REporting quality of PilOt randomised controlled trials in surgery (REPORTS): a methodological survey protocol.

INTRODUCTION: The aim of this methodological review is to evaluate the completeness of reporting of surgical pilot and feasibility randomised trials as per the Consolidated Standards of Reporting Trials (CONSORT) extension to randomised pilot and feasibility trials. Moreover, we aim to assess for the presence of spin reporting and inconsistency between abstract and main text reporting in surgical pilot and feasibility randomised trials. METHODS AND ANALYSIS: A comprehensive, electronic search strategy will be used to identify studies indexed in Medline, Embase and Cochrane Central Register of Controlled Trials (CENTRAL) databases. Studies will be included if they are pilot or feasibility randomised trials of surgical interventions. The primary outcome will be overall CONSORT statement extension to randomised pilot and feasibility trials checklist completeness. This will be defined as trials reporting each of the 40 items in the CONSORT statement extension to randomised pilot and feasibility trials checklist. Secondary outcomes will include the reporting of individual studies as per the CONSORT extension to randomised pilot and feasibility trials, the use of spin reporting strategies, trial factors associated with reporting quality and spin strategy use, and consistency between abstract and main text reporting. Poisson and logistic regressions will be performed to explore the association between trial factors and completeness of reporting as measured by the number of reported CONSORT items. ETHICS AND DISSEMINATION: This is a methodological survey that has been registered a priori on the International Prospective Register for Systematic Reviews (PROSPERO) (CRD42023475512). Local ethics approval is not required. We plan to disseminate study results through peer-reviewed publication and conference presentations.

Pilot and feasibility trials in surgery are incompletely reported according to the CONSORT checklist: a meta-research study.

OBJECTIVES: Given the key role that pilot and feasibility (PAF) trials play in addressing the challenges of surgical trials, adequate reporting completeness is essential. Our aim was to assess completeness of reporting and evaluate if the items of the Consolidated Standards of Reporting Trials (CONSORT) extension for PAF trials have been reported in surgical PAF trials. STUDY DESIGN: This is a metaresearch study reported according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Studies were included if they were pilot or feasibility randomized trials evaluating a surgical intervention. The primary outcome was overall adherence to the CONSORT statement extension to randomized PAF trials checklist. A Poisson regression was performed to explore the association between research factors and reporting completeness. SETTING: MEDLINE, Embase, and Cochrane Central Register of Controlled Trials were searched from January 1-December 31, 2011 and 2021. RESULTS: After screening 1991 citations, 38 studies from 2011 to 34 studies from 2021 were included. The mean CONSORT reporting score across all included studies was 21.5 (standard deviation 6.3). After excluding items that were not applicable to all studies, a mean of 20.1 (standard deviation 6.1) of 34 items (0.59) were reported. Studies published in 2021 (vs 2011) did not have a greater number of CONSORT items reported (incidence rate ratio [IRR] 1.01, 95% confidence interval [CI] 0.89-1.15). Studies registered in a clinical trial registry (IRR 1.29, 95% CI 1.12-1.48) and randomizing more than 50 patients (IRR 1.16, 95% CI 1.04-1.30) were associated with more CONSORT items reported. CONCLUSION: The reporting completeness of surgical PAF trials is poor and has not improved after the publication of the CONSORT extension.

Anti-vascular endothelial growth factor therapy and retinal non-perfusion in diabetic retinopathy: A meta-analysis of randomised trials.

PURPOSE: Retinal non-perfusion (RNP) is fundamental to disease onset and progression in diabetic retinopathy (DR). Whether anti-vascular endothelial growth factor (anti-VEGF) therapy can modify RNP progression is unclear. This investigation quantified the impact of anti-VEGF therapy on RNP progression compared with laser or sham at 12 months. METHODS: A systematic review and meta-analysis of randomised controlled trials (RCTs) were performed; Ovid MEDLINE, EMBASE and CENTRAL were searched from inception to 4th March 2022. The change in any continuous measure of RNP at 12 months and 24 months was the primary and secondary outcomes, respectively. Outcomes were reported utilising standardised mean differences (SMD). The Cochrane Risk of Bias Tool version-2 and the Grading of Recommendations Assessment, Development and Evaluation (GRADE) guidelines informed risk of bias and certainty of evidence assessments. RESULTS: Six RCTs (1296 eyes) and three RCTs (1131 eyes) were included at 12 and 24 months, respectively. Meta-analysis demonstrated that RNP progression may be slowed with anti-VEGF therapy compared with laser/sham at 12 months (SMD: -0.17; 95% confidence interval [CI]: -0.29, -0.06; p = 0.003; I2 = 0; GRADE rating: LOW) and 24-months (SMD: -0.21; 95% CI: -0.37, -0.05; p = 0.009; I2 = 28%; GRADE rating: LOW). The certainty of evidence was downgraded due to indirectness and due to imprecision. CONCLUSION: Anti-VEGF treatment may slightly impact the pathophysiologic process of progressive RNP in DR. The dosing regimen and the absence of diabetic macular edema may impact this potential effect. Future trials are needed to increase the precision of the effect and inform the association between RNP progression and clinically important events. PROSPERO REGISTRATION: CRD42022314418.

