid arterial stiffness (CAS). Additional outcomes determined at least every 6 months were clinical parameters including blood pressure and laboratory measures including metabolic factors, blood rheology parameters, blood coagulation and fibrinolysis factors, inflammatory markers and monocyte/macrophage cellular activation markers. RESULTS: After median 3 years of randomized treatment, annualized rate of change in CIMT and CAS did not significantly differ between nattokinase supplementation and placebo. Additionally, there was no significant effect of nattokinase supplementation on blood pressure or any laboratory determination. CONCLUSIONS: Results of this trial show that nattokinase supplementation has a null effect on subclinical atherosclerosis progression in healthy individuals at low risk for CVD.

Endoscopic cyclophotocoagulation versus second glaucoma drainage device after prior aqueous tube shunt surgery.

BACKGROUND: To evaluate the efficacy in controlling intraocular pressure (IOP) with endoscopic cyclophotocoagulation (ECP) versus implantation of a second glaucoma drainage device (GDD-2) in the treatment of uncontrolled glaucoma with a prior aqueous tube shunt. DESIGN: A nonrandomized retrospective chart review. PARTICIPANTS: Patients with refractory glaucoma following a failed initial tube shunt (Baerveldt Glaucoma Implant 350), who underwent ECP or GDD-2 with Baerveldt Glaucoma Implant as a second surgery. Twenty-five eyes underwent ECP, and 48 eyes received a GDD-2. METHODS: ECP or second tube-shunt surgery. MAIN OUTCOME MEASURES: Reduction in IOP and antiglaucoma medications, and Kaplan-Meier survival with success defined as lOP ≥ 5 mmHg and ≤ 21 mmHg and ≥ 20% reduction from preoperative IOP. Secondary outcome measures were visual acuity and the presence of any postoperative complications. RESULTS: Both ECP and GDD-2 significantly lowered IOP (Student's t test) and number of antiglaucoma medications (Wilcoxon paired signed rank test). There were no significant differences in postoperative IOP (Student's t test) or antiglaucoma medications (Mann Whitney test) between ECP and GDD-2 at 6 and 12 months. There was also no difference in the Kaplan-Meier survival outcomes between the two groups. CONCLUSION: Both ECP and GDD-2 are both effective as second surgeries for refractory glaucoma that has failed a prior aqueous shunt.

Cognitive effects of estradiol after menopause: A randomized trial of the timing hypothesis.

OBJECTIVE: To test the hypothesis that effects of estrogen-containing hormone therapy on cognitive abilities differ between postmenopausal women near to, and further from, menopause. METHODS: In this randomized, double-blind, placebo-controlled trial, healthy women within 6 years of menopause or 10+ years after menopause were randomly assigned to oral 17ß-estradiol 1 mg/d or placebo. Women with a uterus received cyclic micronized progesterone vaginal gel or placebo. The primary outcome assessed at 2.5 and 5 years, compared between treatment groups, was change in a standardized composite of neuropsychological test scores assessing verbal episodic memory. Secondary outcomes assessed executive functions and global cognition. RESULTS: A total of 567 women were included in modified intention-to-treat analyses after a mean treatment duration of 57 months. For verbal memory, the mean estradiol minus placebo standardized difference in composite scores (-0.06, 95% confidence interval -0.22 to 0.09) was not significant (2-tailed p = 0.33). Differences were similar in early and late postmenopause groups (2-tailed interaction p = 0.88). Interactions between postmenopause groups and differences between treatment groups were not significant for executive functions or global cognition. CONCLUSIONS: Estradiol initiated within 6 years of menopause does not affect verbal memory, executive functions, or global cognition differently than therapy begun 10+ years after menopause. Estradiol neither benefits nor harms these cognitive abilities regardless of time since menopause. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that estradiol initiated within 6 years of menopause does not affect cognition at 2.5 years differently than estradiol initiated 10+ years after menopause.

Repeatability of selective laser trabeculoplasty for open-angle glaucoma.

