OR WAIT 15 SECS
Local therapy with intravitreal sustained-release implants may have a place in the management of ocular infectious and inflammatory diseases, especially when the benefits are weighed against those involved with systemic therapy for patients.
"It has been known for a long time that there are definite advantages to local therapy for these diseases," said Dr. Dunn at the 23rd annual Current Concepts in Ophthalmology meeting, held in association with Ophthalmology Times. "These advantages include the ability to get higher levels of drug inside the eye than can be achieved with systemic therapy; the ability-in some cases-to find sustained-release delivery; and the absence of systemic side effects.
"There are a number of different diseases for which local steroid delivery may be very effective, not just for the diseases themselves but for their complications as well," said Dr. Dunn, associate professor of ophthalmology, Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore. "These include macular edema and possibly choroidal neovascularization."
Currently, there are two FDA-approved sustained-release implants: the fluocinolone acetonide intravitreal implant (Retisert, Bausch + Lomb) and the dexamethasone implant (Ozurdex, Allergan).
The fluocinolone acetonide implant contains a 0.59-mg pellet attached to a polyvinyl alcohol bio-inert strut that is sutured to the sclera. Each implant provides about 2.5 years of active drug delivery. The drug-release rate is higher in the first month, and then stabilizes thereafter.
"The fluocinolone acetonide implant has been proven effective in clinical trials compared with the fellow eye in patients with bilateral uveitis," Dr. Dunn said. "It has not, however, been compared with systemic therapy."
According to data from the 34-week follow-up in the initial clinical trial, lens opacity scores increased by 2 or more grades in 27% of phakic eyes.1 In addition, about 20% of eyes with implants had posterior subcapsular cataracts or other types of cataracts that also progressed, compared with 6.2% in fellow eyes, a statistically significant difference.
About 10% of eyes with implants required cataract surgery in that first 34 weeks, compared with 2.7% of fellow eyes. More than 50% of eyes with implants required comparable glaucoma therapy, compared with about 15% of those without implants. Dr. Dunn noted, however, that uveitis "in and of itself" will increase the likelihood of elevated IOP.
Data from the 34-week follow-up also showed that about 6% of patients required glaucoma surgery early on. None of the fellow eyes did. Two eyes had transient hypotony; one had wound leak. There was a single case of endophthalmitis, and a small number of patients had low IOPs. Several patients had retinal detachments.
Researchers published data from the 3-year follow up in 2008, and reported pressure elevations of more than 10 mm Hg in two-thirds of patients, compared with only 23% of the fellow eyes.2 Pressure-lowering drops were required in more than 75% of eyes with implants, compared with 30% of eyes without implants. Glaucoma surgery was required in about 40% of eyes with implants, compared with only 2% of eyes without implants.
"Cataract surgeries were required in the vast majority of patients; 93% of [eyes that were phakic] at the time of implant ended up as pseudo-phakic by the end of the 3-year follow-up," Dr. Dunn said. "Again, other adverse events included retinal detachment in a small percentage, endophthalmitis in one case, and hypotony in about 11%, which was comparable with the level of hypotony in the [eyes without implants].
"The implants were certainly effective compared with [eyes without implants] in terms of improvement in vision, reduction in macular edema, and a decrease in the need for topical steroids, periocular steroid injections, and associated adjuvant systemic therapy," he said.
Rare complications have been reported, and include cytomegalovirus retinitis, scleral melting at the site of the implant, and impending or mild central retinal vein occlusion.
The dexamethasone implant takes a very different delivery approach, continued Dr. Dunn. This implant consists of a 0.7-mg pellet of dexamethasone contained within a polyglycolic acid polymer; the implant is injected through a tunneled scleral incision. It is only designed to last for 2 to 3 months.
"The dexamethasone implant is designed to be delivered in an in-office setting, which reduces the overall cost of the procedure," he said. "This implant has proven efficacy compared with a sham injection in both uveitis and posterior immediate uveitis, as well as with macular edema associated with retinal vein occlusion. It has not, however, been compared with systemic therapy or [with] the fluocinolone implant."
A retinal vein occlusion study by Haller et al.3 published earlier this year showed that ocular hypertension (defined as greater than or equal to 25 mm Hg) was found at 60 days in 16% of patients with implants, a statistically significant difference compared with sham eyes, but was not statistically significantly different by day 180. Cataract occurred in less than 10% of patients, slightly more compared with sham eyes.
"As you can expect, some conjunctival and vitreous hemorrhages occurred as well," he said, adding that there were a small number of retinal detachments, and no cases of endophthalmitis with this implant.