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D-Cycloserine (DCS) is a broad-spectrum antibiotic that is currently FDA-approved to treat tuberculosis (TB) disease and urinary tract infection (UTI). Despite numerous reports showing good clinical efficacy, DCS fell out of favor as a UTI treatment because of its propensity to cause side effects. NRX-101, a fixed-dose combination of DCS and lurasidone, has been awarded Qualified Infectious Disease Product and Fast Track Designation by the FDA. In this study, we tested NRX-101 against the urinary tract pathogens Escherichia coli , Pseudomonas aeruginosa , Klebsiella pneumoniae , and Acinetobacter baumannii in cation-adjusted Mueller-Hinton broth (caMHB) and artificial urine media (AUM). Several strains were multidrug resistant. Test compounds were serially diluted in broth/media. Minimum inhibitory concentration (MIC) was defined as the lowest concentration of the test compound at which no bacterial growth was observed. DCS exhibited antibacterial efficacy against all strains tested while lurasidone did not appreciably affect the antibacterial action of DCS in vitro. In AUM, the MICs ranged from 128 to 512 mcg/mL for both DCS and NRX-101. In caMHB, MICs ranged from 8 to 1024 mcg/mL for NRX-101 and 32 to 512 mcg/mL for DCS alone. Our data confirm that DCS has antibacterial activity against reference and drug-resistant urinary pathogens. Furthermore, lurasidone does not interfere with DCS's antimicrobial action in vitro. These results support the clinical development of NRX-101 as a treatment for complicated urinary tract infections.

Background: We tested the hypothesis that, after initial improvement with intravenous ketamine in patients with bipolar disorder (BD) with severe depression and acute suicidal thinking or behavior, a fixed-dose combination of oral D-cycloserine (DCS) and lurasidone (NRX-101) can maintain improvement more effectively than lurasidone alone., Methods: This was a multi-center, double-blind, twostage, parallel randomized trial. Adult BD patients with depression and suicidal ideation or behavior were infused with ketamine or saline (Stage 1); those who improved were randomized to a fixed-dose combination of DCS and lurasidone vs. lurasidone alone (Stage 2) to maintain the improvement achieved in Stage 1. Depression was measured by the Montgomery Åsberg Depression Rating Scale (MADRS), and suicidal thinking and behavior was measured by the Columbia Suicide Severity Rating Scale (C-SSRS); global improvement was measured by the clinical global severity scale (CGI-S)., Clinicaltrials: gov NCT02974010; Registered: November 22, 2016., Results: Thirty-seven patients were screened and 22 were enrolled, randomized, and treated. All 22 patients treated in Stage 1 (17 with ketamine and 5 with saline) were enrolled into Stage 2, and 11 completed the study. The fixed-dose combination of DCS and lurasidone was significantly more effective than lurasidone alone in maintaining improvement in depression (MADRS LMS Δ-7.7; p = 0.03) and reducing suicidal ideation, as measured by C-SSRS (Δ-1.5; p = 0.02) and by CGI-SS (Δ-2.9; p = 0.03), and with a non-statistically significant decrease in depressive relapse (0% vs. 40%; p = 0.07). This sequential treatment regimen did not cause any significant safety events and demonstrated improvements in patient-reported side effects., Conclusions: Sequential treatment of a single infusion of ketamine followed by NRX-101 maintenance is a promising therapeutic approach for reducing depression and suicidal ideation in patients with bipolar depression who require hospitalization due to acute suicidal ideation and behavior. On the basis of these findings, Breakthrough Therapy Designation was awarded, and a Special Protocol Agreement was granted by the FDA for a registrational trial., (© 2023. Springer-Verlag GmbH Germany, part of Springer Nature.)

