Histopathology of radiation-related ocular toxicity following intravitreal placement of ¹²⁴Iodine-labeled anti-VEGF therapeutic agents in a non-human primate model.

Abstract

Purpose : To determine whether intravitreally placed ¹²⁴I produces intraocular radiation-related toxicity in an owl monkey model.

Methods : Eight owl monkeys were studied, seven of these underwent intravitreal injection with 1.25 mg/0.05 mL ¹²⁴I bevacizumab, 0.5 mg/0.05 mL, ¹²⁴I ranibizumab or 2.0 mg/0.05 mL ¹²⁴I aflibercept in the right eye of each subject, and one subject served as a control. 4 subjects (3 injected and 1 control) were euthanized 6 weeks after injection and 4 injected subjects (all injected) were euthanized 45 weeks after injection. Both eyes from each subject were enucleated and were immersion fixed in 10% neutral-buffered formalin. The non-injected eye of each subject as well as both eyes from the non-injected subject served as control comparisons. Serial sections were routinely stained with hematoxylin & eosin (HE) and anti-CD31 rabbit polyclonal antibody to identify vascular endothelial cells. The following ocular structures were examined for each subject: cornea, iris, ciliary body, canal of Schlemm, lens, retina, choroid, optic nerve, sclera and periocular musculature and adipose tissue.

Results : There were no histopathologic lesions seen in any of the examined ocular structures of the injected eyes at both 6 and 45 weeks following injection with ¹²⁴I-labelled anti-VEGF agents irrespective of the treatment group. All of the control eyes exhibited normal histologic structures and there were no appreciable histologic differences seen between the injected and non-injected eyes and with both eyes of the control subject.

Conclusions : No radiation-related ocular toxicity was seen either at 6 or 45 weeks following ¹²⁴I intravitreal injection in any of the examined subjects. The use of ¹²⁴I-labelled drugs followed by PET imaging to assess the intravitreal pharmacokinetic and systemic biodistribution characteristics of such agents may be considered to be safe for use on primate subjects.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.