Systematic methodological review of health state values in glaucoma cost-utility analyses.

IMPORTANCE: Describing the characteristics and sources of health state utility values and reporting practice in the literature of cost-utility analyses facilitates an understanding of the level of the transparency, validity, and generalizability of cost-utility analyses. Improving the quality of reporting will support investigators in describing the incremental value of emerging glaucoma interventions. OBJECTIVE: To describe the state of practice among published glaucoma cost-utility analysis studies, focusing on valuation of health and the quality of reporting. EVIDENCE REVIEW: We searched several databases including Medline, CINHAL, Embase, Web of Science, Scopus, Biosis previews, the Health Economic Evaluations Database, and the NHS Economic Evaluation Database (NHS EED). We included full-text, English, published cost-utility analyses of glaucoma interventions with quality-adjusted life years (QALYs) as the primary outcome measure to calculate incremental cost-utility ratios. Excluded studies were non-English language, reviews, editorials, protocols, or other types of economic studies (cost-benefit, cost-minimization, cost-effectiveness). Study characteristics, operational definitions of glaucoma health states and health state utilities were extracted. The original source of the health utility was reviewed to determine the scale of measurement and the source of preference weighting. Items from the Systematic Review of Utilities for Cost-Effectiveness (SpRUCE checklist) were used to assess the reporting and quality of health utilities in glaucoma CUA. FINDINGS: 43 CUAs were included, with 11 unique sources of health utilities. A wide range of health utilities for the same Hodapp-Parrish-Anderson glaucoma health states were reported; ocular hypertension (0.84-0.95), mild (0.68-0.94), moderate (0.57-0.92), advanced (0.58-0.88), severe/blind (0.46-0.76), and bilateral blindness (0.26-0.5). Most studies reported the basis for using health utilities (34, 79%) and any assumptions or adjustments applied to the health utilities (22, 51%). Few studies reported a framework for assessing the relevance of health utilities to a decision context (8, 19%). Even fewer (3, 7%) applied a systematic search strategy to identify health utilities and used a structured assessment of quality for inclusion. Overall, reporting has not improved over time. CONCLUSIONS AND RELEVANCE: This review describes that few CUAs describe important rationale for using health state utility values. Including additional details on the search, appraisal, selection, and inclusion process of health utility values improves transparency, generalizability and supports the assessment of the validity of study conclusions. Future investigations should aim to use health utilities on the same scale of measurement across health states and consider the source and relevance to the decision context/purpose of conducting that cost-utility study.

Short-Term Efficacy and Safety of Open Conjunctiva Ab Externo XEN45 Gel Stent Implantation in Glaucoma Patients.

PRCIS: We examined the safety and efficacy of the open conjunctiva ab externo approach for XEN45 gel stent implantation. There was a significant reduction in intraocular pressure (IOP) and number of glaucoma medications at 12 months follow-up. PURPOSE: This study aims to determine the safety and efficacy of the open conjunctiva ab externo approach to XEN45 stent implantation. MATERIALS AND METHODS: Retrospective chart review of all patients between July 2018 and March 2020 who underwent XEN45 implantation. IOP and the number of glaucoma medications were measured at the preoperative, 1 day, 1 week, 1 month, 3 months, 6 months, and 12 months postoperative appointments. The primary outcome of this study is the number of cases achieving complete success at 12 months postoperatively. RESULTS: Forty-four eyes of 44 patients were included. Mean preoperative IOP was 26.2±8.7 mm Hg on 3.2±0.7 IOP-lowering medications. At 12 months postoperative, mean IOP was 18.9±9.1 mm Hg (n=35, P <0.0001; mean reduction of 27.9%) on 0.9±1.4 (n=35, P <0.0001) IOP-lowering medications. Postoperative needling was performed in 5 cases (11.4%). Of the 35 cases with a postoperative visit at 12 months, complete success was achieved in 14 cases (40.0%) and qualified success in 3 cases (8.6%). Eighteen cases (51.4%) were recorded as failures at 12 months, comprised of 4 cases requiring reoperation for glaucoma (2 XEN45 implants, 1 trabeculectomy, and 1 Baerveldt implant), and 14 cases that did not meet the IOP-lowering criteria for success. During the postoperative course, there was 1 case of self-limited hypotony, 2 self-resolving choroidal effusions, and 3 cases of bleb leakage. CONCLUSIONS: The open conjunctiva ab externo approach to XEN45 implantation achieved successful levels of IOP reduction in 48.6% of glaucoma cases within the first year. The most common adverse events included the need for additional glaucoma surgery (excluding needling procedures), transient hypotony, and bleb leak.

