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Evaluating primary treatment for people presenting with advanced glaucoma: 5-year results of the Treatment of Advanced Glaucoma Study

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... 32 However, it is important to note that the medical therapy group in this study was associated with a significantly increased number of trabeculectomies, which may have influenced mean IOP values due to its pronounced IOP-lowering effect. [35][36][37][38][39][40] Moreover, there was a comparable rate of eyes at target IOP at the final assessment. This outcome was further substantiated by our pooled analysis. ...
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Précis Selective laser trabeculoplasty (SLT) and medical therapy groups displayed comparable intraocular pressure (IOP) at most follow-ups. SLT was associated with significantly decreased rates of glaucoma surgeries, antiglaucomatous medications, and ocular adverse effects. Purpose To evaluate the efficacy and safety of selective laser trabeculoplasty (SLT) compared to medical therapy in the treatment of open-angle glaucoma (OAG) or ocular hypertension (OHT). Methods A systematic search was performed in PubMed, Embase, Cochrane Library and Web of Science databases. Randomized controlled trials (RCTs) comparing SLT with medical therapy were included. We computed mean differences (MDs) or standardized mean differences (STDs) for continuous endpoints and risk ratios (RRs) for binary endpoints, with 95% confidence intervals (CIs). Heterogeneity was assessed with I ² statistics. Software R, version 4.2.1, was used for statistical analyses. Subgroup analyses were performed on treatment-naive patients and on the class of drugs in the medical therapy group. Results Fourteen RCTs comprising 1,706 patients were included, of whom 936 were submitted to SLT. Medical therapy was associated with a significantly improved IOP at 1 month and a higher proportion of patients achieving ≥20% IOP reduction. There were no significant differences between groups in IOP at 2, 3, 6, and 12 months, IOP fluctuation, rate of eyes at target IOP, visual field, and quality of life. The SLT group exhibited significantly decreased rates of glaucoma surgeries, antiglaucoma medications, and ocular adverse effects. Conclusion SLT demonstrated comparable efficacy to medical therapy in IOP control at most follow-ups, along with favorable impacts on critical treatment-related factors. Our findings support SLT as a safe and effective treatment for OAG or OHT.
... Moreover, a variety of clinical examinations are necessary for the diagnosis of glaucoma, such as measurement of intraocular pressure (IOP), examination of the optic nerve, testing of the visual field, and structural imaging of the optic nerve and retina. Although these diagnostic techniques are essential for detecting glaucomatous damage, their sensitivity and specificity are naturally limited [17][18][19][20]. For instance, an IOP measurement by itself might not adequately indicate the likelihood that glaucoma will worsen because optic nerve injury can occur in some people with normaltension glaucoma even though their IOP levels are normal [21]. ...
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Glaucoma is progressive and silent, it presents substantial hurdles to early detection and successful therapy. Glaucoma is one of the world's leading causes of irreversible blindness. Novel developments in diagnostic technology have encouraging prospects for tackling these obstacles and enhancing patient results. An overview of the most recent advancements in glaucoma diagnosis, such as imaging modalities, functional evaluations, and artificial intelligence (AI) applications, is given in this abstract. The exact assessment of optic nerve anatomy and visual field function made possible by optical coherence tomography (OCT), confocal scanning laser ophthalmoscopy (CSLO), and frequency-doubling technology (FDT) perimetry helps in early illness detection and progression tracking. Large-scale imaging and clinical data sets are used to train AI-driven algorithms, which improve diagnostic precision and enable individualized risk assessment and treatment planning. With earlier intervention, more individualized care, and better long-term visual results possible, these diagnostic advancements have the potential to completely transform the diagnosis and treatment of glaucoma. To fully appreciate the clinical benefit of these advances, however, standardization, integration, and validation difficulties need to be addressed. To improve the quality of treatment for patients with glaucoma and expedite the translation of these discoveries into clinical practice, industry partners, doctors, and researchers must work together.
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Purpose To investigate the effect of average intraocular pressure (IOP) on the true rate of glaucoma progression (RoP) in the United Kingdom Glaucoma Treatment Study (UKGTS). Methods UKGTS participants were randomized to placebo or Latanoprost drops and monitored for up to two years with visual field tests (VF, 24-2 SITA standard), IOP measurements, and optic nerve imaging. We included eyes with at least three structural or functional assessments (VF with <15% false-positive errors). Structural tests measured rim area (RA) with Heidelberg retina tomography (HRT) and average peripapillary retinal nerve fiber layer (pRNFL) thickness with optical coherence tomography (OCT). One eye of 436 patients (222 on Latanoprost) was analyzed. A Bayesian hierarchical model estimated the true RoP of VF and structural metrics, and their correlations, using sign-reversed multivariable exponential distribution. RA and pRNFL measurements were converted to a dB scale, matching the VF metric (mean deviation [MD]). The effect of average IOP on the true RoPs was estimated. Results True RoP at the mean average IOP (17 mm Hg) was faster (P < 0.001) for VF-MD (−0.59 [−0.73, −0.48] dB/year) than HRT-RA (−0.05 [−0.07, −0.03] dB/year) and OCT-pRNFL (−0.08 [−0.11, −0.06] dB/year). The proportional acceleration of RoP per mm Hg increase was, however, not significantly different (smallest P = 0.15). Accounting for the structural floor-effect largely eliminated the differences in RoPs (smallest P = 0.25). Conclusions VF appeared to deteriorate at a faster rate than structural measurements. However, this could be explained by the floor-effect from nonfunctional tissue. IOP induced a similar acceleration in RoP per mm Hg increase.
Article
Purpose of review The purpose of this review is to summarize past and present findings of established clinical trials in glaucoma with a case-based approach. We provide a general overview of each major trial and provide recommendations for their implementation in clinical practice. Recent findings Summary There have been several large glaucoma clinical trials performed over the last three decades. These trials have guided clinical decision making by helping risk stratify patients and guide medical and surgical management.
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PURPOSE The purpose of the study was to evaluate the efficacy and safety of the PAUL glaucoma implant (PGI) in refractory glaucoma patients, during the early postoperative period. METHODS We conducted a retrospective, cohort study of patients that had received a PGI between February 2022 and December 2023. An intraluminal polypropylene suture was placed to prevent early hypotony in all cases. Demographics, intraocular pressure (IOP), and medication variation were evaluated for up to 6 months. The success rate was stratified into <18 mmHg and 30% from baseline or <15 mmHg and 40% IOP reduction. The safety outcomes were also analyzed. RESULTS Sixteen eyes from 16 patients were included in the analysis. Fifteen of them had had a previous surgical glaucoma procedure. At 6 months, IOP decreased from 26.6 (±6.2) to 15.3 (±4.6) mmHg, with fewer glaucoma medications, from a median (interquartile range) of 3 (2–3) – 1.5 (0–2) ( P < 0.005). Twelve (75%) and seven (43.8%) eyes met the qualified and complete success definition for the first category, and eight (50%) and four (25%) met the second criterion. One case with self-limiting choroidal detachments, but >6 mmHg IOP was found in our cohort. CONCLUSION The PGI seems to be safe and effective from the early postoperative period. The IOP reduction rate could make it suitable for patients with refractory moderate-to-advanced glaucoma.
