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

View Article: PubMed Central - PubMed

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.

No MeSH data available.


Experimental parameters for entire group (N = 51 NHP). Frequency histograms show (A) the number of baseline OCT imaging sessions per animal, (B) the postlaser mean IOP in EG eyes, (C) the postlaser peak IOP in EG eyes, (D) duration of follow-up (number of months between first laser and final OCT imaging session), (E) number of days between final OCT imaging session and euthanasia, (F) age at the end of the experiment.
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i1552-5783-57-10-4403-f02: Experimental parameters for entire group (N = 51 NHP). Frequency histograms show (A) the number of baseline OCT imaging sessions per animal, (B) the postlaser mean IOP in EG eyes, (C) the postlaser peak IOP in EG eyes, (D) duration of follow-up (number of months between first laser and final OCT imaging session), (E) number of days between final OCT imaging session and euthanasia, (F) age at the end of the experiment.

Mentions: Figure 2 graphically depicts important experimental parameters for the entire group of 51 nonhuman primates (NHPs). The number of baseline OCT imaging sessions per animal ranged from 3 to 11 (median, 5; Fig. 2A). Mean IOP over the span of postlaser follow-up ranged from 10.4 to 31.0 mm Hg in EG eyes (median, 19.6 mm Hg; Fig. 2B). Mean IOP over the same period in the fellow control eyes ranged from 8.4 to 23.3 mm Hg (median, 11.4 mm Hg). The peak IOP observed during the postlaser follow-up period ranged from 15.3 to 60.3 mm Hg in EG eyes (median, 43.0 mm Hg; Fig. 2C) and from 10.0 to 31.3 mm Hg in fellow control eyes (median, 15.3 mm Hg). The duration of postlaser follow-up ranged from 3 to 37 months (median, 7.9 months; Fig. 2D). Total study duration ranged from 7 to 46 months (median, 13 months). The median time between the final imaging session and euthanasia was 5 days (range, 0 to 14 days; Fig. 2E). Age at the end of the experiment ranged from 2 to 26 years (median, 11.0 years; Fig. 2F).


Experimental Glaucoma Causes Optic Nerve Head Neural Rim Tissue Compression: A Potentially Important Mechanism of Axon Injury
Experimental parameters for entire group (N = 51 NHP). Frequency histograms show (A) the number of baseline OCT imaging sessions per animal, (B) the postlaser mean IOP in EG eyes, (C) the postlaser peak IOP in EG eyes, (D) duration of follow-up (number of months between first laser and final OCT imaging session), (E) number of days between final OCT imaging session and euthanasia, (F) age at the end of the experiment.
© Copyright Policy - cc-by-nc-nd
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC5016000&req=5

i1552-5783-57-10-4403-f02: Experimental parameters for entire group (N = 51 NHP). Frequency histograms show (A) the number of baseline OCT imaging sessions per animal, (B) the postlaser mean IOP in EG eyes, (C) the postlaser peak IOP in EG eyes, (D) duration of follow-up (number of months between first laser and final OCT imaging session), (E) number of days between final OCT imaging session and euthanasia, (F) age at the end of the experiment.
Mentions: Figure 2 graphically depicts important experimental parameters for the entire group of 51 nonhuman primates (NHPs). The number of baseline OCT imaging sessions per animal ranged from 3 to 11 (median, 5; Fig. 2A). Mean IOP over the span of postlaser follow-up ranged from 10.4 to 31.0 mm Hg in EG eyes (median, 19.6 mm Hg; Fig. 2B). Mean IOP over the same period in the fellow control eyes ranged from 8.4 to 23.3 mm Hg (median, 11.4 mm Hg). The peak IOP observed during the postlaser follow-up period ranged from 15.3 to 60.3 mm Hg in EG eyes (median, 43.0 mm Hg; Fig. 2C) and from 10.0 to 31.3 mm Hg in fellow control eyes (median, 15.3 mm Hg). The duration of postlaser follow-up ranged from 3 to 37 months (median, 7.9 months; Fig. 2D). Total study duration ranged from 7 to 46 months (median, 13 months). The median time between the final imaging session and euthanasia was 5 days (range, 0 to 14 days; Fig. 2E). Age at the end of the experiment ranged from 2 to 26 years (median, 11.0 years; Fig. 2F).

View Article: PubMed Central - PubMed

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.

No MeSH data available.