BACKGROUND: To analyze the results of repeat selective laser trabeculoplasty (SLT). INCLUSION CRITERIA: participants with primary or secondary open-angle glaucoma (excluding uveitic) who had undergone SLT 360° (SLT 1) with diminution of response over time followed by repeat SLT 360° (SLT 2). Six months of follow-up were required and at least 6 months in between SLT 1 and 2. The main outcome measures were IOP reduction at 6 and 12 months and a comparison of the response between SLT 1 and 2. RESULTS: One hundred thirty-seven patients met the inclusion criteria. If only one eye had repeat treatment, that eye was chosen; if both eyes qualified, one was chosen at random. The baseline intraocular pressure (IOP) for SLT 1 = 20.3+/- 5.2 mmHg and SLT 2 = 19.4 +/- 5.0 was reduced to 16.4 +/- 3.9 and 16.7 +/- 4.7 at 1 year, respectively (p < .001). Medication use was not significantly changed, and was 2.2 +/- 1.2 at baseline for SLT 1 and 2.1 +/- 1.3 for SLT 2, and at 1 year was 1.9 +/- 1.3 and 2.2 +/- 1.2, respectively. A subanalysis of 62 patients matched for equivalent baselines showed a baseline IOP = 18.7 +/- 3.8 for SLT 1 and 18.7 +/- 3.5 for SLT 2, reduced to 16.0 +/- 4.3 and 15.3 +/- 3.8 at 1 year (p < .001). CONCLUSION: Repeat SLT laser (360-degree treatment, followed by a loss of effect over time, then a second 360-degree treatment) in this population resulted in IOP lowering similar to that of the initial treatment.

Predictors of Macular Atrophy Detected by Fundus Autofluorescence in Patients With Neovascular Age-Related Macular Degeneration After Long-Term Ranibizumab Treatment.

BACKGROUND AND OBJECTIVE: To study the relationship between baseline morphologic characteristics of the choroidal neovascular (CNV) lesion and long-term development of macular atrophy in eyes with neovascular age-related macular degeneration (AMD) treated with ranibizumab (Lucentis; Genentech, South San Francisco, CA). PATIENTS AND METHODS: Certified graders evaluated baseline and 7-year follow-up (SEVEN-UP study) images of 41 eyes from the MARINA/ANCHOR and HORIZON trials. Using GRADOR software and stepwise linear regression, graders correlated lesion characteristics on fluorescein angiography (FA) at both visits with areas of definite decreased autofluorescence (DDAF) on fundus autofluorescence (FAF) imaging at the SEVEN-UP visit. RESULTS: Three of 41 eyes (7.3%) had macular atrophy on FA at baseline (mean ± standard deviation [SD] size: 0.29 mm(2) ± 1.50 mm(2)), 29 (70.7%) at SEVEN-UP (mean ± standard deviation [SD] area: 7.42 mm(2) ± 7.97 mm(2)). On FAF imaging at the SEVEN-UP visit, all 41 eyes (100%) had DDAF (mean ± SD size: 10.29 mm(2) ± 8.07 mm(2)). Variables significantly associated with area of DDAF at the SEVEN-UP visit were the area of leaking CNV lesion components (coefficient: 0.953; P < .001), the area of other lesion components (coefficient: 1.094; P = .038), and the area of retinal pigment epithelial (RPE) atrophy (coefficient: 1.334; P = .040) on baseline FA imaging. CONCLUSION: The area of DDAF at more than 7 years after initiation of ranibizumab therapy was 35% larger than the original CNV lesion. The baseline area of leaking CNV and other components of the CNV lesion and the baseline area of RPE atrophy were important predictors of the area of definite decreased autofluorescence, presumably corresponding to areas of photoreceptor and RPE loss. The findings from this study may guide hypothesis generation for future AMD trials.

Vascular Effects of Early versus Late Postmenopausal Treatment with Estradiol.