Article
Objective This study aims to conduct an analysis glaucoma surgeries performed over a 13-year period at a tertiary hospital affiliated with the Spanish National Health System, with the goal of assessing temporal trends. Methods This retrospective observational study scrutinized surgeries undertaken in the glaucoma unit of a tertiary center in Spain between 2010 and 2022. Data collected included surgical dates, procedure performed, whether it was standalone or combined, as well as patient demographics including age, sex, and type of underlying glaucoma. Surgeries on individuals under 18 years of age were excluded. An annual comparative analysis was performed to ascertain the evolving trends in glaucoma surgical interventions. Results A total of 12,944 surgeries were included in the analysis, comprising 9428 isolated cataract surgeries and 2975 glaucoma procedures. Trabeculectomy, glaucoma drainage devices (GDD), and cyclodestruction, collectively referred to as traditional surgery, demonstrated a decline from 93.2% to 23.6% over the study duration. Minimally invasive glaucoma surgery (MIGS) and minimally invasive bleb surgery (MIBS) demonstrated a significant increase from 3.8% in 2010 to 74.7% in 2022, relative to the total glaucoma surgeries. Furthermore, combined surgeries manifested a noteworthy increase from 39.0% in 2010 to 44.2% in 2022, with 86.4% of combined procedures in 2022 being MIGS or MIBS. Conclusion In recent years, there has been a noticeable change in the trend of glaucoma surgeries, with MIGS and MIBS procedures experiencing a significant increase and becoming the most commonly performed glaucoma procedures. Consequently, traditional glaucoma surgeries have decreased in frequency.
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Surgical intervention in patients with severe glaucoma remains controversial, especially in unilateral cases with a minimally affected fellow eye. Many question the benefit of trabeculectomy in such cases due to high complication rates and prolonged recovery. In this retrospective, non-comparative, interventional case series we aimed to determine the effect of trabeculectomy or combined phaco-trabeculectomy on the visual function of advanced glaucoma patients. Consecutive cases with perimetric mean deviation loss worse than −20 dB were included. Survival of visual function according to five predetermined visual acuity and perimetric criteria was set as the primary outcome. Qualified surgical success utilizing two different sets of criteria commonly used in the literature constituted secondary outcomes. Forty eyes with average baseline visual field mean deviation −26.3 ± 4.1 dB were identified. The average pre-operative intraocular pressure was 26.5 ± 11.4 mmHg and decreased to 11.4 ± 4.0 mmHg (p < 0.001) after an average follow-up of 23.3 ± 15.5 months. Visual function was preserved at two years in 77% or 66% of eyes respectively according to two different sets of visual acuity and perimetric criteria. Qualified surgical success was 89%, 72% at 1 and 3 years respectively. Trabeculectomy and/or phaco-trabeculectomy is associated with meaningful visual outcomes in patients with uncontrolled advanced glaucoma.
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Background/objectives To explore the attitudes of UK glaucoma specialists regarding the current and future practice of trabeculectomy and the novel PRESERFLO™ MicroShunt (PF-MS) device, and intentions to adopt the PF-MS into routine glaucoma surgical practice. Methods Online survey of UK and Éire Glaucoma Society members. Results 43 glaucoma consultants completed the survey. All surgeons performed trabeculectomies (median of 40 annually) and 51% undertook PF-MS procedures (median of 22.5 annually). The mean duration of surgery was reported as 48.9 (SD 13.3) and 31.2 (SD 9.9) min for trabeculectomy and PF-MS respectively ( p < 0.0001). For surgeons not currently using the PF-MS, 65% planned to do so. Respondents judged completion of 35 trabeculectomies and 10 PF-MS were required to achieve basic competence. 91% of participants predicted their trabeculectomy volume would decrease and 73% expected PF-MS usage to increase. Respondents reported a median of six and four follow-ups within 3 months post surgery for trabeculectomy and PF-MS respectively ( p < 0.0001). Respondents reported trabeculectomy required more post-operative interventions than the PF-MS and 81.8% judged the patient experience to be better with the PF-MS. The PF-MS was deemed suitable for early visual field loss by 72% of respondents, severe visual field loss by 35% and normal tension glaucoma by 21%. Conclusion The PF-MS has seen rapid adoption in the UK. Respondents predict its usage will significantly increase whilst trabeculectomies will decrease. They report the PF-MS is quicker to learn and perform, and requires less post-operative follow-ups and interventions which may facilitate a more efficient service delivery for patients requiring glaucoma surgery.
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Purpose: to compare visual field (VF) progression between the two arms of the Treatment of Advanced Glaucoma Study (TAGS) DESIGN: post-hoc analysis of VF data from a two-arm multicenter randomized controlled clinical trial METHODS: 453 patients with newly diagnosed advanced open-angle glaucoma in at least one eye from 27 centers in the United Kingdom were randomized to either trabeculectomy (N = 227) or medications in their index eye (N = 226) and followed-up for two years with two 24-2 VF tests at baseline, 4, 12 and 24 months. We analyzed data for participants with a reliable VF (False positive rate < 15%) at baseline and at least two other time-points. Main outcome measures: Average difference in rate of progression (RoP) was analyzed using a hierarchical Bayesian model. Time for each eye to progress from baseline beyond specific cut-offs (0.5, 1, 1.5 and 2 dB) was compared using survival analysis. Results: 211 eyes in the trabeculectomy-first arm and 203 eyes in the medications-first arm were analyzed. The average RoPs (Estimate [95% Credible Intervals]) were -0.59 [-0.88, -0.31] dB/year in the medications-first arm and -0.40 [-0.67, -0.13] dB/year in the trabeculectomy-first arm. The difference was not significant (Bayesian p-value = 0.353). More eyes progressed in the medications-first arm: ≥0.5 dB (p = 0.001), ≥1dB (p = 0.014), ≥1.5dB (p = 0.071) and ≥2dB (p = 0.061). Conclusions: there was no significant difference in the average RoP at two years. Initial trabeculectomy significantly reduced the proportion of progressing eyes.
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Background Patients diagnosed with advanced primary open-angle glaucoma are at a high risk of lifetime blindness. Uncertainty exists about whether primary medical management (glaucoma eye drops) or primary surgical treatment (augmented trabeculectomy) provide the best and safest patient outcomes. Objectives To compare primary medical management with primary surgical treatment (augmented trabeculectomy) in patients with primary open-angle glaucoma presenting with advanced disease in terms of health-related quality of life, clinical effectiveness, safety and cost-effectiveness. Design This was a two-arm, parallel, multicentre, pragmatic randomised controlled trial. Setting Secondary care eye services. Participants Adult patients presenting with advanced primary open-angle glaucoma in at least one eye, as defined by the Hodapp–Parrish–Anderson classification of severe glaucoma. Intervention Primary medical treatment – escalating medical management with glaucoma eye drops. Primary trabeculectomy treatment – trabeculectomy augmented with mitomycin C. Main outcome measures The primary outcome was health-related quality of life measured with the Visual Function Questionnaire-25 at 2 years post randomisation. Secondary outcomes were mean intraocular pressure; EQ-5D-5L; Health Utilities Index 3; Glaucoma Utility Index; cost and cost-effectiveness; generic, vision-specific and disease-specific health-related quality of life; clinical effectiveness; and safety. Results A total of 453 participants were recruited. The mean age of the participants was 67 years (standard deviation 12 years) in the trabeculectomy arm and 68 years (standard deviation 12 years) in the medical management arm. Over 65% of participants were male and more than 80% were white. At 24 months, the mean difference in Visual Function Questionnaire-25 score was 1.06 (95% confidence interval –1.32 to 3.43; p = 0.383). There was no evidence of a difference between arms in the EQ-5D-5L score, the Health Utilities Index or the Glaucoma Utility Index. At 24 months, the mean intraocular pressure was 12.40 mmHg in the trabeculectomy arm and 15.07 mmHg in the medical management arm (mean difference –2.75 mmHg, 95% confidence interval –3.84 to –1.66 mmHg; p < 0.001). Fewer types of glaucoma eye drops were required in the trabeculectomy arm. LogMAR visual acuity was slightly better in the medical management arm (mean difference 0.07, 95% confidence interval 0.02 to 0.11; p = 0.006) than in the trabeculectomy arm. There was no evidence of difference in safety between the two arms. A discrete choice experiment updated the utility values for the Glaucoma Utility Index. The within-trial economic analysis found a small increase in the mean EQ-5D-5L score (0.04) and that trabeculectomy has a higher probability of being cost-effective than medical management. The incremental cost of trabeculectomy per quality-adjusted life-year was £45,456. Therefore, at 2 years, surgery is unlikely to be considered cost-effective at a threshold of £20,000 per quality-adjusted life-year. When extrapolated over a patient’s lifetime in a model-based analysis, trabeculectomy, compared with medical treatment, was associated with higher costs (average £2687), a larger number of quality-adjusted life-years (average 0.28) and higher incremental cost per quality-adjusted life-year gained (average £9679). The likelihood of trabeculectomy being cost-effective at a willingness-to-pay threshold of £20,000 per quality-adjusted life year gained was 73%. Conclusions Our results suggested that there was no difference between treatment arms in health-related quality of life, as measured with the Visual Function Questionnaire-25 at 24 months. Intraocular pressure was better controlled in the trabeculectomy arm, and this may reduce visual field progression. Modelling over the patient’s lifetime suggests that trabeculectomy may be cost-effective over the range of values of society’s willingness to pay for a quality-adjusted life-year. Future work Further follow-up of participants will allow us to estimate the long-term differences of disease progression, patient experience and cost-effectiveness. Trial registration Current Controlled Trials ISRCTN56878850. Funding This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment ; Vol. 25, No. 72. See the NIHR Journals Library website for further project information.
