How Specialty Pharmacies Can Help Prevent Vision Loss in Diabetic Macular Edema
New agents for vision conditions related to diabetes show promise, but come with challenges.
Specialty pharmacies are poised to play a key role in treating conditions related to diabetes into the future, according a continuing education session at the Asembia Specialty Pharmacy Summit 2017. Diabetic retinopathy (DR) is the leading cause of blindness in the United States, affecting 7.7 million Americans in 2010.
Furthermore, approximately 746,000 Americans 40 years and younger have had diabetic macular edema (DME). These conditions occur in patients with diabetes because high blood pressure weakens the blood vessels in the eye, causing them to leak a fluid that accumulates in the macula, an area of the eye with the keenest vision. When DME is left untreated, it leads to vision loss. In the United States, there has a been a dramatic increase in DME and DR, which is partly due tohigh obesity rates.
“We are in the middle of an obesity epidemic,” said Nancy M. Holekamp, MD, who led the session titled, Preventing Vision Loss in Diabetic Macular Edema—Role of Specialty Pharmacists, which was presented by Pharmacy Times Continuing EducationTM. “Most of the diabetic macular edema and diabetic retinopathy we are seeing is in type 2 diabetes, and type 2 diabetes is closely linked to obesity.”
Although there is no cure for DME, there are treatment options available, including laser photocoagulation, anti-VEGF (vascular endothelial growth factor) agents, corticosteroid injection/implant, and a vitrectomy. For more than 35 years, laser photocoagulation was the gold standard for DME therapy, but the arrival of anti-VEGF agents has changed the treatment landscape.
“It’s been revolutionary,” Dr Holekamp said. “In the past, we used focal lasers for treating diabetic macular edema, and we could never promise anyone that their vision might improve. With anti-VEGF injections, we know that 30% to 40% of people will get significant improvement in vision. We also know that these anti-VEGF agents can reverse diabetic retinopathy, and that’s truly remarkable and unprecedented.”
In 2014, the FDA approved the first VEGF inhibitor aflibercept (Eylea) for the treatment of DME. More recently, ranibizumab (Lucentis) was granted FDA approval for all forms of DR. Bevacizumab (Avastin) has not yet been approved by the FDA, but is used in practice.
“Again, it’s remarkable,” Dr Holekamp said. “It stems from the fact that in the clinical trials that got ranibizumab FDA-approved for treating diabetic macular edema, they found that ranibizumab could reverse all forms of diabetic retinopathy, including nonproliferative diabetic retinopathy and even proliferative diabetic retinopathy.”
In the 2 clinical trials RIDE and RISE, ranibizumab was compared to the laser treatment for proliferative diabetic retinopathy. The results showed ranibizumab improved vision, had fewer side effects, and showed apparent superiority to laser, according to Dr. Holekamp.
“Every other study looking at anti-VEGF therapy, including the clinical trials for aflibercept, show a reversal of diabetic retinopathy score,” she said. “So, the FDA granted ranibizumab approval for all forms of diabetic retinopathy, with or without diabetic macular edema.”
The randomized, multicenter, double-blind, sham-controlled RISE and RIDE, trials included 759 patients, of whom 34% to 45% administered 0.3-mg of ranibizumab by intravitreal injection monthly gained 3 lines of vision compared with 12% to 18% administered sham injections. Overall, DR was more likely to improve and less likely to progress with ranibizumab. While these agents can stop vision loss and potentially reverse it, the high costs and multiple injections required over several months may limit adherence, according to Dr Holekamp.
To compare the efficacy of ranibizumab, aflibercept, and bevacizumab, investigators conducted the PROTOCOL T study, which was the first comparative trial of the 3 anti-VEGF agents for the treatment of DME. “What they found was that all the agents work but they only give benefit if you had about 9 or 10 [injections] in the first year of treatment,” Dr Holekamp said. “That’s a very important point that a lot of people overlook, because undertreatment with anti-VEGF agents is very a serious problem in this country.”
FROM LAB TO REAL-LIFE
Although the DME landscape continues to evolve, there are still gaps in care. Studies that include anti-VEGF treatments must translate to clinical practice because 9 injections in the first year of treatment are impractical. Additionally, gaining the ability to read 1 more line on an eye chart may not have meaningful functional value.
The lack of evidence for treatment of non-responders also poses an issue in the DME care continuum. Furthermore, DME-related services such as screenings, diagnosis, treatment, and ongoing care may not be covered by insurance. To justify the high cost of anti-VEGF agents, precise data on the DME financial impact to the patient and society are needed.
Specialty pharmacies have several channels that can be used to improve patient care and help prevent vision loss in patients with DME. Identical to treatment for other conditions, adherence is critical in treating DR and DME. Specialty pharmacists should identify patients at risk of DME or DR, and refer all patients with diabetes for complete, routine eye exams, according to Dr Holekamp.
Adherence to scheduled eye exams and treatment regimens should be encouraged for patients with DR or DME. Specialty pharmacists should initiate preventive strategies and patient education, evaluate treatment, and assess adherence.
DME and DR patient education should increase awareness; describe the risk of vision loss; explain ways to prevent vision loss; address barriers to diabetes care, such as communication, depression, and lack of education; provide reminders for routine eye exams; clearly explain therapy requirements, such as frequent visits, costs, and potential adverse events; monitor the safety and efficacy of the therapy; and explain what the patient should expect with therapy.
“Specialty pharmacists are part of the health care team, and everyone that comes into contact with diabetics needs to reinforce the same message so that patients are hearing the same thing from all people: Every diabetic needs at least a yearly eye exam if you’re a diabetic patient who’s currently being treated for diabetic retinopathy or diabetic macular edema,” Dr Holekamp said. “It’s reasonable to have expectations of improvement, but it requires compliance with the treatment regimen, even if that means coming in monthly for a year or more. We have very successful treatments and really great drugs for diabetic retinopathy but patients have to come into the office to get them.”