Three modalities for retinal pathology under investigation

May 31, 2007

Periocular, systemic, and other modalities are being investigated for the treatment of retina pathology, said Kourous A. Rezaei, MD, Department of Ophthalmology, Rush Medical Center, Chicago, United States.

Periocular, systemic, and other modalities are being investigated for the treatment of retina pathology, said Kourous A. Rezaei, MD, Department of Ophthalmology, Rush Medical Center, Chicago, United States.

Anecortave acetate (Retaane, Alcon Laboratories) is one of the three treatments he discussed; none of the three is approved for use.

Anecortave acetate is delivered periocularly and is being studied for posterior juxtascleral depot (PJD) administration.

"The goal of PJD administration is to administer anecortave acetate directly in contact with the sclera over the macula and to establish a depot that would slowly release the drug over months," Dr. Rezaei said.

Small incision size-the smaller the better, application of a counter-pressure device 2 to 3 mm posterior to the injection site, slow injection speed-the angiostatic cortisene should be delivered over 10 seconds, and use of the counter-pressure device for 5 seconds when removing the cannula are important points to remember with this modality, he said. "This is all to prevent the reflux of the drug, which would require a second administration."

Another modality, an implant with fluocinolone acetonide (Medidur, Alimera Sciences), is delivered via a cylindrical polyimide tube in two different dosage sizes.

"This device is being studied in a study called FAME, and it's designed to assess the safety and efficacy of [the drug] in subjects with diabetic macular edema [DME] who have had at least one macular laser treatment," Dr. Rezaei said.

"We know from the data that 0.5 micrograms per day is efficacious for treatment of DME; however, it is associated with significant risks and side effects," he said. "It is not known whether the lower dose of 0.2 micrograms may be efficacious and also maybe with less side effects."

The Fluocinolone Acetonide in Diabetic Macular Edema (FAME) trial has enrolled 900 subjects, "with a 1:3 ratio with the different dosages and the standard of care as placebo," Dr. Rezaei said. "One hundred study centers are participating in the United States, Canada, Europe, and India, and the data will be analyzed at 24 and 36 months."

The third modality Dr. Rezaei discussed, which he said he finds the most interesting, is an encapsulated cell technology (ECT) being developed by Neurotech USA.

"In opposite to the previous two delivery techniques, here we are actually injecting cells that deliver the drug we want for treatment," he said. "In this case, it's human ciliary neurotrophic factor (CNTF), which is delivered by cells that are genetically transfected to produce CNTF. . . . In animal models, it has been shown that CNTF can slow down or rescue the photoreceptors."

The outer membrane of the ECT implant has 15-nm pores that allow oxygen and CNGF to reach the retina while also preventing the immune cells and antibodies from getting access to the cells to destroy them, Dr. Rezaei said.

The implant was studied in a National Eye Institute phase I clinical trial of 10 patients with retinitis pigmentosa.

"When the implants were removed after 6 months, they contained viable cells which were still producing CNTF. There were no adverse effects, and some of the patients actually gained vision," he said.

The implant is being studied now for dry macular degeneration, Dr. Rezaei said.