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Objective To compare the effectiveness and safety of the MicroShunt versus trabeculectomy in patients with primary open-angle glaucoma (POAG). Design One-year results from a 2-year, prospective, randomized, multicenter, non-inferiority study (NCT01881425) conducted in the USA and Europe. Participants Eligible patients were aged 40–85 years with intraocular pressure (IOP) ≥15 and ≤40 mmHg and mild-to-severe POAG inadequately controlled on maximum tolerated medical therapy. Intervention Patients were randomized 3:1 to undergo stand-alone MicroShunt implantation or trabeculectomy, both performed with adjunctive Mitomycin C (0.2 mg/mL for 2 minutes). Main Outcome Measures The primary effectiveness endpoint was surgical success, defined as ≥20% reduction in mean diurnal IOP from baseline (no medication washout) at year 1 without increasing the number of glaucoma medications. Secondary effectiveness endpoints at year 1 were the mean IOP change from baseline and requirement for postoperative intervention. Additional endpoints included glaucoma medication use and adverse events. Results Overall, 395 (MicroShunt) and 132 (trabeculectomy) patients were randomized (mean Humphrey visual field mean deviation −12.34 dB). At year 1, probability of success was lower in the MicroShunt group compared with the trabeculectomy group (53.9% versus 72.7%, respectively; P<0.01). In the MicroShunt group, mean IOP ± standard deviation decreased from 21.1±4.9 mmHg at baseline to 14.3±4.3 mmHg (−29.1%; P<0.01) at year 1, with a mean of 0.6±1.1 glaucoma medications (baseline 3.1±1.0; P<0.01). In the trabeculectomy group, mean IOP decreased from 21.1±5.0 mmHg to 11.1±4.3 mmHg (−45.4%; P<0.01), with a mean of 0.3±0.9 glaucoma medications (baseline 3.0±0.9; P<0.01). Postoperative interventions, including laser suture lysis, were reported in 40.8% (MicroShunt) versus 67.4% (trabeculectomy) of patients (P<0.01). Reported incidence of transient hypotony was higher in the trabeculectomy group versus the MicroShunt group (49.6% versus 28.9%; P<0.01). Vision-threatening complications were uncommon and reported in 1.0% of MicroShunt versus 0.8% of trabeculectomy patients. Conclusions Probability of success was lower with MicroShunt compared with trabeculectomy. Though reductions in IOP and glaucoma medications over 1 year were observed in both groups, the trabeculectomy group had a lower mean IOP on fewer medications.
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Objective To determine whether primary trabeculectomy or primary medical treatment produces better outcomes in term of quality of life, clinical effectiveness, and safety in patients presenting with advanced glaucoma. Design Pragmatic multicentre randomised controlled trial. Setting 27 secondary care glaucoma departments in the UK. Participants 453 adults presenting with newly diagnosed advanced open angle glaucoma in at least one eye (Hodapp classification) between 3 June 2014 and 31 May 2017. Interventions Mitomycin C augmented trabeculectomy (n=227) and escalating medical management with intraocular pressure reducing drops (n=226) Main outcome measures Primary outcome: vision specific quality of life measured with Visual Function Questionnaire-25 (VFQ-25) at 24 months. Secondary outcomes: general health status, glaucoma related quality of life, clinical effectiveness (intraocular pressure, visual field, visual acuity), and safety. Results At 24 months, the mean VFQ-25 scores in the trabeculectomy and medical arms were 85.4 (SD 13.8) and 84.5 (16.3), respectively (mean difference 1.06, 95% confidence interval −1.32 to 3.43; P=0.38). Mean intraocular pressure was 12.4 (SD 4.7) mm Hg for trabeculectomy and 15.1 (4.8) mm Hg for medical management (mean difference −2.8 (−3.8 to −1.7) mm Hg; P<0.001). Adverse events occurred in 88 (39%) patients in the trabeculectomy arm and 100 (44%) in the medical management arm (relative risk 0.88, 95% confidence interval 0.66 to 1.17; P=0.37). Serious side effects were rare. Conclusion Primary trabeculectomy had similar quality of life and safety outcomes and achieved a lower intraocular pressure compared with primary medication. Trial registration Health Technology Assessment (NIHR-HTA) Programme (project number: 12/35/38). ISRCTN registry: ISRCTN56878850 .
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The assessment of safety is an important aspect of the evaluation of new therapies in clinical trials, with analyses of adverse events being an essential part of this. Standard methods for the analysis of adverse events such as the incidence proportion, that is the number of patients with a specific adverse event out of all patients in the treatment groups, do not account for both varying follow‐up times and competing risks. Alternative approaches such as the Aalen–Johansen estimator of the cumulative incidence function have been suggested. Theoretical arguments and numerical evaluations support the application of these more advanced methodology, but as yet there is to our knowledge only insufficient empirical evidence whether these methods would lead to different conclusions in safety evaluations. The Survival analysis for AdVerse events with VarYing follow‐up times (SAVVY) project strives to close this gap in evidence by conducting a meta‐analytical study to assess the impact of the methodology on the conclusion of the safety assessment empirically. Here we present the rationale and statistical concept of the empirical study conducted as part of the SAVVY project. The statistical methods are presented in unified notation, and examples of their implementation in R and SAS are provided.
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Background In individually randomised trials we might expect interventions delivered in groups or by care providers to result in clustering of outcomes for participants treated in the same group or by the same care provider. In partially nested randomised controlled trials (pnRCTs) this clustering only occurs in one trial arm, commonly the intervention arm. It is important to measure and account for between-cluster variability in trial design and analysis. We compare analysis approaches for pnRCTs with continuous outcomes, investigating the impact on statistical inference of cluster sizes, coding of the non-clustered arm, intracluster correlation coefficient (ICCs), and differential variance between intervention and control arm, and provide recommendations for analysis. Methods We performed a simulation study assessing the performance of six analysis approaches for a two-arm pnRCT with a continuous outcome. These include: linear regression model; fully clustered mixed-effects model with singleton clusters in control arm; fully clustered mixed-effects model with one large cluster in control arm; fully clustered mixed-effects model with pseudo clusters in control arm; partially nested homoscedastic mixed effects model, and partially nested heteroscedastic mixed effects model. We varied the cluster size, number of clusters, ICC, and individual variance between the two trial arms. Results All models provided unbiased intervention effect estimates. In the partially nested mixed-effects models, methods for classifying the non-clustered control arm had negligible impact. Failure to account for even small ICCs resulted in inflated Type I error rates and over-coverage of confidence intervals. Fully clustered mixed effects models provided poor control of the Type I error rates and biased ICC estimates. The heteroscedastic partially nested mixed-effects model maintained relatively good control of Type I error rates, unbiased ICC estimation, and did not noticeably reduce power even with homoscedastic individual variances across arms. Conclusions In general, we recommend the use of a heteroscedastic partially nested mixed-effects model, which models the clustering in only one arm, for continuous outcomes similar to those generated under the scenarios of our simulations study. However, with few clusters (3–6), small cluster sizes (5–10), and small ICC (≤0.05) this model underestimates Type I error rates and there is no optimal model. Electronic supplementary material The online version of this article (10.1186/s12874-018-0559-x) contains supplementary material, which is available to authorized users.
