Using real-world experience, a retinal surgeon highlights the optimal settings for use of steroid implants for treatment of diabetic macular edema.
Take-home message: Using real-world experience, a retinal surgeon highlights the optimal settings for use of steroid implants for treatment of diabetic macular edema.
By Michelle Dalton, ELS; Reviewed by Andrew Moshfeghi, MD
Los Angeles-Within the past year, two sustained-release intravitreal injection implants-dexamethasone (Ozurdex, Allergan) and fluocinolone (Iluvien, Alimera Sciences)-were approved for the treatment of diabetic macular edema(DME) by the FDA.
Dexamethasone is designed to be implanted every 6 months, whereas fluocinolone is designed to be have a treatment effect for 36 months; these indications were based off results from the respective pivotal studies.
Retina specialists, however, are finding a diminished durability effect with dexamethasone. (Fluocinolone had not yet started shipping by the end of 2014, limiting its real-world experience.)
“We don’t yet know if there is a diminished real-world durability effect with [fluocinolone], or what the best way to handle the diminished effect may be,” said Andrew Moshfeghi, MD, Los Angeles.
Physicians may opt to “touch up” patients with anti-vascular endothelial growth factor (VEGF) agents until insurance companies determine how often they will reimburse for the implant, Dr. Moshfeghi explained.
“We also have to think about the implications-if we re-implant, are we risking a higher rate of glaucoma?” he posed.
In his real-world experience, those issues have not manifested in patients who needed to be treated earlier than every 6 months with dexamethasone, Dr. Moshfeghi said, although he only has limited experience with early re-treatment.
Most physicians are not likely to use these implants as first-line DME treatments, “but will serve as a second-line therapy for patients who have a suboptimal response to anti-VEGF therapy, Dr. Moshfeghi said.
“That doesn't mean that patients didn't have a measurable, noticeable response to anti-VEGF therapy,” he said. “It just means it wasn’t as robust of a response as would have [been] liked, based primarily on optical coherence tomography (OCT) measurements and assessments, as well as visual acuity outcomes.”
In clinical trials, improved visual acuity is usually a primary outcome, but “in clinical trials, it’s very rigorously measured,” he said. In clinical practice, “it's difficult for everyday clinicians to use visual acuity as a reliable and consistent way to follow a patient, unless there's a dramatic change in the visual acuity.”
For instance, in clinical trials, a change in visual acuity from 20/60 to 20/80 would be considered relevant. However, in real-world settings, that difference may not be dramatic enough to warrant a change in treatment, as there could be a multitude of reasons for the difference. Patients may have worn outdated prescription glasses at one visit but not the next, for example.
Instead, Dr. Moshfeghi recommends relying on qualitative OCT data first, and quantitative OCT data second.
He relies “100% on the appearance of the retina on OCT,” he said. “Second, I evaluate the central retinal thickness (CRT) measurement in microns on OCT or the change from one visit to the next.”
Third, he’ll evaluate the clinical appearance of the lesions, and lastly he’ll consider visual acuity.
If the CRT is not coming down enough or if he continues to see diffuse retinal thickening, that’s when he’ll move from anti-VEGF to steroid implants.
“I anticipate using the [dexamethasone] every 3 to 4 months instead of every 5 to 6 months,” he said.
Having real-world experience with the implant (and additional clinical trial data) on Ozurdex for retinal vein occlusion has bolstered Dr. Moshfeghi’s confidence that “this steroid really only lasts with a clinical therapeutic effect for about 3 to 4 months, which is still pretty good,” he said.
No current scenarios exist where steroid implants should be considered a first-line therapy, Dr. Moshfeghi said, mainly because of the well-known and well-documented potential for IOP spikes and elevations, and the cataractogenic aspects of steroids.
Steroid implants might be considered as a first-line treatment in patients with extreme limited ability to travel to the office. However, if access to the office would be difficult for monthly anti-VEGF injections, it is likely to be difficult for monthly IOP monitoring as well.
“As long as [these patients] were able to get to an optometrist or general ophthalmologist for pressure monitoring, I might be a little more lenient,” he said.
Lens status is not as much of a concern in patients over age 60, but will become a factor in younger patients. However, even in older patients, the retina specialist needs to have a careful discussion about the relationship between corticosteroids and cataract worsening, vis-à-vis, the ultimate need for cataract surgery and its implications.
“Having cataract surgery at a young age has some potentially significant drawbacks, so if I can avoid it in that younger age group, I would,” Dr. Moshfeghi said. “However, the potentially deleterious side effects of cataract surgery at a young age, in my opinion, are outweighed by the potentially deleterious side effects of suboptimally treating DME.”
He advised having a much longer conversation with younger patients before using either steroid implant, beginning with discussing what a cataract is, or how that will affect their vision.
For now, anti-VEGFs remain the primary “go-to” treatment for DME, but steroids should be considered a salvage therapy, Dr. Moshfeghi said.
“I don’t envision a scenario where that would change, not because steroids are not efficacious-but because of the safety profile,” he said. “If we later uncover some negative information about the chronic exposure to anti-VEGF monotherapy, that may change. For now, however, steroids will remain second-line.”
Andrew Moshfeghi, MD
Dr. Moshfeghi did not indicate a proprietary interest in the subject matter.