BACKGROUND: Data suggest that estrogen-containing hormone therapy is associated with beneficial effects with regard to cardiovascular disease when the therapy is initiated temporally close to menopause but not when it is initiated later. However, the hypothesis that the cardiovascular effects of postmenopausal hormone therapy vary with the timing of therapy initiation (the hormone-timing hypothesis) has not been tested. METHODS: A total of 643 healthy postmenopausal women were stratified according to time since menopause (<6 years [early postmenopause] or ≥10 years [late postmenopause]) and were randomly assigned to receive either oral 17ß-estradiol (1 mg per day, plus progesterone [45 mg] vaginal gel administered sequentially [i.e., once daily for 10 days of each 30-day cycle] for women with a uterus) or placebo (plus sequential placebo vaginal gel for women with a uterus). The primary outcome was the rate of change in carotid-artery intima-media thickness (CIMT), which was measured every 6 months. Secondary outcomes included an assessment of coronary atherosclerosis by cardiac computed tomography (CT), which was performed when participants completed the randomly assigned regimen. RESULTS: After a median of 5 years, the effect of estradiol, with or without progesterone, on CIMT progression differed between the early and late postmenopause strata (P=0.007 for the interaction). Among women who were less than 6 years past menopause at the time of randomization, the mean CIMT increased by 0.0078 mm per year in the placebo group versus 0.0044 mm per year in the estradiol group (P=0.008). Among women who were 10 or more years past menopause at the time of randomization, the rates of CIMT progression in the placebo and estradiol groups were similar (0.0088 and 0.0100 mm per year, respectively; P=0.29). CT measures of coronary-artery calcium, total stenosis, and plaque did not differ significantly between the placebo group and the estradiol group in either postmenopause stratum. CONCLUSIONS: Oral estradiol therapy was associated with less progression of subclinical atherosclerosis (measured as CIMT) than was placebo when therapy was initiated within 6 years after menopause but not when it was initiated 10 or more years after menopause. Estradiol had no significant effect on cardiac CT measures of atherosclerosis in either postmenopause stratum. (Funded by the National Institute on Aging, National Institutes of Health; ELITE ClinicalTrials.gov number, NCT00114517.).

COMPARISON OF MANUAL AND SEMIAUTOMATED FUNDUS AUTOFLUORESCENCE ANALYSIS OF MACULAR ATROPHY IN STARGARDT DISEASE PHENOTYPE.

PURPOSE: To evaluate manual and semiautomated grading techniques for assessing decreased fundus autofluorescence (DAF) in patients with Stargardt disease phenotype. METHODS: Certified reading center graders performed manual and semiautomated (region finder-based) grading of confocal scanning laser ophthalmoscopy (cSLO) fundus autofluorescence (FAF) images for 41 eyes of 22 patients. Lesion types were defined based on the black level and sharpness of the border: definite decreased autofluorescence (DDAF), well, and poorly demarcated questionably decreased autofluorescence (WDQDAF, PDQDAF). Agreement in grading between the two methods and inter- and intra-grader agreement was assessed by kappa coefficients (κ) and intraclass correlation coefficients (ICC). RESULTS: The mean ± standard deviation (SD) area was 3.07 ± 3.02 mm for DDAF (n = 31), 1.53 ± 1.52 mm for WDQDAF (n = 9), and 6.94 ± 10.06 mm for PDQDAF (n = 17). The mean ± SD absolute difference in area between manual and semiautomated grading was 0.26 ± 0.28 mm for DDAF, 0.20 ± 0.26 mm for WDQDAF, and 4.05 ± 8.32 mm for PDQDAF. The ICC (95% confidence interval) for method comparison was 0.992 (0.984-0.996) for DDAF, 0.976 (0.922-0.993) for WDQDAF, and 0.648 (0.306-0.842) for PDQDAF. Inter- and intra-grader agreement in manual and semiautomated quantitative grading was better for DDAF (0.981-0.996) and WDQDAF (0.995-0.999) than for PDQDAF (0.715-0.993). CONCLUSION: Manual and semiautomated grading methods showed similar levels of reproducibility for assessing areas of decreased autofluorescence in patients with Stargardt disease phenotype. Excellent agreement and reproducibility were observed for well demarcated lesions.

Endoscopic Cyclophotocoagulation and Pars Plana Ablation (ECP-plus) to Treat Refractory Glaucoma.

