Medical versus surgical interventions for open angle glaucoma

School of Medicine, Medical and Biological Sciences Building, University of St Andrews, Fife, UK. .
Cochrane database of systematic reviews (Online) (Impact Factor: 6.03). 09/2012; 9(9):CD004399. DOI: 10.1002/14651858.CD004399.pub3
Source: PubMed


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) (, Zetoc, the metaRegister of Controlled Trials (mRCT) ( and the WHO International Clinical Trials Registry Platform (ICTRP) ( 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.

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    • "A controlled leaking area for aqueous humor is formed, called a filtration bleb. Although this procedure may be crucial in the management of glaucoma,1,2 it carries a risk of complications. Excessive postoperative wound healing of the conjunctiva and Tenon’s capsule, with subsequent scarring, is known to frequently lead to surgical failure,3 associated with poor postoperative IOP control and consequent progression of glaucomatous disc cupping and visual field loss. "
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    ABSTRACT: Of all the treatments currently used to lower intraocular pressure in glaucoma patients, filtration surgery is known to be the most effective. However, in a significant percentage of cases, the constructed channel closes due to excessive scar formation, resulting in surgical failure. The process of postoperative wound healing is characterized by the coagulative and inflammatory phase, followed by the proliferative and repair phase, and finally the remodeling phase. Perioperative antimitotic agents, such as mitomycin C and 5-fluorouracil, are known to modulate the process of wound healing and to improve surgical outcome, but they carry a risk of vision-threatening complications. New alternative strategies to prevent filtration failure, such as inhibition of transforming growth factor-β, vascular endothelial growth factor, and placental growth factor, have shown promising results in the improvement of surgical success. However, it remains necessary to broaden the therapeutic approach by focusing on combined therapies and on extended drug delivery.
    Full-text · Article · May 2014 · Clinical ophthalmology (Auckland, N.Z.)
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    • "Glaucoma treatments, either pharmacologically or surgically, are directed toward reducing intraocular pressure (IOP). Since it was first introduced in 1968, trabeculectomy (Trab) has been the most effective therapy in reducing IOP in patients with medically uncontrollable glaucoma [2]–[4]. Unlike most other surgical procedures, this filtrating surgery can be successfully performed by inhibiting the wound healing process [5]. "
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    ABSTRACT: We aimed to evaluate the intraoperative application of antimetabolites compared with anti-vascular endothelial growth factor (VEGF) agents with or without antimetabolites in trabeculectomy (Trab) for glaucoma. Relevant studies were selected through extensive search using PubMed, EMBASE, the Cochrane Library, and Web of Science databases in August 2013. The primary efficacy estimate was measured using weighted mean difference of the percentage of intraocular pressure reduction (IOPR%) from baseline to end-point, and the secondary efficacy estimates were odds ratio (OR) and 95% confidence interval (CI) for complete success rate and qualified success rate. ORs were also used to measure the tolerability estimate for adverse events. Meta-analyses of fixed or random effects models were conducted using RevMan software 5.2 to pool the results of the studies included. Heterogeneity was assessed using Chi(2) test and the I(2) measure. Nine studies enrolling a total of 349 patients were included. The weighted mean difference of IOPR% from baseline was 7.23 (95% CI: 2.57-11.89) for antimetabolites vs. anti-VEGF agents and 3.96 (95% CI: -4.18-12.10) for antimetabolites vs. anti-VEGF agents plus antimetabolites. The pooled ORs comparing antimetabolites with anti-VEGF agents were 2.37 (95% CI: 0.78, 7.21) for the complete success rate and 1.93 (95% CI: 0.52, 7.16) for qualified success rate. The pooled ORs comparing antimetabolites with anti-VEGF agents plus antimetabolites were 1.43 (95% CI: 0.48, 4.29) for the complete success rate and 2.11 (95% CI: 0.12, 37.72) for qualified success rate. The rates of adverse events did not significantly differ between antimetabolites and anti-VEGF agents, with pooled ORs of 0.86 (0.28-2.69) for bleb leakage, 3.01 (0.45-20.10) for choroidal effusion, 0.96 (0.23-3.98) for flat anterior chamber, and 0.90 (0.12-6.60) for hypotony. Further, the rates of adverse events were similar between antimetabolites and anti-VEGF agents plus antimetabolites, with pooled ORs of 0.40 (0.08-2.00) and 8.00 (0.93-68.59) for bleb leakage and hypotony, respectively. In comparison with anti-VEGF agents, antimetabolites were more effective in lowering IOP in Trab, while the intraoperative application of these two types of agents did not indicate statistically significant differences in the complete success rate, qualified success rate, or incidence of adverse events.
    Full-text · Article · Feb 2014 · PLoS ONE
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    • "The steps recommended for lowering the intraocular pressure in POAG are topical medications (eye drops), laser procedures and incisional glaucoma surgery. The greatest IOP reduction is achieved with surgical treatment (AGIS Investigators 1998, Lichter et al. 2001, Burr et al. 2012a). In patients with high initial IOP values, surgery is superior to pharmaceutical and laser treatment in reducing visual field progression (e.g. "
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    ABSTRACT: Introduction: Glaucoma is a progressive optic neuropathy associated with neural rim loss of the optic disc and the retinal nerve fibre layer typically causing visual field (VF) deterioration. Generally, glaucomatous lesions in the eye and in the visual field progress slowly over the years. In population-based cross-sectional studies, the percentage of unilateral or bilateral visual impairment varied between 3-12%. In screening studies, 0.03-2.4% of patients have been found to suffer visual impairment. Glaucoma has previously been associated with substantial healthcare costs and resource consumption attributable to the treatment of the disease. The disease also causes reduction in health-related quality of life (HRQoL) in patients with glaucoma. Objective and methods: This study compares patients with diagnosed open-angle glaucoma from two geographically different regions in Finland. A total of 168 patients were examined, 85 subjects from an area with higher per patient treatment costs (Oulu) and 83 patients from a region with lower per patient treatment costs (Turku). All patients had a history of continuous glaucoma medication use for a period of 11 years. For each patient, the total direct costs from glaucoma treatment were calculated and the total amount of resource consumption was determined from registries and patient records. Each patient underwent a clinical examination with visual field assessment and fundus photography. These data were used to determine the current stage of disease for each patient. Health-related quality of life questionnaire (15D) was used in determining each patient's subjective HRQoL score. Results: When applying the current diagnostic criteria for open-angle glaucoma, a total of 40% of patients did not to display any structural or functional damage suggesting glaucoma after 11 years of continuous medical treatment and follow-up. Patients with higher glaucoma stage (worse disease) were found to have statistically higher treatment costs compared with those at lower disease stages. Resource consumption was also greater in the patients in higher glaucoma stage. Patients in the Oulu district consumed more resources, and glaucoma treatment was more expensive than in the Turku area. The total treatment cost in Oulu and Turku was 6010 € and 4452 €, respectively, for the whole 11-year period. There was no statistically significant difference in quality-of-life scores between the two areas. No difference was noted between the higher-spending and lower-spending areas in this respect. However, when the population was analysed as a whole, patients with higher glaucoma stage were found to have lower vision-based 15D scores compared with those at lower disease stages. This observation was made also at both districts independently. Conclusions: Major cost source in open-angle glaucoma treatment is medication, up to 74% of annual costs. In addition, it seems that higher resource consumption and higher treatment costs do not increase the patients' HRQoL as assessed by the 15D instrument.
    Preview · Article · May 2013 · Acta ophthalmologica
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