LEXINGTON, KY-An intravitreal fluocinolone implant may be a safe and effective treatment for diabetic macular edema (DME). Results from a pilot study indicated good improvement in visual acuity and resolution of retinal thickening, according to P. Andrew Pearson, MD.
'Laser photocoagulation effectively reduces the risk of vision loss resulting from diabetic macular edema, but it rarely improves vision,' said Dr. Pearson, associate professor of ophthalmology, University of Kentucky, Lexington. He is also director, Ophthalmic Research, Control Delivery Systems, a research company in Watertown, MA, that helped to develop the implant technology.
A public health issue
'Edema that is refractory to laser treatment remains a major public health issue and a source of frustration for patients and physicians. DME is a leading cause of blindness in the population under 65 years of age. There is no cutrently approved pharmacologic treatment,' Dr. Pearson said.
Because of this, he and his colleagues conducted the initial trial to test the safety and effectiveness of intravitreal fluocinolone implants to treat DME.
Some evidence exists, according to Dr. Pearson, that subTenon's injection of steroids has been effective in transiently improving macular edema. The possible mechanisms are that steroids inhibit vascular endothelial growth factor, which contributes to the development of macular edema. They also regulate tight junctions of endothelial cells, which decreases water and solute permeability.
'We hypothesized that intraocular delivery of steroids might decrease growth factors responsible for macular edema and stabilize the tight junctions, thus resulting in a two-pronged attack on the macular edema,' Dr. Pearson said.
Fluocinolone was selected as the treatment because of its low solubility and high potency, which allow the creation of a small intravitreal implant. Fluocinolone is also lipophilic and, therefore, remains in the posterior ocular segment, which may reduce ocular complications. It also breaks down rapidly, once in systemic circulation, which reduces the potential for systemic exposure, according to Dr. Pearson.
Dr. Pearson and colleagues developed an intravitreal implant that releases about 2 jig of the drug daily, which was expected to produce intravitreal concentrations of about 100 ng/ml. Implants containing 0.6 and 6 mg were also developed. All devices are designed to release drug for 3 years.
Five patients, who had DME that did not respond to one or two laser treatments, received the 6-mg device. One patient received a 2-mg implant.
'The implant is placed easily through a 3-mm sclerotomy with local anesthesia,' Dr. Pearson said.
The first patient to receive the implant had severe diffuse macular edema and a small area of neovascularization on the optic nerve; there were large cysts in the fovea. No laser treatment was apparent because of retinal thickening.
'Postoperatively, we observed resolution of the neovascularization and complete resolution of the macular edema,' he said. 'The laser scars were readily apparent because the retinal thickening resolved. Nine months after implantation, the treatment effect persisted.'
In the other patients with the device implanted, similar results were achieved.
The patients' visual acuity also improved by an average of eight letters by 3 months and 14 letters by 6 and 9 months postoperatively. The average visual acuity preoperatively was 20/158 and postoperatively 20/82. In patients who had vision worse than 20/100, vision improved an average of 19 letters.
The complications included mild intravitreal hemorrhaging at the time of implantation that did not affect vision. All patients with the 6-mg device implanted had an increase in IOP that responded to topical treatment. The patient with the 2-mg implant developed a mild increase in IOP that was left untreated. One patient developed a progressive subcapsular cataract.
'The fluocinolone insert may be a promising treatment for DME. It resuits in resolution of retinal thickening and in this small study a dramatic improvement in some patients,' Dr. Pearson said.
'The side effects and complications are of concern, but they may be acceptable considering the severity of the disease. A large four-center study is under way,' he concluded.
Bausch & Lomb is conducting the multicenter clinical trial. The implant technology has been licensed to them for the treatment of sight-threatening back-of-the-eye diseases. Dr. Pearson acknowledged a proprietary interest in this technology.
