Abstract
The lamina cribrosa likely plays an important role in retinal ganglion cell axon injury in glaucoma. We sought to (1) better understand optic nerve head (ONH) structure and anterior lamina cribrosa surface (ALCS) microarchitecture between fellow eyes of living, normal non-human primates and (2) characterize the time-course of in vivo structural changes in the ONH, ALCS microarchitecture, and retinal nerve fiber layer thickness (RNFLT) in non-human primate eyes with early experimental glaucoma (EG). Spectral domain optical coherence tomography (SDOCT) images of the ONH were acquired cross-sectionally in six bilaterally normal rhesus monkeys, and before and approximately every two weeks after inducing unilateral EG in seven rhesus monkeys. ONH parameters and RNFLT were quantified from segmented SDOCT images. Mean ALCS pore area, elongation and nearest neighbor distance (NND) were quantified globally, in sectors and regionally from adaptive optics scanning laser ophthalmoscope images. In bilaterally normal monkeys, ONH parameters were similar between fellow eyes with few inter-eye differences in ALCS pore parameters. In EG monkeys, an increase in mean ALCS Depth (ALCSD) was the first structural change measured in 6 of 7 EG eyes. A decrease in mean minimum rim width (MRW) simultaneously accompanied this early change in 4 of 6 EG eyes and was the first structural change in the 7th EG eye. Mean ALCS pore parameters were among the first or second changes measured in 4 EG eyes. Mean ALCS pore area and NND increased in superotemporal and temporal sectors and in central and peripheral regions at the first time-point of change in ALCS pore geometry. RNFLT and/or mean ALCS radius of curvature were typically the last parameters to initially change. Survival analyses found mean ALCSD was the only parameter to significantly show an initial change prior to the first measured loss in RNFLT across EG eyes.
Highlights
Glaucoma is a complex group of eye diseases that results in the death of retinal ganglion cells (RGCs) and degeneration of their axons, culminating in irreversible vision loss
This paper provides a better understanding of the physiologic inter-eye differences in anterior lamina cribrosa surface (ALCS) pore microarchitecture and optic nerve head (ONH) structure in normal eyes and of the time-course of structural changes in the ONH, ALCS pore microarchitecture, and RNFL in early experimental glaucoma
Paired t-tests revealed no statistically significant differences (P>.05) in mean ALCS Depth (ALCSD), mean RoC, and mean minimum rim width (MRW) values calculated from marked Spectral domain optical coherence tomography (SDOCT) radial B-scans between left and right eyes across all 6 normal monkeys (S1 Fig and Table 1)
Summary
Glaucoma is a complex group of eye diseases that results in the death of retinal ganglion cells (RGCs) and degeneration of their axons, culminating in irreversible vision loss. Recent work has shown that 10–15% of RGC axons are already lost when a first change in retinal nerve fiber layer thickness (RNFLT) is reliably detected [13]. Several ex vivo studies have shown a posterior displacement of the anterior lamina cribrosa surface (ALCS) in human glaucoma patients [14,15,16] and in non-human primates with early experimental glaucoma [4,17,18]. Increases in mean ALCSD have been measured in vivo prior to a reduction in RNFLT in non-human primates with early experimental glaucoma [21]. Significant decreases in mean minimum rim width (MRW), an ONH parameter that may potentially provide earlier detection of RNFL loss, and significant increases in mean ALCSD have been shown to precede a significant loss in RNFLT in glaucoma [22,23,24,25]
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