A New Imaging Technique to Detect Early Markers of Glaucoma

Ji Yi, PhD
Boston Medical Center (Boston, MA)


Manishi Desai, MD
Boston Medical Center
Year Awarded:
Grant Duration:
July 1, 2017 to June 30, 2019
Award Amount:
Grant Reference ID:
Award Type:
Award Region:
US Northeastern

The more I learn about the disease, the more I believe that my expertise can be applied and translate to the field of glaucoma detection and prevention.

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Exploration of Optical Markers for Glaucoma Early Detection


Glaucoma is an eye disease that affects millions of American’s vision.  The best way to slow and stop the disease is to detect it early; however, existing methods are insufficient to do so.  We plan to develop a new optical imaging technology to examine the eye, which is very sensitive to early glaucoma so that we can use it for early diagnosis.  This project not only may benefit many people by helping to prevent blindness, but also could enhance our understanding how this disease develops.


The goal of our study is to develop a novel imaging technique to quantitatively detect earliest onset of glaucoma for use as a potential screening method.  Glaucoma is a chronic condition that has complicated pathology.  Early screening of glaucoma not only can help prevent vision deterioration, but also allows for a better understanding of the cause.  However, there is no reliable and quantitative technique recommended for the general public to detect the early onset of glaucoma.  A quantitative and sensitive detection will help us prevent glaucoma and lead to better treatments.  

Our laboratory focuses on developing novel retinal imaging techniques that allows us to see beyond the anatomical structures.  The central crux of the glaucoma pathology is the degeneration of retinal ganglion cells (RGCs), which has two common early manifestations.  One is the nanoscale structural breakdown of RGCs, and the other is metabolic alterations associated with cell degeneration.  We will developed a novel imaging techniques called multi-functional optical coherence tomography (mf-OCT) that is capable of quantifying nanoscale structures of neural fiber layers and ganglion cells, and the oxygen consumption of the retina, to detect the two early manifestations of glaucoma.  After implementing the mf-OCT using advanced optical engineering, we will conduct a pilot clinical studies to validate the nanoscale structures and the oxygen metabolic alterations are present in glaucoma patients and normal vision patients.  We will perform statistical analysis to produce a quantitative rules for early diagnostic purpose that are based on the detection parameters. 

There are two unique advantages of mf-OCT comparing the other imaging techniques. First, mf-OCT is capable of detecting nanoscale structures down to several tens of nanometers, which is the size of macromolecules.  This level of structural sensitivity is not possible using any existing retinal imaging methods.  Thus, it provides a huge advantage in early detection of ganglion cell degeneration.  Second, mf-OCT can quantify oxygen metabolism in retina, and further indicates the retinal functions, beyond simply imaging the anatomical structures.  The metabolic dysfunction may well proceed the clinical signs, such as thinning of the neural fiber layer and ganglion cell layer, which offers another synergistic marker in addition to the nanoscale structural markers.  These two unique techniques will allow us to explore new markers for early detection of glaucoma.  

The completion of the study will generate direct clinical impact by introducing a new quantitative diagnostic rule for early detection of glaucoma.  The non-invasive nature of mf-OCT imaging makes it an excellent candidate for glaucoma screening for general public.  Being able to detect glaucoma early will not only prevent glaucoma more effectively, but also provide us with a better understanding of the cause of the disease, and therefore help us to develop better treatment strategies.

About the Researcher

Dr. Ji Yi currently is an assistant professor at Boston University School of Medicine.  His research area is to develop novel optical imaging methods for biomedical applications, and in particular early detection of chronic diseases such as glaucoma.  He obtained his BS from Tsinghua University, and trained in biomedical engineering at Northwestern University.  After his PhD, he continued his postdoctoral training at Northwestern University before joining Boston University.  

He is an expert in the field of biomedical optics.  He has pioneered and patented several novel imaging techniques, including visible light OCT (vis-OCT), as well as inverse spectroscopic OCT (IS-OCT) which are two cornerstones of this study.  The major body of his work has resulted in more than 40 peer-reviewed publications in high-quality journals, five approved/pending U.S. patents and numerous international oral conference presentations. 

Personal Story

My PhD training focused on early detection of colorectal cancer and pancreatic cancer using optical imaging methods.  As strange as it sounds, cancer and glaucoma share some common manifestations despite their distinct etiologies and causes.  For example, I found that the nanoscale structural alterations are present both in precancerous cells (ie, cells with higher chromatin compaction), and also in ganglion cells reflecting chromatin and axons disintegration.  Moreover, metabolic reprogramming is a common hallmark in cancer, and emerging evidence suggests that a metabolic alteration may also be present in early glaucoma, including a change of oxygen consumption in glaucomatous retina.  I was really intrigued by the striking similarity of those common markers, and that is one major reason for me to move from the cancer field to ophthalmic applications as I continue my postdoctoral training.  The more I learn about the disease, the more I believe that my expertise on optical imaging and cancer detection can be applied and translate to the field of glaucoma detection and prevention.  Thanks to the BrightFocus Foundation's support.  I will be able to test those common markers in glaucoma, and this study will be a starting point for translating novel imaging techniques, initially developed for cancer detection, to the early detection of glaucoma.  I hope by pushing innovative imaging technology into the field of glaucoma research, this will eventually lead to increasingly effective screening for glaucoma prevention.

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