Objective: N-methyl-d-aspartate receptor (NMDAR) antagonist antidepressants have known potential for abuse liability. The aim of this study was to evaluate the abuse liability of D-cycloserine (DCS), using a self-administration paradigm in which DCS was tested for its efficacy in substituting for ketamine in ketamine-dependent rats., Methods: A standard intravenous self-administration study was conducted in male adult Sprague-Dawley rats to study abuse liability. Potential for self-administration was assessed in ketamine-habituated subjects. Subjects were trained to press a lever to obtain food, prior to connection of the lever to the intravenous drug administration apparatus. DCS was provided for self-infusion by test subjects at doses of 1.5, 5.0, and 15 mg/kg per lever press., Results: S-ketamine was seen to substitute for ketamine and to result in self-administration at the same frequency. DCS was not seen to result in self-administration at any of the test doses. The self-infusion behavior of DCS was similar to control (saline)., Conclusion: D-cycloserine, a partial agonist of the NMDAR glycine site, which has been shown to have antidepressant and anti-suicidal properties in clinical studies, has no apparent potential for abuse liability in a standard rodent self-administration model., Competing Interests: Declaration of competing interest JCJ owns equity in NRx Pharmaceuticals and derives compensation from NRx pharmaceuticals., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Objectives: Respiratory failure is a lethal complication of COVID-19 that has remained resistant to drug therapy. Vasoactive intestinal peptide (VIP) is shown in nonclinical studies to upregulate surfactant production, inhibit cytokine synthesis, prevent cytopathy, and block replication of the severe acute respiratory syndrome coronavirus 2 virus in pulmonary cells. The study aims to determine whether Aviptadil (synthetic VIP) can improve survival and recovery in patients with COVID-19 respiratory failure compared with placebo and demonstrate biological effects in such patients., Design: A multicenter, placebo-controlled trial., Setting: Ten U.S. hospitals: six tertiary-care hospitals and four community hospitals., Patients: A total of 196 patients with COVID-19 respiratory failure., Interventions: Participants were randomized 2:1 to receive 3 days of IV Aviptadil or placebo., Measurements and Main Results: The primary end point (alive and free from respiratory failure at day 60) did not reach statistical significance (odds ratio [OR], 1.6; 95% CI, 0.86-3.11) for patients treated with Aviptadil when controlling for baseline ventilation status as prespecified in the protocol. There was, however, a statistically significant two-fold odds of improved survival (OR, 2.0; 95% CI, 1.1-3.9) at 60 days ( p = 0.035). There was significant improvement in respiratory distress ratio and reduced interleukin 6 cytokine release ( p = 0.02) by day 3.Subgroup analysis identified a statistically significant likelihood of achieving primary end point among those treated with high-flow nasal oxygen at baseline ( p = 0.039). Subjects on mechanical ventilation also experienced a 10-fold increased odds of survival with drug versus placebo ( p = 0.031)., Conclusions: The primary end point did not reach statistical significance, indicating that there was no difference between Aviptadil versus placebo. However, Aviptadil improves the likelihood of survival from respiratory failure at day 60 in critical COVID-19 across all sites of care. Given the absence of drug-related serious adverse events and acceptable safety profile, we believe the benefit versus risk for the use of Aviptadil is favorable for patient treatment., (Copyright © 2022 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine and Wolters Kluwer Health, Inc.)

Importance: Alcohol-based surgical scrub is recommended for presurgical antisepsis by leading health organizations. Despite this recommendation, water-based scrub techniques remain common practice at many institutions., Objective: To calculate the potential financial savings that a large, subspecialty ophthalmic surgical center can achieve with a conversion to waterless surgical hand preparation., Design, Setting, and Participants: A review of accounting records associated with the purchase of scrubbing materials and water company invoices was conducted to assess direct costs attributable to water consumption and scrub materials for brushless, alcohol-based surgical scrub and water-based presurgical scrub. The flow rate of scrub sinks to estimate water consumption per year was tested. Savings associated with operating room (OR) and personnel time were calculated based on the prescribed scrub times for waterless techniques vs traditional running-water techniques. The study was conducted from January 5 to March 1, 2019., Main Outcomes and Measures: The primary outcomes for this study were the quantity of water consumed by aqueous scrubbing procedures as well as the cost differences between alcohol-based surgical scrub and water-based scrub procedures per OR per year., Results: Scrub sinks consumed 15.9 L of water in a 2-minute period, projecting a savings of 61 631 L and $277 in water and sewer cost per operating room per year. Alcohol-based surgical scrub cost $1083 less than aqueous soap applied from wall-mounted soap dispensers and $271 less than preimpregnated scrub brushes per OR per year in supply costs. The decrease in scrub time from adopting waterless scrub technique could save between approximately $280 000 and $348 000 per OR per year., Conclusions and Relevance: Adopting waterless scrub techniques has the potential for economic savings attributable to water. Savings may be larger for surgical facilities performing more personnel-intensive procedures.

Purpose: To propose the objectives of undergraduate training in direct ophthalmoscopy (DO)., Method: Narrative review of the literature on (i) opinions about the expected proficiency from students in DO, and (ii) estimates of its diagnostic value., Results: (i) Authorities disagree on the proficiency in DO that they expect from students. Textbooks of physical diagnosis differ in their coverage of DO. Surveys have indicated that US physicians expect students to be able to detect optic nerve head abnormalities. The Association of American Medical Colleges expects students to perform ophthalmoscopic examination and describe observations. The International Council of Ophthalmology expects students to recognize also diabetic and hypertensive retinopathies. The Association of University Professors in Ophthalmology requires that students recognize papilloedema, cholesterol emboli, glaucomatous cupping and macular degeneration. (ii) There is evidence that DO, even by ophthalmologists, is inadequate for screening for glaucoma, diabetic and hypertensive retinopathies. Two studies have suggested a limited value of DO in detecting clinical emergencies., Conclusions: The evidence that DO, even by ophthalmologists, is sub-optimal in detecting common abnormalities challenges existing the notions of training medical students. On pending the results of additional studies of the value of DO in detecting emergencies, we suggest that undergraduate teaching of DO should impart the following: (i) an ability to identify the red fundus reflex and optic disc; (ii) an ability to recognize signs of clinical emergencies in patients, mannequins or fundus photographs; and (iii) knowledge about, but not an ability to detect, other retinopathies., (© 2011 The Authors. Acta Ophthalmologica © 2011 Acta Ophthalmologica Scandinavica Foundation.)

