June 2023
Volume 64, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2023
Visual Evoked Potentials Detect Functional Correlates of Axon Loss in Feline Glaucomatous Optic Neuropathy
Author Affiliations & Notes
  • Gillian J McLellan
    Ophthalmology and Visual Sciences, University of Wisconsin-Madison School of Medicine and Public Health, Madison, Wisconsin, United States
    Surgical Sciences, University of Wisconsin-Madison School of Veterinary Medicine, Madison, Wisconsin, United States
  • Kazuya Oikawa
    Ophthalmology and Visual Sciences, University of Wisconsin-Madison School of Medicine and Public Health, Madison, Wisconsin, United States
    Surgical Sciences, University of Wisconsin-Madison School of Veterinary Medicine, Madison, Wisconsin, United States
  • Julie A Kiland
    Ophthalmology and Visual Sciences, University of Wisconsin-Madison School of Medicine and Public Health, Madison, Wisconsin, United States
  • Kevin C Snyder
    Surgical Sciences, University of Wisconsin-Madison School of Veterinary Medicine, Madison, Wisconsin, United States
  • Leandro Teixeira
    Pathobiological Sciences, University of Wisconsin-Madison School of Veterinary Medicine, Madison, Wisconsin, United States
  • Kore Chan
    Surgical Sciences, University of Wisconsin-Madison School of Veterinary Medicine, Madison, Wisconsin, United States
  • Jacob Lindemann
    Ophthalmology and Visual Sciences, University of Wisconsin-Madison School of Medicine and Public Health, Madison, Wisconsin, United States
  • Hennes-Beean Elizabeth
    Ophthalmology and Visual Sciences, University of Wisconsin-Madison School of Medicine and Public Health, Madison, Wisconsin, United States
  • James N Ver Hoeve
    Ophthalmology and Visual Sciences, University of Wisconsin-Madison School of Medicine and Public Health, Madison, Wisconsin, United States
  • Footnotes
    Commercial Relationships   Gillian McLellan None; Kazuya Oikawa None; Julie Kiland None; Kevin Snyder None; Leandro Teixeira None; Kore Chan None; Jacob Lindemann None; Hennes-Beean Elizabeth None; James Ver Hoeve None
  • Footnotes
    Support  NIH K08 EY018609, R01 EY027396, S10OD018221 and P30 EY016665; BrightFocus Foundation G2016129; the University of Wisconsin-Madison Office of the Vice Chancellor for Research and Graduate Education, and an unrestricted award to the UW-Madison Department of Ophthalmology and Visual Sciences from Research to Prevent Blindness.
Investigative Ophthalmology & Visual Science June 2023, Vol.64, 2036. doi:
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    • Get Citation

      Gillian J McLellan, Kazuya Oikawa, Julie A Kiland, Kevin C Snyder, Leandro Teixeira, Kore Chan, Jacob Lindemann, Hennes-Beean Elizabeth, James N Ver Hoeve; Visual Evoked Potentials Detect Functional Correlates of Axon Loss in Feline Glaucomatous Optic Neuropathy. Invest. Ophthalmol. Vis. Sci. 2023;64(8):2036.

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

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Abstract

Purpose : Prevention of optic nerve axon loss and optic nerve regeneration are major treatment goals in glaucoma. Visual evoked potentials (VEP) provide an assessment of optic nerve (ON) function, with latencies and reduced waveform amplitudes reflecting demyelination and axon loss in the ON respectively, but direct evidence that VEP correlates with ON axon numbers in spontaneous glaucoma is lacking. We addressed this lack of definitive function-histopathology correlation in feline congenital glaucoma (FCG) due to LTBP2 mutation, in which IOP elevation is associated with variable loss of ON axons.

Methods : Flash VEPs were recorded in 42 cats with FCG and 15 normal control cats (male and female, aged 1-2yrs). VEP responses were recorded from sub-dermal needle electrodes overlying the right and left occipital cortices, concurrent with full field ERG. Ganzfeld stimuli were 4.1 Hz white flashes delivered monocularly (2.7 cd-s.m^-2 on a white 30-cd m^2 background), averaging 80 sweeps per trial. Root mean square (RMS) of the early wavelets (0-35ms) and peak amplitude and latency (peak time) of the late positive component (“P2”) that characterize the feline VEP waveform were calculated using a custom software routine (Matlab, Mathworks, Natwick, MA). Following paraformaldehyde fixation immediately post mortem, ONs were processed routinely for light and electron microscopy. A semi-automated targeted sampling method was used to quantify ON axons in PPD-stained sections. Log transformed data were compared between groups and Pearson’s product moment correlation coefficient calculated to determine the association between VEP parameters and axon count.

Results : Mean VEP P2 amplitude was significantly lower in FCG (p< 0.0001) but RMS and P2 latency were unaffected in FCG relative to control cats. Cats with FCG exhibited highly variable axon counts (95%CI: 4.3-6.1 x10^4) relative to controls (6.0-8.5 x10^4). In the 49 cats for which there were both scorable VEP waveforms and reliable axon count data available and after exclusion of 3 cats as extreme outliers, there was strong correlation between axon count and P2 amplitude (Pearson r=0.86; p<0.0001) but more modest correlation with RMS of early wavelets (r=0.48; p=0.0005).

Conclusions : These data highlight inter-individual variability in phenotype and validate VEP amplitude as a marker for axon loss in glaucoma.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.

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