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Purpose: The UK Glaucoma Treatment Study (UKGTS) demonstrated the effectiveness of an intraocular pressure-lowering drug in patients with glaucoma using visual field progression as a primary outcome. We now test the hypothesis that responses on patient reported outcome measures (PROMs - secondary outcome measure) differ between patients receiving a topical prostaglandin analogue (Latanoprost) or placebo eye drops in UKGTS. Design: Multi-centre, randomised, triple-masked, placebo-controlled trial. Participants: Newly diagnosed glaucoma patients recruited into the UKGTS with baseline and exit PROM data (n= 182 and n=168 patients from the treatment and placebo group, respectively). Methods: The UKGTS was a multi-centre, randomised, triple-masked, placebo-controlled trial, where patients with newly diagnosed open angle glaucoma were allocated to receive Latanoprost (treatment) or placebo (trial registration number: ISRCTN96423140); the observation period was 24-months. Patients completed general health PROMs (EQ-5D and SF-36) and PROMs specific to glaucoma (GQL-15 and GAL-9) at baseline and at exit from the trial. Percentage change between baseline and exit measurement on PROMs were calculated for each patient and compared between treatment arms. In addition, differences between stable patients (n=272) and those with glaucomatous progression (n=78), as determined by visual field change (primary outcome), were assessed. Main outcome measure: PROMs on health-related and vision-related quality of life. Results: Average percentage change on PROMs was similar for patients in both arms of the trial with no statistically significant differences between treatment and placebo groups (EQ-5D, p = 0.98; EQ-5D VAS, p = 0.88; SF-36, p = 0.94, GQL-15, p = 0.66; GAL-9, p = 0.87). There were statistically significant differences between stable and progressing patients, as determined by visual fields, on glaucoma-specific PROMs (GQL-15, p = 0.02; GAL-9, p = 0.02) but not on general health PROMs (EQ-5D, p = 0.62; EQ-5D VAS, p = 0.23; SF-36, p = 0.65) CONCLUSIONS: Average change in PROMs on health-related and vision-related quality of life was similar for the treatment and placebo group in the UKGTS. PROMs, specifically those used in the UKGTS, may not be sensitive enough to be used as a primary endpoint in clinical trials when participants have newly diagnosed early stage glaucoma.
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Background Presentation with advanced glaucoma is the major risk factor for lifetime blindness. Effective intervention at diagnosis is expected to minimise risk of further visual loss in this group of patients. Aim To compare clinical and cost-effectiveness of primary medical management compared with primary surgery for people presenting with advanced open-angle glaucoma (OAG). Methods Design: A prospective, pragmatic multicentre randomised controlled trial (RCT). Setting Twenty-seven UK hospital eye services. Participants Four hundred and forty patients presenting with advanced OAG, according to the Hodapp-Parish-Anderson classification of visual field loss. Intervention Participants will be randomised to medical treatment or augmented trabeculectomy (1:1 allocation minimised by centre and presence of advanced disease in both eyes). Main outcome measures The primary outcome is vision-related quality of life measured by the National Eye Institute—Visual Function Questionnaire-25 at 24 months. Secondary outcomes include generic EQ-5D-5L, Health Utility Index-3 and glaucoma-related health status (Glaucoma Utility Index), patient experience, visual field measured by mean deviation value, logarithm of the mean angle of resolution visual acuity, intraocular pressure, adverse events, standards for driving and eligibility for blind certification. Incremental cost per quality-adjusted life-year (QALY) based on EQ-5D-5L and glaucoma profile instrument will be estimated. Results The study will report the comparative effectiveness and cost-effectiveness of medical treatment against augmented trabeculectomy in patients presenting with advanced glaucoma in terms of patient-reported health and visual function, clinical outcomes and incremental cost per QALY at 2 years. Conclusions Treatment of Advanced Glaucoma Study will be the first RCT reporting outcomes from the perspective of those with advanced glaucoma. Trial registration number ISRCTN56878850, Pre-results.
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PURPOSE: To investigate the association between control of intraocular pressure after surgical intervention for glaucoma and visual field deterioration. METHODS: In the Advanced Glaucoma Intervention Study, eyes were randomly assigned to one of two sequences of glaucoma surgery, one beginning with argon laser trabeculoplasty and the other trabeculectomy. In the present article we examine the relationship between intraocular pressure and progression of visual field damage over 6 or more years of follow-up. In the first analysis, designated Predictive Analysis, we categorize 738 eyes into three groups based on intraocular pressure determinations over the first three 6-month follow-up visits. In the second analysis, designated Associative Analysis, we categorize 586 eyes into four groups based on the percent of B-month visits over the first 6 follow-up years in which eyes presented with intraocular pressure less than 18 mm Hg, The outcome measure in both analyses is change from baseline in follow-up visual field defect score (range, 0 to 20 units). RESULTS: In the Predictive Analysis, eyes with early average intraocular pressure greater than 17.5 mm Hg had an estimated worsening during subsequent follow-up that was 1 unit of visual field defect score greater than eyes with average intraocular pressure less than 14 mm Hg (P = .002). This amount of worsening was greater at 7 years (1.89 units; P < .001) than at 2 years (0.64 units; P = .071), In the Associative Analysis, eyes with 100% of visits with intraocular pressure less than 18 mm Hg over 6 years had mean changes from baseline in visual field defect score close to zero during follow-up, whereas eyes with less than 50% of visits with intraocular pressure less than 18 mm Hg had an estimated worsening over follow-up of 0.63 units of visual field defect score (P = .083). This amount of worsening was greater at 7 years (1.93 units; P < .001) than at 2 years (0.25 units; P = .572). CONCLUSIONS: In both analyses low intraocular pressure is associated with reduced progression of visual field defect, supporting evidence from earlier studies of a protective role for low intraocular pressure in visual field deterioration.
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Treatments for open-angle glaucoma aim to prevent vision loss through lowering of intraocular pressure, but to our knowledge no placebo-controlled trials have assessed visual function preservation, and the observation periods of previous (unmasked) trials have typically been at least 5 years. We assessed vision preservation in patients given latanoprost compared with those given placebo. In this randomised, triple-masked, placebo-controlled trial, we enrolled patients with newly diagnosed open-angle glaucoma at ten UK centres (tertiary referral centres, teaching hospitals, and district general hospitals). Eligible patients were randomly allocated (1:1) with a website-generated randomisation schedule, stratified by centre and with a permuted block design, to receive either latanoprost 0·005% (intervention group) or placebo (control group) eye drops. Drops were administered from identical bottles, once a day, to both eyes. The primary outcome was time to visual field deterioration within 24 months. Analyses were done in all individuals with follow-up data. The Data and Safety Monitoring Committee (DSMC) recommended stopping the trial on Jan 6, 2011 (last patient visit July, 2011), after an interim analysis, and suggested a change in primary outcome from the difference in proportions of patients with incident progression between groups to time to visual field deterioration within 24 months. This trial is registered, number ISRCTN96423140. We enrolled 516 individuals between Dec 1, 2006, and March 16, 2010. Baseline mean intraocular pressure was 19·6 mm Hg (SD 4·6) in 258 patients in the latanoprost group and 20·1 mm Hg (4·8) in 258 controls. At 24 months, mean reduction in intraocular pressure was 3·8 mm Hg (4·0) in 231 patients assessed in the latanoprost group and 0·9 mm Hg (3·8) in 230 patients assessed in the placebo group. Visual field preservation was significantly longer in the latanoprost group than in the placebo group: adjusted hazard ratio (HR) 0·44 (95% CI 0·28-0·69; p=0·0003). We noted 18 serious adverse events, none attributable to the study drug. This is the first randomised placebo-controlled trial to show preservation of the visual field with an intraocular-pressure-lowering drug in patients with open-angle glaucoma. The study design enabled significant differences in vision to be assessed in a relatively short observation period. Pfizer, UK National Institute for Health Research Biomedical Research Centre. Copyright © 2014 Garway-Heath et al. Open Access article distributed under the terms of CC BY. Published by Elsevier Ltd. All rights reserved.
