Abstract
Introduction
Glaucoma is characterised by progressive optic neuropathy and peripheral visual field loss. The main risk factor for glaucoma is elevated intraocular pressure. This overview is focused on primary acute angle-closure and primary chronic angle-closure glaucoma. The number of people diagnosed with primary angle-closure glaucoma is predicted to rise over the next few years due to an increasingly ageing population and increased awareness of the condition.
Methods and outcomes
We conducted a systematic overview, aiming to answer the following clinical questions: What are the effects of treatments for primary acute angle-closure glaucoma? What are the effects of treatments for primary chronic angle-closure glaucoma? We searched: Medline, Embase, The Cochrane Library, and other important databases up to February 2014 (BMJ Clinical Evidence overviews are updated periodically; please check our website for the most up-to-date version of this overview).
Results
At this update, searching of electronic databases retrieved 683 studies. After deduplication and removal of conference abstracts, 490 records were screened for inclusion in the overview. Appraisal of titles and abstracts led to the exclusion of 467 studies and the further review of 23 full publications. Of the 23 full articles evaluated, three systematic reviews and one RCT were added at this update. We performed a GRADE evaluation for two PICO combinations.
Conclusions
In this systematic overview, we categorised the efficacy for six interventions based on information about the effectiveness and safety of laser treatment (iridotomy or iridoplasty), medical treatments (any route), and surgical treatments (any) to treat people with either primary acute or primary chronic angle-closure glaucoma.
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).
There are two main anatomical types of glaucoma, open angle and closed angle, where the trabecular meshwork (through which fluid drains from the anterior chamber of the eye) is open or closed, respectively. Previous versions of this overview included open-angle glaucoma and normal-tension glaucoma. However, this overview focuses on primary closed-angle glaucoma only. We searched for evidence from RCTs and systematic reviews of RCTs only.
The presentation of primary angle-closure glaucoma can be acute, with sudden painful vision loss. This acute type is considered an ophthalmic emergency, although it has a good prognosis if treated promptly. Although termed 'glaucoma', not all patients will have damage to their optic nerve or glaucomatous field loss.
Chronic primary angle-closure glaucoma usually presents painlessly but has a high incidence of permanent bilateral visual loss. Small eyes, which are usually long sighted, give a predisposition to angle closure, and Asian populations have a higher prevalence.
Overall, we found few RCTs on the interventions considered in this overview. There is a need for further high-quality RCTs in this field to inform clinical practice.
There is a consensus that medical and surgical treatments are beneficial in people with primary acute angle-closure glaucoma, although we don't know this for sure based on RCT evidence because it is unethical to withhold pressure-lowering treatment.
Concerning laser treatment for primary acute angle-closure glaucoma:
We don't know whether laser iridotomy is more effective than surgical iridectomy at preventing deterioration of visual acuity at 3 years in people with uniocular acute angle-closure glaucoma.
The consensus about how laser iridoplasty compares with medical or surgical treatments in people with primary acute angle-closure glaucoma is currently uncertain, and more high-quality evidence is needed. We only found one small RCT, and it didn't report on adverse effects.
We found no RCTs on the effects of medical treatment versus no treatment for people with primary chronic angle-closure glaucoma, or on the effects of surgical treatment versus no treatment.
One small RCT found no significant difference in visual outcomes at 1 year between laser peripheral iridoplasty plus laser peripheral iridotomy versus laser peripheral iridotomy alone in people with primary chronic angle-closure glaucoma, but there is a need for further RCTs to draw robust conclusions.
Clinical context
General background
Glaucoma is the most common cause of irreversible blindness. There are two main anatomical types of glaucoma, open angle and closed angle. The number of people diagnosed with primary angle-closure glaucoma is predicted to rise over the next few years. This is due to an increasingly ageing population worldwide and increased awareness of the condition. The population growth in Asia, where angle-closure glaucoma is as common as open-angle glaucoma, has a particular influence on diagnosis rates. It has been estimated that by the year 2020, more than 20 million people will be affected by angle-closure glaucoma, of which 5 million people will be blind.