Purpose: To assess changes in patient-reported outcomes, satisfaction, vision quality, and visual acuity after bilateral implantation of multifocal intraocular lenses (IOLs) with a 3.00 D addition (add) in cataract patients., Setting: Twelve study centers, United States., Design: Randomized multicenter clinical trial., Methods: In this 6-month trial, cataract patients had bilateral implantation of the AcrySof IQ ReSTOR +3.0 IOL (model SN6AD1). Patient-reported outcomes were collected using the Cataract TyPE questionnaire. Clinical outcomes included uncorrected near (UNVA), uncorrected intermediate (UIVA), and uncorrected distance (UDVA) visual acuities., Results: The study comprised 147 patients. From preoperatively to 6 months postoperatively, the mean UDVA improved from 0.45 logMAR (approximate Snellen, 20/56) to 0.04 logMAR (20/22 Snellen), the mean UIVA from 0.56 logMAR (20/73) to 0.17 logMAR (20/30), and the mean UNVA from 0.62 logMAR (20/83) to 0.10 logMAR (20/25); all improvements were clinically and statistically significant (P<.0001). There was also a statistically significant improvement in patient satisfaction with uncorrected vision (P<.0001). Clinically and statistical significant reductions occurred in trouble with vision (daytime and nighttime), trouble with glare, limitations with UDVA, limitations with UNVA, and limitations in social activities (P<.0001)., Conclusions: Bilateral implantation of multifocal intraocular lenses (IOLs) with a 3.00 D add produced statistically significant and clinically relevant postoperative improvements in UNVA, UIVA, and UDVA. Commensurate significant postoperative improvements were observed in the patient-reported uncorrected functional vision, satisfaction with uncorrected vision, and social activities., (Copyright © 2010 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.)

Purpose of Review: To summarize recent findings implicating toxic agents resulting in photooxidation of cholesterol in the etiology of age-related macular degeneration. Understanding the role of these agents and the existing pathways for their neutralization may lead to novel therapeutic approaches., Recent Findings: The human eye is now known to produce significant quantities of 7-ketocholesterol and related substances as a direct result of photoreceptor function. These substances are highly toxic to retinal cells and the eye has been shown to be unique among human organs in expressing three separate enzymatic pathways that neutralize these agents. Drusen are recently shown to contain significant accumulations of 7-ketocholesterol, likely as a result of failure of these neutralization pathways. In addition to its direct tissue toxicity, which may trigger death of retinal pigment epithelium and photoreceptor cells, ketocholesterol is a potent attractor of macrophages and induces macrophages to express both vascular endothelial growth factor F and metalloproteinases. The role of the former in neovascularization is well understood, whereas the latter is capable of directly inducing breaks in Bruch's membrane., Summary: The toxic role of 7-ketocholesterol and existing pathways for its neutralization may point the way to a unified theory that explains the cause of age-related macular degeneration and points towards novel therapeutic interventions.

Objective: To compare the cost-effectiveness of pegaptanib and usual care within three distinct cohorts of subfoveal neovascular age-related macular degeneration (NV-AMD) patients, that is, those with early, moderate, and late disease, using a comprehensive economic model., Methods: A Markov framework was used to model lifetime movement of a subfoveal NV-AMD cohort through health states based on visual acuity. The model takes a US payer perspective of patients over the age of 65 years. Clinical efficacy was based on published results for the 0.3 mg pegaptanib and usual care groups. Expert interviews were conducted to determine adverse event treatment patterns and vision rehabilitation resource use. Incidence and costs of comorbidities such as depression and fractures associated with the effects of declining visual acuity were based on our previously published analysis of Medicare data. Transition probabilities were derived from published clinical trial data for each 3-month cycle. Utilities were derived from published sources. Three runs of the model were conducted with cohorts of newly diagnosed patients. Patients were classified as having early, moderate, or late NV-AMD defined as visual acuity in the better-seeing eye of 20/40 to more than 20/80, 20/80 to more than 20/200, and 20/200 to more than 20/400, respectively. Costs and outcomes were discounted 3.0% per annum., Results: Incremental costs per vision-year gained and per quality-adjusted life-year (QALY) gained for early NV-AMD patients were approximately one-third those of patients with late disease ($15,279 vs. $57,230 and $36,282 vs. $132,381, respectively). On average, patients treated early with either pegaptanib or usual care incurred lower lifetime total direct costs than those treated later. Sensitivity analysis showed that base-case incremental costs per QALY gained for pegaptanib versus usual care were relatively robust., Conclusions: For patients with subfoveal NV-AMD, treatment with pegaptanib should be started as early as possible to maximize the clinical and economic benefits.

We analyze the effect of a decision support tool designed to help physicians detect and correct medical "missteps". The data comes from a randomized trial of the technology on a population of commercial HMO patients. The key findings are that the new information technology lowers average charges by 6% relative to the control group. This reduction in resource utilization was the result of reduced in-patient charges (and associated professional charges) for the most costly patients. The rate at which identified issues were resolved was generally higher in the study group than in the control group, suggesting the possibility of improvements in care quality along measured dimensions and enhanced diffusion of new protocols based on new clinical evidence.

