Women in research

Dream big with Seang Mei Saw, MBBS, PhD, FARVO

Seang Mei Saw is the SERI Professor in Ophthalmology Research at the Duke-NUS Medical School, and a professor at the Saw Swee Hock School of Public Health. She also heads the Myopia Unit at the Singapore Eye Research Institute (SERI) and serves as deputy chair (Biomedical Research) of the National University of Singapore Institutional Review Board. Highlights of her research include elucidating the genes and environmental factors for myopia and pathologic myopia. Saw has published more than 550 peer-reviewed manuscripts in international journals and is the PI and Co-I of grants totaling over $15 million. She previously served as chair (2010) of ARVO’s Annual Meeting Program Committee (Clinical and Epidemiologic Research Section). Currently, she is an associate editor of ARVO’s Translational Vision Science and Technology (TVST) journal as well as an editorial board member of its Investigative Ophthalmology & Visual Science (IOVS) journal.

Join Women in Eye and Vision Research (WEAVR) leadership committee member Amy Lo, PhD, as she sits down with Saw to talk in-depth about her illustrious career journey and research, plus get her take on how to ascend into and sustain positions of leadership.

On behalf of WEAVR, thank you for taking the time to talk with us. Today, I have the privilege to chat with you regarding your career path. What made you decide to go into ophthalmology and specifically myopia research?

Thank you for the question. I was completing my Master of Public Health at the Johns Hopkins Bloomberg School of Public Health and I transferred to the PhD program. My husband is an ophthalmologist, and he was in the fellowship program at Johns Hopkins, thus I was introduced to the ophthalmologists in the Wilmer Eye Institute.

My supervisors said that myopia was a huge problem in Asia and  there was a large trial in Singapore. That was in the 1990s; there was not much interest in myopia, nor were many people involved in this area of research. My supervisors  asked whether I wanted to conduct my PhD within their trial, meaning I would go back to Singapore, help run the study and collect my data. They suggested I look at why the myopia rates are high and examine the effects of near work (i.e., how much reading and writing, how that causes myopia, etc.).

That was my PhD thesis and how I got involved in myopia research. I had a few mentors, including the founder of the Singapore Eye Research Institute (SERI) — the late Professor Sek-Jin Chew. He was very involved in myopia research; he set up SERI and the Myopia Center Clinic. He persuaded me to do a PhD in myopia and my first international paper was the literature review for my PhD thesis.  It is still being cited now (Saw, SM., Katz, J., Schein, O.D., Chew, S., Chan, T. [1996]. Epidemiology of Myopia.  Epidemiologic Reviews, 18[2], 175–187).

When I returned to Singapore after graduating, I joined the National University of Singapore (NUS) and continued my work on myopia because there were many people internationally just doing the basic science experiments and looking at the causes. We established a strong network in Singapore and I was interested in starting a large, long-term cohort. I knew this did not exist at the time in Asia and I thought if I just started a cross-sectional study, the impact would be less.

In 1999, I received funding, assembled a team and the Ministry of Education supported me by selecting three schools where I started a cohort of 1,979 children called the Singapore Cohort study Of the Risk factors for Myopia (SCORM). I investigated the different perspectives and because it was a cohort, I could add new measurements along the way. For example, if there was a new instrument to measure aberration I could add that; I could add sub-studies; I could measure myopic macular degeneration when they were teenagers. Also, I could look at changing and new risk factors, and add new questions.

I spent a lot of time on this cohort and we published more than 70 papers from this study, which is still ongoing. The participants were 7-9 years old in grades 1-3 when I recruited them. We saw them yearly and performed cycloplegic refraction, instilling three drops of 1% cyclopentolate. We did this in the schools, not in a clinic setting, so I had to bring resuscitation CHARLIE, make sure somebody was on standby, etc. We did that every year in the schools until 2007, then the participants went to national service and different universities. I saw them again about three years ago — when they were about 26-28 years old. Currently, I am working with Johnson & Johnson Vision and a few other partners to call them back, so by then I will have 20 years of data.

We published some of our 19-year data (Li, J., Lanca C., Htoon HM., Wong YL., Nyunt SZ., Tan D., Sabanayagam C., Saw SM. [2020, Dec.]. High Myopes in Singapore: 19-Year Progression from Childhood to Adulthood. Ophthalmology, 127(12), 1768-1770), and we now know the natural long cause of myopia from early childhood all the way until they reach almost the final refractive error. We also have fundus photography images and found that even as a young adult, some of them had a tesselated fundus, which is a precursor of myopic macular degeneration.

Wow, as a 20-year-long study, that must have a large impact on the society and for other school kids?

We had a very large team — many optometrists in training who helped us; many ophthalmologists were involved in the study; we wrote several papers together with a number of collaborators. We also combined our data with the RESC studies in Malaysia and the ALSPAC cohort in the UK.

