Looking beyond the horizon to change the trajectory for vision loss

However, the vessels of people living with retinal conditions are unstable, leaky, inflamed and grow abnormally, leading to vision loss or even blindness. The impact on the person and their families is huge. It devastates quality of life, makes them unable to work and experience life in a very different way.

With millions of people worldwide living with these retinal conditions, ophthalmology scientists at Roche are determined to change the status quo for better treatment. They are tackling the conditions from multiple angles, with an ultimate goal to hopefully prevent, and even reverse, vision loss. To do this, they must look beyond what we already know.

The discovery of anti-VEGF (vascular endothelial growth factor) treatment more than 15 years ago, was transformative for the ophthalmology patients. To improve options for patients yet further, Roche has taken an innovative approach applying insights from research in oncology to ophthalmology. A team of scientists is also taking a pioneering approach to focus its efforts on exploring new potential scientific avenues.

“We know that improving efficacy is one of the most important elements for improving treatment. Anti-VEGF therapy is efficacious, but we also need to tackle additional factors, such as fibrosis, ischemia and inflammation”, says Sascha.

The challenge for Sascha and his team is how to deliver multiple mechanisms to patient’s eyes to enable this multi-target approach. One of the tools to achieve this are bispecific antibodies, and the seminal invention of CrossMab technology, pioneered by Roche.

This unique technology combines two antigen-recognising elements and therefore enables this dual targeting approach.

The next generation of bispecifics is already in clinical development: DutaFabs, an excellent platform developed by a small biotech, which was acquired by Roche in 2014, pave the way for the potential discovery of multiple modes of action (MoAs). This could be game-changing for patients.

Current treatments that are injected into the vitreous require some patients to attend their doctor once a month for this procedure. This can be difficult for patients, not only in terms of making time and getting to their appointment, but also as the procedure can be quite a daunting one for many. Recognising this, Roche scientists are committed to finding and developing new systems for long-acting delivery that reduce the burden on patients. In this area, substantial progress continues to be made.

A next generation capsid to deliver genes

To date, intravitreal injections have been a mainstay of treatment because of the ability to reach the whole retina. Recently, gene therapy has opened up new potential in ophthalmology with the possibility of bringing genes into the retina to actively enable a change in the course of a disease. “New capsids are needed and through our collaborations and partnerships we are seeking to work together to develop the next generation, with better transduction and, low induction of immune response,” Sascha highlights, noting, “Gene therapy could hopefully provide the ultimate durability for patients, even with complex diseases, to give a treatment option lasting years and moving towards cure.”

Advanced imaging and analysis

Alongside the new potential treatment options, an exploration of technologies that will advance personalised healthcare is central to Roche’s work. The level of detail available through imaging technologies used in ophthalmology clinics is astounding, yet somewhat untapped. Roche scientists are working to harness ways to analyse these advanced images to enable understanding of disease and treatment response. Adding to this, by pioneering the molecular analysis of fluid from the eye, the scientists are seeking to identify patterns in disease for a deeply tailored and timely care that reaches a completely new level.

An openness to finding new ways forward, to partner and collaborate with the best scientific minds is enabling a continuous flow of ideas and new approaches.

Sascha describes Roche’s stepwise approach to science in ophthalmology as, a seemingly small percentage change (in sight) can not only make significant improvements in quality of life, but it can build the momentum for huge leaps forward in reversing damage. Some leaps are already being seen and it is just a matter of time before we see more.