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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. 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. 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). 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.
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This article introduces the new 5-level EQ-5D (EQ-5D-5L) health status measure. EQ-5D currently measures health using three levels of severity in five dimensions. A EuroQol Group task force was established to find ways of improving the instrument's sensitivity and reducing ceiling effects by increasing the number of severity levels. The study was performed in the United Kingdom and Spain. Severity labels for 5 levels in each dimension were identified using response scaling. Focus groups were used to investigate the face and content validity of the new versions, including hypothetical health states generated from those versions. Selecting labels at approximately the 25th, 50th, and 75th centiles produced two alternative 5-level versions. Focus group work showed a slight preference for the wording 'slight-moderate-severe' problems, with anchors of 'no problems' and 'unable to do' in the EQ-5D functional dimensions. Similar wording was used in the Pain/Discomfort and Anxiety/Depression dimensions. Hypothetical health states were well understood though participants stressed the need for the internal coherence of health states. A 5-level version of the EQ-5D has been developed by the EuroQol Group. Further testing is required to determine whether the new version improves sensitivity and reduces ceiling effects.
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To determine the medium-term intraocular pressure (IOP) control and visual outcomes for patients with advanced glaucoma undergoing trabeculectomy with mitomycin C. All patients with advanced glaucoma (MD -20 dB or above) undergoing trabeculectomy with mitomycin C between 2000 and 2008 under the care of a single glaucoma surgeon were included. IOP, visual acuity and visual field outcomes were assessed from data prospectively collected into a surgical outcome database. 103 patients were eligible for inclusion. The post-trabeculectomy group mean IOP varied between 11.3 and 13.3 mm Hg between 1 and 7 years. At year 5, 85.2% had an IOP of <16 mm Hg, and 96.3% had an IOP of < 21 mm Hg. The number completing a reliable visual-field exam decreased significantly year on year, but the change in mean MD for the group as a whole and for individual patients remained stable. 28 patients experienced a significant reduction in acuity defined as two or more lines of Snellen, although this was not due to glaucoma surgery in the majority. The only preoperative determinant for a significant reduction in VA was the preoperative MD (-27.00 dB (n=21) compared with -24.79 dB (n=63; p=0.029)). Trabeculectomy is a successsful method of controlling IOP in the short to medium term in patients with advanced glaucoma.
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This study examines health differences between first-generation immigrant and Canadian-born persons who share the same the ethnocultural origin, and the extent to which such differences reflect social structural and health-related behavioural contexts. Data from the 2000/2001 Canadian Community Health Survey show that first generation immigrants of Black and French race/ethnicity tend to have better health than their Canadian-born counterparts, while the opposite is true for those of South Asian, Chinese, and south and east European and Jewish origins. West Asians and Arabs and other Asian groups are advantaged in health regardless of country of birth. Health differences between ethnic foreign- and Canadian-born persons generally converge after adjusting for socio-demographic, SES, and lifestyle factors. Implications for health care policy and program development are discussed.
Article
Background/aims Socioeconomic status (SES) is associated with late disease presentation and poorer outcomes. We evaluate the effect of SES on treatment outcomes and report the correlation between SES and baseline characteristics of participants in the Treatment of Advanced Glaucoma Study. Methods Pragmatic multicentre randomised controlled trial. Four hundred and fifty-three patients presenting with advanced open-angle glaucoma in at least one eye (Hodapp-Parrish-Anderson classification). Participants were randomised to either glaucoma drops (medical arm) or trabeculectomy (surgery arm). Clinical characteristics, Quality of life measurement (QoL) and SES defined by the Index of Multiple Deprivation are reported. Subgroup analysis explored treatment effect modifications of SES at 24 months. Correlation between SES and baseline characteristics was tested with the χ ² test of association for dichotomous variables and pairwise Pearson’s correlation for continuous variables. Results The mean visual field mean deviation was −17.2 (6.7)dB for the most deprived quintile of participants and −13.0 (5.5) for the least deprived quintile in the index eye. At diagnosis, there was a strong correlation between SES and ethnicity, age, extent of visual field loss and number of visits to opticians prior to diagnosis. At 24 months, there was no evidence that the treatment effect was moderated by SES. Conclusions In patients presenting with advanced glaucoma. SES at baseline is correlated with poorer visual function, poorer Visual Function Questionnaire-25 QoL, ethnicity, age and number visits to an optician in the years preceding diagnosis. SES at baseline does not have an effect of the success of treatment at 24 months. Trial registration number ISRCTN56878850 .
Article
Purpose: To report the baseline characteristics of participants enrolled in the Treatment of Advanced Glaucoma Study (TAGS) DESIGN: Pragmatic randomised control trial (RCT). Participants: Patients with open angle glaucoma presenting with advanced glaucoma in at least one eye as defined by the Hodapp-Parrish-Anderson (HPA) criteria of severe defect. Methods: Participants with newly diagnosed advanced glaucoma in at least one eye were recruited. Participants were randomly allocated to receive either primary augmented trabeculectomy or primary medical management. When both eyes were eligible, the same intervention was undertaken in both eyes and the index eye for analysis was the eye with the less severe visual field mean deviation (MD). Main outcome measures: Visual field profile defined by the HPA classification, clinical characteristics, Quality of life measured by the National Eye Institute Visual Function Questionnaire 25 (VFQ-25), EuroQual-5 Dimension (EQ-5D 5L), Health Utility Index-3 (HUI-3) and Glaucoma Profile Instrument (GPI) RESULTS: Four hundred and fifty-three patients were recruited. The mean visual field MD was -15.0dB (SD 6.3) in the index eye and -6.2dB in the non-index eye. Of index eyes (HPA 'severe' classification) at baseline, over 70% had a mean deviation < -12.00dB and nearly 90% had more than 20 points defective at the 1% level. The mean LogMAR visual acuity of the index eye was 0.2 (SD 0.3), CONCLUSIONS: TAGS is the first RCT to compare medical and surgical treatments for patients presenting with advanced open angle glaucoma in a publicly funded health service. It will provide clinical, health related quality of life and economic outcomes to inform future treatment choices for those presenting with advanced glaucoma.
Article
Purpose: To evaluate the relationship between medication adherence and visual field progression in participants randomized to the medication arm of the Collaborative Initial Glaucoma Treatment Study (CIGTS). Design: The CIGTS was a randomized, multicenter clinical trial comparing initial treatment with topical medications to trabeculectomy for 607 participants with newly diagnosed glaucoma. Participants: Three hundred seven participants randomized to the medication arm of the CIGTS. Methods: Participants were followed up at 6-month intervals for up to 10 years. Self-reported medication adherence and visual fields were measured. Medication adherence was assessed by telephone from responses to the question, "Did you happen to miss any dose of your medication yesterday?" The impact of medication adherence on mean deviation (MD) over time was assessed with a linear mixed regression model adjusting for the effects of baseline MD and age, cataract extraction, interactions, and time (through year 8, excluding time after crossover to surgery). Medication adherence was modeled as a cumulative sum of the number of prior visits where a missed dose of medication was reported. Main outcome measure: Mean deviation over time. Results: Three hundred seven subjects (306 with adherence data) were randomized to treatment with topical medications and followed up for an average of 7.3 years (standard deviation, 2.3 years). One hundred forty-two subjects (46%) reported never missing a dose of medication over all available follow-up, 112 patients (37%) reported missing medication at up to one third of visits, 31 patients (10%) reported missing medication at one third to two thirds of visits, and 21 patients (7%) reported missing medication at more than two thirds of visits. Worse medication adherence was associated with loss of MD over time (P = 0.005). For subjects who reported never missing a dose of medication, the average predicted MD loss over 8 years was 0.62 dB, consistent with age-related loss (95% confidence interval [CI], 0.17-1.06; P = 0.007); subjects who reported missing medication doses at one third of visits had a loss of 1.42 dB (95% CI, 0.86-1.98; P < 0.0001); and subjects who reported missing medication doses at two thirds of visits showed a loss of 2.23 dB (95% CI, 1.19-3.26; P < 0.0001). Conclusions: This longitudinal assessment demonstrated a statistically and clinically significant association between medication nonadherence and glaucomatous vision loss.
