A Window Bright

What provoked your interest in ophthalmology?
 

At Moorfields Eye Hospital, I was mentored by the well renowned English ophthalmologist Alan Bird. I spent time with him as a medical student, and that inspired me to become an ophthalmologist. I considered ophthalmology to be the place for the thinking man’s surgery – I apologize to all other surgical specialties with this stereotype! During my time with Alan Bird, I was keen on neuro-ophthalmology, but then I got into my PhD and that changed my whole perspective about being an ophthalmologist alone. I realized that my passion was to become a clinician scientist, and this became much more angled toward doing translational research.

Because the eye is transparent, it’s almost the only place where you have a tissue culture plate of cells. Normally, you grow cells in vitro in the lab and look at cellular activity in that artificial environment, but the amazing thing about the eye is that you can see those cells and their mechanisms non-invasively and in their natural environment. I think that is something that we should feel really privileged about as ophthalmologists.

What excites you most about your work?
 

I’ve always worked under the idea that the eye is a window into the brain; after all, embryologically, the eye comes from the same cells as the brain. And so, the things that you see in the brain you also see in the eye. As ophthalmologists, we can really offer insights into neurology, thus, for many years, I’ve been keen on exploring this similarity.

Changes in the eye almost predict changes in the brain – we’ve shown this from the work we’ve done in Alzheimer’s disease models, in Parkinson’s disease, and even in multiple sclerosis. The eye gives you a non-invasive window to view a world that is difficult to see directly in the brain; MRI, PET scans, and CT head scans – they are all very expensive diagnostic methods.

We are also very privileged in ophthalmology to see new advances all the time. It’s one of the more technologically based specialties, and that’s really important in terms of advancing the science.

Could you share a little about current research into the parallels between brain and eye disease?
 

There are two main levels to this topic. One, as I mentioned, is screening. A very easy test, compared with brain scanning, is doing an eye scan, and picking up an abnormality that allows some type of pathway to treating whatever disease the patient has. The other level, which I think is even more exciting, is monitoring treatment. If you could use the eye as a way of testing whether or not your Alzheimer’s treatment is working – I’m talking about the disease in its early stages – then I think the chances of modifying any neurodegenerative process is much greater than when the disease is fully established.

Which piece of advice has stayed with you throughout your career?
 

The credo I live by to this day – and what I pass on to the people I mentor – is “the more you know, the more you realize how much you don’t know.” When we’re young, we have slightly closed minds, we might think we know it all. But actually, it’s what you don’t know that really makes you appreciate new ideas and new findings, and their potential impact. This is definitely important for a clinician scientist – not closing but opening your mind, and realizing that no one really knows everything.

What’s your view on the near future of eye care?
 

As the aging population is rising, it’s important to remember that ophthalmologists, especially in the UK, won’t be able to tackle absolutely everything. Primary care and allied health professionals in ophthalmology will become more important. I really think optometrists will be key to delivering ophthalmology primary care in the future. We need to embrace that, and use it to the best of our abilities. It’s working together with this group of people that will best serve the eye health of the nation.

For example, DARC (Detection of Apoptosis Retinal Cells) technology that we are currently developing at Novai – the startup that I  founded – could be used. The company is currently working with pharma companies to test their drugs and quickly assess whether they work or not, both clinically and pre-clinically. The next stage will be to look at DARC in the future as a clinical decision-making support tool to improve patient management . Ultimately, it could serve as a screening device, not just for the eye, but for brain disease as well. Optometrists and technicians in a clinic would play a key role in implementing this, as there is no way ophthalmologists would be able to deliver all this. They have to be involved in this research, and I very much embrace that.

In your teaching, you also promote the training of clinician-scientists. Why do you think medical students should consider this career pathway?
 

As you get older, it becomes important to diversify. I don’t want to use the term “burnt out,” but I think concentrating on just one aspect may not be as rewarding as having multiple interests. Many of my colleagues do focus on multiple aspects of the profession – as well as being consultant ophthalmologists, they may also help with training and education or serve as a member of a committee. I think it’s important for medical students to recognize the importance of being a doctor with multiple interests and how this can serve patients’ needs. It doesn’t necessarily have to be through research, but that’s my path and one that I am passionate about.

What big changes have you witnessed in glaucoma and retinal degeneration over the years?
 

When I started off in glaucoma, people were still using timolol twice a day, as well as a drug called pilocarpine, which used to make your pupil pinpoint. There was a revolution when prostaglandins once-a-day treatment arrived. Subsequently, there have been different surgical interventions that have made a huge difference. And then more recently there has been the arrival of laser treatment.

For me, though, there is evidence that neuroprotection would be a really good treatment in glaucoma. By neuroprotection, I mean treatments that stop the process of neurons dying. And that is what I’m still looking forward to. There are some patients who, no matter how much IOP lowering you provide, still continue to lose vision. We know these patients need something else. So, the additive idea of a neuroprotective drug is something we need to establish. To get there, we need better biomarkers and better endpoints. But I think the time will come – and I very much hope that DARC technology will play a role.

Moving away from glaucoma, in terms of age-related macular degeneration (AMD), when I was a trainee there was no treatment for wet AMD or even geographic atrophy (GA). When those patients came in, they may have had laser treatment, but often they continued to go blind. The emergence of anti-VEGF injections has made a huge difference for those patients and also those suffering from diabetic eye disease. More recently in GA, the idea that you can use drugs for preventing the worsening of the disease – well, that’s a great advance.

And then, of course, there are the gene therapies that we’ve seen come through – Luxturna, for example. I would not have anticipated advances like this when I was training.

What future breakthroughs would you like to see?
 

As I mentioned, I would like to see developments in neuroprotection, and this would apply to all of the diseases I’ve mentioned. The same treatments would work in Alzheimer’s, Parkinson’s, and other neurodegenerative diseases – not just in those related to the retina. Ultimately, I want to be in a position where disease processes can be identified so early that the patient doesn’t have functional loss – whether that is losing vision, losing memory, or getting a tremor. When those things have happened, you’ve already lost a large number of the neurons; if you could intervene well before those cells die, you stop that functional loss occurring in the first place. That would really be a transformative development.

I would add that ophthalmology is as exciting as it’s ever been. The future is bright! As I’ve been saying, the eye is a great place to look at new therapies, new diagnostics, and bring this all together in the whole patient. As personalized medicine becomes more important, the eye is going to be increasingly used – not just by ophthalmologists, but also by the wider medical community.