Multiple sclerosis patients have a diminished serologic response to vitamin D supplementation compared to healthy controls.

BACKGROUND: Vitamin D insufficiency is a risk factor for multiple sclerosis (MS), and patients do not always show the expected response to vitamin D supplementation. OBJECTIVE: We aimed to determine if vitamin D supplementation leads to a similar increase in serum 25-hydroxyvitamin-D (25(OH)D) levels in patients with MS and healthy controls (HCs). METHODS: Participants in this open-label study were female, white, aged 18-60 years, had 25(OH)D levels ⩽ 75 nmol/l at screening, and had relapsing-remitting MS (RRMS) or were HCs. Participants received 5000 IU/day of vitamin D3 for 90 days. Utilizing generalized estimating equations we examined the relationship between the primary outcome (serum 25(OH)D level) and the primary (MS versus HC status) and secondary predictors. RESULTS: For this study 27 MS patients and 30 HCs were enrolled. There was no significant difference in baseline 25(OH)D level or demographics except for higher body mass index (BMI) in the MS group (25.3 vs. 23.6 kg/m(2), p=0.035). In total, 24 MS subjects and 29 HCs completed the study. In a multivariate model accounting for BMI, medication adherence, and oral contraceptive use, MS patients had a 16.7 nmol/l (95%CI: 4.2, 29.2, p=0.008) lower increase in 25(OH)D levels compared with HCs. CONCLUSIONS: Patients with MS had a lower increase in 25(OH)D levels with supplementation, even after accounting for putative confounders.

Characteristics of Endophthalmitis after Cataract Surgery in the United States Medicare Population.

PURPOSE: Endophthalmitis is a rare but sight-threatening infection after cataract surgery. Roughly one third of eyes remain blind after treatment. We report United States population-based data on microbiological investigations and treatment patterns plus risk factors for poor outcomes. DESIGN: Retrospective cohort study. PARTICIPANTS: Medicare beneficiaries from 5 states in whom endophthalmitis developed within 6 weeks after cataract surgery in 2003 and 2004. METHODS: We identified endophthalmitis cases occurring after cataract surgery using Medicare billing claims. We contacted treating physicians and requested they complete a questionnaire on clinical and microbiological data and submit relevant medical records. Two independent observers reviewed materials to confirm that cases met a standardized definition. MAIN OUTCOME MEASURES: Positive culture results, vitrectomy status, microbiology spectrum, and final visual acuity. RESULTS: In total, 615 cases met our case definition. Initial visual acuity was counting fingers or worse for 72%. Among 502 cases with known culture results, 291 (58%) had culture positive results. Twelve percent had positive results for streptococci. More than 99% of cases were treated with intravitreal vancomycin. Vitrectomy was performed in 279 cases (45%), including 201 cases with initial acuity better than light perception. Rates of vitrectomy varied across states, with California having the highest rate and Michigan having the lowest (56% and 19% of cases, respectively). Overall, 43% of individuals achieved visual acuity of 20/40 or better. Poor initial acuity (adjusted odds ratio [OR], 1.08; 95% confidence interval [CI], 1.04-1.12 per 0.10 logarithm of the minimum angle of resolution units), older age at diagnosis (OR, 1.22; 95% CI, 1.03-1.45 per 5-year increase), and more virulent organisms were important predictors of poor final visual acuity. Cases with streptococci infection were 10 times more likely to have poor final acuity than coagulase-negative staphylococci cases (adjusted OR, 11.28; 95% CI, 3.63-35.03). Vitrectomy was not predictive of final visual acuity (adjusted OR, 1.26; 95% CI, 0.78-2.04). CONCLUSIONS: Population-based data on the microbiology of acute postoperative endophthalmitis in the United States after cataract surgery are consistent with prior reports. Vitrectomy usage is higher than that recommended from the Endophthalmitis Vitrectomy Study, with no evidence of increased benefit.

Ranibizumab for macular telangiectasia type 2 in the absence of subretinal neovascularization.

PURPOSE: To evaluate the effects of 0.3 mg or 0.5 mg of ranibizumab in eyes with macular telangiectasia type 2 without subretinal neovascularization. METHODS: Ten eyes were randomized to either 0.3 mg or 0.5 mg ranibizumab group in 1 eye only. Study eye received ranibizumab at baseline and at Months 1 and 2. Injections at Months 3, 4, and 5 were at investigator's discretion. Participants were followed monthly through 6 months with best-corrected visual acuity, fluorescein angiography, and optical coherence tomography. RESULTS: For study eyes at baseline, median best-corrected visual acuity letter score was 60 (20/64 Snellen equivalent) and central subfield retinal thickness was 181.5 µm. Median number of injections was six. Median change in best-corrected visual acuity at Month 3 was 4 letters (range: -5 to 9 letters) at both doses in the study eye and 3 letters (range: -10 to 5 letters) in the untreated fellow eye. At Month 3, retinal leakage decreased 0.87 disk area and 0.76 disk area for 0.3 mg and 0.5 mg ranibizumab, respectively. Median change in central subfield retinal thickness was 1 µm and -11 µm for 0.3 mg and 0.5 mg ranibizumab, respectively. CONCLUSION: Ranibizumab (0.3 mg or 0.5 mg) decreases leakage secondary to macular telangiectasia type 2, but accompanying improvements in best-corrected visual acuity appear similar to improvements in the untreated fellow eye where retinal thickness is relatively unchanged.

