Surgery for cataracts in people with age‐related macular degeneration
Abstract
This is a protocol for a Cochrane Review (Intervention). The objectives are as follows:
To evaluate the effectiveness and safety of cataract surgery in eyes with age‐related macular degeneration.
Background
Description of the condition
Age‐related cataract
Cataract is an opacification of the crystalline lens that most often occurs with age (AAO 2006). According to the World Health Organization (WHO), cataract accounts for 48% of world blindness, affecting nearly 17.6 million people (WHO 2004). With projected increases in the elderly population taken into consideration for both developing and developed nations, the WHO estimates that there will be 54 million people 60 years or older that will be blind from cataract by the year 2020.
Age‐related cataract is a term used to describe any idiopathic lens opacification that occurs in people over 50 years of age. In the early stages, they may have minimal or no symptoms, but progression of lens opacification with time generally causes varying levels of gradual, progressive, painless loss of vision. People with cataract may have increasing difficulty with near or distance vision or both. Glare may reduce vision in bright daylight and cause trouble with night driving.
Cataract is diagnosed and assessed with a comprehensive eye exam. Reduction in best‐corrected visual acuity is the standard tool used to estimate visual impairment and slit lamp biomicroscopy allows for classification and grading of the cataract. A dilated fundus examination is performed to assess for retinal disease that could complicate or exacerbate the cataract‐related impairment. The American Academy of Ophthalmology recognizes the primary indication for cataract surgery as "visual function that no longer meets the affected person's needs and for which cataract surgery provides a reasonable likelihood of improved vision" (AAO 2006). Cataract removal is also indicated when the lens opacity inhibits the proper management of posterior segment disease (AAO 2006).
Age‐related macular degeneration
Age‐related macular degeneration (AMD) is the leading cause of legal blindness in people 65 years or older and the incidence is expected to increase further with the continued aging of the population. In Americans 40 years or older, the total prevalence of any AMD has been estimated as 9.2% and the overall prevalence of neovascular AMD or geographic atrophy has been reported as 1.47% (EDPRG 2004; Klein 1995).
Numerous grading systems have been proposed to classify AMD but no universal consensus exists. The International Epidemiological Age‐related Maculopathy Study Group defined age‐related maculopathy (ARM) as the presence of drusen larger than 63 microns and retinal pigment epithelium abnormalities whereas AMD was reserved for late stages of ARM with the occurrence of geographic atrophy (dry AMD) or choroidal neovascularization (wet AMD) (Bird 1995). Although neovascular disease comprises only 15% of AMD, it is responsible for the majority of visual loss (Ferris 1984).
Age‐related macular degeneration may be asymptomatic in the early stages when only drusen are present (AAO 2006). Further progression of the disease and increasing pigment alteration can be associated with a gradual progression of visual loss and contrast sensitivity and a need for increased background illumination. Central geographic atrophy causes irreversible loss of central vision. Choroidal neovascularization (CNV) may cause scotoma, metamorphopsia and varying degrees of loss of visual acuity.
Non‐neovascular AMD has no treatment but high‐dose vitamin supplementation was shown to reduce the incidence rate of CNV in high‐risk participants in the Age‐Related Eye Disease Study (AREDS 2001). Antioxidant vitamin and mineral supplements were shown in a systematic review to slow the progression of AMD (Evans 2006). People with active CNV may be treated with laser photocoagulation, photodynamic therapy (Wormald 2005), or intravitreal injections of steroid (Danis 2000) or anti‐angiogenic agents (Kaiser 2006), depending on the clinical situation. Visual acuity may continue to decline despite appropriate treatment, however.
Description of the intervention
For age‐related cataract, surgery is currently the only treatment option once the lens has opacified and vision is decreasing (AAO 2006; Riaz 2006). There are four main forms of cataract extraction surgery: intracapsular (ICCE), traditional extracapsular (ECCE), phacoemulsification (PHACO) and manual small incision (MSICS). One recent published Cochrane systematic review examined various surgical interventions for eyes with age‐related cataract (Riaz 2006).
