In Vivo Examination of Lamina Cribrosa Microarchitecture and Optic Nerve Head Geometry in Normal Human Aging and Early Glaucoma

Purpose: The lamina cribrosa likely plays an important role in the pathogenesis of glaucoma. The goals of this dissertation were to better understand differences in lamina cribrosa microarchitecture and optic nerve head (ONH) geometry in normal human eyes with axial length and aging and determine whether any differences found in older, normal eyes were similar to changes associated with early glaucoma, but potentially to a lesser extent.

Methods: (1) Images of the ONH were acquired via spectral domain optical coherence tomography (SDOCT) and used to quantify Bruch’s Membrane Opening (BMO) area, mean anterior lamina cribrosa surface depth (ALCSD), mean minimum rim width (MRW) and scaled MRW in young normal subjects to examine ONH structure in eyes with different axial lengths. (2) The aforementioned and additional SDOCT parameters (anterior lamina cribrosa surface [ALCS] radius of curvature [RoC], prelaminar tissue volume [PTV], neuroretinal rim volume) were quantified in normal young (20-30 years) and older (> 50 years) eyes. Images of the ALCS microarchitecture were acquired using adaptive optics and used to quantify mean ALCS pore area, elongation, and nearest neighbor distance (NND). ALCS pore and ONH parameters were compared between fellow eyes of normal subjects and between young and older normal eyes. (3) Images of the ONH and ALCS microarchitecture were also acquired in glaucoma suspects and primary open angle glaucoma (POAG) patients. Global and local ALCS pore geometries and ONH parameters were compared between suspect/POAG and age-matched normal eyes. The relationships between ONH and ALCS pore parameters were also examined.

Results: (1) Mean MRW was significantly thinner in young, normal eyes with more posteriorly-located laminar surfaces (P<.01) and larger BMO areas (P<.01). However, scaled MRW and BMO area were not correlated (P=.77), potentially indicating that all eyes have the same number of axons regardless of the size of the disc. While eyes with longer axial lengths had larger BMO areas (P<.01), no significant relationships were found between axial length and mean MRW (P=.09) or mean ALCSD (P=.07). (2) ONH and mean global ALCS pore parameters were not statistically different between fellow normal eyes. With the exception of mean MRW (significantly thinner in older eyes), all ONH and ALCS pore parameters were similar between older and young eyes. (3) PTV, rim volume, mean MRW and mean RNFL thickness were significant reduced, and ALCS was more posteriorly located and more steeply curved in suspect/POAG eyes compared to normal eyes. ALCS pores were more closely spaced (smaller global mean NND) in suspect/POAG eyes. Local pore analyses revealed that ALCS pores were significantly smaller in the superior-temporal sector of suspect/POAG eyes compared to normal eyes (P=.03). In addition, there were no significant relationships between any ALCS pore and ONH parameter within older normal eyes or suspect/POAG eyes.

Conclusions: This dissertation provides increased understanding of ONH and laminar structure in normal young and older eyes, as well as differences in these structural properties between normal and suspect/POAG eyes. The larger BMO areas found in young eyes with increased axial lengths could result from retinal and scleral stretching forces that occur during development. As the normal eye ages, there is a reduction in mean MRW that likely reflects an age-related loss in retinal ganglion cell axons. In addition to profound differences in ONH structure, we found significant differences in ALCS pore area in the superior-temporal sector of suspect/POAG eyes (relative to normal, older eyes), corresponding to a region that is known to be prone to the development of retinal nerve fiber layer defects in glaucoma.