Retinal nerve fiber layer (RNFL) defects have been recognized for decades as an important diagnostic sign of glaucoma, as they present clinically during an early stage and are predictive of subsequent vision loss.
1–3 However, the minimum loss of RNFL detectable by traditional clinical methods such as ophthalmoscopy and photography may be 50 to 70 μm, or as much as 50% of the normal tissue thickness.
4,5 Thus, it is hoped that recent advancements in imaging techniques will improve glaucoma detection and management by providing reliable, sensitive, and quantitative measurements of the RNFL.
6,7
The two techniques used most commonly for this purpose are scanning laser polarimetry (SLP)
8 and optical coherence tomography (OCT).
9 Confirming earlier findings, both of these techniques have been used to demonstrate that lower baseline RNFL values are predictive of future glaucoma progression, including loss of vision.
10,11 Yet the optical principles underlying these two techniques differ in potentially important ways. OCT measures the relative time-of-flight delay of a (typically) near infrared source after it is reflected by structures at different depths within the tissue sample.
12,13 OCT thus can provide a high-resolution cross-sectional image of retinal layers and an estimate RNFL thickness (RNFLT) by detecting the relatively steep reflectance transition at both its anterior and posterior limits. In contrast, SLP estimates RNFL “thickness” indirectly by measuring the relative phase retardance of orthogonally polarized states of the imaging source after a double pass through the tissue sample.
8 RNFL retardance is caused by form birefringence, an optical property thought to be due—in the case of the RNFL—to the orderly parallel structural array of thin cylindrical cytoskeletal components within retinal ganglion cell (RGC) axons, primarily the microtubules (MTs), and to a lesser extent neurofilaments.
14–16 Empirical evidence supporting this original theoretical framework includes studies demonstrating that RNFL birefringence declines rapidly after chemical disruption of MTs in situ
16 and in vivo.
17 Thus, it has been suggested that measurements of RNFL birefringence could provide a sensitive indicator of compromised cytoskeleton integrity within RGC axons.
16–18 The importance of this idea is underscored by evidence of axonal cytoskeletal changes occurring in experimental models of glaucoma, including their earliest stages,
19–23 some of which may represent mechanisms of further susceptibility.
24,25
RNFL birefringence can be assessed in a clinical setting either directly, such as by polarization-sensitive OCT,
26–29 or it can be inferred by comparing SLP measurements of RNFL retardance with OCT measurements of RNFLT.
17 In one such experiment, we demonstrated that RNFL retardance began to decline prior to and to progress faster than RNFL thinning after an experimental RGC injury by retrobulbar optic nerve transection.
30 This early stage structural abnormality was also associated with specific loss of RGC function as measured by electroretinography (ERG). The results of that study provided clear evidence for the existence of an early stage of RGC degeneration when both axonal cytoskeletal abnormalities and RGC functional abnormalities are found in the absence of significant thinning of axon bundles within the RNFL.
30 Though optic nerve transection and crush are classical experimental models of axonal injury within the central nervous system, they represent a more acute and rapid process as compared with the neurodegenerative course of glaucoma. Therefore, the aim of this study was to test the same hypothesis in a nonhuman primate model of experimental glaucoma. Longitudinal measurements of RNFL retardance obtained by SLP and ERG measures of retinal function were compared with RNFLT measurements made by OCT and specifically evaluated an early stage of experimental glaucoma as defined by the onset of optic nerve head (ONH) surface topography change. This time point was chosen because it is thought to represent a very early stage of experimental glaucoma in nonhuman primates.
31–33