PURPOSE: To report clinical outcomes after pars plana endoscopic cyclophotocoagulation of the ciliary processes and pars plana (ECP-plus), a novel treatment for refractory glaucoma. DESIGN: Retrospective, noncomparative interventional case series. SETTING: multicenter tertiary referral academic and clinical practice. STUDY POPULATION: fifty-three eyes of 53 consecutive subjects undergoing ECP-plus who had uncontrolled intraocular pressure (IOP) despite prior glaucoma surgeries and maximally tolerated medical therapy. OBSERVATION PROCEDURE: retrospective analysis of clinical data after ECP-plus and pars plana vitrectomy. MAIN OUTCOME MEASURES: primary outcome was IOP at 6 and 12 months. Secondary outcomes were number of glaucoma medications and postoperative complications. RESULTS: Diagnoses were primary open-angle glaucoma (32%), chronic angle-closure glaucoma (26%), and secondary open-angle glaucoma (OAG, 42%); 50/53 of subjects had 6 months' and 28/53 had 12 months' follow-up data. Preoperative IOP was 27.9±7.5 mm Hg (mean±SD). Postoperative IOP at 6 mo was 10.2±5.6 and at 12 mo was 10.7±5.2 lower than preoperative levels (all P<0.0001). Cumulative treatment success was 81% at 6 mo and 78% at 12 mo. Number of medications fell from 3.4±1.2 pretreatment to 0.8±1.0 at 1 to 6 mo and 0.7±1.2 at 12 mo postoperatively (all P<0.0001). Complications in the initial postoperative period (<3 mo) were hypotony (3/53, 6%), fibrinous uveitis (2/53, 4%), and cystoid macular edema without hypotony (CME; 4/53, 6%). Complications beyond 6 mo occurred in 8/50 (16%) subjects as hypotony (4/50, 8%), choroidal detachment (4/50, 3 with IOP<5 and 1 with IOP≥5; 8%), CME without hypotony (3/50, 6%), and failed corneal graft (1/50, 2%). CONCLUSIONS: The mean IOP was lowered by at least 61% after ECP-plus and IOP lowering was sustained over the follow-up period. Fewer glaucoma medications were needed. Complication rates were comparable with or slightly higher than anterior endoscopic cyclophotocoagulation and acceptable given the refractory nature of disease being treated.

Inhibition of DNA Methylation and Methyl-CpG-Binding Protein 2 Suppresses RPE Transdifferentiation: Relevance to Proliferative Vitreoretinopathy.

PURPOSE: The purpose of this study was to evaluate expression of methyl-CpG-binding protein 2 (MeCP2) in epiretinal membranes from patients with proliferative vitreoretinopathy (PVR) and to investigate effects of inhibition of MeCP2 and DNA methylation on transforming growth factor (TGF)-ß-induced retinal pigment epithelial (RPE) cell transdifferentiation. METHODS: Expression of MeCP2 and its colocalization with cytokeratin and α-smooth muscle actin (α-SMA) in surgically excised PVR membranes was studied using immunohistochemistry. The effects of 5-AZA-2'-deoxycytidine (5-AZA-dC) on human RPE cell migration and viability were evaluated using a modified Boyden chamber assay and the colorimetric 3-(4,5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide (MTT) assay. Expression of RASAL1 mRNA and its promoter region methylation were evaluated by real-time PCR and methylation-specific PCR. Effects of 5-AZA-dC on expression of α-SMA, fibronectin (FN), and TGF-ß receptor 2 (TGF-ß R2) and Smad2/3 phosphorylation were analyzed by Western blotting. Effect of short interfering RNA (siRNA) knock-down of MeCP2 on expression of α-SMA and FN induced by TGFß was determined. RESULTS: MeCP2 was abundantly expressed in cells within PVR membranes where it was double labeled with cells positive for cytokeratin and α-SMA. 5-AZA-dC inhibited expression of MeCP2 and suppressed RASAL1 gene methylation while increasing expression of the RASAL1 gene. Treatment with 5-AZA-dC significantly suppressed the expression of α-SMA, FN, TGF-ß R2 and phosphorylation of Smad2/3 and inhibited RPE cell migration. TGF-ß induced expression of α-SMA, and FN was suppressed by knock-down of MeCP2. CONCLUSIONS: MeCP2 and DNA methylation regulate RPE transdifferentiation and may be involved in the pathogenesis of PVR.

TGF-ß2 secretion from RPE decreases with polarization and becomes apically oriented.

