Evaluating Primary Treatment for People with Advanced Glaucoma: Five-Year Results of the Treatment of Advanced Glaucoma Study.

PURPOSE: To determine whether primary trabeculectomy or medical treatment produces better outcomes in terms of quality of life (QoL), clinical effectiveness, and safety in patients with advanced glaucoma. DESIGN: Multicenter randomized controlled trial. PARTICIPANTS: Between June 3, 2014, and May 31, 2017, 453 adults with newly diagnosed advanced open-angle glaucoma in at least 1 eye (Hodapp classification) were recruited from 27 secondary care glaucoma departments in the United Kingdom. Two hundred twenty-seven were allocated to trabeculectomy, and 226 were allocated medical management. METHODS: Participants were randomized on a 1:1 basis to have either mitomycin C-augmented trabeculectomy or escalating medical management with intraocular pressure (IOP)-reducing drops as the primary intervention and were followed up for 5 years. MAIN OUTCOME MEASURES: The primary outcome was vision-specific QoL measured with the 25-item Visual Function Questionnaire (VFQ-25) at 5 years. Secondary outcomes were general health status, glaucoma-related QoL, clinical effectiveness (IOP, visual field, and visual acuity), and safety. RESULTS: At 5 years, the mean ± standard deviation VFQ-25 scores in the trabeculectomy and medication arms were 83.3 ± 15.5 and 81.3 ± 17.5, respectively, and the mean difference was 1.01 (95% confidence interval [CI], -1.99 to 4.00; P = 0.51). The mean IOPs were 12.07 ± 5.18 mmHg and 14.76 ± 4.14 mmHg, respectively, and the mean difference was -2.56 (95% CI, -3.80 to -1.32; P < 0.001). Glaucoma severity measured with visual field mean deviation were -14.30 ± 7.14 dB and -16.74 ± 6.78 dB, respectively, with a mean difference of 1.87 (95% CI, 0.87-2.87 dB; P < 0.001). Safety events occurred in 115 (52.2%) of patients in the trabeculectomy arm and 124 (57.9%) of patients in the medication arm (relative risk, 0.92; 95% CI, 0.72-1.19; P = 0.54). Serious adverse events were rare. CONCLUSIONS: At 5 years, the Treatment of Advanced Glaucoma Study demonstrated that primary trabeculectomy surgery is more effective in lowering IOP and preventing disease progression than primary medical treatment in patients with advanced disease and has a similar safety profile. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Five-Year Outcomes of a Randomized Trial of Treatments for Varicose Veins.

BACKGROUND: Endovenous laser ablation and ultrasound-guided foam sclerotherapy are recommended alternatives to surgery for the treatment of primary varicose veins, but their long-term comparative effectiveness remains uncertain. METHODS: In a randomized, controlled trial involving 798 participants with primary varicose veins at 11 centers in the United Kingdom, we compared the outcomes of laser ablation, foam sclerotherapy, and surgery. Primary outcomes at 5 years were disease-specific quality of life and generic quality of life, as well as cost-effectiveness based on models of expected costs and quality-adjusted life-years (QALYs) gained that used data on participants' treatment costs and scores on the EuroQol EQ-5D questionnaire. RESULTS: Quality-of-life questionnaires were completed by 595 (75%) of the 798 trial participants. After adjustment for baseline scores and other covariates, scores on the Aberdeen Varicose Vein Questionnaire (on which scores range from 0 to 100, with lower scores indicating a better quality of life) were lower among patients who underwent laser ablation or surgery than among those who underwent foam sclerotherapy (effect size [adjusted differences between groups] for laser ablation vs. foam sclerotherapy, -2.86; 95% confidence interval [CI], -4.49 to -1.22; P<0.001; and for surgery vs. foam sclerotherapy, -2.60; 95% CI, -3.99 to -1.22; P<0.001). Generic quality-of-life measures did not differ among treatment groups. At a threshold willingness-to-pay ratio of £20,000 ($28,433 in U.S. dollars) per QALY, 77.2% of the cost-effectiveness model iterations favored laser ablation. In a two-way comparison between foam sclerotherapy and surgery, 54.5% of the model iterations favored surgery. CONCLUSIONS: In a randomized trial of treatments for varicose veins, disease-specific quality of life 5 years after treatment was better after laser ablation or surgery than after foam sclerotherapy. The majority of the probabilistic cost-effectiveness model iterations favored laser ablation at a willingness-to-pay ratio of £20,000 ($28,433) per QALY. (Funded by the National Institute for Health Research; CLASS Current Controlled Trials number, ISRCTN51995477.).

Barriers and enablers to diabetic eye screening attendance: An interview study with young adults with type 1 diabetes.

AIM: The aim of this study was to identify barriers and enablers of diabetic eye screening (DES) attendance amongst young adults with diabetes living in the United Kingdom. METHODS: Semistructured qualitative interviews with adults aged 18-34 years with diabetes. Participants were purposively sampled to aim for representation across gender, geographical locations, diabetes type, years since diabetes diagnosis and patterns of attendance (i.e. regular attenders, occasional non-attenders, regular non-attenders). Data were collected and analysed using the Theoretical Domains Framework (TDF) to explore potential individual, sociocultural and environmental influences on attendance. Data were analysed using a combined deductive and inductive thematic analysis approach. Barriers/enablers were mapped to behaviour change techniques (BCTs) to identify potential strategies to increase attendance. RESULTS: Key barriers to attendance reported by the sample of 29 study participants with type 1 diabetes, fell within the TDF domains: [Knowledge] (e.g. not understanding reasons for attending DES or treatments available if diabetic retinopathy is detected), [Social Influences] (e.g. lack of support following DES results), [Social role and Identity] (e.g. not knowing other people their age with diabetes, feeling 'isolated' and being reluctant to disclose their diabetes) and [Environmental Context and Resources] (e.g. lack of appointment flexibility and options for rescheduling). Enablers included: [Social Influences] (e.g. support of family/diabetes team), [Goals] (e.g. DES regarded as 'high priority'). Many of the reported barriers/enablers were consistent across groups. Potential BCTs to support attendance include Instructions on how to perform the behaviour; Information about health consequences; Social support (practical) and Social comparison. CONCLUSIONS: Attendance to diabetic eye screening in young adults is influenced by a complex set of interacting factors. Identification of potentially modifiable target behaviours provides a basis for designing more effective, tailored interventions to help young adults regularly attend eye screening and prevent avoidable vision loss.

