Treatment of monocular deprivation (MD) amblyopia by pharmacological retinal blockade of the fellow eye is effective in a non-human primate model: 1. Efficacy Studies

Abstract

Purpose : Experiments in cats and mice with MD amblyopia have shown that retinal inactivation of the fellow eye with microinjection of tetrodotoxin (TTX) increased responses in V1 to stimulation of the amblyopic eye. Here we report on the effectiveness of TTX treatment in reversing MD amblyopia in a non-human primate model.

Methods : Four rhesus monkeys underwent MD (viewing through LP Bangerter foils) for a duration of four weeks, starting at ~2 weeks of age. Two animals received fellow-eye TTX treatment at ~2.5 months of age (at the end of critical period for MD treatment) while the other two were treated at ~7.5 months (well outside critical period). Fellow-eye TTX treatment consisted of four intravitreal injections (115ng of TTX each) administered once per week. Visual function in each eye was assessed one week after each injection by recording cortical visual evoked potentials (VEP) elicited by monocular stimulation with square wave gratings of spatial frequencies 0.25-4 cyc/°. An ocular dominance index (ODI = [A-B]/[A+B]; A = VEPPower_AmblyopicEye, B = VEPPower_FellowEye) was calculated to estimate amblyopic deficit and its recovery following treatment.

Results : In all four animals, amblyopia was induced in the deprived eye with mean ODI values ranging from -0.18 to -0.33. Amblyopic eye deficits were larger at higher spatial frequencies as is often seen in humans with amblyopia. VEP responses from the TTX inactivated eye were absent two days after injection but recovered to pre-TTX values within one week. In younger animals, amblyopic eye VEP responses were significantly increased one week after the first fellow-eye TTX injection leading to a mean ODI improvement of 55% with larger recovery at higher spatial frequencies. Subsequent injections showed only limited additional improvement that was idiosyncratic across the different spatial frequencies tested. In contrast, monkeys treated at 7.5months of age did not exhibit recovery after the four injections.

Conclusions : Even at a very low dose, intravitreal fellow-eye TTX injection shows great promise as a treatment for MD amblyopia as it promoted recovery in the amblyopic eye and did not compromise function in the fellow eye. Further studies that identify the best treatment strategy (dose, age, frequency) are needed to refine this approach.

This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.