Neuroretinal rim response to transient changes in intraocular pressure in healthy non-human primate eyes
Introduction
Glaucoma is a group of optic neuropathies characterized by progressive vision loss and structural changes to the optic nerve head (ONH) and retinal ganglion cell- (RGC-) containing layers of the retina. Though the mechanism underlying glaucoma remains elusive, intraocular pressure (IOP) is known to be a major risk factor for disease.
The ONH, a relative weak point in the posterior aspect of the globe, is susceptible to the influence of IOP and has been described as the initial site of damage in glaucoma (Downs, 2015; Howell et al., 2007; Quigley et al., 1983). ONH parameters, quantified using optical coherence tomography (OCT), have been shown to change early in disease. In fact, the ONH minimum rim width (BMO-MRW), a measure of the neuroretinal rim, thins prior to other RGC-containing layers such as the retinal nerve fiber layer (RNFL) (Chauhan et al., 2013; He et al., 2014; Ivers et al., 2015; Patel et al., 2014; Reis et al., 2012). These findings suggest that BMO-MRW may have utility in detecting early stages of disease. It has been proposed that early BMO-MRW changes occur as a result of compression and/or stretching of axon bundles within the ONH (Fortune et al., 2016b), but the temporal relationships between BMO-MRW and IOP have not been well-defined. These relationships are necessary to evaluate the general hypothesis that IOP-associated changes of the neuroretinal rim are related to the health of the eye and are a harbinger for IOP susceptibility in glaucoma.
Non-human primates (NHP) are an excellent model for studying ONH structural changes in response to IOP and experimental glaucoma because their ONH anatomy is very similar to that of humans. Studies in healthy NHP have demonstrated that exposure to short-duration changes in IOP results in substantial changes to the neuroretinal rim (Patel et al., 2018; Strouthidis et al., 2011). In our previous work, using 10 mmHg increments in IOP at 10 min intervals, significant changes in ONH BMO-MRW, Bruch's membrane opening (BMO) position, and choroid thickness were seen. While most of these structural measures returned to baseline when IOP was returned to 10 mmHg, there was significant residual thinning of BMO-MRW with IOP reduction (Patel et al., 2018). However, the short periods of IOP challenge did not allow an assessment of neuroretinal rim tissue dynamics with modulation of IOP. As a result, it is not known whether the full extent of neuroretinal rim thinning/recovery was achieved, or if the rim tissue would continue to thin/recover over a longer period. Establishing the dynamics of neuroretinal rim change with short-term, sustained IOP modulation has important implications for both glaucoma pathophysiology and clinical practice. Therefore, the present investigations were undertaken to determine these effects over 2-h periods of mild and moderate IOP elevation, and subsequent IOP reduction, in healthy NHP eyes.
Section snippets
Subjects
Eight healthy NHP (Macaca mulatta) were included in the study. The subjects included six males and two females, ranging in age from 4.8 to 5.8 years (mean age 5.6 years). For each subject, one eye was used in the study. Experimental procedures and animal care protocols were approved by the Institutional Animal Care and Use Committee at the University of Houston and adhered to the National Institutes of Health guidelines for the care and use of laboratory animals.
Animal preparation
Prior to all experimental
Results
All animals maintained good systemic health during the experiments and throughout the duration of the study, and no adverse ocular events occurred as a result of cannulation. For each animal, experimental sessions were separated in time by at least 2 weeks. There was no significant difference in baseline BMO-MRW (p = 0.22) or baseline RNFL thickness (p = 0.72) between the first and second experimental sessions, suggesting that neither elevating IOP for 2 h nor cannulation results in permanent
Discussion
The present study demonstrated that the neuroretinal rim, quantified as minimum rim width (BMO-MRW), thins gradually over a prolonged time course when IOP is elevated and held at a mild-to-moderate level and approaches an asymptote with approximately 2 h of IOP elevation. In addition, the neuroretinal rim does not return to baseline, but rather approaches an asymptote, with 2 h of relatively low IOP. Our results also show that the pressure-induced neuroretinal rim changes are not related to
Conclusions
In conclusion, this study confirms that the neuroretinal rim is sensitive to mild and moderate elevations in IOP and demonstrates that the neuroretinal rim changes over a prolonged time course with substantial residual thinning following IOP reduction and that there is considerable variability among individuals with regards to the extent of thinning and recovery. Characteristics of BMO-MRW dynamics with IOP modulation may provide important information regarding ONH compliance and risk of
Funding
This work was supported by the National Institutes of Health [R01 EY029229, P30 EY007551] and the University of Houston Mary Murphy Research Endowment.
Declaration of competing interest
None.
Acknowledgements
The authors thank Dr. Faith McAllister for her assistance with optical coherence tomography segmentations.
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