Effect of Corneal Cross-linking versus Standard Care on Keratoconus Progression in Young Patients: The KERALINK Randomized Controlled Trial.

PURPOSE: To examine the efficacy and safety of corneal cross-linking (CXL) for stabilization of progressive keratoconus. DESIGN: Observer-masked, randomized, controlled, parallel-group superiority trial. PARTICIPANTS: Sixty participants 10 to 16 years of age with progressive keratoconus, one eye of each deemed the study eye. METHODS: The study eye was randomized to either CXL plus standard care or standard care alone, with spectacle or contact lens correction as necessary for vision. MAIN OUTCOME MEASURES: The primary outcome was steep keratometry (K2) in the study eye as a measure of the steepness of the cornea at 18 months. Secondary outcomes included keratoconus progression defined as a 1.5-diopter (D) increase in K2, visual acuity, keratoconus apex corneal thickness, and quality of life. RESULTS: Of 60 participants, 30 were randomized to CXL and standard care groups. Of these, 30 patients in the CXL group and 28 patients in the standard care group were analyzed. Mean K2 in the study eye 18 months after randomization was 49.7 D (standard deviation [SD], 3.8 D) in the CXL group and 53.4 D (SD, 5.8 D) in the standard care group. The adjusted mean difference in K2 in the study eye was -3.0 D (95% confidence interval [CI], -4.9 to -1.1 D; P = 0.002), favoring CXL. Adjusted differences between groups in uncorrected and corrected vision favored eyes receiving CXL: -0.31 logarithm of the minimum angle of resolution (logMAR; 95% CI, -0.50 to -0.11 logMAR; P = 0.002) and -0.51 logMAR (95% CI, -1.37 to 0.35 logMAR; P = 0.002). Keratoconus progression in the study eye occurred in 2 patients (7%) randomized to CXL compared with 12 patients (43%) randomized to standard care. The unadjusted odds ratio suggests that on average, patients in the CXL arm had 90% (odds ratio, 0.1; 95% CI, 0.02-0.48; P = 0.004) lower odds of experiencing progression compared with those receiving standard care. CONCLUSIONS: CXL arrests progression of keratoconus in the majority of young patients. CXL should be considered as a first-line treatment in progressive disease. If the arrest of keratoconus progression induced by CXL is sustained in longer follow-up, particular benefit may be derived from avoiding a later requirement for contact lens wear or corneal transplantation.

Femtosecond Laser-Assisted Cataract Surgery Versus Phacoemulsification Cataract Surgery (FACT): A Randomized Noninferiority Trial.

PURPOSE: To report the 3-month results of a randomized trial (Femtosecond Laser-Assisted Cataract Trial [FACT]) comparing femtosecond laser-assisted cataract surgery (FLACS) with standard phacoemulsification cataract surgery (PCS). DESIGN: Multicenter, randomized controlled trial funded by the UK National Institute of Health Research (HTA 13/04/46/). PARTICIPANTS: Seven hundred eighty-five patients with age-related cataract. METHODS: This trial took place in 3 hospitals in the UK National Health Service (NHS). Randomization (1:1) was stratified by site, surgeon, and 1 or both eyes eligible using a secure web-based system. Postoperative assessments were masked to the allocated intervention. The primary outcome was unaided distance visual acuity (UDVA) in the study eye at 3 months. Secondary outcomes included corrected distance visual acuity, complications, and patient-reported outcomes measures. The noninferiority margin was 0.1 logarithm of the minimum angle of resolution (logMAR). ISRCTN.com registry, number ISRCTN77602616. MAIN OUTCOME MEASURES: We enrolled 785 participants between May 2015 and September 2017 and randomly assigned 392 to FLACS and 393 to PCS. At 3 months postoperatively, mean UDVA difference between treatment arms was -0.01 logMAR (-0.05 to 0.03), and mean corrected distance visual acuity difference was -0.01 logMAR (95% confidence interval [CI], -0.05 to 0.02). Seventy-one percent of both FLACS and PCS cases were within ±0.5 diopters (D) of the refractive target, and 93% of FLACS and 92% of PCS cases were within ±1.0 D. There were 2 posterior capsule tears in the PCS arm and none in the FLACS arm. There were no significant differences between arms for any secondary outcome. CONCLUSIONS: Femtosecond laser-assisted cataract surgery is not inferior to conventional PCS surgery 3 months after surgery. Both methods are as good in terms of vision, patient-reported health, and safety outcomes at 3 months. Longer-term outcomes of the clinical effectiveness and cost-effectiveness are awaited.

Incidence of idiopathic intracranial hypertension in Fife.