Focus of the review
This overview examines the high-quality RCT evidence available on primary acute angle-closure glaucoma and primary chronic angle-closure glaucoma. We examined the effects of medical treatments, surgical treatments, and laser treatments (iridotomy and iridoplasty). We compared medical and surgical treatments with no treatment and medical, surgical, and laser treatments with each other.
Comments on evidence
We found few RCTs comparing different treatments with no treatment or with each other. The trials we did find were small and of limited quality. There is a need for further high-quality RCTs in this field. Further trials are under way, and their results awaited (e.g., the EAGLE trial, which will compare cataract surgery to the standard treatment, including laser iridotomy for people with newly diagnosed primary angle-closure glaucoma). One issue making evaluation of the evidence more difficult has been the lack of consistency over terminology for these conditions. Glaucoma is an optic neuropathy. In a patient with open angles, elevated pressure would be termed 'ocular hypertension', and only those with evidence of structural or functional changes to the nerve and field, respectively, would be described as having glaucoma. However, common text book definitions for acute angle closure glaucoma have included those with high pressure and scarring of the drainage channel but with no optic nerve or field changes. The use of the term 'glaucoma' to include those populations, with and without glaucomatous optic neuropathy or only those with optic neuropathy makes studies difficult to interpret and compare.
Search and appraisal summary
The update literature search for this overview was carried out from the date of the last search, May 2010, to February 2014. A back search from 1966 was performed for the new options added to the scope at this update. For more information on the electronic databases searched and criteria applied during assessment of studies for potential relevance to the overview, please see the Methods section. Searching of electronic databases retrieved 683 studies. After deduplication and removal of conference abstracts, 490 records were screened for inclusion in the review. Appraisal of titles and abstracts led to the exclusion of 467 studies and the further review of 23 full publications. Of the 23 full articles evaluated, three systematic reviews and one RCT were added at this update.
About this condition
Definition
Glaucoma is a group of diseases characterised by progressive optic neuropathy. It is the most common cause of irreversible blindness.[1] There are two main anatomical types of glaucoma: open angle and closed angle. The trabecular meshwork (through which fluid drains from the anterior chamber of the eye) is open in people with open-angle glaucoma and closed in people with closed-angle glaucoma. Primary open-angle glaucoma occurs in people with an open anterior chamber drainage angle and no secondary identifiable cause. This overview focuses on primary closed-angle glaucoma only. Primary chronic angle closure is due to obstruction of the outflow of the anterior chamber, and may be accompanied by a rise in intraocular pressure (IOP). The obstruction of outflow is due to contact of the iris with the trabecular meshwork and this is usually identified by the examination technique of goniscopy. Iridotrabecular contact and obstruction of more than half of the trabecular meshwork drainage channel is defined as a closed angle. Advanced imaging techniques of the anterior segment can also identify the closure. Primary angle closure is staged and defined as glaucoma when there is evidence of glaucomatous optic neuropathy (please see 'Inconsistency in terminology' for further discussion). Chronic primary angle closure usually presents painlessly. Treatment of pressure is with IOP-lowering medication. However, the underlying mechanism of primary angle closure is treated with pilocarpine to constrict the pupil and laser or surgical peripheral iridotomy to relieve pupil block. More recently, elective lens extraction is being evaluated in an ongoing RCT because this may increase the capacity of the anterior chamber and open the drainage angle. This has been proposed for both acute and chronic angle closure. Primary acute angle closure is a sudden rapid rise in IOP due to obstruction of the outflow of the anterior chamber. The presentation is acute, usually with pain, and may be associated with sudden vision loss. This is considered an ophthalmic emergency. Secondary angle closure (not covered in this overview) requires treating the pressure, underlying cause, and usually