Article
Purpose: To report 3-year results of the Primary Tube Versus Trabeculectomy (PTVT) Study. Design: Unmasked multicenter randomized clinical trial. Participants: Two hundred forty-two eyes of 242 patients with medically uncontrolled glaucoma and no previous incisional ocular surgery, including 125 in the tube group and 117 in the trabeculectomy group. Methods: Patients were enrolled at 16 clinical centers and were assigned randomly to treatment with a tube shunt (350-mm2 Baerveldt glaucoma implant) or trabeculectomy with mitomycin C (MMC; 0.4 mg/ml for 2 minutes). Main outcome measures: The primary outcome measure was the rate of surgical failure, defined as intraocular pressure (IOP) of more than 21 mmHg or reduced less than 20% from baseline, IOP of 5 mmHg or less, reoperation for glaucoma, or loss of light perception vision. Secondary outcome measures included IOP, glaucoma medical therapy, visual acuity, and surgical complications. Results: The cumulative probability of failure after 3 years of follow-up was 33% in the tube group and 28% in the trabeculectomy group (P = 0.17; hazard ratio, 1.39; 95% confidence interval, 0.9-2.2). Mean ± standard deviation IOP was 14.0±4.2 mmHg in the tube group and 12.1±4.8 mmHg in the trabeculectomy group at 3 years (P = 0.008), and the number of glaucoma medications was 2.1±1.4 in the tube group and 1.2±1.5 in the trabeculectomy group (P < 0.001). Serious complications requiring reoperation or producing loss of 2 or more Snellen lines developed in 3 patients (2%) in the tube group and 9 patients (8%) in the trabeculectomy group (P = 0.11). Conclusions: There was no significant difference in the rate of surgical failure between the 2 surgical procedures at 3 years. Trabeculectomy with MMC achieved lower IOP with use of fewer glaucoma medications compared with tube shunt surgery after 3 years of follow-up in the PTVT Study. Serious complications producing vision loss or requiring reoperation occurred with similar frequency after both surgical procedures.
Article
Introduction Glaucoma is a lifelong condition often requiring surgical intervention. To allow us to inform patients’ expectations of surgery effectively, it is important to understand patients’ preferences and concerns regarding outcomes from glaucoma treatments including surgery. Aims To explore what clinical and social outcomes of glaucoma surgery are important to patients. Methods Forty-five glaucoma patients undergoing medical glaucoma treatments or surgery were recruited for focus group interviews to determine their opinions regarding the outcomes of glaucoma treatments. Thematic analysis was performed with NVivo software. Results Themes identified were understanding glaucoma, understanding surgery treatments and understanding treatment outcomes. The most important outcomes of the glaucoma surgery reported by the patients were social factors. Patients felt that being able to maintain their driving licence is a strong indicator of successful glaucoma treatment/surgery. Other important outcomes were independent living, ability to care for their family and having a good-quality social life. When considering novel surgical treatments, most patients felt that certainty of successful outcome and proven longevity of the effect are the primary motivators for choosing these treatments. Conclusions Patients understood that clinical measures were surrogates for maintaining visual function, but ability to maintain independent living was the most important outcome from their treatment. For newer treatments patients wished to know more about long-term outcomes when considering this option.
Article
Objective To provide the results of the Early Manifest Glaucoma Trial, which compared the effect of immediately lowering the intraocular pressure (IOP), vs no treatment or later treatment, on the progression of newly detected open-angle glaucoma. Design Randomized clinical trial. Participants Two hundred fifty-five patients aged 50 to 80 years (median, 68 years) with early glaucoma, visual field defects (median mean deviation, −4 dB), and a median IOP of 20 mm Hg, mainly identified through a population screening. Patients with an IOP greater than 30 mm Hg or advanced visual field loss were ineligible. Interventions Patients were randomized to either laser trabeculoplasty plus topical betaxolol hydrochloride (n = 129) or no initial treatment (n = 126). Study visits included Humphrey Full Threshold 30-2 visual field tests and tonometry every 3 months, and optic disc photography every 6 months. Decisions regarding treatment were made jointly with the patient when progression occurred and thereafter. Main Outcome Measures Glaucoma progression was defined by specific visual field and optic disc outcomes. Criteria for perimetric progression were computer based and defined as the same 3 or more test point locations showing significant deterioration from baseline in glaucoma change probability maps from 3 consecutive tests. Optic disc progression was determined by masked graders using flicker chronoscopy plus side-by-side photogradings. Results After a median follow-up period of 6 years (range, 51-102 months), retention was excellent, with only 6 patients lost to follow-up for reasons other than death. On average, treatment reduced the IOP by 5.1 mm Hg or 25%, a reduction maintained throughout follow-up. Progression was less frequent in the treatment group (58/129; 45%) than in controls (78/126; 62%) (P =.007) and occurred significantly later in treated patients. Treatment effects were also evident when stratifying patients by median IOP, mean deviation, and age as well as exfoliation status. Although patients reported few systemic or ocular conditions, increases in clinical nuclear lens opacity gradings were associated with treatment (P = .002). Conclusions The Early Manifest Glaucoma Trial is the first adequately powered randomized trial with an untreated control arm to evaluate the effects of IOP reduction in patients with open-angle glaucoma who have elevated and normal IOP. Its intent-to-treat analysis showed considerable beneficial effects of treatment that significantly delayed progression. Whereas progression varied across patient categories, treatment effects were present in both older and younger patients, high- and normal-tension glaucoma, and eyes with less and greater visual field loss.
Article
Objective To develop and test the psychometric properties of a 25-list-item version of the National Eye Institute Visual Function Questionnaire (NEI VFQ-25).Design Prospective observational cohort study of persons with 1 of 5 chronic eye diseases or low vision who were scheduled for nonurgent visits in ophthalmology practices and a reference sample of persons without eye disease.Setting Eleven university-based ophthalmology practices and the NEI Clinical Center.Patients Eligible participants had to have 1 of the following eye conditions: age-related cataracts, age-related macular degeneration, diabetic retinopathy, primary open-angle glaucoma, cytomegalovirus retinitis, or low vision from any cause. Seven of the 12 sites also enrolled persons in a reference sample. Reference sample participants had no evidence of underlying eye disease but were scheduled for either screening eye examinations or correction of refractive error. All eligible persons had to be 21 years or older, English speaking, and cognitively able to give informed consent and participate in a health status interview.Measurements and Main Results To provide the data needed to create the NEI VFQ-25, all subjects completed an interview that included the 51-list-item NEI VFQ. Estimates of internal consistency indicate that the subscales of the NEI VFQ-25 are reliable. The validity of the NEI VFQ-25 is supported by high correlations between the short- and long-form versions of the measure, observed between-group differences in scores for persons with different eye diseases of varying severity, and the moderate-to-high correlations between the NEI VFQ-25 subscales that have the most to do with central vision and measured visual acuity.Conclusions The reliability and validity of the NEI VFQ-25 are comparable to those of the 51-list-item NEI VFQ field test version of the survey. This shorter version will be more feasible in settings such as clinical trials where interview length is a critical consideration. In addition, preliminary analyses indicate that the psychometric properties of the NEI VFQ-25 are robust for the eye conditions studied; this suggests that the measure will provide reproducible and valid data when used across multiple conditions of varying severity.
