Localized orbital optic nerve axon loss estimates correlate with localized OCT measurements of retinal nerve fiber layer thickness (RNFLT) and minimum rim width (MRW) experimental glaucoma (EG).

Abstract

Purpose : To evaluate the relationship between localized OCT measures of glaucomatous damage, such as thinning of the MRW and RNFL, and localized optic nerve axon loss caused by EG; in order to inform interpretation of clinical OCT imaging targets for detection of early stage glaucoma.

Methods : Both eyes of 13 NHPs underwent OCT imaging 3-5 times at baseline, then following laser-induced, unilateral IOP elevation. NHPs were sacrificed by perfusion fixation at onset of OCT MRW or RNFLT change. EG and Control (C) eyes were enucleated, post-fixed in glutaraldehyde, then processed for counting (Fig 1). Estimated 30° Fovea-BMO (FoBMO) sectors were projected onto each optic nerve axon count section image by colocalizing it to the orbital optic nerve stump-face image using the temporal and superior cuts common to each nerve. Each axon was automatically identified using custom software (PMCID:3382379) and the number of axons was counted in each sector for the entire eye. Correlations between EG eye OCT RNFLT and MRW % change from baseline and estimated FoBMO sectoral% axon count difference [EG vs C, (EG -C) /C x 100] within each of the 12 sectors of each NHP (n=156 comparisons) were assessed using general estimation equation models (R Studio 1.1.423).

Results : NHP ages, and EG eye cumulative IOP Differences, at sacrifice ranged from 2.7 to 27.4 years and 13 to 1208 mmHgxDays respectively. EG eye % change from baseline ranged from -82.8% to +6.6% for sectoral MRW and from -44.7% to +18.8% for sectoral RNFLT (Fig. 2). EG versus C eye global % axon count differences ranged from -72.3% to +3.3% and sectoral % axon count differences ranged from -83.2% to +51.2%. EG vs C eye sectoral % differences in axon counts were significantly correlated with sectoral % changes in MRW (Count vs MRW: p<0.0001, R² = 0.57) and RNFLT (Count vs RNFLT: p<0.0001, R² = 0.47) (Fig 2). Zero% sectoral RNFLT change corresponded to 13% sectoral axon loss; zero% sectoral MRW change corresponded to 5% sectoral axon loss.

Conclusions : Longitudinal localized OCT MRW and RNFLT thinning predict localized orbital axon loss in NHP early EG eyes. These findings provide support for the importance of early FoBMO aligned local OCT change detection in human ocular hypertensive and early glaucoma eyes.

This abstract was presented at the 2023 ARVO Imaging in the Eye Conference, held in New Orleans, LA, April 21-22, 2023.