How the intervention might work
Cataract surgery typically involves small‐incision phacoemulsification removal of the lens and insertion of a capsule‐supported intraocular lens implant. Vision‐limiting operative complications are uncommon. Pooled results of cataract surgery prior to 1992 showed that 95% of participants without underlying ocular comorbidity obtained best‐corrected vision of 20/40 or better (Powe 1994). When all participants were included, the probability of obtaining 20/40 or better vision was still greater than 90%. Those with underlying ocular conditions such as AMD may experience limited visual improvement. Visual outcomes for various surgical intervention techniques have been systematically reviewed by Riaz et al. (Riaz 2006).
Why it is important to do this review
Our understanding of the interaction of cataract and macular degeneration is still evolving. There is controversy regarding the possible benefits or risks of cataract surgery in eyes with AMD. Some studies have suggested that cataract surgery may worsen the progression of AMD (Cugati 2006; Pollack 1996), although two recent reports have revealed that cataract surgery may be beneficial in this group of patients (Armbrecht 2000; Shuttleworth 1998).
There are several scenarios in which cataract surgery may worsen the progression of AMD. Cataract and AMD share common risk factors such as smoking and nutrition that could cause them to progress simultaneously (Hiller 1997; Jacques 2005; Seddon 2006). In addition, inflammatory factors have been implicated in the causation of AMD (Donoso 2006) and it is feasible that inflammation occurring after cataract surgery could cause progression of macular degeneration. Moreover, the replacement of the natural lens with an artificial lens could be associated with increased exposure to light and damaging ultraviolet rays. Clinicians who think that cataract surgery increases the risk of AMD progression, may discourage cataract surgery despite visual loss and lens opacity. This review will analyze the available evidence from randomized clinical trials regarding the effectiveness and safety of cataract surgery in eyes with AMD.
Objectives
To evaluate the effectiveness and safety of cataract surgery in eyes with age‐related macular degeneration.
Methods
Criteria for considering studies for this review
Types of studies
We will include randomized controlled trials and quasi‐randomized trials in which the methods of allocating people to a treatment arm are not exactly random such as date of birth, day of the week etc. This is in anticipation of not finding many trials on this subject.
Types of participants
We will include trials in which eyes were affected by both cataract and AMD that required cataract surgery. We will exclude trials in which eyes required cataract surgery for angle closure glaucoma, lens subluxation, or clear lens extraction for refractive error.
Types of interventions
We will include trials where cataract surgery is compared to no surgery. We will impose no restrictions based on type of cataract surgery.
Types of outcome measures
Primary outcomes
The primary outcome for this review will be visual acuity in the operated eye at one year follow‐up. It will be measured as:
1) Best‐corrected visual acuity dichotomized into:
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0.3 LogMar (20/40 Snellen equivalent) or better;
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Worse than 0.3 LogMar.
2) Change in visual acuity categorized by:
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Three or more lines improvement from baseline;
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Within three lines from baseline;
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Three or more lines loss.
When continuous LogMAR data is available we will also analyze the visual acuity and degree of change as continuous data. We will analyze visual acuity at other follow‐up times (six months, two and three years) when possible.
Secondary outcomes
The secondary outcomes for this review include:
1) Progression of AMD in the operated eye as measured by:
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Development of geographic atrophy;
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Development of CNV;
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Increase in the number of large drusen (> 63 microns in size);
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Increase of the drusen total area.
2) Vision‐related quality of life as measured by methods applied in each trial.
3) Vision‐threatening complications from cataract surgery, including but not limited to cystoid macular edema and retinal detachment.
We will analyze secondary outcomes at one, two, three years follow‐up when possible.
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) in The Cochrane Library, MEDLINE, EMBASE and Latin American and Caribbean Literature on Health Sciences (LILACS). There will be no date or language restrictions in the electronic search for trials.
See: Appendices for details of search strategies for each database.
Searching other resources
We will handsearch conference proceedings and the reference lists of the included trials for other possible trials.
Data collection and analysis
Selection of studies
Two review authors will independently select the studies for inclusion. The titles and abstracts of all reports identified by the electronic and manual searching will be examined by the authors. The abstracts will be classified as (a) definitely include, (b) unsure or (c) definitely exclude. Full‐text copies of those classified as (a) definitely include and (b) unsure will be obtained and re‐assessed. The studies will be classified as (1) included, (2) awaiting assessment or (3) excluded. The authors of studies classified as (2) awaiting assessment will be contacted for further clarification and the studies will be re‐assessed as further information becomes available. Studies identified by both review authors as (3) excluded will be excluded and documented in the review. Studies identified as (1) included will be included and assessed for methodological quality. The review authors will be unmasked to the report authors, institutions and trial results during this assessment.