BACKGROUND AND AIMS: Idiopathic intracranial hypertension is a clinical syndrome of intracranial hypertension with normal cerebrospinal fluid in the absence of a mass lesion or hydrocephalus on brain imaging. Headache is the most common symptom of idiopathic intracranial hypertension, and about 10-15% of patients suffer from irreversible visual impairment. Previous estimates of the annual incidence of idiopathic intracranial hypertension vary worldwide from 0.03 to 2.2 per 100,000. The major risk factor implicated in idiopathic intracranial hypertension is body mass. Scotland has one of the worst records for obesity in the developed world, and the prevalence of obesity in Fife is higher than the Scottish average. Our aim was to record the incidence of idiopathic intracranial hypertension in NHS Fife over a one-year period. METHODS AND RESULTS: Prospective study including every patient who was seen in the ophthalmology department in NHS Fife with a new diagnosis of idiopathic intracranial hypertension over a one-year period. Thirteen patients were seen with a new diagnosis of idiopathic intracranial hypertension from August 2013 to July 2014 giving an incidence of 3.56 per 100,000. Headache was the most common presenting symptom. Three patients were asymptomatic but were noted to have swollen optic discs during a routine sight test. One patient complained of visual symptoms. All patients were overweight. The mean BMI was 36 (range: 28-49). CONCLUSION: The incidence of idiopathic intracranial hypertension in NHS Fife was significantly higher than previous estimates in the literature. This is probably due to a high level of obesity in Fife. Scotland is in the midst of an obesity epidemic and if this continues we may see increasing levels of idiopathic intracranial hypertension nationally with associated increasing incidence of visual impairment in young adults.

Interventions to increase attendance for diabetic retinopathy screening.

BACKGROUND: Despite evidence supporting the effectiveness of diabetic retinopathy screening (DRS) in reducing the risk of sight loss, attendance for screening is consistently below recommended levels. OBJECTIVES: The primary objective of the review was to assess the effectiveness of quality improvement (QI) interventions that seek to increase attendance for DRS in people with type 1 and type 2 diabetes.Secondary objectives were:To use validated taxonomies of QI intervention strategies and behaviour change techniques (BCTs) to code the description of interventions in the included studies and determine whether interventions that include particular QI strategies or component BCTs are more effective in increasing screening attendance;To explore heterogeneity in effect size within and between studies to identify potential explanatory factors for variability in effect size;To explore differential effects in subgroups to provide information on how equity of screening attendance could be improved;To critically appraise and summarise current evidence on the resource use, costs and cost effectiveness. SEARCH METHODS: We searched the Cochrane Library, MEDLINE, Embase, PsycINFO, Web of Science, ProQuest Family Health, OpenGrey, the ISRCTN, ClinicalTrials.gov, and the WHO ICTRP to identify randomised controlled trials (RCTs) that were designed to improve attendance for DRS or were evaluating general quality improvement (QI) strategies for diabetes care and reported the effect of the intervention on DRS attendance. We searched the resources on 13 February 2017. We did not use any date or language restrictions in the searches. SELECTION CRITERIA: We included RCTs that compared any QI intervention to usual care or a more intensive (stepped) intervention versus a less intensive intervention. DATA COLLECTION AND ANALYSIS: We coded the QI strategy using a modification of the taxonomy developed by Cochrane Effective Practice and Organisation of Care (EPOC) and BCTs using the BCT Taxonomy version 1 (BCTTv1). We used Place of residence, Race/ethnicity/culture/language, Occupation, Gender/sex, Religion, Education, Socioeconomic status, and Social capital (PROGRESS) elements to describe the characteristics of participants in the included studies that could have an impact on equity of access to health services.Two review authors independently extracted data. One review author entered the data into Review Manager 5 and a second review author checked them. Two review authors independently assessed risks of bias in the included studies and extracted data. We rated certainty of evidence using GRADE. MAIN RESULTS: We included 66 RCTs conducted predominantly (62%) in the USA. Overall we judged the trials to be at low or unclear risk of bias. QI strategies were multifaceted and targeted patients, healthcare professionals or healthcare systems. Fifty-six studies (329,164 participants) compared intervention versus usual care (median duration of follow-up 12 months). Overall, DRS attendance increased by 12% (risk difference (RD) 0.12, 95% confidence interval (CI) 0.10 to 0.14; low-certainty evidence) compared with usual care, with substantial heterogeneity in effect size. Both DRS-targeted (RD 0.17, 95% CI 0.11 to 0.22) and general QI interventions (RD 0.12, 95% CI 0.09 to 0.15) were effective, particularly where baseline DRS attendance was low. All BCT combinations were associated with significant improvements, particularly in those with poor attendance. We found higher effect estimates in subgroup analyses for the BCTs 'goal setting (outcome)' (RD 0.26, 95% CI 0.16 to 0.36) and 'feedback on outcomes of behaviour' (RD 0.22, 95% CI 0.15 to 0.29) in interventions targeting patients, and 'restructuring the social environment' (RD 0.19, 95% CI 0.12 to 0.26) and 'credible source' (RD 0.16, 95% CI 0.08 to 0.24) in interventions targeting healthcare professionals.Ten studies (23,715 participants) compared a more intensive (stepped) intervention versus a less intensive intervention. In these studies DRS attendance increased by 5% (RD 0.05, 95% CI 0.02 to 0.09; moderate-certainty evidence).Fourteen studies reporting any QI intervention compared to usual care included economic outcomes. However, only five of these were full economic evaluations. Overall, we found that there is insufficient evidence to draw robust conclusions about the relative cost effectiveness of the interventions compared to each other or against usual care.With the exception of gender and ethnicity, the characteristics of participants were poorly described in terms of PROGRESS elements. Seventeen studies (25.8%) were conducted in disadvantaged populations. No studies were carried out in low- or middle-income countries. AUTHORS' CONCLUSIONS: The results of this review provide evidence that QI interventions targeting patients, healthcare professionals or the healthcare system are associated with meaningful improvements in DRS attendance compared to usual care. There was no statistically significant difference between interventions specifically aimed at DRS and those which were part of a general QI strategy for improving diabetes care. This is a significant finding, due to the additional benefits of general QI interventions in terms of improving glycaemic control, vascular risk management and screening for other microvascular complications. It is likely that further (but smaller) improvements in DRS attendance can also be achieved by increasing the intensity of a particular QI component or adding further components.

