July 2018
Volume 59, Issue 9
Open Access
ARVO Annual Meeting Abstract  |   July 2018
Optical Coherence Tomography Detected Axonal Loss but Failed to Identify Acute Optic Nerve Axonal Injury: A Diffusion MRI Study
Author Affiliations & Notes
  • Tsen-Hsuan (Abby) Lin
    Raiology, Washington University School of Medicine, Saint Louis, Missouri, United States
  • Ying-Bo Shui
    Ophthalmology & Visual Sciences, Washington University School of Medicine, St Louis, Missouri, United States
  • Ying Liu
    Ophthalmology & Visual Sciences, Washington University School of Medicine, St Louis, Missouri, United States
  • Hsin-Chieh Yang
    Raiology, Washington University School of Medicine, Saint Louis, Missouri, United States
  • Michael Wallendorf
    Biostatistics, Washington University School of Medicine, St Louis, Missouri, United States
  • Carla J Siegfried
    Ophthalmology & Visual Sciences, Washington University School of Medicine, St Louis, Missouri, United States
  • Sheng-Kwei Song
    Raiology, Washington University School of Medicine, Saint Louis, Missouri, United States
    The Hope Center for Neurological Disorders , Washington University School of Medicine, St Louis, Missouri, United States
  • Footnotes
    Commercial Relationships   Tsen-Hsuan (Abby) Lin, National Multiple Sclerosis Society (E); Ying-Bo Shui, None; Ying Liu, None; Hsin-Chieh Yang, None; Michael Wallendorf, None; Carla Siegfried, None; Sheng-Kwei Song, DxGPS (I)
  • Footnotes
    Support  NIH R01-NS047592, NIH R01-EY021515, P30EY02687, P01-NS059560, U01-EY025500, NMSS RG 5258-A-5 and RG-1507-05315 and an unrestricted grant from Research to Prevent Blindness
Investigative Ophthalmology & Visual Science July 2018, Vol.59, 1970. doi:
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      Tsen-Hsuan (Abby) Lin, Ying-Bo Shui, Ying Liu, Hsin-Chieh Yang, Michael Wallendorf, Carla J Siegfried, Sheng-Kwei Song; Optical Coherence Tomography Detected Axonal Loss but Failed to Identify Acute Optic Nerve Axonal Injury: A Diffusion MRI Study. Invest. Ophthalmol. Vis. Sci. 2018;59(9):1970.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Optical coherence tomography (OCT) is widely used to assess progressive retinal ganglion cell (RGC) and retinal nerve fiber layer (RNFL) thickness changes for pre-chiasm neuropathy. We have developed a diffusion basis spectrum imaging (DBSI) to assess coexisting optic nerve axonal damage and inflammation. The current study aims to determine the relationship between OCT-detected RGC/RNFL thickness changes and DBSI-derived metrics in pre-chiasm neuropathy.

Methods : C57BL/6 female mice underwent left optic nerve crush (ONC) (approximately 1-2 mm from the eyeball) for 20s. Right eyes served as control (CTL). Spectral domain OCT cross-sectional imaging was performed (around peripapillary region) prior to DBSI scans at 7 days (n=5), 1 (n=5) and 3 (n=6) months post-ONC. The 25-direction DBSI scan was performed on a 4.7-T scanner: TR = 1.5 s, TE = 35 ms, Δ = 18 ms, δ = 6 ms, maximal b-value = 2,200 s/mm2, slice thickness = 1.0 mm, FOV = 22.5 × 22.5 mm2, and matrix size = 192 × 192. DBSI-assessed axonal injury (λ||), demyelination (λ⊥), axonal loss and inflammation were derived using a lab-developed software. After in vivo DBSI, tissues were kept for H&E (retina) or immunohistochemistry (IHC) for optic nerve

Results : Representative H&E images highlight injury evolution of RGC loss and RNFL thinning post-ONC (Fig. 1 A). Quantitative OCT results are consistent with H&E findings (Fig.1 B). Optic nerve IHC exhibits coexisting axonal pathologies and inflammation post-ONC (Fig. 1 C). The RGC/RNFL thickness does not correlate with DBSI λ|| or restricted fraction suggesting that OCT fails to detect acute optic nerve axonal injury or inflammation (Fig. 2 B, D), while strongly correlating with optic nerve λ⊥ and axonal volume (Fig. 2 C, E). Results suggest that demyelination is secondary to traumatic axonal injury (Wallerian degeneration) and chronic axonal loss.

Conclusions : Our findings suggest that OCT-detected RGC/RNFL thinning may not reflect optic nerve axonal injury or inflammation. Thus, the notion that RGC/RNFL thinning may serve as a surrogate marker of pre-chiasm optic nerve injury.

This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.

 

Figure 1 H & E and OCT showed retinal injury (A, B); IHC confirmed coexisting optic nerve pathologies (C).

Black/White bar: 50 μm
Yellow bar: 10 μm

Figure 1 H & E and OCT showed retinal injury (A, B); IHC confirmed coexisting optic nerve pathologies (C).

Black/White bar: 50 μm
Yellow bar: 10 μm

 

Figure 2 Correlations of RGC/RNFL thickness and DBSI metrics.

Figure 2 Correlations of RGC/RNFL thickness and DBSI metrics.

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