Glaucoma Clinical Evidence

Glaucoma Search date November 2007 Rajiv Shah and Richard Wormald ABSTRACT INTRODUCTION: Glaucoma is characterised by progressive optic neuropathy and peripheral visual field loss. It affects 1% to 2% of white people aged over 40 years and accounts for 8% of new blind registrations in the UK. The main risk factor for glaucoma is raised intraocular pressure, but 40% of people with glaucoma have normal intraocular pressure and only 10% of people with raised intraocular pressure are at risk of optic-nerve damage. Glaucoma is more prevalent, presents earlier, and is more difficult to control in black people than in white populations. METHODS AND OUTCOMES: We conducted a systematic review and aimed to answer the following clinical questions: What are the effects of treatments for established primary open-angle glaucoma, ocular hypertension, or both? What are the effects of lowering intraocular pressure in people with normal-tension glaucoma? What are the effects of treatment for acute angle-closure glaucoma? We searched: Medline, Embase, The Cochrane Library, and other important databases up to November 2007 (Clinical Evidence reviews are updated periodically; please check our website for the most up-to-date version of this review). We included harms alerts from relevant organisations such as the US Food and Drug Administration (FDA) and the UK Medicines and Healthcare products Regulatory Agency (MHRA). RESULTS: We found 20 systematic reviews, RCTs, or observational studies that met our inclusion criteria. We performed a GRADE evaluation of the quality of evidence for interventions. CONCLUSIONS: In this systematic review we present information relating to the effectiveness and safety of the following interventions: laser trabeculoplasty (alone or plus topical medical treatment); topical medical treatments; and surgical trabeculectomy.

QUESTIONS What are the effects of treatments for established primary open-angle glaucoma, ocular hypertension, or both?. . 3 What are the effects of lowering intraocular pressure in people with normal-tension glaucoma?. . . . . . . . . . . . 7 What are the effects of treatment for acute angle-closure glaucoma?. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9 INTERVENTIONS IN PRIMARY OPEN-ANGLE GLAUCOMA, OCULAR HYPERTENSION, OR BOTH Likely to be beneficial

LOWERING INTRAOCULAR PRESSURE IN NORMALTENSION GLAUCOMA Unknown effectiveness

Laser trabeculoplasty plus topical medical treatment (more effective than no initial treatment at reducing progression of glaucoma; in people with primary openangle glaucoma) . . . . . . . . . . . . . . . . . . . . . . . . . . . . 3 Topical medical treatment (in people with primary openangle glaucoma, ocular hypertension, or both) . . . . 4 Trade-off between benefits and harms Surgical trabeculectomy (in people with primary openangle glaucoma, ocular hypertension, or both) . . . . 6

Medical treatment (any route; in people with normaltension glaucoma) . . . . . . . . . . . . . . . . . . . . . . . . . . 7 Surgical treatment (any type; in people with normaltension glaucoma) . . . . . . . . . . . . . . . . . . . . . . . . . . 8 IN ACUTE ANGLE-CLOSURE GLAUCOMA Likely to be beneficial Medical treatment* (any route; in acute angle-closure glaucoma) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 9 Surgical treatment* (any type; in acute angle-closure glaucoma) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10

Unknown effectiveness Laser trabeculoplasty (compared with surgical trabeculectomy; in people with primary open-angle glaucoma) . . 5

*No placebo-controlled RCTs, but a strong consensus that treatments are effective

Key Points • Glaucoma is characterised by progressive optic neuropathy and peripheral visual field loss. It affects 1% to 2% of white people aged over 40 years and accounts for 8% of new blind registrations in the UK. The main risk factor for glaucoma is raised intraocular pressure (IOP), but up to 40% of people with glaucoma have normal IOP and only about 10% of people with raised IOP are at risk of optic-nerve damage. Glaucoma is more prevalent, presents earlier, and is more difficult to control in black people (especially those of West African descent) than in white populations. Blindness from glaucoma results from gross loss of visual field or loss of central vision and, when the optic nerve is vulnerable, can progress quickly without treatment. • Lowering IOP by laser trabeculoplasty plus topical medical treatment may be more effective at reducing progression of glaucoma in people with primary open-angle or pseudoexfoliation glaucoma, compared with no treatment.

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• Topical medical treatment may reduce the risk of developing glaucoma in people with ocular hypertension compared with placebo. • We don't know whether topical medical treatment, laser trabeculoplasty, or surgical trabeculectomy are more effective at maintaining visual fields and acuity in primary open-angle glaucoma. Surgery may increase the risk of developing cataracts. • We don't know whether reducing IOP with medical treatment alone or in combination with other treatments including surgery is more effective than no treatment at reducing progression of visual field loss in people with normal-tension glaucoma. • There is a consensus that medical and surgical treatments are beneficial in people with acute angle-closure glaucoma, although we don't know this for sure because it is unethical to withhold pressure-lowering treatment. DEFINITION

Glaucoma is a group of diseases characterised by progressive optic neuropathy. It is usually bilateral but asymmetric and may occur at any intraocular pressure (IOP). All forms of glaucoma show optic-nerve damage (cupping, pallor, or both) associated with peripheral visual field loss. Primary open-angle glaucoma occurs in people with an open anterior chamber drainage angle and no secondary identifiable cause. Knowledge of the natural history of these conditions is incomplete, but it is thought that the problem starts with an IOP that is too high for the optic nerve. However, in a large proportion of people with glaucoma (about 40% at first testing) IOP is within the statistically defined normal range. The term ocular hypertension (OHT) generally applies to eyes with an IOP greater than the statistical upper limit of normal (about 21 mmHg). A thicker cornea leads to an overestimate of the IOP. Conversely, a thinner cornea may lead to underestimation of IOP and may be a risk factor for progression from OHT to glaucoma. Only a relatively small proportion of eyes with raised IOP have an optic nerve that is vulnerable to its effects (about 10%). Previously, trialists were anxious about withholding active treatment in overt primary open-angle glaucoma, and so several placebo or no-treatment trials selected people just with OHT. Trials comparing treatments often include both people with primary open-angle glaucoma and people with OHT, but in these the outcome is usually IOP alone. Normal-tension glaucoma occurs in people with IOPs that are consistently below the statistical upper limit of normal (21 mmHg; 2 standard deviations above the population mean). Acute angle-closure glaucoma is glaucoma resulting from a rapid and severe rise in IOP caused by physical obstruction of the anterior chamber drainage angle. Subacute and chronic angle-closure glaucoma also occur, but are not considered in this review.

