Optical Coherence Tomography Angiography Based Assessment of Retinal Capillary Density as a Biomarker of Vascular Contributions to Cognitive Impairment and Dementia

Amir H. Kashani, MD, PhD
University of Southern California and Roski Eye Institute ( Los Angeles, CA)
Year Awarded:
2020
Grant Duration:
February 24, 2020 to July 31, 2021
Disease:
Alzheimer's Disease
Award Amount:
$599,286
Grant Reference ID:
CA2020004
Award Type:
Other
Award Region:
US Southwestern

This proposal is funded through a partnership between the Brightfocus Foundation and the National Institute of Neurological Disorders and Stroke (NINDS) (as NINDS supplement 3UH3NS100614-04S1). BrightFocus is supporting this study as a part of the NINDS MarkVCID Consortium, of which Dr. Kashani is one of the Principal Investigators.

Amir H Kashani, MD, PhD

Optical Coherence Tomography Angiography Based Assessment of Retinal Capillary Density as a Biomarker of Vascular Cognitive Impairment and Dementia

Summary

Vascular contributions to cognitive impairment and dementia (VCID) arise from stroke and other vascular brain injuries that cause significant changes to memory, thinking, and behavior. VCID often occurs in and contributes to Alzheimer's Disease dementia. The damage in the small blood vessels is very difficult to detect with conventional testing or brain imaging methods like Magnetic Resonance Imaging (MRI). The goal of Dr. Kashani’s research is to develop new methods using the eye to detect the onset, progression and severity of VCID.

Details

The eye is a unique organ, because the retina is essentially a ‘window’ to the brain, reflecting disease processes in real-time. Dr. Kashani’s research group has developed sophisticated tools using a novel FDA-approved technology called Optical Coherence Tomography Angiography (OCTA) to measure the size, shape and blood flow of retinal capillaries in a living human eye without injecting any contrast agents or dye. They can measure blood flow in the retina within individual capillaries while a patient is in the doctor’s office! Using this method they can detect capillary damage in the retina before doctors can detect the damage during a clinic visit or before patients have any symptoms.

As part of this proposal, funded through a partnership between the Brightfocus Foundation and the National Institute of Neurological Disorders and Stroke (NINDS), Dr. Kashani will use OCTA to measure capillary density and perfusion in the eyes of human subjects who are at risk of VCID. This multicenter study is a one-of-a-kind prospective study to comprehensively assess retinal changes with OCTA and correlate them with brain imaging, neurocognitive and neuropsychological testing in subjects who are at risk. Once the study is complete, they hope to have a novel biomarker to identify people at risk for VCID so that potential treatments can be tested. BrightFocus is supporting this study as a part of the NINDS MarkVCID Consortium, of which Dr. Kashani is one of the Principal Investigators.

About the Researcher

Dr. Kashani graduated medical school from Johns Hopkins School of Medicine where he obtained both his MD and PhD. He is now an Associate Professor in the Department of Ophthalmology and the USC Roski Eye Institute at the University of Southern California, Keck School of Medicine. He is a board certified Ophthalmologist and fellowship trained vitreoretinal surgeon. The focus of his research is to combine clinical practice with novel methods for in vivo measurement of human retinal structure and function that will advance our ability to treat disease before irreversible damage is done. For example, Dr. Kashani’s research team was involved in the preclinical testing of the first FDA approved Optical Coherence Tomography Angiography (OCTA) platform in the United States that is now able to detect capillary damage in subjects with Diabetes Mellitus before clinical damage is apparent. He has developed and implemented several measures of retinal vascular structure and function using OCTA. These include measures of 2-dimensional and 3-dimensional retinal capillary density and morphology. Dr. Kashani was one of the first to use quantifiable OCTA metrics to characterize early stages of retinal vascular disease such as including diabetic retinopathy, retinal venous occlusion, uveitis, and vitreoretinal traction. These methods are being applied in two prospective multicenter studies to assess retinal capillary changes in diseases ranging from diabetes mellitus to small vessel disease and dementia. Dr. Kashani's work has been funded by the National Eye Institute, National Institute for Neurologic Diseases, and the Brightfocus Foundation. Dr. Kashani is also Principal Investigator and surgeon of a first-in-man Phase 1/2a study of a novel stem cell derived retinal pigment epithelium monolayer for treatment of geographic atrophy in advanced dry age-related macular degeneration (AMD). Dry AMD is among the leading causes of blindness in the Western world and currently does not have any treatment. His research has been published in leading peer-reviewed journals including Ophthalmology Retina, American Journal of Ophthalmology, PLoS One, Investigative Ophthalmology and Visual Sciences and Science Translation Medicine. In recognition of his work and contributions, Dr. Kashani has been recognized by his peers as one of the Top 50 International Rising Stars in the field of Ophthalmology and is annually recognized as one of Best Doctors in America.

Personal Story

During graduate school I was fascinated by our ability to look inside individual cells using advanced microscopes and imaging methods to visualize disease processes. I wanted to develop similar methods of assessing disease in human subjects so that we could detect and treat before irreversible damage was done. As a medical student I began to realize this opportunity using a new technology called optical coherence tomography (OCT) that allowed us to see individual retinal layers (sometimes only one cell layer thick!) in living human patients. OCT revolutionized the field of ophthalmology because it provided accurate measurements of retinal pathology that enabled testing and validation of numerous treatment regimens. As an ophthalmologist, I realized early on that OCT is just the tip of the iceberg. With advances in microscopy and imaging methods, we can detect cellular and even molecular level changes in the retina. When these technologies are harnessed to take advantage of the wealth of knowledge that basic scientists have discovered, it becomes possible to rationally target a disease process for accurate diagnosis and treatment. This process of translating basic science and engineering principles into practical medical treatments is the field of translational science and medicine and it is what drives my research to help detect, prevent and treat blinding diseases. The Brightfocus funding has allowed me to harness the collective and coordinated efforts of basic scientists, neurologists, ophthalmologists, engineers, physicists, academia, industry and most importantly patients who are at risk of VCID to develop a novel, non-invasive method of detecting capillary level damage in human subjects before the onset of clinical disease.


3D Animation of Retinal Vasculature from OCT Angiography

 Images with assistance of Dr. Amir Kashani’s lab members Sam Kushner-Lenhoff and Mona Sarabi.

 

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