Safety and efficacy of dexamethasone intravitreal implant for treatment of macular edema secondary to retinal vein occlusion in Chinese patients: randomized, sham-controlled, multicenter study

Abstract

Purpose: The purpose of this study was to evaluate the safety and efficacy of dexamethasone intravitreal implant 0.7 mg (DEX) for treatment of macular edema associated with retinal vein occlusion (RVO).

Methods: This study was a six-month, randomized, double-masked, sham-controlled, multicenter, phase 3 clinical trial with a 2-month open-label study extension. Patients with branch or central RVO received DEX (n = 129) or sham procedure (n = 130) in the study eye at baseline; all patients who met re-treatment criteria received DEX at month 6. Efficacy measures included Early Treatment Diabetic Retinopathy Study (ETDRS), best-corrected visual acuity (BCVA), and central retinal thickness (CRT) on optical coherence tomography.

Results: Time to ≥15-letter BCVA improvement from baseline during the first 6 months (primary endpoint) was earlier with DEX than sham (p < 0.001). At month 2 (peak effect), the percentage of patients with ≥15-letter BCVA improvement from baseline was DEX: 35%, sham: 12%; mean BCVA change from baseline was DEX: +10.6 letters, sham: +1.7 letters; and mean CRT change from baseline was DEX: -407 μm, sham: -62 μm (all p < 0.001). Outcomes were better with DEX than sham in both branch and central RVO. The most common treatment-emergent adverse event was increased intraocular pressure (IOP). Increases in IOP generally were controlled with topical medication. Mean IOP normalized by month 4, and no patient required incisional glaucoma surgery.

Conclusions: DEX had a favorable safety profile and provided clinically significant benefit in a Chinese patient population with RVO. Visual and anatomic outcomes were improved with DEX relative to sham for 3-4 months after a single implant.

Keywords: Corticosteroid; Drug delivery system; Intravitreal injection; Macular edema; Randomized controlled trial; Retinal vein occlusion.

Conflict of interest statement

Funding

This study was sponsored by Allergan plc, Dublin, Ireland.

Conflict of interest

Dr. Xiaoxin Li, Dr. Ningli Wang, Dr. Xiaoling Liang, and Dr. Gezhi Xu declare that they have no conflict of interest. Dr. Xiao-Yan Li, Dr. Jenny Jiao, Dr. Jean Lou, and Dr. Yehia Hashad are employees of Allergan plc, Irvine, CA. The authors have full control of all primary data, and they agree to allow Graefe’s Archive for Clinical and Experimental Ophthalmology to review their data upon request.

Ethical approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

Informed consent

Informed consent was obtained from all individual participants included in the study.

Figures

Fig. 1

Patient flow through the study (mITT population). AE adverse event, DEX dexamethasone intravitreal implant, mITT modified intent-to-treat

Fig. 2

Kaplan-Meier analysis of the time to ≥15 ETDRS letters improvement in best-corrected visual acuity from baseline (mITT population). *p < 0.001 versus sham (log rank test comparing cumulative response rate curves across time). DEX dexamethasone intravitreal implant, ETDRS Early Treatment Diabetic Retinopathy Study, mITT modified intent-to-treat

Fig. 3

Mean change in BCVA from baseline (mITT population). Error bars represent the standard error of the mean. *p < 0.001 versus sham. BCVA best-corrected visual acuity, DEX dexamethasone intravitreal implant, ETDRS Early Treatment Diabetic Retinopathy Study, mITT modified intent-to-treat

Fig. 4

Percentage of patients with ≥15-letter gain in BCVA from baseline (mITT population). *p < 0.001 versus sham. BCVA best-corrected visual acuity, DEX dexamethasone intravitreal implant, ETDRS Early Treatment Diabetic Retinopathy Study, mITT modified intent-to-treat

Fig. 5

Mean change in CRT from baseline (mITT population). Error bars represent the standard error of the mean. *p < 0.001 versus sham. CRT central retinal thickness, DEX dexamethasone intravitreal implant, mITT modified intent-to-treat

Fig. 6

Key efficacy parameters in BRVO and CRVO subgroups (mITT population). a Mean change in BCVA from baseline. b Percentage of patients with ≥15 letters gain in BCVA from baseline. c Mean change in CRT from baseline. *p ≤ 0.028 versus sham. BCVA best-corrected visual acuity, BRVO branch retinal vein occlusion, CRT central retinal thickness, CRVO central retinal vein occlusion, DEX dexamethasone intravitreal implant, ETDRS Early Treatment Diabetic Retinopathy Study, mITT modified intent-to-treat

Fig. 7

Mean IOP (safety population). a Mean IOP after initial treatment in the masked phase of the study. b Mean IOP through month 8 in patients who were treated in the open-label study extension. Error bars represent the standard error of the mean. DEX dexamethasone intravitreal implant, IOP intraocular pressure