Optic Nerve Changes after Exposure to Endothelin–1: A Comparison between Confocal Scanning Laser Tomography, Stereoscopic Optic Nerve Photography and Histology

Abstract

Abstract: : </ul> Purpose:Determine the ability of both confocal scanning laser tomography (CSLT) and clinician graded stereoscopic optic nerve photographs (ONP) to detect axon loss following endothelin–1 (ET) induced chronic optic nerve ischemia.Methods:Twelve 8–19 year old monkeys were included. Anesthesia was induced with ketamine and maintained with isoflurane. Ocular akinesia was achieved with a peribulbar injection of lidocaine. Right eyes underwent 7.8 (± 2.7) months of retrobulbar ET exposure (0.34 µg/day) delivered by a mini–pump and left eyes served as controls. Tonometry, CSLT and ONPs were performed at baseline, bimonthly during the study and prior to euthanasia. The mean of 3 Tonopen® readings was recorded before the administration of isoflurane. Three CSLT images per session were used to generate a mean topography and indices were calculated according to 90º sectors (HRT®). ONPs were viewed as right eyes in random order by 2 independent, masked clinicians. Evaluations documented whether change had occurred and, if present, whether it was better or worse. After euthanasia, retrobulbar nerve sections were processed and automated axon counts performed. Normal inter–session limits–of–agreement (± 1.96 times the standard deviation of the difference between baseline and final scores) were calculated for CSLT indices using 26 control eyes (included 14 healthy eyes from another study). Individual ET eye differences lying outside of these limits were considered significantly changed. Intraocular pressure (IOP) and axon density data were examined with ANOVA (repeated measures) and paired t–tests, respectively. Results:No significant differences in IOP were evident between ET and control eyes (p = 0.61). Mean ET group axon density was 208,310 (± 33,579) compared to 220,661(± 35,855) in control eyes (p = .033) with significant loss (11.9% ± 6.7) seen in seven ET eyes (p< 0.05). Although significant CSLT changes were present in 3 ET eyes, only 1 of these had a significant reduction of axon density. Three of the 7 eyes with significant axon loss were detected by ONP evaluation and 2 were misclassified as worsened. Conclusions:ONP evaluation and CSLT were unable to identify the majority of animals with histologically confirmed axon loss although the former method was more sensitive. As the extent of nerve injury in this study was relatively small, further evaluation with prolonged ET exposure may better define both the limits of CSLT sensitivity and the optic disc changes associated with this model of chronic ischemia.

Keywords: imaging methods (CT, FA, ICG, MRI, OCT, RTA, SLO, ultrasound) • optic disc • ischemia