Conducting Advanced Treatment and Research on the Front Lines of Ophthalmology

2022/09/22

More than 104 years since its establishment, the Department of Ophthalmology at the Keio University School of Medicine appointed Professor Kazuno Negishi as its seventh department head in 2021. Here, she shares how she plans to guide one of the country's most storied departments of ophthalmology, which research projects she's focused on, and what the future of ophthalmology may hold. She opens up about her time as a medical student, when she was admittedly more concerned with club activities than academics, and shares her hopes for the next generation of aspiring doctors.

“I was making the rounds as a medical student and happened to train at the ophthalmology department when I saw a cataract operation being performed. It was just so beautiful," she reflects. This is Professor Kazuno Negishi's rather surprising answer to why she decided to become an ophthalmologist.

“Replacing the patient’s cloudy white or browned lens with an artificial lens transformed their eye into something sparkling, limpid, and truly beautiful. The day after surgery, the patient wept with joy when they removed the protective eyepatch. They reached out to shake the hand of a resident who hadn’t even been involved in the surgery, saying, ‘Thank you for letting me see again. The thought that such a beautiful operation could bring so much joy to a patient in need inspired my decision to go into ophthalmology.”

Professor Negishi had always loved mathematics and physics and contemplated entering not the School of Medicine but the Faculty of Engineering to work on robots and other devices. But then she experienced the sudden loss of a family member who died very young. “It was terribly shocking, and I didn't want to see the same thing happen to anyone else. That's when I decided to become a doctor.”

And so she made the quick decision to change direction and entered the Keio University School of Medicine. “I always had an interest in surgery and knew it was something I wanted to pursue from the moment I entered Keio. I was considering obstetrics and gynecology as there were few female doctors in the field at the time. I was also drawn to ophthalmology because of my interest in the eye itself, having been in awe of the miracle of sight since childhood. Pediatrics was also a possibility because kids are just so cute, although I would have gone the route of pediatric internal medicine.” It was then that Professor Negishi encountered the "beautiful" surgery of ophthalmology.

Her road to becoming an ophthalmologist took many twists and turns. For more than 30 years since her time as a student, Professor Negishi has devoted herself to the medical treatment, education, and research of cataracts and other lens diseases in addition to refractive surgery. She has spent her career at the forefront of ophthalmology, performing approximately 900 surgeries each year. Last spring, she assumed leadership of the Keio University Department of Ophthalmology.

The Department of Ophthalmology at Keio is currently home to approximately 150 doctors, graduate students, researchers, and part-time faculty members—that number rising to 200 when including affiliated hospitals—who are working day and night to provide medical care, education, and research.

Each research group is actively engaged in world-leading advanced projects, which include: gene therapy for hereditary retinal diseases, for which expectations are rising as the research nears clinical trials; cornea-focused regenerative medicine using iPS cells; and ophthalmological optics research.

One focus that has gained considerable attention is their research on myopia, an issue on the rise globally, especially in East Asia. In 2021, Professor Negishi and others led the establishment of the Division of Comprehensive Myopia Care and Research. This integrated division covers everything from controlling myopia onset and progression to refractive and cataract surgery, providing an environment that allows them to dedicate even more effort to myopia treatment and research.

Keio's Department of Ophthalmology is known not only for its research but also for its traditionally strong emphasis on clinical practice. “As has always been the case at Keio, the department believes it should be on the front lines of its field, capable of handling any clinical challenge that comes our way. There was a time when the Department of Ophthalmology had to close some of its specialized outpatient clinics to focus on areas like the cornea and dry eye, but we have once again established a practice that covers almost all areas of ophthalmology. I believe this is of great significance for professional development inside the department. We are committed to ophthalmic medicine in all aspects, from medical treatment and education to research and innovation.”

Among the vast field of ophthalmology, ophthalmological optics has made dramatic progress over the past two decades in unraveling the physiology and function of the eye.

Somewhat surprisingly, it was a technological innovation in astronomy that became the catalyst for this new field of ophthalmological optics.

"A longstanding problem with observing space from Earth has been that the stars appear to twinkle due to atmospheric turbulence, causing them to blur when viewed through a telescope. This problem gave rise to ‘adaptive optics,’ a technology that compensates for atmospheric turbulence so that light comes into focus when it reaches an observation device. Simply put, we can now build telescopes with very high resolution. The Subaru Telescope, operated by the National Astronomical Observatory of Japan in Hawaii, uses this adaptive optics system.”

Around 1999, adaptive optics began to be applied to the microscopic observation of living organisms, and from there, ophthalmology research entered a new phase. “Until now, fundus photographs, for example, only showed us a rough image of blood vessels, but it is now possible to analyze the retina down to the cellular level.”

Combined with her natural love of physics and mathematics, Professor Negishi says that she was immediately drawn to this new adaptive optics-based ophthalmology. And participation in conferences at the forefront of the field across Europe and the U.S. helped drive her research forward. The results of her research are now being used to evaluate and improve quality of vision for conditions such as double vision or for patients who cannot see clearly despite otherwise good vision. Her research findings also help inform the development of medical devices to elucidate these issues and improve surgical devices.

“Advances in ophthalmological optics have enhanced ophthalmology diagnostic equipment and helped improve ocular function in patients following cataract surgery. In the future, it may even be possible to restore visual function that has deteriorated with age, offering the ultimate treatment in rejuvenation care. Although we still have a long way to go, I believe ophthalmologists have an essential mission to not only treat eye disease and prevent blindness but also contribute to the pursuit of quality of vision.”

