Inner Nuclear Layer (INL) Cystoid Spaces (Lacunae) Observed in Experimental Glaucoma and Axotomy in Non-Human Primates (NHPs)

Abstract

Purpose: To use in vivo optical imaging to document the presence of INL lacunae in NHP eyes that have undergone hemi-endodiathermy axotomy and/or laser trabecular meshwork destruction (LTD) to induce experimental glaucoma.

Methods: 4 cynomolgus macaques underwent hemi-endodiathermy axotomy (ARVO 2011, #2460). 3 rhesus macaques first underwent hemi-axotomy followed 3 months later by LTD of the same eye. 6 additional cynomolgus macaques had LTD only. All of the animals were imaged with SD-OCT (either a Zeiss Cirrus™ or Heidelberg Spectralis™). The 3 rhesus and the 6 LTD-only cynos were also imaged with adaptive optics (AO) (Imagine Eyes rtx1™)—4 areas centered 8 degrees from the fovea, 2 superior and 2 inferior. At the time of AO imaging, the 3 rhesus had been glaucomatous for 4 months with average intraocular pressures (IOPs) of 40, 50 and 51 mmHg. The LTD for the 6 cynos had been performed between 3 and 9 years prior to imaging and their IOPs on the day of imaging ranged from 11 to 43 mmHg.

Results: Lacunae were evident only in the inferior (axotomized) portion of all 4 of the non-glaucomatous cynos. Histology confirmed that these spaces were at the level of the INL. Amongst the glaucomatous animals, lacunae were identified by SD-OCT in 2 of the 3 rhesus and 4 of the 6 cynos. With AO on these same animals, lacunae were found in 1 of the 3 rhesus and 3 of the 6 cynos. AO imaging and en face views with the SD-OCT showed that the lacunae had a patchy distribution. Lacunae were not found in any of the control eyes.

Conclusions: Lacunae within the INL are a common feature in both rhesus and cynomolgus macaque eyes that have lost retinal ganglion cells as the result of endodiathermy axotomy and/or experimental glaucoma. Although evident with both SD-OCT and AO, lacunae were found in more animals with the SD-OCT probably because it scanned the entire macula, whereas the AO was limited to 4 degree fields of view. The patchy distribution of the lacunae is reminiscent of the irregular nature of visual field loss in humans with glaucoma and other optic neuropathies. Future studies are needed to determine the time course, distribution and association, if any, with IOP of this anatomic feature. If present in human eyes, this finding could have implications for diagnosing and possibly monitoring treatment of patients with optic neuropathies.

Keywords: 552 imaging methods (CT, FA, ICG, MRI, OCT, RTA, SLO, ultrasound) • 568 intraocular pressure • 691 retina: proximal (bipolar, amacrine, and ganglion cells)