We propose 3 interrelated aims to define the biomechanics of the eye rotating (extraocular) muscles (EOMs) & optic nerve (ON) in health & visual disease, understand novel EOM actions, & characterize mechanical effects that may contribute to severe myopia.
We aim to improve treatment of strabismus, misalignment of visual directions of the eyes; glaucoma & non-arteritic anterior ischemic optic neuropathy (NA-AION), both common blinding ON diseases; & high axial myopia, an ocular elongation & distortion that has become a worldwide epidemic & major cause of blindness. We propose a novel & critical nexus linking the EOMs, ON, & structure of the eye's scleral wall that we will explore using modern imaging & artificial intelligence techniques.
Aim I will clarify the kinematic (motion) properties of the human eye, testing by multipositional magnetic resonance imaging (MRI) of the eyeball & EOMs the hypothesis that translational (linear) movement contributes importantly to ocular alignment. MRI will be performed during horizontal convergence & vertical eye rotation in normal people, & in patients who have common forms of strabismus including convergence insufficiency, eye crossing (esotropia), & outward ocular deviation (exotropia), both before & after corrective EOM surgery. Clarification of ocular translation is necessary to understand normal ocular motility and treat its disorders.
Aim II will characterize the mechanical loading on the ON caused by eye movements. We will characterize the mechanical effects of ON tractional loading on the eyeball during horizontal & vertical eye rotations at 2 scales in living people, to test the hypothesis that such ON loading deforms it & adjacent retina & blood vessels as loading translates the eye. We propose that the resulting deformation during eye movements may create repetitive strain injury contributing to glaucoma, NA-AION, & axial myopia. In groups of subjects with the foregoing diseases, & in an equal group of matched healthy subjects, we will study mechanical effects of eye movement within the living eye by imaging its internal micro structure & blood vessels with optical coherence tomography, & outside the eyeball in the eye socket using MRI. Effects of tethering during eye movement will be studied ex vivo by precision 3D optical imaging of fresh human eye bank specimens subjected to mechanical tension on the ON that mimic effects of the eye movements imaged in the living subjects.
Aim III will model the biomechanics of ocular kinematics. The constitutive mechanical properties of the non-muscular ocular & eye socket tissues will be described by finite element models (FEMs) using modern engineering methods for computational simulation to predict ocular kinematics, as well as local mechanical strains in the ON & sclera that may cause glaucoma, NA-AION, & the ocular deformities underlying extreme nearsightedness. We will determine if FEMs employing normal tissue properties can simulate normal ocular translation during horizontal & vertical rotations & convergence. By FEM simulation, we will also test the hypothesis that ocular loading by eye movement might contribute to: normal vergence, strabismus, & the effects of strabismus surgery.

Public Health Relevance

. Strabismus is a common clinical disorder that can cause double vision in adults and vision loss in children. Strabismus is often treated by surgical manipulation of the eye muscles, although current knowledge of their structure and function is incomplete. Proposed functional imaging and biomechanical studies of the properties of the eye muscles, eyeball, and optic nerve will improve understanding of the causes and treatment of strabismus, optic nerve diseases, and nearsightedness.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
2R01EY008313-30
Application #
9972266
Study Section
Special Emphasis Panel (ZRG1)
Program Officer
Araj, Houmam H
Project Start
1991-01-06
Project End
2024-04-30
Budget Start
2020-05-01
Budget End
2021-04-30
Support Year
30
Fiscal Year
2020
Total Cost
Indirect Cost
Name
University of California Los Angeles
Department
Ophthalmology
Type
Schools of Medicine
DUNS #
092530369
City
Los Angeles
State
CA
Country
United States
Zip Code
90095
Chaudhuri, Zia; Demer, Joseph L (2018) Long-term Surgical Outcomes in the Sagging Eye Syndrome. Strabismus 26:6-10
Demer, Joseph L (2018) Knobby Eye Syndrome. Strabismus 26:33-41
Clark, Robert A; Demer, Joseph L (2018) The Globe's Eccentric Rotational Axis: Why Medial Rectus Surgery Is More Potent than Lateral Rectus Surgery. Ophthalmology 125:1234-1238
Shin, Andrew; Park, Joseph; Demer, Joseph L (2018) Opto-mechanical characterization of sclera by polarization sensitive optical coherence tomography. J Biomech 72:173-179
Demer, Joseph L; Clark, Robert A; Suh, Soh Youn et al. (2017) Magnetic Resonance Imaging of Optic Nerve Traction During Adduction in Primary Open-Angle Glaucoma With Normal Intraocular Pressure. Invest Ophthalmol Vis Sci 58:4114-4125
Chang, Melinda Y; Coleman, Anne L; Tseng, Victoria L et al. (2017) Surgical interventions for vertical strabismus in superior oblique palsy. Cochrane Database Syst Rev 11:CD012447
Shin, Andrew; Yoo, Lawrence; Park, Joseph et al. (2017) Finite Element Biomechanics of Optic Nerve Sheath Traction in Adduction. J Biomech Eng 139:
Suh, Soh Youn; Le, Alan; Shin, Andrew et al. (2017) Progressive Deformation of the Optic Nerve Head and Peripapillary Structures by Graded Horizontal Duction. Invest Ophthalmol Vis Sci 58:5015-5021
Rajab, Ghada Z; Suh, Soh Youn; Demer, Joseph L (2017) Magnetic resonance imaging in dissociated strabismus complex demonstrates generalized hypertrophy of rectus extraocular muscles. J AAPOS 21:205-209
Chang, Melinda Y; Shin, Andrew; Park, Joseph et al. (2017) Deformation of Optic Nerve Head and Peripapillary Tissues by Horizontal Duction. Am J Ophthalmol 174:85-94

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