Response To Anti-Vegf Therapy In A Nonhuman Primate Model Of Diabetic Macular Edema

Diabetic macular edema (DME) is one manifestation of diabetic retinopathy (DR), where fluids leak from the retinal vessels into the centre of the macula, causing swelling and blurred vision. VEGF inhibitors (e.g., ranibizumab), have demonstrated clinical efficacy in treating DME; however, it is known that ∼50% of patients do not respond to anti-VEGF therapy. Therefore, DME remains an unmet medical need. To discover novel therapies for DME, animal models that recapitulate clinical phenotypes and validated with anti-VEGF drugs will be of importance. Rodent models of DR have been developed using chemical or dietary induction to mimic the pathophysiological features observed in human. However, differences in the structural and biochemical characteristics of the visual system between rodents and humans hamper their clinical translation. Herein, we aimed to determine the effect of intravitreal administration of ranibizumab in aged, spontaneously dysmetabolic non-human primate with increased average retinal thickness (329 ± 6 µm, vs. age-matched controls 299 ± 10 µm). Seven of them showed signs of non-proliferative DR (NPDR) with presence of intra-retinal cysts, exudates or micro-aneurysms. Changes in retinal thickness and vascular leakage were measured by optical coherence tomography and fluorescein angiography, respectively. Plasma and vitreous levels of VEGF were also determined. Longitudinal data measured over 3-mo. period demonstrated modest, statistical insignificant reduction in average retinal thickness, plasma and vitreous VEGF levels. Some NPDR animals did showed potential improvement in vascular leakage. Considering anti-VEGF drugs are mostly effective in severe DR/DME patients, our results might be reconciled with the early stage of disease condition ascribed to these animals. Further investigation is needed to better understand heterogeneity of individual animal’s drug response and the relationship among imaging, plasma, and vitreous readouts in a longitudinal manner. Disclosure S. Chia: None. L. Gong: None. S. Tiu: Employee; Self; Merck Sharp & Dohme Corp. S.L. Conarello: None. S. Bellum: None. L. Pan: None. C. Lee: None. A. Abu Bakar Ali: Employee; Self; Merck & Co., Inc. L. Hong: Employee; Spouse/Partner; Illumina, Inc. Employee; Self; Merck Sharp & Dohme Corp. Stock/Shareholder; Spouse/Partner; Illumina, Inc. Stock/Shareholder; Self; Merck Sharp & Dohme Corp. W. Zeng: None. C. Chin: None. N.X. Li: Employee; Self; Merck & Co., Inc.