Henny J. M. Beckers

The relationship between visual field loss in glaucoma and health-related quality-of-life

PurposeTo investigate the relationship between visual field loss and health-related quality-of-life (HRQOL) in patients with ocular hypertension (OHT) or primary open-angle glaucoma (POAG).MethodsWe conducted a cross-sectional study among 537 OHT and POAG patients from seven hospitals in The Netherlands. Clinical information was obtained from medical files. Patients completed a questionnaire, containing generic HRQOL instruments (EQ-5D and Health Utilities Index mark 3), vision-specific National Eye Institute Visual Functioning Questionnaire (VFQ-25), and glaucoma-specific Glaucoma Quality-of-Life questionnaire (GQL-15). The impact of visual field loss on HRQOL scores was analysed with multiple linear regression analyses.ResultsA relationship between mean deviation (MD) and HRQOL was found after adjusting for age, gender, visual acuity, medication side effects, laser trabeculoplasty, and glaucoma surgery. We found interaction between MD in both eyes for GQL and VFQ-25 scores. The relationship between MD and utility was non-linear, with utility only affected at MD-values below −25 dB in the better eye. Visual acuity, side effects, and glaucoma surgery independently affected HRQOL. Binocular MD and MD in the better eye had similar impacts on HRQOL, whereas MD in the worse eye had an independent effect. HRQOL was affected more by binocular defects in the inferior than in the superior hemifield.ConclusionVisual field loss in progressing glaucoma is independently associated with a loss in both disease-specific and generic quality-of-life. It is important to prevent progression, both in early and in advanced glaucoma, especially in patients with inferior hemifield defects and severe defects in either eye.

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 Raynauds 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.

Pharmacological management of primary open-angle glaucoma: second-line options and beyond

Glaucoma is one of the leading causes of blindness worldwide. Increased intraocular pressure (IOP) is considered to be the most important risk factor. Major outcome studies from recent years have shown that lowering IOP is beneficial in primary open-angle glaucoma and ocular hypertension. The introduction of new classes of IOP-lowering drugs (α2-adrenoceptor agonists, topical carbonic anhydrase inhibitors and hypotensive lipids) in the last decade has contributed to a change in the drug prescription pattern. Together with β-adrenoceptor antagonists (β-blockers), these drugs are now considered to be first-choice classes, giving ophthalmologists ample opportunities to choose from a broad spectrum of IOP-lowering drugs. The number of possible medical treatment combinations has increased likewise.We review medical treatment combinations of two, three or four drugs from the four major first-choice glaucoma drug classes and provide an overview of the scientific evidence for IOP efficacy of second-line medical options when first-line therapy has been effective but additional IOP lowering is necessary. A systematic search of the literature initially revealed 2729 publications. After a thorough selection process, 42 studies were found to be eligible for inclusion in the review. Publications were excluded if the primary endpoint of the study was not IOP or if glaucoma topics other than IOP lowering of drugs were studied. In addition, studies that reported results for monotherapies only were excluded. The vast majority of study arms reported on combinations of a β-blocker with either a carbonic anhydrase inhibitor or a hypotensive lipid. For a number of treatment combinations no eligible studies were available or could be included.This review shows that combining drugs from the different first-choice classes results in an additional IOP decrease. The exact magnitude of this additional decrease and the patients to whom it applies remain unclear. In many studies, no information on IOP before the run-in phase was available. However, such data are important in order to determine whether patients with high untreated IOP or patients non-responsive to the run-in drug(s) were preferentially included. Another issue that hampers interpretation is the fact that the timepoints of measurements of IOP before and after adding a drug should be related to the peak and trough times of the drugs. Finally, differences between concomitant use and fixed combined use of drugs may have consequences for the interpretation of results.

Modeling Complex Treatment Strategies: Construction and Validation of a Discrete Event Simulation Model for Glaucoma

OBJECTIVE Discrete event simulation (DES) modeling has several advantages over simpler modeling techniques in health economics, such as increased flexibility and the ability to model complex systems. Nevertheless, these benefits may come at the cost of reduced transparency, which may compromise the models face validity and credibility. We aimed to produce a transparent report on the construction and validation of a DES model using a recently developed model of ocular hypertension and glaucoma. METHODS Current evidence of associations between prognostic factors and disease progression in ocular hypertension and glaucoma was translated into DES model elements. The model was extended to simulate treatment decisions and effects. Utility and costs were linked to disease status and treatment, and clinical and health economic outcomes were defined. The model was validated at several levels. The soundness of design and the plausibility of input estimates were evaluated in interdisciplinary meetings (face validity). Individual patients were traced throughout the simulation under a multitude of model settings to debug the model, and the model was run with a variety of extreme scenarios to compare the outcomes with prior expectations (internal validity). Finally, several intermediate (clinical) outcomes of the model were compared with those observed in experimental or observational studies (external validity) and the feasibility of evaluating hypothetical treatment strategies was tested. RESULTS The model performed well in all validity tests. Analyses of hypothetical treatment strategies took about 30 minutes per cohort and lead to plausible health-economic outcomes. CONCLUSION There is added value of DES models in complex treatment strategies such as glaucoma. Achieving transparency in model structure and outcomes may require some effort in reporting and validating the model, but it is feasible.

