Aqueous cytokine levels associated with severity of type 1 retinopathy of prematurity and treatment response to ranibizumab

Abstract

Purpose: To determine the aqueous humor levels of cytokines in eyes with type 1 retinopathy of prematurity (ROP) before primary intravitreal injection of ranibizumab (IVR).

Methods: Forty-nine infants with type 1 ROP (56 eyes of 28 infants in the threshold ROP group and 42 eyes of 21 infants in the type 1 pre-threshold ROP group) received primary IVR and 49 aqueous humor samples were obtained preoperatively. Aqueous humor samples from 15 infants (15 eyes) undergoing congenital cataract surgery were used as controls. The concentrations of 27 cytokines were measured by a multiplex bead assay. Infants with persistent, recurrent, or progressive ROP after IVR were retreated.

Results: The preoperative aqueous levels of 16 cytokines were significantly different among type 1 pre-threshold, threshold ROP, and control groups (P < 0.05). The concentrations of vascular endothelial growth factor (VEGF) (P < 0.001), interferon-γ (P < 0.001), interleukin (IL)-10 (P < 0.001), and IL-12 (P < 0.001) were the highest in the threshold ROP group, less in the type 1 pre-threshold ROP group, and the lowest in the control group. Retreatment was given to 55% of infants with ROP within a 48-week follow-up period after primary IVR. Higher VEGF (hazard ratio [HR] = 1.001, P = 0.001) and macrophage inflammatory protein-1β (HR = 1.085, P = 0.022) levels were independently correlated with ROP retreatment.

Conclusions: Higher aqueous levels of VEGF and inflammatory cytokines were associated with more severe type 1 ROP and ROP retreatment after primary IVR.

Keywords: Aqueous humor; Cytokine; Ranibizumab; Retinopathy of prematurity.