Effectiveness and cost-effectiveness of MicroShunt implantation versus standard trabeculectomy for open-angle glaucoma (a SIGHT study): study protocol of a multicentre randomised controlled trial.

BACKGROUND: Trabeculectomy is the "gold standard" initial surgical procedure for open-angle glaucoma worldwide. During the last decade, the introduction of less invasive procedures, including new bleb-forming surgery such as the MicroShunt, has altered the approach of glaucoma management. At present, there is insufficient evidence comparing the effectiveness between these procedures nor versus trabeculectomy. Furthermore, there is no data available on patient impact and cost-effectiveness. This study aims to address this gap in evidence and establish whether MicroShunt implantation is non-inferior compared to trabeculectomy with regard to effectiveness and whether it is cost-effective. METHODS: A multicentre, non-inferiority, randomised controlled trial (RCT) studying open-angle glaucoma with an indication for surgery will be conducted. Patients with previous ocular surgery except for phacoemulsification are excluded, as are patients with ocular comorbidity compromising the visual field or requiring a combined procedure. After informed consent is obtained, patients will be randomly allocated to the intervention, a PRESERFLO™ MicroShunt implantation, or the control group, trabeculectomy, using block randomisation (blocks of 2, 4 or 6 patients). In total, 124 patients will be randomised in a 1:1 ratio, stratified by centre. The primary endpoint will be intraocular pressure (IOP) one year after surgery. Secondary outcomes include IOP-lowering medication use, treatment failure, visual acuity, visual field progression, additional interventions, adverse events, patient-reported outcome measures (PROMs), and cost-effectiveness. Study outcomes will be measured up to 12 months postoperatively. DISCUSSION: This study protocol describes the design of a multicentre non-inferiority randomised controlled trial. To this date, cost-effectiveness studies evaluating the MicroShunt have not been undertaken. This multicentre RCT will provide more insight into whether MicroShunt implantation is non-inferior compared to standard trabeculectomy regarding postoperative IOP and whether MicroShunt implantation is cost-effective. TRIAL REGISTRATION: ClinicalTrials.gov, Identifier: NCT03931564 , Registered 30 April 2019.

Prediction of Glaucomatous Visual Field Progression Using Baseline Clinical Data.

PURPOSE: To develop a prediction model for glaucomatous visual field progression using easily accessible baseline clinical data. PATIENTS AND METHODS: We collected baseline data of 613 consecutive patients with open-angle glaucoma from 2001 to 2003. The rate of visual field progression was calculated using the Visual Field Index (VFI) of routine follow-up examinations until 2010. Baseline data of 333 patients from 3 hospitals were used to develop a model to predict the rate of VFI progression using a linear regression analysis and univariate preselection (P<0.1) of 8 candidate predictors. The performance of the model was investigated using R, the area under the receiver-operating characteristic curve, and calibration plots. The prediction model was internally validated using bootstrapping and externally validated in 280 patients from 2 other hospitals. RESULTS: After a mean follow-up period of 5.8 years of all 613 eyes, the mean rate of VFI progression was -1.6% per year. The final model contained the following predictors: age, baseline intraocular pressure, and baseline visual field status. During model development, 10.3% of the observed variation in VFI rates was explained by the model. The area under the receiver-operating characteristic curve was 0.76 when the prediction model was used to detect a VFI rate of -3% per year or worse, which decreased to 0.71 at external validation. CONCLUSIONS: Although our prediction model could explain only a small amount of the variance in visual field progression, it may offer the possibility to identify subgroups of treated patients with high rates of visual field progression, thereby providing an opportunity to select those patients for more intensive treatment.

Prevalence of end-of-life visual impairment in patients followed for glaucoma.

PURPOSE: To assess the prevalence of end-of-life visual impairment in patients followed for glaucoma. METHODS: Data of 122 patients followed for glaucoma who had died between July 2008 and July 2010 and who had visited the ophthalmology outpatient department of a large non-academic Dutch hospital were collected from the medical files. Sixty-one patients had open-angle glaucoma (OAG), and 61 patients were suspect for glaucoma or had ocular hypertension (OHT). Visual impairment was defined as a mean deviation value <-15 dB or a Snellen visual acuity <0.3 (20/60) of the better eye. We determined the number of patients with visual impairment on the last patient visit before death and investigated its main explanations. RESULTS: Overall, the mean age at death was 81.8 years after a mean follow-up period of 9.2 years. Seventy-three per cent of all patients had their last visit in the year preceding death. In OAG, 16 patients (26%) had an end-of-life visual impairment. In nine patients (15%), this was caused by glaucoma. Eight of them had substantial visual loss at the initial visit. Six (10%) impaired OAG cases were mainly explained by ocular comorbidity, and there was an equal contribution of comorbidity and glaucoma in one case. Five glaucoma suspects or patients with OHT (8%) were visually impaired at death and these were all caused by ocular comorbidity. CONCLUSION: The prevalence of end-of-life visual impairment is considerable in patients with OAG. Substantial visual loss at baseline is an important contributing factor. In glaucoma suspects or patients with OHT, the prevalence is lower and can be attributed to ocular comorbidity.

An evidence-based review of prognostic factors for glaucomatous visual field progression.

