Although there is high-level evidence that treatment decreases IOP and reduce the risk of structural and functional progression in OHT and glaucoma compared to no treatment, the direct effects of treatments on visual impairment and the comparative efficacy of different treatments are not clear. Which treatments improve patient-reported outcomes is also unclear.
Based on the economic simulation models in the US, UK, Holland, and China, treating glaucoma appears to be cost effective compared to ‘no treatment’. There is uncertainty whether to treat none, some or all patients with ocular hypertension. When treated, the cost-effectiveness models of different therapeutic interventions give variable results.
Comment
All published simulation models are based on characteristics of participants enrolled in relatively small and tight randomized controlled trials (RCTs) which may not include all important predictors in the general population and every-day practice. In addition, RCTs may give an optimistic impression of outcomes compared to ‘real life' with poorer compliance and adherence to care both in patients and clinicians in implementing the guidelines and care protocols. As the data of glaucoma induced visual disability are limited, the blindness rates in the modeling studies have different estimates.Similarly, the data on utility values and influence of glaucoma severity in health status are limited. Reliable and ‘realistic' data (preferably from large randomized trials or prospective cohorts of ‘usual patients') is not available so far. Retrospective observational data is incomplete and selective.
Systematic review
Systematic review searched for systematic reviews published by March 2011 as well primary studies without imposed language, sample size, or date restrictions up to 30 July 2012.
High-level evidence suggests that medical and surgical treatments for open-angle glaucoma lower intraocular pressure and reduce the risk for optic nerve damage over the short to medium term. Which treatments best prevent visual disability and improve patient-reported outcomes is unclear. The limitations included heterogeneous outcome definitions and measurements among the included studies; exclusion of many treatment studies that did not stratify results by glaucoma type.
No systematic reviews of medical or surgical interventions for OAG were identified directly addressing visual impairment. Primary studies that met inclusion criteria were identified. However, none were of sufficient duration or size to identify outcomes that plausibly could be related to visual impairment due to glaucoma «Boland MV, Ervin AM, Friedman DS ym. Comparative e...»1.
Study 1 (external validation of the OHTS-EGPS model for predicting the 5-year risk of open-angle glaucoma in ocular hypertensives)
The study independently evaluated and compared the performance of the Ocular Hypertension Treatment Study-European Glaucoma Prevention Study (OHTS-EGPS) prediction equation for estimating the 5-year risk of open-angle glaucoma (OAG) in four cohorts of adults with ocular hypertension. Data from two randomised controlled trials and two observational studies were analysed individually to assess transferability of the prediction equation between different geographical locations and settings. To make best use of the data and to avoid bias, missing predictor values were imputed using multivariate imputation by chained equations. Using the OHTS-EGPS risk prediction equation, predicted risk was calculated for each patient in each cohort.
Analyses were based on 393, 298, 188 and 159 patients for the Rotterdam, Moorfields, Dunfermline, and Nottingham cohorts, respectively. The discriminative ability was good, with c-indices between 0.69 and 0.83. In calibration analyses, the risk of OAG was generally overestimated, although for the Rotterdam cohort the calibration slope was close to 1 (1.09, 95% CI 0.72 to 1.46), the ideal value when there is perfect agreement between predicted and observed risks. The OHTS-EGPS risk prediction equation has predictive utility, but further validation in a population-based setting is needed «Takwoingi Y, Botello AP, Burr JM ym. External vali...»2.
Review
Simulation model
An economic simulation model determining the cost-effectiveness of treating NTG with IOP lowering therapy to prevent progressive visual field loss.
Transitional probabilities were derived from the Collaborative Normal Tension Glaucoma Study and cost data obtained from the literature and the Medicare fee schedule.
The extra cost of treating all patients with NTG over a 10-year period in the US was $34,225 per QALY, patients with disc hemorrhage US $24,350, migraine US $25,533, and females US $27,000 per QALY.
The cost-effectiveness of treating all NTG patients was sensitive to cost fluctuation of medications, choice of utility score associated with disease progression, and insensitive to cost of consultations and laser/surgery «Li EY, Tham CC, Chi SC ym. Cost-effectiveness of t...»4.
Systematic review and simulation model
The UK Health Technology Assessment compared five alternative surveillance and treatment pathways in OHT.
The two most intensive pathways were based on the NICE guidelines (check-ups from every 4-12 -month to 6-24 -month intervals depending on initial risk), two further pathways followed biennial follow-up schemes differing in location (surveillance either in hospital or in primary care), and in the fifth ‘Treat all' pathway, all IOPs > 21 mmHg were treated with prostaglandins. In ‘Treat all' pathway, IOP was measured annually in community optometry with referral to a hospital only if IOP reduction was <15%.
The results of the model indicated no clear benefit from intensive monitoring in OHT. ‘Treat all' was the least and ‘NICE intensive' was the most costly pathway.
Compared to 'Treat all' –strategy, however, the pathway with 2-year check ups in an eye hospital (and treatment with > 5% glaucoma risk in 5 years) reduced the incidence of conversion to glaucoma and provided more QALYs. However, simultaneously this pathway cost considerably more - above the limit of the society's willingness to pay in the UK.
For the cost-benefit analysis the biennial hospital pathway was the only pathway relative to ‘no surveillance' that had a positive net benefit.
The results of the UK model were sensitive treatment adherence. Due to sparse evidence, the UK model (based on expert opinion) assumed adherence of 50% in 'Treat all' pathway and 75% in the other four monitoring pathways «Burr JM, Botello-Pinzon P, Takwoingi Y ym. Surveil...»5.
Systematic reviews and simulation models (Holland)
An economic simulation model in Holland (built on systematic evaluation of literature)
The results suggested that treating all OHT patients with IOP > 21 mmHg would be cost saving compared to watchful waiting – even if 43% of the simulated untreated OHT patients never converted to glaucoma in their entire lifetime.
Non-adherence to the medication was not considered in the model. It was assumed that including adherence would have a small impact of the outcomes but would have unnecessarily increased the complexity of the model.
In eyes with manifest glaucoma, in lieu of 'guessing' the initial target pressure and redefining it according to rate of progression, the model suggested to aim at a standard IOP < 15 mmHg in all glaucoma patients - even if it the model indicated that 72% would need direct combination therapy and 46% would require glaucoma surgery.
According to the model, these simplified strategies would decrease demand for intensive monitoring «van Gestel A. Glaucoma management. Economic evalua...»6.