What’s New in DME Care

BY DESIREE IFFT, CONTRIBUTING EDITOR

➤ Iluvien, approved by the FDA last year, is the first DME treatment designed to have a therapeutic effect for 36 months. In a subgroup analysis from the pivotal Phase III FAME clinical trial,¹ 34% of patients who had chronic DME (duration of ≥3 years) at baseline gained ≥15 letters of vision with Iluvien at 36 months compared with 22.3% of those with nonchronic DME. This may lend credence to the hypothesis that there are pathologic differences between chronic and nonchronic DME. “DME may progress through stages,” explains Pravin U. Dugel, MD. “For instance, it likely begins as a permeability-driven disease but over time becomes primarily an inflammation-driven disease. That means different treatments may be more or less effective at various stages, a concept we may someday be able to apply to clinical practice.”

For similar reasons, “As we gain more experience with Iluvien, we may find it to be useful as part of combination therapy,” notes Michael A. Singer, MD. “I’m currently following the first several patients in whom I’m using Iluvien.” (Figure 1)

Figure 1. Prior to implantation of Iluvien, central foveal thickness (CFT) as measured by OCT in this eye with DME was 485 µm (a) and visual acuity was 20/150. One month after implantation, CFT had improved to 198 µm (b) and visual acuity was 20/70. Peripheral ischemia is also being monitored, and the implant had begun to have an effect on the ischemic index at 1 month. The index (area of ischemia defined as a percentage of the total visible retina) decreased from 71.4% prior to implantation (c and d) to 69.4% 1 month after implantation (e and f).

➤ Combination therapy for macular edema secondary to retinal vein occlusion (RVO) is being evaluated in a Phase II clinical trial, which will likely have eventual implications for DME as well. The trial is comparing the safety and efficacy of a suprachoroidal injection of a proprietary formulation of triamcinolone (CLS-TA, Clearside Biomedical) combined with a single intravitreal injection of an anti-VEGF agent vs. the anti-VEGF agent alone.

“This is definitely an exciting concept because suprachoroidal delivery of the medication may produce fewer side effects, such as IOP elevation, than intravitreal treatments or drops, and the combination of steroid and anti-VEGF may have a longer-lasting effect than either treatment alone,” says Daniel Kiernan, MD. “Suprachoroidal delivery and new drug delivery strategies like nanoparticles will probably be how we treat retinal diseases in the future.”

Clearside recently announced results from another of its clinical trials, a Phase I/II study in which noninfectious uveitis was treated with a suprachoroidal injection of triamcinolone. At 6 months, the treatment led to anatomic and visual improvements and no patient required IOP-lowering medication.

➤ Widefield imaging has been an essential tool for exploring concepts related to macular edema and peripheral retinal ischemia. “Widefield angiography will be a game-changer for the DME patient population,” says Dr. Singer. “We’ve shown in RVO² that the extent of peripheral ischemia (assessed with the 200Tx, Optos) varies and fluctuates over time, changes dynamically in response to treatment and correlates with severity of edema and vision loss. We’ll be able to use this knowledge to monitor and perhaps even predict response to different treatments.”

Dr. Singer and colleagues have also used widefield imaging to map peripheral ischemia in patients with rebound edema so it can be treated with guided/targeted photocoagulation (Navilas laser, OD-OS). The company recently reported its finding that in order to achieve the best results, ischemia should be measured at the time of macular edema.³ “The map to follow is what’s measured when the retina is most swollen,” he says. “Steroid or anti-VEGF treatment can then be given prior to laser treatment.”

➤ OCT angiography (AngioVue, Optovue and Spectralis, Heidelberg Engineering), which enables 3D visualization of the retinal vasculature without a contrast agent, is also on the cutting edge of imaging for DME. According to Dr. Dugel, “New therapies and combination therapies being explored^4,5 appear able to alter or stabilize the eye’s blood vessels in ischemic retinopathies such as diabetic eye disease. What better way to assess these types of changes than with OCT angiography?” ■

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