Effectiveness of early lens extraction for the treatment of primary angle-closure glaucoma (EAGLE): a randomised controlled trial.

BACKGROUND: Primary angle-closure glaucoma is a leading cause of irreversible blindness worldwide. In early-stage disease, intraocular pressure is raised without visual loss. Because the crystalline lens has a major mechanistic role, lens extraction might be a useful initial treatment. METHODS: From Jan 8, 2009, to Dec 28, 2011, we enrolled patients from 30 hospital eye services in five countries. Randomisation was done by a web-based application. Patients were assigned to undergo clear-lens extraction or receive standard care with laser peripheral iridotomy and topical medical treatment. Eligible patients were aged 50 years or older, did not have cataracts, and had newly diagnosed primary angle closure with intraocular pressure 30 mm Hg or greater or primary angle-closure glaucoma. The co-primary endpoints were patient-reported health status, intraocular pressure, and incremental cost-effectiveness ratio per quality-adjusted life-year gained 36 months after treatment. Analysis was by intention to treat. This study is registered, number ISRCTN44464607. FINDINGS: Of 419 participants enrolled, 155 had primary angle closure and 263 primary angle-closure glaucoma. 208 were assigned to clear-lens extraction and 211 to standard care, of whom 351 (84%) had complete data on health status and 366 (87%) on intraocular pressure. The mean health status score (0·87 [SD 0·12]), assessed with the European Quality of Life-5 Dimensions questionnaire, was 0·052 higher (95% CI 0·015-0·088, p=0·005) and mean intraocular pressure (16·6 [SD 3·5] mm Hg) 1·18 mm Hg lower (95% CI -1·99 to -0·38, p=0·004) after clear-lens extraction than after standard care. The incremental cost-effectiveness ratio was £14 284 for initial lens extraction versus standard care. Irreversible loss of vision occurred in one participant who underwent clear-lens extraction and three who received standard care. No patients had serious adverse events. INTERPRETATION: Clear-lens extraction showed greater efficacy and was more cost-effective than laser peripheral iridotomy, and should be considered as an option for first-line treatment. FUNDING: Medical Research Council.

A randomized trial comparing treatments for varicose veins.

BACKGROUND: Ultrasound-guided foam sclerotherapy and endovenous laser ablation are widely used alternatives to surgery for the treatment of varicose veins, but their comparative effectiveness and safety remain uncertain. METHODS: In a randomized trial involving 798 participants with primary varicose veins at 11 centers in the United Kingdom, we compared the outcomes of foam, laser, and surgical treatments. Primary outcomes at 6 months were disease-specific quality of life and generic quality of life, as measured on several scales. Secondary outcomes included complications and measures of clinical success. RESULTS: After adjustment for baseline scores and other covariates, the mean disease-specific quality of life was slightly worse after treatment with foam than after surgery (P=0.006) but was similar in the laser and surgery groups. There were no significant differences between the surgery group and the foam or the laser group in measures of generic quality of life. The frequency of procedural complications was similar in the foam group (6%) and the surgery group (7%) but was lower in the laser group (1%) than in the surgery group (P<0.001); the frequency of serious adverse events (approximately 3%) was similar among the groups. Measures of clinical success were similar among the groups, but successful ablation of the main trunks of the saphenous vein was less common in the foam group than in the surgery group (P<0.001). CONCLUSIONS: Quality-of-life measures were generally similar among the study groups, with the exception of a slightly worse disease-specific quality of life in the foam group than in the surgery group. All treatments had similar clinical efficacy, but complications were less frequent after laser treatment and ablation rates were lower after foam treatment. (Funded by the Health Technology Assessment Programme of the National Institute for Health Research; Current Controlled Trials number, ISRCTN51995477.).

Medical expulsive therapy in adults with ureteric colic: a multicentre, randomised, placebo-controlled trial.

BACKGROUND: Meta-analyses of previous randomised controlled trials concluded that the smooth muscle relaxant drugs tamsulosin and nifedipine assisted stone passage for people managed expectantly for ureteric colic, but emphasised the need for high-quality trials with wide inclusion criteria. We aimed to fulfil this need by testing effectiveness of these drugs in a standard clinical care setting. METHODS: For this multicentre, randomised, placebo-controlled trial, we recruited adults (aged 18-65 years) undergoing expectant management for a single ureteric stone identified by CT at 24 UK hospitals. Participants were randomly assigned by a remote randomisation system to tamsulosin 400 µg, nifedipine 30 mg, or placebo taken daily for up to 4 weeks, using an algorithm with centre, stone size (≤5 mm or >5 mm), and stone location (upper, mid, or lower ureter) as minimisation covariates. Participants, clinicians, and trial personnel were masked to treatment assignment. The primary outcome was the proportion of participants who did not need further intervention for stone clearance within 4 weeks of randomisation, analysed in a modified intention-to-treat population defined as all eligible patients for whom we had primary outcome data. This trial is registered with the European Clinical Trials Database, EudraCT number 2010-019469-26, and as an International Standard Randomised Controlled Trial, number 69423238. FINDINGS: Between Jan 11, 2011, and Dec 20, 2013, we randomly assigned 1167 participants, 1136 (97%) of whom were included in the primary analysis (17 were excluded because of ineligibility and 14 participants were lost to follow-up). 303 (80%) of 379 participants in the placebo group did not need further intervention by 4 weeks, compared with 307 (81%) of 378 in the tamsulosin group (adjusted risk difference 1·3% [95% CI -5·7 to 8·3]; p=0·73) and 304 (80%) of 379 in the nifedipine group (0·5% [-5·6 to 6·5]; p=0·88). No difference was noted between active treatment and placebo (p=0·78), or between tamsulosin and nifedipine (p=0·77). Serious adverse events were reported in three participants in the nifedipine group (one had right loin pain, diarrhoea, and vomiting; one had malaise, headache, and chest pain; and one had severe chest pain, difficulty breathing, and left arm pain) and in one participant in the placebo group (headache, dizziness, lightheadedness, and chronic abdominal pain). INTERPRETATION: Tamsulosin 400 µg and nifedipine 30 mg are not effective at decreasing the need for further treatment to achieve stone clearance in 4 weeks for patients with expectantly managed ureteric colic. FUNDING: UK National Institute for Health Research Health Technology Assessment Programme.

