Diabetic macular edema intravitreal insert treatment aims high

Key Points

"The insert is designed to release fluocinolone acetonide at low and high doses," said Frank G. Holz, MD, professor and chairman, Department of Ophthalmology at the University of Bonn, Bonn, Germany, and a co-investigator in the study. "Preliminary data show that the device appears to be beneficial, as the functional improvements in terms of visual acuity have improved in these patients at both dosages."

The administration of corticosteroids commonly is associated with secondary increases in IOP. The study data showed that although it was only temporary, at least 12% of the patients who received the high dosage of the drug demonstrated increases in IOP recorded at more than 30 mm Hg. The low-dose group did not show any increases in IOP.

One of the mainstay therapeutic approaches for patients with DME is frequent intravitreal injections of corticosteroids. Repeated injections pose an increased risk of infection. Though effective in subduing the disease, the therapeutic approach is fraught with adverse events that include cataracts and increased IOP that often leads to glaucoma.

"One of the great advantages of the insert is that it is designed to maintain drug release for up to 36 months at the low dosage and 24 months at the high dosage," said Joao Figueira, MD, of the Department of Ophthalmology at the University Hospital of Coimbra, Coimbra, Portugal, and co-investigator in the study. "This approach could effectively do away with the necessity to administer frequent injections of corticosteroids."

According to Dr. Holz, current therapy of repeated intravitreal injections may have to be done once a month, underscoring the advantages of long-acting therapies such as the fluocinolone acetonide insert.

A look at other therapies

Other therapies used in DME include laser photocoagulation; currently, trials under way are exploring the efficacy of anti-vascular endothelial growth factor agents such as bevacizumab (Avastin, Genentech) and ranibizumab (Lucentis, Genentech). Though effective, corti-costeroid therapy can increase the risk of IOP increase in patients with DME, a disadvantage to this therapeutic approach. The general direction in ophthalmology today concerning the treatment of DME is gravitating toward pharmacologic therapies and away from destructive therapies.

"The hope is that we can treat macular edema more efficiently than by using destructive laser treatments and have a better functional outcome in terms of visual acuity," Dr. Holz said. "However, we still need to be wary of the potential adverse events that corticosteroid therapies can elicit, and, therefore, we simply must wait and see what the final results will be at the end of the study."

Potential indications

Other potential indications for this approach include retinal vein occlusions of the branch vein or central vein or uveitis-related intraocular inflammation resulting in intraocular edema as well as Irvine-Gass syndrome.

A non-biodegradable intravitreal device (Retisert, Bausch & Lomb) is approved by the FDA for posterior non-infectious uveitis but not for DME. The device is implanted surgically in the posterior segment and sutured to the pars plana. The release of the drug occurs in the anterior vitreous, which may explain the higher rate of adverse events seen, according to Dr. Figueira.

Another implant (Posurdex, Allergan) has a similar concept to the fluocinolone acetonide insert in that it also can be deployed via an injection but consists of dexamethasone mixed with a biodegradable polymer. In this case, as the polymer degrades, the corticosteroid is released. The implant is estimated to be effective for only 4 to 6 months, i.e., shorter in duration than the insert containing fluocinolone acetonide. It is placed farther from the anterior segment of the eye, allowing for lower concentrations of the drug, and may be the reason that the adverse events are less pronounced compared with the non-biodegradable intravitreal device.

Dr. Figueira said that although increased IOP was measured in those patients who received the high-dose insert, the adverse event nevertheless is not as frequent as those seen with similar devices such as the non-biodegradable intravitreal device. According to Dr. Figueira, the effectiveness of the fluocinolone acetonide insert appears to be similar to that of the dexamethasone implant-with the major difference that the fluocinolone acetonide insert appears to remain effective for up to 3 years, much longer than the dexamethasone implant.

"A consistent and sustained delivery of corticosteroids in low doses directly into the posterior segment of the eye can be an efficacious treatment for DME," Dr. Figueira said. "[The fluocinolone acetonide insert] and similar intravitreal devices could play a role in future therapeutic approaches for macular edema, but I believe that the use of corticosteroids will not be enough. Anti-angiogenic drugs may also play an important role, as well as laser photocoagulation, as an adjunct therapy."