The overall goal of this research program is to develop novel methodologies with enhanced sensitivity for use in evaluating visual function, assessing the efficacy of therapeutic interventions, and providing new insight into the underlying causes of vision loss in ocular diseases. The goal of this proposal is to identify the mechanisms that form the basis for the spatial contrast sensitivity deficits observed in patients with retinitis pigmentosa (RP), a group of hereditaty retinal degenerations that are that are the most common genetic cause of blindness in adults. This goal Will be achieved by completing two specific aims:
Aim 1 is to develop a computerimplemented vlsual-riolse-based testing strategy. Visual-noise-based techniques can provide more information than standard clinical tests because perfomnance is factored into the components that govern contrast sensitivity. However, several issues regarding visual-noise-based approaches have been identified in pilot work that must be resolved.
Aim 2 will apply the novel testing strategy to individuals with RP to test three distinct, non-mutually exclusive hypotheses regarding tiie factors underlying their contrast sensitivity losses: patients with RP have elevated levels of additive noise within the visual pathway, patients with RP have elevated levels of multiplicative noise within the visual pathway, or patients with RP have an Inability to extract signal information from the noise. In addition to providing a better understanding ofthe source of contrast sensitivity losses In patients with RP, this research will yield a sensitive technique that will be useful for evaluating the efficacy of future therapeutic interventions in a variety of ocular disorders. The development of more sensitive metfiods of assessing visual function, such as that proposed here, is becoming increasingly important as gene-directed therapies and retinal cell transplantation therapies begin to enter clinical trials.

Public Health Relevance

(RELEVANCE) This study will develop a test that will permit the factors underlying contrast sensitivity deficits in patients with retinitis pigmentosa to be defined. This research addresses the need for Improved testing strategies with enhanced sensitivity for evaluating ocular disease progression, subtyping patients for inclusion In treatment trails, and In assessing the outcomes of future therapeutic interventions. Novel tests with enhanced sensitivity are becoming increasingly needed as gene-directed therapies and retinal cell transplantation therapies begin to enter clinical trials.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Transition Award (R00)
Project #
5R00EY019510-05
Application #
8535156
Study Section
Special Emphasis Panel (NSS)
Program Officer
Shen, Grace L
Project Start
2009-09-01
Project End
2014-08-31
Budget Start
2013-09-01
Budget End
2014-08-31
Support Year
5
Fiscal Year
2013
Total Cost
$226,200
Indirect Cost
$77,294
Name
University of Illinois at Chicago
Department
Ophthalmology
Type
Schools of Medicine
DUNS #
098987217
City
Chicago
State
IL
Country
United States
Zip Code
60612
Barrionuevo, Pablo A; Nicandro, Nathaniel; McAnany, J Jason et al. (2014) Assessing rod, cone, and melanopsin contributions to human pupil flicker responses. Invest Ophthalmol Vis Sci 55:719-27
McAnany, J Jason (2014) The effect of exposure duration on visual acuity for letter optotypes and gratings. Vision Res 105:86-91
McAnany, J Jason; Nolan, Philip R (2014) Changes in the harmonic components of the flicker electroretinogram during light adaptation. Doc Ophthalmol 129:1-8
McAnany, J Jason; Wanek, Justin; Zelkha, Ruth et al. (2014) Neural constraints on visual acuity in proliferative diabetic retinopathy. Optom Vis Sci 91:194-9
Salvatore, Serena; Fishman, Gerald A; McAnany, J Jason et al. (2014) Association of dark-adapted visual function with retinal structural changes in patients with Stargardt disease. Retina 34:989-95
Collison, Frederick T; Fishman, Gerald A; McAnany, J Jason et al. (2014) Psychophysical measurement of rod and cone thresholds in stargardt disease with full-field stimuli. Retina 34:1888-95
Gowrisankaran, Sowjanya; McAnany, J Jason; Alexander, Kenneth R (2013) Poststimulus response characteristics of the human cone flicker electroretinogram. Vis Neurosci 30:147-52
Jivrajka, R V; Genead, M A; McAnany, J J et al. (2013) Microperimetric sensitivity in patients on hydroxychloroquine (Plaquenil) therapy. Eye (Lond) 27:1044-52
McAnany, J Jason; Alexander, Kenneth R; Genead, Mohamed A et al. (2013) Equivalent intrinsic noise, sampling efficiency, and contrast sensitivity in patients with retinitis pigmentosa. Invest Ophthalmol Vis Sci 54:3857-62
McAnany, J Jason; Genead, Mohamed A; Walia, Saloni et al. (2013) Visual acuity changes in patients with leber congenital amaurosis and mutations in CEP290. JAMA Ophthalmol 131:178-82

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