PURPOSE: To examine which prognostic factors are associated with glaucomatous visual field progression. DESIGN: Knowledge of prognostic factors helps clinicians to select patients at risk of glaucomatous visual field progression and intensify their treatment. METHODS: By consulting relevant databases, we identified 2733 articles published up to September 2010, of which 85 articles investigating prognostic factors for visual field progression in patients with open-angle glaucoma (OAG) were eligible. We summarized results for each factor in tables, noting the direction of the association between the prognostic factor and progression, and the accompanying P value. Four authors, working blind to the factors, independently judged the extent to which a prognostic factor was associated with glaucomatous visual field progression. If there were different associations for normal-tension glaucoma (NTG) studies, they were judged separately. Consensus was reached during group meetings. MAIN OUTCOME MEASURES: A ranking of all studied prognostic factors for glaucomatous visual field progression according to their likelihood of being prognostic. RESULTS: A total of 103 different prognostic factors were investigated in 85 articles. The following factors were clearly associated with glaucomatous visual field progression: age, disc hemorrhages (for NTG), baseline visual field loss, baseline intraocular pressure (IOP), and exfoliation syndrome. An association was unlikely for family history of glaucoma, atherosclerosis, systemic hypertension, visual acuity, sex (for NTG), systolic blood pressure, myopic refractive error (for NTG), and Raynaud's phenomenon. CONCLUSIONS: The factors we found clearly associated with progression could be used in clinical practice and for developing clinical prediction models. For many other factors, further research is necessary.

The evidence base to select a method for assessing glaucomatous visual field progression.

A large number of methods have been developed for assessing glaucomatous visual field progression, but their properties have not yet been systematically evaluated. In this systematic literature review, we summarize the evidence base for selecting a method by providing answers to ten relevant questions on the variety, validity and reproducibility of methods. In total, we found 301 different methods in 412 articles. The majority of studies (54%) used the Humphrey Field Analyzer. No data have been published about the reproducibility of methods. Although there is no gold standard to assess glaucomatous visual field progression, we found evidence on validity for 48 different methods. Some methods were less capable of distinguishing between progressive and nonprogressive patients. Choosing among twelve methods is supported by some evidence of their validity. These methods still differ in sensitivity, specificity and predictive values of test results within studies comparing several methods. In conclusion, the current evidence base is not perfect. A selection should be made from a limited number of methods, according to the clinical purpose of progression assessment. Methods that quantify the rate of visual field progression seem to be the most appropriate for guiding subsequent medical actions in individual patients. Future studies should investigate whether using one method to monitor patients is superior to another method in preventing loss of quality of life.

The influence of the assessment method on the incidence of visual field progression in glaucoma: a network meta-analysis.

PURPOSE: To study and quantify the difference in incidence of progression between methods for the assessment of glaucomatous visual field progression. METHODS: We identified 2450 articles published up to April 2009 in the following data sources: PubMed, EMBASE, and Cochrane. Ten studies covering 30 methods were included. All studies aimed to compare different methods for the assessment of glaucomatous visual field progression in the same study population. A network meta-analysis using a mixed-effects model was performed to combine within-study between-method comparisons with indirect comparisons from other studies. The summarized incidence of progression was calculated for every method, and methods were ranked according to this incidence. RESULTS: In total, methods were compared in 1040 eyes of 948 patients with glaucoma. On average, 21% of the eyes progressed. When all 30 methods were ranked, the incidence ranged from 2% to 62%. These incidences are corrected for a baseline mean deviation (MD) value of -7 decibels and a mean follow-up time of 6 years. Besides the assessment method, the incidence was only determined by the follow-up period and baseline MD value, leaving no unexplained variance in the incidence of progression. CONCLUSION: The incidence of progression varies considerably between different studies. This is mainly caused by the variety of methods used to assess progression but also by differences in follow-up time and baseline visual field loss.

Outcome of ABCA4 microarray screening in routine clinical practice.

PURPOSE: To retrospectively analyze the clinical characteristics of patients who were screened for mutations with the ATP-binding cassette transporter gene ABCA4 (ABCA4) microarray in a routine clinical DNA diagnostics setting. METHODS: We performed a retrospective analysis of the medical charts of 65 patients who underwent an ABCA4 microarray screening between the years 2002 and 2006. An additional denaturing gradient gel electrophoresis (DGGE) was performed in these patients if less than two mutations were found with the microarray. We included all patients who were suspected of autosomal recessive Stargardt disease (STGD1), autosomal recessive cone-rod dystrophy (arCRD), or autosomal recessive retinitis pigmentosa at the time of microarray request. After a retrospective analysis of the clinical characteristics, the patients who were suspected of STGD1 were categorized as having either a typical or atypical form of STGD1, according to the age at onset, fundus appearance, fluorescein angiography, and electroretinography. The occurrence of typical clinical features for STGD1 was compared between patients with different numbers of discovered mutations. RESULTS: Of the 44 patients who were suspected of STGD1, 26 patients (59%) had sufficient data available for a classification in either typical (six patients; 23%) or atypical (20 patients; 77%) STGD1. In the suspected STGD1 group, 59% of all expected pathogenic alleles were found with the ABCA4 microarray. DGGE led to the finding of 12 more mutations, resulting in an overall detection rate of 73%. Thirty-one percent of patients with two or three discovered ABCA4 mutations met all typical STGD1 criteria. An age at onset younger than 25 years and a dark choroid on fluorescein angiography were the most predictive clinical features to find ABCA4 mutations in patients suspected of STGD1. In 18 patients suspected of arCRD, microarray screening detected 22% of the possible pathogenic alleles. CONCLUSIONS: In addition to confirmation of the diagnosis in typical STGD1, ABCA4 microarray screening is usually requested in daily clinical practice to strengthen the diagnosis when the disease is atypical. This study supports the view that the efficiency and accuracy of ABCA4 microarray screening are directly dependent upon the clinical features of the patients who are screened.