Efficacy and safety of corticosteroid implants for DME an active area of research

May 8, 2007

The central role of blood-retinal-barrier breakdown in the development of diabetic macular edema provides a rationale for exploring the use of corticosteroids as a treatment option, said Glen J. Jaffe, MD, professor of ophthalmology, Duke University Eye Center, Durham, NC.

The central role of blood-retinal-barrier breakdown in the development of diabetic macular edema provides a rationale for exploring the use of corticosteroids as a treatment option, said Glen J. Jaffe, MD, professor of ophthalmology, Duke University Eye Center, Durham, NC.

Dr. Jaffe explained that steroids can potentially restore the blood-retinal-barrier through a variety of mechanisms, including effects on tight junction proteins and VEGF. In addition, they may have benefit associated with their anti-inflammatory activity.

Attention has focused on local delivery of corticosteroids because of its many advantages compared with systemic administration. The treatment can be delivered with a trans-scleral approach or intravitreally using injections or implants.

Published results of clinical studies indicate that at least at the doses that have been tested, intravitreal injection of triamcinolone acetonide is more effective than administration via the trans-scleral route using a periocular injection. However, the magnitude and duration of benefits for reducing macular thickness and improving visual acuity with intravitreal treatment are dose-dependent and so is the risk of IOP elevation. In addition, repeated injections are necessary for a sustained effect.

Various implant technologies have been developed to increase the duration of action of steroid treatment. In the March issue of the Archives of Ophthalmology, Kupperman et al. reported the results from a phase II multicenter, dose-ranging clinical trial evaluating two doses (350 mcg and 700 mcg) of the investigational dexamethasone intravitreous delivery system (Posurdex, Allergan). That study randomized more than 300 patients with persistent macular edema despite previous laser photocoagulation or medical treatment to one of the two dexamethasone groups or observation; more than half of the patients had diabetic retinopathy.

The results after 90 days showed the proportion of eyes achieving a 3-line or greater improvement in visual acuity was significantly greater in the dexamethasone delivery system groups compared with observation; the treatment effect was dose-dependent and was observed in the subgroup of patients with diabetic retinopathy as well as in those with other diagnoses. There was also a statistically significant improvement in fluorescein leakage and central retinal thickness with the dexamethasone treatment relative to the controls.

"IOP elevation was not particularly problematic in this study with only 11% of eyes having an IOP increase of 10 mm Hg or higher, and there was no increase in cataract development with the steroid treatment, although the study was relatively short-term," Dr. Jaffe said.

He also mentioned that a phase II study is planned evaluating a helical coil implant eluting triamcinolone acetonide (I-vation, SurModics), a few trials have evaluated the available fluocinolone acetonide implant (Retisert, Bausch & Lomb), and an investigational, next-generation fluocinolone acetonide implant (Medidur, Alimera Sciences/pSivida) is now in a phase III study.

"The studies completed to date suggest the corticosteroid implants have promise in providing a longer-lasting therapeutic effect, and we are looking forward to outcomes being reported over the next several years from ongoing studies," Dr. Jaffe concluded.