The cost of glaucoma care provided to Medicare beneficiaries from 2002 to 2009.

PURPOSE: To estimate payments for glaucoma care among Medicare beneficiaries from 2002 to 2009. DESIGN: Database study. PARTICIPANTS: Data from a 5% random sample of Medicare billing information from 2002 to 2009. METHODS: Medicare beneficiaries, aged 65 years or older, with both Parts A and B fee-for-service (FFS) enrollment comprised the annual denominator. For each year, we included those with a defined glaucoma diagnostic code linked to a glaucoma visit, diagnostic test, or laser/surgical procedure. Open-angle, angle-closure, and other glaucoma were categorized separately. Claims were classified into glaucoma care, other eye care, and other medical care. MAIN OUTCOME MEASURES: Cost of glaucoma care in the Medicare Fee-for-Service Population. RESULTS: In 2009, total glaucoma payments by Medicare were $37.4 million for this subset, for an overall estimated cost of $748 million, or 0.4% of an estimated cost of $192 billion for all Medicare FFS payments. Office visits comprised approximately one half, diagnostic testing was approximately one-third, and surgical and laser procedures were approximately 10% of glaucoma-related costs. Coded open-angle glaucoma (OAG) and OAG suspects accounted for 87.5% of glaucoma costs, whereas cost per person was highest in "other glaucoma." In 2009, <3% of patients with OAG underwent incisional surgery and approximately 5% had laser trabeculoplasty. Laser iridotomy was the highest cost category among patients with angle-closure glaucoma, whereas office visits was the highest cost category among the "other glaucoma" group. The total cost of nonglaucoma eye care for patients with glaucoma was 67% higher than their glaucoma care costs; these were chiefly costs for cataract surgery and treatment of retinal diseases. From 2002 to 2009, FFS glaucoma care costs calculated in 2009 dollars were stable and cost per person per year in 2009 dollars decreased from $242 to $228 (P = 0.01 by test for linear trend). CONCLUSIONS: Annual glaucoma care costs per person decreased in constant dollars from 2002 to 2009. Cataract and retinal eye care for patients with glaucoma substantially exceeded the cost of their glaucoma care each year. Visit payments represented the largest category of costs.

A Phase 1b, Open-Label Study to Evaluate the Safety and Tolerability of the Putative Remyelinating Agent, Liothyronine, in Individuals with MS.

Thyroid hormones are essential during developmental myelination and may play a direct role in remyelination and repair in the adult central nervous system by promoting the differentiation of oligodendrocyte precursor cells into mature oligodendrocytes. Since tri-iodothyronine (T3) is believed to mediate the majority of important thyroid hormone actions, liothyronine (synthetic T3) has the potential to induce reparative mechanisms and limit neurodegeneration in multiple sclerosis (MS). We completed a phase 1b clinical trial to determine the safety and tolerability of ascending doses of liothyronine in individuals with relapsing and progressive MS. A total of 20 people with MS were enrolled in this single-center trial of oral liothyronine. Eighteen participants completed the 24-week study. Our study cohort included mostly women (11/20), majority relapsing MS (12/20), mean age of 46, and baseline median EDSS of 3.5. Liothyronine was tolerated well without treatment-related severe/serious adverse events or evidence of disease activation/clinical deterioration. The most common adverse events included gastrointestinal distress and abnormal thyroid function tests. No clinical thyrotoxicosis occurred. Importantly, we did not observe a negative impact on secondary clinical outcome measures. The CSF proteomic changes suggest a biological effect of T3 treatment within the CNS. We noted changes primarily in proteins associated with immune cell function and angiogenesis. Liothyronine appeared safe and was well tolerated in people with MS. A larger clinical trial will help assess whether liothyronine can promote oligodendrogenesis and enhance remyelination in vivo, limit axonal degeneration, or improve function.

High-dose vitamin D3 supplementation in relapsing-remitting multiple sclerosis: a randomised clinical trial.