dilation of the pupil. Inconsistency in terminology Clinicians commonly use the term 'glaucoma' in the context of angle closure, even without evidence of nerve or field damage, especially in acute cases. Although the term 'glaucoma' should be used where there is evidence of optic neuropathy, older papers and text books have used the term 'acute angle closure glaucoma' to describe the mechanism of angle closure in the presence of elevated pressure with occlusion of the outflow mechanism, either by pupil block causing the peripheral iris to move forward and/or peripheral adhesion of the iris to the drainage channel caused by intracocular inflammation, as in secondary angle closure. But, in the absence of glaucomatous optic neuropathy, this is now termed 'primary or secondary angle closure'. The new definition proposes to distinguish between the mechanism (i.e., closed or open angle), by which IOP becomes elevated and the resultant damage that is caused by primary angle closure glaucoma.[2] Population for this overview We have used the terminology as reported in the trials and, where possible, have retrieved detail on presence or absence of evidence of optic neuropathy and added this information to our reporting. For the question, What are the effects of treatments for primary acute angle-closure glaucoma?, the population included people with acute primary angle-closure glaucoma (resulting from a rapid and severe rise in intraocular pressure caused by physical obstruction of the anterior chamber drainage angle), including people with any comorbid conditions, but excluding people with secondary primary angle-closure glaucoma. For the question, What are the effects of treatments for primary chronic angle-closure glaucoma?, the population included people with chronic primary angle-closure glaucoma (resulting from slow rise in intraocular pressure caused by physical obstruction of the anterior chamber drainage angle), including people with any comorbid conditions, but excluding people with secondary chronic angle-closure glaucoma.
Incidence/ Prevalence
Glaucoma (all types) 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.[3] [4] Glaucoma-related blindness is responsible for 8% of new blind registrations in the UK.[5] Primary angle-closure glaucoma occurs at about one tenth of the frequency of open-angle glaucoma in white Europeans, with a prevalence of 0.4% in people who are over 40 years and of European ancestry.[6] It is more common in Chinese people.[7] The number of people diagnosed with primary angle-closure glaucoma is predicted to rise over the next few years. This is due to an increasingly ageing population worldwide, and an increased awareness of the condition. The population growth in Asia particularly has an influence on diagnosis rates. It has been estimated that by the year 2020, over 20 million people will be affected by angle-closure glaucoma, of which 5 million people will be blind.[8]
Aetiology/ Risk factors
Angle closure is a result of the iris being in contact with the trabecular meshwork. Risk factors for angle closure include Asian ethnicity, family history, female sex, being long-sighted, large lens, cataracts, and older age. 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.[9]
Prognosis
Primary acute angle closure is considered an ophthalmic emergency, although it has a good prognosis if treated promptly. Chronic primary angle closure has a high incidence of permanent bilateral visual loss.
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 reported combined outcomes including these measures. In these cases, we report these surrogate outcomes as part of the combined outcome reported. Adverse effects.
Methods
Search strategy BMJ Clinical Evidence search and appraisal date February 2014. Databases used to identify studies for this systematic overview include: Medline 1966 to February 2014, Embase 1980 to February 2014, The Cochrane Database of Systematic Reviews 2014, issue 1 (1966 to date of issue), the Database of Abstracts of Reviews of Effects (DARE), and the Health Technology Assessment (HTA) database. Inclusion criteria Study design criteria for inclusion in this systematic overview were systematic reviews and RCTs published in English, at least single-blinded, and containing 20 or more individuals (with a minimum of 10 in each arm), of whom more than 80% were followed up. There was no minimum length of follow-up. We excluded split eye studies (that is, a study in which one eye of a person is allocated to one treatment, and the other eye gets another treatment). We excluded all studies described as 'open', 'open label', or not blinded unless blinding was impossible. We