A systematic literature review of surgical interventions for limbal stem cell deficiency in humans

PURPOSE: To evaluate the relative benefits and to identify any adverse effects of surgical interventions for limbal stem cell deficiency (LSCD).

DESIGN: Systematic literature review.

METHODS: We searched the following electronic databases from January 1, 1989 through September 30, 2006: MEDLINE, EMBASE, Science citation index, BIOSIS, and the Cochrane Library. In addition, reference lists were scanned to identify any additional reports. The quality of published reports was assessed using standard methods. The main outcome measure was improvement in vision of at least two Snellen lines of best-corrected visual acuity (BCVA). Data on adverse outcomes also were collected.

RESULTS: Twenty-six studies met the inclusion criteria. There were no randomized controlled studies. All 26 studies were either prospective or retrospective case series. For bilateral severe LSCD, keratolimbal allograft was the most common intervention with systemic immunosuppression. Other interventions included eccentric penetrating keratolimbal allografts and cultivated autologous oral mucosal epithelial grafts. An improvement in BCVA of two lines or more was reported in 31% to 67% of eyes. For unilateral severe LSCD, the most common surgical intervention was contralateral conjunctival limbal autograft, with 35% to 88% of eyes gaining an improvement in BCVA of two lines or more. The only study evaluating partial LSCD showed an improvement in BCVA of two lines or more in 39% of eyes.

CONCLUSIONS: Studies to date have not provided strong evidence to guide clinical practice on which surgery is most beneficial to treat various types of LSCD. Standardized data collection in a multicenter LSCD register is suggested.

The effectiveness of early lens extraction with intraocular lens implantation for the treatment of primary angle-closure glaucoma (EAGLE): Study protocol for a randomized controlled trial

BACKGROUND: Glaucoma is the leading cause of irreversible blindness. Although primary open-angle glaucoma is more common, primary angle-closure glaucoma (PACG) is more likely to result in irreversible blindness. By 2020, 5·3 million people worldwide will be blind because of PACG. The current standard care for PACG is a stepped approach of a combination of laser iridotomy surgery (to open the drainage angle) and medical treatment (to reduce intraocular pressure). If these treatments fail, glaucoma surgery (eg, trabeculectomy) is indicated. It has been proposed that, because the lens of the eye plays a major role in the mechanisms leading to PACG, early clear lens extraction will improve glaucoma control by opening the drainage angle. This procedure might reduce the need for drugs and glaucoma surgery, maintain good visual acuity, and improve quality of life compared with standard care.EAGLE aims to evaluate whether early lens extraction improves patient-reported, clinical outcomes, and cost-effectiveness, compared with standard care.

METHODS/DESIGN: EAGLE is a multicentre pragmatic randomized trial. All people presenting to the recruitment centres in the UK and east Asia with newly diagnosed PACG and who are at least 50 years old are eligible.The primary outcomes are EQ-5D, intraocular pressure, and incremental cost per quality adjusted life year (QALY) gained. Other outcomes are: vision and glaucoma-specific patient-reported outcomes, visual acuity, visual field, angle closure, number of medications, additional surgery (e.g., trabeculectomy), costs to the health services and patients, and adverse events.A single main analysis will be done at the end of the trial, after three years of follow-up. The analysis will be based on all participants as randomized (intention to treat). 400 participants (200 in each group) will be recruited, to have 90% power at 5% significance level to detect a difference in EQ-5D score between the two groups of 0·05, and a mean difference in intraocular pressure of 1·75 mm Hg. The study will have 80% power to detect a difference of 15% in the glaucoma surgery rate.

TRIAL REGISTRATION: ISRCTN44464607.

