Abstract
Purpose: :
In–vitro studies demonstrated that pegaptanib is a selective VEGF165 antagonist, approved for the treatment of neovascular ARMD. However, in vivo studies involving non–human primates have not been published. Therefore, the purpose of the study is to evaluate the effectivness of Macugen® in suppressing the choroidal neovascularization (CNV) induced by laser irradiation in a monkey model.
Methods: :
Six cynomolgus monkeys 3–4.5 kg participated in the study. Standard (clinically used) pre–filled dose of Macugen® (0.3 mg, 90µl) was applied to the central vitreous via inferior–temporal injection in one eye. Equivalent volume of balanced salt solution (BSS) was injected in the contraleteral eye as a control. One week post–injection, 12 laser burns (4 central and 8 peripheral) were applied to the retina of both eyes to induce CNV. Follow–up examinations were conducted 2,3,4,6,8 weeks after CNV induction. Baseline and follow–up evaluation included clinical examination of the anterior chamber, intraocular pressure measurement, optical coherence tomography (OCT), color fundus photography, fluorescein angiography (FA) and multifocal electroretinography (mfERG). Histopathological evaluation (haematoxylin–eosin) was performed at 4 (n=2), 6 (n=2) and 8 (n=2) weeks.
Results: :
Application of either pegaptanib sodium or BSS was well tolerated in all eyes and did not show any signs of anterior segment or retinal toxicity at one week. FA leakage from the CNV lesions (as graded by 3 independent graders) was slightly more intensive in eyes pre–treated with pegaptanib sodium compared to eyes pre–treated with BSS at 6 and 8 weeks (p=0.003, p=0.011, Wilcoxon test). For peripheral lesions at 6 or 8 weeks, or for all lesions at weeks 2, 3, and 4 the leakage intensity was not different between eyes pre–treated with pegaptanib or BSS. Preliminary analysis of OCT data showed no significant difference in central foveal thickness between the two groups of eyes. Similarly, the values of global N1P1 amplitude or P1 peak time of mfERG were not significantly different between the two groups. In accordance with OCT and mfERG data, histological evaluation revealed similar cellular and tissue response from the Macugen® pre–treated and the control group.
Conclusions: :
One week pre–treatment with a clinical dose of Macugen® was insufficient to suppress the response in a monkey model of experimental CNV.
Keywords: drug toxicity/drug effects • retina • electroretinography: non-clinical