In-Depth Analysis of the Intravitreal Biocompatibility of Polyethylene Glycol of Different Molecular Weight in an In Vivo Porcine Model.

Abstract

PURPOSE: Polyethylene glycol (PEG)ylation is an established, increasingly used method to prolong the half-lives of active compounds applied intravitreally. However, the biocompatibility of high doses of high molecular weight PEG has never been systematically assessed in a translational in vivo model. The aim of this study was to evaluate the intraocular inflammatory and pro-angiogenic response as well as structural and functional retinal alterations after the intravitreal injection of PEG of varying molecular weight injected intravitreally in a large animal in vivo pig model. METHODS: This cohort study includes 12 pigs divided into 4 cohorts. Each cohort received an intravitreal injection of either 0.1 mL with 400 mg/mL of PEG-400, PEG-2000, PEG-40000 or an injection of balanced salt solution (BSS), respectively. Biocompatibility measurements including fundoscopy, optical coherence tomography (OCT) and electroretinography (ERG) were performed prior and 2, 4, and 6 weeks post-injection. Six weeks post-injection, the animals were euthanized, aqueous and vitreous taps were taken for cytokine and signal protein measurements, and immunostainings were performed. RESULTS: All animals with intravitreal PEG-injections showed significant preretinal vitreous cells, most likely hyalocytes, as evidenced by OCT, but no signs of intraretinal inflammation were seen in the immunostainings conducted 6 weeks after injection. Untreated left control eyes and eyes injected with BSS showed no signs of inflammation throughout the whole study period. Functional and structural retinal parameters showed no significant alterations over the course of 6 weeks. Cytokine analyses showed no prolonged inflammatory reaction. CONCLUSIONS: The one-time intravitreal injection of PEG causes mild intravitreal inflammatory reactions, as evidenced in OCT by increased vitreous cells. However, retinal structure and function is not affected.