Retinal pigmented epithelium (RPE) secretes transforming growth factor beta 1 and 2 (TGF-ß1 and -ß2) cytokines involved in fibrosis, immune privilege, and proliferative vitreoretinopathy (PVR). Since RPE cell polarity may be altered in various disease conditions including PVR and age-related macular degeneration, we determined levels of TGF-ß from polarized human RPE (hRPE) and human stem cell derived RPE (hESC-RPE) as compared to nonpolarized cells. TGF-ß2 was the predominant isoform in all cell culture conditions. Nonpolarized cells secreted significantly more TGF-ß2 supporting the contention that loss of polarity of RPE in PVR leads to rise of intravitreal TGF-ß2. Active TGF-ß2, secreted mainly from apical side of polarized RPE, represented 6-10% of total TGF-ß2. In conclusion, polarity is an important determinant of TGF-ß2 secretion in RPE. Low levels of apically secreted active TGF-ß2 may play a role in the normal physiology of the subretinal space. Comparable secretion of TGF-ß from polarized hESC-RPE and hRPE supports the potential for hESC-RPE in RPE replacement therapies.

Comparison of reaction response time between hand and foot controlled devices in simulated microsurgical testing.

PURPOSE: We hypothesized that reaction times (RTs) for a switch release are faster for hand-controlled than for foot-controlled switches for physiological and anatomical reasons (e.g., nerve conduction speed). The risk of accidental trauma could be reduced if the surgeon reacted quicker and therefore improve the surgical outcome. METHOD: We included 47 medical professionals at USC. Demographics and handedness were recorded. Under a microscope, a simple reaction time test was performed, testing all extremities multiple times in a random order. Additionally, a subjective questionnaire was administered. RESULTS: The mean RTs for hands are 318.24 ms ± 51.13 and feet 328.69 ± 48.70. The comparison of hand versus foot showed significant shorter RTs for the hand (P = 0.025). Partially significant differences between and within the experience level groups could be demonstrated by level of education (LE) and microscopic surgeries/week (MSW) (P = 0.57-0.02). In the subjective questionnaire, 91.5% (n = 43/47) of test subjects prefer to use hand controls. CONCLUSION: Our data show that the RT for hands is faster than feet. Similarly the subjective questionnaire showed a greater preference for hand actuation. This data suggest a hand-controlled ophthalmic instrument might have distinct advantages; however, clinical correlation is required.

Endoscopic cyclophotocoagulation combined with phacoemulsification versus phacoemulsification alone in medically controlled glaucoma.

PURPOSE: To compare the outcomes of combined endoscopic cyclophotocoagulation (ECP) and phacoemulsification cataract extraction versus cataract extraction alone in eyes with medically controlled open-angle glaucoma (OAG) and visually significant cataract. SETTING: Clinical practices of glaucoma specialists and comprehensive ophthalmologists. DESIGN: Prospective nonrandomized matched-control study. METHODS: Consecutive patients with medically controlled OAG and visually significant cataracts were treated with ECP and cataract extraction (study group) or cataract extraction alone (control group). The groups were matched in age and baseline intraocular pressure (IOP). The main outcome measures were the change in IOP and number of glaucoma medications. Secondary measures included visual acuity and postoperative complications. RESULTS: In the study group (n = 80) the mean IOP decreased (baseline: 18.1 mm Hg ± 3.0 [SD]; 1 year: 16.0 ± 2.8 mm Hg; 2 years: 16.0 ± 3.3 mm Hg). The number of glaucoma medications decreased from 1.5 ± 0.8 to 0.4 ± 0.7 (1 year and 2 years). In the control group (n = 80), the mean IOP was 18.1 ± 3.0 mm Hg (baseline), 17.5 ± 3.6 mm Hg (1 year), and 17.3 ± 3.2 mm Hg (2 years). The mean number of glaucoma medications was 2.4 ± 1.0, 1.8 ± 1.2, and 2.0 ± 1.0, respectively. The difference in IOP and medication reduction between the 2 groups was statistically significant at all timepoints. Visual acuity outcomes and complication rates were similar between the 2 groups. CONCLUSION: Combined ECP and cataract extraction resulted in lower IOP and a greater reduction in glaucoma medications than cataract extraction alone in medically controlled OAG patients with visually significant cataract. FINANCIAL DISCLOSURES: Proprietary or commercial disclosures are listed after the references.

Visual function assessment in simulated real-life situations in HIV-infected subjects.