How will the role of ophthalmology change in a future society where the expected lifespan could reach 100? “People get 80-90% of their information from their vision, so a decline in visual function leads to a significant decline in quality of life. We also know that vision loss is closely related to several risks, including cerebrovascular disease, dementia, bone fractures, and falls. As Japan becomes a super-aging society, expectations for ophthalmic care directly related to healthy longevity will increase.”

In recent years, Professor Negishi and her colleagues have also been studying the impact of eye diseases on overall health and quality of life. “For example, it is well known that some patients with cataracts experience sleep issues. The human body naturally secretes melatonin via OPN4 (melanopsin) in the retina in response to blue light exposure to maintain its circadian rhythm, which can be disrupted when the amount of blue light that reaches the retina is reduced due to cataracts. It has been demonstrated that cataract surgery not only improves visual function but also remedies related sleep disorders and reduces the risk of developing MCI (mild cognitive impairment).”

Moreover, the Department of Ophthalmology has published studies showing that walking speed and motor function improve after cataract surgery, and outcomes may enhance patient happiness and satisfaction as defined by the Subjective Happiness Scale (SHS).

“Eye and vision care offers valuable medical treatments that can improve overall health. As an ophthalmologist, I wish this information was more widespread. I would also like to enhance our systems for research and treatment so that we can fully contribute to healthy longevity and an improvement in quality of life.”

Professor Negishi has spent most of her career as an ophthalmologist at Keio University Hospital. We asked her what she likes most about Keio as a doctor, researcher, and educator.

“Well, many professors here personify the School of Medicine's philosophy of unifying basic and clinical science in medicine. In education, we also aim to train physician-scientists who are research-minded, and they get to experience our top-class facilities during their clinical training. This is the kind of environment that only Keio can provide.”

She also says that through her various experiences, she has come to realize the wonders of the “Keio network.”

“The School of Medicine’s Sanshikai and Keio University’s Mita-kai alumni associations have been beneficial in many aspects, such as facilitating introductions, joint research, and data collection. I’m so grateful to have such a reassuring network of support, both tangible and intangible, not only throughout Japan but also in many places abroad. And strange as it may sound, even when meeting someone for the first time, you get a warm feeling of being a part of the same Keio family. I never really thought about it as a student, but I believe that the philosophy of the ‘Keio community’ is yet another wonderful asset of the university.”

Professor Negishi also mentions her special connection with the School of Medicine Orchestra. “I shouldn't say that I was more focused on music than coursework [laughs], but no matter how many years pass, I still feel as close with the members of the orchestra now as I did then—with my seniors, juniors, and fellow classmates. Many of us still work together, including on the Faculty Board, so we help each other and cooperate in any way we can. I realize that the friends and the connections I made as a student are irreplaceable.”

Lastly, when asked to offer her thoughts to the next generation aspiring to careers in medicine, Professor Negishi utters an audible “hmm...” After thinking for a moment, her expression turns serious.

“Some students enter the School of Medicine without giving it much thought simply because they have good grades and are encouraged to go to medical school,” she says. “That’s fine if it aligns with the student’s own desires, but once the medical coursework begins in earnest, only then do some students realize that this isn’t at all what they want to do. That’s why I want anyone thinking of applying to medical school to ask themselves if they are truly motivated to become a doctor for the right reasons.”

She also notes that working as a front-line physician day in and day out can be very demanding, even for the most motivated individuals. "It is a fundamentally hectic job, and I often can't control my schedule the way I’d like. Above all, it is a job with great responsibility and no room for failure. Moreover, medicine is a never-ending pursuit. A doctor has to be a lifelong learner. I hope students fully understand that this is the job description and that they should not continue if they can’t fully commit themselves.”

We asked Professor Negishi about her source of inspiration, the force that has kept her pushing forward for more than 30 years. “When I say doctors must be lifelong learners, what I mean is that medicine is constantly evolving. When it comes to progress, there is no profession more interesting, and I believe it is a job worth devoting your life to. My days are indeed full, but whether I’m working in the lab or the clinic, I always tell myself that the harder I work right here and now, the better I can serve my patients. And if my patients are happy, I'm happy, even if that is just me tooting my own horn. [laughs] In all honesty, though, I just want my patients to be happy, and I feel that is reason enough for me to continue working hard every day.”

"The School of Medicine is a place for those who want to go beyond medicine as merely a profession. Whether you want to contribute to the advancement of medicine through research as a physician-scientist or you have dreams of leading the next generation of medicine, I hope you will consider joining us here at Keio University. I look forward to welcoming you here.”

Kazuno Negishi
Kazuno Negishi graduated from the Keio University School of Medicine in 1988. After working at the NHO Tokyo Medical Center and serving as chief in the Departments of Ophthalmology at NHO Saitama Hospital and Tokyo Electric Power Company Hospital, she became a full-time lecturer in Keio University’s Department of Ophthalmology in 2001. She became an associate professor in 2007 and has served as a professor since 2017. In April 2021, she was appointed Head of the Department of Ophthalmology at the Keio University School of Medicine. She specializes in cataract and refractive surgery and ophthalmological optics. Having served in numerous roles over a successful professional career, she now works as a trustee for the Japanese Ophthalmological Society and the Japanese Society for Cataract Research, Vice President of the Japanese Society of Ophthalmological Optics, and President of the Japan Presbyopia Society.