Three aims are proposed to study the chorioretinal complex (choroid, choriocapillaris, Bruch's membrane, retinal pigment epithelium, photoreceptors) in age-related macular degeneration (AMD).
Each aim i ncludes both technical goals involving optical imaging and tests of hypotheses related to the pathogenesis of this disease.
Aim 1 will use phase changes between successive optical coherence tomography (OCT) B-scans (frames) to visualize the vascular layers behind the retina, specifically the choriocapillaris, Sattler's and Haller's layers of the choroid. Use of a 1050 nm light source will provide deep penetration through the retinal pigment epithelium to study changes in vascularization associated with nonexudative AMD, a condition for which there is currently no effective treatment. It will also permit in vivo examination of changes in subretinal vascularization associated with anti-VEGF treatment for neovascular AMD, a treatment that is generally effective but not completely understood.
Aim 2 will measure fundus autofluorescence (FAF) and morphology of the retinal pigment epithelium in geographic atrophy using ultrahigh-resolution adaptive optics (AO) with simultaneous reflectance and fluorescent scanning laser ophthalmoscopy and OCT volumetric imaging to co- localize disease-related changes visualized with the two modalities.
This aim will investigate the hypothesis that some of the changes in FAF characterizing AMD are secondary to changes in rhodopsin photopigment screening of the excitation and emitted light. This result may alter interpretations of FAF changes in AMD and other diseases of the chorioretinal complex associated with rod photoreceptor losses, and will be critical in developing or assessing new treatments.
Aim 3 will use a newly constructed afocal AO-OCT system and phase retrieval algorithm to measure changes in length and renewal rates of the photoreceptor outer segments in normal retinae and those with drusen characteristic of early and intermediate stage AMD. Changes in photoreceptors will be characterized over short- and long-term time scales. These results may provide new and sensitive functional indicators of AMD progression and a leading indicator of changes in the health of the chorioretinal complex at the intersection between biological aging and eye disease.

Public Health Relevance

The purpose of this research is to study structure and function in the retinal layers underlying development of age-related macular degeneration. New tools for precise optical imaging of microscopic structure, combined with sensitive characterization of cellular function, will identify changes in retinal landmarks, characterize the interaction of celllar systems over time, and contribute to our understanding of the breakdown of those systems that are critical in both the wet and dry forms of the disease.

Agency
National Institute of Health (NIH)
Institute
National Eye Institute (NEI)
Type
Research Project (R01)
Project #
1R01EY024239-01
Application #
8665661
Study Section
Special Emphasis Panel (DPVS)
Program Officer
Greenwell, Thomas
Project Start
2014-04-01
Project End
2019-03-31
Budget Start
2014-04-01
Budget End
2015-03-31
Support Year
1
Fiscal Year
2014
Total Cost
$563,632
Indirect Cost
$165,872
Name
University of California Davis
Department
Ophthalmology
Type
Schools of Medicine
DUNS #
047120084
City
Davis
State
CA
Country
United States
Zip Code
95618
Schwartz, Daniel M; Fingler, Jeff; Kim, Dae Yu et al. (2014) Phase-variance optical coherence tomography: a technique for noninvasive angiography. Ophthalmology 121:180-7
Zawadzki, Robert J; Capps, Arlie G; Kim, Dae Yu et al. (2014) Progress on Developing Adaptive Optics-Optical Coherence Tomography for In Vivo Retinal Imaging: Monitoring and Correction of Eye Motion Artifacts. IEEE J Sel Top Quantum Electron 20: