Euretina – To imagine how ophthalmology could be in 10 years from now, amidst the challenges of the ongoing pandemic, and the state of the art of modern medicine and technology. A better, safer, more effective and more advanced clinical practice was the topic and the aim of “The Ophthalmology Clinic of 2030: What is on the Horizon?” Symposium that took place at the Euretina 2021 virtual congress. Chaired by Marc D. de Smet, MDCM, PhD, FRCSC, FRCOphth, DABO, FMH, the Symposium hosted four worldwide-renown Thought Leaders and posterior segment experts who discussed the latest solutions for an advancement not only in clinical practice but for the future of medicine itself. 

“What will be the future of home monitoring?”

Bringing diagnostics directly into patients’ homes has shown to be an invaluable resource for medical doctors all over the world, especially in ophthalmology and for the remote monitoring of retinal diseases. According to Anat Loewenstein, MD, MHA, a virtuous use of telemedicine had already been able to increase efficiency in hospital referrals, leading to a more efficient ability to screen at-risk populations and to a reduced number of visits and travel burden for patients. 

“I think it will become increasingly important in the future for the continuity of optimal patient’s care,” Loewenstein said. “Home monitoring of the visual field, functional, and of the retinal fluid, morphological, has been studied in prospective trials as well as in the real world, showing that it can allow for close monitoring of the retinal fluid in patients with nAMD with the potential to improve the outcomes. We think that all these recent developments may help to meet the future challenges in ophthalmology coming up with more treatments and more regimens to follow.” 

How can AI help us and our patients?

Artificial Intelligence is becoming more and more present in everybody’s lives. During his presentation, Hrvoje Bogunović, PhD underlined the immense potential of AI in medicine, imaging and diagnostics.
“The first aspect comes in the form of automated diagnostic systems and screening,” Bogunović said. “Second, is the ability to provide localised identification of retinal fluid and essentially a volumetric measurement of fluid and disease activity, which is also correlated with therapeutic efficacy. Lastly, by searching for predictive factors we have found that VA at the beginning of the treatment is still the most important predictive factor for the treatment success.” 

How can we optimize our existing treatments and have self-administered treatments?

The future of pharmacology should aim to improve durability and efficacy of intravitreal treatments, according to Paolo Lanzetta, MD. This goal has proved difficult to achieve by following the path of co-inhibition treatments.
“In reported experience, co-inhibition of PDGF and Ang-2 alongside VEGF-A/PIGF provided no additional benefit over anti-VEGF/PIGF monotherapy with aflibercept,” Lanzetta said.
“Alternatively, to multiply inhibition we can improve the durability of treatments available: increasing the initial concentration of an efficacious anti-VEGF agent we may obtain a reduced burden thanks to a longer suppression of VEGF.” According to Lanzetta, this may be a possible path towards better tolerated and more efficacious treatment options. 

“Can we improve durability? Theoretically yes, by increasing the molar dose of existing and approved treatments,” Lanzetta pointed out. In the foreseeable future, a reduction of treatment burden and the overall improvements of clinical practice along with other strategies will effectively tackle the long and well-known problem of non-adherence in anti-VEGF treatments.
“Recently, during the pandemic, a number of measures were taken to limit the spread of infection. For example, Anat Loewenstein and her team brought the treatment directly to the patient’s home,” Lanzetta said. “Topical treatments on the other half, whilst already trialed for nAMD, resulted unfortunately in a lower efficacy as compared to the current intravitreal agents. Novel drugs with newer mechanisms of action such as sGC activators may open to self-administered oral treatments and these may solve any practical issue that we have with intravitreal delivery of medications today.”

How to treat the incurable. 

Finding a treatment for inherited diseases is one of the greatest aims of ophthalmology. Genetic testing is already an invaluable tool and many treatment options at a genetic level have been emerging in recent years.

“I think that in the near future we are going to advance to doing whole exome and genome sequencing, hopefully allowing us to solve even cases unsolvable today,” Mark Pennesi, MD, PhD said. “Further into the future, whole genome sequencing will become the standard of care, and by that time we will solve almost all the genetic causes of retinal degenerations.”
Gene augmentation, gene editing and spliceosome-mediated RNA trans-splicing, RNA silencing and RNA silencing and replacement are already available tools to further push the boundaries of modern medicine.
“By 2030 I think we will have several therapies approved and will have additional therapies, probably also using novel technologies that can deliver larger genes as dual vectors and nanoparticles,” Pennesi said.
Present and future ophthalmologists should also look into gene independent strategies, like neuroprotective strategies, optogenetics and cell therapy. According to Pennesi, cell therapy promises to be the ultimate cure for many inherited diseases, and is currently investigated in a number of different trials in the very early phases.
“In terms of where we are right now it is still very early days. Ultimately what we really want to get here is true cell replacement, where we are actually putting in new photoreceptors and new RPE cells to replace what has been lost. That kind of technology is on the horizon,” Pennesi concluded. 

A ten-year horizon.

“We tried to think about what is going to come along in the next ten years and of course we could think of many different things, but among them we have all been exposed to monitoring patients at a distance and having to do that using the internet. Home monitoring and Artificial Intelligence are going to become more and more important in the upcoming ten years,” Marc de Smet said during the symposium, “and if we think about existing anti-VEGF therapy, we would all like to see it work for longer and to be able to achieve and extend the treatment intervals for our patients.”
“Among the many unmet needs that we hear about more and more today are the advancements in cell and gene therapy that can add to the benefit of the vision of our patients, and also the idea of being able to use oral medication. It will be very interesting to see if oral therapeutics are going to make our change to the care of our patients in the future,” de Smet said. “Preclinical studies in cell and gene therapy are also very encouraging and they show they have potential for targeting many of the inherited retinal diseases and demonstrate that these may be able to rescue for the receptors and restore damaged retinal tissue, thereby improving visual function and of course we are also interested to know whether some of these approaches could be used for some of the diseases we see in the elderly,” de Smet concluded.