As a diagnosis, DME often has company

Whatever the other condition, consider speaking to an expert in that field. Everyone benefits.

By Wendy Lyons Sunshine, Contributing Editor

The patient has diabetic macular edema (DME), but he also has had a stroke within the last six to 12 months. Using steroids to treat the DME is certainly an option, especially the shorter-acting steroids, but going down that road is also risky — orbital fibrosis and global perforation can ensue.

Other patients with DME might be resistant to an anti-VEGF medication; others need cataract surgery.

Retina specialists — and cataract and refractive specialists — agree that co-management of these complex patients is not an option; it’s a necessity.

Treatment often demands a multi-layered strategy, says Seenu M. Hariprasad, MD, University of Chicago, director of Clinical Research, chief of the Vitreoretinal Service, and professor of Ophthalmology & Visual Science. “Retinovascular diseases are multifactorial and need a combination therapy approach to optimize outcomes.”

Agreed, says cataract specialist Johnny L. Gayton, MD, of Eyesight Associates in Warner Robins, Ga. “Because diabetic macular edema is such a serious issue, I feel that it is imperative to work closely with retina specialists to ensure the patient have the best outcome.”

Fellow cataract surgeon Lisa Brothers Arbisser, MD, calls it a surgeon’s “obligation to rule out, or in, diabetic retinopathy prior to performing the surgery.”

The questions, of course, revolve around: if this is the complexity, then what treatments do we choose, and for how long does the patient endure that treatment, and what comes next.

Reducing the VEGF load

FDA-approved anti-VEGF medications include ranibizumab (Lucentis, Genentech) which is injected monthly, and aflibercept (Eylea, Regeneron), which is injected monthly for the first five months, then every other month. Reduced dosing is appealing, because it limits adverse reactions and requires less time and discomfort for the patient.

J. John Woo, MD, a solo retina specialist at Advanced Retina Center in Vienna, Va., treats many DME patients. “Most retina specialists prefer anti-VEGF as first-line therapy for center-involving DME, because studies show that anti-VEGF medicines have more prolonged benefit than steroids.”

Managing side effects is nuanced, says Dr. Woo. “Anti-VEGF does slightly increase the risk of stroke or heart attack. For patients who had a stroke or heart attack within the last six months to a year, I am very wary to use anti-VEGF and will recommend steroids. After they have been stable for more than a year, I think it’s reasonable to consider anti-VEGF.”

Barry A. Schechter, MD, director of Cornea & Cataract Services, Glaucoma, External Disease & Comprehensive Ophthalmology at Florida Eye Microsurgical Institute, has seen Kenalog (triamcinolone acetonide; Bristol-Myers Squibb; Triesence, Alcon) and steroid injections widely replaced by anti-VEGF medications.

Dr. Schechter notes that the shorter-acting steroids, requiring frequent periocular injections, can lead to complications such as orbital fibrosis, global perforation and ptosis. A patient’s insurance coverage can also affect the choice of compounds, he notes.

Corticosteroids offer alternative benefits

Historically, triamcinolone acetonide was among the drugs used off label to reduce inflammation. Dexamethasone (Ozurdex, Allergan) and fluocinolone acetonide (Iluvien, Alimera Sciences) are newer corticosteroid intravitreal implants approved for DME. Both are sustained-release to give patients more time between office visits. However, the extended steroid exposure can affect IOP and speed cataract formation.

If a patient doesn’t respond sufficiently to anti-VEGF treatment, steroids can provide a good option. “Some people can get monthly anti-VEGF injections and still have macular edema and their vision is not improved significantly. For those patients, if you inject steroids, you can see a remarkable improvement,” says Dr. Woo.

