Professor Timothy Jackson, Professor of Retinal Research, King's College London

AUTHORS:  Dr Sanketh Rampes and Dr Anvarjon Mukhammadaminov 

In this series the Medspire team interviews doctors about their career, their specialty, the choices they have made and their advice for doctors and medical students. 

Here the subject is Professor Timothy Jackson, professor of retinal research at King's College London. Professor Jackson has a strong interest in retinal disease.  

A podcast of this interview is available here:

 

How did you get to where you are today?

So I did my medical degree in New Zealand, came to the UK and just floated around for a bit, not really knowing quite where I wanted to end up.I did a casualty job, and then decided I wanted to do ophthalmology.

I took an SHO job, did my main registrar training at Moorfields, and then stayed on to do a fellowship there. I had a consultant job, and then did a PhD en route, not as a medical student, but during the registrar years., I took some time out to do that, and that's when the research started. That was really a project designed around laboratory-type work, albeit with a clinical endpoint, but it was lab-based. 

I ended up working at King's, and then drifting into clinical research, where I actually do very little lab work. I had some PhD students, but mostly moved into clinical research doing clinical trials - mainly looking at devices, and in particular at retinal disease.

I did a vitreoretinal fellowship, so tried to marry up the clinical work, which is surgical retina and medical retina, alongside the treatments of retinal disease. 

 

What was your PhD in?

My PhD was based at St Thomas' under a chap called John Marshall. We were looking at a number of things, but, basically at how molecules move across the retina - so the idea of what size of molecule can cross the retina - and then also looking at trying to use antibodies with fluorescent tags on them to identify ocular tissue. 

The idea was that you could ultimately use stains or dyes to recognise tissue when you're operating. One of the problems with operating in the retina, is that it is designed to be clear to allow the light to go through it and hit the photoreceptors. But that's not very helpful when you're trying to operate on it, because if it's clear you don't see it so well. 

The idea would be to use agents that would highlight the bits of the retina that we want to manipulate. So my PhD was lab-based, but very much with a clinical endpoint in mind. 

 

How did you go about identifying your research interests, and what was the process?

So wouldn't it be nice if you sat down one day and got out a bit of paper and designed where you're going to be for the next five years? But of course it probably doesn't unfold that way, and the reality is that actually most of it happens by happenstance.

The researchers came to us - they wanted to investigate some new technologies that were going to be within the retinal sphere, because that's my subspecialty. 

Then we built up the skills that we needed to evaluate the technologies, and that meant that we could test a lot of other surgical devices and medical interventions. So I wouldn't say it was by design. AMD, age-related macular degeneration is a hugely important disease that causes more blindness than all the other eye diseases combined. 

Albeit, about 51% of blind registrations are due to AMD, but if you think of it as by far the most important disease, even with my retinal bias, most people would agree it's pretty important. 

One of the things I really want to focus on is diseases that affect a big number of people. There are lots of very interesting diseases, and these patients often suffer because they don't have the critical mass that brings technologies and investment in their direction, but equally, if you have something, it's going to be so much more impactful if it affects a large number of patients.

 

What are the biggest changes and advancements during your career?

In my field, the intravitreal anti-VEGF therapies for AMD were by the far the biggest change, because lots of other changes are incremental. The surgical technology has got progressively better, but they're incremental changes. 

Whereas before, when patients had wet AMD there was really nothing we could do for them. It was a progressive blinding disease, and would often become bilateral, and it was catastrophic for these patients.

They went from being fully independent to being often being very dependent on other people, and other than emotional support and low-vision aids, that was it, really. In fact, most of them were discharged from the hospital. 

Then all of a sudden an injection comes along that treats the underlying cause - it stops the blood vessels growing in the back of the eye and leaking - and we went from an untreatable to a treatable disease almost overnight. 

Now, intravitreal injections are the second most common eye procedure we do after cataract surgery. So it went from being nothing to an extremely common treatment in no time at all, and fundamental to being able to change people's quality of life. 

 

Out of all your ongoing research, is there a particular area that really excites you?

I can't point to one thing in particular, but the challenges are really about how you assess different technologies. The project that we've got up and running at the minute, which is very much my focus of attention, is a trial looking at giving injections.t's a tPA - a tissue plasminogen activator -the same that you'll be familiar with for using for stroke and pulmonary embolus. 

The idea is that we could inject that underneath the retina and dissolve haemorrhage that comes from AMD. Patients with AMD have new blood vessels growing, but they're very fragile, they can have this catastrophic haemorrhage underneath the retina, and if it affects the fovea, then that will massively damage the vision, because the blood is toxic. 

So the idea is we do an operation, inject through the retina a small amount of tPA underneath the retina, and then fill up the eye with a bubble of gas. The patient is put face-down so that the clot-busting drug - the tPA - dissolves the clot, and then the blood and a bubble of gas pushes the haemorrhage away from the macular. 

The results we've got on case series are very positive, because even with the anti-VEGF injections, most of these patients do very badly even though we can control the AMD, the haemorrhage is toxic pretty quickly. So that's an exciting treatment for patients who otherwise have no greater option. But it's been challenging. Brexit has been a big issue. 