Can Automated Imaging for Optic Disc and Retinal Nerve Fiber Layer Analysis Aid Glaucoma Detection?

PURPOSE: To compare the diagnostic performance of automated imaging for glaucoma. DESIGN: Prospective, direct comparison study. PARTICIPANTS: Adults with suspected glaucoma or ocular hypertension referred to hospital eye services in the United Kingdom. METHODS: We evaluated 4 automated imaging test algorithms: the Heidelberg Retinal Tomography (HRT; Heidelberg Engineering, Heidelberg, Germany) glaucoma probability score (GPS), the HRT Moorfields regression analysis (MRA), scanning laser polarimetry (GDx enhanced corneal compensation; Glaucoma Diagnostics (GDx), Carl Zeiss Meditec, Dublin, CA) nerve fiber indicator (NFI), and Spectralis optical coherence tomography (OCT; Heidelberg Engineering) retinal nerve fiber layer (RNFL) classification. We defined abnormal tests as an automated classification of outside normal limits for HRT and OCT or NFI ≥ 56 (GDx). We conducted a sensitivity analysis, using borderline abnormal image classifications. The reference standard was clinical diagnosis by a masked glaucoma expert including standardized clinical assessment and automated perimetry. We analyzed 1 eye per patient (the one with more advanced disease). We also evaluated the performance according to severity and using a combination of 2 technologies. MAIN OUTCOME MEASURES: Sensitivity and specificity, likelihood ratios, diagnostic, odds ratio, and proportion of indeterminate tests. RESULTS: We recruited 955 participants, and 943 were included in the analysis. The average age was 60.5 years (standard deviation, 13.8 years); 51.1% were women. Glaucoma was diagnosed in at least 1 eye in 16.8%; 32% of participants had no glaucoma-related findings. The HRT MRA had the highest sensitivity (87.0%; 95% confidence interval [CI], 80.2%-92.1%), but lowest specificity (63.9%; 95% CI, 60.2%-67.4%); GDx had the lowest sensitivity (35.1%; 95% CI, 27.0%-43.8%), but the highest specificity (97.2%; 95% CI, 95.6%-98.3%). The HRT GPS sensitivity was 81.5% (95% CI, 73.9%-87.6%), and specificity was 67.7% (95% CI, 64.2%-71.2%); OCT sensitivity was 76.9% (95% CI, 69.2%-83.4%), and specificity was 78.5% (95% CI, 75.4%-81.4%). Including only eyes with severe glaucoma, sensitivity increased: HRT MRA, HRT GPS, and OCT would miss 5% of eyes, and GDx would miss 21% of eyes. A combination of 2 different tests did not improve the accuracy substantially. CONCLUSIONS: Automated imaging technologies can aid clinicians in diagnosing glaucoma, but may not replace current strategies because they can miss some cases of severe glaucoma.

A Framework for Developing the Structure of Public Health Economic Models.

BACKGROUND: A conceptual modeling framework is a methodology that assists modelers through the process of developing a model structure. Public health interventions tend to operate in dynamically complex systems. Modeling public health interventions requires broader considerations than clinical ones. Inappropriately simple models may lead to poor validity and credibility, resulting in suboptimal allocation of resources. OBJECTIVE: This article presents the first conceptual modeling framework for public health economic evaluation. METHODS: The framework presented here was informed by literature reviews of the key challenges in public health economic modeling and existing conceptual modeling frameworks; qualitative research to understand the experiences of modelers when developing public health economic models; and piloting a draft version of the framework. RESULTS: The conceptual modeling framework comprises four key principles of good practice and a proposed methodology. The key principles are that 1) a systems approach to modeling should be taken; 2) a documented understanding of the problem is imperative before and alongside developing and justifying the model structure; 3) strong communication with stakeholders and members of the team throughout model development is essential; and 4) a systematic consideration of the determinants of health is central to identifying the key impacts of public health interventions. The methodology consists of four phases: phase A, aligning the framework with the decision-making process; phase B, identifying relevant stakeholders; phase C, understanding the problem; and phase D, developing and justifying the model structure. Key areas for further research involve evaluation of the framework in diverse case studies and the development of methods for modeling individual and social behavior. CONCLUSIONS: This approach could improve the quality of Public Health economic models, supporting efficient allocation of scarce resources.

Optical coherence tomography for the monitoring of neovascular age-related macular degeneration: a systematic review.