Subthreshold Compared with Threshold Macular Photocoagulation for Diabetic Macular Edema: A Systematic Review and Meta-Analysis.

TOPIC: To compare the efficacy and safety of subthreshold macular laser to conventional focal laser photocoagulation for the treatment of vision loss secondary to diabetic macular edema (DME). CLINICAL RELEVANCE: Macular laser remains an important and cost effective treatment option for vision loss secondary to DME. Although anti-VEGF therapy is often first-line, macular laser is of utility in low-resource or remote settings, for patients at risk of loss to follow-up, and for DME not meeting country-specific reimbursement criteria for anti-VEGF therapy. Subthreshold laser is a modality that does not produce clinical or histologic evidence of thermal damage, thereby potentially limiting the common complications of conventional laser. METHODS: Ovid MEDLINE, EMBASE, and CENTRAL databases were searched for randomized controlled trials (RCTs) from inception to September 28, 2022. Meta-analyses were performed using random-effects modeling. Data were collected at 12 and 24 months for best-corrected visual acuity (BCVA), central retinal thickness, diabetic retinopathy severity scale, rate of adverse events, rate of enrolled patients not completing treatment, rate of patients receiving retreatment, and quality-of-life measures. The risk of bias and certainty of evidence were assessed using Cochrane's Risk-of-Bias version 2 and the Grading of Recommendations, Assessment, Development and Evaluation (GRADE) frameworks, respectively. Subgroup analysis was performed between subthreshold laser modalities and evaluated with Instrument to assess the Credibility of Effect Modification Analyses tool. RESULTS: Fourteen RCTs comprising 514 eyes receiving conventional laser and 574 eyes receiving subthreshold laser were included. Subthreshold laser likely results in no difference to BCVA (moderate GRADE certainty) compared with conventional laser. Conventional laser demonstrated a small, statistically significant improvement in central retinal thickness (low GRADE certainty); however, the magnitude of this improvement is unlikely to be clinically important. There may not be a difference in the rate of adverse events (low GRADE certainty) at 12 months when comparing subthreshold laser to conventional laser for DME. CONCLUSION: Randomized controlled trial literature to date suggests subthreshold laser to be as effective as conventional laser in the treatment of DME. Increased follow-up duration is needed to observe any long-term safety benefit from reduced retinal damage. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Role of Positioning after Full-Thickness Macular Hole Surgery: A Systematic Review and Meta-Analysis.

TOPIC: The importance of postoperative face-down positioning (FDP) to achieve anatomic and functional success after full-thickness macular hole (FTMH) surgery is explored in this meta-analysis of randomized controlled trials (RCTs). CLINICAL RELEVANCE: There is considerable variability in clinical practices regarding the need and length of FDP recommended to patients after FTMH surgery. There is also a lack of robust clinical guidelines on the topic. As such, an updated estimate of the effect size of FDP on clinically important outcomes is critical to inform practice. METHODS: Ovid MEDLINE, EMBASE, CENTRAL, and SCOPUS databases were searched from inception to October 3, 2021, for RCTs evaluating FDP versus non-FDP (nFDP). Data were collected for 7 clinically important outcomes after macular hole surgery: closure rate, visual acuity (VA) improvement, recurrence of FTMH, visual function, quality of life, patient satisfaction, and complication rates. We used the Cochrane risk-of-bias tool for randomized trials (RoB 2) to assess the risk of bias and followed the Grade of Recommendations, Assessment, Development, and Evaluation (GRADE) approach to assess the certainty in the evidence across outcomes. We conducted meta-analyses using random-effects modeling. Subgroup analyses were carried out based on hole size, type of gas, and duration of FDP. RESULTS: Eight RCTs of 709 eyes were included. The relative risk (RR) of FTMH closure rate comparing FDP versus nFDP was RR 1.05 (95% confidence interval [CI]: 0.99, 1.12, P = 0.09, I2 = 44%, GRADE rating: LOW). The mean difference (MD) regarding VA improvement comparing FDP and nFDP was MD -0.07 (95% CI: -0.12 to 0.01, P = 0.03, I2 = 16%, GRADE rating: LOW). CONCLUSION: The current review did not demonstrate a difference between FDP and nFDP with respect to FTMH closure, although the CIs were wide. There was a visual benefit to FDP; however, the CIs included values of trivial clinical significance. Subgroup analyses demonstrated that the VA benefit observed was driven by large holes. Limited data precluded analysis regarding the rate of FTMH recurrence, measures of visual function, quality of life measures, and patient satisfaction metrics. Further prospective trials are required to assess the gaps in the literature and improve the certainty of evidence for the outcomes examined.

