Premise and Prediction???How Optic Nerve Head Biomechanics Underlies the Susceptibility and Clinical Behavior of the Aged Optic Nerve Head

Abstract

We propose that age-related alterations in optic nerve head (ONH) biomechanics underlie the clinical behavior and increased susceptibility of the aged ONH to glaucomatous damage. The literature which suggests that the aged ONH is more susceptible to glaucomatous damage at all levels of intraocular pressure is reviewed. The relevant biomechanics of the aged ONH are discussed and a biomechanical explanation for why, on average, the stiffened peripapillary scleral and lamina cribrosa connective tissues of the aged eye should lead to a shallow (senile sclerotic) form of cupping is proposed. A logic for why age-related axon loss and the optic neuropathy of glaucoma in the aged eye may overlap is discussed. Finally, we argue for a need to characterize all forms of clinical cupping into prelaminar and laminar components so as to add precision to the discussion of clinical cupping which does not currently exist. Such characterization may lead to the early detection of ONH axonal and connective tissue pathology in ocular hypertension and eventually aid in the assessment of etiology in all forms of optic neuropathy including those that may be purely age-related. The Susceptibility of the Aged Optic Nerve Head (ONH)A variety of data suggest that the ONH becomes more susceptible to progressive glaucomatous damage as it ages, though this concept remains unproven through direct experimentation, and may not be true for every aged eye. These data can be summarized as follows. First, in most [1][2][3][4][5] , but not all 6,7 , population based studies, intraocular pressure (IOP) either does not increase with age or if it does, the magnitude of increase is not likely to be clinically important. Thus, the fact that the prevalence of the neuropathy increases with age 8 is likely explained by a greater susceptibility to IOP and other non-IOP-related risk factors, rather than a higher prevalence of IOP elevation, with increasing age. Second, in an extensive review of the literature, we can find only a few reports of the onset and progression of normal tension glaucoma (NTG) in infants, children and young adults 9 . While we acknowledge that accurate NTG prevalence estimates require long-term telemetric characterization of untreated IOP and rigorous population based ONH and visual field examinations, all existing studies suggest that NTG is most commonly a disease of the elderly [10][11][12][13][14][15] in the young 9 . Third, age is an independent risk factor for both the prevalence 16 and progression of the neuropathy at all stages of damage [17][18][19] . The Clinical Behavior of the Aged ONHApart from the issue of ONH susceptibility, we predict that if all aspects of insult are equal (alterations in IOP, the volume flow of blood and nutrient transfer from the laminar capillary to the ONH astrocyte are all of the same magnitude, duration and fluctuation), the aged eye will demonstrate clinical cupping that is on average shallow and pale (at all stages of field loss) compared to the eye of a child or young adult. This clini...

Characterization of age-related variation in corneal biomechanical properties

“…Albon et al (2000) observed a decrease in both the mechanical compliance and resilience of the human lamina cribrosa with age, and similar observations were made by Krag et al (1997) in the lens capsule. Strong association was found between the age-related alterations in the optic nerve head and its increased susceptibility to glaucomatous damage (Burgoyne & Downs 2008). The asphericity of both the anterior and posterior corneal surfaces was reported to undergo significant changes with age, leading to a more spherical topography (Lam & Douthwaite 2002) and peripheral thinning (Dubbelman et al 2006).…”

Excitotoxic Injury to Retinal Ganglion Cells

“…It has been proposed that IOP can generate mechanical forces at or near the lamina cribrosa resulting in direct injury to RGC axons. These same IOP-induced stresses will compromise local vascular perfusion of the tissue resulting indirectly in ischemic insult of RGC axons (Burgoyne & Downs, 2008). Mechanisms for ischemic injury to RGC axons have been explored using an isolated perfused rat optic nerve preparation in combination with methods for induction of experimental ischemia.…”

Factors associated with topographic changes of the optic nerve head induced by acute intraocular pressure reduction in glaucoma patients

“…6,[22][23][24][25][26] Previous studies have suggested that systemic and ocular factors, such as ageing, [27][28][29] chronically elevated IOP, [30][31][32] level of glaucomatous damage, 1,17,33 and disc size (scleral canal diameter), 34 could influence the susceptibility of an individual ONH to a given level of IOP. More recently, it has been suggested that other factors could be either directly or indirectly related to ONH response to pressure-induced damage, such as corneal parameters (both CCT and CH) 13,[35][36][37] and diabetes.…”