Remodeling of the Connective Tissue Microarchitecture of the Lamina Cribrosa in Early Experimental Glaucoma

Abstract

Purpose To characterize the trabeculated connective tissue microarchitecture of the lamina cribrosa (LC) in terms of total connective tissue volume (CTV), connective tissue volume fraction (CTVF), predominant beam orientation, and material anisotropy in monkeys with early experimental glaucoma (EG). Methods The optic nerve heads from three monkeys with unilateral EG and four bilaterally normal monkeys were three dimensionally reconstructed from tissues perfusion fixed at an intraocular pressure of 10 mm Hg. A three-dimensional segmentation algorithm was used to extract a binary, voxel-based representation of the porous LC connective tissue microstructure that was regionalized into 45 subvolumes, and the following quantities were calculated: total CTV within the LC, mean and regional CTVF, regional predominant beam orientation, and mean and regional material anisotropy. Results Regional variation within the laminar microstructure was considerable within the normal eyes of all monkeys. The laminar connective tissue was generally most dense in the central and superior regions for the paired normal eyes, and laminar beams were radially oriented at the periphery for all eyes considered. CTV increased substantially in EG eyes compared with contralateral normal eyes (82%, 44%, 45% increases; P < 0.05), but average CTVF changed little (−7%, 1%, and −2% in the EG eyes). There were more laminar beams through the thickness of the LC in the EG eyes than in the normal controls (46%, 18%, 17% increases). Conclusions The substantial increase in laminar CTV with little change in CTVF suggests that significant alterations in connective and nonconnective tissue components in the laminar region occur in the early stages of glaucomatous damage.

Optic nerve head perfusion in normal eyes and eyes with glaucoma using optical coherence tomography-based microangiography

“…Our OMAG prototype was not able to measure accurately the ONH perfusion in the lamina cribrosa (LC), because with its 840 nm laser source, the visibility of the LC tissue was limited and highly affected by the pre-laminar tissue. However, since previous studies have shown that early glaucomatous damage is primarily found in preLC tissue, the results of our cohort with early to moderate glaucoma (MD range −7.96 to 0.63 dB) are notable (21,22). A light source with a longer wavelength, or using sweptsource OCT at 1,060 nm wavelength (25), might enable accurate measurement of microcirculation within LC tissue.…”

“…We found OMAG-derived ONH perfusion metrics had significant correlations with VF MD, VF PSD, RNFL thickness, and ONH cup-to-disc ratio and rim area. A strength of OMAG is the ability to isolate preLC, which is relevant to early glaucomatous damage (21,22). We specifically limited our glaucoma group to those with mild-moderate glaucoma, to determine the ability of OMAG to distinguish earlier disease from normal, and found it performed well, with high correlation with both structural and functional measures of glaucoma.…”

Polarization microscopy for characterizing fiber orientation of ocular tissues

“…8) Even in areas with pigment on the lamina beams (Fig. 9) [43], the calculated orientations were smooth and continuous with adjacent unpigmented regions, demonstrating that the method was robust and produced satisfactory results.…”

Differential Gene Expression in Glaucoma

“…The retina and, in particular, the ganglion cells themselves (Danias et al 2003;Jakobs et al 2005;Schlamp et al 2006;Morgan 2012) are affected. Finally, the optic nerve head (ONH), including the lamina cribrosa (Hernandez 2000;Hernandez et al 2008;Roberts et al 2009;Burgoyne 2011), the optic nerve proper (Nakazawa et al 2006), and the central projection targets of the ganglion cells in the lateral geniculate body and the superior colliculus (Gupta et al 2007;Liu et al 2011) all can display pathological changes in glaucoma.…”