SCORE Study updates CRVO, BRVO

Las Vegas-The lack of highly effective treatments for macular edema associated with central retinal vein occlusion (CRVO) and branch retinal vein occlusion (BRVO), coupled with conflicting studies on the safety and effectiveness of treatment with triamcinolone acetonide (Kenalog, Bristol-Myers), highlight the need for a definitive clinical study. Such a study is under way, with an enrollment of nearly 500 patients at more than 80 sites, said Ingrid U. Scott, MD, MPH.

Dr. Scott presented an update on the Standard of Care versus COrticosteroid for REtinal Vein Occlusion (SCORE) Study during a symposium on evolving algorithms in the management of retinal vascular diseases here at the American Academy of Ophthalmology meeting. The SCORE study compares standard of care with intravitreal injections of triamcinolone for the treatment of macular edema associated with CRVO and BRVO. Dr. Scott is professor of ophthalmology and health evaluation sciences, Penn State College of Medicine, Hershey, PA.

Corticosteroids for macular edema associated with CRVO or BRVO were first utilized in the United States in 1999, with intravitreal injection of the commercially available formulation of triamcinolone acetonide.

“The initial reports appeared positive, with dramatic improvement in macular edema and visual acuity reported in some patients to a level that had not been reported previously in this disease process,” Dr. Scott said.

“Because of the potential efficacy of this treatment modality, this therapeutic intervention was widely adopted in the retina community,” she said.

In five studies published from 2001 to 2004, anatomic improvement was reported in all 47 patients. All of the studies also reported improvement in the mean visual acuity from baseline to the final follow-up.

“Of note, however, is the relatively short follow-up duration in these reports,” Dr. Scott said.

Four additional published studies (including 77 patients) have appeared in the past 2 years.

“Here again, short-term gain in visual acuity and anatomic improvement is reported,” Dr. Scott said.

“The results of the use of intravitreal triamcinolone acetonide for macular edema associated with retinal vein occlusion are not unequivocal, however,” she continued. “If one looks at the more recent reports that have longer-term follow-up, one can see that often what is reported is visual stabilization rather than visual improvement. These conflicting reports in the literature underscore the need for a definitive study.”

Safety of triamcinolone

The literature also includes conflicting reports on the safety of intravitreal triamcinolone acetonide injections, Dr. Scott said.

One recent report indicates possible in vivo toxicity. Rabbit retinas with 4, 8, or 20 mg of triamcinolone injected showed destruction of photoreceptor outer segments and migration of macrophage-like cells in the subretinal space. Eyes with the 20-mg dose injected showed more extensive damage and increased pigment granules in the retinal pigment epithelial cells. The source of triamcinolone in this study was the commercially available formulation.

Another recent report suggests in vitro toxicity from intravitreal triamcinolone. This study evaluated the effect of preservative-free triamcinolone on the viability of human retinal pigment epithelial and rat retinal neurosensory cells in culture.

“It was concluded that triamcinolone is potentially toxic to these two cell lines in a dose-response fashion,” Dr. Scott said.

In contrast, a third study in an in vivo model found that triamcinolone was not toxic to the retina. Rabbit eyes had up to 16 mg of triamcinolone injected; normal histologic and electrophysiologic results were observed.

In another study in a rabbit model, the effects of both preservative-free triamcinolone and the commercially available formulation were analyzed 20 weeks after intravitreal injection. Vacuolization of the outer retina and inner nuclear layers and decreased density of the outer nuclear layer were observed in eyes with the commercial formulation injected, whereas normal histology was observed in eyes with the preservative-free formulation injected.

The SCORE Study

In light of these conflicting reports on safety and efficacy, it is hoped that the SCORE Study will provide definitive data on the long-term safety and efficacy of intravitreal triamcinolone acetonide injections for macular edema associated with retinal vein occlusion, Dr. Scott said. The study was funded by the National Eye Institute (NEI) in May 2003.

Patients with CRVO and BRVO are randomly assigned in a 1:1:1 fashion to 1 mg of steroids, 4 mg of steroids, or standard of care. The drug used in these trials is a preservative-free, endotoxin-free triamcinolone acetonide formulation prepared in a preloaded syringe.

Enrollment is currently more than 460 patients, and recruitment is planned until February. The primary outcome is improvement by 15 or more letters from baseline in best-corrected ETDRS visual acuity score at the 12-month visit. Secondary outcomes include changes from baseline in best-corrected ETDRS visual acuity score, changes in retinal thickness as assessed by stereoscopic color fundus photography and optical coherence tomography, and adverse ocular outcomes.

The SCORE Study is a collaborative effort among ophthalmologists in private practice and academia, the NEI, regulatory agencies, and an industry partner. Eighty-four clinical sites are participating, and eye-care providers are encouraged to refer potentially eligible patients to a participating clinical site. Additional information about patient eligibility criteria and the SCORE Study can be found online at https://web.emmes.com/study/score/. A list of participating clinical sites can be found at https://web.emmes.com/study/score/Site_Roster_Web.pdf.

Currently, no proven effective treatment for macular edema is associated with CRVO; standard of care treatment is observation. Although grid laser photocoagulation may be effective for some patients for macular edema associated with BRVO, the benefits are limited for many patients undergoing this therapy.

“The SCORE Study provides us the opportunity to find an effective treatment for patients with macular edema associated with CRVO and a more effective treatment for patients with macular edema associated with BRVO,” Dr. Scott said.OT