So we were awarded - there was a sort of pan-European call to fund the trial - and we won the competition. We had the right skills to bid for it, and they were very keen on us doing it, and then the Brexit issue came up and they suddenly thought: ‘Well, maybe Britain shouldn't be leading a trial across Europe, because we're outside of the EU’.

We very nearly lost the grant because the funders were, not unreasonably, concerned that we wouldn't have the regulatory connections we’d need when we're outside of Brexit. So that's been a big issue. We've overcome it, but then, of course, COVID has come along as well, so doing clinical trials is hard work sometimes. 

 

Do you have any insights on securing funding for projects?

Getting funding is extremely difficult. The UK is pretty good. They have a good research base, and they have robust ways of assessing grants, but roughly speaking, only 1:5 bids of the big bids to big funders are successful. 

I sit on a grant panel and we look at maybe 25 bids, of which ten, 15 are very good. And yet we'll only be able to fund maybe one or two or three in a round, and you see some extremely good research that doesn't get funded. The applications can run to 80, 90 pages, so it's a massive amount of effort putting in for a funding call that you might only have a 1:5 chance of getting. 

So it's tough out there; it really is. It's not like clinical work, which appears in front of you and you just do the work, move on to the next patient, and at the end of the day or evening or morning you go home. This is the opposite. There's no guarantees. You can do a lot of work with little to show for it sometimes. 

On the other hand, when you get it, there are big grants that can sometimes last you for many years, so you've just got to accept, like many industries, that when you bid for a project you might not get it. 

 

Is there one paper that you have published in particular that you're most proud of?

Interestingly, one of the projects I'm most proud of is a trial that we did for a technology that didn't work. What you're usually looking for is a positive result, - actually the journals much prefer to publish positive outcomes - but we tested something that looked very good in the initial phases of assessment, and then did a trial and showed it didn't work. 

The impact was that the device was withdrawn from the market -, it was a disappointment, but actually, that's pretty impactful, because if the technology doesn't work you shouldn't be using it. So with those kinds of negative trial results, the paradox is that they still matter. 

 

What's still unknown within your field?

That's a really hard one to answer. There's what you know you don't know, and there's unknown unknowns. Certainly in AMD, there's a huge amount we don't know, and there's a lot of gaps in our knowledge in terms of the causation. 

Lots of patients respond very well to anti-VEGF therapy, but by no means all, and over time these patients do still lose vision, albeit much slower than they used to in the past. So we've got a long way to go. My research isn't really mechanistic. I'm not sitting in a laboratory trying to work out new chemical pathways and things.

I'm more at the end of evaluating those technologies once they've got to a later phase, or at least to clinical testing, but there's so much going on in this field. There will be lots of new treatments. What I would like to see is the evaluation of devices to evolve in a way that the evaluation of drug assessments have. So we're very good at testing drugs. 

The RCT is an extremely good device for working out whether or not something is safe and effective. You can't randomise the devices. You've got to do an operation where the patient knows what's happening, the surgeon knows what's happening, and it's very hard to use the RCT template.It's not as evolved as the evaluation of drugs. 

So what I'd like to see is that we can apply the same kind of rigour that we do for drugs to the evaluation of devices, but the reality is that's going to be a challenge, because of some of the fundamentals that you can't get around. 

 

As a clinician and an academic researcher, what is a typical week for you?

On a Monday I'll have a clinic in the morning and then theatre in the afternoon, so that's a pure clinical day. On Tuesday, again, it starts off with a clinic, and then I usually spend most of the afternoon meeting with my team. So that will be the main day for touching base with them and finding out what questions they need answered - what direction we're going to travel in. 

It's a lot of meetings, but actually they're very good, because those people have been busy through the rest of the week, and it's about just coming together and making sure that they continue to work efficiently. Wednesday, again, is more clinical work. 

Thursday, I'm usually at home. Strangely, my most productive time is when I'm away from the office, because you're then dealing with the things that you need to deal with. Friday we used to do teaching in the afternoon, but of course, that's changed to Zoom, so although we still have meetings, I can still get a little bit of admin done. 

So it's a mix of meeting people, supervising MD and PhD students. This Thursday we did a medical student workshop where we were teaching clinical skills. Basically, a series of stations and the students move between them, and we teach them how to use ophthalmoscopy, or examine the visual field - so that was more to do with medical students. It's terribly varied. 

You've heard the collective noun for professors? An ‘absence of professors’ they call it, because they're allegedly never actually in the office. You do end up spending a lot of time away, because you're at conferences or you've got meetings with people - maybe less so with Zoom - but the wonderful thing about the job is it's hugely varied. 

At your stage of learning it's great fun learning new clinical skills, and getting to grips with new diseases, and helping patients - it's wonderful - but actually if you do exactly the same thing for decades, it can become a bit repetitive once you've acquired those skills and you're maybe too far into your comfort soon. 

