A Vision for the Future

Tell us a bit about yourself and your career to date – was there a particular moment you decided to specialize in ophthalmology?
 

My current role is in research and development, but my background is as a practicing ophthalmologist. I spent over 16 years in the clinic seeing patients, specializing in medical and surgical retina. I also hold a position as Professor of Ophthalmology at the University of Cologne, Germany. 

I can’t really say there was ever an exact moment I decided to pursue ophthalmology; for me, it was more about naturally following my interests. In medical school, one of my earliest passions was exploring the molecular and genetic causes of disease, and, at that time, ophthalmology was really leading the way for the discovery of many monogenetic diseases. So, I suppose I came into ophthalmology via molecular genetics, and I have never regretted it.

What led you to make the move from the clinic to working in research and development? 
 

Similar to my entry into ophthalmology, moving from the clinic to research and development definitely felt like a natural progression. Throughout my time as a practicing retinal surgeon, I was also active in research – and that led to my being recruited as the lead of the dedicated ophthalmology pharma research and early development (pRED) group at Roche.

It is a change I have embraced; I get the chance to work with colleagues from many different areas, including fellow clinicians, academic partners, computer scientists and manufacturing experts. Ultimately, I consider it a real privilege to work in a space that has the resources, the connections, and – frankly – the patience it requires to deliver the next generation of treatments that, if we do our jobs well, could improve the lives of millions of people. 

What do you think is the next big “frontier” in the treatment of retinal vascular diseases?
 

For me, there are two main components to this. Firstly, there is the delivery of the next big breakthrough retinal disease treatment. Around 15 years ago, vascular endothelial growth factor-A (VEGF-A) inhibitors revolutionized eye care by offering an effective way to treat certain retinal diseases, but we now understand more about the potential limits of this approach. For instance, not everyone achieves a good outcome with anti-VEGFs. It is plausible that these complex diseases cannot be treated by targeting only one cytokine. Additionally, we’re pushing up against something of an “efficacy ceiling” with anti-VEGF treatments. And that is something the team I work with are really laser-focused on: how can we break this status quo? It’s a significant challenge and one Roche is tackling from multiple angles. As a community, I do believe we are making great strides, and I’m optimistic that the next big breakthrough is on the horizon.  

Secondly, and perhaps with a more long-term perspective, I think it’s going to be critical to move beyond control of disease and towards more preventative and even regenerative treatment approaches. We all know our population is aging, and with that we expect to see significant increases in retinal diseases. We’re not there yet, but the science and the technology are definitely maturing and so my hope – my belief – is that we will be able to shift from treating vision loss towards reversing, and even curing it, in the not-too-distant future.

How can combination therapies improve on the standard of care?
 

Combination therapies are exciting as they have the potential to address the mechanisms that are driving retinal disease from multiple angles at once with several potential benefits. First and foremost, there is the potential for improvements in vision outcomes for patients. It may be the key to surpassing the efficacy ceiling we are currently seeing with anti-VEGF treatments. Additionally, combination therapies have the potential to reduce treatment burden by using lower doses of complementary therapies rather than relying on escalating doses of monotherapy. In the future, combination treatments could also provide a more personalized approach to care in retinal disease. If we can successfully develop a number of combination therapies targeted to different pathways, it would offer flexibility to tailor the treatment approach to individual patients. This approach would ensure we are really delivering the best vision outcomes on a case-by-case basis. It is a rapidly advancing area, and I am looking forward to seeing how it delivers over the coming years.

Which pathways do you think are good candidates for new treatments? 
 

That is the big question! Currently, there is a great deal of excitement about targeting inflammatory processes, which contribute to the development and progression of various retinal conditions – for example, uveitic macular edema. We have been hearing a lot of buzz around this as a potential treatment target on the conference circuit this year, and it’s certainly something the Roche pRED team and I are actively working on. 

Beyond this, we know that, for some individuals who don’t respond so well to anti-VEGF therapy, additional factors, such as fibrosis, ischemia, and atrophy, can limit the vision gains they are able to achieve. It seems logical then that the mechanisms underlying these processes will also be good candidates for future targeted treatment.

What are the challenges associated with targeting multiple pathways at once?
 

There are several potential hurdles. There’s always an element of caution of not wanting to “over treat” – more molecules targeting more pathways can open up greater potential for off-target effects. It is a delicate balancing act. Once you have a viable candidate, establishing the right dosing and administration, combined with the manufacturing implications of needing to produce multiple active ingredients in combination can also be a challenge. Finally, clinical trial design for combination therapies can be particularly complex, including determining what is the appropriate control group, or groups, to test against. It is challenging science to grapple with, but that’s also what makes it so satisfying when you are able to get all the pieces to come together.

What is being done in the ophthalmology space beyond exploring novel pathways?
 

It is something of a hot topic these days, but there are some truly impressive advances using artificial intelligence (AI) that have the potential to revolutionize how we detect signs of retinal disease and monitor disease progression. You could say that we are somewhat lucky in ophthalmology in that we already have some of the most advanced imaging technologies in the clinic, generating incredibly detailed information about the structure of the eye as part of daily practice. But with AI we can take this a step further. Indeed, at Roche, we’re particularly excited about exploring how we can use advances in machine learning to maximize this wealth of imaging information. For example, by using pattern identification to allow us not only to detect disease earlier, but also to go beyond that and predict how an individual’s disease is going to progress. We have already been able to tap into this technology to offer patients at-home eye health monitoring via a prescription smartphone app that can detect changes in their vision in between clinic visits. The app connects directly to the patient’s care team, so it opens up whole new avenues for tailored, timely interventions. 

As systems and tools become smarter, we also now have more ways than ever before to gather information about people’s experiences outside of clinical trial settings. This “real-world” data gives us much more to work on when we are looking at why certain people might not experience the full benefit of a treatment – or where the “pain points” in delivery of care really hit. From a research and development perspective, this additional data can help us make smarter decisions in terms of where to focus our efforts to deliver treatments and tools that will really meet the needs of patients and clinics.

Thinking about the next year or so, what new developments are you most excited to see?
 

I think we’re seeing most progress in retinal diseases at the moment. There are many new technologies – for example, new antibody formats that cover more aspects of disease than ever before and many exciting diagnostic tools coming through. The key now will be to see how these can best be translated to tangible benefits to patients. I alsoremain deeply interested in advances in molecular genetics, and I think we’re going to see some promising updates about gene therapy candidates for a range of eye conditions.