INCIDENCE/ PREVALENCE

Glaucoma occurs in 1% to 2% of white people aged over 40 years, rising to 5% at 70 years. Primary open-angle glaucoma accounts for two-thirds of those affected, and normal-tension glaucoma for [1] [2] about one-quarter. Glaucoma is more prevalent, presents at a younger age with higher IOPs, is more difficult to control, and is the main irreversible cause of blindness in black populations, es[1] [3] pecially those of West African origin. Glaucoma-related blindness is responsible for 8% of [4] new blind registrations in the UK. Angle closure occurs at about one tenth of the frequency of open-angle glaucoma in white Europeans but is more common in Chinese people and Native American people — especially the Inuit people.

AETIOLOGY/ The major risk factor for developing primary open-angle glaucoma is raised IOP. In one RCT (90 RISK FACTORS people with IOP >22 mmHg, another glaucoma risk factor, and normal visual fields; mean age 55–56 years), three baseline risk factors were identified to be independently associated with glau[5] comatous field loss. These were higher IOP (P = 0.047; IOP per mmHg), suspect discs [6] (P = 0.007), and older age (P = 0.034; age per year). Lesser risk factors include family history and ethnic origin. The relationship between systemic blood pressure and IOP may be an important determinant of blood flow to the optic-nerve head and, as a consequence, may represent a risk [6] factor for glaucoma. Systemic hypotension, vasospasm (including Raynaud's disease and migraine), and a history of major blood loss have been reported as risk factors for normal-tension [7] glaucoma in hospital-based studies. Risk factors for acute angle-closure glaucoma include family history, female sex, being long sighted, and cataracts. One systematic review (search date 1999, 6 observational studies, 594,662 people with mydriasis) found no evidence supporting the theory that routine pupillary dilatation with short-acting mydriatics was a risk factor for acute angle[8] closure glaucoma. PROGNOSIS

Advanced visual field loss is found in about 20% of people with primary open-angle glaucoma at [9] [10] diagnosis and is an important prognostic factor for glaucoma-related blindness. Blindness from glaucoma is caused initially by loss of the peripheral visual field and ultimately by loss of central vision. Once early field defects have appeared, and where the IOP is greater than 30 mmHg, [11] untreated people may lose the remainder of the visual field in 3 years or less. As the disease progresses, people with glaucoma have difficulty moving from a bright room to a darker room, and judging steps and kerbs. Progression of visual field loss is often slower in normal-tension glaucoma.

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Acute angle glaucoma leads to rapid loss of vision, initially from corneal oedema, and subsequently from ischaemic optic neuropathy. Once optic-nerve damage has occurred, it cannot be repaired. AIMS OF To prevent progression of visual field loss and to minimise adverse effects of treatment. INTERVENTION OUTCOMES

Onset or progression of glaucoma; visual acuity; visual fields. Optic disc cupping and IOP are surrogate outcomes, which we do not report in this review. However, some RCTs have reported combined outcomes including these measures. In these cases, we have reported these surrogate outcomes as part of the combined outcome reported.

METHODS

Clinical Evidence search and appraisal November 2007. The following databases were used to identify studies for this systematic review: Medline 1966 to November 2007, Embase 1980 to November 2007, and The Cochrane Database of Systematic Reviews and Cochrane Central Register of Controlled Clinical Trials, 2007, Issue 4. Additional searches were carried out using these websites: NHS Centre for Reviews and Dissemination (CRD) — for Database of Abstracts of Reviews of Effects (DARE) and Health Technology Assessment (HTA), Turning Research into Practice (TRIP), and NICE. We also searched for retractions of studies included in the review. Abstracts of the studies retrieved from the initial search were assessed by an information specialist. Selected studies were then sent to the contributors for additional assessment, using pre-determined criteria to identify relevant studies. Study design criteria for inclusion in this review were: published systematic reviews and RCTs in any language, at least single blinded, and containing more than 20 individuals of whom more than 80% were followed up. There was no minimum length of followup required to include studies. We excluded all studies described as "open", "open label", or not blinded, unless blinding was impossible. In addition, we use a regular surveillance protocol to capture harms alerts from organisations such as the FDA and the UK Medicines and Healthcare products Regulatory Agency (MHRA), which are added to the reviews as required. To aid readability of the numerical data in our reviews, we round many percentages to the nearest whole number. Readers should be aware of this when relating percentages to summary statistics such as relative risks (RRs) and odds ratios (ORs). We have performed a GRADE evaluation of the quality of evidence for interventions included in this review (see table, p 12 ).

QUESTION

What are the effects of treatments for established primary open-angle glaucoma, ocular hypertension, or both?

OPTION

LASER TRABECULOPLASTY PLUS TOPICAL MEDICAL TREATMENT (IN PEOPLE WITH PRIMARY OPEN-ANGLE GLAUCOMA, OCULAR HYPERTENSION, OR BOTH). . . . . . . . . . . .

Disease progression Compared with no treatment Laser trabeculoplasty plus topical betaxolol hydrochloride may be more effective than no initial treatment at reducing the proportion of people with progression of glaucoma (defined by objective visual field changes, optic disc changes in one or both eyes of the person, or both) at 6 years in people aged 50 to 80 years with newly detected primary open-angle glaucoma or pseudoexfoliation glaucoma, who were previously untreated (low-quality evidence). Adverse effects Compared with no treatment Laser trabeculoplasty plus topical betaxolol hydrochloride may be associated with a more rapid development of lens opacities (low-quality evidence). For GRADE evaluation of interventions for glaucoma, see table, p 12 . Benefits:

Laser trabeculoplasty plus topical medical treatment versus no treatment: We found one systematic review (search date 2007; 1 RCT; 255 people aged 50–80 years with newly detected primary open-angle glaucoma or pseudoexfoliation glaucoma, previously untreated) comparing topical medical treatment (betaxolol hydrochloride) plus laser trabeculoplasty with no [12] [13] treatment. Latanoprost eye drops were also allowed in both groups if the intraocular pressure exceeded 25 mmHg at two consecutive visits in the treatment group or exceeded 35 mmHg in the [13] no-treatment control group. Progression of glaucoma was defined by objective visual field changes, optic disc changes in one or both eyes of the person, or both. The RCT found that laser trabeculoplasty plus topical betaxolol hydrochloride significantly reduced the proportion of people with progression of glaucoma after 6 years compared with control (definite visual field and optic disc defect progression: 58/129 [45%] with treatment v 78/126 [62%] with control; P = 0.007). It found that the average time to progression was longer with laser trabeculoplasty plus topical betaxolol hydrochloride than with control (median time to progression: 66 months with treatment v 48 [13] months with control; P value not reported).

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Laser trabeculoplasty plus topical medical treatment versus topical medical treatment alone: We found no RCTs. Harms:

Laser trabeculoplasty plus topical medical treatment versus no treatment: In the RCT comparing treatment with laser trabeculoplasty plus topical betaxolol hydrochloride with no initial treatment, there was a significantly more rapid development of lens opacities in the [13] treatment group (results presented graphically; P = 0.002). Laser trabeculoplasty plus topical medical treatment versus topical medical treatment alone: We found no RCTs.

