Relative course of retinal nerve fiber layer birefringence and thickness and retinal function changes after optic nerve transection.
OBJECTIVE
To test the hypothesis that alterations of RNFL birefringence precede changes in RNFL thickness in an experimental model of RGC injury and, secondarily, to determine the time course of RGC functional abnormalities relative to RNFL birefringence and thickness changes.


METHODS
RNFL birefringence was measured by scanning laser polarimetry (GDx VCC; Carl Zeiss Meditec, Inc., Dublin, CA). RNFL thickness was measured by spectral domain optical coherence tomography (SD-OCT, Spectralis HRA+OCT; Heidelberg Engineering, GmbH, Heidelberg, Germany). Retinal function was assessed by three forms of electroretinography (ERG): slow-sequence multifocal (mf)ERG (VERIS; EDI, San Mateo, CA); pattern-reversal (P)ERG (Utas-E3000; LKC Technologies, Inc. Gaithersburg, MD); and photopic full-field flash (ff)ERG (Utas-E3000; LKC Technologies). All measurements were obtained in both eyes of four adult rhesus macaque monkeys (Macaca mulatta) during two baseline sessions, and again 1 week and 2 weeks after unilateral optic nerve transection (ONT).


RESULTS
ONT was successfully completed in three subjects. RNFL birefringence declined by 15% 1 week after ONT (P = 0.043), whereas there was no significant change in RNFL thickness (+1%, P = 0.42). Two weeks after ONT, RNFL retardance had declined by 39% (P = 0.018), whereas RNFL thickness had declined by only 15% (P = 0.025). RGC functional abnormalities were present 1 week after ONT, including decreased amplitudes relative to baseline of the mfERG high-frequency components (-65%, P = 0.018), the PERG N95 component (-70%, P = 0.007), and the photopic negative response of the ffERG (-44%, P = 0.005).


CONCLUSIONS
RNFL birefringence declined before and faster than RNFL thickness after ONT. RGC functional abnormalities were present 1 week after ONT, when RNFL thickness had not yet begun to change. RNFL birefringence changes after acute RGC injury are associated with RGC dysfunction. Together, they reflect RGC abnormalities that precede axonal caliber changes and loss.
Discoveries in Sight Research Laboratories, Devers Eye Institute, LegacyHealth System, Portland, Oregon 97232, USA. bfortune@deverseye.org
Brad
B
Fortune
Grant A
GA
Cull
Claude F
CF
Burgoyne
D000818:Animals; D001718:Birefringence; D003941:Diagnostic Techniques, Ophthalmological; D004596:Electroretinography; D005260:Female; D005451:Fluorescein Angiography; D007834:Lasers; D008253:Macaca mulatta; D008297:Male; D018613:Microscopy, Confocal; D009412:Nerve Fibers / Q000502:physiology*; D009900:Optic Nerve / Q000503:physiopathology*; D020221:Optic Nerve Injuries / Q000503:physiopathology*; D010775:Photic Stimulation; D012160:Retina / Q000503:physiopathology*; D012165:Retinal Ganglion Cells / Q000502:physiology*; D041623:Tomography, Optical Coherence