Whereas, research is constantly changing. You're under pressure the whole time to publish, to get funding, to attract students, so it's more challenging, but it is deeply satisfying. 

 

How can someone get involved in research? 

If you've got an interest in research, I'd strongly encourage you to give it a go. It's not for everybody, and there was a period when it was very difficult to get through to the next stage of training.

A good number of people did higher degrees, MDs and PhDs, to make their way up the ladder and to make themselves more competitive, but they didn't really have a fundamental interest in it. It's a terrible waste of resources, because you put a lot of effort in, and so does your supervisor.

You know that lots of people are just not going to continue with it, and it's hard work. So unless you need to do that,  I wouldn't do it unless you want to. But if you want to, probably the best thing to do is to try and get some papers, if you can, because one of the biggest discriminators if you can get onto an academic post, is having some publications.

So it's nice to have done audits and presentations and bits and pieces, but actually the publications are hugely important in terms of building up your CV. 

If you know which area of medicine you want to go into then try and connect with someone. Look out for a good researcher who's got a good track record. Don't be embarrassed to go up and chat to the most senior person in the department. Often, people are a bit afraid to do that, but I would literally go knocking on the door of the head of department, or the key researcher in that area and just say: 'I'm interested in an academic career. 

I'd like to try some things out. Are there some projects I can help with to get a taster, or is there anything you need written up that could be published?' Be persistent. Students will come and knock on the door quite often, but it's the ones that keep coming back that will get the attention eventually. 

So you might not get a welcome reception from the first person you see, but if you keep at it you will get engaged with someone. 

 

What advice would you give to those interested in pursuing a career in ophthalmology?

Ophthalmology is horrifically competitive. It's one of the tougher specialties in that sense, and it's also fairly niche, which is not good, because with lots of other specialties you can try them for a bit and if you don't like them then you've built up skills that are very relevant to other specialties. 

Whereas, ophthalmology, in a sense, you don't want to just do it for a few years and then hope to move into A&E, for example, because it's not going to open up those opportunities. The key thing is to connect with someone. Let some people know that’s what you want to do. Make sure your CV is ‘buffed up’. 

Again, get some experience in departments, if you can. Chat to very senior people - and I'm happy for people to get in touch with me if they want to - but also chat to some people who have just gone through that process of selection, because actually the best advice won't come from me, it will be coming from someone who's just got into ophthalmology the year or two beforehand, because the goalposts shift. 

What was probably true when I got into ophthalmology, may not be exactly right now. So go for senior advice, and very recent advice, but also just chat to lots of people, because you don't want to spend a whole amount of effort doing something that turns out to be irrelevant. 

 

What advice would you give to your younger self?

You've just got to be robust enough to hang in there, because there will be disappointments, and it's very easy to get disappointed with something and think: well, I'll give up now. So I would just say, absolutely stick at it. Accept that things might not happen straight away, but persevere.

 

What useful habits have you developed?

Oh, God, I wish. I don't actually look to myself to answer that question, because the thing I would love to be able to do better is not waste so much time. I'm a terrible procrastinator. I can think of lots of people I know who don't waste time, and they just get on with those things, and their life is a model of efficiency. So don't come looking to me for advice on that one, sorry.

 

What advice would you give about work-life balance?

So to be very clear, if you want a career in research, you will not have a work-life balance, because the problem is you've got to do all the clinical work and you've got to compete with full-time researchers.

So for the non-clinicians, they have the full working week to dedicate to research, whereas you've got to maybe give half your time or more to the clinical side of things. 

You've got to be clinically capable. You're going to have to work in, essentially, a university hospital, so you're going to have to climb that ladder as well. So I would not expect to have a great work-life balance, at least in the early part of your career. You will make sacrifices, if you want to pump out papers and get higher degrees and other things that you need. 

Something will have to give. Later life once you've got a tenured position, or you've at least got some dedicated time to do research, then the work-life balance is easier. But that may not come until your 40s, maybe not even until your 50s. So, unfortunately, work-life balance is something - you wouldn't promise to anyone if they're going to go down an academic career.

 

If you could recommend one ophthalmology paper what would it be?

Do you know what, I cannot think of a single paper that you should go and read. Unfortunately, the ophthalmology ones, at least the ones that I'm aware of, are going to be so boring to look at. Until you're in your subspeciality years, most of them would be as dull as dishwater, so go out and read a good novel. 

 

Any novels that you'd recommend? 

I read at the pace of a drunk snail. It takes me ages to get through a book, but I have at least just finished White Tiger, which is a really good book. I thoroughly enjoyed it. More interestingly, I'm reading something about fungi at the moment, which sounds incredibly dull, but it's this guy called Sheldrake, and it's fascinating, actually. It's really quite ‘out there’ in terms of some of the ways fungi are. I don't know how they've turned it into a good read, but it is. 

 

Medspire podcasts are produced by Dr Sanketh Rampes and Dr Anvarjon Mukhammadaminov, both full-time junior doctors. They aim to inspire the next generation of doctors and scientists by exploring the career journeys of leading clinicians and researchers.