- About 537 million adults globally live with diabetes, with 90–95% of those cases being type 2 diabetes.
- People with diabetes are at an increased risk for several eye health conditions, including diabetic retinopathy and diabetic macular edema.
- Current treatments for diabetic retinopathy and diabetic macular edema are invasive and include medication injections into the eye and laser therapy.
- Data recently released for the phase 1b/2a trial of a new eye drop treatment for diabetic retinopathy and diabetic macular edema reported it to be safe and tolerable with 100% of participants completing the study.
- Researchers also reported a significant decrease in central macular thickness after 85 days of use, as well as inhibition of further increases in vascular leakage in study participants using the eye drop.
About 537 million adults around the world live with diabetes, with 90–95% of those cases being type 2 diabetes.
People with diabetes are at an increased risk for several health problems, including those related to the eyes. These include
There is currently no cure for either diabetic retinopathy or diabetic macular edema. Current treatment options for both conditions include medications injected directly into the eye, laser treatments, and eye surgery.
Soon, a less invasive treatment for diabetic retinopathy and diabetic macular edema may be available in the form of a simple eye drop.
Data recently released from the new treatment’s phase 1b/2a trial reported it to be safe and tolerable, with 100% of participants completing the study.
Additionally, researchers reported a significant decrease in central macular thickness after 85 days of use and inhibition of further increases in vascular leakage.
The researchers will present the full results of the phase 1b/2a trial at the annual meeting of the Association for Research in Vision and Ophthalmology (ARVO) in May 2024.
According to Dr. Loic Lhuillier, chief operating officer of Exonate Ltd. — the manufacturer of the new eye drops — and presenting author of this study, new ways to treat diabetic retinopathy and diabetic macular edema are needed because the current standard of care for diabetic macular edema involves frequent injections of
“There is a need for a noninvasive solution, which would improve [the] quality of life for these patients, by increasing patient comfort and, being self-administered, reducing inconvenience,” Dr. Lhuillier explained to Medical News Today.
As for people with non-proliferative diabetic retinopathy — at the early stage of the disease — Dr. Lhuillier said they are not offered any solution, except being placed in a “watch and wait” cycle until their disease evolves to either proliferative diabetic retinopathy — a more advanced stage of the condition — or diabetic macular edema, when they are then prescribed anti-VEGF injections.
“Finding a noninvasive, safe, and efficacious treatment for non-proliferative diabetic retinopathy patients would help prevent progression to more severe disease at an early stage,” he continued.
“In the [United States] alone, it is estimated that around 7.7 million people have non-proliferative diabetic retinopathy, while 1.8 million have progressed to more severe forms of the disease, so there is a clear incentive to act early and minimize the appearance of sight-threatening complications,” said Dr. Lhuillier.
The new eye drop, called EXN407, is reportedly the first topical treatment for retinal vascular diseases such as diabetic retinopathy and diabetic macular edema.
The eye drop is a small-molecule therapy using a
“Development of diabetic eye disease is driven by many factors, mainly the overgrowth of blood vessels in the retina,” Dr. Lhuillier detailed. “These blood vessels then become leaky, leading to the appearance of subretinal edema, and ultimately blindness. This phenomenon is triggered by a growth factor called
“EXN407 is a molecule that allows the re-balancing of VEGF by only inhibiting the disease-causing members of the family while leaving the non-disease-causing members intact,” he added. “It offers a more subtle approach than anti-VEGF agents, added to the convenience of being an eyedrop formulation vs injection.”
According to the results of the phase 1b/2a clinical trial for EXN407, the eye drops were considered safe and well-tolerated as 100% of study participants completed the study and no major or serious adverse effects were reported.
After the study, researchers reported that EXN407-administered study participants experienced a significant decrease in central macular thickness after 85 days.
“Central macular thickness is a key anatomical trait of diabetic macular edema, which measures the size of the retinal edema,” Dr. Lhuillier explained.
“A decrease in central macular thickness is well correlated with an improvement in visual acuity for patients with severe disease, so our results indicate that EXN407 could be beneficial in improving vision in these patients, something that we will assess in the next clinical trial.”
– Dr. Loic Lhuillier
Scientists also found that 60% of participants receiving EXN407 sustained a significant decrease in vascular leakage and 10% of those taking the eye drop did not experience further increases in vascular leakage, compared to those receiving the placebo.
“Vascular leakage measures how blood vessels leak fluid in the retina,” Dr. Lhuillier said. “As such, it is a trait of the early stages of the disease, i.e. non-proliferative diabetic retinopathy, prior to the appearance of edema. Reducing vascular leakage is extremely significant as it is a clear indication that EXN407 could help slow the progression of the disease towards more severe forms.”
Looking ahead, Dr. Lhuillier said the phase 1b/2a trial only enrolled participants with mild non-proliferative diabetic retinopathy and diabetic macular edema.
The next step with the phase 2b trial, he explained, is to demonstrate the effect of EXN407 in participants at a more advanced stage of the disease, presenting with non-proliferative diabetic retinopathy and significant diabetic macular edema.
“This is essential as it will help to conclude whether EXN407 could be useful in [non-proliferative diabetic retinopathy], [diabetic macular edema], or both,” Dr. Lhuillier said. “We expect this next trial to deliver its results in around three years.”
“Phase 3 trials will then need to be conducted to compare the efficacy of EXN407 against standard of care in the same patient population before applying for a market authorization,” he added. “These trials will be required to see patients treated for 12 months or more, so we are not expecting to see EXN407 being prescribed before 2031.”
MNT spoke with Dr. Benjamin Bert, a board-certified ophthalmologist at MemorialCare Orange Coast Medical Center in Fountain Valley, CA, about EXN407’s phase 1b/2a trial results. Dr. Bert was not involved in the research.
“We see the rates of diabetes increasing in the population and just by the nature of having more people with diabetes, we see more of the complications that happen with diabetes, and a good portion of those happen in the eyes,” he said.
“The treatments that we have right now, the best treatments are typically injections into the eye itself that need to be repeated, sometimes on a monthly basis. So having an eye drop that you simply put in twice a day as they did with this experimental drug, instead of having to have an invasive procedure done, would be a huge benefit in being able to reduce the risks, especially of damage to the eye or the rates of infections.”
– Dr. Benjamin Bert
MNT also spoke to Dr. David Geffen, director of optometric and refractive services at the Gordon Schanzlin New Vision in La Jolla, CA, who commented that this study gives great promise to our diabetic retinopathy patients.
“The ability to have an eyedrop rather than shots in the eye will be much more comforting for our patients and easier to maintain compliance,” Dr. Geffen continued. “With diabetes reaching epidemic proportions in this country, any new treatments will be most welcome to all medical providers. Blindness is one of the most feared side effects of diabetes and this treatment should come as a welcome addition to our treatment regime.”