Visual function abnormalities are common in people living with HIV disease (PLWH) without retinitis, even after improvement in immune status. Abnormalities such as reduced contrast sensitivity, altered color vision, peripheral visual field loss, and electrophysiological changes are related to a combination of retinal dysfunctions, involving inner and outer retinal structures. The standard protocol for testing vision performance in clinical practice is the Early Treatment Diabetic Retinopathy Study (ETDRS) chart. However, this method poorly correlates with activities of daily living that require patients to assess visual stimuli in multiple light/contrast conditions, and with limited time. We utilized a novel interactive computer program (Central Vision Analyzer) to analyze vision performance in PLWH under a variety of light/contrast conditions that simulate stressful and real-world environments. The program tests vision in a time-dependent way that we believe better correlates with daily living activities than the non-timed ETDRS chart. We also aimed to correlate visual scores with retinal neuro-fiber layer thickness on optical coherence tomography. Here we show that visual acuity is more affected in PLWH in comparison to HIV-seronegative controls in varying contrast and luminance, especially if the nadir CD4+ T-cell count was lower than 100 cells/mm3. Visual impairment reflects the loss of retinal nerve fiber layer thickness especially of the temporal-inferior sector. In PLWH the ETDRS chart test led to better visual acuity compared to the Central Vision Analyzer equivalent test, likely because patients had indefinite time to guess the letters. This study confirms and strengthens the finding that visual function is affected in PLWH even in absence of retinitis, since we found that the HIV serostatus is the best predictor of visual loss. The Central Vision Analyzer may be useful in the diagnosis of subclinical HIV-associated visual loss in multiple light/contrast conditions, and may offer better understanding of this entity called "neuroretinal disorder".

Age distribution of various corneal diseases in China by histopathological examination of 3112 surgical specimens.

PURPOSE: To analyze the age distribution of corneal disease in China by histopathological examination. METHODS: A retrospective histopathological analysis of the prevalence and age distribution of corneal disease was performed on corneal specimens from 3112 patients who underwent corneal surgery between 2001 and 2012 in the Henan Eye Institute. RESULTS: Infectious keratitis (2212 specimens, 71.08%) was the most common corneal disease. The distribution of age groups was significantly higher after age 30 (16.29%), reaching a peak by age 40 (22.04%) and remaining high until age 59 (21.05%, P < 0.01). The highest age-specific percentage of corneal infection was between the ages of 50 and 59 (83.21%, P < 0.01). Noninfectious corneal diseases occurred mainly in the age range of 10 to 19 years (42.47%) and 20 to 29 years (40.78%). Between the ages of 10 and 19, the leading pathologic diagnosis was keratoconus, accounting for 21.29% of cases. In patients aged 80 and older, the most common noninfectious corneal diseases were Terrien-marginal degeneration (8.33%) and Mooren's ulcer (4.17%). The highest incidence of corneal tumor was seen between the ages of 0 and 9 years (65.83%) and age 80 and older (45.86%; P < 0.01). CONCLUSIONS: The age distribution of corneal diseases in the Chinese population is distinct from other countries. The corneal diseases tend to increase in prevalence in middle age, especially for infectious corneal disease. The prevalence of corneal tumor is high in early and late life. Corneal degenerative disease occurs predominately in seniors.

Cognition, mood, and physiological concentrations of sex hormones in the early and late postmenopause.

Variations in the hormonal milieu after menopause may influence neural processes concerned with cognition, cognitive aging, and mood, but findings are inconsistent. In particular, cognitive effects of estradiol may vary with time since menopause, but this prediction has not been assessed directly using serum hormone concentrations. We studied 643 healthy postmenopausal women not using hormone therapy who were recruited into early (<6 y after menopause) and late (10+ y after menopause) groups. Women were administered a comprehensive neuropsychological battery and assessed with the Center for Epidemiologic Studies Depression Scale. They provided serum for free estradiol, estrone, progesterone, free testosterone, and sex hormone binding globulin measurements. Cognitive outcomes were standardized composite measures of verbal episodic memory, executive functions, and global cognition. Covariate-adjusted linear regression analyses were conducted for each hormone separately and after adjustment for other hormone levels. Endogenous sex steroid levels were unassociated with cognitive composites, but sex hormone binding globulin was positively associated with verbal memory. Results for early and late groups did not differ significantly, although progesterone concentrations were significantly positively associated with verbal memory and global cognition in early group women. Hormone concentrations were not significantly related to mood. Results fail to support the hypothesis that temporal proximity to menopause modifies the relation between endogenous serum levels of estradiol and verbal memory, executive functions, or global cognition. Physiological variations in endogenous postmenopausal levels of sex steroid hormones are not substantially related to these aspects of cognition or mood; positive associations for progesterone and sex hormone binding globulin merit additional study.

