Glaucomatous cupping of the lamina cribrosa: A review of the evidence for active progressive remodeling as a mechanism

The purpose of this review is to examine the literature in an attempt to elucidate a biomechanical basis for glaucomatous cupping. In particular, this work focuses on the role of biomechanics in driving connective tissue remodeling in the progression of laminar morphology from a normal state to that of an excavated glaucomatous state. While there are multiple contributing factors to the pathogenesis of glaucoma, we focus on laminar extracellular matrix (ECM) remodeling in glaucoma and the feedback mechanisms and signals that may guide progressive laminar cupping. We review the literature on the potential mechanisms of glaucomatous changes in the laminar ECM at the anatomic, structural, cellular and subcellular levels in the context of the biomechanical paradigm of glaucomatous onset and progression. Several conclusions can be drawn from this review. First, extensive remodeling of the lamina cribrosa ECM occurs in primary open angle glaucoma. Second, there is surprisingly little evidence to support acute mechanical damage to the lamina as the principal mechanism of cupping. Third, ONH astrocytes and lamina cribrosa cells can sense their mechanical environment and respond to mechanical stimuli by remodeling the ECM. Fourth, there is evidence suggesting that chronic remodeling of the lamina results in a progressive posterior migration of the laminar insertion into the canal wall, which eventually results in the posterior lamina inserting into the pia mater. Finally, modeling studies suggest that laminar remodeling may be a biomechanical feedback mechanism through which cells modify their environment in an attempt to return to a homeostatic mechanical environment. It is plausible that biomechanics-driven connective tissue remodeling is a mechanism in the progression of laminar morphology from a normal state to that of a cupped, excavated glaucomatous state. (C) 2010 Elsevier Ltd. All rights reserved.