Background: Vitamin D insufficiency is associated with risk of multiple sclerosis (MS) relapse; whether supplementation influences prognosis is unknown. The Vitamin D to Ameliorate MS (VIDAMS) trial aimed to determine if high dose (5000 International Units (IU)/day) versus low dose (600 IU/day) vitamin D3, added to daily glatiramer acetate (GA), reduced the risk of clinical relapse in people with established relapsing remitting MS (RRMS) over 96 weeks. Methods: VIDAMS is a randomised, phase 3, double-blind, multi-centre, controlled trial conducted at sixteen neurology clinics in the United States. Participants with MAGNIMS 2010 RRMS, aged 18-50 years, with recent disease activity were eligible to enroll if they had an Expanded Disability Status Scale score ≤4.0; minimum serum 25-hydroxyvitamin D level of 15 ng/ml within 30 days of screening; and average ≤ 1000 IU supplemental vitamin D3 daily in the 90 days prior to screening. Of 203 screened, 183 were eligible for the 30-day run-in to assess GA adherence, after which 172 were randomised 1:1 to low dose vitamin D3 (LDVD) or high dose vitamin D3 (HDVD), and were followed every 12 weeks for 96 weeks. The primary outcome was the proportion that experienced a confirmed relapse and analyses used Kaplan Meier and Cox proportional hazards models. 165 participants returned for ≥1 follow-up visit and were included in the primary and safety analyses; 140 completed a week 96 visit. This study was registered with ClinicalTrials.gov, NCT01490502. Findings: Between March 22, 2012 and March 8, 2019, 172 participants were enrolled and randomised (83 LDVD, 89 HDVD) and differed at baseline only in gender and race: more males received HDVD (31%) than LDVD (16%), and fewer Black participants received HDVD (12%) than LDVD (22%). Among 165 participants with at least one follow-up visit, the proportion experiencing confirmed relapse did not differ between LDVD and HDVD [at 96 weeks: 32% vs. 34%, p = 0.60; hazard ratio (HR): 1.17 (0.67, 2.05), p = 0.57]. There was no hypercalcaemia. Three participants developed nephrolithiasis or ureterolithiasis (1 in the LDVD and 2 in the HDVD group). Two were possibly related to study drug; and one was presumed related to concomitant treatment with topiramate for migraine. Interpretation: VIDAMS provides evidence that HDVD supplementation, added to GA, does not reduce the risk of clinical relapse in people with RRMS. Taken together with the null findings of previous trials, these results suggest that prescribing higher doses of vitamin D for purposes of modifying the RRMS course may not be beneficial. Funding: This investigation was supported by a grant from the National Multiple Sclerosis Society (RG 4407A2/1). Teva Neuroscience, Inc. provided Copaxone (GA) for the duration of the trial.

Postcataract surgery endophthalmitis in the United States: analysis of the complete 2003 to 2004 Medicare database of cataract surgeries.

OBJECTIVE: To estimate endophthalmitis incidence after cataract surgery nationally and at the state level in 2003 and 2004 and to explore risk factors. DESIGN: Analysis of Medicare beneficiary claims data. PARTICIPANTS: We evaluated billed claims for cataract surgery and endophthalmitis diagnosis and treatment for all Medicare fee-for-service beneficiaries in 2003-2004. METHODS: Cataract surgeries were identified by procedure codes and merged with demographic information. Cataract annual surgical volume was calculated for all surgeons. Presumed postoperative endophthalmitis cases were identified by International Classification of Diseases-9 Clinical Modification Codes on claims within 42 days after surgery. Endophthalmitis rates and 95% confidence intervals (CI) were calculated at state and national levels. Logistic regression was used to investigate the association between developing endophthalmitis and surgery location and surgeon factors. MAIN OUTCOME MEASURES: Endophthalmitis incidence and risk factors. RESULTS: We included 4006 cases of presumed endophthalmitis, which occurred after 3 280 966 cataract surgeries. The national rate in 2003 was 1.33 per 1000 surgeries (95% CI, 1.27-1.38) and decreased to 1.11 per 1000 (95% CI, 1.06-1.16) in 2004. Males (relative risk [RR], 1.23; 95% CI, 1.15-1.31), older individuals (RR, 1.53; 95% CI, 1.38-1.69; ≥85 compared with 65-74 years), blacks (RR, 1.17; 95% CI, 1.03-1.33), and Native Americans (RR, 1.72; 95% CI, 1.07-2.77) had increased risk of disease. After adjustment, surgeries by surgeons with low annual volume (RR, 3.80; 95% CI, 3.13-4.61 for 1-50 compared with ≥1001 annual surgeries) and less experience (RR, 1.41; 95% CI, 1.25-1.59 for 1-10 compared with ≥30 years), and surgeries performed in 2003 (RR, 1.20; 95% CI, 1.13-1.28) had increased endophthalmitis risk. CONCLUSIONS: Endophthalmitis rates are lower than previous yearly US estimates, but remain higher than rates reported from a series of studies from Sweden; patient factors or methodologic differences may contribute to differences across countries. Patient age, gender, and race, and surgeon volume and years of experience are important risk factors.

Regional variations and trends in the prevalence of diagnosed glaucoma in the Medicare population.