Adenosine A1 and A2A receptors are not upstream of caffeine's dopamine D2 receptor-dependent aversive effects and dopamine-independent rewarding effects.

Caffeine is widely consumed throughout the world, but little is known about the mechanisms underlying its rewarding and aversive properties. We show that pharmacological antagonism of dopamine not only blocks conditioned place aversion to caffeine, but also reveals dopamine blockade-induced conditioned place preferences. These aversive effects are mediated by the dopamine D(2) receptor, as knockout mice showed conditioned place preferences in response to doses of caffeine that C57Bl/6 mice found aversive. Furthermore, these aversive responses appear to be centrally mediated, as a quaternary analog of caffeine failed to produce conditioned place aversion. Although the adenosine A(2A) receptor is important for caffeine's physiological effects, this receptor seems only to modulate the appetitive and aversive effects of caffeine. A(2A) receptor knockout mice showed stronger dopamine-dependent aversive responses to caffeine than did C57Bl/6 mice, which partially obscured the dopamine-independent and A(2A) receptor-independent preferences. Additionally, the A(1) receptor, alone or in combination with the A(2A) receptor, does not seem to be important for caffeine's rewarding or aversive effects. Finally, excitotoxic lesions of the tegmental pedunculopontine nucleus revealed that this brain region is not involved in dopamine blockade-induced caffeine reward. These data provide surprising new information on the mechanism of action of caffeine, indicating that adenosine receptors do not mediate caffeine's appetitive and aversive effects. We show that caffeine has an atypical reward mechanism, independent of the dopaminergic system and the tegmental pedunculopontine nucleus, and provide additional evidence in support of a role for the dopaminergic system in aversive learning.

A Canadian Cost-Utility Analysis of 2 Trabecular Microbypass Stents at Time of Cataract Surgery in Patients with Mild to Moderate Open-Angle Glaucoma.

PURPOSE: To assess, from the Canadian public payer perspective, the cost-utility of implanting iStent Inject trabecular bypass stent (TBS) devices in conjunction with cataract surgery versus cataract surgery alone in patients with open-angle glaucoma (OAG) and visually significant cataract. DESIGN: Cost-utility analysis using efficacy and safety results of pivotal randomized clinical trial. PARTICIPANTS: Modeled cohort of patients with OAG (83.1% with mild disease, 16.9% with moderate disease) and visually significant cataract. METHODS: Open-angle glaucoma treatment costs and effects were projected over a 15-year time horizon using a Markov model with Hodapp-Parrish-Anderson glaucoma stages (mild, moderate, advanced, severe or blind) and death as health states. Patients in the mild or moderate OAG health states received implantation of iStent Inject during cataract surgery versus cataract surgery alone. On worsening of visual field defect and optic disc damage, patients could receive selective laser trabeculoplasty and trabeculectomy. We measured treatment effect as reduction in intraocular pressure (IOP) and mean medication use and estimated transition probabilities based on efficacy-adjusted visual field mean deviation decline per month. Healthcare resource utilization and utility scores were obtained from the literature. Cost inputs (2017 Canadian dollars [C$]) were derived using the Ontario Health Insurance Plan, expert opinion, medication claims datasets, and Ontario Drug Benefit Formulary medication consumption costs. We conducted deterministic and probabilistic sensitivity analyses to examine the impact of alternative model input values on results. MAIN OUTCOME MEASURES: Incremental cost per quality-adjusted life year (QALY) gained. RESULTS: Compared with cataract surgery alone, TBS plus cataract surgery showed a 99% probability of being more effective (+0.023 QALYs; 95% confidence interval [CI], 0.004 to 0.044) and a 73.7% probability of being cost-saving (net cost, -C$389.00; 95% CI, -C$1712.00 to C$850.70). In 95% of all simulations, TBS plus cataract surgery showed a cost per QALY of C$62 366 or less. Results were robust in additional sensitivity and scenario analyses. CONCLUSIONS: iStent Inject TBS implantation during cataract surgery seems to be cost effective for reducing IOP in patients with mild to moderate OAG versus cataract surgery alone.

