Circulating VEGF-A Levels in Relation to Retinopathy of Prematurity and Treatment Effects: A Systematic Review and Meta-Analysis.

TOPIC: Retinopathy of prematurity (ROP) is a severe retinal vascular disorder affecting preterm infants, potentially leading to retinal detachment and blindness. This review aims to elucidate the relationship between systemic VEGF levels and ROP. CLINICAL RELEVANCE: This systematic review aims to consolidate evidence from available studies to guide future research and inform clinical practice. In particular, the role of circulating VEGF-A levels in predicting ROP onset and progression, and evaluating the impact of anti-VEGF therapy on these levels, is crucial in ensuring efficacy and safety in patient care. METHODS: Scopus and PubMed were searched to identify studies investigating circulating VEGF-gene products in ROP patients using immunologic assays. Two authors independently screened the literature and extracted data, employing a random-effects meta-analysis to compare VEGF levels as the ratio of means between ROP patients and controls before and after treatment, heterogeneity was reported by I(2)-statistics. Risks of bias and publication bias were assessed using Quality Assessment of Diagnostic Accuracy Studies-2 and funnel plots/Egger's tests, respectively. RESULTS: Out of 941 papers, 54 were included, with 26 providing posttreatment data and 31 providing biomarker data. Findings show a significant decrease in VEGF-A levels in the first week after ROP treatment (ratio of means [95% confidence interval] 0.34 [0.25-0.45], I(2) = 97%, 17 publications). Anti-VEGF therapy showed a significantly more pronounced decrease (0.31 [0.25-0.38], I(2) = 40%, 7 publications) than laser treatment in the first week after treatment (0.77 [0.61-0.97], I(2) = 42%, 2 publications, subgroup difference, P < 0.01), among studies with a low risk of bias. Serum samples demonstrated a more marked decrease in VEGF-A than plasma (subgroup difference P < 0.01). However, the use of blood VEGF-A concentration as a biomarker for ROP prediction has shown inconsistent trends. The risk of bias mainly stems from unclear patient selection and lack of sample timing or analytical method details. CONCLUSION: While anti-VEGF treatment significantly reduced blood VEGF-A levels in the first week post-ROP treatment, blood VEGF-A levels did not consistently predict ROP development. Heterogeneity in the results underscores the need for optimized analytical methods and emphasizes the importance of considering individual variation in VEGF-A concentrations independent of ROP diagnosis. FINANCIAL DISCLOSURES: The author(s) have no proprietary or commercial interest in any materials discussed in this article.