The big interview: Professor Lyndon da Cruz

To people of a certain generation, the bionic eye was a trope of science fiction. Sitting unnoticed on the face of Steve Austin, hero of The Six Million Dollar Man (a series popular around the world in the late 1970s), it could zoom in on distant subjects, magnify microscopic objects and even offer infra-red vision. It was regarded in much the same way as Doctor Who’s Tardis—a lovely idea, but one confined to the far reaches of the fictional world.

However, in the last few years, due to the work of people like pioneering ophthalmologist Professor Lyndon da Cruz, the idea that we might be able to use technology to enhance or restore human vision has taken its first steps along a very long and difficult path.

“My motivation to work in this area came from the patients sitting across the desk from me during consultations,” says Professor Da Cruz, in a bright and airy consulting room deep inside the London Claremont Clinic in Marylebone. “I work with people who have suffered profound vision loss and it was very frustrating for me to have nothing to offer those with a severe retinal disease. Suddenly, advances in technology made it plausible to investigate solutions to conditions we had no treatment for.”

An artificial retina
The first thing that Professor Da Cruz wants to make clear is that the ‘bionic eye’ he has helped to create isn’t really an eye, with the many complex structures that would entail. It is instead a device designed to replicate the role of the retina: turning light into electrical signals which are then sent off to the brain. “A better—but less catchy—name would be an artificial retina,” Professor Da Cruz continues, “because the device has to be implanted into a normally-shaped and structured eye, with a functioning optic nerve.”

The task Professor Da Cruz and the team have set themselves is incredibly complex. The human retina works its magic using cells of about one micron wide and 100 microns long—a micron being 1,000th of a millimetre—so a straight replication of retinal structures is still a long way off. Instead, the team have developed a multi-part system, which Professor Da Cruz describes as “a bit clunky”—but truly remarkable nonetheless. The system is made up of a video camera set within a pair of glasses, and a computer which converts the feed from the camera into a series of electrical signals. These signals are transmitted wirelessly to a receiver on the eye, which passes the signals to the electrode array of the artificial retina, that stimulates the residual retina, and the signals created are sent to the brain.

“The artificial retina is the heart of the system—the interface between the technological and biological realm,” Professor Da Cruz explains. “It is made up of 60 electrodes, laid out in a six-by-10 grid. The signals it receives stimulate the electrodes to produce specific patterns in set time sequences. In a sense, it is drawing a moving picture on this grid— it’s this picture that is sent down the optic nerve to the brain. We have a long way to go in terms of replicating the density of electrical stimulation that you get in the normal eye, but it is still quite an extraordinary micro-engineering feat. My role as the surgeon was to develop the nature of the retinal implant and then refine the procedures needed to put the implant in place, to the point where they can be carried out by any competent ophthalmic surgeon. I was then responsible for monitoring the operation of the device after the procedure, collating the data provided by patients about living and working with it.”

Sophisticated developments
Professor Da Cruz’s work represents the final link in the technological chain. The visual environment is incredibly complex, so the first task was to enable the device to extract useful information from the camera feed. This involves incredibly subtle computer algorithms, which sift through the signals to filter out extraneous information and build a useful image out of what is left. This is then transmitted to the eye and to the retinal implant, which must operate without damaging the optic nerves in any way. This technological-tobiological interface has required some very sophisticated developments by material scientists. “So, as you can see, this has been a hugely collaborative effort.”

Initial trials involved people with true blindness—those with no perception of light at all—or patients with very limited light perception, but no ability to perceive form. As this was a proofof-concept trial, testing the system on these patients made it easier to quantify the nature of the vision the system was providing. But there was an additional benefit which appealed to the professor: the people who qualified for the trial were the subset of patients his profession can currently do the least for, meaning any progress they could make was all the more meaningful. “We soon saw that the system was proving itself as a concept,” he says. “Patients who had been totally blind could see light. The very best patients could read letters two or three centimetres high on a computer screen. That was an incredible moment for all of us—here was someone who had been completely blind, reading letters on a screen. It was a remarkable achievement.”

The team have recently published a paper detailing the five-year outcome of the 30 patients in the first study, and when it comes to the practicalities of the device—functionality, stability and safety—Professor Da Cruz believes the results are extremely positive. But the research also highlighted an issue that the team had slowly become aware of: that of usefulness. It turned out that the people with the best technical outcomes—that is, with the best ‘vision’—were not necessarily the ones who used it the most.

“Functionality and usefulness are two entirely different things. People adapt their behaviour once they lose their vision. If you read braille or have your computer read your messages, reading letters on a screen is of no use in daily life. This led us to investigate this concept of usefulness much more carefully.”

A mismatch
One patient the surgeon recalls working with was a blind receptionist. She wasn’t among those with the best outcome in terms of visual acuity, but the device was useful for her in a very different way. If a visitor was quiet, they could come right up to the reception desk without her noticing. Eventually, feeling as though they were being ignored, they would do something to attract her attention. Although any ill feeling evaporated when they realised she was blind, the situation would leave her embarrassed. “With this device, she could perceive the door opening and the person coming across the room,” says Professor Da Cruz. “It completely transformed her working life. What was a limited visual function proved to be extremely useful. It also meant that in some small way she had re-entered the visual world, which was important to her. This patient’s experience demonstrates the mismatch between acuity and usefulness.”