Disease-specific Preference-based Measure of Glaucoma Health States: HUG-5 Psychometric Validation.

PURPOSE: Glaucoma is the second leading cause of irreversible blindness in the world, with 60 million people worldwide estimated to suffer from the condition. Health utility is an important outcome measure of treatment effect in economic outcomes. The available tools for the measurement of health utility in glaucoma patients do not support a preference-based algorithm required to estimate health utility. To resolve this gap in the literature, the HUG-5 (Health Utility for Glaucoma-5 dimensions) was developed. The objective of the present study was to validate the HUG-5 with accepted measures of health state and vision-specific quality of life. MATERIALS AND METHODS: The HUG-5 measures patient self-reported levels of visual discomfort, mobility, daily life activities, emotion, and social activities, as affected by the progression and management of glaucoma. To evaluate the psychometric properties, the HUG-5 was assessed for construct validity between similar and dissimilar dimensions of the National Eye Institute Visual Function Questionnaire-25 (NEI-VFQ-25) and the EuroQol's 5 Dimensions. The HUG-5 was evaluated for test-retest reliability after a 2-week period. The HUG-5 composite distributions of mild/moderate and advanced glaucoma patients were tested for differences to measure sensitivity. RESULTS: A total of 124 patients with glaucoma were administered the NEI-VFQ-25, the HUG-5, and the EuroQol's 5 Dimensions. The HUG-5 demonstrated construct validity, with convergent and discriminant support for visual discomfort, mobility, daily life activities, emotional distress, and social activities. The HUG-5 concurrently measured health-related quality of life associated with best-eye visual field loss (r=0.63, P<0.001). The HUG-5 measured health state consistently with test-retest reliability (intraclass correlation=0.91, P<0.001). The HUG-5 was established to be sensitive in detecting differences between patients with mild/moderate glaucoma and those with advanced glaucoma with a rank-sum test with continuity correction (W=693.5, P<0.001). CONCLUSIONS: This study demonstrates promising results for the HUG-5's response range and relationship with the NEI-VFQ-25 and best-eye visual field loss, highlighting the value of disease-specific preference-based scoring systems in measuring health state changes in glaucoma patients.

Cost-effectiveness analysis of standalone trabecular micro-bypass stents in patients with mild-to-moderate open-angle glaucoma in Canada.

OBJECTIVES: To estimate the cost-utility of two trabecular micro-bypass stents (TBS) implantation vs standard of care (SOC) in patients with mild-to-moderate open-angle glaucoma (OAG) in the Canadian healthcare setting. METHODS: The deterioration in visual field (VF) defect over a 15-year time horizon was tracked using a Markov model with Hodapp-Parrish-Anderson stages of glaucoma (mild, moderate, advanced, severe/blind) and death as health states. Meta-analyses of randomized clinical trials were conducted to estimate the pooled reduction in intraocular pressure (IOP) and medication use due to TBS and SOC. The rate of decline in VF loss was adjusted by the extent of IOP reduction to estimate transition probabilities. Healthcare resource utilization, unit costs (2017 CAD), and progression-related utility scores were obtained by literature review, and medication costs with wastage were obtained from IMS Brogan PharmaStat. The impact of parameter and methodological uncertainty on costs and quality-adjusted life years (QALYs) was examined using probabilistic and 1-way sensitivity analyses. RESULTS: The meta-analysis showed an additional reduction of 1.13 medications/patient and an additional decrease in IOP of -1.10 mmHg at 36 months favoring TBS. TBS strongly dominated medication alone, due to higher improvement in quality-of-life (0.068 QALYs), fewer blind eyes (-0.0031), and a decrease in total healthcare costs of C$2,908.3 per patient over the time horizon (C$9,394.1 TBS vs C$12,302.4 medication alone). Sensitivity analyses showed that results were robust to the uncertainties in model inputs and assumptions. Time-to-dominance was 44 months (3.7 years). CONCLUSIONS: The TBS procedure was cost-effective over SOC in a 15-year time horizon, with quality-of-life gains.

