Sit, Arthur J.

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 < 0.001) compared with normal eyes. There was no difference in age or IOP (P > 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.

Abstract Objective: Several attributes of female reproductive history, including age at natural menopause (ANM), have been related to primary open-angle glaucoma (POAG). We assembled 18 previously reported common genetic variants that predict ANM to determine their association with ANM or POAG. Methods: Using data from the Nurses’ Health Study (7,143 women), we validated the ANM weighted genetic risk score in relation to self-reported ANM. Subsequently, to assess the relation with POAG, we used data from 2,160 female POAG cases and 29,110 controls in the National Eye Institute Glaucoma Human Genetics Collaboration Heritable Overall Operational Database (NEIGHBORHOOD), which consists of 8 datasets with imputed genotypes to 5.6+ million markers. Associations with POAG were assessed in each dataset, and site-specific results were meta-analyzed using the inverse weighted variance method. Results: The genetic risk score was associated with self-reported ANM (P = 2.2 × 10–77) and predicted 4.8% of the variance in ANM. The ANM genetic risk score was not associated with POAG (Odds Ratio (OR) = 1.002; 95% Confidence Interval (CI): 0.998, 1.007; P = 0.28). No single genetic variant in the panel achieved nominal association with POAG (P ≥0.20). Compared to the middle 80 percent, there was also no association with the lowest 10th percentile or highest 90th percentile of genetic risk score with POAG (OR = 0.75; 95% CI: 0.47, 1.21; P = 0.23 and OR = 1.10; 95% CI: 0.72, 1.69; P = 0.65, respectively). Conclusions: A genetic risk score predicting 4.8% of ANM variation was not related to POAG; thus, genetic determinants of ANM are unlikely to explain the previously reported association between the two phenotypes.