PURPOSE: To determine the prevalence of diagnosed glaucoma in the Medicare population and to assess regional variations and trends. DESIGN: Retrospective, cross-sectional study. PARTICIPANTS: A 5% random sample of Medicare beneficiaries aged ≥ 65 years, excluding those in health maintenance organizations. METHODS: All claims with a glaucoma diagnosis code submitted by ophthalmologists, optometrists, or ambulatory surgery centers were used to estimate prevalence of the diagnosis of glaucoma for each year from 2002 to 2008. Regional variation in diagnosed glaucoma was examined in 9 large geographic regions and in 179 smaller subregions, controlling for patient characteristics and provider supply. MAIN OUTCOME MEASURES: The prevalence of diagnosed open-angle glaucoma suspect (OAG-s), open-angle glaucoma (OAG), angle-closure glaucoma suspect (ACG-s), and angle-closure glaucoma (ACG), trends over time, and regional variations in prevalence. RESULTS: The overall prevalence increased from 10.4% in 2002 to 11.9% by 2008, largely owing to increase in diagnosed OAG-s (from 3.2% to 4.5%; P<0.001). The relative prevalence of diagnosed OAG compared with diagnosed ACG was 32:1. In 2008, multivariable models showed that the New England and Mid-Atlantic regions had 1.7 times more diagnosed OAG-s than the reference region (East South Central; New England: odds ratio [OR], 1.66; 95% confidence interval [CI], 1.58-1.75; Mid-Atlantic: OR, 1.66; 95% CI, 1.59-1.73). The odds of diagnosed OAG was 36% higher in New England (OR, 1.36; 95% CI, 1.30-1.42) and 31% higher in the Mid-Atlantic (OR, 1.31; 95% CI, 1.26-1.36) than in the reference region. The New England and Mid-Atlantic regions had the highest odds of diagnosed ACG-s and the Mid-Atlantic region had the highest odds of diagnosed ACG. Among 179 subregions, the New York area had high diagnosis rates of all glaucoma types. CONCLUSIONS: The relative prevalence of diagnosed ACG compared with diagnosed OAG was lower than expected from population-based data, possibly owing to failure to perform gonioscopy. Substantial regional differences in diagnosed rates existed for all types of glaucoma, even after adjusting for patient characteristics and provider concentration, suggesting possible overdiagnosis in some areas and/or underdiagnosis in other areas. Regionally higher diagnosis rates in the New York area deserve further study.

Detection of new-onset choroidal neovascularization using optical coherence tomography: the AMD DOC Study.

PURPOSE: To determine the sensitivity of time domain optical coherence tomography (OCT) in detecting conversion to neovascular age-related macular degeneration (AMD) in eyes at high risk for choroidal neovascularization (CNV), compared with detection using fluorescein angiography (FA) as the gold standard. DESIGN: Prospective, multicenter, observational study. PARTICIPANTS: Individuals aged ≥50 years with nonneovascular AMD at high risk of progressing to CNV in the study eye and evidence of neovascular AMD in the fellow eye. METHODS: At study entry and every 3 months through 2 years, participants underwent best-corrected visual acuity, supervised Amsler grid testing, preferential hyperacuity perimetry (PHP) testing, stereoscopic digital fundus photographs with FA, and OCT imaging. A central Reading Center graded all images. MAIN OUTCOMES MEASURES: The sensitivity of OCT in detecting conversion to neovascular AMD by 2 years, using FA as the reference standard. Secondary outcomes included comparison of sensitivity, specificity, positive predictive value, and negative predictive value of OCT, PHP, and supervised Amsler grid relative to FA for detecting incident CNV. RESULTS: A total of 98 participants were enrolled; 87 (89%) of these individuals either completed the 24-month visit or exited the study after developing CNV. Fifteen (17%) study eyes had incident CNV confirmed on FA by the Reading Center. The sensitivity of each modality for detecting CNV was: OCT 0.40 (95% confidence interval [CI], 0.16-0.68), supervised Amsler grid 0.42 (95% CI, 0.15-0.72), and PHP 0.50 (95% CI, 0.23-0.77). Treatment for incident CNV was recommended by the study investigator in 13 study eyes. Sensitivity of the testing modalities for detection of CNV in these 13 eyes was 0.69 (95% CI, 0.39-0.91) for OCT, 0.50 (95% CI, 0.19-0.81) for supervised Amsler grid, and 0.70 (95% CI, 0.35-0.93) for PHP. Specificity of the OCT was higher than that of the Amsler grid and PHP. CONCLUSIONS: Time-domain OCT, supervised Amsler grid, and PHP have low to moderate sensitivity for detection of new-onset CNV compared with FA. Optical coherence tomography has greater specificity than Amsler grid or PHP. Among fellow eyes of individuals with unilateral CNV, FA remains the best method to detect new-onset CNV.

Intermittent calorie restriction alters T cell subsets and metabolic markers in people with multiple sclerosis.

