Lens extraction for chronic angle‐closure glaucoma
Abstract
This is a protocol for a Cochrane Review (Intervention). The objectives are as follows:
The objective of this review is to assess the effectiveness of lens extraction as a treatment modality for primary chronic angle‐closure glaucoma compared to other interventions for the condition.
Background
Introduction
Aqueous humor is secreted in the posterior chamber of the eye, passes through the pupil into the anterior chamber and is drained through the trabecular meshwork. Angle‐closure glaucoma (ACG) is characterized by obstruction to the outflow of aqueous humor and consequent rise in intraocular pressure. The obstruction may result from an anatomical predisposition of the eye or due to pathophysiologic processes in any part of the eye. The former is considered the primary form and the latter a secondary form of angle‐closure.
Epidemiology and pathogenesis
Primary angle‐closure glaucoma (PACG) has variable prevalence in different parts of the world. Higher prevalence rates were reported in Eskimos of Canada and Greenland compared to white populations in Europe (Bankes 1968; Clemmesen 1971; Drance 1973; Hollows 1966). Recent studies in Asian countries including China, India, Singapore, Japan, and Taiwan, besides studies in South Africa and Mongolia, reported higher prevalence and incidence rates of primary angle‐closure glaucoma compared to those reported in studies of white populations, suggesting a role of race in development of the condition (Chew 2001; Dandona 2000; Foster 1996; Foster 2000; Jacob 1998; Lai 2000; Okabe 1991; Salmon 1994; See 2004; Wang 2002; Zhao 1990).
Relative pupillary block obstructing free flow of aqueous from the posterior chamber of the eye to the anterior chamber is considered to be the most common mechanism of angle‐closure, although some have postulated other mechanisms as playing a substantial role (plateau iris configuration, prominent last iris role, choroidal expansion, and others). Relative pupillary block can be a consequence of a more anteriorly‐placed lens coupled with a steeper anterior surface resulting in an increased area of contact between the lens and iris (Mapstone 1968). The raised pressure in the posterior chamber causes the iris to bow forwards, which occludes the angle of the eye and aqueous drainage through apposition. Synechiae or adhesions may develop in the long‐term, compounding the occlusion.
Another mechanism, which often coexists with pupillary block and can also cause angle‐closure glaucoma by itself, is crowding of the angle. This results from an anterior placement of the lens due to either an increase in thickness of the lens or anterior displacement by a posterior force.
Secondary angle‐closure glaucoma is a consequence of pupillary block secondary to any of the following pathological mechanisms:
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uveitis resulting in posterior synechiae of the iris and a secluded pupil;
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neovascularization of the anterior chamber angle and subsequent fibrovascular closure;
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adhesions resulting from a shallow anterior chamber following an incisional surgery;
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a massive exudative retinal detachment with anterior displacement of the lens and iris.
In a retrospective chart review of patients younger than 40 years angle‐closure was found to be more frequently associated with structural or developmental abnormalities than with relative pupillary block (Ritch 2003). Advanced age is also postulated to be associated with angle‐closure due to a thicker, anterior‐located lens in old age (Foster 2002).
Presentation and diagnosis
Angle‐closure glaucoma may present in acute and chronic forms. An acute attack is considered an ocular emergency. Presenting symptoms include pain; frontal headache; decreased vision; halos around lights; nausea; and vomiting, in combination or alone. Signs of an acute attack include an elevated intraocular pressure; conjunctival congestion; corneal haziness due to epithelial or stromal edema; flattened anterior chamber; and a semi‐dilated pupil with a sluggish response to light. A narrow angle is usually observed in the fellow eye.
In contrast, primary chronic angle‐closure glaucoma presents either asymptomatically or with symptoms that are a consequence of long‐standing damage to the optic nerve due to raised intraocular pressure. Signs of primary chronic angle‐closure glaucoma include disc cupping or nerve fiber layer defects, elevated intraocular pressure and visual field defects.
Treatment options
Many treatments have been suggested for the management of both acute and chronic forms of primary angle‐closure glaucoma. These include laser iridotomy, medications, laser iridoplasty, and surgical procedures. The effectiveness of these interventions for chronic angle‐closure glaucoma is being examined in a separate Cochrane systematic review that is currently underway. While traditional trabeculectomy is often used in angle‐closure glaucoma, others have proposed trabeculotomy/gonioplasty as one alternative surgical approach. Finally, since the lens is clearly involved in the development of angle‐closure glaucoma, researchers have suggested that lens extraction alone may be adequate to treat some cases of angle‐closure glaucoma.
Rationale for a systematic review
Pupillary block and angle crowding, important mechanisms for the development of angle‐closure glaucoma, can be effectively managed by extraction of the lens. However, the effectiveness of lens extraction compared to other interventions for both chronic and acute primary angle‐closure is unknown. This review proposes to examine systematically the evidence regarding the effectiveness of lens extraction as a treatment for primary chronic angle‐closure glaucoma.
