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Mary A Johnson, Neil R Miller, Steven L Bernstein; Lucentis is Not Neuroprotective in a Primate Model of Non-Arteritic Anterior Ischemic Optic Neuropathy (NAION). Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):5543.
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Non-Arteritic Anterior Ischemic Optic Neuropathy (NAION) is the most common cause of acute optic nerve-related vision loss in people over 50. There is no treatment. A retrospective study (Saati et al., 2013) and 2 small case studies (Bennett et al., 2007; Bajin et al., 2011) suggested that a single intravitreal (IVT) injection of ranibizumab protects against vision loss in NAION. A Genentech-supported clinical trial was completed in 2012; the results have not been announced. The relatively rare nature of the disorder and the 40% incidence of spontaneous improvement (IONDT, 1995) are challenges for NAION clinical studies. For this reason, we tested the efficacy of a single IVT injection of ranibizumab (Lucentis) in our primate model of NAION (pNAION).
Four normal male rhesus monkeys (8 - 12kg) were given a single IVT injection of Lucentis (1.25mg in 0.05ml) immediately following induction of experimental NAION (Chen & Johnson et al., 2008) in one eye. Four weeks later the fellow eye was induced and injected with a single IVT dose of vehicle. Spectral-domain OCT (Heidelberg, Inc), flash electroretinograms (ERGs), and simultaneous pattern ERG (pERG) and pattern visual evoked potentials (VEPs) were recorded, and fundus photography and fluorescein angiography (FA) were performed on each animal before and at 1 day, 1 week, 2 weeks, 4 weeks and 8-12 weeks after induction of pNAION. Animals were sacrificed within 2 weeks of final assessment. Differences in the retinal ganglion cell (RGC) numbers in each eye were estimated by stereological analysis of optic nerve axons. Optic nerve axons, myelin and inflammatory cells were evaluated using immunohistochemistry.
Lucentis conferred no advantage to the treated eye in development or resolution of macular (p = 0.45) or peripapillary edema (by OCT), in retention of VEP (p = 0.19) and pERG (p = 0.28) amplitudes, in the time course of optic nerve leakage and fluorescein dye staining, or in preservation of RGCs, compared with vehicle controls. Three of the 4 Lucentis-treated eyes showed more peripapillary leakage and eventual atrophy than the vehicle-treated eyes.
IVT administration of Lucentis showed no evidence of neuroprotection in a primate model of NAION, despite maximal dosing and immediate treatment post-induction. This finding suggests that VEGF inhibition is likely to be ineffective in clinical NAION treatment.
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