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. 2022 May 9:9:884608.
doi: 10.3389/fmed.2022.884608. eCollection 2022.

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

Nada O Taher  1   2 , Abdullah A Ghaddaf  1   2 , Sarah A Al-Ghamdi  3 , Jumanah J Homsi  4   5 , Bandar J Al-Harbi  3 , Lugean K Alomari  1   2 , Hashem S Almarzouki  1   2   6
Affiliations

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

Nada O Taher et al. Front Med (Lausanne). .

Abstract

Background: Laser 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.

Methods: We 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.

Results: Seven 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).

Conclusion: Overall, 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].

Keywords: anti-vascular endothelial growth factor; bevacizumab; laser photocoagulation; ranibizumab; retinopathy of prematurity.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Study flow diagram. CENTRAL, Cochrane Central Register of Controlled Trial; RCT, randomized controlled trial.
FIGURE 2
FIGURE 2
Risk of bias graph.
FIGURE 3
FIGURE 3
Risk of bias summary.
FIGURE 4
FIGURE 4
Forest plot of the recurrence rate. CI, confidence interval; IV, inverse variance; VEGF, vascular endothelial growth factor.
FIGURE 5
FIGURE 5
Funnel plot of recurrence rate. SE, standard error; RR: risk ratio.
FIGURE 6
FIGURE 6
Grading of Recommendations Assessment, Development and Evaluation (GRADE) evidence profile. CI, confidence interval; RCT, randomized controlled trial; ROP, retinopathy of prematurity; RR, risk ratio; VEGF, vascular endothelial growth factor.
FIGURE 7
FIGURE 7
Forest plot of treatment switching. CI, confidence interval; IV, inverse variance; VEGF, vascular endothelial growth factor.
FIGURE 8
FIGURE 8
Funnel plot of treatment switching. SE, standard error; RR, risk ratio.
FIGURE 9
FIGURE 9
Forest plot of retreatment. CI, confidence interval; IV, inverse variance; VEGF, vascular endothelial growth factor.
FIGURE 10
FIGURE 10
Funnel plot of retreatment. SE, standard error; RR: risk ratio.
FIGURE 11
FIGURE 11
Forest plot of adverse events. CI, confidence interval; IV, inverse variance; VEGF, vascular endothelial growth factor.
FIGURE 12
FIGURE 12
Funnel plot of adverse events. SE, standard error; RR, risk ratio.
FIGURE 13
FIGURE 13
Forest plot of mortality rate. CI, confidence interval; IV, inverse variance; VEGF, vascular endothelial growth factor.
FIGURE 14
FIGURE 14
Funnel plot of mortality rate. SE, standard error; RR, risk ratio.
See this image and copyright information in PMC

References

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