Intraocular pharmacokinetics of anti‐vascular endothelial growth factor agents by intraoperative subretinal versus intravitreal injection in silicone oil‐filled eyes of proliferative diabetic retinopathy: a randomized controlled pilot study

Abstract Purpose Intraoperative subretinal anti‐vascular endothelial growth factor (VEGF) injections have been used clinically in some case, but the pharmacokinetic characteristics have not yet been determined. In this pilot study, we investigate the pharmacokinetic parameters of anti‐VEGF agents by intraoperative subretinal or intravitreal injection in silicone oil (SiO)‐filled eyes of patients with proliferative diabetic retinopathy (PDR). Methods Randomized controlled trial including 13 patients (16 eyes) with PDR underwent pars plana vitrectomy (PPV) with SiO tamponade and randomly received a subretinal (8 eyes) or intravitreal (8 eyes) conbercept injection (0.5 mg/0.05 ml) intraoperatively. Aqueous humour (AH) was obtained on the 1st, 3rd, 7th, 10th, 14th, 21st and 28th day after the injection. Drug concentrations in the AH were determined by enzyme‐linked immunosorbent assay (ELISA). The last best‐corrected visual acuity (BCVA) was examined 6 months postoperatively. Results The clearance rate of anti‐VEGF agents by subretinal injection was reduced in vitrectomized eyes with SiO tamponade (p < 0.05). With the same drug dose, subretinal injection (5.49 ± 6.11 μg/ml) resulted in higher drug concentrations in the AH when compared with intravitreal injection (0.42 ± 0.46 μg/ml, p = 0.001) 4 weeks after the treatment. The mean residence time last (MRT 0‐t ) by subretinal injection (11.57 ± 0.83 days) was significantly longer than the mean MRT 0‐t by intravitreal injection (7.10 ± 1.00 days, p < 0.001). A self‐paired analysis showed that subretinal injection led to the BCVA improvement by +28.59 letters 6 months postoperatively (p = 0.028) while the BCVA did not improve significantly by intravitreal injection (p = 0.715). Conclusions The drug maintenance phase was prolonged by intraoperative subretinal injection in SiO‐filled eyes of PDR. The results suggest that subretinal injection might be a valuable treatment option for the management of PDR.