Comment:

OPTION

The review found no evidence comparing selective laser trabeculoplasty, or newer topical medical [12] treatments including prostaglandin analogues, brimonidine, or carbonic anhydrase inhibitors. TOPICAL MEDICAL TREATMENT (IN PEOPLE WITH PRIMARY OPEN-ANGLE GLAUCOMA, OCULAR HYPERTENSION, OR BOTH). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Disease progression Compared with placebo or no treatment Topical medical treatment (beta-blockers, dorzolamide, or unspecified) may be more effective than placebo at reducing the proportion of people with ocular hypertension who develop visual field loss (low-quality evidence). Compared with laser trabeculoplasty We don't know whether initial topical medical treatment is more effective than initial laser trabeculoplasty at reducing visual field defect progression at 2 years in people with primary open-angle glaucoma (very low-quality evidence). Compared with surgical trabeculectomy We don't know whether topical medical treatment is more effective at preventing visual field loss or deterioration of visual acuity scores in people with primary, pseudoexfoliative, and pigmentary open-angle glaucoma (low-quality evidence). Adverse effects Compared with laser trabeculoplasty Initial topical medical treatment may be associated with lower incidence of peripheral anterior synechiae (moderate-quality evidence). Compared with surgical trabeculectomy Topical medical treatment is associated with a lower risk of developing cataracts and of requiring cataract surgery in people with primary, pseudoexfoliative, and pigmentary open-angle glaucoma (high-quality evidence). Note Topical medical treatments may be associated with uncommon but potentially serious systemic adverse effects including exacerbation of chronic obstructive airways disease after use of non-selective topical beta-blockers. For GRADE evaluation of interventions for glaucoma, see table, p 12 . Benefits:

Topical medical treatment versus placebo or no treatment: [14] [15] We found two systematic reviews (search dates 2004, 2007 ) comparing topical medical treatments with placebo or no treatment. The reviews identified five RCTs in common; however, they used different meta-analyses and applied different inclusion/exclusion criteria. The first review identified five RCTs (2326 people with ocular hypertension), all of which were also identified by the second review comparing timolol, betaxolol, or various topical medical treatments [14] with placebo or no treatment. It found that topical medical treatment significantly reduced the proportion of people with visual field loss, deterioration of optic disc, or both compared with placebo over 5 to10 years (proportion with deterioration: 81/1159 [7%] with topical medical treatment v 151/1161 [13%] with control; HR 0.56, 95% CI 0.3 to 0.81; P = 0.01). Many of the identified RCTs [14] had high dropout rates. The second review (10 RCTs: of which 5 were identified by and 1 excluded by the first review owing to an inadequate control group [comparing eyes rather than people]; 3648 people mainly with ocular hypertension [some RCTs also allowed open-angle glaucoma, pseudoexfoliation syndrome, and pigment dispersion syndrome]) compared any topical medical treatment (beta-blockers, dorzolamide, [15] or unspecified) with placebo or no treatment. It found significantly lower visual field defect progression with any topical medical treatment compared with placebo or no treatment at 2 to 3 years' follow-up (proportion of people with visual field defect progression: 89/1822 [5%] with any topical medical treatment v 140/1826 [8%] with placebo or no treatment; OR 0.62, 95% CI 0.47 to 0.81). A subgroup analysis of beta-blockers as a group versus placebo or no treatment found a borderline significant difference at 2 to 3 years' follow-up (proportion of people with visual field defect progres-

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sion: 45/460 [10%] with beta-blockers as a group v 64/466 [14%] with placebo or no treatment; OR 0.67, 95% CI 0.45 to 1.00). However, subgroup analyses of each individual treatment versus placebo or no treatment found no significant difference in visual field defect progression between [15] groups. Studies may have been underpowered to detect a difference between groups. A subsequent analysis of longer term data on the cohort of African-American people in one of the identified [16] RCTs was reported in a separate publication. It found that topical medical treatment significantly reduced the proportion of people in this subgroup who developed primary open-angle glaucoma over a median 6.5 years (17/203 [8%] with topical medical treatment v 33/205 [16%] with placebo; [16] HR 0.50, 95% CI 0.28 to 0.90; P = 0.02). Topical medical treatment alone versus topical medical treatment plus laser trabeculoplasty: See benefits of laser trabeculoplasty plus topical medical treatment in people with primary openangle glaucoma, ocular hypertension, or both, p 3 . Topical medical treatment alone versus laser trabeculoplasty: See benefits of laser trabeculoplasty in people with primary open-angle glaucoma, ocular hypertension, or both, p 5 . Topical medical treatment versus surgical trabeculectomy: See benefits of surgical trabeculectomy in people with primary open-angle glaucoma, ocular hypertension, or both, p 6 . Harms:

Topical medical treatment versus placebo or no treatment: [14] The first review gave no information on adverse effects. The second review reported the number of people who dropped out owing to side effects (details not reported). It found no significant difference between the number of dropouts with beta-blockers compared with placebo or no treatment (OR 0.95, 95% CI 0.40 to 2.26). It found a significantly higher number of dropouts owing to adverse effects with dorzolamide compared with placebo (1 RCT: 116/536 [22%] with dorzolamide v 51/541 [15] [9%] with placebo; OR 2.54, 95%CI 1.83 to 3.53). The RCT identified by the review, comparing dorzolamide with placebo, reported that ocular adverse effects, including burning or stinging when using the drops, were reported more frequently in people using dorzolamide than in people using placebo (23% of visits with dorzolamide v 7% of visits with placebo; absolute numbers and CI not [17] reported). One non-systematic review assessing systemic adverse effects of topical medical treatments found that they were uncommon but may be serious, including exacerbation of COPD [18] after use of non-selective topical beta-blockers. It found that non-selective topical beta-blockers can also cause systemic hypotension and reduction in resting heart rate. One RCT (80 people) assessing harms of prostaglandin analogues compared five interventions: bimatoprost, latanoprost, travoprost, unoprostone, and placebo. It found that bimatoprost, latanoprost, and travoprost all significantly increased aqueous flare (breakdown of blood aqueous barrier) from baseline over 6 months compared with unoprostone (P < 0.02) and placebo (P < 0.001 for difference among groups). [19]

Topical medical treatment alone versus topical medical treatment plus laser trabeculoplasty: See harms of laser trabeculoplasty plus topical medical treatment in people with primary openangle glaucoma, ocular hypertension, or both, p 3 . Topical medical treatment alone versus laser trabeculoplasty: See harms of laser trabeculoplasty in people with primary open-angle glaucoma, ocular hypertension, or both, p 5 . Topical medical treatment versus surgical trabeculectomy: See harms of surgical trabeculectomy in people with primary open-angle glaucoma, ocular hypertension, or both, p 6 . Comment: OPTION

None. LASER TRABECULOPLASTY (IN PEOPLE WITH PRIMARY OPEN-ANGLE GLAUCOMA, OCULAR HYPERTENSION, OR BOTH) . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Disease progression Compared with surgical trabeculectomy We don't know whether laser trabeculoplasty is more effective at reducing vision loss (measured by visual acuity and visual field) at 5 to 7 years in people with newly diagnosed primary openangle glaucoma or advanced glaucoma (low-quality evidence). Compared with topical medical treatment We don't know whether initial laser trabeculoplasty is more effective than medical treatment alone at reducing visual field defect progression at 2 years in people with primary open-angle glaucoma (very low-quality evidence). © BMJ Publishing Group Ltd 2009. All rights reserved.