BACKGROUND: Intermittent fasting or calorie restriction (CR) diets provide anti-inflammatory and neuroprotective advantages in models of multiple sclerosis (MS); data in humans are sparse. METHODS: We conducted a randomised-controlled feeding study of different CR diets in 36 people with MS over 8 weeks. Participants were randomised to 1 of 3 diets: 1) a control diet, in which the participant received 100% of his or her calorie needs 7 days per week, 2) a daily CR diet, in which the participant received 78% of his or her calorie needs 7 days per week, or 3) an intermittent CR diet, in which the participant received 100% of his or her calorie needs on 5 days per week and 25% of his or her calorie needs 2 days per week (i.e., a "5:2" style diet). Untargeted metabolomics was performed on plasma samples at weeks 0, 4 and 8 at Metabolon Inc (Durham, NC). Flow cytometry of cryopreserved peripheral blood mononuclear cells at weeks 0 and 8 were used to identify CD3+;CD4+ (CD4+) and CD3+;CD4- (as a proxy for CD8+) T cell subsets including effector memory, central memory, and naïve cells. FINDINGS: 31 (86%) completed the trial. Over time, individuals randomised to intermittent CR had significant reductions in effector memory (for CD4-EM: -3.82%; 95%CI: -7.44, -0.21; for CD4-: -6.96%; 95%CI: -11.96, -1.97) and Th1 subsets (-4.26%; 95% CI: -7.11, -1.40) and proportional increases in naïve subsets (for CD4-: 10.11%; 95%CI: 3.30, 16.92%). No changes were observed for daily CR or weight-stable diets. Larger within-person changes in lysophospholipid and lysoplasmalogen metabolites in intermittent CR were associated with larger reductions in memory T cell subsets and larger increases in naïve T cell subsets. INTERPRETATION: In people with MS, an intermittent CR diet was associated with reduction in memory T cell subsets and certain biologically-relevant lipid markers. FUNDING: National MS Society, NIH, Johns Hopkins Catalyst Award.

Intraoperative phacoemulsification complication rates of second- and third-year ophthalmology residents a 5-year comparison.

OBJECTIVE: To determine whether year of residency is associated with intraoperative phacoemulsification complication rates. DESIGN: Retrospective cohort study. PARTICIPANTS: One attending physician supervised 691 resident-performed phacoemulsification procedures on 492 patients. Second- and third-year residents performed 228 and 463 cases, respectively. METHODS: All resident-performed phacoemulsification procedures performed between October 2003 and June 2008 and supervised by one attending surgeon (SR) were considered for this study. Data were collected on the residency year of the physician performing the surgery, preoperative risk indicators, and intraoperative complications, including anterior and posterior capsular tears with or without vitreous loss, zonular dialysis or dehiscence, burns, nuclear fragment loss, and Descemet's membrane tear. Cases were classified as difficult if they had 1 or more preoperative risk indicators including: pseudoexfoliation; proliferative diabetic retinopathy; prior vitrectomy; a 4+ dense, white, or brunescent cataract; current Flomax (Boehringer-Ingelheim, Ingelheim, Germany) use, pre-existing zonular dialysis; and intraoperative use of Trypan blue, iris hooks, or pupil dilator. Intraoperative complications are presented as rate per 100 surgeries (95% confidence intervals [CIs]). MAIN OUTCOME MEASURES: Intraoperative complication rates and case difficulty. RESULTS: Fifty-three patients experienced at least 1 complication, with 25 cases experiencing multiple complications. Intraoperative complication rates were similar among second- and third-year resident groups (7.9% vs. 7.6%; P = 0.88). Similarly, vitreous loss rates among second- and third-year residents were comparable (4.8% vs. 3.0%; P = 0.27). Risk indicators were more common among third-year cases (24.6% vs. 15.8%; P = 0.008). Having 1 or more risk indicators increased the odds of an intraoperative complication (odds ratio [OR], 3.09; 95% CI, 1.73-5.49). After controlling for risk indicators, second-year resident surgeries still had a similar risk of intraoperative complications as third-year resident surgeries (OR, 1.15; 95% CI, 0.6-2.19). CONCLUSIONS: The year of residency did not significantly influence intraoperative complication rates, even after controlling for differences in case difficulty.

Association of Disease Severity and Socioeconomic Status in Black and White Americans With Multiple Sclerosis.

OBJECTIVE: To compare clinical and imaging features of multiple sclerosis (MS) severity between Black Americans (BAs) and White Americans (WAs) and to evaluate the role of socioeconomic status. METHODS: We compared BA and WA participants in the Multiple Sclerosis Partners Advancing Technology Health Solutions (MS PATHS) cohort with respect to MS characteristics, including self-reported disability, objective neurologic function assessments, and quantitative brain MRI measurements, after covariate adjustment (including education level, employment, or insurance as socioeconomic indicators). In a subgroup, we evaluated within-race, neighborhood-level indicators of socioeconomic status (SES) using 9-digit zip codes. RESULTS: Of 1,214 BAs and 7,530 WAs with MS, BAs were younger, had lower education level, and were more likely to have Medicaid insurance or to be disabled or unemployed than WAs. BAs had worse self-reported disability (1.47-fold greater odds of severe vs mild disability, 95% confidence interval [CI] 1.18, 1.86) and worse performances on tests of cognitive processing speed (-5.06 fewer correct, 95% CI -5.72, -4.41), walking (0.66 seconds slower, 95% CI 0.36, 0.96), and manual dexterity (2.11 seconds slower, 95% CI 1.69, 2.54). BAs had more brain MRI lesions and lower overall and gray matter brain volumes, including reduced thalamic (-0.77 mL, 95% CI -0.91, -0.64), cortical (-30.63 mL, 95% CI -35.93, -25.33), and deep (-1.58 mL, 95% CI -1.92, -1.23) gray matter volumes. While lower SES correlated with worse neuroperformance scores in WAs, this association was less clear in BAs. CONCLUSION: We observed a greater burden of disease in BAs with MS relative to WAs with MS, despite adjustment for SES indicators. Beyond SES, future longitudinal studies should also consider roles of other societal constructs (e.g., systemic racism). Such studies will be important for identifying prognostic factors; developing optimal treatment strategies among BAs with MS is warranted.

