This application requests a career development award for a dually trained pediatric and neuro- ophthalmologist with a scientific interest in developing large-scale randomized clinical trials evaluating strabismus surgery (the most commonly performed pediatric ophthalmic surgery) using a comprehensive battery of psychophysical and electrophysiological tests. This will allow the candidate to create an individual research program that evaluates binocular summation, a novel measure of binocular function not currently evaluated by strabismus researchers, using functional measures. Through the completion of this research, the candidate will establish preliminary data for further independent research, and she will also define novel objective measures by which to measure binocular function in larger clinical trials of strabismus treatments (surgical and non-surgical). In addition, by completing the proposed didactic program leading to a M.S. degree in Epidemiology and involvement in the multi-center Pediatric Eye Disease Investigators Group (PEDIG), the candidate will by the end of the award period, gain the valuable hands-on experience, knowledge, and mentorship required to design, propose and implement randomized clinical trials related to strabismus surgery. The candidate's long-term goal is to lead clinical trials that will improve evidence based recommendations for strabismus treatments. This project will be under the supervision of senior investigators who will jointly provide guidance in strabismus research, epidemiology, and psychophysics The candidate will have the following objectives during the award period: 1) Development of an individual research program in strabismus outcomes;2) Completion of coursework in epidemiology, biostatistics, clinical trial design, and the responsible conduct of research through participation in an M.S. degree program in Epidemiology and the UCLA K30 program;3) Develop expertise in psychophysics and the use of the sweep visual evoked responses;4) Gain experience in multi-center clinical trial design and implementation with PEDIG. Presently, strabismus treatment outcomes are evaluated by subjective and insensitive tests, such as clinical examination and stereopsis that often do not adequately assess the binocular function. The development of objective outcome measures for strabismus surgery research is essential in order to provide meaningful evidence-based recommendations. The overall goal of the research component of this proposal is to evaluate binocular summation, which is defined as the improvement in binocular vision compared to monocular vision, in patients with strabismus using a comprehensive battery of functional psychophysical and electrophysiological tests. This goal will be accomplished with 3 specific aims: 1. Determine the effect of ocular misalignment on binocular summation. In a large population of strabismic individuals, we will test the hypothesis that ocular misalignment impairs binocular summation by comparing subjects with various forms of strabismus to control subjects. Our hypothesis is that binocular summation in strabismic subjects will be lower than non-strabismic controls, and that binocular summation scores can distinguish between these two populations. We will also test the effect of contrast level, strabismus sub-type, and onset age on binocular summation. 2. Determine the impact of surgical realignment on binocular summation. We will test the hypothesis that ocular realignment surgery improves binocular summation in most strabismic subjects. We will also evaluate the influence of age of strabismus onset, timing of ocular realignment, interocular differences in acuity, and strabismus type on improvement in binocular summation. 3. Evaluate binocular summation as a surrogate measure for other outcomes used in clinical trials, including ocular alignment before and after surgery, strabismus control, and quality of life. Together, this project will characterize a novel outcome that describes functional binocular visual status in strabismic subjects that can be used in future clinical trials. Beyond the development of this individual research program, the experienced gained by the candidate in the proposed interactions with expert mentors and collaborators will provide training in clinical trial design, psychophysical outcomes, and sweep visual evoked responses. The institution, mentors, and collaborators outlined in this proposal are dedicated to research and cultivating the careers of early investigators. This structured career development plan will to position the candidate for independent investigator status at the end of the award period.

Public Health Relevance

Strabismus or ocular misalignment is a common ocular disorder, affecting 3-5% of the population. Untreated strabismus can lead to permanent loss of vision from amblyopia or loss of binocular function and depth perception. Strabismus surgery is the most commonly performed ocular surgery in children;however, currently there are very few randomized, controlled trials to evaluate strabismus with functional measures. This work will aim to further define objective and functional measures to characterize strabismus surgery outcomes and to further define the binocular experience of patients with strabismus. The career development goals of the principal investigator include developing the skills to propose, implement, and analyze large randomized trials to improve evidence-based recommendations for strabismus treatments, which will improve the care of patients with strabismus.

National Institute of Health (NIH)
National Eye Institute (NEI)
Mentored Patient-Oriented Research Career Development Award (K23)
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Special Emphasis Panel (ZEY1-VSN (11))
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Agarwal, Neeraj
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University of California Los Angeles
Schools of Medicine
Los Angeles
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Chang, Melinda Y; Velez, Federico G; Demer, Joseph L et al. (2018) Reply. Ophthalmology 125:e24
Chang, Melinda Y; Phasukkijwatana, Nopasak; Garrity, Sean et al. (2017) Foveal and Peripapillary Vascular Decrement in Migraine With Aura Demonstrated by Optical Coherence Tomography Angiography. Invest Ophthalmol Vis Sci 58:5477-5484
Chang, Melinda Y; Pineles, Stacy L (2017) Pediatric Optic Neuritis. Semin Pediatr Neurol 24:122-128
Chang, Melinda Y; Demer, Joseph L; Isenberg, Sherwin J et al. (2017) Decreased Binocular Summation in Strabismic Amblyopes and Effect of Strabismus Surgery. Strabismus 25:73-80
Velez, Federico G; Chang, Melinda Y; Pineles, Stacy L (2017) Inferior Rectus Transposition: A Novel Procedure for Abducens Palsy. Am J Ophthalmol 177:126-130
Yulek, Fatma; Velez, Federico G; Isenberg, Sherwin J et al. (2017) Binocular Summation and Control of Intermittent Exotropia. Strabismus 25:81-86
Chang, Melinda Y; Velez, Federico G; Demer, Joseph L et al. (2017) Accuracy of Diagnostic Imaging Modalities for Classifying Pediatric Eyes as Papilledema Versus Pseudopapilledema. Ophthalmology 124:1839-1848
Kattan, Jaffer M; Velez, Federico G; Demer, Joseph L et al. (2016) Relationship Between Binocular Summation and Stereoacuity After Strabismus Surgery. Am J Ophthalmol 165:29-32
Pineles, Stacy L (2016) Fixation Switch Diplopia. J Neuroophthalmol 36:118-9
Kim, J Anna; Velez, Federico G; Pineles, Stacy L (2016) Strabismus Surgery in Patients With Ocular Neuromyotonia: Potential Unmasking of the Condition and Effective Management Tool. J Neuroophthalmol 36:259-63

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