Vitrectomy Status Alters Early Intravitreal Drug Distribution: An Ex Vivo PET-CT Study

Purpose: We aimed to evaluate the ex-vivo early-phase spatial drug distribution of intravitreally applied bevacizumab and vancomycin in human and porcine eyes with a native vitreous body compared to vitrectomized eyes filled with balanced salt solution (BSS), silicone oils and a hyaluronic acid-based vitreous body substitute hydrogel. Methods: Porcine eyes were vitrectomized minutes post-mortem and filled with BSS, silicone oil, or hydrogel. Native non-vitrectomized human and porcine eyes served as controls. Intravitreal injections consisted of either bevacizumab or vancomycin labeled with Gallium-68 (68-Ga). Positron emission computer tomography (PET-CT) imaging of cadaver eyes was performed for up to six hours after injection followed by qualitative depiction and quantification of intravitreal distribution of the labeled drugs. Results: Radioactive labeling with 68-Ga and subsequent purification of bevacizumab and vancomycin was successfully applied. Vitrectomized eyes presented an increased early spatial spread of both tested drugs compared to native vitreous body (intravitreal bevacizumab filled volume 36.5% vs. 16.5% [P < 0.0001], intravitreal vancomycin filled volume 31.8% vs. 12.0% [P = 0.0146] after injection). Bevacizumab tended to show a faster diffusion in native vitreous body compared to vancomycin. Bevacizumab appeared not to be soluble in silicone oil. Diffusion within a vitreous body replacement hydrogel is slower compared to BSS-filled eyes in the early phase. Conclusions: Ophthalmic surgical interventions and used endotamponades have a significant impact on early phase spatial diffusion within the vitreous cavity. Based on these preliminary results, early phase diffusion of protein drugs within a hyaluronic acid-based hydrogel is comparable to the native vitreous body.