The objective of this research is to learn more about the mechanisms underlying both normal ocular motor control in normal humans and disordered eye movements in human and non-human primates, mechanisms providing plasticity, and strategies to restore normal function in patients with strabismus. The research strategy is to make quantitative measurements of oculomotor function in both normal volunteers and superior oblique palsy patients, perform adaptive manipulations and to use systems approaches to interpret findings. A novel haploscopic viewing device is used to create full-field cyclovertical disparity without errors in magnification (as would be expected if flat prisms were used). Next, we analyze static and dynamic eye movements in monkeys with superior oblique muscle palsy (SOP), investigating how ocular alignment changes with time. We also develop clinically useful diagnostic tests to stratify patients into different treatment categories. Finally, we dissect the neural circuitry and muscular mechanisms that provide plasticity to the ocular motor system. Specifically, we examine the role of global multiply-innervated fibers (MIF's), which have been previously overlooked because of their lack of fast twitch fibers, and their palisade endings in both proprioception and effecting static eye alignment. The focus is on mechanisms that maintain oculomotor accuracy with emphasis on binocularity and adaptive mechanisms. Particular attention will be given to the concept of abnormal cyclovertical vergence tonus and its effect on transient eye misalignment in normal subjects or as an etiology for primary cyclovertical strabismus (currently lumped with congenital superior oblique palsy). These results will provide new information about adaptive control of eye alignment relative to strabismus and provide the basis for non-surgical therapy in the future.

Public Health Relevance

Strabismus, a static misalignment of the eyes, prevents single binocular vision and depth perception. This disorder affects 3% of the U.S.A. population and results in the need for 0.8 surgeries/1000 persons in the U.S.A annually. This project seeks to understand ocular motor control in normal humans and disordered eye movements in patients, to elucidate mechanisms providing plasticity, and to improve strategies to restore normal function in patients with strabismus.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
5R01EY019347-04
Application #
8212541
Study Section
Central Visual Processing Study Section (CVP)
Program Officer
Araj, Houmam H
Project Start
2008-09-30
Project End
2013-11-30
Budget Start
2012-03-01
Budget End
2012-11-30
Support Year
4
Fiscal Year
2012
Total Cost
$389,664
Indirect Cost
$152,064
Name
Johns Hopkins University
Department
Ophthalmology
Type
Schools of Medicine
DUNS #
001910777
City
Baltimore
State
MD
Country
United States
Zip Code
21218
Muthusamy, Brinda; Irsch, Kristina; Peggy Chang, Han-Ying et al. (2014) The sensitivity of the bielschowsky head-tilt test in diagnosing acquired bilateral superior oblique paresis. Am J Ophthalmol 157:901-907.e2
Newman-Toker, David E; Saber Tehrani, Ali S; Mantokoudis, Georgios et al. (2013) Quantitative video-oculography to help diagnose stroke in acute vertigo and dizziness: toward an ECG for the eyes. Stroke 44:1158-61
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Tian, Jing; Ying, Howard S; Zee, David S (2013) Revisiting corrective saccades: role of visual feedback. Vision Res 89:54-64
Irsch, Kristina; Guyton, David L; Ramey, Nicholas A et al. (2013) Vertical vergence adaptation produces an objective vertical deviation that changes with head tilt. Invest Ophthalmol Vis Sci 54:3108-14
Jung, Brian C; Choi, Soo I; Du, Annie X et al. (2012) MRI shows a region-specific pattern of atrophy in spinocerebellar ataxia type 2. Cerebellum 11:272-9
Lienbacher, Karoline; Mustari, Michael; Ying, Howard S et al. (2011) Do palisade endings in extraocular muscles arise from neurons in the motor nuclei? Invest Ophthalmol Vis Sci 52:2510-9
Shan, Xiaoyan; Hamasaki, Ichiro; Tian, Jing et al. (2011) Vertical alignment in monkeys with unilateral IV section: effects of prolonged monocular patching and trigeminal deafferentation. Ann N Y Acad Sci 1233:78-84
McLeod, D Scott; Ying, Howard S; McLeod, Colin A et al. (2011) Retinal and optic nerve head pathology in Susac's syndrome. Ophthalmology 118:548-52
Quaia, Christian; Ying, Howard S; Optican, Lance M (2011) The nonlinearity of passive extraocular muscles. Ann N Y Acad Sci 1233:17-25

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