TOPIC: To compare the accuracy of optical coherence tomography (OCT) with alternative tests for monitoring neovascular age-related macular degeneration (nAMD) and detecting disease activity among eyes previously treated for this condition. CLINICAL RELEVANCE: Traditionally, fundus fluorescein angiography (FFA) has been considered the reference standard to detect nAMD activity, but FFA is costly and invasive. Replacement of FFA by OCT can be justified if there is a substantial agreement between tests. METHODS: Systematic review and meta-analysis. The index test was OCT. The comparator tests were visual acuity, clinical evaluation (slit lamp), Amsler chart, color fundus photographs, infrared reflectance, red-free images and blue reflectance, fundus autofluorescence imaging, indocyanine green angiography (ICGA), preferential hyperacuity perimetry, and microperimetry. We searched the following databases: MEDLINE, MEDLINE In-Process, EMBASE, Biosis, Science Citation Index, the Cochrane Library, Database of Abstracts of Reviews of Effects, MEDION, and the Health Technology Assessment database. The last literature search was conducted in March 2013. We used the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) to assess risk of bias. RESULTS: We included 8 studies involving more than 400 participants. Seven reported the performance of OCT (3 time-domain [TD] OCT, 3 spectral-domain [SD] OCT, 1 both types) and 1 reported the performance of ICGA in the detection of nAMD activity. We did not find studies directly comparing tests in the same population. The pooled sensitivity and specificity of TD OCT and SD OCT for detecting active nAMD was 85% (95% confidence interval [CI], 72%-93%) and 48% (95% CI, 30%-67%), respectively. One study reported ICGA with sensitivity of 75.9% and specificity of 88.0% for the detection of active nAMD. Half of the studies were considered to have a high risk of bias. CONCLUSIONS: There is substantial disagreement between OCT and FFA findings in detecting active disease in patients with nAMD who are being monitored. Both methods may be needed to monitor patients comprehensively with nAMD.

Vitrectomy with internal limiting membrane peeling versus no peeling for idiopathic full-thickness macular hole.

OBJECTIVE: To determine whether internal limiting membrane (ILM) peeling improves anatomic and functional outcomes of full-thickness macular hole (FTMH) surgery when compared with the no-peeling technique. DESIGN: Systematic review and individual participant data (IPD) meta-analysis undertaken under the auspices of the Cochrane Eyes and Vision Group. Only randomized controlled trials (RCTs) were included. PARTICIPANTS AND CONTROLS: Patients with idiopathic stage 2, 3, and 4 FTMH undergoing vitrectomy with or without ILM peeling. INTERVENTION: Macular hole surgery, including vitrectomy and gas endotamponade with or without ILM peeling. MAIN OUTCOME MEASURES: Primary outcome was best-corrected distance visual acuity (BCdVA) at 6 months postoperatively. Secondary outcomes were BCdVA at 3 and 12 months; best-corrected near visual acuity (BCnVA) at 3, 6, and 12 months; primary (after a single surgery) and final (after >1 surgery) macular hole closure; need for additional surgical interventions; intraoperative and postoperative complications; patient-reported outcomes (PROs) (EuroQol-5D and Vision Function Questionnaire-25 scores at 6 months); and cost-effectiveness. RESULTS: Four RCTs were identified and included in the review. All RCTs were included in the meta-analysis; IPD were obtained from 3 of the 4 RCTs. No evidence of a difference in BCdVA at 6 months was detected (mean difference, -0.04; 95% confidence interval [CI], -0.12 to 0.03; P=0.27); however, there was evidence of a difference in BCdVA at 3 months favoring ILM peeling (mean difference, -0.09; 95% CI, -0.17 to-0.02; P=0.02). There was evidence of an effect favoring ILM peeling with regard to primary (odds ratio [OR], 9.27; 95% CI, 4.98-17.24; P<0.00001) and final macular hole closure (OR, 3.99; 95% CI, 1.63-9.75; P=0.02) and less requirement for additional surgery (OR, 0.11; 95% CI, 0.05-0.23; P<0.00001), with no evidence of a difference between groups with regard to intraoperative or postoperative complications or PROs. The ILM peeling was found to be highly cost-effective. CONCLUSIONS: Available evidence supports ILM peeling as the treatment of choice for patients with idiopathic stage 2, 3, and 4 FTMH.

Is primary trabeculectomy cost-effective for patients with advanced primary open angle glaucoma? Results from the Treatment of Advanced Glaucoma Study economic model.

BACKGROUND/AIMS: Advanced primary open angle glaucoma (POAG) is a lifelong condition. The aim of this study is to compare medical treatment against trabeculectomy for patients presenting with advanced POAG using an economic evaluation decision model. METHODS: A Markov model was used to compare the two treatments, medical treatment versus trabeculectomy for the management of advanced POAG, in terms of costs and quality-adjusted life-years (QALYs). The uncertainty surrounding the model findings was assessed using probabilistic sensitivity analysis and deterministic analysis. Data for the model came from Treatment of Advanced Glaucoma Study supplemented with data from the literature. The main outcomes of the model presented in terms of Incremental costs and QALYs based on responses to the EQ-5D-5L, Health Utilities Index-3 and a Glaucoma Utility Index. RESULTS: In the base-case analysis (lifetime horizon and EQ-5D-5L measure), participants receiving trabeculectomy had on average, an additional cost of £2687, an additional 0.28 QALYs and an incremental cost per QALY of £9679 compared with medical treatment. There was a 73% likelihood of trabeculectomy being considered cost-effective when society was willing to pay £20 000 for a QALY. Over shorter time horizons, the incremental cost per QALY gained from trabeculectomy compared with medical treatment was higher (47 663) for a 2-year time horizon. Our results are robust to changes in the key assumptions and input parameters values. CONCLUSION: In patients presenting with advanced POAG, trabeculectomy has a higher probability of being cost-effective over a patient's lifetime compared with medical treatment.

Antimicrobial catheters for reduction of symptomatic urinary tract infection in adults requiring short-term catheterisation in hospital: a multicentre randomised controlled trial.

