Arash Kazemi

In Vivo Noninvasive Measurement of Young’s Modulus of Elasticity in Human Eyes: A Feasibility Study

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.

Comparison of aqueous outflow facility measurement by pneumatonography and digital schiøtz tonography

Purpose It is not known if outflow facilities measured by pneumatonography and Schiøtz tonography are interchangeable. In this study we compared outflow facility measured by pneumatonography to outflow facility measured by digital Schiøtz tonography. Methods Fifty-six eyes from 28 healthy participants, ages 41 to 68 years, were included. Intraocular pressure (IOP) was measured in the sitting and supine positions with a pneumatonometer. With the subject in the supine position, IOP was recorded for 2 minutes by using a pneumatonometer with a 10-g weight and for 4 minutes by using a custom digital Schiøtz tonometer. Outflow facility was determined from the changes in pressure and intraocular volume and a standard assumed ocular rigidity coefficient for each instrument, respectively, and by using an ocular rigidity coefficient calculated by measuring pressure without and with a weight added to the pneumatonometer tip. Results The outflow facility was 0.29 ± 0.09 μL/min/mm Hg by Schiøtz tonography and 0.24 ± 0.08 μL/min/mm Hg by pneumatonography (P < 0.001) when using the standard assumed constant ocular rigidity coefficient. Mean calculated ocular rigidity coefficient was 0.028 ± 0.01 μL−1, and outflow facility determined by using this coefficient was 0.23 ± 0.08 μL/min/mm Hg by Schiøtz tonography and 0.21 ± 0.07 μL/min/mm Hg by pneumatonography (P = 0.003). Outflow facilities measured by the two devices were correlated when the ocular rigidity was assumed (r = 0.60, P < 0.001) or calculated (r = 0.70, P < 0.001). Conclusions Outflow facilities measured by pneumatonography were correlated with those measured by Schiøtz tonography, but Schiøtz tonography reported approximately 10% to 20% higher facilities when using the standard method. When ocular rigidity was determined for each eye, differences were smaller. Measurements from these devices cannot be compared directly.

Continuous Monitoring of Intraocular Pressure: An Overview of New Techniques

Elevated intraocular pressure (IOP) is the main risk factor for glaucoma and is currently the only treatable risk factor. IOP is dynamic with regular circadian variations and random short-term and long-term fluctuations. Current glaucoma management is mostly based on single IOP measurements during office visits which may not accurately represent a patient’s 24-h pressure profile. Most of glaucoma patients have their highest IOP outside clinic hours, usually during the nocturnal period. Currently, the only available approach for 24-h IOP monitoring is by using repeated tonometry which is inconvenient, expensive, and does not provide continuous monitoring of IOP. The goal of continuous IOP monitoring is to provide automated 24-h ambulatory recording of IOP. In this article, we review the existing technologies for IOP monitoring and evaluate new innovative methods for continuous 24-h IOP monitoring, including temporary non-invasive and permanent invasive approaches that currently being developed.

The Effects of Netarsudil Ophthalmic Solution on Aqueous Humor Dynamics in a Randomized Study in Humans.

Abstract Purpose: Netarsudil, an inhibitor of Rho kinase and a norepinephrine transporter, has been shown to lower elevated intraocular pressure (IOP) in controlled studies of patients with open-angle glaucoma and ocular hypertension, and in healthy volunteers. The mechanism of this ocular hypotensive effect in humans is unknown. Methods: The objective of this study was to evaluate the effect of netarsudil 0.02% on aqueous humor dynamics (AHD) parameters. In this double-masked, vehicle-controlled, paired-eye comparison study, 11 healthy volunteers received topical netarsudil ophthalmic solution 0.02% or its vehicle once daily for 7 days (morning dosing). The primary endpoints were the change in AHD parameters, compared between active and vehicle-treated eyes. Results: In netarsudil-treated eyes, diurnal outflow facility increased from 0.27 ± 0.10 μL/min/mmHg to 0.33 ± 0.11 μL/min/mmHg (+22%; P = 0.02) after 7 days of treatment. In placebo-treated eyes, diurnal outflow facility did not significantly change (P = 0.94). The difference between netarsudil and placebo eyes in diurnal change of outflow facility was 0.08 μL/min/mmHg (P < 0.001). Diurnal episcleral venous pressure (EVP) in netarsudil-treated eyes decreased from 7.9 ± 1.2 mmHg to 7.2 ± 1.8 (-10%; P = 0.01). Diurnal EVP was not significantly different between netarsudil- and placebo-treated eyes. There was a trend toward decreasing aqueous humor flow rate (-15%; P = 0.08). No treatment changes were seen in uveoscleral outflow rate. Conclusions: Once-daily dosing of netarsudil ophthalmic solution 0.02% lowered IOP through increasing trabecular outflow facility and reducing EVP. This suggests a combination of mechanisms that affect both the proximal and distal outflow pathways.

Ultrasound surface wave elastography of the living human eye

The purpose of this paper was to demonstrate a noninvasive technique to measure elastic properties of human eyes using ultrasound surface wave elastography (USWE) technique. Twenty eyes of 10 healthy subjects (age 44-63; mean 51 years) were studied. A localized harmonic vibration for 0.1 second at 100 Hz was generated by using a spherically-tipped vibrator (3 mm diameter) placed on the closed eyelid. The subjects only felt a gentle vibration on their eyes. The wave propagation in the eye was measured by using a linear array ultrasound transducer. The wave speed was determined from the change in phase with distance. Mean wave speed in the cornea was 1.82 ± 0.10 m/s (± SD) at 100 Hz. Intraocular pressure (IOP) was measured by using Goldmann applanation tonometry. Mean IOP was 12.8 ± 2.7 mmHg (± SD). The wave speed correlated well with IOP (r=0.74; p<;0.001). USWE is a safe and noninvasive technique for generating and measuring wave propagation in the eye. Further improvement and validation of USWE in the eye experiments is needed.