Looking forward, questions of usefulness will be at the fore. “In some ways it is like going back to the beginning, because we are having to ask fundamentally different questions. What activities are the device useful for? At what point did that usefulness end? Were there things the device allowed you to do but you never used? If so, what stopped you? Essentially, we are establishing the device’s limits. One of the things this taught us is that the training a patient gets when they are first fitted with the device can have a major impact on how useful it goes on to be, so we are investigating which limitations are a result of the technology and which are a result of the training we have given to the patients.”

It would be very easy to get swept up in the bioengineering marvel that the artificial retina represents. But for this surgeon, the technology is not the attraction—it is the fact that it could now be used to tackle areas previously off limits to his field. It was also a chance to collaborate with people from very different fields—something that he saw as an exciting challenge. “By their nature, these projects are truly multidisciplinary. It is a joint venture between the engineering, bioengineering, computer science, material science, biological, medical and psychiatric departments of institutes. It has taken this wide range of disciplines, all pushing the boundaries of their fields, to make the progress we have.” As well as being multi-disciplinary, the group is also multiregional, with project directors scouring institutions across the globe to find the best talent. “I have to say, the development of the artificial retina has been a real exemplar for the multidisciplinary approach. This is a screaming example of how it is possible to get diverse specialties to successfully work together, in what is a very complex programme,” he enthuses.

Multidisciplinary teams
In fact, Professor Da Cruz believes that one of the biggest successes of the project has been in understanding the nature of running this kind of multidisciplinary project—learning to appreciate the types of communication necessary between the different teams and ensuring that within their working environment, everybody still feels connected to the overall project. “I don’t pretend to understand the software programming, just as the programmers wouldn’t dream of telling the material scientist what materials to use in the retinal panel. The communication and logistical structures we develop have to ensure the decisions we make as individuals gel, otherwise the device wouldn’t work.”

However, recent political events have given Professor Da Cruz some genuine concerns about future participation in such cutting edge projects. “The decision to leave the EU will have a profound effect on medical research in the UK,” he explains. “We will have to see what the government does to mitigate the effects on UK scientific collaboration. With its well-established international networks and attractiveness to medical researchers from all over the world, London has traditionally been particularly good at developing multidisciplinary teams. Also, with two great universities linked to teaching hospitals—UCL and Imperial—at the forefront, we have also been extremely good at producing the translational science which takes research work and brings it into the therapeutic sphere, where it can be used to help patients. While the device I have worked on was developed in the US, the surgical and research excellence was based in London. In fact, the site I ran at Moorfields Eye Hospital was the largest recruiter of patients for the international trial, which put the UK right at the heart of this pioneering research.”

With these concerns in mind, if he had a silver bullet, what aspect would he aim it at to push the project forward? His answer, delivered with more than a hint of frustration in his voice, is revealing. “For me the silver bullet would be convincing the government of the crucial importance of research and development funding—convincing them of the need to divert some of the enormous amounts of money it controls into fantastic projects like this,” he says. “The UK was the main site for the artificial retina system trial, it contributed a high percentage of the data which gained the technique regulatory approval across the world and yet it is the only country involved in the trials where it is not available on some form of publicly funded programme, which here would mean the NHS. Many countries which didn’t take part in the trials offer some form of public access to their citizens. They understand there are some limitations, but those countries have made the decision that this is an area that deserves commitment, both to what is available now and to what it can become. This is crucial—helping people is why we do this in the first place. I think it’s very important to see this type of research as an area in which the UK is a world leader. We should celebrate it and do what we can to drive it forward. Having done the hard work over many years to be in this position, it is vital that we don’t let a situation develop where we let that position slip and other countries step into the void. To be frank, I’m not seeing that kind of commitment, which I find very frustrating.”

The big win
Returning to the artificial retina, I ask if he sees it someday developing into a full blown bionic eye—on which subject Professor Da Cruz is ambivalent. “In the long term, the ultimate medicine is prevention, so as an ophthalmologist, my holy grail is getting to the point where people do not lose their vision in the first place—things like early identification and treatment, using the patient’s personal genome to detect susceptibility to problems before symptoms emerge, for example, or using the genome to develop therapies for those who have developed problems. These are the things that I would like to see.” However, he accepts that these therapies are some way off and sadly, there are going be people who suffer from profound vision loss for some time to come. “So, for me, the big win will be getting this technology to many more people.”

When you take a step back and look at what has been achieved to date, it is extraordinary. “But we can’t stop there,” he insists. “This project is about devising a safe, simple implant system which we can use to improve as many people’s lives as possible, not sitting back and congratulating ourselves on how clever we are. As a doctor, I am in the business of helping people who have suffered profound visual loss, not building fancy toys restricted to helping a lucky few.”

For more information, visit London Claremont Clinic