New ophthalmologic imaging techniques for detection and monitoring of neurodegenerative changes in diabetes: a systematic review

Optical coherence tomography (OCT) of the retina and around the optic nerve head and corneal confocal microscopy (CCM) are non-invasive and repeatable techniques that can quantify ocular neurodegenerative changes in individuals with diabetes. We systematically reviewed studies of ocular neurodegenerative changes in adults with type 1 or type 2 diabetes and noted changes in the retina, the optic nerve head, and the cornea. Of the 30 studies that met our inclusion criteria, 14 used OCT and 16 used CCM to assess ocular neurodegenerative changes. Even in the absence of diabetic retinopathy, several layers in the retina and the mean retinal nerve fibre layer around the optic nerve head were significantly thinner (-5·36 μm [95% CI -7·13 to -3·58]) in individuals with type 2 diabetes compared with individuals without diabetes. In individuals with type 1 diabetes without retinopathy none of the intraretinal layer thicknesses were significantly reduced compared with individuals without diabetes. In the absence of diabetic polyneuropathy, individuals with type 2 diabetes had a lower nerve density (nerve branch density: -1·10/mm(2) [95% CI -4·22 to 2·02]), nerve fibre density: -5·80/mm(2) [-8·06 to -3·54], and nerve fibre length: -4·00 mm/mm(2) [-5·93 to -2·07]) in the subbasal nerve plexus of the cornea than individuals without diabetes. Individuals with type 1 diabetes without polyneuropathy also had a lower nerve density (nerve branch density: -7·74/mm(2) [95% CI -14·13 to -1·34], nerve fibre density: -2·68/mm(2) [-5·56 to 0·20]), and nerve fibre length: -2·58 mm/mm(2) [-3·94 to -1·21]). Ocular neurodegenerative changes are more evident when diabetic retinopathy or polyneuropathy is present. OCT and CCM are potentially useful, in addition to conventional clinical methods, to assess diabetic neurodegenerative changes. Additional research is needed to determine their incremental benefit and to standardise procedures before the application of OCT and CCM in daily practice.

The intraocular pressure-lowering effect of prostaglandin analogs combined with topical β-blocker therapy: a systematic review and meta-analysis.

OBJECTIVE To estimate the intraocular pressure (IOP)-lowering effect of prostaglandin analogs (PGAs) when added to topical β-blocker (BB) therapy. DESIGN Systematic review and meta-analyses of randomized clinical trials. PARTICIPANTS Twenty-nine articles reporting on 33 study arms and 3 control arms. METHODS Articles published between January 1, 1990, and August 18, 2009, were identified in relevant databases. The pooled IOP-lowering effects at the 1- to 3-month follow-ups were calculated by performing random effects meta-analyses. MAIN OUTCOME MEASURES Absolute and relative change in IOP for mean diurnal curve and highest and lowest IOP decrease on the diurnal IOP curve. RESULTS Adding 0.005% latanoprost in the evening to 0.5% timolol twice daily resulted in a pooled change of -6.3 mmHg (95% CI, -7.1 to -5.5 mmHg, mean IOP curve); switching to the fixed combination of 0.5% timolol and 0.005% latanoprost in the morning resulted in a pooled change of -2.8 mmHg (95% CI, -3.3 to -2.3 mmHg, mean IOP curve). Starting with any fixed combination of 0.5% timolol and a PGA in the morning resulted in a pooled change of -8.4 mmHg (95% CI, -9.1 to -7.6 mmHg, mean IOP curve) and varied between -9.1 mmHg (95% CI, -9.9 to -8.2 mmHg, highest) and -7.9 mmHg (95% CI, -8.5 to -7.2 mmHg, lowest); starting with any fixed combination of 0.5% timolol and a PGA in the evening resulted in a pooled change of -8.6 (95% CI, -9.2 to -8.0 mmHg, mean IOP curve) and varied between -10.1 mmHg (95% CI, -11.0 to -9.2 mmHg, highest) and -7.3 mmHg (95% CI, -8.1 to -6.4 mmHg, lowest). CONCLUSIONS The concomitant use of latanoprost and timolol leads to a larger additional IOP reduction when compared with the fixed combination. There is no difference in mean IOP-lowering effect between evening and morning dosing of a fixed combination of timolol and a PGA, although the largest IOP decreases are seen with evening dosing. These findings are explained by differences in study design. When time points of IOP measurements close to the peak or trough moment of a drug are included, the IOP-lowering effect will be overestimated or underestimated, respectively. FINANCIAL DISCLOSURE(S) Proprietary or commercial disclosure may be found after the references.

