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Las Vegas-Patients with recurrent noninfectious posterior uveitis fared well in a European trial of an implant of fluocinolone acetonide (Bausch & Lomb) compared with the standard of care-systemic therapy.
After 2 years of follow-up, the implanted fluocinolone acetonide provided better control of inflammation and visual acuity levels that were equivalent to those of the standard systemic therapy. The major drawback to the device is the number of complications that arise as a result of its implantation, according to Carlos E. Pavesio, MD, FRCOphth.
"The management of noninfectious posterior uveitis is not a simple, standardized management. The current strategy is the use of a combination of periocular and systemic therapies. Unfortunately, the success in controlling the disease is limited and the disease often recurs," Dr. Pavesio explained at the American Academy of Ophthalmology annual meeting.
Fluocinolone acetonide was chosen because the drug is very potent and allowed the creation of a very small implantable device.
"The original idea behind this form of drug delivery was based on the Vitrasert implant (Bausch & Lomb) that allows ganciclovir to be delivered to treat cytomegalovirus retinitis in patients with AIDS. In addition, fluocinolone acetonide also has a very short systemic half-life, so any amount of medication that might get into the systemic circulation is reduced," he explained. Dr. Pavesio is a consultant ophthalmic surgeon, Moorfields Eye Hospital, London.
To test the safety and efficacy of sustained-release fluocinolone acetonide, he and his colleagues conducted a randomized, phase IIb/III multicenter study in which 140 patients with recurrent noninfectious posterior uveitis were randomly assigned to receive either the intraocular implant with a dose of 0.59 mg of the drug or the standard of care for this type of uveitis. Sixty-six patients had the drug-delivery device implanted and 74 patients received standard of care. In patients with bilateral disease who were randomly assigned to the implant, the worse eye was chosen for inclusion in the study.
Patients were included in the study if they had a history of recurrent uveitis for at least 1 year, with at least two recurrences, and the second occurrence had to have been within 8 months of the start of the study. The patients had to have taken systemic medication for at least 1 month, and the visual acuity had to be at least 1.4 logMAR. In addition, the eye had to be quiet before entrance into the study; in some cases this required treating the eye before the patient entered the study. The exclusion criteria included patients with uveitis due to infectious etiology, a retinal detachment in the area of the implantation, IOP that exceeded 25 mm Hg with two or more medications, and the need for medication to control systemic disease, Dr. Pavesio explained.
The patients in the implant group had their systemic medication tapered over 12 weeks after implantation. The patients in the standard-of-care group maintained the systemic medications for the first 6 months of the study to guarantee that recurrences of the disease were not induced by tapering of the medications.
The primary endpoint was the time to recurrence of uveitis. This was defined as an increase of two steps in anterior chamber reaction or in vitreous haze or a decrease in vision of at least 0.30 logMAR units, which is 15 letters on the EDTRS chart. The secondary endpoints were a 2-year recurrence rate between the groups, the frequency of recurrences, visual acuity levels, and safety, which included the visual acuity level, IOP level, the development of cataracts, and adverse events.
Dr. Pavesio pointed out that the difference between the European trial of fluocinolone acetonide and the American trial of the drug was that in the American trial two concentrations, 0.59 mg and 2.1 mg, were tested without a standard-of-care group.