Women in research

Aim high ― M. Francesca Cordeiro, MD, PhD

M. Francesca Cordeiro, MD, PhD, is a clinician-scientist, chair of ophthalmology at the Imperial College London, professor at University College London (UCL), honorary consultant ophthalmologist & director of the ICORG Clinical Trials Unit at the Western Eye Hospital London, and recently founder and director of Novai Ltd. — a start-up company based on DARC (Detection of Apoptosing Retinal Cells ) Technology. Her research, funded continuously by the Wellcome Trust since 1996, focuses on translational approaches to saving sight and reducing disability, with over 190 peer-reviewed publications. She has received a number of international awards for this work, including the GG2 Diversity Award for Outstanding Achievement in Medicine 2017 and 2019 Duke Elder Award (RCOphth) and is frequently asked to give keynote lectures abroad. Passionate about eye research and its funding, Cordeiro is also a trustee for Fight for Sight/Vision Foundation.

Cordeiro sat down with Women in Eye and Vision Research (WEAVR) leadership committee member Neena Haider, PhD, to talk about her journey into ophthalmology, her passion for translational research and and her advice for young women considering careers in the field.

It is so exciting to do this interview! Let's start with what was your inspiration for becoming a clinical scientist and particularly in the field of ophthalmology?

Going into ophthalmology was inspired really because it was a good choice between doing surgery and medicine. I always associated an ophthalmologist as being like a thinking surgeon. Initially I was drawn to neurology, so neuro-ophthalmology was very high in my sights. At medical school we used to have what we call short electives, where you do an elective period of study. I did mine, I think the year before finals, with Professor Alan Bird at Moorfields Eye Hospital and anyone who has ever had any contact with him will know that his work is inspirational and he really did get me thinking about the field. The other side is, I come from a family of doctors on my mother's side and one of my uncles was an ophthalmologist in Canada. So those two things drove me and I was fairly ambitious about that, knowing that maybe neuro-ophthalmology was going to be my field.

Following this I managed to pass two important exams, which narrowed my focus and propelled my career into ophthalmology. The first exam I did was the membership of the Royal College of Physicians and then I went straight on to do FRCOpth, which is part of The Royal College of Ophthalmologists.andpassed both exams within a short span having managed to get jobs providing just the right experience to allow me to pass those exams with the minimum amount of time needed. At that stage (my focus) was all on just going to become an ophthalmologist.

Then I began getting interested in research and started publishing clinical type papers. At the time, in the U.K. system, you had to shine above your peers if you wanted a very good consulting job, your attending position. So, I started my PhD and was very lucky I got funding straight away from Guide Dogs for the Blind due to some of my mentors at St Thomas' Hospital in London. Then my research was done at the Institute of Ophthalmology, which is basically where I've been since 1994.

So I've always had an interest in basic science research translating to clinic. I think all of my projects, even my PhD in those early days, involved translation. I might start off with a basic science question and then immediately go on to how that could be moved to patients. And that is still very much what my lab at the UCL does, but also because I'm director of the clinical trials unit now at the Western Eye (Hospital) it has allowed me to see some really nice translation of varous technologies from pre-clinical stage through to early clinical phases.  So, it's been an interesting journey, but that has dominated now what I see as my greatest passion — translation to the patient.

That is beautiful and inspiring. Can you tell us a little about what you are working on now and what's next for you professionally?

One of my babies has been the DARC technology, which is a way of picking up stressed and apoptosing cells at the back of the eye and using this to look at disease activity. That was funded initially through the Wellcome Trust — over four million pounds were from them — which allowed for the next stage, which is commercialization. So a main focus now is a start-up called Novai Limited which is using that technology to help pharma companies around the world test their drugs in AMD (Age-related Macular Degeneration), GA (Geographic Atrophy) and glaucoma, predominantly, amongst other diseases like diabetic retinopathy and more recently inherited eye disease.

That's very exciting because the goal is to try to get DARC recognized as a surrogate endpoint so it can be integrated as a decision-making support tool for every clinician. And that would mean you could use it to find the best or most appropriate treatment for your patient as well as eventually, when we have enough data, to use it as a screening tool. Currently it's intravenously given, but we've got a nasal formulation under development, which means it will be totally non-invasive. In a well-man screening scenario, you could use DARC to look not only at diseases of the eye, but also my other big thing — and I think this may go back to my days of wanting to consider neurology — of using the eyes as a window onto the brain. Because I've always been interested in Alzheimer's, Parkinson's, MS and their retinal manifestations.

