Intravitreal Anti-vascular Endothelial Growth Factor Injection for Retinopathy of Prematurity: A Systematic Review and Meta-Analysis

Abstract

BackgroundLaser photocoagulation and/or intravitreal anti-vascular endothelial growth factor (anti-VEGF) injections constitute the current standard treatment for retinopathy of prematurity (ROP). This systematic review and meta-analysis aimed to assess the efficacy and safety of anti-VEGF monotherapy for ROP treatment using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.MethodsWe searched the Medline, Embase, and Cochrane Central Register of Controlled Trials (CENTRAL) databases. We included randomized controlled trials (RCTs) that compared intravitreal anti-VEGF monotherapy (e.g., bevacizumab, ranibizumab, aflibercept, and pegaptanib) with laser photocoagulation in preterm infants with ROP. We evaluated the rates of recurrence, treatment switching, retreatment, adverse events, and mortality. The risk ratio (RR) was used to represent dichotomous outcomes. Data were pooled using the inverse variance weighting method. The quality of evidence was assessed using the GRADE approach. Risk of bias was assessed using the Revised Cochrane risk of bias tool for randomized trials.ResultsSeven RCTs (n = 579; 1,158 eyes) were deemed eligible. Three RCTs had an overall low risk of bias, three had some concerns, and one had an overall high risk of bias. The pooled effect estimate showed a statistically significant reduction in adverse events in favor of anti-VEGF monotherapy [RR = 0.17, 95% confidence interval (CI) 0.07–0.44]. The pooled analysis showed no significant difference between the anti-VEGF and laser groups in terms of recurrence rate (RR = 1.56, 95% CI 0.23–10.54), treatment switching (RR = 2.92, 95% CI 0.40–21.05), retreatment (RR = 1.56, 95% CI 0.35–6.96), and mortality rate (RR = 1.28, 95% CI 0.48–3.41).ConclusionOverall, intravitreal anti-VEGF monotherapy was associated with fewer adverse events than laser therapy, rated as high quality of evidence according to the GRADE criteria. Pooled analysis revealed no significant difference between the two arms with respect to the recurrence rate, treatment switching, retreatment, and mortality rate, with quality of evidence ranging from moderate to very low as per the GRADE approach.Systematic Review Registration[https://www.crd.york.ac.uk/prospero/#recordDetails], identifier [CRD42021270077].

The efficacy and ocular safety following aflibercept, conbercept, ranibizumab, bevacizumab, and laser for retinopathy of prematurity: a systematic review and meta-analysis

“…With respect to safety outcomes, some studies reported the potential risk of complications like retinal detachment, visual field loss, and cataracts after laser treatment [ 53 , 54 ]. A meta-analysis by Taher et al [ 55 ] suggested that anti-VEGF injections were associated with significantly fewer adverse events than laser in general. However, Popovic et al [ 52 ] found there was no significant difference between anti-VEGF and laser for all analyzed complications, including vitreous hemorrhage, retinal detachment, and retinal hemorrhage.…”

Non-surgical treatment of stage 4A retinopathy of prematurity

“…Moreover, the amount of VEGF in the vitreous body is high in ROP stage 4 [4]. Several studies reported good anatomical and visual outcomes for intravitreal anti-VEGFs in ROP stage 4 [4,5]. The conventional treatment for high-risk pre-threshold retinopathy of prematurity (ROP) involves traditional laser therapy targeting the non-vascularized retina, eliminating cells producing Vascular Endothelial Growth Factor (VEGF) [6].…”

Avascular Peripheral Retina in Infants

“…Ophthalmic treatment includes laser photocoagulation for peripheral avascular retina and intravitreal anti-VEGF for neovascularization. 61 , 62 …”

“…Treatment focuses on symptom management and includes skin grafting, surgery to repair skin lesions and skull abnormalities, prostheses for limb malformations, laser photocoagulation to the avascular retina to arrest the potential evolution from ischemia to neovascularization, and intravitreal anti-VEGF for neovascularization. 62 , 66 …”

“…Ocular management includes laser photocoagulation to the avascular retina, intravitreal anti-VEGF for neovascularization, and pars plana vitrectomy for RDs. 62 , 70 Life-long follow-up is required to monitor for systemic and ocular disease. 69 , 70 …”