Diabetes Forecast

Macular Edema Treatments

By Allison Tsai ,

People with diabetes are more susceptible to developing macular edema, a swelling of the retina, than those without. Fortunately, there are multiple treatments available, and one even has the potential to restore lost vision.

Anti-VEGF Therapy

The most groundbreaking treatment for diabetic macular edema to date hit the market about five years ago in the form of anti-vascular endothelial growth factor inhibitor (anti-VEGF) therapy, says Neil Bressler, MD, professor of ophthalmology and chief of the Retina Division at Johns Hopkins University School of Medicine. After the eye is numbed, these drugs are injected into the eye to stop blood vessels from leaking. Prior to that, the standard treatment was to use laser surgery to seal some of the vessels in the areas where leaks were occurring.

While laser therapy could prevent further vision loss in many people, it could not improve vision in most people. Anti-VEGF therapy can. “Instead of 1 out of 6 people losing vision [with laser treatment] maybe 1 out of 20 people lose vision [with anti-VEGF treatment],” says Bressler. And instead of only a third of people improving with laser, two-thirds improve with injections, he says. “I’ve had many patients who are legally blind [and] whose vision has been restored to the point where many of them can now drive with anti-VEGF agents,” says Raj Maturi, MD, associate professor of clinical ophthalmology at Indiana University School of Medicine and partner at the Midwest Eye Institute in Indianapolis.

There are three injectable agents currently on the market: ranibizumab (Lucentis), aflibercept (Eylea), and bevacizumab (Avastin). The Food and Drug Administration (FDA) has not approved Avastin for the treatment of macular edema, but studies have shown it to be an effective treatment. The medications are delivered in a series of injections, usually eight or nine in the first year and tapering off each year until you may no longer need injections.

The Process: It may sound scary to have something injected into your eye, but Bressler says it’s painless. “We use a needle about the size of a hair, and with topical numbing drops, you feel like a hair pushing against the white part of your eye for second,” he says. After the injection, you can typically resume normal activity, though some people prefer to have a bandage over the eye for 15 minutes, especially on bright days, Maturi says.

The Timeline: The treatment schedule can be pretty rigorous in the first year. “You have to get monitored almost monthly for a year to get it under control, and you’re often treated eight or nine times in the first year,” says Bressler. Treatment tapers off each year until, around the five-year mark, you may no longer need injections. “We try to convince people to stick with us,” he says, because if you can get it under control in the first year, you may not have a problem for the rest of your life. Continuing control of blood glucose levels is important, however.

The Cost: The anti-VEGF agents can be very costly, particularly Lucentis and Eylea. Avastin is the least expensive because it’s used off label and is not packaged as an eye injection. Compounding pharmacies can dose Avastin for eye injections at a much lower cost. Based on a recent study from the National Eye Institute that compared the three agents, Medicare will cover Eylea at $1,960, Lucentis at $1,200, and Avastin at $70. With Medicare or Medicaid, there’s no residual cost. But for those with commercial insurance, the copay or direct cost may vary.

The Comparison: The National Eye Institute study, which was conducted by the Diabetic Retinopathy Clinical Research Network and published in 2015 in the New England Journal of Medicine, compared the effectiveness of these three agents. The findings are important for how doctors will use these drugs, particularly because cost is an issue. 

They found that when starting vision loss was moderate or severe (20/50 or worse), Eylea showed greater visual improvement on average than Lucentis or Avastin. But, for people with mild vision loss (20/40 to 20/32), all three drugs showed similar average improvements. In addition, there were no major safety differences among the three agents.

“I think the key here is that this study shows we have choices,” says Frederick Ferris, MD, clinical director and director of the Division of Epidemiology of Clinical Applications at the National Eye Institute. “Any of the three are effective, but especially for those with moderate to severe vision loss, the more effective one seems to be Eylea.”

Keep in mind: These are averages of improvement for the drug, not for an individual, which means some participants saw greater improvements than others. And, because many factors go into the decision of which to use, these study results will help ophthalmologists and their patients to individualize the best treatment choice.

Steroid Implants

When anti-VEGF agents aren’t enough for a person with macular edema, Maturi will sometimes use a steroid implant to further reduce retinal swelling. “They work on the retina quite well due to their proximity,” he says. Although steroids are known to increase blood glucose levels, these implants contain too small of a dose to impact blood glucose control, says Maturi.

You have two options: a dexamethasone intravitreal implant (Ozurdex) or a fluocinolone acetonide intravitreal implant (Iluvien). There is a difference in side effects, so discuss your options with your doctor.

The Process: After the eye is numbed, a special applicator and 22-gauge needle are used to inject a tiny, rod-shaped implant into the white portion of the eye, near the retina.

The Timeline: Ozurdex works for about four months. After that, swelling and inflammation may return. If this happens, you may need another implant. Iluvien works for about two years.

Once you have an injection, your doctor will want to check your eye pressure because the implant may cause glaucoma. You also may experience temporary blurry vision after the injection, so arrange for a ride home ahead of time.

The Cost: Maturi estimates Ozurdex costs about $1,500 per implant while Iluvien runs around $7,000.

The Comparison: Because Iluvien lasts for two years—during which time the eye is constantly exposed to steroids—cataracts and glaucoma are likely to develop, says Maturi. According to clinical trial data for Iluvien, 82 percent of enrolled patients developed cataracts and 34 percent developed glaucoma.

With those risks, some people with macular edema may skip treatment. But in certain cases, the risk is worth the reward: In a 2014 study published in the Journal of Ophthalmology, which compared effectiveness and side effects of these two steroid implants, researchers concluded that Iluvien was best used for people who do not respond well to anti-VEGF agents or who, due to frequent recurrences of macular edema, require treatment lasting more than four to six months. If a person is seeing results with Ozurdex, has no rise in eye pressure, but continues to need multiple injections, “Iluvien may be an option at that time,” says Maturi. For those people, this would mean fewer office visits to receive the injection (and thus fewer opportunities for infection) and less cost over the course of two years.

But Ozurdex works for only four months, limiting a person’s steroid exposure. Because of this, eye complications usually don’t have a chance to develop as quickly. That gives doctors a bit more flexibility in dosing: They can assess patients after four months and decide whether or not to continue treatment.

In some cases, Maturi will use triple therapy, using anti-VEGF agents, a steroid implant, and a laser therapy simultaneously.


Learn more about diabetes-related eye disease.

Read up on treatments for proliferative retinopathy.



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