The United Kingdom Glaucoma Treatment Study:a multicenter, randomized, placebo-controlled clinical trial: design and methodology

Elevated intraocular pressure (IOP) is a major risk factor for the deterioration of open-angle glaucoma (OAG); medical IOP reduction is the standard treatment, yet no randomized placebo-controlled study of medical IOP reduction has been undertaken previously. The United Kingdom Glaucoma Treatment Study (UKGTS) tests the hypothesis that treatment with a topical prostaglandin analog, compared with placebo, reduces the frequency of visual field (VF) deterioration events in OAG patients by 50% over a 2-year period.

Alternative treatments to inhibit VEGF in age-related choroidal neovascularisation: 2-year findings of the IVAN randomised controlled trial

Background: Bevacizumab has been suggested to have similar effectiveness to ranibizumab for treatment of neovascular age-related macular degeneration. The Inhibition of VEGF in Age-related choroidal Neovascularisation (IVAN) trial was designed to compare these drugs and different regimens. Here, we report the findings at the prespecified 2-year timepoint. Methods: In a multicentre, 2×2 factorial, non-inferiority randomised trial, we enrolled adults aged at least 50 years with active, previously untreated neovascular age-related macular degeneration and a best corrected distance visual acuity (BCVA) of at least 25 letters from 23 hospitals in the UK. Participants were randomly assigned (1:1:1:1) to intravitreal injections of ranibizumab (0·5 mg) or bevacizumab (1·25 mg) in continuous (every month) or discontinuous (as needed) regimens, with monthly review. Study participants and clinical assessors were masked to drug allocation. Allocation to continuous or discontinuous treatment was masked up to 3 months, at which point investigators and participants were unmasked. The primary outcome was BCVA at 2 years, with a prespecified non-inferiority limit of 3·5 letters. The primary safety outcome was arterial thrombotic event or hospital admission for heart failure. Analyses were by modified intention to treat. This trial is registered, number ISRCTN92166560. Findings: Between March 27, 2008, and Oct 15, 2010, 628 patients underwent randomisation. 18 were withdrawn; 610 received study drugs (314 ranibizumab; 296 bevacizumab) and were included in analyses. 525 participants reached the visit at 2 years: 134 ranibizumab in continuous regimen, 137 ranibizumab in discontinuous regimen, 127 bevacizumab in continuous regimen, and 127 bevacizumab in discontinuous regimen. For BCVA, bevacizumab was neither non-inferior nor inferior to ranibizumab (mean difference -1·37 letters, 95% CI -3·75 to 1·01; p=0·26). Discontinuous treatment was neither non-inferior nor inferior to continuous treatment (-1·63 letters, -4·01 to 0·75; p=0·18). Frequency of arterial thrombotic events or hospital admission for heart failure did not differ between groups given ranibizumab (20 [6%] of 314 participants) and bevacizumab (12 [4%] of 296; odds ratio [OR] 1·69, 95% CI 0·80-3·57; p=0·16), or those given continuous (12 [4%] of 308) and discontinuous treatment (20 [7%] of 302; 0·56, 0·27-1·19; p=0·13). Mortality was lower with continuous than discontinuous treatment (OR 0·47, 95% CI 0·22-1·03; p=0·05), but did not differ by drug group (0·96, 0·46-2·02; p=0·91). Interpretation: Ranibizumab and bevacizumab have similar efficacy. Reduction in the frequency of retreatment resulted in a small loss of efficacy irrespective of drug. Safety was worse when treatment was administered discontinuously. These findings highlight that the choice of anti-VEGF treatment strategy is less straightforward than previously thought.

Treatments for macular oedema following central retinal vein occlusion: systematic review

Objectives: To review systematically the randomised controlled trial (RCT) evidence for treatment of macular oedema due to central retinal vein occlusion (CRVO).

Data sources: MEDLINE, EMBASE, CDSR, DARE, HTA, NHSEED, CENTRAL and meeting abstracts (January 2005 to March 2013).

Study eligibility criteria, participants and interventions: RCTs with at least 12 months of follow-up assessing pharmacological treatments for CRVO were included with no language restrictions.