Article
PurposeLarge archives of visual field (VF) records from automated perimetry are used to examine severity of vision loss at diagnosis in glaucoma patients over a 13 year period in England.MethodsA total of 473 252 Humphrey VFs recorded at four regionally different glaucoma clinics in England were retrospectively examined. Patients were required to have a Humphrey mean deviation (MD) outside 95% normative limits in at least one eye and had at least two visits to the glaucoma clinic in a study period between the start of 1999 and the end of 2011. No other clinical data was considered. MD of the worse eye at the first hospital visit was used as an estimate of vision loss for a patient at diagnosis; proportion of patients categorised as having ‘early’ (better than −6 dB) or ‘advanced’ (worse than −12 dB) VF loss were also calculated. Simple linear regression of MD against the date of first visit was used to estimate changes in vision loss at diagnosis over time.ResultsMedian age, at the time of diagnosis, of the 25 521 patients included in the analysis was 67 (interquartile range 55–76) years. Average level of glaucoma vision loss at diagnosis, in those patients presenting to secondary care with a VF defect, improved by an average 0.11 dB per year over the study period (95% confidence interval: 0.08–0.13 dB per year; p < 0.0001). Percentage of patients with ‘advanced’ VF loss in at least one eye at diagnosis changed from 30% (1999–2001) to 21% in (2009–2011) (p < 0.0001).Conclusions Severity of vision loss at the point of glaucoma detection, in those patients diagnosed with a VF defect, is improving over time in England. Nevertheless, the improvement is modest and large numbers of patients still present at glaucoma clinics with significant vision loss in at least one eye. Large scale digital VF data can be used to help monitor and audit health service delivery of glaucoma.
Article
To evaluate the efficacy and safety of current trabeculectomy surgery in the United Kingdom. Cross-sectional, multicenter, retrospective follow-up. A total of 428 eyes of 395 patients. Consecutive trabeculectomy cases with open-angle glaucoma and no previous incisional glaucoma surgery from 9 glaucoma units were evaluated retrospectively. Follow-up was a minimum of 2 years. Surgical success, intraocular pressure (IOP), visual acuity, complications, and interventions. Success was stratified according to IOP, use of hypotensive medications, bleb needling, and resuturing/revision for hypotony. Reoperation for glaucoma and loss of perception of light were classified as failures. Antifibrotics were used in 400 cases (93%): mitomycin C (MMC) in 271 (63%), 5-fluorouracil (5-FU) in 129 (30%), and no antifibrotic in 28 (7%). At 2 years, IOP (mean ± standard deviation) was 12.4±4 mmHg, and 342 patients (80%) achieved an IOP ≤21 mmHg and 20% reduction of preoperative IOP without IOP-lowering medication, whereas 374 patients (87%) achieved an IOP ≤21 mmHg and 20% reduction of preoperative IOP overall. An IOP ≤18 mmHg and 20% reduction of preoperative IOP were achieved by 337 trabeculectomies (78%) without IOP-lowering treatment and by 367 trabeculectomies (86%) including hypotensive medication. Postoperative treatments included suture manipulation in 184 patients (43%), resuturing or revision for hypotony in 30 patients (7%), bleb needling in 71 patients (17%), and cataract extraction in 111 of 363 patients (31%). Subconjunctival 5-FU injection was performed postoperatively in 119 patients (28%). Visual loss of >2 Snellen lines occurred in 24 of 428 patients (5.6%). A total of 31 of the 428 patients (7.2%) had late-onset hypotony (IOP <6 mmHg after 6 months). In 3 of these, visual acuity decreased by >2 Snellen lines. Bleb leaks were observed in 59 cases (14%), 56 (95%) of which occurred within 3 months. Two patients developed blebitis. Bleb-related endophthalmitis developed in 1 patient within 1 month postoperatively and in 1 patient at 3 years. There was an endophthalmitis associated with subsequent cataract surgery. This survey shows that good trabeculectomy outcomes with low rates of surgical complications can be achieved, but intensive proactive postoperative care is required. The author(s) have no proprietary or commercial interest in any materials discussed in this article.
Article
Open angle glaucoma (OAG) is a common cause of blindness. To assess the effects of medication compared with initial surgery in adults with OAG. We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2012, Issue 7), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to August 2012), EMBASE (January 1980 to August 2012), Latin American and Caribbean Literature on Health Sciences (LILACS) (January 1982 to August 2012), Biosciences Information Service (BIOSIS) (January 1969 to August 2012), Cumulative Index to Nursing and Allied Health Literature (CINAHL) (January 1937 to August 2012), OpenGrey (System for Information on Grey Literature in Europe) (www.opengrey.eu/), Zetoc, the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com) and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 1 August 2012. The National Research Register (NRR) was last searched in 2007 after which the database was archived. We also checked the reference lists of articles and contacted researchers in the field. We included randomised controlled trials (RCTs) comparing medications with surgery in adults with OAG. Two authors independently assessed trial quality and extracted data. We contacted study authors for missing information. Four trials involving 888 participants with previously untreated OAG were included. Surgery was Scheie's procedure in one trial and trabeculectomy in three trials. In three trials, primary medication was usually pilocarpine, in one trial it was a beta-blocker.The most recent trial included participants with on average mild OAG. At five years, the risk of progressive visual field loss, based on a three unit change of a composite visual field score, was not significantly different according to initial medication or initial trabeculectomy (odds ratio (OR) 0.74, 95% confidence interval (CI) 0.54 to 1.01). In an analysis based on mean difference (MD) as a single index of visual field loss, the between treatment group difference in MD was -0.20 decibel (dB) (95% CI -1.31 to 0.91). For a subgroup with more severe glaucoma (MD -10 dB), findings from an exploratory analysis suggest that initial trabeculectomy was associated with marginally less visual field loss at five years than initial medication, (mean difference 0.74 dB (95% CI -0.00 to 1.48). Initial trabeculectomy was associated with lower average intraocular pressure (IOP) (mean difference 2.20 mmHg (95% CI 1.63 to 2.77) but more eye symptoms than medication (P = 0.0053). Beyond five years, visual acuity did not differ according to initial treatment (OR 1.48, 95% CI 0.58 to 3.81).From three trials in more severe OAG, there is some evidence that medication was associated with more progressive visual field loss and 3 to 8 mmHg less IOP lowering than surgery. In the longer-term (two trials) the risk of failure of the randomised treatment was greater with medication than trabeculectomy (OR 3.90, 95% CI 1.60 to 9.53; hazard ratio (HR) 7.27, 95% CI 2.23 to 25.71). Medications and surgery have evolved since these trials were undertaken.In three trials the risk of developing cataract was higher with trabeculectomy (OR 2.69, 95% CI 1.64 to 4.42). Evidence from one trial suggests that, beyond five years, the risk of needing cataract surgery did not differ according to initial treatment policy (OR 0.63, 95% CI 0.15 to 2.62).Methodological weaknesses were identified in all the trials. Primary surgery lowers IOP more than primary medication but is associated with more eye discomfort. One trial suggests that visual field restriction at five years is not significantly different whether initial treatment is medication or trabeculectomy. There is some evidence from two small trials in more severe OAG, that initial medication (pilocarpine, now rarely used as first line medication) is associated with more glaucoma progression than surgery. Beyond five years, there is no evidence of a difference in the need for cataract surgery according to initial treatment.The clinical and cost-effectiveness of contemporary medication (prostaglandin analogues, alpha2-agonists and topical carbonic anhydrase inhibitors) compared with primary surgery is not known.Further RCTs of current medical treatments compared with surgery are required, particularly for people with severe glaucoma and in black ethnic groups. Outcomes should include those reported by patients. Economic evaluations are required to inform treatment policy.
