Intravitreal neuroglobin treatment significantly reduces minimal rim width thinning and lamina cribrosa depth loss in the microbead primate model of chronic intraocular pressure elevation

Abstract

Purpose : To determine the effects of a single intravitreal (IVT) Neuroglobin (NGB) injection on the optical coherence tomography (OCT) minimal rim width (MRW) and lamina cribrosa (LC) depth measurements in a primate model of chronic experimental glaucoma.

Methods : Experimental procedures were conducted in accordance with the ARVO Statement for the Use of Animals in Ophthalmic and Vision Research. Singhealth institutional IACUC approval was obtained. Simultaneous bilateral IOP induction was induced in our AAALAC accredited lab according to published protocols. Bilateral eyes of 6 (age 2-5 years) Cynomolgus macaque monkeys received repeated anterior chamber polystyrene microbeads injections until IOP elevation >25mmHg was achieved. IOP, MRW and LC depth was monitered for a period of 11 months. At week 14, right eyes (OD) received a single 50ul intravitreal (IVT) injection of NGB (1mg/ml, ProSpec-Tany Technogene Ltd) whilst the left eye (OS) received a sham injection of balanced salt solution (BSS). Complications such as retinal detachment and inflammation was monitored.

Results : Bilateral IOP elevations were sustained after week 6 with an average of 8±SD 2 injections (Figure 1A). No statistical significance (p=0.857) in mean elevated IOP was detected in both eyes (Figure 1A, similar mean IOP 29mmHg achieved in both eyes). OD NGB IVT-treated eyes showed significantly reduced LC depth loss (p=0.0001, Figure 1B) and MRW thinning (p<0.0001, Figure 1C) compared to contralateral OS Sham-treated eyes. Complications included transient anterior chamber and vitreous inflammation post IVT injection of NGB which resolved with topical corticosteroids.

Conclusions : Neuroglobin protein therapy by IVT injection 8 weeks after chronic IOP elevation shows significantly reduced structural damage by OCT and suggests that NGB may play a protective role without having to correct IOP. Additionally, OCT parameters: MRW and LCD are useful for the in vivo follow up of therapeutic intervention in this primate microbead model of chronic IOP elevation to detect treatment response

This is a 2020 ARVO Annual Meeting abstract.

 

Fig A: Similar bilateral IOP elevation in 6 primates was achieved by week 6. Intravitreal NGB was given on week 14 only to the Right (OD) eye
Fig B: LC depth loss was significantly less in the NGB treated eye.
Fig C: MRW loss was significantly less in th NGB treated eye.