This study shows that GCL+IPL thickness is normal at presentation of acute NAION. Thinning, which represents permanent loss of inner retinal neurons, retinal ganglion cell atrophy, or reduction of dendritic arborization, occurs at 1 month and in some cases even earlier. Retinal ganglion cell layer and IPL loss is more profound with NAION than reported for optic neuritis.21 Ganglion cell layer plus inner plexiform layer thinning below the fifth percentile of normal eyes occurred while the OCT still showed RNFL thickening, which confounds the ability of OCT to show RNFL loss early in an episode. Generally, the amount of GCL+IPL thinning correlated with the visual acuity and visual field MD deficit at 1 to 2 months to 6 months. Although it appears the trajectories for GCL+IPL and RFNL thickness reduction were similar, the RNFL thinning below the normal fifth percentile did not occur until 3 months and early reduction from baseline was likely due to less swelling. In contrast, affected eyes had the greatest amount of reduction in GCL+IPL thickness between presentation and 1 to 2 months. Ganglion cell layer plus inner plexiform layer thinning in all of the affected eyes at 3 and 6 months shows that NAION affects the macula region even if the visual field does not initially appear to affect the macula region. However, at presentation the visual field spared the macula in only 10% of affected eyes.
Using three-dimensional segmentation, the GCL+IPL thickness was normal and not thinned at presentation in the majority of eyes with NAION, when compared with the normal fellow eyes. However, method 2 for determining GCL+IPL thickness frequently failed when the peripapillary RNFL or macula was considerably thickened, presumably due to processes that distort normal retinal layer architecture. The method 2 algorithm failure caused GCL+IPL thickness at presentation to appear significantly thinned compared with the corresponding values obtained using method 1 for NAION affected eyes. However, in eyes without algorithm failure, the two methods gave similar results. At the 1- to 2-month follow up evaluation, the GCL+IPL thickness measurement showed no algorithm failures, and the mean values were similar between the two methods and correlated to each other. The likely explanation for failure in the setting of optic nerve head and retina swelling is due to the fact that method 2 utilizes an algorithm that assumes a quantitative relationship between the internal limiting membrane and the other layers of the retina. Thus, method 2 would be more susceptible to failure with any process, such as edema due to swelling of the peripapillary RNFL and adjacent retina, which disrupts the regular retinal layer position or shape or boundaries. In contrast, method 1 uses an algorithm that incorporates three-dimensional contextual information into the optimization process, which in general helps to reduce failures due to local distortions in retinal layers. In clinical practice, it is important to carefully evaluate algorithm performance in OCT scans, since methodological failures may lead to false interpretations of data and may adversely influence clinical decisions.
Optical coherence tomography demonstration of thinning of the RNFL and GCL+IPL is clinically important in determining irreversible neuronal loss and correlates with measures of vision loss in glaucoma,
22 NAION,
6,16,23 optic neuritis, and MS.
10,11,15–17,24 Ganglion cell layer loss has long been shown on histopathology in glaucoma
22 and recently in eyes of patients with MS, even without a history of optic neuritis.
24,25 Further, optical coherence tomography shows that even after months, NAION spares the other retinal layers, such as the inner and outer nuclear, outer plexiform, retinal pigment epithelium, and photo receptor layers.
26 Studies are needed to show the earliest signs of structural injury with all optic neuropathies. For example, with NAION, scanning layer polarimetry at presentation shows a loss of retinal birefringence suggesting that early axonal damage can be detected and is likely to be irreversible.
27 Our study suggests that permanent structural loss or atrophy or size reduction of retina ganglion cells can occur prior to the 1-month time point with NAION. Further, we showed 92% of NAION eyes had reduction of the macula region average GCL+IPL thickness at 1 to 2 months and majority of the loss for also occurred during this interval. In contrast to the GCL+IPL measurement, at 1 to 2 months the RNFL thickness cannot be used to demonstrate consistent axonal loss due to the persistence of edema and swelling.
In a small group of our patients, who happened to return for follow up evaluation earlier than scheduled, GCL+IPL thinning developed within 2 to 3 weeks after presentation. These cases suggest that retinal ganglion cell body loss or atrophy or reduced dendritic arborizations could occur prior to the 1-month time point in NAION.
After 1 month, the RNFL swelling lessens, and the RNFL thickness measurement in part reflects the loss and thinning of affected axons. By 3 months, most eyes show RNFL thinning while the GCL+IPL thinning had essentially stopped. These data suggest that the subclinical edema or swelling persists in the RNFL for at least 3 months.
The early GCL+IPL thinning appears to be greatest in NAION eyes with worse presentation visual acuity, a possible reflection of greater initial injury. This is consistent with a profound ischemic injury of axons that are close to their cell bodies and the persistent, likely permanent vision loss in almost all cases of NAION. GCL+IPL thickness measurement appears to be a better biomarker of early structural injury with acute optic nerve injury than OCT measured peripapillary RNFL thickness, particularly when optic nerve head or RNFL swelling is present. The amount of GCL+IPL thinning correlates with the amount of visual acuity and visual field loss better than the actual thickness measurements.
26 Given that the most profound GCL+IPL thinning occurs early, potential neural preservation or protection therapy must be delivered before 1 month to reduce retinal ganglion cells loss.