Study appraisal and synthesis methods: 2 authors screened titles and abstracts and conducted data extracted and Cochrane risk of bias assessment. Meta-analysis was not possible due to lack of comparable studies.

Results: 8 studies (35 articles, 1714 eyes) were included, assessing aflibercept (n=2), triamcinolone (n=2), bevacizumab (n=1), pegaptanib (n=1), dexamethasone (n=1) and ranibizumab (n=1). In general, bevacizumab, ranibizumab, aflibercept and triamcinolone resulted in clinically significant increases in the proportion of participants with an improvement in visual acuity of ≥15 letters, with 40–60% gaining ≥15 letters on active drugs, compared to 12–28% with sham. Results for pegaptanib and dexamethasone were mixed. Steroids were associated with cataract formation and increased intraocular pressure. No overall increase in adverse events was found with bevacizumab, ranibizumab, aflibercept or pegaptanib compared with control. Quality of life was poorly reported. All studies had a low or unclear risk of bias.

Limitations: All studies evaluated a relatively short primary follow-up (1 year or less). Most had an unmasked extension phase. There was no head-to-head evidence. The majority of participants included had non-ischaemic CRVO.

Conclusions and implications of key findings: Bevacizumab, ranibizumab, aflibercept and triamcinolone appear to be effective in treating macular oedema secondary to CRVO. Long-term data on effectiveness and safety are needed. Head-to-head trials and research to identify ‘responders’ is needed to help clinicians make the right choices for their patients. Research aimed to improve sight in people with ischaemic CRVO is required.

Clinical Characteristics of Reticular Pseudodrusen in the Fellow Eye of Patients with Unilateral Neovascular Age-Related Macular Degeneration

Purpose: To describe associations between reticular pseudodrusen, individual characteristics, and retinal function.

Design: Cohort study.

Participants: We recruited 105 patients (age range, 52–93 years) who had advanced neovascular age-related macular degeneration (AMD) in only 1 eye from 3 clinical centers in Europe.

Methods: Minimum follow-up was 12 months. The eye selected for study was the fellow eye without advanced disease. Clinical measures of vision were distance visual acuity, near visual acuity, and results of the Smith-Kettlewell low-luminance acuity test (SKILL). Fundus imaging included color photography, red-free imaging, blue autofluorescence imaging, fluorescein angiography, indocyanine green angiography, and optical coherence tomography using standardized protocols. These were used to detect progression to neovascular AMD in the study eye during follow-up. All imaging outputs were graded for the presence or absence of reticular pseudodrusen (RPD) using a multimodal approach. Choroidal thickness was measured at the foveal center and at 2 other equidistant locations from the fovea (1500 μm) nasally and temporally. Metrics on retinal thickness and volume were obtained from the manufacturer-supplied automated segmentation readouts.

Main Outcome Measures: Presence of RPD, distance visual acuity, near visual acuity, SKILL score, choroidal thickness, retinal thickness, and retinal volume.

Results: Reticular pseudodrusen was found in 43 participants (41%) on 1 or more imaging method. The SKILL score was significantly worse in those with reticular drusen (mean score ± standard deviation [SD, 38±12) versus those without (mean score ± SD, 33±9) (P = 0.034). Parafoveal retinal thickness, parafoveal retinal volume, and all of the choroidal thickness parameters measured were significantly lower in those with reticular drusen than in those without. The presence of RPD was associated with development of neovascular AMD when corrected for age and sex (odds ratio, 5.5; 95% confidence interval, 1.1–28.8; P = 0.042). All participants in whom geographic atrophy developed during follow-up had visible RPD at baseline.

Conclusions: Significant differences in retinal and choroidal anatomic features, visual function, and risk factor profile exist in unilateral neovascular AMD patients with RPD compared with those without; therefore, such patients should be monitored carefully because of the risk of developing bilateral disease.

