The Role of Capillary Flow and Autoregulation in Primary Open Angle Glaucoma Project Summary This K23 application is submitted by Osamah Saeedi, MD, an Assistant Professor in the Department of Ophthalmology and Visual Sciences in the University of Maryland, Baltimore. My long-term goal is to become an independent clinical investigator focusing on the role of ocular blood flow at the capillary level in the development and progression of primary open angle glaucoma. Towards this goal, I propose a mentored career development plan that includes training in novel techniques of angiography capable of imaging erythrocyte movement and quantification of absolute blood flow; human subjects training; and the conduction of clinical trials. During the grant period I will obtain a Master's o Science in Clinical Research. Primary open angle glaucoma (POAG) is a leading cause of blindness worldwide. Although intraocular pressure (IOP) lowering remains the only proven therapy for the disease, many patients continue to experience irreversible vision loss despite effective IOP-lowering therapy. A critical need, therefore, exists to identify alternative, potentilly modifiable biomarkers for POAG. The proposed research focuses on identifying and developing sensitive imaging biomarkers as they relate to capillary erythrocyte flow. There is strong evidence for a vascular component in the development and progression of POAG. Capillary erythrocyte flow (which differs from bulk blood flow) refers to individual erythrocyte movement within the capillaries, which is closely linked to the metabolic capacity of blood circulations to support the ocular tissues. One of my mentors, Dr. Robert Flower, has developed advanced techniques to evaluate and quantify ocular blood flow at the individual capillary level, using Erythrocyte Mediated Indocyanine Green Angiography (EMA) and Fluorescent Mediated Photo-Photoplethysmography (FM-PPG). EMA permits direct observation of erythrocyte movement within the capillaries and quantification of erythrocyte velocity and motility as well as local hematocrit. FM-PPG is a method that allows for the absolute quantification of blood flow using Indocyanine Green (ICG) angiography. The overall goal of this research is to determine the role of capillary blood flow and capillary erythrocyte flow in POAG.
In specific aim 1, I propose cross-sectional human studies to measure and compare erythrocyte motility, erythrocyte velocity, blood flow, and local hematocrit in patients with POAG, POAG suspects, and controls.
In specific aim 2, I propose cross-sectional human studies to measure the autoregulation of these variables. I hypothesize that patients with POAG have less erythrocyte velocity and erythrocyte motility, lower blood flow, lower local hematocrit, and poorer vascular autoregulation as compared to controls. I further hypothesize that local changes in these parameters will correlate to structural and functional glaucomatous deficits, specifically retinal nerve fiber laye (RNFL) thickness and visual field deficits.

Public Health Relevance

The only proven way to treat primary open angle glaucoma is to lower eye pressure, but many patients continue to lose vision in spite of this treatment. The goal of this project is to develop new tests to measure blood flow in the eye at the capillary leve that will indicate if a patient is developing open angle glaucoma or if their disease is progressing. This will potentially lead to new treatments for the disease that will use these tests to improve blood flow in the eye.

National Institute of Health (NIH)
National Eye Institute (NEI)
Mentored Patient-Oriented Research Career Development Award (K23)
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Special Emphasis Panel (ZEY1)
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Agarwal, Neeraj
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University of Maryland Baltimore
Schools of Medicine
United States
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Saeedi, Osamah J; Chang, Luke Y; Ong, Sharon R et al. (2018) Comparison of cumulative dispersed energy (CDE) in femtosecond laser-assisted cataract surgery (FLACS) and conventional phacoemulsification. Int Ophthalmol :
Rege, Abhishek; Cunningham, Samantha I; Liu, Yusi et al. (2018) Noninvasive Assessment of Retinal Blood Flow Using a Novel Handheld Laser Speckle Contrast Imager. Transl Vis Sci Technol 7:7
Schehlein, Emily M; Im, Lily T; Robin, Alan L et al. (2017) Nonmedical Out-of-Pocket Patient and Companion Expenditures Associated With Glaucoma Care. J Glaucoma 26:343-348
Zhang, Xuemin; Cole, Emily; Pillar, Angelique et al. (2017) The Effect of Change in Intraocular Pressure on Choroidal Structure in Glaucomatous Eyes. Invest Ophthalmol Vis Sci 58:3278-3285
Thiel, Cassandra L; Schehlein, Emily; Ravilla, Thulasiraj et al. (2017) Cataract surgery and environmental sustainability: Waste and lifecycle assessment of phacoemulsification at a private healthcare facility. J Cataract Refract Surg 43:1391-1398
DeVience, Eva; Chaudhry, Sona; Saeedi, Osamah J (2017) Effect of intraoperative factors on IOP reduction after phacoemulsification. Int Ophthalmol 37:63-70
Schehlein, Emily M; Kaleem, Mona A; Swamy, Ramya et al. (2017) Microinvasive Glaucoma Surgery: An Evidence-Based Assessment. Expert Rev Ophthalmol 12:331-343
Saeedi, Osamah; Ashraf, Hasan; Slade, Eric P et al. (2017) Trends in Prevalence of Diagnosed Ocular Disease and Utilization of Eye Care Services in American Veterans. Am J Ophthalmol 173:70-75
Saeedi, Osamah J; Chang, Luke Y; Arora, Karun S et al. (2016) Unilateral Glaucoma Associated with Conjunctival Angioma and Choroidal Thickening without Facial Angioma. Middle East Afr J Ophthalmol 23:280-2
Zhang, Xuemin; Soni, Nishant; Alexander, Janet et al. (2016) Pupillary block due to reverse implantation of a sulcus intraocular lens. JCRS Online Case Rep 4:41-44

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