Note: Project inclusion amended to include nAMD eyes only to reduce potential bias and confounders. However, despite the exclusion of DME and CRVO + ME eyes, the conclusions or significance of any findings did not change.
Purpose: Intravitreal injections (IVI) of anti-vascular endothelial growth factor (anti-VEGF) agents are pivotal in the treatment armamentarium of neovascular retinal diseases. Treat-and-extend (T&E) dosing aims to reduce cost barriers and the burden of frequent injections; however, the efficacy and safety of T&E versus other dosing regimens remains unclear. This meta-analysis comprehensively consolidates the data from published randomized clinical trials (RCTs) to answer this clinically relevant question.
Study design: Systematic review and meta-analysis.
Methods: We conducted a systematic literature search of Ovid MEDLINE, EMBASE, and Cochrane CENTRAL to September 2020. English-language RCTs reporting on efficacy and/or safety outcomes of T&E, bimonthly, monthly, and/or pro re nata (PRN) dosing regimens of anti-VEGF IVIs were included. Critical appraisal of trials for risk of bias and strength of evidence was performed using the Cochrane and GRADE guidelines, respectively. The primary outcome was improvement in best-corrected visual acuity (BCVA), while secondary outcomes included changes in central subfield thickness (CSFT), mean number of injections, mean number of follow-up visits, and incidence of adverse events. All outcomes were collected at last follow-up. Meta-analyses were conducted using a random effects model. If data were available, subgroup analyses were performed based on IVI agent and retinal disease.
Results: Across 11 included RCTs, 1140 eyes were treated with a T&E IVI dosing regimen, 866 with monthly, 123 with bimonthly, and 253 with PRN-dosed IVIs. One of 11 trials had a target follow-up of 6 months, five of 12 months, and five of 24 months (mean: 16.4 ± 7.0 months per eye). Across all trials, risk of bias was generally low-to-moderate. Mean change in BCVA and CSFT at last follow-up were non-significantly different between T&E versus monthly (P = 0.23 and 0.22, respectively), bimonthly (P = 0.88 and 0.18, respectively), and PRN (P = 0.30 and 0.54, respectively) dosing regimens. T&E conferred significantly fewer injections versus monthly (P < 0.001) but significantly higher injections versus PRN (P < 0.001) dosing regimens by final follow-up. There was no significant difference in safety outcomes amongst comparators.
Conclusions: Efficacy and safety differences are non-significant between T&E, bimonthly, monthly, and PRN regimens. T&E confers a statistically significant benefit of reduced injection burden relative to monthly dosing and reduced clinic visits relative to PRN. T&E remains efficacious while potentially enhancing patient satisfaction, improving treatment adherence, stabilizing visual function, conferring cost savings, and aiding in capacity planning to treat neovascular retinal disease.