Purpose: To determine whether comorbidities are more prevalent among individuals with neovascular age-related macular degeneration (NV-AMD) than individuals without AMD., Methods: This 2-year, retrospective, case-control study included Medicare beneficiaries (standard 5% analytic sample) continuously enrolled from January 1, 2003, to December 31, 2004, excluding those in managed care plans. The NV-AMD cohort included individuals >or=65 at baseline with a diagnosis of NV-AMD in 2003 and 2004. Age-, gender-, and race-matched controls were selected from those with no AMD. Comparisons were made for 13 general categories of non-eye-related diseases and 18 specific comorbidities based on ICD-9-CM codes. Two-year prevalence was calculated by condition and cohort; odds ratios and 99% confidence intervals were calculated (logistic regression)., Results: Analyses included 26,057 subjects and an equal number of controls. Nearly all subjects had at least one comorbidity, and >80% in each cohort had five or more comorbidities across general disease categories. Prevalence of 7/13 general disease categories exceeded 50% in both cohorts; rates for 12/13 categories were significantly higher in those with NV-AMD (P < 0.001). Prevalence of 13/14 non-eye-related and 4/4 eye-related specific comorbidities was significantly higher among NV-AMD subjects (P < 0.05). A more than 20% greater odds for NV-AMD subjects was noted for hypertension, hypercholesterolemia, emphysema, chronic obstructive pulmonary disease, atherosclerosis, arthritis, coronary heart disease, cataract, glaucoma, and myopia., Conclusion: Patients with NV-AMD are significantly more likely to have comorbidities, many of which could be life-threatening.

Purpose: To identify the cost to the Medicare program for patients with either stable or progressive vision loss and to estimate the impact on eye-related and non-eye related care., Design: Retrospective cohort study., Participants: The study population was Medicare beneficiaries included in the standard 5% analytic sample and continuously enrolled from 1999 to 2003, excluding Medicare managed-care enrollees., Methods: Vision loss was categorized as moderate loss, severe loss, and blindness, based on International Classification of Diseases 9, Clinical Modification codes., Main Outcome Measures: Average yearly cost of eye-related and non-eye related medical care during 1999 to 2003, in 2003 dollars., Secondary Outcomes: (1) depression, (2) injury, (3) skilled nursing facility (SNF) utilization, and (4) long-term care facility (LTC) admission., Results: Compared with patients with normal vision, excess adjusted mean eye-related costs were 345 dollars, 407 dollars, and 237 dollars annually for those with moderate loss, severe loss, and blindness, respectively; annual excess non-eye related costs were 2193 dollars, 3301 dollars, and 4443 dollars, respectively. At each level of vision loss, those progressing from a presumably normal state at baseline incurred higher Medicare costs than those with that level of vision loss at baseline. Any degree of progressive vision loss was associated with an increased risk of depression, injury, SNF utilization, and LTC admission. Identifiable costs attributable to these complications explained 27% to 41% of the excess costs associated with vision loss., Conclusions: Medicare beneficiaries with coded diagnoses of vision loss incur significantly higher costs than those with normal vision, and approximately 90% of these costs are non-eye related medical costs. Extrapolating to the entire Medicare population, blindness and vision loss are associated with $2.14 billion in 2003 non-eye related medical costs. Preventing vision loss is not only a medical imperative but also an economic one.

Objective: To demonstrate the potential effect of deploying a sentinel system that scans administrative claims information and clinical data to detect and mitigate errors in care and deviations from best medical practices., Methods: Members (n = 39 462; age range, 12-64 years) of a midwestern managed care plan were randomly assigned to an intervention or a control group. The sentinel system was programmed with more than 1000 decision rules that were capable of generating clinical recommendations. Clinical recommendations triggered for subjects in the intervention group were relayed to treating physicians, and those for the control group were deferred to study end., Results: Nine hundred eight clinical recommendations were issued to the intervention group. Among those in both groups who triggered recommendations, there were 19% fewer hospital admissions in the intervention group compared with the control group (P < .001). Charges among those whose recommendations were communicated were dollar 77.91 per member per month (pmpm) lower and paid claims were dollar 68.08 pmpm lower than among controls compared with the baseline values (P = .003 for both). Paid claims for the entire intervention group (with or without recommendations) were dollar 8.07 pmpm lower than those for the entire control group. In contrast, the intervention cost dollar 1.00 pmpm, suggesting an 8-fold return on investment., Conclusion: Ongoing use of a sentinel system to prompt clinically actionable, patient-specific alerts generated from administratively derived clinical data was associated with a reduction in hospitalization, medical costs, and morbidity.

The United States is poised to move the debate over electronic information systems for health care beyond the question of whether to computerize to how to computerize. Developers should heed the experiences of those who have already attempted similar efforts in vertically integrated environments. A key lesson is that the expertise and design perspectives of IT professionals should be supplemented with practical input from the caregivers and administrators who will actually use these systems. The paper by Douglas Bell and colleagues offers a ray of hope, as these authors have begun their process by asking the user community exactly what it needs.