Glaucoma after corneal replacement.

Glaucoma is a well-known complication after corneal transplantation surgery. Traditional corneal transplantation surgery, specifically penetrating keratoplasty, has been slowly replaced by the advent of new corneal transplantation procedures: primarily lamellar keratoplasties. There has also been an emergence of keratoprosthesis implants for eyes that are high risk of failure with penetrating keratoplasty. Consequently, there are different rates of glaucoma, pathogenesis, and potential treatment in the form of medical, laser, or surgical therapy.

Preference-based Glaucoma-specific Health-related Quality of Life Instrument: Development of the Health Utility for Glaucoma.

PURPOSE: To develop a descriptive system for a glaucoma-specific preference-based health-related quality of life (HRQoL) instrument: the Health Utility for Glaucoma (HUG-5). METHODS: The descriptive system was developed in 2 stages: item identification and item selection. A systematic literature review of HRQoL assessment of glaucoma was conducted using a comprehensive search strategy. Purposeful sampling was used to recruit patients with different clinical characteristics. Relevant items were presented to glaucoma patients through face-to-face, semistructured interviews. Framework methodology was applied to analyze interview content. The recurring themes identified through an iterative content analysis represented topics of most importance and relevance to patients. These themes formed the domains of the HUG-5 descriptive system. Three versions of the descriptive system, differing in explanatory detail, were pilot tested using a focus group. RESULTS: The literature review identified 19 articles which contained 266 items. These items were included for the full-text review and were used to develop an interview guide. From 12 patient interviews, 22 themes were identified and grouped into 5 domains that informed the 5 questions of the descriptive system. The HUG-5 measures visual discomfort, mobility, daily life activities, emotional well-being, and social activities. Each question has 5 response levels that range from "no problem" to "severe problem." The focus group comprised 7 additional patients unanimously preferred the version that contained detailed, specific examples to support each question. CONCLUSIONS: A 5-domain descriptive system of a glaucoma-specific preference-based instrument, the HUG-5, was developed and remains to be evaluated for validity and reliability in the glaucoma patient population.

Preference-based disease-specific health-related quality of life instrument for glaucoma: a mixed methods study protocol.

INTRODUCTION: A primary objective of healthcare services is to improve patients' health and health-related quality of life (HRQoL). Glaucoma, which affects a substantial proportion of the world population, has a significant detrimental impact on HRQoL. Although there are a number of glaucoma-specific questionnaires to measure HRQoL, none is preference-based which prevent them from being used in health economic evaluation. The proposed study is aimed to develop a preference-based instrument that is capable of capturing important effects specific to glaucoma and treatments on HRQoL and is scored based on the patients' preferences. METHODS: A sequential, exploratory mixed methods design will be used to guide the development and evaluation of the HRQoL instrument. The study consists of several stages to be implemented sequentially: item identification, item selection, validation and valuation. The instrument items will be identified and selected through a literature review and the conduct of a qualitative study. Validation will be conducted to establish psychometric properties of the instrument followed by a valuation exercise to derive utility scores for the health states described. ETHICS AND DISSEMINATION: This study has been approved by the Trillium Health Partners Research Ethics Board (ID number 753). All personal information will be de-identified with the identification code kept in a secured location including the rest of the study data. Only qualified and study-related personnel will be allowed to access the data. The results of the study will be distributed widely through peer-reviewed journals, conferences and internal meetings.

Fixation stability as a goal in the treatment of macular disease.

Recent advances in the treatment of macular diseases have improved macular anatomy and function as measured and quantified by visual acuity, retinal thickness, and vascular changes detailed by fluorescein angiography. Such observed changes do not always explain improvement in visual function and do not always correlate with patient satisfaction. In some cases, there is poor correlation between anatomic changes and functional improvement. Microperimetry studies on fixation stability after treatment of macular diseases have shown a strong correlation between better fixation stability and visual acuity. Furthermore, achieving better fixation stability facilitates low-vision rehabilitation. These microperimetry findings suggest that fixation stability should be regarded as an important outcome measure in studies of macular disease treatment and should be considered in clinical and research studies of low-vision rehabilitation in cases of treated macular diseases.

