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1 Discoveries in Sight, 1225 NE Second Avenue, Portland, Oregon, 97208-3950, United States
2 Discoveries in Sight Research Laboratories, Devers Eye Institute, Portland, Oregon, United States
3 Optic Nerve Head Research Laboratory, Devers Eye Institute, Portland, Oregon, United States
* To whom correspondence should be addressed. E-mail: bfortune{at}deverseye.org.
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Abstract |
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Purpose: To test the hypothesis that alterations of RNFL birefringence precede changes in RNFL thickness (RNFLT) in an experimental model of RGC injury. Secondarily, to determine the time course of RGC functional abnormalities relative to RNFL birefringence and RNFL thickness changes. Methods: RNFL birefringence was measured by scanning laser polarimetery (GDx VCC, Carl Zeiss Meditec, Inc). RNFL thickness was measured by spectral domain optical coherence tomography (sd-OCT, SpectralisTM HRA+OCT, Heidelberg Engineering, GmbH). Retinal function was assessed by three forms of electroretinography (ERG): slow-sequence multifocal ERG (mfERG, VERIS, EDI); pattern-reversal ERG (PERG, Utas-E3000, LKC Technologies, Inc); and photopic full-field flash ERG (ff-ERG, Utas E3000). 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 3 subjects. RNFL birefringence declined by 15% one week after ONT (p = 0.043), while 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) while 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 ff- ERG (-44%, p = 0.005). Conclusions: RNFL birefringence declined prior to, 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.
Key Words: retinal ganglion cell, scanning laser polarimetry, optical coherence tomography, electroretinography, retinal nerve fiber layer, birefringence
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