Results from the phase II TANZANITE clinical trial support further investigation of adding suprachoroidal triamcinolone acetonide to anti-vascular endothelial growth factor therapy for treatment-naïve retinal vein occlusion.
Reviewed by David M. Brown, MD
Combination therapy with suprachoroidal triamcinolone acetonide (Zuprata, Clearside Biomedical) injection plus an intravitreal anti-vascular endothelial growth factor (VEGF) agent is a promising approach for treating eyes with macular edema and vision loss associated with retinal vein occlusion (RVO), said David M. Brown, MD.
The suprachoroidal injection is administered using a proprietary microinjector syringe featuring a proprietary short (900 μm), 30-gauge needle.
Evaluation in animal models showed the technique resulted in compartmentalization of the corticosteroid with high levels achieved in target tissues (choroid and retina) and limited penetration to the anterior segment.
In the 3-month TANZANITE trial, patients receiving a single suprachoroidal injection of triamcinolone acetonide plus intravitreal
aflibercept 2 mg (Eylea, Regeneron) had a significantly reduced need for further anti-VEGF injections compared with the control group assigned to an initial aflibercept injection plus a sham suprachoroidal procedure, explained Dr. Brown, TANZANITE investigator and clinical professor of ophthalmology, Baylor College of Medicine, Houston.
In addition, significant differences favoring the combination approach were achieved in analyses of functional and anatomic outcomes. Delivery of triamcinolone to the suprachoroidal space showed promise for mitigating corticosteroid-related ocular side effects, Dr. Brown said.
“Monotherapy with intravitreal injection of an anti-VEGF agent or triamcinolone has been shown to improve visual acuity and reduce macular edema in eyes with RVO, but only the corticosteroid has the potential to affect the acute thrombus and the secondary lymphocytic infiltration that occur with RVO,” he said.
Traditionally, corticosteroids, however, have been relegated to second-line treatment status for this indication because of their potential to induce cataract and cause IOP elevation, he noted.
“The results of the TANZANITE trial support the hypothesis that suprachoroidal injection of triamcinolone acetonide could provide the benefits of corticosteroid treatment with reduced risk,” said Dr. Brown, who is also director, Greater Houston Retina Research Center, Houston.
“They also suggest that early intervention for RVO with a corticosteroid plus anti-VEGF therapy may improve outcomes for eyes with treatment-naïve RVO,” he said.
These issues will be investigated further in phase III trials.
About the study
About the study
TANZANITE was a multicenter, masked phase II study that randomly assigned 46 patients equally to the combination or monotherapy treatment groups. Eligible patients had macular edema secondary to RVO that was present for no longer than 12 months, best-corrected visual acuity (BCVA) between 20 and 70 letters, and had received no prior treatment for the macular edema.
Patients were followed monthly over 3 months and received additional aflibercept as needed according to protocol-specified criteria.
The study met its primary endpoint, finding that the total number of additional aflibercept injections administered was significantly lower (–61%) in eyes treated with the suprachoroidal corticosteroid compared with the monotherapy controls (9 versus 23 injections).
In addition, the proportion of patients who received no additional aflibercept injections was significantly less in the combination therapy group compared with the controls (78% versus 30%, respectively).
Changes in BCVA and central subfield thickness (CST) were analyzed as secondary endpoints. The functional assessments showed an early difference in BCVA improvement favoring the combination treatment group that increased with longer follow-up despite the greater number of aflibercept injections received by the monotherapy group.
At month 1, eyes receiving suprachoroidal triamcinolone acetonide had gained 16.1 letters from baseline BCVA compared with an improvement of 11.3 letters in the controls. The average gain from baseline at 3 months was 18.9 letters in the combination arm and remained 11.3 letters in the control group.
The eyes treated with combination therapy also had greater reduction in macular edema at month 1 and at the end of the study.
Mean CST at baseline was about 730 μm in both groups. In the combination therapy arm, mean CST was 285 μm at month 1 and was the same at month 3. In the monotherapy arm, mean CST was 323 μm at month 1 and 384 μm at month 3.
The safety review showed no cases of cataract exacerbation in the combination therapy group. Two eyes (8.7%) developed IOP ≥30 mm Hg, and both were controlled on topical medication.
“Because this was a small study with short follow-up, we would not expect to see any significant corticosteroid-induced cataract changes,” Dr. Brown said. “The safety of suprachoroidal triamcinolone acetonide will receive further scrutiny in trials of its use in uveitis that are investigating multiple doses and over longer follow-up.”
David M. Brown, MD
This article was adapted from Dr. Brown’s presentation at Retina Subspecialty Day during the 2016 meeting of the American Academy of Ophthalmology. Dr. Brown receives research grant funding and is a consultant/scientific advisory board member for Clearside Biomedical and other companies marketing or developing treatments for retinal vein occlusion.