The worse eye is not as bad as it seems to be in AMD cases.

OBJECTIVE: It is the aim of this study to review residual vision in the less used eye of patients with age-related macular degeneration (AMD) using modern concepts for residual visual functions in addition to traditional methods for assessing visual acuity. DESIGN: The study was designed as a retrospective, nonrandomized, observational case series. PARTICIPANTS: Consecutive cases tested with microperimetry instruments were identified from archives. Included were cases with diagnosed AMD of all age groups and all visual acuity levels. METHODS: In all cases, microperimetric technology was used to assess residual visual function. Outcome measures selected for analysis were visual acuity, preferred retinal loci (PRL) topography, fixation stability, and PRL span. RESULTS: Data were collected and analyzed for both eyes from 51 patients with AMD low vision. There were 23 males and 28 females whose mean age was 84 (± 7) years. Within the group the difference in visual acuity estimates between the better seeing and the less used eye was statistically significant (p = 0.001). Similar positive statistical significant differences were noticed at all spatial frequencies (except at 6 cycles/degree) when testing contrast sensitivity. All other measurements were not statistically different between the better seeing and the poorer eye. This applies to the fixation stability and PRL span estimates. Almost half (49%) of the cases showed retinal noncorrespondence of PRLs between the 2 eyes. CONCLUSIONS: Visual acuity estimates are not a reliable measure for residual vision. The less used eye in AMD cases has much better residual vision than thought before according to modern outcome measures. This new concept should be taken into account by all practitioners and be applied during all low vision rehabilitation interventions.

A comparison of hand- and foot-activated surgical tools in simulated ophthalmic surgery.

OBJECTIVE: To compare the performance characteristics of hand-activated surgical tools with those of foot-activated surgical tools using a virtual-reality simulator of intraocular surgery. DESIGN: Prospective, unmasked, interventional cohort study. PARTICIPANTS: Eighteen ophthalmology residents at the University of Toronto. METHODS: The EYESi ophthalmic surgery simulator was used for the study. The surgical tool evaluated was a simulation of intraocular forceps activated by either a handpiece or a foot pedal. Each resident completed 2 modules-a dexterity module and a capsulorrhexis/cataract module. Each module was completed 4 times, alternating between the hand-activated forceps and the foot-activated forceps. An overall score was calculated for each task on the basis of the efficiency and accuracy of completion of the task, with 100 representing a perfect score. Overall scores were compared between hand and foot control for both modules. RESULTS: For the dexterity module, there was no significant difference in the overall scores between the 2 groups (91 ± 6 and 93 ± 6 for the foot- and hand-activated forceps groups, respectively; p > 0.05, t test). For the capsulorrhexis module, overall scores were also similar for both groups, the scores being 50 ± 21 and 53 ± 16 for the foot- and hand-activated forceps groups, respectively (p > 0.05, t test). An exit survey of the study's participants revealed that subjects did not have a preference for the hand or foot modality of the forceps tool, with 10 preferring the hand-activated forceps tool and 8 preferring the foot-activated tool. CONCLUSIONS: During simulated intraocular surgery, foot- and hand-activated surgical tools appear to have similar performance characteristics and are equally well received by residents.

Visual assessment of the spine bruckel instrument, a novel status tool to reflect appearance of the spine in patients with ankylosing spondylitis.

