Vitreous Levels of Erythropoietin and Vascular Endothelial Growth Factor in Eyes with Retinopathy of Prematurity

Purpose: To determine the vitreous levels of erythropoietin and vascular endothelial growth factor (VEGF) in eyes with retinopathy of prematurity (ROP) and to study the correlation between the 2 levels. Design: Retrospective case-control study. Participants: Forty eyes of 27 infants with stage 4 ROP (4A, 30 eyes; 4B, 10 eyes) were studied. Five eyes of 4 patients with congenital cataract were used as controls. Methods: The eyes with ROP were classified by the vascular activity into 3 groups: highly vascular-active ROP (n = 16), moderately vascular-active ROP (n = 10), and mildly vascular-active ROP (n = 14). Eyes with highly vascular-active ROP initially received an intravitreal injection of 0.5 mg bevacizumab and underwent vitrectomy approximately 1 week after the injection. The eyes in the other groups underwent vitrectomy without bevacizumab. Undiluted vitreous samples were obtained at the beginning of vitrectomy, and the vitreous concentrations of erythropoietin and VEGF were measured by enzyme-linked immunosorbent assay. Main Outcome Measures: The vitreous concentrations of erythropoietin and VEGF were determined and compared among the 4 groups. Results: The vitreous level of erythropoietin was significantly higher (P<0.05) in the highly and moderately vascular-active ROP eyes than in control eyes. The median concentration of erythropoietin was 744.6 mlU/ml in the highly vascular-active ROP eyes, 729.9 mlU/ml in the moderately vascular-active ROP eyes, 478.0 mlU/ml in the mildly vascular-active ROP eyes, and 0 mlU/ml in control eyes. The vitreous VEGF level was significantly higher (P<0.05) in the moderately vascular-active ROP eyes than in control eyes. The median concentration of VEGF was 44.7 pg/ml in the highly vascular-active ROP eyes that had received an intravitreal bevacizumab injection, 360.8 pg/ml in the moderately vascular-active ROP eyes, 0 pg/ml in the mildly vascular-active ROP eyes, and 11.4 pg/ml in control eyes. There was a significant positive correlation (r = 0.410; P = 0.047) between the erythropoietin and VEGF levels in moderately and mildly vascular-active ROP eyes. Conclusions: The elevated level of erythropoietin and its correlation with the VEGF level in eyes with stage 4 ROP suggest that not only VEGF but also erythropoietin may contribute to the pathogenesis of ROP.