Purpose: To design and validate a survey instrument that measures vision-related functional status, which is appropriate for self-administration in a clinical practice and mail survey setting., Design: Observational, validation study in sequential patients., Methods: A prototype visual function instrument (the Cataract TyPE Spec) was developed based on focus group input and then validated in an outcomes study conducted among 1,823 patients who underwent cataract extraction performed by 22 surgeons at six centers in the United States. Reliability was determined by calculating Cronbach alpha for different types of administration (self-administration at the site of care and mailed survey) and across race and gender. Criterion validity was determined by correlating scores on the TyPE Spec with baseline measures and changes in visual acuity, overall rating of vision, and general quality of life., Results: The instrument was internally valid (Chronbach alpha = 0.94), both on self-administration in the patient care setting and upon mailed survey administration and across patient race and gender. The TyPE Spec score was highly correlated with overall rating of vision (r =.54, P <.0001) and moderately correlated with Snellen acuity (r =.32, P <.0001), rating of vision in the better eye (r =.42, P <.0001), and quality of life, as measured by the physical component summary score of the SF-36 (r =.27, P <.001). Change in TyPE Spec similarly correlated with change in rating of vision overall, change in best-corrected Snellen acuity, and change in rating of vision in the operated eye., Conclusions: The cataract TyPE Spec instrument was found to be equally valid and internally consistent when administered in the patient care setting and by mail survey.

Purpose: To estimate the 3-year incidence of exudative age-related macular degeneration (AMD) and its treatment by laser photocoagulation in elderly Americans., Design: Population-based cohort study using insurance claims data., Participants: A random 5% sample of Medicare beneficiaries, age 65 and older., Methods: Incidence of exudative AMD and of laser photocoagulation for this condition was assessed based on four categories of ascertainment criteria that included procedure and diagnosis codes associated with exudative AMD, choroidal neovascularization, and its treatment., Main Outcome Measures: Incidence of AMD and of associated laser photocoagulation., Results: Overall, the 3-year incidence of exudative AMD is estimated to be between 9.4 per 1000 and 11.4 per 1000 Americans age 65 and older (depending on ascertainment criteria), based on those diagnosed and treated by ophthalmologists for the condition. These estimates bracket the measured incidence of exudative AMD in the Beaver Dam Eye Study and lie within its 95% confidence interval. The 3-year incidence of exudative AMD with attendant laser photocoagulation was 2.3 per 1000. Women were found to have a slightly higher incidence of AMD than men using all ascertainment criteria (P < 0.001), and white Americans were found to have a fivefold-to-sixfold higher ascertainment criteria than black Americans (P < 0.001)., Conclusions: The reported incidence of exudative AMD identified in the population of Medicare beneficiaries suggests that measurements on incidence for this condition derived from the Beaver Dam Eye Study can be generalized to the U.S. population.

Objective: Two million cataract extractions are performed annually in the United States. The procedure is nearly always accompanied by implantation of a monofocal intraocular lens (IOL), which corrects the patient's distance vision. The authors' objective was to measure visual function and quality-of-life outcomes associated with bilateral implantation of a multifocal IOL, which corrects distance and near vision, and to compare the outcomes with those of the standard therapy., Design: A prospective, randomized, double-masked, clinical trial was conducted at eight sites in the United States, seven sites in Germany, and one site in Austria., Participants: Participants included 245 cataract patients, 127 of whom received the multifocal IOL bilaterally and 118 of whom received a monofocal IOL of nearly identical construction bilaterally., Methods: Clinical data included visual acuity (VA), complications, and adverse events. Quality-of-life data were collected using a previously validated survey instrument at baseline, after first eye surgery, and after second eye surgery., Results: At 3 months after surgery, patients who had received multifocal IOLs had significantly better uncorrected and distance corrected binocular near VA compared with patients who had received monofocal IOLs (mean uncorrected VA, 20/26 multifocal vs. 20/40 monofocal; mean distance corrected VA, 20/28 multifocal vs. 20/45 monofocal; P < 0.0001). Additionally, 96% of patients who had received multifocal IOLs and 65% of patients who had received monofocal IOLs achieved both 20/40 and J3 (Jaeger) or better uncorrected, binocular distance and near visual acuities (P < 0. 0001). Patients who had received multifocal IOLs were more likely than patients who had received monofocal IOLs to never wear glasses overall (32% multifocal vs. 8% monofocal; P < 0.0001). On a 4-point scale, patients who had received multifocal IOLs on average reported having between "a little bit" and "some" glare or halo, whereas patients who had received monofocal IOLs reported between "none" and "a little bit" of glare or halo (1.57 vs. 0.43; P < 0.001). Patients who had received multifocal IOLs rated their vision without glasses better overall at near and at intermediate distances (P < or = 0.002) and demonstrated better visual function for near tasks and social activities., Conclusions: Cataract patients who received multifocal IOLs at time of surgery obtained better uncorrected and distance corrected near VA and reported better overall vision, less limitation in visual function, less spectacle dependency, and more glare or halo than those who received traditional monofocal IOLs.

Purpose: To compare the clinical success rates and quality of life impact of brimonidine 0.2% with timolol 0.5% in newly diagnosed patients naive to glaucoma therapy., Methods: A prospective, multicenter, randomized, double-masked, clinical effectiveness trial in which the clinical outcomes of twice daily brimonidine tartrate 0.2% were compared with those of timolol maleate 0.5% in patients with glaucoma and' ocular hypertension was conducted. Two hundred nineteen patients were enrolled--111 in the brimonidine group and 108 in the timolol group. Patients instilled their study medications twice daily for 4 months. Factors for determining clinical success were reduction of intraocular pressure (IOP), safety, and adverse events. Quality of life effects were assessed with the SF-36 Health Survey and Glaucoma Disability Index questionnaires., Results: Clinical success was 71% (75/106) with brimonidine and 70% (73/105) with timolol as initial treatment. The overall mean decrease in IOP was 6.5 mm Hg with brimonidine and 6.2 mm Hg with timolol. Few patients reported a specific adverse event and, with the exception of a slightly higher rate of ocular burning and stinging in the brimonidine group, there were no significant between-group differences. No significant chronotropic effects on the heart were seen with brimonidine, while small but significant mean decreases in heart rate were seen at months 1 and 4 with timolol. Mean systolic and diastolic blood pressure remained relatively stable in both groups. Quality of life remained stable, with no significant between-group differences., Conclusions: As a first-line agent for the treatment of glaucoma and ocular hypertension, brimonidine has clinical effectiveness equivalent to timolol, but with less chronotropic effect on the heart. Brimonidine is a viable alternative to timolol for first-line therapy in glaucoma and ocular hypertension.

