Diabetic retinopathy debate resurfaces with new perspectives

May 9, 2016

Article

The debate over pharmacologic therapy versus laser treatment for diabetic eye disease is back. The players are different–anti-VEGF agents and panretinal laser photocoagulation instead of anti-VEGF agents and macular laser photocoagulation.

Michael Ip, MDThe debate over pharmacologic therapy versus laser treatment for diabetic eye disease is back. The players are different–anti-VEGF agents and panretinal laser photocoagulation instead of anti-VEGF agents and macular laser photocoagulation–but the result could be the same: more anti-VEGF treatment and less laser treatment.

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“Panretinal laser photocoagulation is a proven, effective and safe therapy that we have been using for many decades in the management of our patients who develop proliferative diabetic retinopathy,” outlined Michael Ip, MD, associate professor of ophthalmology and co-director, Fundus Photography Reading Center, University of Wisconsin School of Medicine and Public Health. “But the preponderance of the evidence, what we have been seeing in the clinic anecdotally, secondary outcomes from clinical trials, and from Protocol S indicate that we have a new treatment option for those patients who have proliferative diabetic retinopathy. In some patients, we may wish to start with anti-VEGF.”

Or maybe not

“Protocol S is the first good prospective study looking at laser versus injection for the treatment of proliferative diabetic retinopathy,” explained Rishi Singh, MD, staff physician, Cole Eye Institute/Cleveland Clinic and associate professor of ophthalmology, Case Western Reserve University, Cleveland. “This study validated the safety and benefits of anti-VEGF therapy. The question is whether and how you can apply those findings in clinical practice. When you try to apply findings from clinical studies in real patients, the benefits don’t always gel.”

Drs. Ip and Singh faced off during a debate on whether “Anti-VEGF Injection is the New Standard of Care for Proliferative Diabetic Retinopathy” at the 2015 American Academy of Ophthalmology meeting. For some patients and practices, anti-VEGF can transform the course of disease. For others, laser remains the treatment of choice.

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For Dr. Singh, who argued against anti-VEGF as a new standard of care, it comes down practical issues, such as patient adherence. Anti-VEGF treatment can be as effective as laser, but only if patients come into the clinic for scheduled follow-up evaluations and successive injections.

“If you look at patients with diabetes who get anti-VEGF injections and macular degeneration (AMD) patients who are much older and also get anti-VEGF injections, the rate of no shows in the diabetic population is almost twice the rate in the AMD population,” he said. “That’s telling, because if you are the clinician trying to get something into your patients’ eye once a month, you expect them to be able and willing to come back for monitoring and therapy. If they don’t come back and you have a high rate of no shows, you can’t apply the successful clinical trial practice to that patient and the outcome is poor.”

Laser easier

The problem is less that patients actively resist anti-VEGF treatment, Dr. Singh added, and more that they have other pressing commitments to make appointments. Getting in for a checkup and possibly an injection every month can be difficult for patients with diabetes.

Individuals with diabetes tend to be younger than patients with AMD. They may still be working, may be the primary caregivers for parents or children-or both-and have a variety of societal commitments.

Rearranging their normal activities to accommodate a monthly medical visit amounts to a significant lifestyle change. Lifestyle changes have never been shown to be successful in many diabetic patients.

Panretinal laser photocoagulation is no less effective than anti-VEGF treatment, Dr. Singh said, and it is easier for patients to accommodate. Laser treatment patients in most trials have an average of 2 or 3 sessions during the first year and treatment is finished. Once laser treatment is completed, treatment effects endure for decades.

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“The 2-year data on anti-VEGF treatment looks promising, but patient follow-up and adherence are essential to making sure that you can actually execute such a protocol,” Dr. Singh explained. “As we know from multiple studies, this population with diabetes is not the most successful in following up. We have a breakthrough therapy with anti-VEGF treatment, but we have to temper that enthusiasm with the fact that we don’t have good adherence in this population and we don’t have enough long-term data to call this the new standard of care.”

Anti-VEGF more effective

Dr. Ip agreed that it can be difficult to get some patients into the office on a regular basis for follow-up and continuing treatment. But adherence issues are not unique to anti-VEGF therapy.

“Anti-VEGF has to be given quite frequently and patients have to be monitored quite frequently,” Dr. Ip said. “You can’t just inject them once or twice and then lose them in follow-up.”

In Protocol S, these patients with proliferative diabetic retinopathy received a mean of 7 to 9 injections the first year, depending on whether or not they had concomitant diabetic macular edema, he added. If a patient cannot maintain that kind of adherence, photocoagulation is most appropriate.

Protocol S and clinical observations show that there are two distinct populations of patients who present with proliferative diabetic retinopathy: patients who have concomitant diabetic macular edema (DME) and those who do not.

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For patients with proliferative diabetic retinopathy and DME, anti-VEGF is the treatment of choice unless adherence is a problem. Anti-VEGF treatment not only deals with the progressive retinopathy, it is also helpful for DME. Anti-VEGF treatment also produces less visual field loss than laser treatment and, is associated with both less need for vitrectomy and with better visual acuity.

The decision for or against anti-VEGF treatment is not clear-cut for patients who have proliferative diabetic retinopathy without concomitant DME. Dr. Ip recommended laying out the alternative and present the evidence so the patient can be part of the decision. Most patients, he added, seem to choose anti-VEGF.

“Protocol S showed that visual acuity with anti-VEGF was somewhat better compared with panretinal laser photocoagulation,” Dr. Ip said. “It also showed less development of DME in those eyes randomized to anti-VEGF. There are also multiple case series showing that anti-VEGF is highly effective in regressing diabetic retinopathy.”