Treatment of choroidal neovascularisation secondary to membranoproliferative glomerulonephritis type II with intravitreal ranibizumab

Membranoproliferative glomerulonephritis type II (MPGN II) is characterised by electron-dense deposits of complement components in the glomerular basement membrane and retinal pigment epithelium. Approximately, 10% of affected individuals develop serious ocular complications similar to age-related macular degeneration such as choroidal neovascularisation (CNV), which has been managed with photocoagulation or photodynamic therapy; however, these treatments can impact visual acuity. We report the case of a 42-year-old woman with MPGN II presenting with decreased visual acuity and paracentral scotoma in her left eye due to an extrafoveal choroidal neovascular membrane (growth of new vessels under the retina). The patient was successfully treated with intravitreal ranibizumab (Lucentis) with restoration of visual function. This case highlights the successful management of CNV secondary to MPGN II with the antivascular endothelial growth factor agent ranibizumab and emphasises the importance of early referral of patients with MPGN II who are reporting of visual 'distortion'.

Drug treatment of macular oedema secondary to central retinal vein occlusion: a network meta-analysis

Objective
To indirectly compare aflibercept, bevacizumab, dexamethasone, ranibizumab and triamcinolone for treatment of macular oedema secondary to central retinal vein occlusion using a network meta-analysis (NMA).

Design
NMA.

Data sources
The following databases were searched from January 2005 to March 2013: MEDLINE, MEDLINE In-process, EMBASE; CDSR, DARE, HTA, NHSEED, CENTRAL; Science Citation Index and Conference Proceedings Citation Index-Science.

Eligibility criteria for selecting studies
Only randomised controlled trials assessing patients with macular oedema secondary to central retinal vein occlusion were included. Studies had to report either proportions of patients gaining ≥3 lines, losing ≥3 lines, or the mean change in best corrected visual acuity. Two authors screened titles and abstracts, extracted data and undertook risk of bias assessment. Bayesian NMA was used to compare the different interventions.

Results
Seven studies, assessing five drugs, were judged to be sufficiently comparable for inclusion in the NMA. For the proportions of patients gaining ≥3 lines, triamcinolone 4 mg, ranibizumab 0.5 mg, bevacizumab 1.25 mg and aflibercept 2 mg had a higher probability of being more effective than sham and dexamethasone. A smaller proportion of patients treated with triamcinolone 4 mg, ranibizumab 0.5 mg or aflibercept 2 mg lost ≥3 lines of vision compared to those treated with sham. Patients treated with triamcinolone 4 mg, ranibizumab 0.5 mg, bevacizumab 1.25 mg and aflibercept 2 mg had a higher probability of improvement in the mean best corrected visual acuity compared to those treated with sham injections.

Conclusions
We found no evidence of differences between ranibizumab, aflibercept, bevacizumab and triamcinolone for improving vision. The antivascular endothelial growth factors (VEGFs) are likely to be favoured because they are not associated with steroid-induced cataract formation. Aflibercept may be preferred by clinicians because it might require fewer injections.

Optical coherence tomography for the diagnosis of neovascular age-related macular degeneration: a systematic review

The purpose is to study the diagnostic performance of optical coherence tomography (OCT) and alternative diagnostic tests for neovascular age-related macular degeneration (nAMD). Methods employed are as follows:systematic review and meta-analysis; Index test: OCT including time-domain (TD-OCT) and the most recently developed spectral domain (SD-OCT); comparator tests: visual acuity, clinical evaluation (slit lamp), Amsler chart, colour fundus photographs, infra-red reflectance, red-free images/blue reflectance, fundus autofluorescence imaging (FAF), indocyanine green angiography (ICGA), preferential hyperacuity perimetry (PHP), and microperimetry; reference standard: fundus fluorescein angiography. Databases searched included MEDLINE, MEDLINE In Process, EMBASE, Biosis, SCI, the Cochrane Library, DARE, MEDION, and HTA database. Last literature searches: March 2013. Risk of bias assessed using QUADAS-2. Meta-analysis models were fitted using hierarchical summary receiver operating characteristic (HSROC) curves. Twenty-two studies (2 abstracts and 20 articles) enrolling 2124 participants were identified, reporting TD-OCT (12 studies), SD-OCT (1 study), ICGA (8 studies), PHP (3 studies), Amsler grid, colour fundus photography and FAF (1 study each). Most studies were considered to have a high risk of bias in the patient selection (55%, 11/20), and flow and timing (40%, 8/20) domains. In a meta-analysis of TD-OCT studies, sensitivity and specificity (95% CI) were 88% (46–98%) and 78% (64–88%), respectively. There was insufficient information to undertake meta-analysis for other tests. TD-OCT is a sensitive test for detecting nAMD, although specificity was only moderate. Data on SD-OCT are sparse. Diagnosis of nAMD should not rely solely on OCT.