Prospective one-year study of ranibizumab for predominantly hemorrhagic choroidal neovascular lesions in age-related macular degeneration.

PURPOSE: To determine the safety and effect of ranibizumab on predominantly hemorrhagic choroidal neovascular lesions due to age-related macular degeneration. METHODS: Seven subjects with predominantly hemorrhagic choroidal neovascular lesions were treated with intravitreal injections of ranibizumab at baseline, Month 1, and Month 2. Additional monthly injections were given through Month 11 at the discretion of the examiner for a potential maximum of 12 injections. RESULTS: At 12 months, the median visual acuity letter score was 30 (Snellen equivalent: 20/250), with a median change from baseline to last follow-up of +7 letters. Three of 7 subjects (43%) gained 2 or more lines of vision, while no subject lost 2 or more lines. The median change in OCT central subfield thickness from baseline to Month 12 was -109 microm, with a mean of -120 +/- 158 microm. Two eyes had retinal pigment epithelial tears. No ocular adverse events or systemic adverse events were reported related to the usage of ranibizumab. CONCLUSION: With no subject losing 2 or more lines of visual acuity over 12 months and no new safety concerns identified, these predominantly hemorrhagic lesions treated with ranibizumab appeared to have a better visual acuity outcome than the natural history controls of the submacular surgery trials. While the study is limited by few cases enrolled, the results suggest that ranibizumab is able to penetrate through the subretinal hemorrhage to affect the underlying hemorrhagic choroidal neovascular lesion and the natural history.

A cost-effectiveness analysis of three treatments for age-related macular degeneration.

PURPOSE: The purpose of this study was to evaluate the cost effectiveness of pegaptanib sodium and ranibizumab injections compared with photodynamic therapy (PDT) with verteporfin for the treatment of choroidal neovascularization secondary to age-related macular degeneration. METHODS: The analyses were performed using outcomes data from the pivotal trials for each treatment and the medicare reimbursable costs for each treatment and associated medical procedures. A multistate transition model with 3-month cycles was created to compare incremental medical costs associated with pegaptanib or ranibizumab versus PDT for patients with starting vision of 20/40, 20/80, and 20/200 Snellen equivalent. RESULTS: Two-year medical treatment costs ranged from $3,100 to $54,100 depending on treatment and lesion type. Photodynamic therapy was less costly and more effective than pegaptanib for predominantly classic and minimally classic lesions. Ranibizumab was not only more effective but also more costly than PDT for all lesion types. CONCLUSION: Compared with PDT, pegaptanib is inferior in both cost and effectiveness, whereas ranibizumab has a greater effectiveness. Because ranibizumab does not meet 1 of the common thresholds for being considered cost effective (<$50,000 per quality-adjusted life year), there is rationale to seek other therapies that are more cost effective.

The prevalence and utility of screening for urinary tract infection at the time of presumed multiple sclerosis relapse.

BACKGROUND: Methods of screening for infections at the time of suspected relapse in people with multiple sclerosis (MS) vary across physicians. People with multiple sclerosis (MS) are at an increased risk of urinary tract infection (UTI). Data evaluating the utility of screening for potential UTI at the time of suspected relapse and whether there are key subgroups of patients in which screening would be most effective are sparse. OBJECTIVES: To evaluate demographic and clinical predictors of UTI in the context of a suspected acute relapse in (1) a retrospective hospital admission cohort and (2) a prospectively-enrolled, ambulatory care-based cohort, and to determine an approximate number needed to screen to detect one UTI in both healthcare settings. METHODS: For the hospital admissions cohort, we included individuals with a known or new diagnosis of MS or clinically isolated syndrome who were admitted at least once to the Johns Hopkins Neurology Inpatient Service (March 2012 to December 2014). We considered those screened via urinalysis. Possible UTI was defined as leukocyte esterase OR nitrite positive. For the ambulatory population, we enrolled a cohort of RRMS patients aged 18-65 who were suspected of suffering from an acute MS relapse who either called or came into clinic. Participants were screened via urinalysis; possible UTI was similarly defined. Participants also completed questionnaires (disability, history of Uhthoff's-type phenomenon, recent sexual intercourse, and new urologic symptoms). For both cohorts, we calculated an approximate number needed to screen, and tested if demographic and patient characteristics were associated with possible UTI using logistic regression models. RESULTS: For the hospital admissions cohort, we included 158 individuals; 48 (30.4%) were identified as possibly having a UTI. For possible UTI, the approximate number needed to screen in order to detect 1 possible UTI is 3 (95% CI: 2, 6). Female sex was the only factor associated with increased odds of UTI (odds ratio [OR]: 3.90; 95% CI: 1.59-9.61; p = 0.003). For the ambulatory cohort, we included 50 participants; 10 (20.0%) with possible UTI. The approximate number needed to screen in order to detect 1 possible UTI was 5 (95% CI: 3, 11) in this cohort. Foul-smelling urine was positively associated with UTI (OR: 5.36; 95% CI: 1.10, 26.17; p = 0.04); no men had a possible UTI in this cohort, so we could not estimate odds ratios associated with sex. CONCLUSION: UTIs at the time of a suspected MS relapse are relatively uncommon. Female sex is a strong risk factor for UTI in people with MS; foul-smelling urine is a potential predictor of UTI in people with MS. Larger studies are needed to comprehensively evaluate the utility of screening and risk factors for UTI at the time of suspected MS relapse.

