Scleral biomechanics and glaucoma--a connection?

I ntraocular pressure (IOP) is well known to play an important role in the pathogenesis of some forms of glaucoma. Furthermore, significant, sustained pressure reduction is known to be beneficial in the clinical management of glaucoma patients. 1 Less well understood is the mechanism by which elevated IOP leads to the loss of retinal ganglion cells that is the hallmark of glaucomatous optic neuropathy. Two theories have been proposed that may explain the pressure-damage pathway. The biomechanical theory hypothesizes that elevated IOP deforms (stretches) the optic nerve head tissues, and in particular, the lamina cribrosa (LC), leading to several effects. First, it causes misalignment of pores between lamellae, which in turn causes kinking and distortion of nerve fibre bundles as they traverse the LC. Second, LC deformation may alter local cellular function. This hypothesis is consistent with histologic and other studies showing that elevated IOP causes retrograde bowing of the LC, 2–6 can disrupt the organisation of the LC, 7–9 and that there is decreased connective tissue density in the superior and inferior poles of the optic nerve head. 10,11 The latter observation correlates with clinical findings that the arcuate bundles that enter the optic nerve head at the superior and inferior poles are usually first affected in glaucoma. 12,13 In this theory, differences in the mechanical characteristics of optic nerve head (ONH) tissues are hypothesized to account for differences in susceptibility to IOP-induced damage. In other words, individuals with " weak " ONHs are at increased risk of optic neuropathy due to elevated IOP. The vasogenic theory proposes that glaucomatous optic neuropathy is due to insufficient vascular per-fusion at the level of the LC, resulting in ischemic injury. Inadequate autoregulatory function in the branches of the short posterior ciliary arteries supplying the laminar region, complications in the haemo-dynamics between the peripapillary choroidal flow and the anterior optic nerve flow, 14 or other haemo-tologic factors could then account for differences in susceptibility to IOP-induced damage (for reviews see references 14–17). It is clear that these theories are not mutually exclusive ; in fact, biomechanical and vasogenic effects are likely to be synergistic. Here we focus on the biome-chanical theory, since recent developments in this area are quite interesting and may lead to a new way of thinking about how elevated IOP leads to retinal ganglion cell damage. In order to evaluate the effects of IOP on optic nerve head biology, …