Yuhua Zhang, PhD

The retina is the only portion of the central nervous system (CNS) that can be studied non-invasively through the unique optical window of the eye. In principle, the neural, glial, and vascular tissue in the retina of a living human subject can be observed at the histologic level. Retinal imaging has thus been a primary diagnostic modality for retinal disease and plays a critical role in the clinical management of systemic and CNS diseases. My research interests are advanced ophthalmoscopy, emphasizing adaptive optics (AO) imaging to facilitate in vivo study of chorioretinal disease and systemic disease at the cellular and sub-cellular levels.

I am leading an Advanced Ophthalmic Imaging Laboratory (AOIL). We have developed state-of-art high-resolution retinal imaging instruments that integrate adaptive optics (AO), scanning laser ophthalmoscopy (SLO), and optical coherence tomography (OCT). SLO and OCT represent two modern revolutionary imaging mechanisms that reveal the 3-D retinal structure in the living eye. AO is a technique that can compensate for the eye’s optical defects, thereby enabling SLO and OCT with (near) diffraction-limited resolution. The AOIL AO-SLO-OCT imaged cone and rod photoreceptors in the human retina. Another imaging instrument that was recently built in the AOIL is a high-speed adaptive optics near-confocal scanning ophthalmoscope (AONCO). This device can image the human retina with a frame rate of up to 800 Hz, representing the fastest en-face imaging instrument for the living human eye in the world to date. High-speed, high-resolution imaging enables direct and accurate measurement of the movement of individual erythrocytes and leukocytes flowing in human retinal capillaries without using any exogenous contrast agents, opening a new horizon for studying high-order retinal hemodynamics that reflect the mechanical property of retina capillaries. In addition, a new generation of technology is being developed for in vivo imaging of the retina at the molecular level.

We are looking forward to gaining the ability to unveil the molecular signatures of retinal health by objective characterization of the compounds in the retina and its supportive retinal pigment epithelium, which are associated with retinal metabolism and implicated in the process of aging and the pathogenesis of various retinal diseases.

My long-term goal is to develop technological advancements that improve the understanding and treatment of diseases that blind the human eye and affect the central nervous system. With research grants from the National Institute of Health, the National Sciences Foundation, the EyeSight Foundation of Alabama, the International Retinal Research Foundation, the Keck Foundation, Research to Prevent Blindness Foundation, and Carl Marshall Reeves & Mildred Almen Reeves Foundation, advance AO enhanced retinal imaging developed in the AOIL is employed for in vivo investigation of age-related macular degeneration and providing important avenues to study various common medical and neurologic conditions such as hypertension, diabetes, and Alzheimer’s disease.

Zhang Y, Poonja S, and Roorda A, MEMS based Adaptive Optics Scanning Laser Ophthalmoscopy, Opt. Lett.. 2006; 31, 1268-1270. PMID: 16642081

Sincich LC, Zhang Y, Tiruveedhula P, Horton1 JC, and Roorda A. Resolving Single Cone Inputs to Visual Receptive Fields. Nat Neurosci. 2009; 12(8):967-9. PMID: 19561602

Meadway A, Girkin CA, Zhang Y, A dual-modal retinal imaging system with adaptive optics. Opt. Express , 21(24):29792-29807 (2013). PMID: 24514529

Meadway A, Wang X, Curcio CA, Zhang Y, The microstructure of subretinal drusenoid deposits revealed by adaptive optics imaging. Opt. Express, 2014; 5 (3):713-727. PMID: 24688808

Zhang Y, Wang X, Rivero EB, Clark ME, Witherspoon CD, Spaide RF, Girkin CA, Owsley C, and Curcio CA, Photoreceptor perturbation around subretinal drusenoid deposits revealed by adaptive optics scanning laser ophthalmoscopy. Am J Ophthalmol. 2014; 158(3):584-96.e1. PMID: 24907433

Zhang T, Gordara P, Rivero EB, Griffin RL, Wang X, Curcio CA, and Zhang Y, Variability in human cone topography assessed by adaptive optics scanning laser ophthalmoscopy. Am J Ophthalmol. 2015; 160(2):290-300. PMID: 25935100

Yu Y, Zhang T, Meadway A, Wang X, Zhang Y, High speed adaptive optics for human eye. Opt. Express. 2015; 23(18):23035-52. PMID: 26368408

Lu J, Gu B, Wang X, Zhang Y, Adaptive Optics Parallel Confocal Scanning Ophthalmoscopy. Opt. Lett.. 2016, 41(16): 3852-3855. PMID 27519106

Litts KM, Wang X, Clark ME, Owsley C, Freund KB, Curcio CA, Zhang Y. Exploring photoreceptor reflectivity through multimodal imaging of outer retinal tubulation in advanced age-related macular degeneration. Retina. 2017 May; 37(5):978-988. doi: 10.1097/IAE.0000000000001265. PMID: 27584549; PMCID: PMC5332477

Zhang Y, Wang X, Gordara P, Zhang T, Witherspoon CD, Spaide RF, Owsley C, Curcio CA, Dynamism of dot subretinal drusenoid deposits in age-related macular degeneration demonstrated with adaptive optics imaging, Retina. 2017 Feb 10. doi: 10.1097/IAE.0000000000001504. PMID: 28196054

Xu X, Liu X, Wang X, Owsley C, Curcio CA, Zhang Y, Retinal pigment epithelium degeneration associated with subretinal drusenoid deposits in age-related macular degeneration, Am J Ophthalmol. 2017 Mar;175:87-98. PMID 27986424

Gu B, Lu J, Wang X, Tam J, Twa MD, Girkin CA, and Zhang Y, Noninvasive in vivo characterization of erythrocyte motion in human retinal capillaries using high-speed adaptive optics near-confocal imaging, Opt. Express 9, 3653-3677 (2018). https://doi.org/10.1364/BOE.9.003653, PMID: 30338146 PMCID: PMC6191635

Lu J, Gu B, Wang X, Zhang Y, High-speed adaptive optics ophthalmoscopy with anamorphic point spread function. Opt. Express. 2018, 26(11): 14356-14374. https://doi.org/10.1364/OE.26.014356, PMID: 29877476 PMCID: PMC6005671

Zhang Y, Wang X, Sadda SR, Clark ME, Witherspoon CD, Spaide RF, Owsley C, Curcio CA. Lifecycles of individual subretinal drusenoid deposits and evolution of outer retinal atrophy in age-related macular degeneration. Ophthalmology Retina. 2020;4(3):274-283.PMC7065956

Zhang Y, Wang X, Clark ME, Curcio CA, Owsley C. Imaging of Age-Related Macular Degeneration by Adaptive Optics Scanning Laser Ophthalmoscopy in Eyes With Aged Lenses or Intraocular Lenses. Transl Vis Sci Technol. 2020; 9(8):41. Published 2020 Jul 29. PMID: 32855887, PMCID: PMC7422803

2022 Dr. Zhang was awarded a new NIH R01 grant to support his research on retinal hemodynamics using novel adaptive optics ophthalmoscopy.

2021 Dr. Zhang receives the Catalyst Award from Research to Prevent Blindness

2007 R&D 100 Awards, MEMS-based Adaptive Optics Scanning Laser Ophthalmoscope