Diabetic Macular Edema Vastly Undertreated, Real-World Data Suggest

Caroline Helwick

November 14, 2017

NEW ORLEANS — Most patients with newly diagnosed diabetic macular edema (DME) are inadequately treated, according to findings from the American Academy of Ophthalmology's IRIS Registry.

"We found that DME patients are likely undertreated in the real-world setting," said study investigator Jeffrey R. Willis, MD, PhD, from the University of California Davis in Sacramento, who is also employed by Genentech, the study's sponsor. "Even when patients receive anti-VEGF [vascular endothelial growth factor] treatment, they are likely to get a suboptimal number of injections."

The Intelligent Research in Sight (IRIS) registry is the United States' first comprehensive eye disease clinical database. Approximately 70% of ophthalmologists, or about 13,000 physicians, contribute data to the registry.

IRIS has provided information that has been lacking regarding the treatment of diabetic macular edema," Dr Willis said during his presentation at the American Academy of Ophthalmology (AAO) 2017 Annual Meeting.

He reported that three fourths of patients with DME received no treatment within the first month of diagnosis, and 60% remained untreated for a year. When patients were treated, which was mostly with anti-VEGF agents, at least half received three or fewer injections during the first year of follow-up.

"While anti-VEGF treatment has been shown to be efficacious and well tolerated, these results indicate that other factors may influence the decision to use anti-VEGF treatment. DME may be undertreated in a real-world population….This suggests there are barriers to optimal treatment in the US," he said.

Most Patients Were Only Observed

Overall the registry includes 197,220 patients with a record of DME diagnosed between July 1, 2013, and March 31, 2016. After relevant exclusions, the final study population included 13,410 patients (mean age, 66 years) with newly diagnosed treatment-naive disease.

DME was unilateral in 49% of patients and bilateral in 51%. More than two thirds of the patients had some form of public health insurance. Most patients (58%) received care from retina specialists, followed by general ophthalmologists (30%), with the remainder seen by optometrists (5%) or unknown (7%). Vision impairment was considered mild in 37%, moderate in 35%, and severe in 16%; 12% had no vision impairment.

Three-quarters of patients (74.5%) received no treatment during the first 28 days after diagnosis and only 15.6% started anti-VEGF therapy. A year after diagnosis, more than half (60.4%) remained untreated, including 81% of those who were only observed during the first month.

Table. Treatment of Newly Diagnosed DME in the IRIS Registry (n = 13,410)

Time Point Observation (%) Anti-VEGF (%) Laser (%) Steroid/Other (%)
28 d 74.5 15.6 8.5 1.5
1 y 60.4/td> 23.5 13.7 2.4


At both 28 days and 1 year, the preferred anti-VEGF agent was bevacizumab, which was given to 71.3% and 70.1%, at the respective time points. Aflibercept was administered to 17.1% and 18.3%, respectively, and ranibizumab to 11.6% and 11.7%.

"Among individuals who were started on anti-VEGF therapy during the first 4 weeks, we found that the mean number of injections during the first year was around 4.2," Dr Willis said. "About 50% of individuals received three or fewer injections during the first year. This is quite low and really underlines the undertreatment of DME."

Dr Willis acknowledged that the diagnosis of DME was based on International Classification of Diseases coding and "may not indicate clinically significant disease." Also, patients categorized as "observed" may have been referred to an ophthalmologist outside of the IRIS registry, leading to an underestimation of treatment prevalence. There could also be incomplete data capture and selection bias from practices where data collection is more stringent, he said.

What Conclusions Can Be Drawn?

Several panelists at the session were surprised by the findings and also expressed caution in their interpretation of them.

"I'm actually floored by the results — that we are so vastly undertreating diabetic macular edema despite all these great protocols that we have," said Michael Ip, MD, from the Doheny Eye Institute and University of California Los Angeles.

"The question is, how much do we actually believe the data? One of the problems is, who is actually making the diagnosis? What percentage of diagnoses were made by ophthalmologists versus optometrists versus retina specialists? If it's a retina specialist practice, I would definitely believe it," he said.

The key criterion for inclusion in the study was stringent electronic health record (EHR) reporting practices. Dr Willis acknowledged that standardization of EHR reporting could lend more validation and credence to the findings.

IRIS participants do not yet include ophthalmologists at academic medical centers, which use an EHR that is incompatible with IRIS. Marco Zarbin, MD, from Rutgers New Jersey Medical School in Newark, suggested this could create imbalances in representation across the country, and he urged caution in assuming treatment is inadequate.

"In the world that I live in, the failure of people to get their injections is not because we're not showing up at work every day. It's because there are problems with access to care, such as transportation," Dr Zarbin said.

Dr Willis is employed by Genentech, which sponsored this study.

American Academy of Ophthalmology (AAO) 2017 Annual Meeting. Abstract PA017. Presented November 13, 2017.

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