Optical Coherence Tomography for the Monitoring of Neovascular Age-Related Macular Degeneration: A Systematic Review

Topic

To compare the accuracy of optical coherence tomography (OCT) with alternative tests for monitoring neovascular age-related macular degeneration (nAMD) and detecting disease activity among eyes previously treated for this condition.

Traditionally, fundus fluorescein angiography (FFA) has been considered the reference standard to detect nAMD activity, but FFA is costly and invasive. Replacement of FFA by OCT can be justified if there is a substantial agreement between tests.

Systematic review and meta-analysis. The index test was OCT. The comparator tests were visual acuity, clinical evaluation (slit lamp), Amsler chart, color fundus photographs, infrared reflectance, red-free images and blue reflectance, fundus autofluorescence imaging, indocyanine green angiography (ICGA), preferential hyperacuity perimetry, and microperimetry. We searched the following databases: MEDLINE, MEDLINE In-Process, EMBASE, Biosis, Science Citation Index, the Cochrane Library, Database of Abstracts of Reviews of Effects, MEDION, and the Health Technology Assessment database. The last literature search was conducted in March 2013. We used the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) to assess risk of bias.

We included 8 studies involving more than 400 participants. Seven reported the performance of OCT (3 time-domain [TD] OCT, 3 spectral-domain [SD] OCT, 1 both types) and 1 reported the performance of ICGA in the detection of nAMD activity. We did not find studies directly comparing tests in the same population. The pooled sensitivity and specificity of TD OCT and SD OCT for detecting active nAMD was 85% (95% confidence interval [CI], 72%–93%) and 48% (95% CI, 30%–67%), respectively. One study reported ICGA with sensitivity of 75.9% and specificity of 88.0% for the detection of active nAMD. Half of the studies were considered to have a high risk of bias.

There is substantial disagreement between OCT and FFA findings in detecting active disease in patients with nAMD who are being monitored. Both methods may be needed to monitor patients comprehensively with nAMD.

Optical coherence tomography for the diagnosis, monitoring and guiding of treatment for neovascular age-related macular degeneration:a systematic review and economic evaluation

BACKGROUND: Age-related macular degeneration is the most common cause of sight impairment in the UK. In neovascular age-related macular degeneration (nAMD), vision worsens rapidly (over weeks) due to abnormal blood vessels developing that leak fluid and blood at the macula.

OBJECTIVES: To determine the optimal role of optical coherence tomography (OCT) in diagnosing people newly presenting with suspected nAMD and monitoring those previously diagnosed with the disease.

DATA SOURCES: Databases searched: MEDLINE (1946 to March 2013), MEDLINE In-Process & Other Non-Indexed Citations (March 2013), EMBASE (1988 to March 2013), Biosciences Information Service (1995 to March 2013), Science Citation Index (1995 to March 2013), The Cochrane Library (Issue 2 2013), Database of Abstracts of Reviews of Effects (inception to March 2013), Medion (inception to March 2013), Health Technology Assessment database (inception to March 2013).

REVIEW METHODS: Types of studies: direct/indirect studies reporting diagnostic outcomes.