Dr. Woo likes to start with a shorter-acting steroid and monitor IOP. “If a patient already has open-angle glaucoma and is on medical treatment, we try not to use steroids,” he says. “Those patients are much more susceptible to IOP rise from steroids.” Provided there is no IOP issue, Dr. Woo does not co-manage these patients. If IOP rises post-steroid injection, he manages with medical eye drops. “I will either refer patients back to their ophthalmologist or a glaucoma specialist if IOP is not responding to a single glaucoma med and additional meds need to be started, or if the patient’s cup to disc ratio is concerning [0.5 or higher],” Dr. Woo explains. “I stress the importance of all the doctors involved being aware of the DME and IOP issues.”

“Intraocular steroids can play a valuable role in cases resistant to VEG-F blockage,” agrees Norman C. Nelson, Jr., MD of Retina Associates of Middle Georgia. Because of the associated cataract and IOP risks, he prefers intraocular steroids as a final long-term effort to control DME.

With the newer drugs, IOP rise (if it occurs) is more predictable and the magnitude of IOP rise is typically less, says Dr. Hariprasad. “In my experience with Ozurdex and Iluvien, the IOP rise is not as violent as with off-label triamcinolone acetonide.” Patients with potential IOP elevation are excluded by Iluvien’s current FDA label.

When surgery is needed

When steroids lead to cataracts, surgery is the natural next step. Dr. Schechter, a cataract/cornea specialist who frequently operates with his retina specialist partner, sees steroids as helpful adjuvants to anti-VEGF compounds in more advanced cases with severe edema or in cases refractory to anti-VEGF injections alone.

“Maintaining a low but constant drug level should, theoretically, reduce the ocular damage as well as reduce steroidal side effects,” he says. “On average, most patients will have raised IOP and cataract development in response to the use of intraocular steroids. The underlying disease process will also contribute to cataract formation and elevated intraocular pressure.”

Dr. Schechter advises, “In advanced cases of proliferative vitreoretinopathy or vitreous hemorrhage, vitreo-retinal surgery may need to be combined with cataract surgery. Once the DME is controlled, any additional surgery, such as a cataract or glaucoma procedure can be safely done by the specialist best trained to [do so].”

Dr. Nelson uses a VEGF blockade pre-operatively to eliminate or at least stabilize the edema. “Treatment should continue until a relatively stable amount of edema is present,” he says. “Three timely treatments should achieve near maximum VEGF blockade. Despite this, the DME may still only slowly resolve but I see no general prohibition to cataract extraction at that point.” He generally treats with VEGF-blocking agents two weeks prior to cataract extraction and then follows up with the patient about three to four weeks after surgery.

Optimizing cataract surgery in DME patients

To optimize outcomes, Dr. Hariprasad urges cataract surgeons to send any patient with known DME to a retina specialist for pre-cataract surgery evaluation. The specialist can provide treatment to protect the macula during surgery.

For patients with a clear area in the cataract, Dr. Arbisser, an adjunct professor in the Department of Ophthalmology at Moran Eye Center at the University of Utah, will do a functional test to evaluate macular function and visual acuity. She starts with the pinhole occluder test at near, using a +3 lens and having the patient read up close. “That can give us a fine idea, because the pinhole eliminates blur from the cataract. The ultimate test to identify macular edema thickening is OCT.” She also checks the patient’s hemoglobin, blood pressure and systemic status, so these can be addressed along with lifestyle issues.

Only after the retinologist confirms that the patient’s DME is adequately controlled will she schedule surgery. A preoperative baseline OCT helps Dr. Arbisser know how aggressive to be with anti-inflammatory medication. Because these patients are prone to swelling, she uses nonsteroidal and steroidal coverage for seven days presurgery, instead of the usual two-day coverage.

“I’ll use some Triesence intracamerally at the end of surgery to reduce inflammation immediately postop, and make sure they get to the retinologist for follow-up within three months,” says Dr. Arbisser. She prescribes NSAIDs for six to 12 weeks after surgery, depending on how they’re doing with DME.

Dr. Arbisser says it’s vital to get DME under control before operating. “Cataract surgery creates inflammation, and inflammation promotes edema. Any vision lost to DME is hard to regain, so first we want to get control of the underlying disease.” OM