BACKGROUND: Catheter-associated urinary tract infection (CAUTI) is a major preventable cause of harm for patients in hospital. We aimed to establish whether short-term routine use of antimicrobial catheters reduced risk of CAUTI compared with standard polytetrafluoroethylene (PTFE) catheterisation. METHODS: In our parallel, three group, multicentre, randomised controlled superiority trial, we enrolled adults (aged ≥16 years) requiring short-term (≤14 days) catheterisation at 24 hospitals in the UK. Participants were randomly allocated 1:1:1 with a remote computer allocation to receive a silver alloy-coated catheter, a nitrofural-impregnated catheter, or a PTFE-coated catheter (control group). Patients undergoing unplanned catheterisation were also included and consent for participation was obtained retrospectively. Participants and trial staff were unmasked to treatment assignment. Data were collected by trial staff and by patient-reported questionnaires for 6 weeks after randomisation. The primary outcome was incidence of symptomatic urinary tract infection for which an antibiotic was prescribed by 6 weeks. We postulated that a 3·3% absolute reduction in CAUTI would represent sufficient benefit to recommend routine use of antimicrobial catheters. This study is registered, number ISRCTN75198618. FINDINGS: 708 (10%) of 7102 randomly allocated participants were not catheterised, did not confirm consent, or withdrew, and were not included in the primary analyses. Compared with 271 (12·6%) of 2144 participants in the control group, 263 (12·5%) of 2097 participants allocated a silver alloy catheter had the primary outcome (difference -0·1% [95% CI -2·4 to 2·2]), as did 228 (10·6%) of 2153 participants allocated a nitrofural catheter (-2·1% [-4·2 to 0·1]). Rates of catheter-related discomfort were higher in the nitrofural group than they were in the other groups. INTERPRETATION: Silver alloy-coated catheters were not effective for reduction of incidence of symptomatic CAUTI. The reduction we noted in CAUTI associated with nitrofural-impregnated catheters was less than that regarded as clinically important. Routine use of antimicrobial-impregnated catheters is not supported by this trial. FUNDING: UK National Institute for Health Research Health Technology Assessment Programme.

Vitrectomy with internal limiting membrane (ILM) peeling versus vitrectomy with no peeling for idiopathic full-thickness macular hole (FTMH).

BACKGROUND: Several observational studies have suggested the potential benefit of internal limiting membrane (ILM) peeling to treat idiopathic full-thickness macular hole (FTMH). However, no strong evidence is available on the potential benefit(s) of this surgical manoeuvre and uncertainty remains among vitreoretinal surgeons about the indication for peeling the ILM, whether to use it in all cases or in long-standing and/or larger holes.  OBJECTIVES: To determine whether ILM peeling improves anatomical and functional outcomes of macular hole surgery compared with the no-peeling technique and to investigate the impact of different parameters such as presenting vision, stage/size of the hole and duration of symptoms in the success of the surgery. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) which contains the Cochrane Eyes and Vision Group Trials Register (The Cochrane Library 2013, Issue 2), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE, (January 1950 to February 2013), EMBASE (January 1980 to February 2013), Latin American and Caribbean Literature on Health Sciences (LILACS) (January 1982 to February 2013), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov) and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We searched the reference lists of included studies for any additional studies not identified by the electronic searches. We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 28 February 2013.We searched reference lists of the studies included in the review for information about other studies on ILM peeling in macular hole surgery. We searched Proceedings for the following conferences up to February 2013: American Academy of Ophthalmology (AAO), Annual Meeting of the American Society of Retina Specialists (ASRS), Annual Meeting of the Retina Society, Congress of the Asia-Pacific Academy of Ophthalmology (APAO), European Association for Vision and Eye Research (EVER) Annual Congress, European Vitreoretinal Society (EVRS) Annual Meeting, Association for Research in Vision and Ophthalmology (ARVO) Meeting, International Vitreoretinal Meeting, and World Ophthalmology Congress. SELECTION CRITERIA: Only randomised controlled trials (RCTs) comparing ILM peeling with the no-peeling counterpart were included. DATA COLLECTION AND ANALYSIS: Two review authors (KSC and NL) independently assessed the titles and abstracts of all RCTs identified by electronic and manual searches.We obtained Individual patient data (IPD) from three of the four identified eligible trials. The fourth identified RCT had only been published in abstract form and no IPD were available; we included data from this published abstract for one outcome (macular hole closure).The primary outcome was distance visual acuity at six months. Secondary outcomes included distance and near  visual acuity at three and 12 months postoperatively, near visual acuity at six months postoperatively, primary (after a single surgery) and final (following more than one surgery) macular hole closure, need for additional surgical interventions, vision-related quality of life and intraoperative and postoperative complications.We performed meta-analysis using standard techniques (the Mantel-Haenszel odds ratio (OR) for binary outcomes, mean difference (MD) for continuous outcomes) using a fixed-effect model. For two outcomes we also used the IPD to perform adjusted analyses using regression methods. MAIN RESULTS: We identified and included four RCTs; these were conducted in Denmark, France, Hong Kong and the United Kingdom/Republic of Ireland and randomised 47, 80, 49 and 141 participants respectively.There was no evidence of a difference in the primary outcome (distance visual acuity at six months), nor in distance visual acuity at 12 months between randomised groups. However, there was evidence of improved best corrected distance visual acuity in the ILM peeling group at three months (WMD -0.09, 95% CI -0.17 to -0.02). We found no evidence for a difference in near vision between groups at any of the time points investigated.Overall, more participants in the ILM peeling group than in the no-peeling group had primary macular hole closure (OR 9.27, 95% CI 4.98 to 17.24); this held true when results were stratified by the stage of the macular hole. There was also evidence that those in the ILM peeling group were more likely to have final macular hole closure (OR 3.99, 95% CI 1.63 to 9.75). Fewer participants required further surgery in the ILM peeling group than in the no-peeling group (OR 0.11, 95% CI: 0.05 to 0.23).Rates of intraoperative and postoperative complications were similar in both groups.Based on the results of one study, there was no evidence that total VFQ-25 or EQ-5D scores differed between the groups at six months.  Based on this same study, ILM peeling is highly likely to be cost-effective. AUTHORS' CONCLUSIONS: Although we found no evidence of a benefit of ILM peeling in terms of the primary outcome (visual acuity at six months), ILM peeling appears to be superior to its no-peeling counterpart as it offers more favourable cost effectiveness by increasing the likelihood of primary anatomical closure and subsequently decreasing the likelihood of further surgery, with no differences in unwanted side-effects compared with no peeling. 

