Functional and Ultrastructural Assessment of Novel OCT Findings in the Cynomolgus Monkey

Abstract

Purpose : Two transient, novel optical coherence tomography (OCT) findings (a sub-foveal hyper-reflective band, HRB; and a hyporeflective line, HFL at the junction of the photoreceptor outer segments and retinal pigment epithelium) associated with intravitreal (ITV) injection in cynomolgus monkeys were identified when OCT imaging was conducted within 24hr post-dose. Findings were observed subsequent to dosing with a number of different test articles, vehicles, and following trochar insertion into the globe. OCT findings lacked histological correlates on light microscopy. Here we describe efforts to further characterise these OCT findings in cynomolgus monkeys to better understand the potential for translation and human risk.

Methods : Eight cynomolgus monkeys were dosed bilaterally via ITV injection with a 100μl (2 x 50μl) vehicle previously identified as producing these OCT findings. Following dosing, OCT was conducted to establish the presence and character of any changes in OCT from baseline, followed by multi-focal electroretinography (mfERG), to help understand the functional consequence of these OCT findings. The animals were then euthanized, underwent upper body perfusion fixation, and the eyes were processed for ultrastructural examination.

Results : OCT findings of HRB were observed in 5/8 dosed eyes; and HFL were observed in 6/8 dosed eyes. No functional consequences, manifest as changes in mfERG, were observed. Ultrastructurally, the HFL was correlated with expansion of the photoreceptor layer, with increased space between the photoreceptor outer segments (consistent with edema). The HRB observed was consistent with regions of disk separation and distortion at the junction of the inner and outer photoreceptor segments. Ultrastructural correlates of both HRBs and HFLs were considered consistent with a transient, reversible lesion, in line with the rapid resolution of these findings on OCT.

Conclusions : The light microscopic and ultrastructural characteristics of these lesions, transient nature and lack of functional correlates, suggests that these novel OCT findings should be considered non-adverse and reversible.

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