Lamina cribrosa shape is different between humans and monkeys at baseline IOP and is changed differently with IOP elevations

Abstract

Purpose : The shape of the lamina cribrosa (LC) is an important determinant of IOP-induced mechanical stress. Our goals were to analyze monkey LC shapes under normal and elevated IOPs and compare our data to published studies of human LC shape. We measured shape index (SI) and curvedness (C), two measures of intrinsic lamina shape that are independent of external structures.

Methods : Optic nerve heads of 7 eyes (6 monkeys) were imaged with SD-OCT while IOP was modulated through cannulas and set at 4 levels: low (5-8 mmHg), baseline (15 mmHg), high (30 mmHg) and very high (40-50 mmHg). Custom code was used to reconstruct anterior LC (ALC) surfaces from manual markings (Tran et al, ARVO 2016) and quantify SI and C (Koenderink, Image & Vis Comp, 1992; Thakku, IOVS, 2015). ALC curvatures K were measured every 1° as the inverse radius of a circular arc fit, and the SI and C of a surface calculated from the maximum and minimum Ks (Fig 1i). Within each eye, changes of SI and C were compared with baseline and fitted with linear regressions, using eye and IOP as predictors.

Results : At baseline IOPs, SI (-0.81±0.08, mean ± SD) was more similar across eyes and monkeys than C (-33±12 10^-5 µm^-1) (Fig 1ii). Neither IOP nor eye were correlated with changes in SI (Fig 2i). IOP was positively correlated with changes in C (β=1.4x10^-6, p=0.015) (Fig 2ii).

Conclusions : At baseline IOP, monkey ALCs had a trough-like shape, without the characteristic central ridge that makes human ALCs saddle rut shaped (Fig 1iii). As IOP increased, monkey ALCs became curvier, without much change in its shape. This is different from human ALCs in which IOP increases cause a decrease in SI from a saddle rut to a trough (Fig 2iii). The fact that there are differences between monkey and human LCs does not mean that the monkey model is not the best model to study LC biomechanics, however, there are differences that we must be aware of. The implications on the susceptibility to glaucoma remain to be determined.

This is an abstract that was submitted for the 2017 ARVO Annual Meeting, held in Baltimore, MD, May 7-11, 2017.

 

(i) Shape index (SI) and curvedness (C) as functions of principal curvatures (kmax, kmin). (ii) Parameters at baseline IOP. (iii) Top: Illustration of SI. Bottom: Baseline SI for monkey and human.

 

Plots of IOP versus changes in (i) SI and (ii) C, and regression results. (iii) Comparison of changes in IOP and SI between monkey and human. Values are mean ± SD.