To assess how preference values that cataract surgery patients assign to their preoperative visual states relate to visual acuity and problems in specific aspects of daily life, the authors interviewed 47 patients scheduled to have cataract surgery. Using a rating-scale technique with a scale from 0 (death) to 1 (excellent health), the patients had a mean preference value of 0.68 for their preoperative vision. Patients' preference values for their preoperative vision were more closely related to problems in specific aspects of daily life (especially feelings of depression and problems interacting with people) than to visual acuity in the operative eye, better eye, or worse eye, or a weighted average of visual acuities in both eyes. These results provide a rationale for relying more on patients' views about the effects of visual impairment than on measures of visual acuity when assessing the need for cataract surgery.

Purpose: To identify the location of barriers to treatment for glaucoma and cataract among African-American Medicare beneficiaries., Methods: We examined the receipt of eye care in general and care for glaucoma and cataract in particular among black and white Medicare beneficiaries using 1991 Medicare physician claims data. Racial differences in treatment for glaucoma and cataract were examined both for the Medicare population as a whole and for identified eye care users. The results were compared to the expected value of black-white difference based on population prevalence data for each specific condition., Results: Thirty percent of black beneficiaries and 45% of white Medicare beneficiaries used eye care services in 1991. After adjusting for the expected difference in prevalence, black beneficiaries were half as likely to be surgically treated for glaucoma compared to white beneficiaries, and 80% as likely for cataract. When the analysis was restricted to those using eye care services, blacks continued to have lower than expected rates of treatment for glaucoma (observed RR = 3.2, 95% confidence interval = 3.1-3.4 vs an expected RR of 4.3, 95% confidence interval = 3.5-5.4), but a higher rate of treatment for cataract (RR = 1.2, 95% confidence interval = 1.2-1.3). Among those with physician-diagnosed glaucoma and cataract, blacks were more likely to undergo surgical treatment for these conditions than whites (RR = 1.5 for glaucoma, 95% confidence interval = 1.4-1.5; RR = 1.2 for cataract, 95% confidence interval = 1.2-1.3)., Conclusion: Barriers to treatment for glaucoma and cataract among black Medicare beneficiaries involve primarily limitations in access to the eye care system. The undertreatment for glaucoma among black beneficiaries was reduced, but not eliminated, after removing the effect of unequal access to the eye care system.

Objective: The authors measured functional status after bilateral implantation of a multifocal versus a monofocal intraocular lens (IOL)., Methods: A retrospective, case-control study was done on 100 subjects implanted bilaterally with a silicone-optic foldable zonal progressive IOL under United States Food and Drug Administration Investigational Device Exemption protocol and 103 control subjects implanted bilaterally with a monofocal IOL of similar design who were matched on age and postoperative corrected distance acuity. The Cataract TyPE specification, a 17-item functional status instrument, was modified, validated, and administered via telephone interview. The measures of vision, functional status, and quality of life were compared between patients and controls., Results: The instrument was valid (Cronbach's alpha = 0.94) and correlated moderately (Pearson's r= 0.34) with Snellen acuity. Multifocal subjects were more likely than monofocal controls to never wear spectacles (41% vs. 11.7%; P < 0.001). Multifocal subjects rated their vision without spectacles significantly better than those with monofocal IOLs (9.0 vs. 7.9; P < 0.001). The difference was most significant in rating of near vision without spectacles (7.8 vs. 5.0; P < 0.001). Multifocal subjects reported less limitation in specific visual tasks without spectacles (0.3 vs. 0.8; P < 0.001, where 1.0 represents "slightly" limited). This difference was consistently observed in subscales related to distance vision activities (0.1 vs. 0.4; P < 0.001), near vision activities (0.6 vs. 1.4; P < 0.001), and social activities (0.1 vs. 0.6; P < 0.001)., Conclusions: In this study, subjects with bilateral multifocal IOLs reported better overall vision, less limitation in visual function, and less spectacle usage than monofocal controls.

