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Anti-VEGF patterns of use for DME may vary in clinical practice


Though anti-vascular endothelial growth factor therapy for diabetic macular edema showed impressive results in trials, clinicians have reported less success on their own.

Take-home message: Though anti-vascular endothelial growth factor therapy for diabetic macular edema showed impressive results in trials, clinicians have reported less success on their own.


By Laird Harrison; Reviewed by Kevin J. Blinder, MD

St. Louis, MO-Anti-vascular endothelial growth factor (VEGF) treatments for diabetic macular edema (DME) have not worked as well in clinical practice as in clinical trials, according to one clinician.

“Treatment was less effective than in the registration trials, most likely due to the infrequency of the injections,” said Kevin J. Blinder, MD, partner, The Retina Institute, and professor of clinical ophthalmology and visual sciences, Washington University in Saint Louis, MO.

To examine this phenomenon, Dr. Blinder and his colleagues, in a trial sponsored by Allergan, reviewed the records of 156 patients who had received at least three anti-VEGF injections for DME at 10 sites.

Study design

The patients’ mean age was 63.4 years. More than 80% had type II diabetes, and more than 40% had a history of focal laser photocoagulation treatments.


The mean best-corrected visual acuity (BCVA) was 11.8 ETDRS lines, the Snellen equivalent of 20/63. The mean central retinal thickness (CRT) was 413 µm.

Patients received a total of 1,222 anti-VEGF injections-of which 51.3% were bevacizumab (Avastin, Genentech) and 48.6% were ranibizumab (Lucentis, Genentech). Only 1 patient received aflibercept (Eylea, Regeneron), which had not yet been FDA approved for DME during the study period.

The researchers set as their primary endpoint a BCVA of 20/40 or better and a CRT of 250 µm or less on time-domain optical coherence tomography (TD-OCT) or 300 µm on spectral-domain optical coherence tomography (SD-OCT). After the first anti-VEGF injection, 11.2% reached this endpoint. Even after 19 injections, the proportion never exceeded 25% of the patients.

Likewise, the mean increase in BCVA from baseline across all injections was 1.1 lines. It was a statistically significant change (p < 0.001), but not as robust a result as seen in the clinical trials. The results of this survey of outcomes in practice cannot be compared directly with the clinical trials because the two studies used different outcome measures, Dr. Blinder said.

The larger point, however, is that “we are not doing a great job treating these patients,” he said.

Infrequency of injections

Disappointing results clinical practice most likely stem from the low number of injections, Dr. Blinder said.


While patients received monthly injections in the trials, the mean number of injections in practice was 5.8 in the first year, 5.0 in the second year and 3.4 in the third year.

“There are many reasons for the lower frequency of injections,” Dr. Blinder said. “One is that patients don’t like injections. They can’t understand why they have to have them so often to maintain vision or see better.”

In addition, caregivers may not be able to drive patients to appointments every month. Some patients run out of money to pay for the injection co-payments and or transportation.

“Lastly, the physicians may not have the ability to treat as often as they’d like due to patient flow issues,” Dr. Blinder said.

Response to therapy

Overall, the patients tolerated anti-VEGF therapy well. IOP increased from baseline by more than 10 mm Hg in 5.1%, by more than 25 mm Hg in 7.7% and by more than 35 mm Hg in 1.3%.

There were 6 instances of ocular hypertension or glaucoma, 2 of floaters, and 2 of subconjunctival hemorrhage.

Given these findings, clinicians should strive to treat their DME patients more often, Dr. Blinder said. But for some patients, other solutions may be necessary.

“Not all patients respond optimally to anti-VEGF therapy,” he said. “We should consider other treatment options for these patients.”


Kevin J. Blinder, MD


This article was adapted from Dr. Blinder’s presentation at the 2015 meeting of the American Society of Retina Specialists. He did not indicate any proprietary interest in the subject matter.

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