Noninvasive ultrasound vibro-elastography for assessing ocular disorders

PROJECT ABSTRACT Our understanding of the role of ocular biomechanical properties, such as elasticity and viscosity, is incomplete as there are no clinical methods for their in vivo clinical measurement. We propose to develop and refine a novel noninvasive ultrasound vibro-elastography (USVE) technique to measure viscoelastic properties of ocular tissues, and use the technique to assess two diseases, glaucoma and papilledema. We recently completed a R21 grant, evaluating USVE for assessing glaucoma. Glaucoma is the second leading cause of blindness in the US and worldwide, and the only available treatment is reduction of intraocular pressure (IOP). Our pilot study found significant differences in wave speed in the posterior sclera between glaucomatous and normal eyes. In another pilot project, we evaluated USVE in papilledema patients. Papilledema is optic nerve swelling, caused by increased intracranial pressure, and can cause significant vision loss. Papilledema from idiopathic intracranial hypertension (IIH) is typically bilateral and symmetric but can sometimes be asymmetric and even unilateral. We found that wave speeds in the posterior sclera of IIH patients were significantly higher than healthy subjects. In addition, wave speeds in patients with unilateral papilledema were significantly higher in affected eyes, compared with unaffected contralateral eyes. Both diseases depend on the biomechanics of ocular tissues including the posterior sclera surrounding the optic nerve head. However, they are on opposite ends of the spectrum where the deformation of the lamina cribrosa is back bowing in glaucoma and forward bowing in papilledema. Studying both diseases will help us to better understand the role of ocular tissue properties in disease risk and development, and the basic viscoelastic characteristics of the eye. In Aim 1, we will develop and refine USVE for measuring ocular viscoelastic properties. We will study various wave models in ocular tissues and develop advanced viscoelastic models to analyze ocular tissue’s elasticity and viscosity based on the wave speed dispersion measurements. In Aim 2, we will develop and refine USVE for assessing 50 patients with normal tension glaucoma (NTG) – glaucoma occurring at normal intraocular pressure – and 50 healthy control subjects. Since ocular biomechanical properties will be related to IOP, recruitment of NTG patients will allow comparison with IOP matched controls. In Aim 3, we will develop and refine USVE for assessing patients with papilledema. We will enroll a large cohort of 50 patients with papilledema from IIH and compare them with 50 age- and gender- matched healthy control subjects. We will study the changes of USVE measurements at baseline and after resolution of papilledema after treatment. Successful accomplishment of this project will provide fundamental knowledge about the role of ocular tissue biomechanical properties in glaucoma and papilledema. USVE may have the ability to stratify the risk of glaucomatous damage and the propensity toward the development of papilledema and vision loss, and identify novel targets for therapy.