In 1988, we started a six-year parallel cohort in Xiamen, China, with the Xiamen Eye Institute — we had two schools in the city and two schools in the country — using the same instruments. In the beginning we found much lower rates of myopia in China. However, that has changed tremendously; the rates of myopia are extremely high now in China. Indeed, we did have a glimpse of what was happening more than 20 years ago.

Do you think there may be different influences depending on the geographical location?

I think it is primarily environmental. In Singapore, we traced the rates of myopia, which have increased from about 30% to approximately 83% in adults. In 2018, we refracted 28,000 national service men (cycloplegic refraction was compulsory) and we found those rates have increased in the past 30 years. The gene pool has not changed very much in our country, but we gained independence about 56 years ago and our education system has changed. It is more intensive, there is more homework and children attend extra classes in tuition centers. Thus, the near work activity and outdoor activity has changed along with the education system.

How do you see your research expanding then in the next 10-15 years?

I wrote a perspective article in IOVS about a year ago looking at the prevention of high myopia. Myopia is very common in urban Asian cities, about 80-90% of the population is myopic with around 15% being highly myopic. The WHO (World Health Organization) definition is more than -5 diopters. We have established that high myopia and more severe myopia is related to visually disabling complications, such as pathologic myopia and myopic macular degeneration. Pathologic myopia may cause a reduction in visual function, it may affect your emotions as well as your quality of life and it can cause a visual impairment. This disease is age related and because we found that age-related pathology myopia may be visually disabling, in the past decade or so the topic myopia has attracted a large amount of interest, especially amongst ophthalmologists. Knowing that high myopia may cause pathologic myopia, myopia  is no longer regarded as a benign ocular disease, whereby you will just wear spectacles and contact lenses to correct your vision.

Our SERI team conducted a study of 8,000 adults, called the SEED Study, where we examined myopia in more than 8,000 fundus photographs. From this we know that even if you do not have high myopia, with mild and moderate myopia you still have a risk of myopic macular degeneration, but that risk is lower. Once myopia is much higher, that risk increases. If you are older, especially over 70, again that risk increases.

So, we want to prevent blindness and visually disabling diseases. I have now developed a three-pronged strategy:

1. The first strategy is primary prevention — I want from the outset to prevent myopia from developing, especially in children. Myopia is a lifelong disease; once you have developed myopia you are never cured, you remain myopic forever. Usually the onset is in childhood, unlike other diseases like cataracts and glaucoma where the onset is in adulthood. In Singapore, the average age of onset of myopia is eight-and-a-half years old and 10% of preschoolers are myopic.

I have written a few papers on how early onset myopia gives rise later to an increased risk of high myopia. If you develop myopia in kindergarten or in preschool, your myopia will continue progressing until about 25 years old. Thus, your final myopia value at adulthood  will be quite high. Even if you develop myopia later in primary school, before the age of 10, your risk of high myopia is much higher. You want to prevent myopia from occurring early in life, and especially in preschoolers. If a very young child has myopia, I think that it potentially can be a very serious disease and the parents should take extra care. We want to prevent it. The major risk factor, which is preventable and modifiable, is outdoor time. The evidence from large community trials is good; we want to encourage the provision of opportunities for outdoor time in the schools and providing parents or families with the capabilities to increase outdoor time for the children.

2. The second strategy is secondary prevention or treatment. If we see a very young child with myopia, we need to predict the possible progression of myopia and risk of high myopia later in life. A large proportion of my work now is on precision medicine. We have set up myopia clinics that might be run by ophthalmologists or optometrists in hospitals for example.  Not all children, especially in east Asia where 80% are myopic, have the same risk of myopia. We cannot treat all 80%, that is almost the entire population. So, we need to predict and differentiate between a high-risk and low-risk child.

If we can identify factors which could be genetic and develop a polygenic risk score — it could be environmental, it could be ocular (e.g., the age of onset of myopia, the baseline refraction, or the initial myopia progression) — if the eye care professional can differentiate, then they can tailor the treatment for myopia progression.  The pattern of progression is not the same for every child; the start and end point is not the same for every child. If a child is high risk and we think there is very high risk of low vison later in life, then we would suggest more aggressive treatment. For example, combining atropine eyedrops with another treatment, such as novel contact lens or spectacles. Then we might advocate a longer duration of treatment, to cap the myopia progression and  ensure it is controlled for a longer period.

You do not want to stop  the treatment early, because progression occurs for a long time. Instead, you might think of sequential treatment. For example, when the progression is very high in young adults, you might want to give atropine. Or, especially in girls when they are teenagers, they are happy wearing contact lenses and the progression is not so fast. So, tailoring is the second approach.