excluded any studies in people with secondary angle-closure glaucoma, where included populations were not clear or were mixed, and RCTs that did not report on our outcomes of interest. BMJ Clinical Evidence does not necessarily report every study found (e.g., every systematic review). Rather, we report the most recent, relevant, and comprehensive studies identified through an agreed process involving our evidence team, editorial team, and expert contributors. Evidence evaluation A systematic literature search was conducted by our evidence team, who then assessed titles and abstracts, and finally selected articles for full text appraisal against inclusion and exclusion criteria agreed a priori with our expert contributor. In consultation with the expert contributor, studies were selected for inclusion and all data relevant to this overview extracted into the benefits and harms section of the overview. In addition, information that did not meet our pre-defined criteria for inclusion in the benefits and harms section may have been reported in the 'Further information on studies' or 'Comment' sections (see below). Adverse effects All serious adverse effects, or those adverse effects reported as statistically significant, were included in the harms section of the overview. Pre-specified adverse effects identified as being clinically important were also reported, even if the results were not statistically significant. Although BMJ Clinical Evidence presents data on selected adverse effects reported in included studies, it is not meant to be, and cannot be, a comprehensive list of all adverse effects, contraindications, or interactions of included drugs or interventions. A reliable national or local drug database must be consulted for this information. Comment and Clinical guide sections In the Comment section of each intervention, our expert contributors may have provided additional comment and analysis of the evidence, which may include additional studies (over and above those identified via our systematic search) by way of background data or supporting information. As BMJ Clinical Evidence does not systematically search for studies reported in the Comment section, we cannot guarantee the completeness of the studies listed there or the robustness of methods. Our expert contributors add clinical context and interpretation to the Clinical guide sections where appropriate. Structural changes this update At this update, we have removed the following previously reported 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? We have added the following new question: What are the effects of treatment for primary chronic angle-closure glaucoma? Data and quality To aid readability of the numerical data in our overviews, 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). BMJ Clinical Evidence does not report all methodological details of included studies. Rather, it reports by exception any methodological issue or more general issue that may affect the weight a reader may put on an individual study, or the generalisability of the result. These issues may be reflected in the overall GRADE analysis. 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: acute and chronic primary angle-closure.
| Important outcomes | Disease progression | ||||||||
| Studies (Participants) | Outcome | Comparison | Type of evidence | Quality | Consistency | Directness | Effect size | GRADE | Comment |
| What are the effects of treatment for primary acute angle-closure glaucoma? | |||||||||
| 1 (48) | Disease progression | Surgical treatment (any type) versus laser treatment (iridotomy or iridoplasty) | 4 | –2 | 0 | 0 | 0 | Low | Quality points deducted for sparse data and incomplete reporting of results |
| What are the effects of treatment for primary chronic angle-closure glaucoma? | |||||||||
| 1 (126) | Disease progression | Laser peripheral iridoplasty plus laser peripheral iridotomy versus laser peripheral iridotomy alone | 4 | –2 | 0 | 0 | 0 | Low | Quality points deducted for sparse data and weak methods (blinding, outcome assessment, follow-up) |
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.
- Dysphotopsia
Disturbed vision that includes a light phenomenon, such as a subjective halo or streak of light in the vision.
- 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.
- Surgical iridectomy
Opening the eye at the corneal limbus and removing a triangle of tissue from the base of the iris.
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.
Contributor Information
Mr Richard P. L. Wormald, Moorfields Eye Hospital, London, UK.
Miss Emma Jones, Accident and Emergency and Glaucoma, Moorfields Eye Hospital, London, UK.
References
- 1.Resnikoff S, Pascolini D, Mariotti SP, et al; World Health Organization. Global magnitude of visual impairment caused by uncorrected refractive errors in 2004. Jan 2008. Available at http://www.scielosp.org/scielo.php?script=sci_arttext&pid=S0042-96862008000100017&lng=en&nrm=iso&tlng=en (last accessed 25 June 2015). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Foster PJ, Buhrmann R, Quigley HA, et al. The definition and classification of glaucoma in prevalence surveys. Br J Ohthalmol 2002;86:238–242. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.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. [DOI] [PubMed] [Google Scholar]
- 4.Coffey M, Reidy A, Wormald R, et al. Prevalence of glaucoma in the west of Ireland. Br J Ophthalmol 1993;77:17–21. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 5.Government Statistical Service. Causes of blindness and partial sight amongst adults. London, UK: HMSO, 1988. [Google Scholar]
- 6.Day AC, Baio G, Gazzard G, et al. The prevalence of primary angle closure glaucoma in European derived populations: a systematic review. Br J Ophthalmol 2012;96:1162–1167. [DOI] [PubMed] [Google Scholar]
- 7.He M, Foster PJ, Ge J, et al. Prevalence and clinical characteristics of glaucoma in adult Chinese: a population-based study in Liwan District, Guangzhou. Invest Ophthalmol Vis Sci 2006;47:2782–2788. [DOI] [PubMed] [Google Scholar]
- 8.Quigley HA, Broman AT. The number of people with glaucoma worldwide in 2010 and 2020. Br J Ophthalmol 2006;90:262–267. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 9.Pandit RJ, Taylor R. Mydriasis and glaucoma: exploding the myth. A systematic review. Diabet Med 2000;17:693–699. [DOI] [PubMed] [Google Scholar]
- 10.Saw SM, Gazzard G, Friedman DS. Interventions for angle-closure glaucoma: an evidence-based update. Ophthalmology 2003;110:1869–1878. [DOI] [PubMed] [Google Scholar]
- 11.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. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 12.Lam DS, Lai JS, Tham CC, et al. Argon laser peripheral iridoplasty versus conventional systemic medical therapy in treatment of acute primary angle-closure glaucoma: a prospective, randomized, controlled trial. Ophthalmology 2002;109:1591–1596. [DOI] [PubMed] [Google Scholar]
- 13.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 (Lond) 1991;5:315–321. [DOI] [PubMed] [Google Scholar]
- 14.Vera V, Naqi A, Belovay GW, et al. Dysphotopsia after temporal versus superior laser peripheral iridotomy: a prospective randomized paired eye trial. Am J Ophthalmol 2014;157:929–935. [DOI] [PubMed] [Google Scholar]
- 15.Pollack IP, Robin AL, Dragon DM, et al. Use of the neodymium:YAG laser to create iridotomies in monkeys and humans. Trans Am Ophthalmol Soc 1984;82:307–328. [PMC free article] [PubMed] [Google Scholar]
- 16.Moster MR, Schwartz LW, Spaeth GL, et al. Laser iridectomy. A controlled study comparing argon and neodymium:YAG. Ophthalmology 1986;93:20–24. [PubMed] [Google Scholar]
- 17.Yip JL, Foster PJ, Uranchimeg D, et al. Randomised controlled trial of screening and prophylactic treatment to prevent primary angle closure glaucoma. Br J Ophthalmol 2010;94:1472–1477. [DOI] [PubMed] [Google Scholar]
- 18.Friedman DS, Vedula SS. Lens extraction for chronic angle-closure glaucoma. In: The Cochrane Library, Issue 1, 2014. Chichester, UK: John Wiley & Sons, Ltd. Search date 2006. [Google Scholar]
- 19.Ng WS, Ang GS, Azuara-Blanco A. Laser peripheral iridoplasty for angle-closure. In: The Cochrane Library, Issue 1, 2014. Chichester, UK: John Wiley & Sons, Ltd. Search date 2012. [Google Scholar]
- 20.Sun X, Liang YB, Wang NL, et al. Laser peripheral iridotomy with and without iridoplasty for primary angle-closure glaucoma: 1-year results of a randomized pilot study. Am J Ophthalmol 2010;150:68–73. [DOI] [PubMed] [Google Scholar]
- 21.Del Priore LV, Robin AL, Pollack IP. Neodymium: YAG and argon laser iridotomy. Long-term follow-up in a prospective, randomized clinical trial. Ophthalmology 1988;95:1207–1211. [DOI] [PubMed] [Google Scholar]
- 22.de Silva DJ, Day AC, Bunce C, et al. Randomised trial of sequential pretreatment for Nd:YAG laser iridotomy in dark irides. Br J Ophthalmol 2012;96:263–266. [DOI] [PubMed] [Google Scholar]