Effect of age on aortic atherosclerosis.

OBJECTIVE: To examine the association of atherosclerosis burden in the survivors of an asymptomatic elderly cohort study and its relationship to other coronary risk factors (specifically, age) by evaluating aortic atherosclerotic wall burden by magnetic resonance imaging (MRI). METHODS: A total of 312 participants in an ongoing observational cohort study underwent cardiac and descending thoracic aorta imaging by MRI. Maximum wall thickness was measured and the mean wall thickness calculated. Wall/outer wall ratio was used as a normalized wall index (NWI) adjusted for artery size difference among participants. Percent wall volume (PWV) was calculated as NWI × 100. RESULTS: IN THIS ASYMPTOMATIC COHORT (MEAN AGE: 76 years), the mean (SD) aortic wall area and wall thickness were 222 ± 45 mm(2) and 2.7 ± 0.4 mm, respectively. Maximum wall thickness was 3.4 ± 0.6 mm, and PWV was 32% ± 4%. Women appeared to have smaller wall area, but after correcting for their smaller artery size, had significantly higher PWV than men (P = 0.03). Older age was associated with larger wall area (P = 0.04 for trend) with similar PWVs. However, there were no statistically significant associations between standard risk factors, Framingham global risk, or metabolic syndrome status, therapy for cholesterol or hypertension, coronary or aortic calcium score, and the aortic wall burden. Aortic calcification was associated with coronary calcification. CONCLUSIONS: Asymptomatic elderly in this cohort had a greater descending thoracic aortic wall volume that correlated with age, and women had a significantly increased PWV compared to men. In these survivors, the atherosclerotic aortic wall burden was not significantly associated with traditional risk factors or with coronary or aortic calcium scores or coronary calcium progression. Results suggest that age, or as yet unidentified risk factor(s), may be responsible for the increase in atherosclerosis.

Angiofibrotic response to vascular endothelial growth factor inhibition in diabetic retinal detachment: report no. 1.

OBJECTIVES To assess the effect of bevacizumab injection on connective tissue growth factor (CTGF) and vascular endothelial growth factor (VEGF) in the ocular fluids of patients with diabetic traction retinal detachment, and to determine whether intraoperative and postoperative complications are decreased in eyes given adjunctive preoperative bevacizumab injection. METHODS Twenty eyes of 19 patients were randomized to receive intravitreal bevacizumab or sham injection 3 to 7 days before vitrectomy for severe proliferative diabetic retinopathy. We collected aqueous samples before injection and at the time of vitrectomy and extracted undiluted vitreous samples. RESULTS Five eyes had decreased vascularization of membranes from preinjection to the time of vitrectomy (all in the bevacizumab treatment arm). Median visual acuities were 20/400 in control eyes at baseline and postoperative month 3 (POM3) and 8/200 in the bevacizumab-treated group at baseline and 20/100 at POM3 (P= .30 between control and bevacizumab-treated groups at POM3). All retinas were attached at POM3. Vitreous levels of VEGF were significantly lower in the bevacizumab group than in the control group (P= .03). Vitreous levels of CTGF were slightly lower in the bevacizumab group compared with the control group, but this difference was not statistically significant (P= .38). Levels of CTGF in the aqueous were strongly correlated with CTGF levels in the vitreous of controls (Spearman correlation coefficient, 0.95 [P< .001]). CONCLUSIONS Intravitreal bevacizumab injection reduces vitreous levels of VEGF and produces a clinically observable alteration in diabetic fibrovascular membranes. Ocular fluid levels of CTGF are not significantly affected within the week after VEGF inhibition. Retinal reattachment rates and visual acuity are not significantly altered by preoperative intravitreal bevacizumab injection at POM3. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01270542.

Morphometric spectral-domain optical coherence tomography features of epiretinal membrane correlate with visual acuity in patients with uveitis.

