Lamina Cribrosa Microstructure in Non-Human Primates with Naturally Occurring Peripapillary Retinal Nerve Fiber Layer Thinning

Abstract

Purpose : The lamina cribrosa (LC) is hypothesized to be the site of initial axonal damage in glaucoma with the peripapillary retinal nerve fiber layer (RNFL) thickness is widely used as a standard metric for quantifying this damage. The purpose of this study was to determine in vivo changes in the microstructure of the LC in eyes of non-human primates (NHP) with naturally occurring RNFL thinning.

Methods : Spectral-domain OCT scans (Leica, Chicago, IL) of the optic nerve head (ONH) were acquired in vivo from a colony of 50 adult rhesus monkeys, suspected of having high prevalence of naturally occurring glaucoma. The circumpapillary global and quadrant RNFL thickness was analyzed using a custom automated segmentation software. From the set of 100 eyes, the 10 eyes with the thinnest global RNFL values were selected as the study group, while 10 eyes with RNFL values around the 50^th percentile were used as the control group. A previously described automated segmentation algorithm was used for LC microstructure analysis. The LC microstructure was analyzed globally and in the following volumetric sectors: quadrants, central and peripheral lamina, and 3 depth slabs (anterior, middle, posterior; Figure). Beam thickness/pore diameter ratio (BPR) and connective tissue volume fraction (CTVF: beam volume/total volume) were calculated globally and in sectors.

Results : 20 eyes (15 animals) were analyzed (Table 1). While no significant difference was detected between groups for age, weight or disc size, the study group had significantly thinner RNFL than the control group (p<0.01). The study group had significantly larger BPR and CTVF compared with the control group (Table 2). Significant sectoral differences between study and control group RNFL thickness were noted for BPR and CTVF in the nasal and temporal quadrants, central LC, and in LC depth. Across eyes, the global RNFL thickness was moderately negatively correlated only with the global CTVF (lower RNFL thickness associated with higher CTVF; r²=0.63, p=0.045).

Conclusions : Eyes with thinner circumpapillary RNFL had thicker LC BPR and CTVF globally and in various sectors when compared to eyes with normal RNFL thickness. Whether these LC changes are the cause of RNFL damage or the result of remodeling of the LC requires further investigation.

This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.