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Adverse effects Compared with topical medical treatment Initial laser trabeculoplasty may be associated with higher incidence of peripheral anterior synechiae compared with initial medical treatment (moderate-quality evidence). For GRADE evaluation of interventions for glaucoma, see table, p 12 . Benefits:

Laser trabeculoplasty versus surgical trabeculectomy: See benefits of surgical trabeculectomy in people with primary open-angle glaucoma, ocular hypertension, or both, p 6 . Laser trabeculoplasty versus topical medical treatment: We found one systematic review (search date 2007, 4 RCTs) comparing initial laser trabeculoplasty with initial medical treatment in people with newly diagnosed open-angle glaucoma (majority with primary open-angle glaucoma, some with pseudoexfoliation syndrome and pigment dispersion [12] syndrome). Two identified RCTs reported outcomes of interest for this review. The first included RCT (271 people; 542 eyes) compared argon laser trabeculoplasty with timolol.The second included RCT (82 people; 82 eyes) compared argon laser trabeculoplasty with pilocarpine. The review found no significant difference in visual field loss progression between groups at 2 years' follow-up (23/311 [7%] with laser trabeculoplasty v 33/313 [11%] with topical medical treatment; RR 0.70, 95% CI [12] 0.42 to 1.16). The first RCT allowed addition of medication or change in medication during the trial according to a stepped regimen (timolol, dipivefrin, low-dose pilocarpine, high-dose pilocarpine, timolol plus high-dose pilocarpine, or dipivefrin plus high-dose pilocarpine) on the basis of confirmed increased intraocular pressure, deterioration in visual field, optic disc, or systemic adverse effects. The analysis was by intention to treat; however, only 20% of people in the laser trabeculoplasty and 15% of the people in timolol group had not received additional treatments at median 3 years' [20] follow-up. The review reported uncertainty about additional medications or interventions allowed [12] in the second RCT.

Harms:

Laser trabeculoplasty versus surgical trabeculectomy: See harms of surgical trabeculectomy in people with primary open-angle glaucoma, ocular hypertension, or both, p 6 . Laser trabeculoplasty versus topical medical treatment: The review found a significantly higher incidence of peripheral anterior synechiae formation with laser trabeculoplasty compared with medical treatment (84/311 [27%] with laser trabeculoplasty v [12] 8/313 [3%] with medical treatment; RR 11.15, 95% CI 5.63 to 22.09).

Comment:

OPTION

The review reported no evidence comparing selective laser trabeculoplasty or newer topical medical [12] treatments including prostaglandin analogues, brimonidine, or carbonic anhydrase inhibitors. SURGICAL TRABECULECTOMY (IN PEOPLE WITH PRIMARY OPEN-ANGLE GLAUCOMA, OCULAR HYPERTENSION, OR BOTH). . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .

Disease progression Compared with topical medical treatment We don't know whether surgical trabeculectomy is more effective at preventing visual field loss or deterioration of visual acuity scores in people with primary, pseudoexfoliative, and pigmentary open-angle glaucoma (low-quality evidence). Compared with laser trabeculoplasty We don't know whether surgical trabeculectomy is more effective at preventing deterioration of vision (measured by visual acuity and visual field) at 5 to 7 years in people with newly diagnosed primary open-angle glaucoma or advanced glaucoma (low-quality evidence). Adverse effects Compared with topical medical treatment Surgical trabeculectomy increases the risk of developing cataracts and the risk of requiring cataract surgery in people with primary, pseudoexfoliative, and pigmentary open-angle glaucoma (high-quality evidence). Note Surgical trabeculectomy has been reported to be associated with a reduction in central vision. For GRADE evaluation of interventions for glaucoma, see table, p 12 . Benefits:

Surgical trabeculectomy versus topical medical treatment: We found one systematic review (search date 2005; 4 RCTs; 888 people with primary, pseudoexfoliative, and pigmentary open-angle glaucoma) comparing surgical with topical medical treatment. [21] The earliest RCT identified by the review was initiated in 1968 and the surgical treatment was a Scheie's procedure, which is no longer done as a surgical procedure for glaucoma. Therefore,

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we present results only for the remaining three RCTs. Two RCTs found no significant difference in visual field loss between topical medical treatment and surgical trabeculectomy at 2 to 5 years (first RCT: 25/40 [63%] with medical treatment v 34/48 [71%] with trabeculectomy; OR 0.69, 95% CI 0.29 to 1.67; second RCT; 607 people: OR 0.74, 95% CI 0.54 to 1.01; absolute numbers not reported). However, the third RCT found that, at a mean of 4.6 years, significantly more participants initially treated with topical medical treatment than trabeculectomy had progressed by at least one stage of visual field severity (proportion with visual field loss: 27/57 [47%] with topical medical treatment v 13/50 [26%] with primary trabeculectomy; OR 2.56, 95% CI 1.12 to 5.83). Two RCTs (284 people) found no significant difference in mean visual acuity scores at 4 to 5 years between surgical and medical treatment (OR 1.48, 95% CI 0.58 to 3.51 in 1 RCT; reported as not significant; no further data reported in the other RCT). However, one large RCT (607 people) found that participants initially treated with topical medical treatment had a significantly lower risk of a defined visual acuity loss (loss of about 2 Snellen lines) than people treated surgically (adjustment for age, race, history of diabetes, and time in study; OR 0.50, 95% CI 0.33 to 0.75; time to outcome not reported). The treatment effect remained significant after adjustment for cataract surgery (OR 0.47, [21] 95% CI 0.31 to 0.74). Surgical trabeculectomy versus laser trabeculoplasty: [22] [23] We found two RCTs. The first RCT (789 eyes with advanced glaucoma; 451 black people, 325 white people) compared surgical trabeculectomy versus laser trabeculoplasty as initial treat[22] ments. Initial surgical trabeculectomy was followed by laser trabeculoplasty and repeat surgical trabeculectomy as required; initial laser trabeculoplasty was followed by surgical trabeculectomy as required. Race–treatment interactions were found to be significant for the primary outcome measures, and therefore results were analysed by race. Subgroup analysis found that initial laser trabeculoplasty significantly improved vision compared with initial surgical trabeculectomy in black people (both visual acuity and visual field; P < 0.01; other results presented graphically; CI not reported), although in white people the RCT found no significant difference between treatments in vision after 7 years (results presented graphically). A 10-year follow-up of the RCT has been published, but it is not reported here because of loss to follow-up (loss of 30% of black people and [24] 20% of white people). The second RCT (186 people with newly diagnosed primary open-angle glaucoma) compared three treatments: topical medical treatment (pilocarpine ± timolol ± a sympa[23] thomimetic), laser trabeculoplasty, and surgical trabeculectomy. It found no significant difference among treatments in visual acuity after 5 years (results presented graphically; P reported as not significant). Harms:

Surgical trabeculectomy is associated with a reduction in central vision. In one observational study, [25] 83% of people lost two lines of Snellen visual acuity. Surgical trabeculectomy versus topical medical treatment: The review found that surgical trabeculectomy significantly increased the risk of developing cataracts compared with topical medical treatment (proportion with cataracts: 57/403 [14%] with trabeculec[21] tomy v 24/416 [6%] with topical medical treatment; OR 2.69, 95% CI 1.64 to 4.42). The review reported that in one large RCT (607 people), primary trabeculectomy was associated with almost three times the risk of requiring cataract surgery at up to 3 years (HR 2.72, 95% CI 1.51 to 4.89). [21]

Surgical trabeculectomy versus laser trabeculoplasty: [22] The two RCTs did not report on adverse effects of treatment. Comment:

[23]

None.

QUESTION

What are the effects of lowering intraocular pressure in people with normal-tension glaucoma?

OPTION

MEDICAL TREATMENT IN PEOPLE WITH NORMAL-TENSION GLAUCOMA . . . . . . . . . . . . . .

Disease progression Topical medical treatment compared with placebo or no treatment Topical medical treatment may be more effective than placebo at reducing the proportion of people with glaucoma progression at 5 to 6 years in people with normaltension or primary open-angle glaucoma, although subgroup analysis in people with normal-tension glaucoma alone found no significant difference between groups. Treatment to reduce intraocular pressure by 30% (using drugs, trabeculectomy, or both) may be more effective than no treatment at reducing progression of visual field loss at 8 years in people with normal-tension glaucoma (very low-quality evidence). Note

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We found no direct information about medical treatment (any route other than topical) in people with normal-tension glaucoma. For GRADE evaluation of interventions for glaucoma, see table, p 12 . Benefits:

Topical medical treatment versus placebo or no treatment: We found one systematic review (search date 2004; 2 RCTs; 400 people with either primary open[14] angle or normal-tension glaucoma). It found that interventions including topical medical treatment significantly reduced the proportion of people with glaucoma progression at 5 to 6 years compared with no treatment (80/195 [41%] with interventions including topical medical treatment v 109/205 [53%] with no treatment; HR 0.65, 95% CI 0.49 to 0.87; P = 0.003). One RCT (255 people with primary open-angle glaucoma or normal-tension glaucoma) identified by the review compared [13] topical medical treatment (betaxolol) plus laser trabeculoplasty with no treatment. The second RCT (145 people with normal-tension glaucoma; 145 eyes) identified by the review compared treatments to lower intraocular pressure by 30% (medical or surgical treatment [all allowed treatments [26] not defined], or both) with no treatment. The review conducted a subgroup analysis in people with normal-tension glaucoma and found no significant difference, although fewer people having interventions including topical medical treatment had glaucoma progression (49/134 [37%] with interventions including topical medical treatment v 63/143 [44%] with no treatment; HR 0.70, 95% [14] CI 0.48 to 1.02). The subgroup analysis is likely to have been underpowered to detect a clinically important difference between groups. A companion paper to the second RCT (145 people) used a different analysis from the intentionto-treat analysis included in the review, and it reported the incidence of visual field progression from a new baseline after a 30% intraocular pressure reduction was achieved in the treated group. [27] Progression of visual field loss was defined by deepening of an existing scotoma, a new or expanded field defect coming close to central vision, or a fresh scotoma in a previously normal part of the visual field. The RCT found that treatment with topical medical treatment or trabeculectomy significantly reduced progression of visual field loss after 8 years after a 30% reduction in intraocular pressure compared with no treatment (140 people, 140 eyes: 7/61 [12%] eyes with treatment v 28/79 [35%] eyes with no treatment; RR 0.32, 95% CI 0.15 to 0.70; NNT 5, 95% CI 3 to 9). Topical medical treatment versus surgical treatment: We found no systematic review or RCTs comparing topical medical treatment with surgical treatment in people with normal-tension glaucoma.

Harms:

Topical medical treatment versus placebo or no treatment: [14] The review gave no information on adverse effects. The RCT (145 people) found that treatment (medical or surgical) significantly increased cataract formation after 8 years compared with no treatment (23/66 [35%] with interventions including topical medical treatment v 11/79 [14%] with [26] no treatment; P = 0.0011). Subgroup analysis found that the excess risk of cataract formation was confined to those people treated surgically (P = 0.0001). See harms of surgical trabeculectomy in people with normal-tension glaucoma, p 8 . Topical medical treatment versus surgical treatment: We found no RCTs. [13]

Comment:

OPTION

The RCT (255 people) included in the review, comparing topical medical treatments plus laser trabeculoplasty with no treatment is also reported in the option on laser trabeculoplasty plus topical [26] medical treatment in people with primary open-angle glaucoma. The RCT (145 people) included [14] [27] in the review and the companion paper comparing medical or surgical treatment with no treatment is also described in the option on surgical treatment in people with normal-tension glaucoma. The RCT suggested that the overall favourable effect of intraocular pressure-lowering treatment using drugs or surgery compared with no treatment was evident only when the cataractinducing effect of trabeculectomy was removed. Not all cases of normal-tension glaucoma progress [26] when untreated (40% had not progressed at 5 years). SURGICAL TREATMENT IN PEOPLE WITH NORMAL-TENSION GLAUCOMA . . . . . . . . . . . .

Disease progression Compared with placebo or no treatment Treatment to reduce intraocular pressure by 30% (using trabeculectomy, drugs, or both) may be more effective than no treatment at reducing progression of visual field loss at 8 years in people with normal-tension glaucoma (very low-quality evidence). Adverse effects © BMJ Publishing Group Ltd 2009. All rights reserved.