Effect of intermittent vs. daily calorie restriction on changes in weight and patient-reported outcomes in people with multiple sclerosis.

An intermittent fasting or calorie restriction diet has favorable effects in the mouse forms of multiple sclerosis (MS) and may provide additional anti-inflammatory and neuroprotective advantages beyond benefits obtained from weight loss alone. We conducted a pilot randomized controlled feeding study in 36 people with MS to assess safety and feasibility of different types of calorie restriction (CR) diets and assess their effects on weight and patient reported outcomes in people with MS. Patients were randomized to receive 1 of 3 diets for 8 weeks: daily CR diet (22% daily reduction in energy needs), intermittent CR diet (75% reduction in energy needs, 2 days/week; 0% reduction, 5 days/week), or a weight-stable diet (0% reduction in energy needs, 7 days/week). Of the 36 patients enrolled, 31 (86%) completed the trial; no significant adverse events occurred. Participants randomized to CR diets lost a median 3.4 kg (interquartile range [IQR]: -2.4, -4.0). Changes in weight did not differ significantly by type of CR diet, although participants randomized to daily CR tended to have greater weight loss (daily CR: -3.6 kg [IQR: -3.0, -4.1] vs. intermittent CR: -3.0 kg [IQR: -1.95, -4.1]; P = 0.15). Adherence to study diets differed significantly between intermittent CR vs. daily CR, with lesser adherence observed for intermittent CR (P = 0.002). Randomization to either CR diet was associated with significant improvements in emotional well-being/depression scores relative to control, with an average 8-week increase of 1.69 points (95% CI: 0.72, 2.66). CR diets are a safe/feasible way to achieve weight loss in people with MS and may be associated with improved emotional health.

Corneal Sensitivity and Presence of Pathogenic Organisms Among Participants Who Have Undergone Trichiasis Surgery Differ by Surgical Outcome.

PURPOSE: To explore the potential association between reduced corneal sensation and/or conjunctival bacterial colonization and postoperative trichiasis and eyelid contour abnormalities after corrective eyelid surgery among participants with a history of trachomatous trichiasis. METHODS: As an ancillary study to the Partnership for Rapid Elimination of Trachoma (PRET) Surgery Trial in southern Tanzania, we collected data on 580 PRET participants who had undergone trichiasis surgery 1 year earlier and 200 age-group-matched individuals without trichiasis. Assessments included eyelid status evaluation (presence and severity of postoperative trichiasis and/or eyelid contour abnormality), corneal sensitivity by Cochet-Bonnet aesthesiometer, a questionnaire on symptoms of ocular irritation, and conjunctival microbiology. We divided PRET participants based on their eyelid status and compared results across PRET groups and versus normals. RESULTS: PRET participants had reduced corneal sensitivity compared with age-matched normals (mean sensitivity ranged from 2.8 to 3.8 cm in PRET participants vs. 5.9 cm in normals), and increasing severity of postoperative trichiasis was associated in a stepwise fashion with reduced corneal sensitivity (mean = 3.5 cm for mild and 2.6 cm for severe postoperative trichiasis). Conjunctival colonization with pathogenic bacteria was also associated with more severe postoperative trichiasis (Cochran-Armitage trend test P = 0.001) and with reduced corneal sensitivity (trend test P < 0.0001). Symptoms of ocular irritation were not associated with previous trichiasis surgery, postoperative trichiasis, or eyelid contour abnormality. CONCLUSIONS: These findings indicate that reduced corneal sensitivity accompanies trachomatous trichiasis and suggest that reduced corneal sensitivity may play an important role in the harboring of pathogenic bacteria on the ocular surface.

Donor Corneal Transplantation vs Boston Type 1 Keratoprosthesis in Patients with Previous Graft Failures: A Retrospective Single Center Study (An American Ophthalmological Society Thesis).