Disagreements between the two review authors will be resolved by a third review author.
Data extraction and management
Two review authors will independently extract the data for the primary and secondary outcomes onto paper data extraction forms developed by the Cochrane Eyes and Vision Group. A pilot test of this form will be done using a small number of studies. Discrepancies will be resolved by discussion. One review author will enter all data into RevMan 4.2. A second review author will independently re‐enter the data into RevMan 4.2 using the double data entry facility.
Assessment of risk of bias in included studies
Two review authors will independently assess the included trials for bias according to the methods described in Section 6 of the Cochrane Handbook for Systematic Reviews of Interventions 4.2.6 (Higgins 2006). The following parameters will be assessed: (a) generation of random allocation sequence and allocation concealment (selection bias); (b) completeness of follow up and Intention‐to‐treat analysis (attrition bias); and (c) masking of outcome assessment (detection bias). Masking of participants and care providers is not feasible in these trials and hence will not be used as a measure of methodological quality.
Allocation concealment will be classified as A ‐ adequate, B ‐ unclear, C ‐ inadequate or D ‐ not used. Any method of allocation concealment such as sequentially numbered opaque envelopes, centralized random allocation, will be considered to be adequate. If the information available in the published trial reports is inadequate to assess the allocation concealment, we will contact the trial authors for clarification. If they do not respond within a reasonable period of time, we will classify the trial based on the available information. When studies do not report any concealment approach, adequacy will be considered unclear. We will also assess the impact of any assumptions made in this regard in a sensitivity analysis.
We will consider a trial to have conducted an intention‐to‐treat analysis only if it includes all participants who were randomized including those randomized but not treated, who were excluded after randomization for other reasons and those who were lost to follow‐up.
Measures of treatment effect
Data analysis will follow guidelines as in Section 8 of the Cochrane Handbook for Systematic Reviews of Interventions 4.2.6 (Deeks 2006). For dichotomous outcomes we will calculate a summary risk ratio. We will also report the risk difference and number needed to treat. We will calculate a mean difference for continuous outcomes. We will calculate a standardized mean difference if different scales are used to measure continuous outcomes.
Unit of analysis issues
The unit of analysis will be individual eyes. If both eyes from one person were included in the trial, we will extract the data and perform analyses that properly accounts for the non‐independence of the bilateral surgery design following section 8.11 of the Cochrane Handbook for Systematic Reviews of Interventions 4.2.6 (Deeks 2006).
Dealing with missing data
We will conduct an intention‐to‐treat analysis when data are missing due to drop‐out of participants. We will contact the authors for details when statistics such as standard deviations or outcome data are not clearly reported.
Assessment of heterogeneity
We will look for clinical heterogeneity by examination of the study details then test for statistical heterogeneity between trial results using the Chi‐square test and the I‐square value. We will consider a P value of the Chi‐square test less than 0.1 or I‐square values of more than 50% or both to be substantial statistical heterogeneity. We will also examine the funnel plot for statistical heterogeneity. When only one trial is included, we will not assess heterogeneity.
Assessment of reporting biases
Asymmetry of the funnel plot will be used to identify publication bias.
Data synthesis
If there is no substantial statistical heterogeneity, and if there is no clinical heterogeneity between the trials, we will combine the results in a meta‐analysis using a random‐effects model. A fixed‐effect model will be used if the number of trials is three or less. In case of substantial statistical or clinical heterogeneity we will not combine study results but present a narrative or tabulated summary.
Subgroup analysis and investigation of heterogeneity
We will conduct subgroup analyses by types of cataract surgery and by the presence of CNV in the unoperated eye.
Sensitivity analysis
Sensitivity analyses will be conducted to determine the impact of exclusion of studies with lower methodological quality, exclusion of unpublished studies and exclusion of industry‐funded studies.
Methods for future updates
Updates of this review will be conducted every two years after initial publication.