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Compared with placebo or no treatment Treatment to reduce intraocular pressure by 30% (using trabeculectomy, drugs, or both) may be associated with increased cataract formation at 8 years in people with normal-tension glaucoma, the excess risk of cataract formation being confined to the subgroup of people who were treated surgically (very low-quality evidence). For GRADE evaluation of interventions for glaucoma, see table, p 12 . Benefits:

Surgical treatment versus no treatment: [14] We found one systematic review (search date 2004), which identified one RCT (145 eyes in 145 people with normal-tension glaucoma) comparing treatment to reduce intraocular pressure by 30% (with medical or surgical treatment [all allowed treatments not defined] or both; 66 eyes) with [26] no treatment (79 eyes). The RCT found no significant difference between groups in progression of visual field loss after 5 years compared with no treatment (22/66 [33%] eyes with treatment v [26] 31/79 [39%] eyes with no treatment; P = 0.21; analysis by ITT). A companion paper to this RCT used a different analysis (not by ITT) and reported the incidence of visual field progression from a new baseline after a 30% intraocular pressure reduction was [27] achieved in the treated group. Progression of visual field loss was defined by deepening of an existing scotoma, a new or expanded field defect coming close to central vision, or a fresh scotoma in a previously normal part of the visual field. The RCT found that topical medical treatment or trabeculectomy significantly reduced progression of visual field loss after 8 years after a 30% reduction in intraocular pressure compared with no treatment (140 people, 140 eyes: 7/61 [12%] eyes with treatment v 28/79 [35%] eyes with no treatment; RR 0.32, 95% CI 0.15 to 0.70; NNT 5, 95% CI 3 [27] to 9). Surgical treatment versus topical medical treatment: See benefits of medical treatment in people with normal-tension glaucoma, p 7 .

Harms:

Surgical treatment versus no treatment: [14] The RCT identified by the review found that treatment (medical or surgical) significantly increased cataract formation after 8 years compared with no treatment (23/66 [35%] with treatment v 11/79 [26] [14%] with no treatment; P = 0.0011). Subgroup analysis found that the excess risk of cataract formation was confined to those people treated surgically (P = 0.0001). Surgical treatment versus topical medical treatment: See harms of medical treatment in people with normal-tension glaucoma, p 7 .

Comment:

[26]

The RCT comparing topical medical or surgical treatment with no treatment is also described in the option on medical treatment in people with normal-tension glaucoma. The RCT suggested that the overall favourable effect of intraocular pressure-lowering treatment using medical treatment or surgery compared with no treatment was evident only when the cataract-inducing effect of trabeculectomy was removed. Not all cases of normal-tension glaucoma progress when untreated [26] (40% had not progressed at 5 years).

QUESTION

What are the effects of treatment for acute angle-closure glaucoma?

OPTION

MEDICAL TREATMENT (ACUTE ANGLE-CLOSURE GLAUCOMA) . . . . . . . . . . . . . . . . . . . . . .

Note We found no direct information about whether medical treatment (any route) is better than no active treatment. RCTs comparing pilocarpine with placebo are considered unethical. Consensus suggests that medical treatments are effective for acute angle-closure glaucoma. For GRADE evaluation of interventions for glaucoma, see table, p 12 . Benefits:

We found one systematic review (search date 2002), which identified no RCTs assessing our out[28] comes of interest .

Harms:

We found no RCTs.

Comment:

Clinical guide: RCTs comparing pilocarpine with placebo are considered unethical. There is consensus that medical treatment with pressure-lowering drugs (especially those that can be given parenterally, such as iv acetazolamide) are effective in acute angle-closure glaucoma. We found no evidence from RCTs to support or challenge this view.

© BMJ Publishing Group Ltd 2009. All rights reserved.

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Eye disorders

Glaucoma

OPTION

SURGICAL TREATMENT (ACUTE ANGLE-CLOSURE GLAUCOMA) . . . . . . . . . . . . . . . . . . . .

Disease progression Surgical peripheral iridectomy compared with Nd:YAG laser iridotomy We don't know whether surgical iridectomy is more effective than laser iridotomy at preventing deterioration of visual acuity at 3 years in people with uniocular acute angle-closure glaucoma (low-quality evidence). Note We found no direct information about whether surgical treatment (any type) is better than no active treatment. Consensus suggests that surgical treatments are effective for acute angle-closure glaucoma. For GRADE evaluation of interventions for glaucoma, see table, p 12 . Benefits:

Surgical procedure versus no treatment: We found one systematic review (search date 2002), which identified no RCTs (see comment below). [28]

Surgical peripheral iridectomy versus Nd:YAG laser iridotomy: We found one systematic review (search date 2002, 1 RCT that met Clinical Evidence inclusion [28] criteria). The RCT identified by the review (48 people with uniocular acute angle-closure glau[7] coma) compared peripheral iridectomy with Nd:YAG laser iridotomy. It found no significant difference between groups in visual acuity after 3 years (0.30 logMAR units with peripheral iridectomy v 0.57 logMAR units with laser iridotomy; statistical data not reported). Harms:

Surgical iridectomy involves an open operation on the eye, with risk of serious complications including intraocular infection or haemorrhage. We found no published evidence quantifying these risks. Nd:YAG laser iridotomy is associated with haemorrhage from the iris, pressure spikes, and [29] corneal oedema. Nd:YAG and argon laser iridotomy can produce focal, non-progressive lens [30] opacity. In one non-RCT, iris haemorrhage was more common with the Nd:YAG laser but pupil [31] distortion, iritis, and late blockage were more common with the argon laser. Surgical procedure versus no treatment: We found no RCTs. Surgical peripheral iridectomy versus Nd:YAG laser iridotomy: [28] The review gave no information on adverse effects.

Comment:

Clinical guide: Consensus suggests that surgical treatments are effective in the treatment of acute angle-closure glaucoma. Management of acute angle-closure glaucoma is aimed at restoring flow of aqueous humour to the anterior chamber angle and adjacent trabecular meshwork. One non-RCT found that the mean number of laser burns required to penetrate the iris was six with the Nd:YAG laser [31] and 73 with the argon laser.

GLOSSARY Drainage angle Area in the anterior chamber of the eye where the iris meets the sclera, and where fluid from the aqueous humour drains by the trabecular meshwork. Laser iridotomy Involves making a hole in the base of the iris (without opening the eye) using either an argon or Nd:YAG laser. Laser trabeculoplasty Laser trabeculoplasty is performed with a laser, using a contact lens with an internal mirror, which allows focal burning of the pigmented trabecular meshwork. Scotoma Visual field defect consisting of an area of partial or complete loss of vision, surrounded by an area of normal vision. Surgical iridectomy Opening the eye at the corneal limbus and removing a triangle of tissue from the base of the iris. High-quality evidence Further research is very unlikely to change our confidence in the estimate of effect. Low-quality evidence Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate. Moderate-quality evidence Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate. Trabeculectomy A microsurgical procedure in which a partial thickness trapdoor in the sclera is elevated at its junction with the cornea under the conjunctiva. Under the trapdoor, a small hole is fashioned from the sclera to the anterior chamber. This allows drainage of aqueous humour into the subconjunctival space. An iridectomy is performed at the site of the hole in the sclera. Very low-quality evidence Any estimate of effect is very uncertain.