PURPOSE: To compare short-term outcomes of repeat penetrating keratoplasty (PK) to those of Boston type 1 keratoprosthesis (KPro). Our hypothesis was that visual outcomes were superior for KPro compared to PK. METHODS: This is a retrospective, nonrandomized, intermediate-term case series. Consecutive adults with one or more failed PKs who underwent either PK or KPro between January 2008 and December 2010 were included. Demographics, indication for the initial PK, comorbidities, concomitant procedures, and complications were considered. Only one procedure in each eye was included. All KPro procedures were retained in the analyses. RESULTS: Fifty-three patients underwent PK and 27 received KPro. Mean follow-up was 19.5 months in the PK group and 16.5 months in the KPro group. KPro eyes had worse mean preoperative vision (hand motions vs counting fingers, P=.01) and more comorbidities. In the postoperative period, 35% of PK eyes and 45% of KPro eyes attained best-ever visual acuity of 20/70. Forty-seven percent of PK eyes vs 40% of KPro eyes were able to retain this visual acuity. Two-year rate of failure to retain visual acuity better than the baseline was higher for PK eyes, though not at a statistically significant level (hazard ratio [HR]=1.67; 95% CI, 0.78-3.60; P=.19). Two-year cumulative rate of graft failure (loss of clarity for PK and removal/replacement for KPro) was higher for PK eyes (HR=3.23; 95% CI, 1.12-9.28; P=.03). Retinal detachment, endophthalmitis, and glaucoma rates were similar (P=.6 for all). CONCLUSIONS: These results demonstrate less frequent graft failure, greater visual improvement, and greater likelihood of maintaining the visual improvement in KPro eyes vs PK.

Risk factors for endophthalmitis following cataract surgery-our experience at a tertiary eye care centre in India.

AIM: To determine the risk factors for acute endophthalmitis after cataract extraction in a tertiary care centre in India. METHODS: We performed a nested case control study within a retrospective cohort. The surgical records of all patients with clinically diagnosed endophthalmitis within one month after cataract surgery, performed between January 2006 and December 2009, were reviewed. These were compared with randomly selected age and gender-matched controls, from patients having routine cataract surgery within ±1wk of the endophthalmitis case. Univariable and multivariable analysis were performed to identify risk factors for endophthalmitis. RESULTS: Of the total 33 856 cataract surgeries performed during this period, there were 57 cases of postoperative acute endophthalmitis that met our study criteria. Thus, the overall incidence of endophthalmitis in our cohort was 1.6 per 1000 cataract extractions performed. Mean age of cases was 55.9y (SD: 10.9y) and for controls was 55.6y (SD: 9.8y). Thirty-five cases (61.4%) and 133 controls (59.6%) were males. Median time of onset of endophthalmitis was 4d (IQR 2-9d; range: 1-30d). Thirty-nine cases (68.4%) presented within 7d and 27 cases (47.4%) were culture positive. Two hundred and twenty-three age and gender matched controls were selected. In multivariate analysis, endophthalmitis was associated with posterior capsular rupture (PCR) during surgery (OR 6.98, 95%CI: 2.22-21.98), phacoemulsification via scleral incision with a foldable intraocular lens (IOL) implantation (OR 3.02, 95%CI: 1.13-8.04) and ocular co-morbidity (OR 2.32, 95%CI: 1.11-4.87). CONCLUSION: PCR, presence of ocular co-morbidity, and phacoemulsification via scleral incision with foldable-IOL were found to be independent risk factors for acute endophthalmitis.

Patients' Perceptions of Trichiasis Surgery: Results from the Partnership for Rapid Elimination of Trachoma (PRET) Surgery Clinical Trial.

PURPOSE: While quality of life surveys have been conducted in trachomatous trichiasis (TT) surgery populations, little is known about patients' perceptions of the surgical experience and outcomes. METHODS: We interviewed a subset of Partnership for the Rapid Elimination of Trachoma (PRET) surgery trial participants 24 months after surgery. Questions focused on current ocular symptoms, perceived daily functioning, physical appearance, and overall perception of surgery. We stratified participants based on surgical outcomes: normal upper eyelid, postoperative TT, or eyelid contour abnormality (ECA) in one or both eyelids. We compared responses between sexes and surgical outcome groups using contingency tables and Fisher's exact tests. RESULTS: A total of 483 individuals participated and 86% were very satisfied with surgery results; 96% reported ocular symptom improvement. Participants with moderate to severe ECA or postoperative TT were more likely to report current ocular problems than those with normal eyelids (46% and 58% vs 34%, respectively; p = 0.01 for each comparison). The most common symptom among participants with moderate to severe postoperative TT was feeling lashes touching (blurred vision was the most common among participants with moderate to severe ECA). Overall, 83% stated surgery improved daily life; participants with ECA were less likely to report improvement than others (p = 0.002). Participants who had moderate or severe postoperative TT were least likely to state that they would undergo repeat surgery (80%), followed by participants with ECA (86%). CONCLUSIONS: Postoperative TT and ECA both reduced satisfaction with surgery, but appeared to influence different aspects of life. Improving surgical outcomes both by reducing recurrence rates and limiting ECAs are essential.