Longitudinal assessment of optic nerve head changes using optical coherence tomography in a primate microbead model of ocular hypertension

Abstract

In humans, the longitudinal characterisation of early optic nerve head (ONH) damage in ocular hypertension (OHT) is difficult as patients with glaucoma usually have structural ONH damage at the time of diagnosis. Previous studies assessed glaucomatous ONH cupping by measuring the anterior lamina cribrosa depth (LCD) and minimal rim width (MRW) using optical coherence tomography (OCT). In this study, we induced OHT by repeated intracameral microbead injections in 16 cynomolgus primates (10 unilateral; 6 bilateral) and assessed the structural changes of the ONH longitudinally to observe early changes. Elevated intraocular pressure (IOP) in OHT eyes was maintained for 7 months and serial OCT measurements were performed during this period. The mean IOP was significantly elevated in OHT eyes when compared to baseline and compared to the control eyes. Thinner MRW and deeper LCD values from baseline were observed in OHT eyes with the greatest changes seen between month 1 and month 2 of OHT. Both the mean and maximum IOP values were significant predictors of MRW and LCD changes, although the maximum IOP was a slightly better predictor. We believe that this model could be useful to study IOP-induced early ONH structural damage which is important for understanding glaucoma pathogenesis.

Intravitreal Neuroglobin Mitigates Primate Experimental Glaucomatous Structural Damage in Association with Reduced Optic Nerve Microglial and Complement 3-Astrocyte Activation

“…Using our modified version [ 30 , 36 ] of the previously established primate microbead ocular hypertension (OHT) model [ 37 , 38 ], the IOP was elevated by repeated injections of Dye-Trak (F) fluorescent polystyrene microspheres/microbeads (15 µm diameter) obtained from Triton technology Inc. (San Diego, CA, USA). The microbeads were received at a concentration of 1 million/mL of injectable saline solution containing 0.05% Tween 80 (polysorbate 80, Sigma-Aldrich, St. Louis, MO, USA) and 0.01% Thimerosal.…”

“…The mean RNFL thickness was measured by identifying the internal limiting membrane (ILM) and upper edge of the ganglion cell layer. The LCD was defined as the perpendicular distance from the Bruch’s membrane opening (BMO) reference plane to the anterior lamina cribrosa (LC) surface ( Figure 1 E,F) [ 30 , 39 , 40 ]. The anterior LC surface was defined by a sharp increase in axial signal intensity (corresponding to collagen) extending laterally up to the LC insertion points in the peripapillary sclera [ 30 , 39 , 40 ].…”

“…Primates, which are phylogenetically similar to humans, are a useful model in clinical translation studies. The primate microbead model of experimental glaucoma (EG) is useful for the investigation of the progressive changes in the optic nerve head (ONH) that are secondary to the IOP risk factor in glaucoma [ 30 , 31 , 32 ]. Since studies have shown that Ngb gene therapy is protective in rodent EG models [ 16 ], we hypothesised that intravitreal treatment (IVT) with Ngb (IVT-Ngb) may similarly prevent structural changes to the ONH in primate EG.…”

“…Since studies have shown that Ngb gene therapy is protective in rodent EG models [ 16 ], we hypothesised that intravitreal treatment (IVT) with Ngb (IVT-Ngb) may similarly prevent structural changes to the ONH in primate EG. Furthermore, in optical coherence tomography (OCT), parameters such as the anterior lamina cribrosa depth (LCD), minimum rim width (MRW) thickness, and peripapillary retinal nerve fibre layer (RNFL) thickness [ 33 , 34 ] can be used to monitor the dynamic and progressive structural damage to the ONH in EG [ 30 , 35 ]. Therefore, in this study, we investigated the neuroprotective effects of IVT-Ngb against IOP-mediated structural changes, microgliosis, and astrogliosis in the optic nerve as well as the ocular safety profile of IVT-Ngb using serial OCT measurements in a primate model of EG.…”

A Robust Microbead Occlusion Model of Glaucoma for the Common Marmoset

“… 6 , 7 Over the past few decades, experimental NHP models of glaucoma have been developed based mainly on laser photocoagulation of the perilimbal region, 8 – 11 cauterization of episcleral veins, 12 hypertonic saline injection into the episcleral veins, 13 and intracameral injection of microbeads. 14 – 17 …”