© BMJ Publishing Group Ltd 2009. All rights reserved.

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SUBSTANTIVE CHANGES Laser trabeculoplasty (in people with primary open-angle glaucoma, ocular hypertension, or both) One sys[12] tematic review added. It found no significant difference in visual field loss progression with initial laser trabeculoplasty versus initial medical treatment in people with newly diagnosed glaucoma at 2 years' follow-up. Categorisation unchanged (Unknown effectiveness). Laser trabeculoplasty plus topical medical treatment (in people with primary open-angle glaucoma, ocular [12] hypertension, or both) One systematic review added. It identified one RCT already included in this Clinical Evidence review, so no new data added. Categorisation unchanged (Likely to be beneficial). Topical medical treatment (in people with primary open-angle glaucoma, ocular hypertension, or both) Two [12] [15] systematic reviews added. One review found reduced visual field loss progression with topical medical [15] treatment (beta-blockers, dorzolamide, or unspecified) versus placebo or no treatment at 2 to 3 years' follow-up. The other review found no significant difference in visual field loss progression with initial medical treatment versus [12] initial laser trabeculoplasty in people with newly diagnosed glaucoma at 2 years' follow-up. Categorisation unchanged (Likely to be beneficial).

REFERENCES 1.

Sommer A, Tielsch JM, Katz J, et al. Relationship between intraocular pressure and primary open angle glaucoma among white and black Americans. Arch Ophthalmol 1991;109:1090–1095. [PubMed]

2.

Coffey M, Reidy A, Wormald R, et al. The prevalence of glaucoma in the west of Ireland. Br J Ophthalmol 1993;77:17–21. [PubMed]

3.

Leske MC, Connell AM, Wu SY, et al. Incidence of open-angle glaucoma: the Barbados Eye Studies. The Barbados Eye Studies Group. Arch Ophthalmol 2001;119:89–95. [PubMed]

4.

Government Statistical Service. Causes of blindness and partial sight amongst adults. London: HMSO, 1988.

5.

Araie M, Azuma I, Kitazawa Y. Influence of topical betaxolol and timolol on visual field in Japanese open-angle glaucoma patients. Jpn J Ophthalmol 2003;47:199–207. [PubMed]

6.

Tielsch JM, Katz J, Quigley HA, et al. Diabetes, intraocular pressure, and primary open-angle glaucoma in the Baltimore Eye Survey. Ophthalmology 1995;102:48–53. [PubMed]

7.

Fleck BW, Wright E, Fairley EA. A randomised prospective comparison of operative peripheral iridectomy and Nd:YAG laser iridotomy treatment of acute angle closure glaucoma: 3 year visual acuity and intraocular pressure control outcome. Br J Ophthalmol 1997;81:884–888. [PubMed]

8.

Pandit RJ, Taylor R. Mydriasis and glaucoma: exploding the myth. A systematic review. Diabet Med 2000;17:693–699. Search date 1999; primary sources Medline, Embase, and hand searches of reference lists of articles retrieved. [PubMed]

17.

Migkior S, Zeyen T, Pfeiffer N, et al. Results of the European Glaucoma Prevention Study. Ophthalmology 2005;112:366–337. [PubMed]

18.

Diamond JP. Systemic adverse effects of topical ophthalmic agents: implications for older patients. Drugs Aging 1997;11:352–360. [PubMed]

19.

Arcieri ES, Santana A, Rocha FN, et al. Blood-aqueous barrier changes after the use of prostaglandin analogues in patients with pseudophakia and aphakia: a 6month randomized trial. Arch Ophthalmol 2005;123:186–192. [PubMed]

20.

Glaucoma Laser Trial Group. The glaucoma laser trial (GLT) and glaucoma laser trial follow-up study: results. Am J Ophthalmol 1995;120:718–731. [PubMed]

21.

Burr J, Azuara-Blanco A, Avenell A. Medical versus surgical interventions for open angle glaucoma. In: The Cochrane Library, Issue 4, 2007. Chichester, UK: John Wiley & Sons, Ltd. Search date 2005. [PubMed]

22.

The AGIS investigators. The Advanced Glaucoma Intervention Study (AGIS): 4. Comparison of treatment outcomes within race. Seven year results. Ophthalmology 1998;105:1146–1164. [PubMed]

23.

Migdal C, Gregory W, Hitchins R, et al. Long-term functional outcome after early surgery compared with laser and medicine in open angle glaucoma. Ophthalmology 1994;101:1651–1657. [PubMed]

24.

The AGIS investigators. The Advanced Glaucoma Intervention Study (AGIS): 13. Comparison of treatment outcomes within race: 10-year results. Ophthalmology 2004;111:651–664. [PubMed]

25.

Costa UP, Smith M, Spaeth GL, et al. Loss of vision after trabeculectomy. Ophthalmology 1993;100:599–612. [PubMed]

9.

Sheldrick JH, Ng C, Austin DJ, et al. An analysis of referral routes and diagnostic accuracy in cases of suspected glaucoma. Ophthalmic Epidemiol 1994;1:31–38. [PubMed]

26.

Collaborative Normal-tension Glaucoma Study Group. The effectiveness of intraocular pressure reduction in the treatment of normal-tension glaucoma. Am J Ophthalmol 1998;126:498–505. [PubMed]

10.

Fraser S, Bunce C, Wormald R, et al. Deprivation and late presentation of glaucoma: case-control study. BMJ 2001;322:639–643. [PubMed]

27.

11.

Jay JL, Murdoch JR. The rates of visual field loss in untreated primary open angle glaucoma. Br J Ophthalmol 1993;77:176–178. [PubMed]

Collaborative Normal-tension Glaucoma Study Group. Comparison of glaucomatous progression between untreated patients with normal-tension glaucoma and patients with therapeutically reduced intraocular pressure. Am J Ophthalmol 1998;126:487–497. [PubMed]

12.

Rolim-de Moura C, Paranhos A, Wormald R. Laser trabeculoplasty for open angle glaucoma. In: The Cochrane Library, Issue 4, 2007. Chichester, UK: John Wiley & Sons, Ltd. Search date 2007. [PubMed]

28.

13.

Heijl A, Leske MC, Bengtsson B, et al. Reduction of intraocular pressure and glaucoma progression: results from the Early Manifest Glaucoma Trial. Arch Ophthalmol 2002;120:1268–1279. [PubMed]

Saw SM, Gazzard G, Friedman DS. Interventions for angle-closure glaucoma: an evidence-based update. Ophthalmology 2003;110:1869–1878; quiz 1878–1879, 1930. Search date 2002; primary sources Medline, Pubmed, Embase, Cochrane Collaborations, and hand searches of reference lists of important articles. [PubMed]

29.

