Effect of Cholinergic Drugs on Optic Nerve Structure and Function in Glaucoma

Abstract

Purpose: : To characterize effects of topical (demecarium bromide-DB) and systemic (citicoline-citi) cholinergic drugs on optic nerve (ON) function and structure in canine model of primary glaucoma.

Methods: : Nerve fiber layer (NFL) thickness was evaluated by optical coherence tomography (OCT) in healthy (HB) and glaucomatous (GB) Bassets. Diameter of retinal vessels (on OCT scans) and ON function (recorded using pattern electroretinography - pERG) was evaluated in GB before and after cholinergic therapy (DB and citi). GB treated with cholinergic drugs and non-treated GB were subjected to provocative test of ON function by acute elevation of intraocular pressure with concurrent pERG recording.

Results: : OCT analysis showed early thickening of NFL in glaucomatous dogs. Topical DB and systemic citicoline did not have significant effect on NFL thickness (p>0.5, Paired t-test), but caused significant vasodilatation of retinal blood vessels (DB: p=0.046, citi: p<0.0001, Paired t-test). Baseline pERG amplitudes significantly improved in DB treated dogs (before treatment = 3.6+0.3µV; post treatment = 4+0.4µV; p=0.0004, Paired t-test) but not in citi treated dogs. However, both DB and citi had significant protective effect on ON function during acute IOP stress challenge: at IOP of 50 mmHg, pERG amplitude was 0.5 + 0.17µV in non-treated GB, 0.98 + 0.3µV in DB-treated GB (p=0.0245, Unpaired t-test) and 1.83 + 0.24µV in citi-treated GB (p=0.0003, Unpaired t-test).

Conclusions: : Early changes in glaucomatous canine eyes are characterized by structural (NFL thickening) and functional (pERG deficits) changes. Topical and systemic cholinergic drugs reversed functional optic nerve deficits and/or significantly improved optic nerve resistance to acute IOP stress. Both citi and DB caused dilation of retinal vasculature. Cholinergic agents should be considered as possible neuroprotective therapeutic agents for treatment of glaucoma.

Keywords: intraocular pressure • electroretinography: clinical • imaging methods (CT, FA, ICG, MRI, OCT, RTA, SLO, ultrasound)