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Gillian J. McLellan, James N. VerHoeve, Carol A. Rasmussen, Elizabeth A. Hennes-Beean, Galen W. Heyne, Charlene B.Y. Kim; Visual Evoked Cortical Potentials As A Marker Of Early Functional Loss In A Spontaneous Feline Glaucoma Model. Invest. Ophthalmol. Vis. Sci. 2011;52(14):2463.
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To evaluate visual evoked potentials (VEP) as a non-invasive marker of glaucomatous damage in a feline model of inherited primary congenital glaucoma (PCG).
Glaucomatous cats were derived from a colony that represents the ortholog of human PCG (GLC3D) caused by an LTBP2 mutation. Cortical VEPs were recorded under ketamine-xylazine anesthesia in 21 adult cats (12 normal; 9 PCG) and 16 six-month-old cats (8 normal, 8 PCG). Responses were recorded from 2 active sub-dermal needle electrodes overlying the occipital cortices, referenced to a single electrode located at the mid-point of the dorsal surface of the neck, with averaging of 80 sweeps for each response recorded. Stimuli were 4.1 Hz white flashes (2.7 cd-s/m2 on a photopic background of 30 cd/m2), presented monocularly. Additional testing included recording of Pattern ERG (PERG) responses to horizontal stripes, presented at 5 spatial frequencies from 0.039-0.623cpd reversing at the rate of 4 /sec, as well as Spectral domain Optical Coherence Tomography imaging (SD-OCT; Cirrus, Carl Zeiss Meditec Inc.). All tests were conducted over 4-6 wks; testing sessions were separated by at least 7d. Intraocular pressure (IOP) was measured weekly from about 12 wks of age in all cats, and at the time of test sessions. Testing was only conducted if IOP was <45mmHg. Amplitude of the late positive component ("P2") and RMS of the early deflections were calculated for each VEP waveform. For PERG analysis, amplitude of the N95 component was calculated for each test condition. RNFL measurements were calculated by averaging the results from at least 3 optic disc cube scans. Test results were averaged for each eye.
Normal feline VEPs were characterized by a complex of early wavelets (within 80msec) and a late, positive-going wave ("P2"). The amplitude of these components was highly variable between animals but showed good reproducibility between sessions. Both RMS of the early components and "P2" amplitudes were significantly reduced early in PCG. VEP deficits showed progression with age, and preceded significant PERG deficits and thinning of the RNFL, both of which were identified in adult cats with PCG.
Our results provide evidence of early functional deficits in six-month-old cats with PCG. VEPs offer an efficient means of charting longitudinal disease progression in this spontaneous "large eyed" glaucoma model.
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