Article
Recent National Institute of Clinical Excellence guidance suggests primary surgery should be offered to patients presenting with glaucoma with severe visual field loss. We undertook a survey of UK consultant ophthalmologists to determine if this represents current practice and explore attitudes towards managing patients with advanced glaucoma at presentation. Questionnaire evaluation study. All consultant ophthalmologists currently practicing in the UK. A single-page questionnaire was posted to all consultants (n = 910) currently practicing in the UK along with a pre-paid return envelope. A second questionnaire was sent to non-responders (n = 459). Questionnaire responses. 626 responses were received representing 68.8% of the population surveyed. 152 (24%) volunteered a specialist interest in glaucoma. Consensus opinion for both glaucoma specialists (64.9%) and non-glaucoma specialists (62.4%) was to start with primary medical therapy, most commonly citing surgical risk as the primary reason (23% and 22%, respectively) for this approach. Most felt the highest intraocular pressure measurement during follow up (measured in clinic) was the most important variable for prevention of further visual loss (60% of glaucoma specialists and 55% of non-glaucoma specialists). Eighty-three per cent of all responders suggested they would change their practice if evidence supporting primary surgery as a safe and more effective approach existed. Recent National Institute of Clinical Excellence guidance does not reflect the current management approach of UK ophthalmologists. The primary concern was related to potential complications of surgery although most practitioners would be willing to change their practice if evidence existed supporting primary surgery in patients presenting with advanced glaucoma.
Article
Research on surgical interventions is associated with several methodological and practical challenges of which few, if any, apply only to surgery. However, surgical evaluation is especially demanding because many of these challenges coincide. In this report, the second of three on surgical innovation and evaluation, we discuss obstacles related to the study design of randomised controlled trials and non-randomised studies assessing surgical interventions. We also describe the issues related to the nature of surgical procedures-for example, their complexity, surgeon-related factors, and the range of outcomes. Although difficult, surgical evaluation is achievable and necessary. Solutions tailored to surgical research and a framework for generating evidence on which to base surgical practice are essential.
Article
To evaluate the influence of socio-economic factors on severity of glaucoma at presentation All newly diagnosed glaucoma patients at the University Hospitals-NHS, Aberdeen and South Glasgow University Hospitals-NHS, in 2006, were included. Glaucoma was severe at presentation if there was a repeatable visual-field loss with a mean deviation index greater than 12 dB in the Humphreys visual fields test or an absolute paracentral scotoma within the central 5 degrees of the visual fields. Home address was used to determine the Scottish Index of Multiple Deprivation (SIMD) rank. The SIMD rank, demographics and severity of glaucoma at presentation were investigated using general linear modelling. There were 48 patients with severe glaucoma and 74 patients with non-severe glaucoma. In four, the severity could not be determined. Severity of glaucoma at presentation was significantly associated with SIMD rank, being most severe in patients from areas with the lowest ranks (p = 0.026). Age was a significant factor (p = 0.024), with severe glaucoma being more common in elderly patients. Age and socio-economic deprivation were associated with severity of glaucoma at presentation, with patients from areas of higher socio-economic deprivation presenting with more advanced glaucoma.
Article
To develop and test the psychometric properties of a 25-item version of the National Eye Institute Visual Function Questionnaire (NEI VFQ-25). Prospective observational cohort study of persons with 1 of 5 chronic eye diseases or low vision who were scheduled for nonurgent visits in ophthalmology practices and a reference sample of persons without eye disease. Eleven university-based ophthalmology practices and the NEI Clinical Center. Eligible participants had to have 1 of the following eye conditions: age-related cataracts, age-related macular degeneration, diabetic retinopathy, primary open-angle glaucoma, cytomegalovirus retinitis, or low vision from any cause. Seven of the 12 sites also enrolled persons in a reference sample. Reference sample participants had no evidence of underlying eye disease but were scheduled for either screening eye examinations or correction of refractive error. All eligible persons had to be 21 years or older, English speaking, and cognitively able to give informed consent and participate in a health status interview. To provide the data needed to create the NEI VFQ-25, all subjects completed an interview that included the 51-item NEI VFQ. Estimates of internal consistency indicate that the subscales of the NEI VFQ-25 are reliable. The validity of the NEI VFQ-25 is supported by high correlations between the short- and long-form versions of the measure, observed between-group differences in scores for persons with different eye diseases of varying severity, and the moderate-to-high correlations between the NEI VFQ-25 subscales that have the most to do with central vision and measured visual acuity. The reliability and validity of the NEI VFQ-25 are comparable to those of the 51-item NEI VFQ field test version of the survey. This shorter version will be more feasible in settings such as clinical trials where interview length is a critical consideration. In addition, preliminary analyses indicate that the psychometric properties of the NEI VFQ-25 are robust for the eye conditions studied; this suggests that the measure will provide reproducible and valid data when used across multiple conditions of varying severity.
Article
There is an abundance of evidence from recent randomized clinical trials showing that lowering the IOP is beneficial to the optic nerve and visual field. Setting and achieving a target IOP range is in keeping with evidence-based medicine. The benefits of reaching this target must be weighed against the risks of the treatment itself. Target IOP is a dynamic concept, needing constant reevaluation. What is lacking are established guidelines for determining the target IOP range that can be used in general ophthalmology practice.
Article
To determine by conjoint analysis which factors in the management and treatment of glaucoma were of most importance to patients and to relate these factors to the patient's clinical glaucoma condition. An interview-based study was performed. Demographic and visual function data are recorded. Participants completed the Visual Function Questionnaire-25 and ranked 10 hypothetical patient scenarios that contained different risks of moderate visual loss, postoperative complications, long-term blindness, use of topical medication, and glaucoma surgery. Conjoint analysis was performed to determine the relative importance of these factors for individuals and the group as a whole. Eighty-two patients were interviewed from two consultants' outpatient clinics. Forty-five were male and 37 female. Seventy-nine were white. The most important factors to patients with glaucoma were the risk of moderate visual impairment and the risk of blindness, with an importance of 38% and 27%, respectively. The use of topical medication had an importance of 11%. Proceeding to surgical intervention (trabeculectomy) had an importance of 15%, and the small risk of visual deterioration after surgery (trabeculectomy) had an importance of 9%. To patients, the most important factors regarding glaucoma and its treatment are the risks of moderate visual loss (the ability to continue to drive) and long-term blindness. The treatment methods used are of much less importance.
Article
To estimate a utility-based glaucoma health outcome measure, known as the Glaucoma Utility Index. Based on focus group studies, involving people with glaucoma, existing profile measures relevant to glaucoma were modified and a six-dimensional profile instrument was developed. Dimensions were: central and near vision; lighting and glare; mobility; activities of daily living; eye discomfort and other effects. Each dimension was assigned four levels (no difficulty; some difficulty; quite a lot of difficulty; and severe difficulty). The discrete choice experiment (DCE) approach was employed to move from this profile instrument to a preference-based utility measure. Experimental design techniques were used to derive a sample of health states for which preferences were elicited using the DCE. Four hundred and seventy-three people with glaucoma received the choice questionnaire. The regression analysis was based on 286 consistent responses to the DCE. The regression coefficients for three of the dimensions ("central and near vision," "mobility," and "activities of daily living") moved as expected. Moving from "no difficulty" to "severe difficulty" for central and near vision resulted in the most loss of utility, followed by activities of daily living and mobility. Systemic ("other effects") and local side effects were considered the least important. Utility weights were related to self-reported glaucoma state. Utility estimates moved in line with generic measures of health outcome. This study developed a preference-based utility measure (Glaucoma Utility Index) using the DCE approach. The index, estimated on the basis of 286 respondents, demonstrated both theoretical and convergent validity with other generic health outcome measures and measures of glaucoma severity. Further research investigating preferences by clinically defined glaucoma health status is indicated. Methodological research should focus on alternative methods of scaling for use within a generic Quality Adjusted Life Year framework.
Terminology and Guidelines for Glaucoma
  • European Glaucoma Society
The relationship between control of intraocular pressure and visual field deterioration.The AGIS Investigators
Primary open angle glaucoma: Preferred Practice Patterns
  • American Academy
  • Ophthalmology
Certificate of Vision Impairment: Explanatory Notes for Consultant Ophthalmologists and Hospital Eye Clinic Staff in England. Leeds: Department of Health
  • Department
  • Health
Will the PRESERFLO™ MicroShunt impact the future of trabeculectomy practice?
  • Kuet