Aim: To estimate risk of infectious endophthalmitis after cataract extraction in Denmark and to compare results with the risk of this complication in the USA., Methods: In the national Danish administrative hospital register, 19,426 patients were identified who underwent first eye cataract surgery from 1985 to 1987 and who were 50 years of age or older. Of these, 61 patients had postoperative endophthalmitis., Results: A 12 month cumulative risk of rehospitalisation for endophthalmitis was estimated at 0.18% (95% CI 0.09-0.26) after extracapsular cataract extraction with lens implant. Advanced age, male sex, intracapsular cataract extraction, and anterior vitrectomy were all associated independently with an increased risk of postoperative endophthalmitis. When restricting the sample to patients aged 65 years or older, in order to allow comparisons to be made with the US National Study of Cataract Outcomes, a 12 month risk of 0.17% (95% CI 0.08-0.25) was estimated. The previously reported US risk of 0.12% is included in the confidence interval of the risk estimated in the Danish sample., Conclusion: Despite considerable differences in the healthcare systems, no statistically significant difference in outcome of surgery as measured by risk of endophthalmitis was shown between Denmark and the USA.

Purpose: The purpose of the study is to understand current pattern of eye care use among people with diabetes., Methods: Study population included 175,015 Medicare beneficiaries who had physician-diagnosed diabetes. The authors estimated overall rate of eye care visits among these beneficiaries in 1992 and 1993 using Medicare physician claims data. In combination of Area Resource File, the authors examined association of eye care use with demographic characteristics, regional socio-economic characteristics, and regional eye care provider supply., Results: Fifty-three percent of the population had at least 1 eye care visit in a 1-year period and 67% in a 2-year period. Younger age (ages < 75 years), male gender, black race, high regional poverty, and fewer ophthalmologist supply were related to lower rate of eye care use. There was no association between eye care use and regional education level and optometrist supply., Conclusion: The findings suggest that a large portion of elderly people with diabetes is not obtaining the necessary eye care, especially blacks, men, and those residing in poor areas with fewer ophthalmologists.

Objective: To evaluate the association between cataract extraction and atherosclerosis and its complications., Design: A nationwide case-control study., Setting and Participants: Using a 5% random sample of all Medicare beneficiaries, we analyzed Medicare claims data on 60803 persons 65 years of age and older who underwent cataract extraction in 1986 or 1987 and a control group of 63765 persons matched to the cases for age, race, sex, ZIP code, and reason for Medicare entitlement., Main Outcome Measure: Atherosclerosis and atherosclerosis-related disease and procedures were defined by International Classification of Diseases, Ninth Revision, Clinical Modification, codes or by Health Care Financing Administration Common Procedure Classification System (Current Procedural Terminology) codes. The strength of evidence for atherosclerotic disease was categorized on the basis of the types of bills in the Medicare claims file., Results: Odds of atherosclerosis-related morbidity and procedures were higher for cases than for controls. The association decreased with patient age and was strongest in beneficiaries aged 65 to 69 years (odds ratio, 1.30; 95% confidence interval, 1.13-1.48)., Conclusion: Our findings suggest that there is a weak association between a visually significant cataract requiring surgery and atherosclerosis in the younger elderly.

Purpose: Previous analyses of Medicare claims data, as well as clinical series, have suggested that performance of neodymium:YAG (Nd:YAG) laser posterior capsulotomy after extracapsular cataract surgery increases significantly the risk of retinal detachment. However, methodologic problems with previous research limit the strength of conclusions that can be drawn from these earlier studies. This study was designed to resolve those methodological limitations while using a population-based approach for assessment of the independent association between the performance of Nd:YAG laser posterior capsulotomy and pseudophakic retinal detachment., Methods: A nested case-control study was conducted. Medicare beneficiaries who had undergone extracapsular cataract extraction from 1988 to 1990 were identified from a 5% sample of Medicare claims data. Within this cohort, people who were diagnosed or treated for retinal detachment during the years 1988 through 1991 (cases) were identified from Medicare records. Four controls were matched to each case of retinal detachment using an incidence density design. Providers of the patients' cataract and retinal surgery were contacted and asked to provide clinical data for all cases and controls that they had treated., Results: Seven hundred six cases of retinal detachment were originally identified from Medicare records. After exclusions due to ineligibility, a total of 291 cases and 870 matched controls were available for analysis. Conditional logistic regression models showed that a number of factors were associated independently with an excess risk of retinal detachment after cataract surgery. These included Nd:YAG laser capsulotomy (odds ratio [OR] = 3.8; 95% confidence interval [CI], 2.4-5.9), a history of retinal detachment (OR = 2.7; 95% CI, 1.2-6.1), a history of lattice degeneration (OR = 6.6; 95% CI, 1.6-27.1), axial length (OR = 1.21/mm; 95% CI, 1.03-1.43), refractive error (OR = 0.92/diopter; 95% CI, 0.88-0.95), and a history of ocular trauma after cataract surgery (OR = 6.1; 95% CI, 4.3-28.2)., Conclusion: Performance of Nd:YAG laser posterior capsulotomy is associated with a significantly elevated risk of retinal detachment in patients who have undergone extracapsular cataract extraction. Other independent risk factors for retinal detachment include axial length, myopia, posterior capsular rupture during surgery, history of retinal detachment or lattice degeneration, and ocular trauma after cataract surgery.

