Siyu Chen, PhD

What inspired you to pursue a career in ophthalmology?

There is a saying, echoed in both Western and Eastern cultures, that the eye is the window to the mind. Though intended figuratively, it also carries a physiological truth. The eye is, in many respects, an extension of the central nervous system.

My research career began in brain imaging, using optical microscopy to study blood perfusion changes in small animal models during sensory stimulation. During my PhD, I worked on visible light optical coherence tomography (vis-OCT), a functional extension of the OCT technology widely adopted in ophthalmic clinics. By detecting differences in the wavelength-dependent light attenuation of oxygenated and deoxygenated hemoglobin, vis-OCT has the unique capability to measure blood oxygen saturation in the retinal circulation. It soon became clear that altered delivery and consumption of oxygen is not only caused by retinal pathologies, but also reflects a wide range of systemic conditions. It has been striking to realize how much can be learned about the rest of the body simply by imaging the eye, ranging from systemic metabolism to cognitive disorders. What truly inspires me is that the eye offers a window into neuronal physiology, signaling, and disease pathology all in one place, and that this window is accessible through non-invasive optical imaging. It is a rare combination of biological information and accessibility, and it has shaped the direction I want my career to take: to integrate science, engineering, and medicine in service of accessible, precision-guided medical care that improves people’s quality of life.

What has been a defining moment in your professional journey?

As a researcher trained in biomedical engineering, my default instinct had long been to develop instruments with ever-higher performance capabilities. A turning point came during a group meeting when my postdoctoral mentor, Prof. James Fujimoto, told us, “We need to think like scientists, not as engineers.” He did not mean it as a slight to engineers. He meant that true innovation is not about building something simply because we have the skills and believe we can; it is about identifying and addressing unmet needs that genuinely benefit people.

That perspective has stayed with me, and it is especially relevant in medicine. It has shaped the direction of my work, which focuses on ophthalmic imaging methods with strong translational potential and clinical utility, whether through earlier diagnosis, more sensitive monitoring of disease progression, or better evaluation of treatment response. My hope is that with earlier detection, a deeper understanding of visual physiology and disease mechanisms, and more reliable trial endpoints, our work can help accelerate the development of therapies that preserve or restore vision for the millions of patients affected by vision-threatening disease. This conviction has also shaped how I build collaborations. Much of my recent research is anchored in close partnerships with clinician-scientists, which keeps the engineering grounded in genuine clinical priorities and, I hope, improves the chances that what we develop will ultimately reach the patients who need it.

What makes this community unique compared to other professional organizations?

IntRIS is unique in being a tightly knit family of clinicians and imaging scientists. In contrast to larger ophthalmology professional organizations such as ARVO and AAO, it offers a far more intimate setting for interaction. The Annual Symposium is a great example: world-leading experts, thought leaders, early-career researchers like myself, and trainees all share the same forum. The atmosphere is informal enough to invite genuine, critical discussion. As we all know, it is constructive criticism that ultimately propels science forward.

Another distinguishing feature is how deeply interdisciplinary the community is. While most major conferences organize their sessions along narrowly defined technical fields, IntRIS brings people together across fields and imaging modalities, from preclinical studies to large clinical trials, and from optical methods such as optical coherence tomography to ultrasound and magnetic resonance imaging. This reflects the multifaceted nature of modern retinal imaging research, and it is one of the reasons the conversations here feel uniquely productive. I always come back with a better understanding of the current unmet needs in our shared effort to combat vision-threatening diseases, and inspired by new ideas to test in my own lab. For an early-career researcher, the candid feedback and direct access to senior figures across the field that this community offers have been genuinely beneficial, and the collaborations and friendships fostered here continue to shape both my scientific perspective and my professional trajectory in ways that would be difficult to find elsewhere.

What is one change or improvement you would most like to see in ophthalmology?

I will admit I am biased on this one, but I would love to see ophthalmic care move toward more objective and quantitative assessment of visual function.

Many promising clinical trials have failed not because the therapy lacked efficacy, but because the outcome measures were not sensitive or reliable enough to detect it, representing many missed opportunities for patients. Trials are also extremely expensive, and for slowly progressing diseases such as age-related macular degeneration, current visual endpoints often require very long follow-up before a beneficial effect can be demonstrated. My hope is that with more sensitive and reliable markers of visual function, we will be able to better track disease-related visual changes and more accurately evaluate responses to treatment. This would allow more therapies to be rigorously tested, increase the number that reach regulatory approval, and ultimately bring more options to patients.

This is also the direction in which I have oriented my own research program. By developing functional imaging biomarkers (e.g., for objectively quantifying photoreceptor responses to light over a clinically meaning retinal area) that capture early and reversible changes in retinal physiology, I hope to contribute tools that improve our ability to detect disease earlier, stratify high risk patients, and identify those most likely to benefit from treatments. In the longer term, such markers could underpin a more individualized model of ophthalmic care, in which treatment decisions are guided by objective, quantifiable imaging results rather than coarse tests such as visual acuity. Contributing to that shift is one of the most meaningful goals I can imagine for my career.

Please share your top 5 retinal imaging papers from the past year that you believe had the greatest impact on the field.

The first two papers are from my postdoctoral work under the supervision of Prof. James Fujimoto. We identified and investigated structural OCT and OCT angiography (OCTA) imaging markers that are closely linked to the underlying physiological and pathological mechanisms. We expect that such mechanistically grounded markers can meaningfully improve their clinical interpretability.

• Chen S, Moult EM, Zangwill LM, Weinreb RN, Fujimoto JG. Geometric perfusion deficits: a novel OCT angiography biomarker for diabetic retinopathy based on oxygen diffusion. American Journal of Ophthalmology. Feb 2021;222:256-270. doi:10.1016/j.ajo.2020.09.007

• Chen S, Abu-Qamar O, Kar D, et al. Ultrahigh resolution OCT markers of normal aging and early age-related macular degeneration. Ophthalmology Science. Sep 2023;3(3):100277. doi:10.1016/j.xops.2023.100277

The following three papers are from my recent work on functional imaging of photoreceptors. We developed split-spectrum amplitude-decorrelation optoretinography (SSADOR), an OCT-based, integrated hardware-software approach that objectively quantifies photoreceptor responses to light stimuli. Because SSADOR is compatible with most existing OCT configurations, it carries strong translational potential. In what are, to our knowledge, the largest optoretinography clinical studies to date, we demonstrated its ability to detect photoreceptor dysfunction in both inherited retinal diseases and age-related macular degeneration.

• Chen S, Ni S, Jiménez-Villar A, Jian Y, Jia Y, Huang D. Optical coherence tomography split-spectrum amplitude-decorrelation optoretinography. Optics Letters. Aug 1 2023;48(15):3921-3924. doi:10.1364/OL.492178

• Wongchaisuwat N, Amato A, Yang P, Everett L, Pennesi ME, Huang D, Chen S. Optical coherence tomography split-spectrum amplitude-decorrelation optoretinography detects early Central cone photoreceptor dysfunction in retinal dystrophies. Translational Vision Science & Technology. Oct 1 2024;13(10):5-5. doi:10.1167/tvst.13.10.5

• Zhou L, White E, Matteson A, Andrews A, Bailey ST, Lujan BJ, Jia Y, Huang D, Chen S. Split-spectrum amplitude-decorrelation optoretinography detects impaired photoreceptor function in age-related macular degeneration. Ophthalmology Science. Accepted