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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.


Methods used to quantitatively compare MRA to RNFLA. The left column shows baseline data, the right column shows final follow-up data. (A) B-scan through the horizontal meridian of the ONH. The inset shows the B-scan location indicated by the bold green line overlaid onto the infrared confocal scanning laser ophthalmoscopy (CSLO) reflectance image. Structures delineated in each radial B-scan include the ILM (yellow) and BMO points (red). The green segments connecting BMO points to the ILM represent the pair of MRW measurements made in each radial B-scan. (B) B-scan through the vertical meridian of the ONH. (C) Results for all 80 B-scans shown projected from 3D. (D) Derivation of MRA from the 160 radial trapezoidal sectors of each ONH (see Methods text for details). Note deformation of the ONH apparent in the right column for MRW/MRA, including a deeper “cup” and thinner “rim.” In this EG eye, global average MRA decreased from 1.16 mm2 at baseline to 0.63 mm2 at the final time point (−45.6%). (E) Segmentation of peripapillary circular B-scans to obtain the parameter RNFLA are shown for the same eye and time points, ILM (red), and posterior RNFL boundary (green). Retinal nerve fiber layer thickness decreased from 113.8 μm at baseline to 96.1 μm at the final time point; RNFLA decreased from 1.07 mm2 at baseline to 0.90 mm2 at the final time point (−15.5%). (F) Retinal nerve fiber layer area represented by the gold colored ribbon in projected 3D image from baseline (left) and final time point (right). The much larger decrease in MRA than RNFLA suggests substantial transverse compression of axons (and possibly also astrocytes) at the ONH rim. This can be appreciated by comparison of the images inset at the bottom of each column, which are the infrared CSLO reflectance image painted onto the ILM surface at each time point; the RNFL appears stretched over the ONH rim at the final time point.
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i1552-5783-57-10-4403-f01: Methods used to quantitatively compare MRA to RNFLA. The left column shows baseline data, the right column shows final follow-up data. (A) B-scan through the horizontal meridian of the ONH. The inset shows the B-scan location indicated by the bold green line overlaid onto the infrared confocal scanning laser ophthalmoscopy (CSLO) reflectance image. Structures delineated in each radial B-scan include the ILM (yellow) and BMO points (red). The green segments connecting BMO points to the ILM represent the pair of MRW measurements made in each radial B-scan. (B) B-scan through the vertical meridian of the ONH. (C) Results for all 80 B-scans shown projected from 3D. (D) Derivation of MRA from the 160 radial trapezoidal sectors of each ONH (see Methods text for details). Note deformation of the ONH apparent in the right column for MRW/MRA, including a deeper “cup” and thinner “rim.” In this EG eye, global average MRA decreased from 1.16 mm2 at baseline to 0.63 mm2 at the final time point (−45.6%). (E) Segmentation of peripapillary circular B-scans to obtain the parameter RNFLA are shown for the same eye and time points, ILM (red), and posterior RNFL boundary (green). Retinal nerve fiber layer thickness decreased from 113.8 μm at baseline to 96.1 μm at the final time point; RNFLA decreased from 1.07 mm2 at baseline to 0.90 mm2 at the final time point (−15.5%). (F) Retinal nerve fiber layer area represented by the gold colored ribbon in projected 3D image from baseline (left) and final time point (right). The much larger decrease in MRA than RNFLA suggests substantial transverse compression of axons (and possibly also astrocytes) at the ONH rim. This can be appreciated by comparison of the images inset at the bottom of each column, which are the infrared CSLO reflectance image painted onto the ILM surface at each time point; the RNFL appears stretched over the ONH rim at the final time point.

Mentions: All SDOCT scans were acquired using a Spectralis instrument (Heidelberg Engineering, GmbH, Heidelberg, Germany) 30 minutes after IOP was manometrically stabilized to 10 mm Hg. This is important to minimize elastic components of deformation that are known to exert a greater effect on the ONH than on peripapillary RNFL thickness.22,23 A clear, rigid gas permeable contact lens filled with 0.5% carboxymethylcellulose solution was placed over the apex of each cornea. Spectral-domain OCT scans recorded at each session included an 80-radial B-scan pattern centered on the ONH (30° wide, 1536 A-scans/B-scan, Figs. 1A, 1B) and a peripapillary circular B-scan with 12° diameter (1536 A-scans, Fig. 1E). In all cases, nine to 16 individual sweeps were averaged in real time to form each B-scan. At the first baseline imaging session, SDOCT scans were centered manually on the ONH by the operator. All follow-up scans were acquired at the same location as baseline using the instrument's automatic active eye tracking software.