Side effects of commonly used glaucoma medications: comparison of tolerability, chance of discontinuation, and patient satisfaction

BackgroundTo compare the tolerability of commonly prescribed topical glaucoma medications by determining frequency and bother of side effects, patient satisfaction with their medication, and the chance of discontinuation of eye drops.MethodsThe tolerability of topical glaucoma medication was studied in glaucoma patients from nine hospitals. The frequency and severity of side effects was investigated together with patient satisfaction with the medication and the probability to change medication due to reported side effects. To register side effects of topical glaucoma medication, patients were requested to fill in a questionnaire based on “the Comparison of Ophthalmic Medications for Tolerability” (COMTOL) questionnaire supplemented with items based on the most frequently observed and severe side effects.ResultsThe number of patients responding was 3,333 (87%). Most patients (79%) were satisfied with their eye medication. The median score for ocular side effects was 58 on a scale ranging from 0 to 320. The probability that medication would be changed by the ophthalmologist at the next visit due to reported side effects occurring since the patients’ last or last but one visit to the ophthalmologist was 9%. The most frequently prescribed drugs were timolol, latanoprost, and the fixed combinations of dorzolamide/timolol (Cosopt®) and latanoprost/timolol (Xalcom®). Only small differences in tolerability were found between these drugs.ConclusionsThe tolerability of timolol, latanoprost, and the fixed combinations of latanoprost/timolol (Xalcom®) and dorzolamide/timolol (Cosopt®) seem to be comparable. Patients are satisfied with their glaucoma medication and have a low chance of discontinuation of eye drops due to side effects.

Toric vs Aspherical Control Intraocular Lenses in Patients With Cataract and Corneal Astigmatism: A Randomized Clinical Trial

IMPORTANCE Spectacle independence is becoming increasingly important in cataract surgery. Not correcting corneal astigmatism at the time of cataract surgery will fail to achieve spectacle independency in 20% to 30% of patients. OBJECTIVE To compare bilateral aspherical toric with bilateral aspherical control intraocular lens (IOL) implantation in patients with cataract and corneal astigmatism. DESIGN, SETTING, AND PARTICIPANTS A multicenter, hospital-based, randomized clinical trial was conducted. The participants included 86 individuals with bilateral cataract and bilateral corneal astigmatism of at least 1.25 diopters (D) who were randomized to receive either bilateral toric (n = 41) or bilateral control (n = 45) IOL implantation. INTERVENTIONS Bilateral implantation of an aspherical toric IOL or an aspherical control IOL. MAIN OUTCOMES AND MEASURES Spectacle independency for distance vision, uncorrected distance visual acuity, refractive astigmatism, contrast sensitivity, wavefront aberrations, and refractive error-related quality-of-life questionnaire. RESULTS Preoperatively, mean (SD) corneal astigmatism was 2.02 (0.95) D and 2.00 (0.84) D in the toric and control groups, respectively. Four patients (5%) were lost to follow-up. At 6 months postoperatively, 26 (70%) of the patients in the toric group achieved an uncorrected distance visual acuity of 20/25 or better compared with 14 (31%) in the control group (P < .001; odds ratio, 5.23; 95% CI, 2.03-13.48). Spectacle independency for distance vision was achieved in 31 patients (84%) in the toric group compared with 14 patients (31%) in the control group (P < .001; odds ratio, 11.44; 95% CI, 3.89- 33.63). Mean refractive astigmatism was -0.77 (0.52) D and -1.89 D (1.00) D, respectively. Vector analysis of toric IOLs showed a mean magnitude of error of +0.38 D, indicative of overcorrection. No significant differences were found in contrast sensitivity, higher-order aberrations, or refractive error-related quality of life. CONCLUSIONS AND RELEVANCE In patients with cataract and corneal astigmatism, bilateral toric IOL implantation results in a higher spectacle independency for distance vision compared with bilateral control IOL implantation. No significant differences were identified in contrast sensitivity, higher-order aberrations, or refractive error-related quality of life following both treatments. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01075542.

The role of the expected value of individualized care in cost-effectiveness analyses and decision making

OBJECTIVE To explore the feasibility and potential role of the expected value of individualized care (EVIC) framework. METHODS The EVIC quantifies how much benefits are forgone when a treatment decision is based on the best-expected outcomes in the population rather than in the individual patient. We have reviewed which types of patient-level attributes contribute to the EVIC and how they affect the interpretation of the outcomes. In addition, we have applied the EVIC framework to the outcomes of a microsimulation-based cost-effectiveness analysis for glaucoma treatment. RESULTS For EVIC outcomes to inform decisions about clinical practice, we need to calculate the parameter-specific EVIC of known or knowable patient-level attributes and compare it with the real costs of implementing individualized care. In the case study, the total EVIC was €580 per patient, but patient-level attributes known at treatment decision had minimal impact. A subgroup policy based on individual disease progression could be worthwhile if a predictive test for glaucoma progression could be developed and implemented for less than €130 per patient. CONCLUSIONS The EVIC framework is feasible in cost-effectiveness analyses and can be informative for decision making. The EVIC outcomes are particularly informative when they are (close to) zero. When the EVIC has a high value, implications depend on the type of patient-level attribute. EVIC can be a useful tool to identify opportunities to improve efficiency in health care by individualization of care and to quantify the maximal investment opportunities for implementing subgroup policy.

The long-term outcomes of four alternative treatment strategies for primary open-angle glaucoma.

Purpose:  To evaluate the long‐term effects and costs of four treatment strategies for primary open‐angle glaucoma compared to usual care.