Citations

Precis: In this population-based study of 509 open-angle glaucoma (OAG) patients over a 36-year period, we identified a decreased rate of developing dementia compared with the rate in the general population. Purpose: The aim was to determine the incidence of dementia and Alzheimer disease (AD) among patients with OAG. Patients and Methods: Retrospective, population-based cohort study. All residents of Olmsted County, Minnesota (≥40 y) who were diagnosed with OAG between January 1, 1965 and December 31, 2000, were eligible for inclusion in this study. A total of 509 patients were included over the 36-year period. The cumulative probability of developing dementia was calculated and compared with the population risk of dementia. Results: Of the 509 patients included, 300 (58.9%) were female, the median age was 67.5 years, and 278 patients (54.6%) had primary OAG. Other subgroups were pseudoexfoliation in 15.1%, treated ocular hypertension in 14.1%, normal tension glaucoma in 10.6%, and pigmentary glaucoma in 5.5% of the patients. Respectively, 118 (23.0%) and 99 (19.4%) patients developed dementia and AD. The 10-year cumulative probability of developing dementia and AD was 12.0% and 9.9%, with a 95% confidence interval of 9.3%-15.3% and 7.5%-13%, respectively. The observed 10-year incidence of dementia and AD were significantly lower than the expected population incidence (19.0% and 19.0%; P<0.001). Older age at diagnosis of glaucoma was a strong predictor for the development of dementia by multivariate analysis (hazard ratio: 3.31, 95% confidence interval: 2.61-4.20, P<0.001). Conclusion: The risk of developing dementia or AD was decreased in OAG patients compared with the general population. OAG with onset at a later age may present as a different etiopathogenetic entity compared with onset at a younger age, and represent the optic nerve findings of generalized neurodegenerative processes.

Papilledema is optic nerve swelling caused by increased intracranial pressure, which has the potential to cause significant vision loss. Papilledema is typically bilateral and symmetric but can sometimes be asymmetric and even unilateral. The cause for this asymmetry is unknown. The purpose of this study was to utilize ultrasound vibro-elastography (UVE) to assess for biomechanical differences in eyes with papilledema. Nine patients with papilledema and 9 age-matched controls were enrolled. An external harmonic vibration was used to generate wave propagation through the eyelid with three excitation frequencies of 100, 150, and 200 Hz. A 6.4 MHz ultrasound probe was used to noninvasively measure the wave propagation in the posterior sclera to provide shear wave speeds and viscoelasticity (fit with Voigt model). The magnitudes of the shear wave speed and viscoelasticity of the idiopathic intracranial hypertension patients’ posterior sclera were significantly higher than those of healthy subjects. Moreover, for patients with unilateral papilledema, the magnitudes of wave speed and viscoelasticity of the posterior sclera were statistically higher in eyes with papilledema than in the contralateral eyes without papilledema. UVE provides a noninvasive technique to measure the viscoelastic properties of the posterior sclera, which is stiffer in eyes with papilledema.

Biomechanical properties of the eye are important in understanding glaucoma. However, specific tissues that may be affected are unclear. In this study, we compared glaucomatous and normal eyes for differences in corneal tissue elasticity (as indicated by wave speed) and global ocular rigidity. Both eyes of 10 glaucoma patients and 10 normal controls, matched for age and intraocular pressure (IOP), were included. The ocular rigidity coefficient was calculated from supine IOP measured with and without a 10 g weight added to the tonometer. The wave speed in the cornea was measured by ultrasound surface wave elastography. With this technique, a spherical-tipped probe (4 mm diameter) was placed on the closed eyelid and vibrated at 100 Hz for 0.1 s. The wave speed was calculated using the phase gradient method. Measurements for normal and glaucoma eyes were compared using generalized estimating equation models. The corneal wave speed was similar between normal and glaucomatous eyes (P = 0.4). However, ocular rigidity was significantly lower in glaucomatous eyes (P &lt; 0.001) compared with normal eyes. There was no difference in age or IOP (P &gt; 0.3). Lower ocular rigidity in glaucomatous eyes suggests that a more compliant ocular shell may predispose to glaucoma. However, the lack of difference in the corneal wave speed suggests that corneal tissue is not significantly affected, and changes likely involve the sclera.

Purpose: Abnormal ocular biomechanical properties may be important for understanding the risk of glaucoma. However, there are no clinical methods for measuring standard material properties in patients. In this feasibility study we demonstrated proof-of-principle for a novel method, ultrasound surface wave elastography (USWE), to determine the in vivo Young’s modulus of elasticity of corneas in normal human eyes. Methods: In total, 20 eyes of 10 healthy subjects (mean age, 51.4±7.2; ±SD; range, 43 to 64 y) were studied. A spherical-tipped probe (3-mm diameter) was placed on closed eyelids and generated a gentle harmonic vibration at 100 Hz for 0.1 second. Wave speed propagation in the cornea was measured by USWE, and Young’s modulus was calculated from the wave speed. Associations between Young’s modulus and intraocular pressure (IOP), age, central corneal thickness, and axial length were explored by the Pearson correlation. Statistical significance was determined by using generalized estimating equation models to account for possible correlation between fellow eyes. Results: Mean IOP was 12.8±2.7 mm Hg. Mean wave speed in the cornea was 1.82±0.10 m/s. Young’s modulus of elasticity was 696±113 kPa and was correlated with IOP (r=0.57; P=0.004), but none of the other variables (P>0.1). Conclusions: USWE is a novel noninvasive technique for measuring ocular biomechanical properties. Corneal Young’s modulus in normal eyes is associated with IOP, consistent with measurements in cadaver eyes. Further work is needed to determine elasticity in other ocular tissues, particularly the sclera, and if elasticity is altered in glaucoma patients.