Then my newest thing is a little bit different. Obviously, like everybody else, I have AI aspects in my research, I think we're all on that bandwagon. I've become increasingly interested in microglia and the microglia interaction with neurons. That's going to be sort of the next chapter of my basic science research. Also, another Wellcome Trust grant, which has taken an inordinate amount of time to translate, is eye drops we developed with Lucentis. We haven't actually reached the clinical trial stage of that yet because everything was held back by COVID. Our manufacturing factory that was going to make the eye drops shifted to manufacturing the vaccine and so years have been spent trying to find an alternative manufacturer.

And then there are other things that I'm interested in, such as looking at tear fluid diagnosis; looking at how one can improve things for visually impaired people and working with others to do that. I'm a trustee for the Fight for Sight charity, which is tryingthe leading U.K. charity dedicated to stopping sight loss through pioneering research.

These all sound very exciting! Each of these aspects are all different, but related to your passion of bringing things to the patient. Can you tell us what's the best advice you were given and received as a young female scientist?

This is not just for science, but I think it was the doctrine my father gave me, which was 'aim high and always do one's best'. And I think that's the thing I give to all the people who I mentor, which is you probably don't realize how good you are. And that often holds people back from aiming high because there's a bit of under confidence. I think if you do your best, whatever the results, you're not going to look back in hindsight with regret.

The other thing, and I believe with age I appreciate it much more, is the more you know, the more you realise you don't know. I'm the first person who would hold up their hand if I don't understand something; I will ask a question because I'm not embarrassed to admit that I don't know something. Often it's the underconfident people who think, "Oh my gosh, I can't possibly ask that question because they'll think that I haven't got it." But that's the wrong attitude in the world where you're learning and you're trying to help people; you need to help yourself first. Being honest with yourself and with others about where the gaps are in your knowledge is the best thing you can do. That's what a scientist should be doing, asking questions. A clinician-scientist asks questions in a way that's to try and help the patients. I think also that you're really looking at what can you stretch in knowledge that you could be part of.

I think that's fantastic! To expand, what advice would you give to young females who are considering a career in ophthalmology?

I would suggest it's a very rewarding career. The system in this country is just about to change again. We've had in my professional career three or four different changes of how the training is to be done. However, I still think your ability to realise whether you want to do research should not be at the end of your training. I think it needs to be at the time that you're in the middle of the training and I think this is where we're missing out in this country. I'm not sure about America but from some of my friends (I understand) it may be the same where this brand of being a clinician-scientist is becoming less and less prevalent because there are not enough trainees who want to do both. Most of them will say, "I've worked really hard, I want to be an ophthalmologist, I want to earn my money as an ophthalmologist." Or if you're into the science side, you may never want to go back into training as a clinical person.

So, I think it is difficult how you set about it, but my advice for an ophthalmologist is to really embrace these years you have of learning and try and see how you could make a difference. Whether it is at a clinical level or whether it is even service improvement...all of those things are important. Being rewarded in what you do, that self-satisfaction, can come in a number of ways but you have to be open to rising to the challenge each time. Don't just sit back and expect it all to come towards you, you have to work towards it.

I think one thing that emulates from this conversation is that you found your passion.

Yes, absolutely! One of the other bits of advice I will give is if you're going through your professional career, keeping your passion is possibly also part of being able to diversify. So having multiple roles or doing multiple things. I have some friends who were at medical school with me who are non-ophthalmologists and in this group the ones who just stuck to one thing, by the time they get to the age where they're thinking about retiring they're burnt out. And working purely in the health service in this country, I think can burn you out. Those of us who do other things, and I'm not saying I spend a long time providing much service commitment anymore, but if you do other things, be it administrative or something akin to what you feel you're good at, that diversification means you can keep your interest and your passion and your enthusiasm. At the end of the day, you want to go through your life every day feeling enthusiastic for what you do. There are different ways of achieving that but I do think branching out and having multiple pockets in your timetable, which can be diametrically opposite, can help.

Thank you so much for taking time for this interview. It's really fascinating to hear about all the amazing things you're doing and I hope we can catch up another time.