Experimental Glaucoma Causes Optic Nerve Head Neural Rim Tissue Compression: A Potentially Important Mechanism of Axon Injury
Methods used to quantitatively compare MRA to RNFLA. The left column shows baseline data, the right column shows final follow-up data. (A) B-scan through the horizontal meridian of the ONH. The inset shows the B-scan location indicated by the bold green line overlaid onto the infrared confocal scanning laser ophthalmoscopy (CSLO) reflectance image. Structures delineated in each radial B-scan include the ILM (yellow) and BMO points (red). The green segments connecting BMO points to the ILM represent the pair of MRW measurements made in each radial B-scan. (B) B-scan through the vertical meridian of the ONH. (C) Results for all 80 B-scans shown projected from 3D. (D) Derivation of MRA from the 160 radial trapezoidal sectors of each ONH (see Methods text for details). Note deformation of the ONH apparent in the right column for MRW/MRA, including a deeper “cup” and thinner “rim.” In this EG eye, global average MRA decreased from 1.16 mm2 at baseline to 0.63 mm2 at the final time point (−45.6%). (E) Segmentation of peripapillary circular B-scans to obtain the parameter RNFLA are shown for the same eye and time points, ILM (red), and posterior RNFL boundary (green). Retinal nerve fiber layer thickness decreased from 113.8 μm at baseline to 96.1 μm at the final time point; RNFLA decreased from 1.07 mm2 at baseline to 0.90 mm2 at the final time point (−15.5%). (F) Retinal nerve fiber layer area represented by the gold colored ribbon in projected 3D image from baseline (left) and final time point (right). The much larger decrease in MRA than RNFLA suggests substantial transverse compression of axons (and possibly also astrocytes) at the ONH rim. This can be appreciated by comparison of the images inset at the bottom of each column, which are the infrared CSLO reflectance image painted onto the ILM surface at each time point; the RNFL appears stretched over the ONH rim at the final time point.
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i1552-5783-57-10-4403-f01: Methods used to quantitatively compare MRA to RNFLA. The left column shows baseline data, the right column shows final follow-up data. (A) B-scan through the horizontal meridian of the ONH. The inset shows the B-scan location indicated by the bold green line overlaid onto the infrared confocal scanning laser ophthalmoscopy (CSLO) reflectance image. Structures delineated in each radial B-scan include the ILM (yellow) and BMO points (red). The green segments connecting BMO points to the ILM represent the pair of MRW measurements made in each radial B-scan. (B) B-scan through the vertical meridian of the ONH. (C) Results for all 80 B-scans shown projected from 3D. (D) Derivation of MRA from the 160 radial trapezoidal sectors of each ONH (see Methods text for details). Note deformation of the ONH apparent in the right column for MRW/MRA, including a deeper “cup” and thinner “rim.” In this EG eye, global average MRA decreased from 1.16 mm2 at baseline to 0.63 mm2 at the final time point (−45.6%). (E) Segmentation of peripapillary circular B-scans to obtain the parameter RNFLA are shown for the same eye and time points, ILM (red), and posterior RNFL boundary (green). Retinal nerve fiber layer thickness decreased from 113.8 μm at baseline to 96.1 μm at the final time point; RNFLA decreased from 1.07 mm2 at baseline to 0.90 mm2 at the final time point (−15.5%). (F) Retinal nerve fiber layer area represented by the gold colored ribbon in projected 3D image from baseline (left) and final time point (right). The much larger decrease in MRA than RNFLA suggests substantial transverse compression of axons (and possibly also astrocytes) at the ONH rim. This can be appreciated by comparison of the images inset at the bottom of each column, which are the infrared CSLO reflectance image painted onto the ILM surface at each time point; the RNFL appears stretched over the ONH rim at the final time point.
Mentions: All SDOCT scans were acquired using a Spectralis instrument (Heidelberg Engineering, GmbH, Heidelberg, Germany) 30 minutes after IOP was manometrically stabilized to 10 mm Hg. This is important to minimize elastic components of deformation that are known to exert a greater effect on the ONH than on peripapillary RNFL thickness.22,23 A clear, rigid gas permeable contact lens filled with 0.5% carboxymethylcellulose solution was placed over the apex of each cornea. Spectral-domain OCT scans recorded at each session included an 80-radial B-scan pattern centered on the ONH (30° wide, 1536 A-scans/B-scan, Figs. 1A, 1B) and a peripapillary circular B-scan with 12° diameter (1536 A-scans, Fig. 1E). In all cases, nine to 16 individual sweeps were averaged in real time to form each B-scan. At the first baseline imaging session, SDOCT scans were centered manually on the ONH by the operator. All follow-up scans were acquired at the same location as baseline using the instrument's automatic active eye tracking software.

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.