A MULTICENTER REVIEW EVALUATING THE RISK OF RHEGMATOGENOUS RETINAL DETACHMENT POST ENDOPHTHALMITIS: A Canadian Retina Research Network Investigation.

PURPOSE: To describe the characteristics of rhegmatogenous retinal detachments (RDs) that developed after endophthalmitis and to provide insight regarding incidence, management, and outcomes. METHODS: Retrospective chart review of consecutive patients diagnosed with endophthalmitis at two Canadian institutions and from one surgeon at a third center over a 10-year period. RESULTS: Three hundred sixteen eyes presented with endophthalmitis of which 32 (10%) were complicated by subsequent RD. The mean age (SD) of patients was 72.0 (13.77) years. Intravitreal injections (33%) and cataract surgery (31%) were the most common inciting events for the endophthalmitis. Cases were managed with tap and inject (16%), vitrectomy (30%), or both (47%). There were no differences in the rate of RD when comparing the inciting events, microbial growth, or management approaches. Baseline visual acuity was the only predictor of RD ( P = 0.009). There was an improvement in visual acuity following management of the RD (logarithm of the minimum angle of resolution 2.33 vs. 1.69 or Snellen hand motion vs. 20/980, P = 0.009), but final visual acuity in these patients was worse than in those who did not develop RD (logarithm of the minimum angle of resolution 1.69 vs. 1.27 or Snellen 20/980 vs. 20/372, P = 0.029). CONCLUSION: All patients with RD post endophthalmitis required additional surgery, and functional outcomes remained poor. Nevertheless, repair of these RDs can preserve some vision and be globe saving.

Treat-and-extend versus alternate dosing strategies with anti-vascular endothelial growth factor agents to treat center involving diabetic macular edema: A systematic review and meta-analysis of 2,346 eyes.

Anti-vascular endothelial growth factor (Anti-VEGF) agents are the standard of care for diabetic macular edema (CI-DME) with vision loss. They are commonly administered using several treatment protocols, including fixed, pro re nata (PRN) and treat-and-extend (T&E) regimens. Because of the lack of evidence defining an ideal treatment paradigm, we systematically compared T&E with fixed or PRN regimens. Visual acuity improvement was similar when comparing T&E to fixed or PRN dosing at 12 and 24 months. Regarding anatomic outcomes, no significant difference was found between T&E and fixed regimens for central retinal thickness or central subfoveal thickness at 12 and 24 months. Similarly, no significant difference was found for central retinal thickness at 12 months for T&E versus PRN regimen. Regarding total number of injections, no significant difference existed between T&E versus fixed regimens at 12 months. PRN regimens delivered fewer injections compared to T&E regimens at 12 months. The results of this analysis support that visual acuity and anatomic outcomes at 12 and 24 months are similar between T&E with either fixed or PRN regimens. More head-to-head trials comparing T&E versus fixed and PRN dosing are needed to provide visual and functional outcome data beyond year 2. PROSPERO Registration: CRD42021249362.

The 12- and 24-Month Effects of Intravitreal Ranibizumab, Aflibercept, and Bevacizumab on Intraocular Pressure: A Network Meta-Analysis.

