Abstract
Purpose: :
To describe changes in the multifocal electroretinogram (mfERG) following selective local ablation of retinal ganglion cell (RGC) axons by endodiathermy in non-human primates. We have previously shown that endodiathermy of the inferior retinal nerve fiber bundle can produce complete loss of axons in the lower half of the optic nerve without disrupting outer retinal anatomy, opsinregulation, retinal or choroidal blood flow (Dashek et al ARVO 2011 #2460). Here, we present an analysis of latency changes associated with the ‘optic nerve head component’ (ONHC) of the mfERG following axotomy by endodiathermy.
Methods: :
Four adult cynomolgus monkeys underwent placement of contiguous endodiathermy spots along the inferior portion of the optic nerve margin of one eye. Fundus photography, fluorescein angiography, sdOCT, and mfERG were obtained at baseline and for up to 4 months following axotomy. Seven baseline mfERG recordings and 5-6 post-axotomy recordings were obtained from each animal. The mfERG stimulus consisted of 241 equal-sized (4 deg) hexagons presented using a conventional fast m-sequence (75 Hz frame rate). mfERG data were collected and K1 and K2.1 kernels extracted using a VERIS 4.9 system (EDI, San Mateo CA). Waveforms were digitally filtered off-line to extract a low frequency component (LFC) and a high frequency component (HFC).
Results: :
Baseline recordings showed that the implicit times of N1, P1, and N2 waves (mean 16.5, 31.5, and 47 msec, respectively) of the LFC K1 mfERG from the superior and inferior retina increase linearly and symmetrically with a maximum delay of ~4 msec at the elements at the furthest distance from the optic nerve head. After axotomy, N1 and P1implicit times were unchanged from baseline. However, N2 implicit times were decreased in the region of the axotomy. The HFC K1 mfERG did not show a pronounced latency shift associated with the optic nerve head component, yet the amplitude of certain wavelets of the HFC K1 were selectively reduced within axotomized regions. LFC K2.1 and HFC K2.1 also showed optic nerve-head component-like changes in latency but were more variable than K1 mfERGs across subjects.
Conclusions: :
Endodiathermy allows a controlled, localized axotomy of the retinal ganglion cells that provides a less invasive alternative to neurotoxins, lasers, and nerve transection for the study of the contribution of the RGCs to electrophysiologic measures. Using standard stimulation techniques we show the implicit time of the N2 wave of LFC K1 mfERG, which normally increases with distance from the optic nerve head, is selectively altered by local endodiathermy axotomy.
Keywords: electroretinography: non-clinical • optic nerve • retina: proximal (bipolar, amacrine, and ganglion cells)