Objectives
The objective of this review is to assess the effectiveness of lens extraction as a treatment modality for primary chronic angle‐closure glaucoma compared to other interventions for the condition.
Methods
Criteria for considering studies for this review
Types of studies
We will include randomized and quasi‐randomized controlled trials in this review. Studies that have not used randomization to allocate participants to treatment groups but have used techniques intended to allocate patients in an unbiased fashion will be considered to be quasi‐randomized trials. Some examples include allocation based on day of the week, year of birth, hospital admission number, or social security number of consecutive patients.
If we fail to find any relevant randomized controlled trials we will include non‐randomized studies in an attempt to summarize the existing information on lens extraction for primary chronic angle‐closure glaucoma. In such a situation we will consider inclusion of prospective and retrospective non‐randomised comparative studies. We will not include studies with a case‐series design. There will be no restriction based on language, date of publication or number of participants.
Types of participants
We will include studies enrolling participants diagnosed with primary chronic angle‐closure glaucoma. This will have been defined as gonioscopic evidence of angle‐closure in association with either glaucomatous optic neuropathy with or without visual field defects or elevated intraocular pressure. For the purpose of this review chronic angle‐closure glaucoma will not include persons with known symptomatic attacks in the past. Such persons may develop chronic disease, but symptomatic patients may be substantially different from those with asymptomatic disease. It is possible that studies may present together data on participants with chronic angle‐closure glaucoma with known symptomatic attacks in the past and those without. We will attempt to procure data on participants with no known symptomatic attacks in the past from the authors of such randomized or quasi‐randomized studies. There will be no restrictions with respect to age, gender, ethnicity, co‐morbidities, use of adjunctive medications or the number of participants.
Types of interventions
We will include studies that compare lens extraction with other modalities of treatment for chronic angle‐closure glaucoma including, but not limited to, laser iridotomy, medications, and laser iridoplasty.
Types of outcome measures
Primary outcomes
The primary outcomes for this review are as follows.
(1) Proportion of participants with evidence of progression of visual field loss at different times of follow up. The outcome at one year of follow‐up will be the main primary outcome for the review. We will adopt the criteria in the included studies to define progression of visual field loss as measured using a validated method.
(2) Mean change in intraocular pressure from baseline at one year and measured by any method. We will also report the mean change in intraocular pressure from baseline at different times of follow up. If the data on mean change from baseline and the standard deviation of change is not reported in the manuscript, and cannot be obtained from the authors, we will analyze the final mean intraocular pressures at one year and at different times of follow up.
Secondary outcomes
The secondary outcomes for this review are as follows.
(1) Mean change in depth of the anterior chamber from baseline in millimeters as measured by any method.
(2) Number of medications to control intraocular pressure at six months, one year and at different times of follow up as reported in the included studies.
(3) We suspect that few, if any, studies would report gonioscopic findings in the participants. We will summarize the available information on examination of the angle, including angle‐width, from the included studies.
(4) We will summarize any visual acuity changes reported in the included studies.
Adverse effects
We will summarize adverse effects related to lens extraction that are reported in the included studies.
Quality of life measures
We will summarize quality of life outcomes reported in the included studies.
Follow up
There will be no restriction based on length of follow up.
Search methods for identification of studies
Electronic searches
We will search the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Group Trials Register) on The Cochrane Library, MEDLINE, EMBASE and LILACS. The searches will not be restricted by language or date of publication.
We will use the following strategy to search MEDLINE.
#1 explode "Glaucoma‐Angle‐Closure" / all SUBHEADINGS in MIME, MJME
#2 ((glaucoma* near angle* near closure*) in TI )or( (glaucoma* near angle* near closure*) in AB )
#3 #1 or #2
#4 explode "Lens‐Implantation‐Intraocular" / all SUBHEADINGS in MIME,MJME
#5 explode "Cataract‐Extraction" / all SUBHEADINGS in MIME, MJME
#6 (((lens* or cataract*) near (remov* or extract*) in AB) or (((lens* or cataract*) near (remov* or extract*) in TI)
#7 #4 or #5 or #6
#8 #3 and #7
We will search CENTRAL, EMBASE and LILACS using similar keywords.
We will conduct a single search for randomized and non‐randomized studies. We will go through the reference lists of the retrieved papers and, if we find it necessary, we will run additional searches with keywords on outcomes and angle‐closure glaucoma or outcomes and lens extraction.
Manual searches
We will search the reference lists of included studies. We will contact the primary investigators of identified randomized trials for details of any additional trials not found by our electronic and manual searches. We will use the Science Citation Index to search for references that cite the included studies.
Data collection and analysis
Assessment of search results
Two authors independently will assess the title and abstracts of all reports identified by the electronic and manual searches. Each report will be labelled as (a) definitely exclude or (b) unsure or (c) definitely include. The full text of abstracts labelled as 'unsure' will be re‐assessed according to the inclusion criteria for this review. Any differences between the two authors will be resolved through discussion. Studies labelled as 'definitely exclude' will be excluded from the review. Studies labelled as 'definitely include' will be assessed for methodological quality.