TOPIC: To investigate the effect of anti-vascular endothelial growth factor (VEGF) therapy on intraocular pressure (IOP) 12 and 24 months after initiation. CLINICAL RELEVANCE: It is unclear whether serial anti-VEGF injections result in sustained IOP increases. METHODS: Randomized controlled trials (RCTs) comparing anti-VEGF agents with each other or with controls for the treatment of neovascular age-related macular degeneration, retinal vein occlusions, or diabetic macular edema were included. Pairwise meta-analysis and Bayesian network meta-analysis examined the proportion of patients whose IOP (1) increased 5 mmHg or more from baseline on consecutive visits, (2) increased 10 mmHg or more from baseline at any visit, (3) was 21 mmHg or more on consecutive visits, (4) was 25 mmHg or more at any visit, (5) was 30 mmHg or more at any visit, (6) prompted initiation of IOP-lowering medications, or (7) increased as per the clinicians' discretion. Grading of Recommendations Assessments, Development, and Evaluations methodology informed the certainty of evidence. RESULTS: Twenty-six RCTs of 12 522 eyes were included. Aflibercept, bevacizumab, ranibizumab (0.3 mg and 0.5 mg), and noninjection controls were analyzed. Eighty-three of 84 network estimates for comparisons between anti-VEGF agents demonstrated no statistically significant difference (low to moderate certainty of evidence). Ranibizumab 0.5 mg showed higher rates than bevacizumab of IOP measurements of 30 mmHg or more at 12 months (low certainty of evidence). Fifty-three of 56 network estimates for comparisons between anti-VEGF agents and controls demonstrated no statistically significant difference (low to moderate certainty of evidence). Ranibizumab 0.5 mg showed higher rates of consecutive IOP increases of 5 mmHg or more at 24 months (low certainty of evidence) and higher rates of IOP increases as per the clinicians' discretion at 12 and 24 months (low and very low certainty of evidence, respectively). The 95% credible intervals in comparisons without statistically significant effects did not rule out important clinical effects. The certainty of evidence in these comparisons is limited by imprecision. CONCLUSION: This network meta-analysis does not show any clear difference in IOP increases 12 and 24 months after treatment initiation between anti-VEGF agents and controls. Imprecision precludes definitive conclusions.

Treat-and-extend regimens of anti-vascular endothelial growth factor therapy for retinal vein occlusions: a systematic review and meta-analysis.

OBJECTIVE: To investigate treat-and-extend (T&E) regimens of anti-vascular endothelial growth factor (anti-VEGF) therapy for the treatment of macular oedema secondary to retinal vein occlusions (RVOs). METHODS: Ovid MEDLINE, Ovid EMBASE and CENTRAL were searched on 25 February 2021. Randomized controlled trials, cohort studies, case-control studies and case series were included. The primary outcome was the change in Early Treatment Diabetic Retinopathy Score (ETDRS) letters from baseline. Conversions from Snellen to ETDRS letters were performed utilizing a published protocol. Secondary outcomes included improvement in retinal thickness from baseline, number of anti-VEGF injections and frequency of adverse events. Outcomes were examined at 12 and 24 months. Certainty of evidence was assessed utilizing GRADE (Grading of Recommendations Assessments, Development and Evaluations) guidelines. RESULTS: Seven hundred eighty-six eyes from 16 studies were included. Meta-analysis demonstrated a mean improvement of 15.7 (95% CI: 13.3-18.0) ETDRS letters at 12 months. Central retinal thickness improved 269.7 µm (95% CI: 233.64-305.90) at 12 months. Injections were performed 8.1 (95% CI: 7.4-8.7) and 13.1 (95% CI: 9.4-16.8) times at 12 and 24 months respectively. Adverse events were infrequent across all studies. Grading of Recommendations Assessments, Development and Evaluations (GRADE) certainty of evidence was very low across all outcomes. CONCLUSIONS: The results support the viability of T&E regimens for the treatment of macular oedema secondary to RVOs.

The Muranga Teleophthalmology Study: A Comparison of Virtual (Teleretina) Assessment with in-person Clinical Examination to Diagnose Diabetic Retinopathy and Age-related Macular Degeneration in Kenya.

PURPOSE: This study compares a web-based teleophthalmology assessment with a clinical slit lamp examination to screen for diabetic retinopathy (DR) and age-related macular degeneration (AMD) among diabetic patients in a rural East African district. METHODS: Six hundred and twelve eyes from 306 diabetic patients underwent both a clinical slit lamp examination and a teleretina (TR) assessment by an experienced ophthalmologist. Both assessments were compared for any DR and AMD using the early treatment diabetic retinopathy study and age-related eye disease study grading scales, respectively. RESULTS: Of the 612 TR assessment photos, 74 (12%) were deemed ungradable due to media opacities, poor patient cooperation, or unsatisfactory photographs. The ability to detect DR and AMD showed a fair agreement (kappa statistic 0.27 and 0.23, respectively) between the TR and clinical slit lamp examination. Relative to a clinical slit lamp evaluation, a positive TR diagnosis carried a 75.0% positive predictive value when diagnosing DR and a 27.3% positive predictive value when diagnosing AMD. A negative TR diagnosis carried a 97.2% negative predictive value for the diagnosis of DR and a 98.1% negative predictive value for the diagnosis of AMD. CONCLUSION: When comparing TR assessments to clinical slit lamp examinations to diagnose DR and AMD, there was a fair agreement. Although further validation is needed, the TR approach provides a promising method to diagnose DR and AMD, two major causes of ocular impairment worldwide.