INDEX TEST: time domain optical coherence tomography (TD-OCT) or spectral domain optical coherence tomography (SD-OCT).

COMPARATORS: clinical evaluation, visual acuity, Amsler grid, colour fundus photographs, infrared reflectance, red-free images/blue reflectance, fundus autofluorescence imaging, indocyanine green angiography, preferential hyperacuity perimetry, microperimetry. Reference standard: fundus fluorescein angiography (FFA). Risk of bias was assessed using quality assessment of diagnostic accuracy studies, version 2. Meta-analysis models were fitted using hierarchical summary receiver operating characteristic curves. A Markov model was developed (65-year-old cohort, nAMD prevalence 70%), with nine strategies for diagnosis and/or monitoring, and cost-utility analysis conducted. NHS and Personal Social Services perspective was adopted. Costs (2011/12 prices) and quality-adjusted life-years (QALYs) were discounted (3.5%). Deterministic and probabilistic sensitivity analyses were performed.

RESULTS: In pooled estimates of diagnostic studies (all TD-OCT), sensitivity and specificity [95% confidence interval (CI)] was 88% (46% to 98%) and 78% (64% to 88%) respectively. For monitoring, the pooled sensitivity and specificity (95% CI) was 85% (72% to 93%) and 48% (30% to 67%) respectively. The FFA for diagnosis and nurse-technician-led monitoring strategy had the lowest cost (£39,769; QALYs 10.473) and dominated all others except FFA for diagnosis and ophthalmologist-led monitoring (£44,649; QALYs 10.575; incremental cost-effectiveness ratio £47,768). The least costly strategy had a 46.4% probability of being cost-effective at £30,000 willingness-to-pay threshold.

LIMITATIONS: Very few studies provided sufficient information for inclusion in meta-analyses. Only a few studies reported other tests; for some tests no studies were identified. The modelling was hampered by a lack of data on the diagnostic accuracy of strategies involving several tests.

CONCLUSIONS: Based on a small body of evidence of variable quality, OCT had high sensitivity and moderate specificity for diagnosis, and relatively high sensitivity but low specificity for monitoring. Strategies involving OCT alone for diagnosis and/or monitoring were unlikely to be cost-effective. Further research is required on (i) the performance of SD-OCT compared with FFA, especially for monitoring but also for diagnosis; (ii) the performance of strategies involving combinations/sequences of tests, for diagnosis and monitoring; (iii) the likelihood of active and inactive nAMD becoming inactive or active respectively; and (iv) assessment of treatment-associated utility weights (e.g. decrements), through a preference-based study.

STUDY REGISTRATION: This study is registered as PROSPERO CRD42012001930.

FUNDING: The National Institute for Health Research Health Technology Assessment programme.

A population study of binocular function

As part of a genome-wide association study (GWAS) of perceptual traits in healthy adults, we measured stereo acuity, the duration of alternative percepts in binocular rivalry and the extent of dichoptic masking in 1060 participants. We present the distributions of the measures, the correlations between measures, and their relationships to other psychophysical traits. We report sex differences, and correlations with age, interpupillary distance, eye dominance, phorias, visual acuity and personality. The GWAS, using data from 988 participants, yielded one genetic association that passed a permutation test for significance: The variant rs1022907 in the gene VTI1A was associated with self-reported ability to see autostereograms. We list a number of other suggestive genetic associations (p<10^-5).

Retinopathy in type 1 diabetes mellitus: Major differences between rural and urban dwellers in northwest Ethiopia

Aim: To audit levels of diabetes-related eye disease in Type 1 diabetes mellitus (T1DM) patients in northwest Ethiopia. In particular to establish whether, despite identical clinical goals, major differences between the physically demanding life-style of rural subsistence farmers and the sedentary life-style of urban dwellers would influence the prevalence of diabetes-related eye complications. 

