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Invest Ophthalmol Vis SciAugust 201647 citations

Experimental Glaucoma Causes Optic Nerve Head Neural Rim Tissue Compression: A Potentially Important Mechanism of Axon Injury.

Fortune Brad, Reynaud Juan, Hardin Christy, Wang Lin, Sigal Ian A, Burgoyne Claude F


AI Summary

Experimental glaucoma in monkeys caused significantly more optic nerve head neural rim thinning than peripapillary nerve fiber layer thinning, suggesting axon compression within the optic nerve head.

Abstract

Purpose

We tested the hypothesis that experimental glaucoma (EG) results in greater thinning of the optic nerve head (ONH) neural rim tissue than the peripapillary retinal nerve fiber layer (RNFL) tissue.

Methods

Longitudinal spectral-domain optical coherence tomography (SDOCT) imaging of the ONH and peripapillary RNFL was performed every other week under manometric IOP control (10 mm Hg) in 51 nonhuman primates (NHP) during baseline and after induction of unilateral EG. The ONH parameter minimum rim area (MRA) was derived from 80 radial B-scans centered on the ONH; RNFL cross-sectional area (RNFLA) from a peripapillary circular B-scan with 12° diameter.

Results

In control eyes, MRA was 1.00 ± 0.19 mm2 at baseline and 1.00 ± 0.19 mm2 at the final session (P = 0.77), while RNFLA was 0.95 ± 0.09 and 0.95 ± 0.10 mm2, respectively (P = 0.96). In EG eyes, MRA decreased from 1.00 ± 0.19 mm2 at baseline to 0.63 ± 0.21 mm2 at the final session (P < 0.0001), while RNFLA decreased from 0.95 ± 0.09 to 0.74 ± 0.19 mm2, respectively (P < 0.0001). Thus, MRA decreased by 36.4 ± 20.6% in EG eyes, significantly more than the decrease in RNFLA (21.7 ± 19.4%, P < 0.0001). Other significant changes in EG eyes included increased Bruch's membrane opening (BMO) nonplanarity (P < 0.05), decreased BMO aspect ratio (P < 0.0001), and decreased MRA angle (P < 0.001). Bruch's membrane opening area did not change from baseline in either control or EG eyes (P = 0.27, P = 0.15, respectively).

Conclusions

Optic nerve head neural rim tissue thinning exceeded peripapillary RNFL thinning in NHP EG. These results support the hypothesis that axon bundles are compressed transversely within the ONH rim along with glaucomatous deformation of connective tissues.


MeSH Terms

AnimalsAxonsDisease Models, AnimalDisease ProgressionFemaleGlaucomaIntraocular PressureMacaca mulattaMaleNerve FibersOptic DiskOptic Nerve DiseasesRetinal Ganglion CellsTime FactorsTomography, Optical Coherence

Key Concepts6

In experimental glaucoma (EG) eyes of nonhuman primates (NHP), the minimum rim area (MRA) decreased significantly from 1.00  0.19 mm2 at baseline to 0.63  0.21 mm2 at the final session (P < 0.0001).

MechanismBasic ScienceLongitudinal spectral-domain optical coherence tomography (SDOCT) imaging studyn=51 nonhuman primates (NHP)Ch5Ch12

In experimental glaucoma (EG) eyes of nonhuman primates (NHP), the retinal nerve fiber layer cross-sectional area (RNFLA) decreased significantly from 0.95  0.09 mm2 at baseline to 0.74  0.19 mm2 at the final session (P < 0.0001).

MechanismBasic ScienceLongitudinal spectral-domain optical coherence tomography (SDOCT) imaging studyn=51 nonhuman primates (NHP)Ch5Ch12

In experimental glaucoma (EG) eyes of nonhuman primates (NHP), the minimum rim area (MRA) decreased by 36.4  20.6%, which was significantly more than the decrease in retinal nerve fiber layer cross-sectional area (RNFLA) (21.7  19.4%, P < 0.0001).

MechanismBasic ScienceLongitudinal spectral-domain optical coherence tomography (SDOCT) imaging studyn=51 nonhuman primates (NHP)Ch5Ch12

In experimental glaucoma (EG) eyes of nonhuman primates (NHP), other significant changes included increased Bruch's membrane opening (BMO) nonplanarity (P < 0.05), decreased BMO aspect ratio (P < 0.0001), and decreased MRA angle (P < 0.001).

MechanismBasic ScienceLongitudinal spectral-domain optical coherence tomography (SDOCT) imaging studyn=51 nonhuman primates (NHP)Ch5Ch12

Bruch's membrane opening (BMO) area did not change from baseline in either control eyes (P = 0.27) or experimental glaucoma (EG) eyes (P = 0.15) of nonhuman primates (NHP).

MechanismBasic ScienceLongitudinal spectral-domain optical coherence tomography (SDOCT) imaging studyn=51 nonhuman primates (NHP)Ch5Ch12

Longitudinal spectral-domain optical coherence tomography (SDOCT) imaging was performed every other week under manometric IOP control (10 mm Hg) in 51 nonhuman primates (NHP) during baseline and after induction of unilateral experimental glaucoma (EG).

MethodologyBasic ScienceLongitudinal spectral-domain optical coherence tomography (SDOCT) imaging studyn=51 nonhuman primates (NHP)Ch5

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