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-A therapy on these levels, is crucial to 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 immunological 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 (ROM) between ROP patients and controls before and after treatment, heterogeneity was reported by I2-statistics. Risks of bias and publication bias were assessed using QUADAS-2 and funnel plots/Egger’s tests, respectively. Results Out of 942 papers, 54 were included, with 26 providing post-treatment data and 31 providing biomarker data. Findings show a significant decrease in VEGF-A levels in the first week after ROP treatment (ROM [95% CI] 0.34 [0.25-0.45], I2=97%, 17 publications). Anti-VEGF therapy showed a significantly more pronounced decrease (0.31 [0.25-0.38], I2=40%, 7 publications) than laser treatment in the first week after treatment (0.77 [0.61-0.97], I2=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.