Theoretical and empirical dimensions of the Aberdeen Glaucoma Questionnaire: a cross sectional survey and principal component analysis.

BACKGROUND: To develop patient-reported outcome instruments, statistical techniques (e.g., principal components analysis; PCA) are used to examine correlations among items and identify interrelated item subsets (empirical factors). However, interpretation and labelling of empirical factors is a subjective process, lacking precision or conceptual basis. We report a novel and reproducible method for mapping between theoretical and empirical factor structures. We illustrate the method using the pilot Aberdeen Glaucoma Questionnaire (AGQ), a new measure of glaucoma-related disability developed using the International Classification of Functioning and Disability (ICF) as a theoretical framework and tested in a sample representing the spectrum of glaucoma severity. METHODS: We used the ICF to code AGQ item content before mailing the AGQ to a UK sample (N = 1349) selected to represent people with a risk factor for glaucoma and people with glaucoma across a range of severity. Reflecting uncertainty in the theoretical framework (items with multiple ICF codes), an exploratory PCA was conducted. The theoretical structure informed our interpretation of the empirical structure and guided the selection of theoretically-derived factor labels. We also explored the discrimination of the AGQ across glaucoma severity groups. RESULTS: 656 (49%) completed questionnaires were returned. The data yielded a 7-factor solution with a simple structure (using cut-off point of a loading of 0.5) that together accounted for 63% of variance in the scores. The mapping process resulted in allocation of the following theoretically-derived factor labels: 1) Seeing Functions: Participation; 2) Moving Around & Communication; 3) Emotional Functions; 4) Walking Around Obstacles; 5) Light; 6) Seeing Functions: Domestic & Social Life; 7) Mobility. Using the seven factor scores as independent variables in a discriminant function analysis, the AGQ scores resulted in correct glaucoma severity grading of 32.5% of participants (p < 0.001). CONCLUSIONS: This paper addresses a methodological gap in the application of classical test theory (CTT) techniques, such as PCA, in instrument development. Labels for empirically-derived factors are often selected intuitively whereas they can inform existing bodies of knowledge if selected on the basis of theoretical construct labels, which are more explicitly defined and which relate to each other in ways that are evidence based.

Predictors of long-term intraocular pressure control after lens extraction in primary angle closure glaucoma: results from the EAGLE trial.

BACKGROUND/AIMS: To assess baseline ocular parameters in the prediction of long-term intraocular pressure (IOP) control after clear lens extraction (CLE) or laser peripheral iridotomy (LPI) in patients with primary angle closure (PAC) disease using data from the Effectiveness of Early Lens Extraction for the treatment of primary angle-closure glaucoma (EAGLE) tria. METHODS: This study is a secondary analysis of EAGLE data where we define the primary outcome of 'good responders' as those with IOP<21 mm Hg without requiring additional surgery and 'optimal responders' as those who in addition were medication free, at 36-month follow-up. Primary analysis was conducted using a multivariate logistic regression model to assess how randomised interventions and ocular parameters predict treatment response. RESULTS: A total of 369 patients (182 in CLE arm and 187 in LPI arm) completed the 36-month follow-up examination. After CLE, 90% met our predefined 'good response' criterion compared with 67% in the LPI arm, and 66% met 'optimal response' criterion compared with 18% in the LPI arm, with significantly longer drops/surgery-free survival time (p<0.05 for all). Patients randomised to CLE (OR=10.1 (6.1 to 16.8)), Chinese (OR=2.3 (1.3 to 3.9)), and those who had not previously used glaucoma drops (OR=2.8 (1.6 to 4.8)) were more likely to maintain long-term optimal IOP response over 36 months. CONCLUSION: Patients with primary angle closure glaucoma/PAC are 10 times more likely to maintain drop-free good IOP control with initial CLE surgery than LPI. Non-Chinese ethnicity, higher baseline IOP and using glaucoma drops prior to randomisation are predictors of worse long-term IOP response.

Systematic review of the agreement of tonometers with Goldmann applanation tonometry.

OBJECTIVE: To assess the agreement of tonometers available for clinical practice with the Goldmann applanation tonometer (GAT), the most commonly accepted reference device. DESIGN: A systematic review and meta-analysis of directly comparative studies assessing the agreement of 1 or more tonometers with the reference tonometer (GAT). PARTICIPANTS: A total of 11 582 participants (15 525 eyes) were included. METHODS: Summary 95% limits of agreement (LoA) were produced for each comparison. MAIN OUTCOME MEASURES: Agreement, recordability, and reliability. RESULTS: A total of 102 studies, including 130 paired comparisons, were included, representing 8 tonometers: dynamic contour tonometer, noncontact tonometer (NCT), ocular response analyzer, Ocuton S, handheld applanation tonometer (HAT), rebound tonometer, transpalpebral tonometer, and Tono-Pen. The agreement (95% limits) seemed to vary across tonometers: 0.2 mmHg (-3.8 to 4.3 mmHg) for the NCT to 2.7 mmHg (-4.1 to 9.6 mmHg) for the Ocuton S. The estimated proportion within 2 mmHg of the GAT ranged from 33% (Ocuton S) to 66% and 59% (NCT and HAT, respectively). Substantial inter- and intraobserver variability were observed for all tonometers. CONCLUSIONS: The NCT and HAT seem to achieve a measurement closest to the GAT. However, there was substantial variability in measurements both within and between studies.