– FOR IMMEDIATE RELEASE –

Doheny Eye Institute To Receive Funding from NIH Award Supporting Cerebral Small Vessel Disease Detection

Yuhua Zhang, Ph.D., Principal Investigator at Doheny Eye Institute and Professor of Ophthalmology at the David Geffen School of Medicine, UCLA, will lead the development of the next generation of advanced retinal imaging technology to study cerebral small vessel disease with a multidisciplinary team of scientists

PASADENA, CA, October 2, 2024 – Doheny Eye Institute, one of the nation’s leading vision research institutions, announced that Yuhua Zhang, Ph.D., Principal Investigator at Doheny Eye Institute and Professor of Ophthalmology at the David Geffen School of Medicine, UCLA, is among an esteemed multidisciplinary group of scientists to receive a major award from the National Institutes of Health (NIH) Common Fund Venture Program Oculomics Initiative. The $4.7M a year award will be distributed annually for three years among the scientists collaborating to develop a noninvasive ocular imaging approach that can detect and characterize cerebral small vessel disease (CSVD), a common central nervous system disorder that causes failures of blood flow and contributes to vascular cognitive impairment and dementia.

The Team: This effort is a multi-PI collaboration among leading research institutions, led by Jianhua (Jay) Wang, M.D., Ph.D., of the Bascom Palmer Eye Institute at the University of Miami School of Medicine. Dr. Zhang, an expert in adaptive optics high-resolution imaging and retinal hemodynamics, will serve as the principal investigator at Doheny Eye Institute. Dr. Zhang and his team at Doheny’s Advanced Ophthalmic Imaging Laboratory will design and develop the instrument at Doheny Eye Institute. Liang Liang, Ph.D., of the University of Miami Coral Gables, will be the principal investigator leading the development of Artificial Intelligence (AI) enhanced software to facilitate the measurement of the blood flow in the small retinal blood vessels including arterioles, capillaries, and venioles.

Additional Bascom Palmer physicians and scientists include: Hong Jiang, M.D., Ph.D., a professor of clinical ophthalmology and neurology, who will conduct the screening and clinical efforts; Felipe Medeiros, M.D., Ph.D., professor of ophthalmology and vice-chair of research, who will provide expertise in data science, bioinformatics, and clinical studies; and statistician, Robert O’Brien, Ph.D., who will use AI to further improve the methodology.

Other Miller School collaborators include physicians and scientists from the departments of radiology and neurology, including: Tatjana Rundek, M.D., Ph.D., scientific director of the Evelyn F. McKnight Brain Institute; Victor Andrade, M.D., and Jose Romano, M.D., in the Department of Neurology; Pradip Pattany, Ph.D., in the Department of Radiology and Juan Pablo de Rivero Vaccari, Ph.D., at the Miami Project to Cure Paralysis. In addition, John Detre, M.D., professor of neurology and radiology at the Perelman School of Medicine at the University of Pennsylvania, an expert on blood flow in the brain, will consult on the project.

The Scientific Project: Microcirculation in the capillaries is essential for supporting the brain’s intense metabolic activities and maintaining normal brain health. The delivery of oxygen and removal of metabolic waste at the tissue level is primarily accomplished by the red blood cells that compress and flow in single file through the capillaries.  While current technology such as Magnetic Resonance Imaging (MRI) can detect blood flow in larger vessels, it is unable to do so in the much smaller capillaries. As a result, new methods are needed to investigate capillary health – especially as CVSD is understood to play a major role in dementia. Oculomics, which uses the eye as a window into the health of the body and brain, is being explored as a method to help fill this important gap in detecting what is happening in the brain. With this NIH award, the team will develop a new generation of high-speed, widefield adaptive optics near-confocal ophthalmoscope (AONCO).

“The retina offers a unique, non-invasive window into the central nervous system’s vascular system through optical imaging,” noted Dr. Zhang. “Capillary rarefaction — a hallmark of microvascular degeneration — plays a crucial role in the pathogenesis of various systemic diseases and associated retinopathies. It also serves as a predictor of multiple end-organ damage and life-threatening cardiovascular conditions. Nevertheless, understanding functional alterations within the capillary system remains a significant knowledge gap.”

Dr. Zhang further explained, “The pulsatile blood flow in retinal capillaries presents a distinctive biomechanical model for studying microcirculation function at the capillary level and assessing the impact of CSVD on the central nervous system’s microvasculature.”

The rapid fluctuations in blood velocity during a cardiac cycle reflect the time-varying hemodynamic forces and flow impedance experienced by blood cells, as well as the dynamic stress on capillary walls. These factors are crucial for blood flow regulation and vessel structural remodeling. Disruptions in normal pulsatility have been linked to systemic and central nervous system pathologies, with excess pressure and flow pulsatility potentially damaging the capillary network and resulting in target organ damage.

In a pilot study, Dr. Zhang’s lab has developed an innovative adaptive optics near-confocal ophthalmoscope (AONCO) capable of precisely measuring pulsatile erythrocyte flow velocity throughout the cardiac cycle. The characteristics derived from continuous velocity waveforms in retinal capillaries, akin to those used for assessing macrovasculature (e.g., arterial stiffness), demonstrate the potential to identify functional alterations in capillary pathophysiology previously unrecognized. Building on these theoretical insights and experimental successes, the team will develop a new high-speed, wide-field AONCO. This advanced instrument will enable precise assessment of higher-order flow dynamics in retinal vessels of varying sizes, from the largest arterioles to the smallest capillaries, and establish AONCO-measured retinal capillary pulsatile hemodynamics as a sensitive biomarker for cerebrovascular and systemic diseases.

“Assessing microcirculation function by precisely measuring the higher-order hemodynamics of the pulsatile blood flow in retinal capillaries is conceptually innovative and a huge technological advance,” said Dr. Zhang, “Higher-order hemodynamics highlights the ‘dynamic’ aspect of the capillary system’s mechanical property and functional status, extending beyond the measurements provided by existing methods. Unlike traditional approaches, which focus on average velocity and static characteristics such as vessel wall thickness, lumen diameter, and their changes under visual stimulation or gas breathing perturbations, this innovative approach provides a more comprehensive understanding of the microvascular function.”

The NIH award number is OT2 OD038131.

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For more information contact:

Molly Ann Woods
Doheny Eye Institute
310-717-0955