Assessment of methodological quality
Two authors independently will assess the included studies for the following sources of systematic bias using forms that will be developed for this purpose. The forms will be developed based on criteria for validity of non‐randomized studies discussed by Deeks et al (Deeks 2003) and using an adaptation of the form developed by Zaza et al (Zaza 2000). Randomized trials will be assessed for methodological quality according to the guidelines in Section 6 of the Cochrane Handbook for Systematic Review of Interventions (Higgins 2005). We will assess the included studies for different biases in the following manner.
Selection bias
Were the participants selected to different treatment groups in an unbiased fashion? For randomized studies, we will assess the method of allocation and allocation concealment. Allocation concealment will be graded as A (adequate), B (inadequate) or C (unclear). We will contact the primary investigators of trials classified as C (unclear) for clarification. If they do not respond within a reasonable time period we will grade allocation concealment based on available information. We will also assess the trials for exclusions after randomization and reasons for any.
If the study has not adopted some method of random or quasi‐random allocation of participants we will examine the following.
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Were the criteria for allocation of participants to the treatment groups specified explicitly?
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Does the selection method adopted minimize the chance that participants with favorable outcomes were preferentially selected?
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Were the two groups comparable at baseline with respect to important prognostic factors?
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Were appropriate statistical methods used to adjust for the confounding factors?
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Were the factors adjusted for specified a priori?
The measurement of the confounding factors in the participants will be assessed for consistency.
Performance bias
We will examine whether the intervention has been clearly defined as per a pre‐specified protocol for prospective studies and whether the intervention was determined in an objective fashion (medical records etc.) rather than self‐reporting in prospective and retrospective studies. Further, information on whether the interventions were administered consistently to all participants will be assessed.
Masking of participants and care‐givers is not possible for the intervention under consideration and will not be assessed.
Attrition bias
The follow‐up times and losses to follow up in each group will be examined. We will also consider any reasons for losses to follow‐up that are described to assess whether any differential losses are likely to influence the conclusion of the particular study. Randomized studies will also be assessed for analysis on an intention‐to‐treat basis ‐ whether participants were analyzed in the group to which they were randomized. We will also examine whether randomized participants for whom no outcome was collected, and those who received only some or none of their allotted treatment, have been included in the analysis. We will consider it to be an intention‐to‐treat analysis if all three criteria mentioned above are met.
Detection bias
For prospective study designs we will examine masking of outcome assessors, standardization, pre‐specification of methods used to assess the outcome and adherence to pre‐specified measurement protocol for the outcomes to identify any detection bias.
For retrospective studies we will assess whether explicit criteria stated a priori for identifying a clinical condition were used for inclusion of participants in the study. We will also assess adherence to such criteria.
Data collection
Two authors independently will extract the data for the primary and secondary outcomes onto paper data collection forms developed by the Cochrane Eyes and Vision Group. We will resolve discrepancies by discussion. We will contact study authors for missing data. One author will enter all data into RevMan 4.2. The second author will independently re‐enter the data using the double data‐entry facility to verify the data entered.
Data synthesis
Data analysis will follow the guidelines set out in Section 8 of the Cochrane Handbook for Systematic Review of Interventions (Deeks 2005). Due to the anticipated methodological variability and susceptibility to different kinds of bias, non‐randomized studies eligible for inclusion in this review will not be combined in a meta‐analysis. Instead we will present a tabulated or narrative summary of such studies if included.
For a meta‐analysis of randomized and quasi‐randomized clinical trials that are included we will calculate a summary risk ratio for dichotomous outcomes. Weighted mean difference will be calculated for continuous outcomes. Standardized mean difference will be reported if outcomes are measured using different scales. We will attempt to quantify the proportion of variability within included randomized studies that is explained by heterogeneity using the I2 statistic (Higgins 2002). If the I2 statistic is greater than 50% we will consider it as substantial heterogeneity and will not combine the study results in a meta‐analysis. Instead we will present the studies in a tabulated summary. We will examine funnel plot symmetry for evidence of other sources of heterogeneity. If there is no substantial heterogeneity as per the I2 statistic we will combine the results of the included studies in a meta‐analysis using a random‐effects model. We will use a fixed‐effect model if there are fewer than three studies.
Sensitivity analysis
Sensitivity analyses will be conducted to determine the impact of excluding randomized studies with lower methodological quality, excluding quasi‐randomized studies, varying cut‐off points for inclusion criteria and excluding unpublished studies and industry‐funded studies.
Subgroup analysis
If the variability in effect estimates of the included studies explained by heterogeneity, as defined by the I2 statistic, is greater than zero we will explore the possible causes through subgroup analyses based on age of participants if adequate data are available.