Methods: A robust infrastructure for chronic disease management that comprehensively includes all rural dwellers was a pre-requisite for the investigation. A total of 544 T1DM were examined, representing 80% of all T1DM patients under regular review at both the urban and rural clinics and representative of patient age and gender (62.1% male, 37.9% female) of T1DM patients from this region; all were supervised by the same clinical team. Eye examinations were performed for visual acuity, cataract and retinal changes (retinal photography). HbA1c levels and the presence or absence of hypertension were recorded. 

Results/conclusions: Urban and rural groups had similar prevalences of severe visual impairment/blindness (7.0% urban, 5.2% rural) and cataract (7.3% urban, 7.1% rural). By contrast, urban dwellers had a significantly higher prevalence of retinopathy compared to rural patients, 16.1% and 5.0%, respectively (OR 2.9, p <. 0.02, after adjustment for duration, age, gender and hypertension). There was a 3-fold greater prevalence of hypertension in urban patients, whereas HbA1c levels were similar in the two groups. Since diabetic retinopathy is closely associated with microvascular disease and endothelial dysfunction, the possible influences of hypertension to increase and of sustained physical activity to reduce endothelial dysfunction are discussed.

Cataract extraction and patient vision-related quality of life: a cohort study

Aims: Cataract surgery is one of the most common surgeries performed, but its overuse has been reported. The threshold for cataract surgery has become increasingly lenient; therefore, the selection process and surgical need has been questioned. The aim of this study was to evaluate the changes associated with cataract surgery in patient-reported vision-related quality of life (VR-QoL).

Methods: A prospective cohort study was conducted. Consecutive patients referred to cataract clinics in an NHS unit in Scotland were identified. Those listed for surgery were invited to complete a validated questionnaire (TyPE) to measure VR-QoL pre- and post-operatively. TyPE has five different domains (near vision, distance vision, daytime driving, night-time driving, and glare) and a global score of vision. The influence of pre-operative visual acuity (VA) levels, vision, and lens status of the fellow eye on changes in VR-QoL were explored. 

Results: A total of 320 listed patients were approached, of whom 36 were excluded. Among the 284 enrolled patients, 229 (81%) returned the questionnaire after surgery. Results revealed that the mean overall vision improved, as reported by patients. Improvements were also seen in all sub-domains of the questionnaire.

Conclusion: The majority of patients appear to have improvement in patient-reported VR-QoL, including those with good pre-operative VA and previous surgery to the fellow eye. VA thresholds may not capture the effects of the quality of life on patients. This information can assist clinicians to make more informed decisions when debating over the benefits of listing a patient for cataract extraction.

Design characteristic of randomised controlled trials for geographic atrophy in age-related macular degeneration: selection of outcomes and sample size calculation

PurposeThe selection of suitable outcomes and sample size calculation are critical factors in the design of a randomised controlled trial (RCT). The goal of this study was to identify the range of outcomes and information on sample size calculation in RCTs on geographic atrophy (GA).MethodsWe carried out a systematic review of age-related macular degeneration (AMD) RCTs. We searched MEDLINE, EMBASE, Scopus, Cochrane Library, www.controlled-trials.com, and www.ClinicalTrials.gov. Two independent reviewers screened records. One reviewer collected data and the second reviewer appraised 10% of collected data. We scanned references lists of selected papers to include other relevant RCTs.ResultsLiterature and registry search identified 3816 abstracts of journal articles and 493 records from trial registries. From a total of 177 RCTs on all types of AMD, 23 RCTs on GA were included. Eighty-one clinical outcomes were identified. Visual acuity (VA) was the most frequently used outcome, presented in 18 out of 23 RCTs and followed by the measures of lesion area. For sample size analysis, 8 GA RCTs were included. None of them provided sufficient Information on sample size calculations.ConclusionsThis systematic review illustrates a lack of standardisation in terms of outcome reporting in GA trials and issues regarding sample size calculation. These limitations significantly hamper attempts to compare outcomes across studies and also perform meta-analyses.