14.

Maier PC, Funk J, Schwarzer G, et al. Treatment of ocular hypertension and open angle glaucoma: meta-analysis of randomised controlled trials. BMJ 2005;331:134. [PubMed]

Fleck BW, Dhillon B, Khanna V, et al. A randomised, prospective comparison of Nd:YAG laser iridotomy and operative peripheral iridectomy in fellow eyes. Eye 1991;5:315–321. [PubMed]

30.

15.

Vass C, Hirn C, Sycha T, et al. Medical interventions for primary open angle glaucoma and ocular hypertension. In: The Cochrane Library, Issue 4, 2007. Chichester, UK: John Wiley & Sons, Ltd. Search date 2007. [PubMed]

Pollack IP, Robin AL, Dragon DM, et al. Use of neodymium:YAG laser to create iridotomies in monkeys and humans. Trans Am Ophthalmol Soc 1984;82:307–328. [PubMed]

31.

16.

Higginbotham EJ, Gordon MO, Beiser JA, et al. The Ocular Hypertension Treatment Study: topical medication delays or prevents primary open-angle glaucoma in African American individuals. Arch Ophthalmol 2004;122:813–820. [PubMed]

Moster MR, Schwartz LW, Spaeth GL, et al. Laser iridectomy. A controlled study comparing argon and neodymium:YAG. Ophthalmology 1986;93:20–24.

Rajiv Shah Ophthalmic Surgeon Department of Ophthalmology St Vincent's Hospital Sydney Australia Richard PL Wormald Consultant Ophthalmic Surgeon Moorfields Eye Hospital London UK Competing interests: RS none declared. RW has received honoraria for speaking and attending meetings from various pharmaceutical companies producing treatments for [12] [2] [10] glaucoma including Alcon, Allergan, and Pfizer, and is a co-author of one systematic review cited in this review, and two studies cited in the background section. We would like to acknowledge the previous contributors of this review, including Jeremy Diamond and Colm O'Brien.

© BMJ Publishing Group Ltd 2009. All rights reserved.

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Glaucoma

TABLE

GRADE evaluation of interventions for glaucoma

Important outcomes

Disease progression, adverse effects

Number of studies (participants)

Outcome

Comparison

Type of evidence

Quality

Consistency

Directness

Effect size

GRADE

Comment

What are the effects of treatments for established primary open-angle glaucoma, ocular hypertension, or both? 1 (255)

[13]

Disease progression

Laser trabeculoplasty plus topical medical treatment v no treatment

4

–1

0

–1

0

Low

Quality point deducted for incomplete reporting of results. Directness point deducted for composite outcome

1 (255)

[13]

Adverse effects

Laser trabeculoplasty plus topical medical treatment v no treatment

4

–1

0

–1

0

Low

Quality point deducted for incomplete reporting of results. Directness point deducted for multiple interventions used

Disease progression

Topical medical treatment v placebo or no treatment

4

–1

0

–1

0

Low

Quality point deducted for methodological weaknesses (high dropout rates). Directness point deducted for composite outcome

2 (624 [12] eyes)

Disease progression

Laser trabeculoplasty v topical medical treatment

4

–2

0

–1

0

Very low

Quality points deducted for incomplete reporting of results and analysis flaws. Directness point deducted for multiple interventions used

2 (624 [12] eyes)

Adverse effects

Laser trabeculoplasty v topical medical treatment

4

–2

0

–1

+2

Moderate

Quality points deducted for incomplete reporting of results and analysis flaws. Directness point deducted for multiple interventions used. Effect-size points added for RR >5

10 [14] (3648) [15]

[16]

[17]

[20]

[20]

3 (802)

[21]

Disease progression

Surgical trabeculectomy v topical medical treatment

4

–1

–1

0

0

Low

Quality point deducted for incomplete reporting of results. Consistency point deducted for different results between studies

3 (819)

[21]

Adverse effects

Surgical trabeculectomy v topical medical treatment

4

–1

0

0

+1

High

Quality point deducted for incomplete reporting of results. Effectsize point added for OR >2

2 (962)

[22]

Disease progression

Surgical trabeculectomy v laser trabeculoplasty

4

–1

0

–1

0

Low

Quality point deducted for incomplete reporting of results. Directness point deducted for different results in different populations

[23]

What are the effects of lowering intraocular pressure in people with normal-tension glaucoma? 2 (400)

[14]

Disease progression

Topical medical treatment v placebo or no treatment

4

–2

0

–2

0

Very low

Quality points deducted for incomplete reporting of intervention and unclear outcome measurement. Directness points deducted for inclusion of people with primary open-angle glaucoma and inclusion of multiple interventions

1 (145)

[14]

Disease progression

Surgical treatment v placebo or no treatment

4

–2

0

–1

0

Very low

Quality points deducted for sparse data and incomplete reporting of intervention. Directness point deducted for inclusion of multiple interventions

1 (145)

[14]

Adverse effects

Surgical treatment v placebo or no treatment

4

–2

0

–1

0

Very low

Quality points deducted for sparse data and incomplete reporting of results. Directness point deducted for subgroup analysis

0

0

0

Low

Quality points deducted for sparse data and incomplete reporting of results

[26]

[26]

[26]

What are the effects of treatment for acute angle-closure glaucoma? 1 (48)

[28]

Disease progression

Surgical peripheral iridectomy v Nd:YAG laser iridotomy

© BMJ Publishing Group Ltd 2009. All rights reserved.

4

–2

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Eye disorders

Glaucoma

Important outcomes

Disease progression, adverse effects

Number of studies (participants)

Outcome

Comparison

Type of evidence

Quality

Consistency

Directness

Effect size

GRADE

Comment

Type of evidence: 4 = RCT; 2 = Observational Consistency: similarity of results across studies Directness: generalisability of population or outcomes Effect size: based on relative risk (RR) or odds ratio (OR)

Disclaimer The information contained in this publication is intended for medical professionals. Categories presented in Clinical Evidence indicate a judgement about the strength of the evidence available to our contributors prior to publication and the relevant importance of benefit and harms. We rely on our contributors to confirm the accuracy of the information presented and to adhere to describe accepted practices. Readers should be aware that professionals in the field may have different opinions. Because of this and regular advances in medical research we strongly recommend that readers' independently verify specified treatments and drugs including manufacturers' guidance. Also, the categories do not indicate whether a particular treatment is generally appropriate or whether it is suitable for a particular individual. Ultimately it is the readers' responsibility to make their own professional judgements, so to appropriately advise and treat their patients. To the fullest extent permitted by law, BMJ Publishing Group Limited and its editors are not responsible for any losses, injury or damage caused to any person or property (including under contract, by negligence, products liability or otherwise) whether they be direct or indirect, special, incidental or consequential, resulting from the application of the information in this publication.

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Glaucoma