Comparing Optic Nerve Head Rim Width, Rim Area, and Peripapillary Retinal Nerve Fiber Layer Thickness to Axon Count in Experimental Glaucoma

Abstract

PurposeWe compare spectral-domain optical coherence tomography (SDOCT) measurements of minimum rim width (MRW), minimum rim area (MRA), and peripapillary retinal nerve fiber layer thickness (RNFLT) to complete orbital optic nerve axon counts in nonhuman primates (NHP) with unilateral experimental glaucoma (EG).MethodsBiweekly SDOCT measurements of MRW, MRA, and RNFLT were acquired under manometric IOP control (10 mm Hg) in 51 NHP during baseline (mean ± SD, 5.0 ± 1.6 sessions) and after laser photocoagulation was applied to the trabecular meshwork of one eye to induce chronic IOP elevation. At the study endpoint (predefined for each NHP), 100% axon counts were obtained from each optic nerve.ResultsFor SDOCT parameters at baseline, the correlation between the two eyes of each animal was strongest for RNFLT (R = 0.97) and MRW (R = 0.97), but lower for MRA (R = 0.85). At the final time point, average values in EG eyes relative to control eyes were: −22% for RNFLT, −38% for MRW, −36% for MRA, and −36% for optic nerve axons. The correlation with axon counts was strongest for RNFLT (R = 0.81), compared to MRW (R = 0.72, P = 0.001) or MRA (R = 0.70, P = 0.001). Diagnostic sensitivity was 75% for RNFLT, 90% for MRW, and 88% for MRA; all had 100% specificity.ConclusionsPeripapillary RNFLT was correlated more closely with total orbital optic nerve axon count than were the ONH parameters MRW or MRA. This is likely because glaucomatous deformation (beyond axon loss alone) has a greater influence on the ONH parameters MRW and MRA than on RNFLT.

The connective tissue phenotype of glaucomatous cupping in the monkey eye - Clinical and research implications

“…Because a monkey that has been sacrificed at the detection of 7 to 10% global RNFL thinning by OCT may have 30 degree sectoral axon loss that ranges from 0 to 25% (Fortune et al, 2015; Fortune et al, 2016a), paraffin sections from EG eye 30 degree sectors with 0–10% and 11–20% axon loss (compared to the contralateral control) may eventually provide meaningful insights into protein expression changes that precede, coincide and progress from the onset of detectible axonal injury and or loss. Changes in protein expression that precede detectible axon loss (by counts), may then be staged by co-localized IHC markers of axon cytoarchitecture disruption (Fortune et al, 2014).…”

Comparing three different modes of electroretinography in experimental glaucoma: diagnostic performance and correlation to structure

“…29/43 EG eyes (67%) and 0/43 of the fellow control eyes exhibited statistically significant (>7%) loss of RNFLT from baseline[32,33,27]; thus 33% of the EG eyes were still early-stage EG at final follow-up[25–27]. …”

“…1) [25–27]. Nine to sixteen individual sweeps were averaged in real time to comprise the final stored B-scan at each session.…”

Protruded retinal layers within the optic nerve head neuroretinal rim

“…Fortune et al. () previously identified PRL in OCT images of monkey ONHs and speculated that the PRL could be one of the reasons for the weaker correlation between rim parameters and axons counts compared to that between peripapillary RNFL thickness and axons counts. In the present study, we assessed the frequency with which PRL were detected within the neuroretinal rim and the impact they had on MRW measurements in a multiracial sample of healthy subjects.…”

“…Fortune and colleagues (Fortune et al. ) recently reported in monkeys that MRW measurements could contain not just the RNFL, but portions of the outer and middle retinal layers. Indeed, they argued that the presence of these ‘protruded’ retinal layers in the rim measurement could be another reason why the observed correlation between MRW and actual axonal counts in monkey was not as strong as the correlation between RNFL thickness and axon counts.…”