OBJECTIVE: The Visual Assessment of the Spine Bruckel Instrument (VASBI) is a new status tool developed by the Spondylitis Association of America and the University of Toronto to reflect spinal appearance in patients with ankylosing spondylitis (AS). Our objective was to validate the VASBI according to the Outcome Measures in Rheumatoid Arthritis Clinical Trials filter (truth, discrimination, and feasibility). METHODS: Three hundred patients with AS were asked to rate their degree of perceived spinal deformity using the VASBI. To evaluate construct validity, VASBI scores were compared with functional outcome, spinal mobility, and radiographic spinal damage. Test-retest reliability was evaluated using kappa statistic (kappa). RESULTS: Patient VASBI demonstrated strong correlation with spinal mobility (r = 0.543) and moderate correlation with functional impairment (r = 0.490) and structural damage (r = 0.309). Reliability for VASBI was very good (kappa = 0.973, p < 0.001). CONCLUSION: The VASBI is a novel tool with practical applications in a busy clinical setting as it simplifies assessment of AS spinal deformity. Our study demonstrates that the VASBI has good feasibility, construct validity, and reliability.

Pediatric eye injuries in a Canadian emergency department.

OBJECTIVE: This study assesses the descriptive epidemiology of children with eye injuries presenting to the emergency department of a major Canadian pediatric hospital. STUDY DESIGN: A retrospective cohort study. PARTICIPANTS: All pediatric patients (up to 18 years of age) presenting with ocular injuries to a tertiary care pediatric emergency department between January 1 and December 31, 2002. METHODS: Chart review was conducted using Canadian Hospital Injury Reporting and Prevention Program forms. All injuries were classified by Birmingham Eye Trauma Terminology (BETT). RESULTS: There were 149 patients who presented with eye injuries to the emergency department in 2002, and all of them were included in the study. Patient ages ranged from 3 months to 18 years with a median age of 8 years 8 months (interquartile range 4-11 years). Boys accounted for 73.2% of the patient total. Most of the cases (57.7%) needed some treatment and required follow-up. Eleven patients (7.3%) had vision-threatening eye injuries that required surgical management, and 3 of these required multiple surgeries. Seven of the 11 patients suffered open globe lacerations, 3 open globe ruptures, and 1 closed globe injury. CONCLUSIONS: Most eye injuries occurred at home during the summer, and over 7% of children presenting to the emergency department with eye trauma had vision-threatening injuries that required surgical management. Increasing awareness of the serious nature of ocular injuries will help to develop a comprehensive plan for educating both parents and children to minimize preventable pediatric eye injuries.

Significance of clinical evaluation of the metacarpophalangeal joint in relation to synovial/bone pathology in rheumatoid and psoriatic arthritis detected by magnetic resonance imaging.

OBJECTIVE: Rheumatologists base many clinical decisions regarding the management of inflammatory joint diseases on joint counts performed at clinic. We investigated the reliability and accuracy of physically examining the metacarpophalangeal (MCP) joints to detect inflammatory synovitis using magnetic resonance imaging (MRI) as the gold standard. METHODS: MCP joints 2 to 5 in both hands of 5 patients with rheumatoid arthritis (RA) and 5 with psoriatic arthritis (PsA) were assessed by 5 independent examiners for joint-line swelling (visually and by palpation); joint-line tenderness by palpation (tender joint count, TJC) and stress pain; and by MRI (1.5 Tesla superconducting magnet). Interrater reliability was assessed using kappa statistics, and agreement between examination and corresponding MRI assessment was assessed by Fisher's exact tests (p < 0.05 considered statistically significant). RESULTS: Interrater agreement was highest for visual assessment of swelling (kappa = 0.55-0.63), slight-fair for assessment of swelling by palpation (kappa = 0.19-0.41), and moderate (kappa = 0.41-0.58) for assessment of joint tenderness. In patients with RA, TJC, stress pain, and visual swelling assessment were strongly associated with MRI evaluation of synovitis. Visual swelling assessment demonstrated high specificity (> 0.8) and positive predictive value (= 0.8). For PsA, significant associations exist between TJC and MRI synovitis scores (p < 0.01) and stress pain and MRI edema scores (p < 0.04). Assessment of swelling by palpation was not significantly associated with synovitis or edema as determined by MRI in RA or PsA (p = 0.54-1.0). CONCLUSION: In inflammatory arthritis, disease activity in MCP joints can be reliably assessed at the bedside by examining for joint-line tenderness (TJC) and visual inspection for swelling. Clinical assessment may have to be complemented by other methods for evaluating disease activity in the joint, such as MRI, particularly in patients with PsA.