Objectives: To assess the frequency and content of post-operative examinations by ophthalmologists and optometrists for cataract surgery patients without operative complications and to assess the referral patterns of optometrists when complications are identified., Design: In 1992 we conducted a survey of randomly selected members of the American Academy of Ophthalmology and American Optometric Association. Responses were obtained from 538 (82%) of 655 eligible ophthalmologists and 130 (84%) of 154 eligible optometrists., Results: Eighty-eight percent of responding ophthalmologists reported that patients had 4 or more visits within 4 months after surgery, 97% of ophthalmologists performed the first postoperative examination on their cataract surgery patients, and 60% of ophthalmologists reported that no other eye professional saw their patients postoperatively. Forty-six percent of responding optometrists participated in postoperative care of cataract surgery patients, and usually performed their first postoperative examination 7 days after surgery; 78% of these optometrists reported that they saw patients 3 or more times after surgery. Postoperatively, 83% of ophthalmologists and 75% of optometrists usually performed at least 1 dilated fundus examination, 87% of ophthalmologists and 47% of optometrists performed 4 or more slit-lamp examinations, 74% of ophthalmologists and 42% of optometrists performed 4 or more tonometry tests, and 83% of both groups performed 2 or more refractions. More than 80% of responding optometrists involved in postoperative care of cataract surgery patients immediately refer a patient to an ophthalmologist if there is evidence of acute glaucoma or an unexplained decrease in vision in the eye that was operated on. For less urgent complications, most optometrists promptly make a referral to an ophthalmologist., Conclusions: In 1992, a small percentage of ophthalmologists and optometrists were performing fewer follow-up examinations and tests for cataract patients than recommended by the American Academy of Ophthalmology. Not all optometrists immediately refer to an ophthalmologist any acute complication that they identify postoperatively.

Aims: To estimate the risk of retinal detachment (RD) following cataract extraction in Denmark, and to compare the risk with that following cataract extraction in the USA, and with that in a sample of Danish patients who did not have ocular surgery., Methods: A sample was created from the administrative Danish Hospital Register and included 19,252 patients who underwent first eye cataract surgery between 1985 and 1987, and who were 50 years of age or older. The patients were then followed for 4-6 years using the register data. The design and definition of events were identical to the US National Study of Cataract Outcomes., Results: In Denmark a 4 year cumulative risk of hospitalisation for RD of 0.93% (95% confidence interval (CI) 0.71-1.16) was observed following an extracapsular cataract extraction with a lens implant. A similar cumulative risk of RD was reported from the US study. Thus, no difference in outcomes concerning risk of RD was shown between Denmark and the USA. In a multivariate analysis younger age, male sex, and intracapsular cataract extraction were all associated with higher risk of postoperative RD. A reference group of 7636 people not undergoing any ocular surgery was created and the incidence of RD in this group was calculated. During the sixth year following cataract surgery, the incidence of RD in the cataract group was still 7.5 (95% CI 1.6-22.0) times higher than that observed in the reference group.

Background and Objective: To examine the change in volume and costs of physician services for ophthalmic surgical procedures associated with physician fee cuts., Materials and Methods: The authors analyzed the physician claims (Part B) data for a 5% random sample of the Medicare population. Number, rate, average allowed charge, and total cost of physician services for ophthalmic surgical procedures were compared for 1988 and 1991., Results: An estimated 3.1 million (98 per 1000) ophthalmic surgical procedures were performed on Medicare beneficiaries in 1991, compared with 2.3 million (76 per 1000) in 1988. There was a 35% increase in number and a 28% increase in rate. The average allowed charge for these services decreased by 26% ($1155 vs $852 per procedure), with an overall cost of $2.6 billion in both years., Conclusion: A reduction in fee for physician services for ophthalmic surgical procedures from 1988 to 1991 was associated with an increase in the volume of the services. The overall costs of physician services for ophthalmic surgical procedures remained consistent between the two years.

Cataract is the leading cause of blindness, accounting for 50% of blindness worldwide. Although significant progress has been made toward identifying risk factors for cataract, there is no proven primary prevention or medical treatment. Surgical removal of cataract remains the only therapy. In this paper, we reviewed (a) the prevalence and incidence data of cataract, (b) the findings on risk factors for cataract, and (c) health service utilization and outcome of cataract surgery in both developed and developing countries.

Objective: To determine, from the health insurer's perspective, the cost of preventing vision loss in patients with diabetes mellitus through ophthalmologic screening and treatment and to calculate the cost-effectiveness of these interventions as compared with that of other medical interventions., Design: Computer modeling, incorporating data from population-based epidemiologic studies and multicenter clinical trials. Monte Carlo simulation was used, combined with sensitivity analysis and present value analysis of cost savings., Results: Screening and treatment of eye disease in patients with diabetes mellitus costs $3190 per quality-adjusted life-year (QALY) saved. This average cost is a weighted average (based on prevalence disease) of the cost-effectiveness of detecting and treating diabetic eye disease in those with insulin-dependent diabetes mellitus ($1996 per QALY), those with non-insulin-dependent diabetes mellitus (NIDDM) who use insulin for glycemic control ($2933 per QALY), and those with NIDDM who do not use insulin for glycemic control ($3530 per QALY)., Conclusions: Our analysis indicates that prevention programs aimed at improving eye care for diabetic persons not only result in substantial federal budgetary savings but are highly cost-effective health investments for society. Ophthalmologic screening for diabetic persons is more cost-effective than many routinely provided health interventions. Because diabetic eye disease is the leading cause of new cases of blindness among working-age Americans, these results support the widespread use of screening and treatment for diabetic eye disease.