3. The third approach is tertiary prevention when the person as an adult already has the pathology of myopia. That is the really difficult question to answer, and we are still looking at biomarkers — the choroid, the sclera, the remodeling and the shape of the eye — to try to predict which high myope may develop that pathology, as not all of them will (only 30% of the high myopes in our study developed myopic macular degeneration). Then we think about how to treat them. My colleagues are doing scleral crosslinking work in rabbits. Hopefully, we can translate that to humans.

In addition, we are moving into digitalization — AI (artificial intelligence) analysis and diagnosis of myopic macular degeneration, as well as personalized treatment using AI. The other frontier is the FitSight tracker I invented in 2014 to document minute by minute whether a child is outdoors or indoors. In that variable there is a target of two hours per day outdoors that will encourage the child to go outside. We also use it in our research studies, where we obtain minute-by-minute readings.

Very impressive! You have achieved so much in research, but you have also been assistant dean, vice dean and deputy co-chair. What made you go into these leadership roles?

I think there is a place for women in leadership positions. In universities there are many female faculty members and I think they look up to female leaders to be an inspiration. It would be good if a female leader could speak up for them, be a mentor and understand the special situation women have. Women may have families and children as well as responsibilities at home. In that aspect, I think having women in leadership positions will allow for flexibility and understanding. We want to see equal opportunity available in all aspects of research and academic life.

I also think women should have a more long-term view of their career. Even though in between there might be some other commitments or responsibilities, if you know what your goals are and you aim for them, you can assume these leadership positions at the peak of your career. Then you can help and develop programs for many other women as well.

Currently I am deputy co-chair of the National University of Singapore’s Institutional Review Ethics Board. We review applications to ensure the protection of research subjects, which is a very important responsibility. However, with that responsibility we also guide many of the researchers with their ethics applications, including PhD students and young female researchers.

You mentioned female researchers or professors should have some long-term view about their career. How do you strike a balance though between career and other responsibilities such as family?

I think it is important to spend time with your family. Time management will help to prioritize what you need to do at work — to determine whether something requires a lot of time or can be done quickly; to make the right decision to get involved in the right projects at the right time; to find the right team and collaborators; to do work that will make a difference and is groundbreaking, so high-quality research work.

Also, really look after your family because having a happy family helps in your work as well. So, it is all connected! It is important to have that balance and flexibility (e.g., if sometimes you need to work part time, or from home, or work flexible hours). If you need to bring your child to see a doctor or someone, then you need that flexibility and to have bosses who understand that. That is why we need women in leadership positions who have gone through the same situation, and they understand if you have children that you need to spend some time with them.

I think if women have a long-term view, then if they are not so involved for a couple of months or years, they know they will get back to their career full-time. We will need more perseverance. Maybe you find you are not so far ahead because you are involved in other responsibilities of your life, then you will need to be bolder. So, there might be more setbacks for women in their career, whether minor or major, but when everything is settled and you can spend more time in your research career, you can bounce back and catch up. You can continue what you have done before and do it even better than the rest. I think the ability to persevere for a long time is important so you can sustain it long term.

So, it is not an easy journey?

The journey is not easy, and you must be able to take risks because we learn from the mistakes we make and failures. We must be able to pick ourselves up and if we have that ability, then we can continue with our journey and again progress in our careers, assuming those leadership positions.

Have you encountered any problems when you were trying to get these leadership roles?

When I was asked to be assistant dean, I was trying to build up my research career. I was at that time writing many grants, getting funded, etc. So, there was a tussle between whether I should spend more time on administration — that led to my position as vice dean of research — or to really expand my research program. At the end, I did both and continued teaching as well.

Quite often, at the point your research is very successful that might be about the same time you may be asked to assume those positions. You need to rethink how you want to continue your research career. For research, it is important to continue to write papers, to work together closely with a team and to really keep up with the latest knowledge in the area, so what you do will be of added value and will be groundbreaking as well.

It will be not easy to achieve so much, just like you. For a  young woman who is trying to begin her career in ophthalmology, do you have any advice for her?

Dream big and have a passion for what you do. Ultimately there is a better goal of helping others and knowing that what we find can improve the vision of others in society and your patients. Having that passion will keep you going even if there might be a few setbacks, especially as a woman. Your research career may be more demanding or more difficult, and you may face more challenges than others, especially if you have a family and children. But manage your time well, so you have a good work life balance and are still able to continue your passion at work and to persevere as well.

Do have any additional advice for our ARVO members who are women in ophthalmology?

When you start off your career with that passion and you pursue it and continue to persevere, as a woman, if you have a family, it is important to manage not only your time but your stress and be able to cope with it. Have downtime and hobbies as well, otherwise you also must manage how intensive your schedule might be. You need to look after yourself, prioritize well and manage your time in all aspects of your career.  If you face difficulties and setbacks, get support from your mentors, colleagues and your team. A network of collaborators and supporters is very important.

I have certainly learned a lot! On behalf of WEAVR, we thank you for taking the time to talk with us about your career path and giving us all this career advice.