PURPOSE: To identify visually significant spectral-domain optical coherence tomography (SD-OCT) features of epiretinal membranes (ERM) in patients with uveitis. DESIGN: Retrospective cohort and cross-sectional study. METHODS: Eighty consecutive eyes with uveitis and SD-OCT-documented ERM were included. Clinical data were collected at the time of diagnosis of ERM and at the final visit. SD-OCT images at the last visit were evaluated to identify fovea and ERM configuration and structural changes. Changes of 10% and 20% in central subfield thickness between initial and last SD-OCT were calculated and correlated with visual acuity (VA). An ERM thickness map was created using validated SD-OCT grading software. RESULTS: VA improved significantly in eyes with more than 12 months of follow-up (P = .03). Although inflammation activity and medical treatment methods were no different in eyes with more or less than 12 months of follow-up, 16 eyes in the subset with longer follow-up underwent cataract extraction and intraocular lens implantation. Kaplan-Meier analysis demonstrated few vision losses during the follow-up period. Change in central subfield thickness did not correlate with VA. Foveal center involvement (P < .001), focal attachment of the ERM (P = .003), and foveal inner segment and outer segment junction disruption (P = .006) were associated independently with lower VA. ERM was thinner in eyes with 20/40 or better VA (4.6 ± 0.6 µm) compared with eyes with VA of less than 20/200 (P = .02). Longer duration of ERM was associated with thicker ERM (P < .05). CONCLUSIONS: In most eyes with uveitis and ERM, VA remains stable if ocular inflammation and comorbidities are addressed appropriately.

Fundus autofluorescence not predictive of treatment response to intravitreal bevacizumab in exudative age-related macular degeneration.

PURPOSE: Foveal autofluorescence (AF) has been suggested to be a potential predictor of treatment outcome in choroidal neovascularization (CNV) secondary to age-related macular degeneration and could be a useful marker to help prognosticate for patients and for clinical trials. This retrospective study aims to determine if pretreatment foveal AF can predict treatment response to intravitreal bevacizumab monotherapy in CNV secondary to age-related macular degeneration. METHODS: Ninety-five eyes (85 patients) with naive CNV secondary to age-related macular degeneration, treated with intravitreal bevacizumab monotherapy were included in this study. Lesion size, CNV type on fluorescein angiography, pretreatment best-corrected visual acuity, and foveal AF pattern (intact/nonintact) were used as predictors. Multivariate linear regression and logistic regression were performed using best-corrected visual acuity change and anatomical response at 6 months as the dependent variables separately. RESULTS: Pretreatment foveal AF (intact or nonintact) did not predict visual outcome (P = 0.17) nor did lesion size (P = 0.2) or CNV type (P = 0.61). Foveal AF did correlate with the visual acuity but it did not predict any treatment response. Pretreatment best-corrected visual acuity was the only predictive factor for the visual outcome (P = 0.043). CONCLUSION: Pretreatment AF is not a predictor for the treatment response to intravitreal bevacizumab monotherapy in eyes with CNV secondary to age-related macular degeneration.

High blood pressure in Chinese ethnic minorities: report from rural Yunnan province.

BACKGROUND: Hypertension (HTN) is a growing cause of morbidity and mortality among rural Chinese. While HTN has been studied in various regions of China, little is known about HTN among ethnic minorities in rural China. METHODS: A total of 36 villages were randomly selected from Yunnan province, China. From these villages, a total of 1,676 subjects from 10 ethnic minorities and the Han ethnic majority were selected for interview and blood pressure (BP) measurement. From each village, 50-80 men and women between the ages of 50 and 70 years were randomly selected. HTN prevalence, treatment, and control rates of HTN were evaluated in these 11 ethnic groups. RESULTS: After controlling for age, gender, body mass index (BMI), smoking, alcohol, and monosodium glutamate intake, prevalence of HTN varied between 25% in the Hani minority and 64% in the Tibetan minority (P < 0.001). Treatment rates varied between 0% in the Hani minority and 41% in the Tibetan minority (P = 0.006). Control rates varied between 0% in the Hani minority and 17% in the Tibetan minority (P = 0.28). Prevalence, treatment, and control rates in the Han ethnic group were 35, 22, and 12%, respectively. CONCLUSIONS: The prevalence of HTN varies widely among China's ethnic groups. Treatment and control rates of HTN also vary and are inadequate in the minority ethnic groups as well as in the Han majority.