Glaucoma

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 May 2010 (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 12 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.

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.

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 is 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.

The consensus about how laser treatments compare with medical or surgical treatments in people with acute angle-closure glaucoma is currently uncertain, and more high-quality evidence is needed.

About this condition

Definition

Glaucoma is a group of diseases characterised by progressive optic neuropathy. It is usually bilateral but asymmetrical, 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 normal-tension glaucoma is often used to describe this condition. It exhibits the same clinical picture as primary open-angle glaucoma with some additional risk factors. The division between the two conditions is an artificial one based on IOP, but they are really two diseases at different ends of a spectrum. 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. 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 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, especially those of West African origin. Glaucoma-related blindness is responsible for 8% of new blind registrations in the UK. Angle-closure glaucoma 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.

Aetiology/ Risk factors

The major risk factor for developing primary open-angle glaucoma is raised IOP. In one RCT (90 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 glaucomatous field loss. These were higher IOP (P = 0.047; IOP per mmHg), suspect discs (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 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 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-closure glaucoma.

Prognosis

Advanced visual field loss is found in about 20% of people with primary open-angle glaucoma at 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, 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. 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 intervention

To prevent progression of visual field loss and to minimise adverse effects of treatment.

Outcomes

Disease progression: 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. Adverse effects of treatment.

Methods

Clinical Evidence search and appraisal May 2010. The following databases were used to identify studies for this systematic review: Medline 1966 to May 2010, Embase 1980 to May 2010, and The Cochrane Database of Systematic Reviews, May 2010 (1966 to date of issue). An additional search within The Cochrane Library was carried out for the Database of Abstracts of Reviews of Effects (DARE) and Health Technology Assessment (HTA). When editing this review we used The Cochrane Database of Systematic Reviews 2010, Issue 3. 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 contributor for additional assessment, using predetermined criteria to identify relevant studies. Study design criteria for inclusion in this review were: published systematic reviews of RCTs and RCTs in any language, at least single blinded, and containing >20 individuals of whom >80% were followed up. There was no minimum length of follow-up required to include studies. We excluded all studies described as "open", "open label", or not blinded unless blinding was impossible. We included systematic reviews of RCTs and RCTs where harms of an included intervention were studied applying the same study design criteria for inclusion as we did for benefits. In addition we use a regular surveillance protocol to capture harms alerts from organisations such as the FDA and the 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). The categorisation of the quality of the evidence (high, moderate, low, or very low) reflects the quality of evidence available for our chosen outcomes in our defined populations of interest. These categorisations are not necessarily a reflection of the overall methodological quality of any individual study, because the Clinical Evidence population and outcome of choice may represent only a small subset of the total outcomes reported, and population included, in any individual trial. For further details of how we perform the GRADE evaluation and the scoring system we use, please see our website (www.clinicalevidence.com).

Table.

GRADE Evaluation of interventions for Glaucoma.

Important outcomes	Adverse effects, Disease progression
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)	Disease progression	Laser trabeculoplasty plus topical medical treatment versus no treatment	4	–1	0	–1	0	Low	Quality point deducted for incomplete reporting of results. Directness point deducted for composite outcome
1 (255)	Adverse effects	Laser trabeculoplasty plus topical medical treatment versus no treatment	4	–1	0	–1	0	Low	Quality point deducted for incomplete reporting of results. Directness point deducted for multiple interventions used
10 (3648)	Disease progression	Topical medical treatment versus placebo or no treatment	4	–1	0	–1	0	Low	Quality point deducted for methodological weaknesses (high withdrawal rates). Directness point deducted for composite outcome
2 (624 eyes)	Disease progression	Laser trabeculoplasty versus 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 eyes)	Adverse effects	Laser trabeculoplasty versus 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
3 (802)	Disease progression	Surgical trabeculectomy versus 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
at least 2 (at least 819)	Adverse effects	Surgical trabeculectomy versus topical medical treatment	4	–1	0	0	+1	High	Quality point deducted for incomplete reporting of results. Effect-size point added for OR >2
2 (962)	Disease progression	Surgical trabeculectomy versus 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
What are the effects of lowering intraocular pressure in people with normal-tension glaucoma?
2 (400)	Disease progression	Topical medical treatment versus 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)	Disease progression	Surgical treatment versus 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)	Adverse effects	Surgical treatment versus 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
What are the effects of treatment for acute angle-closure glaucoma?
1 (48)	Disease progression	Surgical peripheral iridectomy versus Nd:YAG laser iridotomy	4	–2	0	0	0	Low	Quality points deducted for sparse data and incomplete reporting of results

We initially allocate 4 points to evidence from RCTs, and 2 points to evidence from observational studies. To attain the final GRADE score for a given comparison, points are deducted or added from this initial score based on preset criteria relating to the categories of quality, directness, consistency, and effect size. Quality: based on issues affecting methodological rigour (e.g., incomplete reporting of results, quasi-randomisation, sparse data [<200 people in the analysis]). Consistency: based on similarity of results across studies. Directness: based on generalisability of population or outcomes. Effect size: based on magnitude of effect as measured by statistics such as relative risk, odds ratio, or hazard ratio.

Glossary

Argon laser iridoplasty

A procedure that involves placing circumferential argon laser burns (approximately 16–20 burns) in the peripheral iris to induce a contraction and pulling away of the peripheral iris from the drainage angle with the aim of opening the angle.

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.

High-quality evidence

Further research is very unlikely to change our confidence in the estimate of effect.

Laser iridotomy

Involves making a hole in the base of the iris (without opening the eye) using either an argon or Nd:YAG laser.

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.

Surgical iridectomy

Opening the eye at the corneal limbus and removing a triangle of tissue from the base of the iris.

Very low-quality evidence

Any estimate of effect is very uncertain.

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.