Safety and efficacy of dexamethasone intravitreal implant for treatment of macular edema secondary to retinal vein occlusionin Chinese patients: randomized, sham-controlled, multicenter study_Chinese Journal of Ocular Fundus Diseases

Authors：

 Li Xiaoxin , Wang Ningli , Liang Xiaoling , Xu Gezhi , Xiao-yan Li , Jenny Jiao , Jean Lou , Yehia Hashad , China Ozurdexin RVO Study Group

Department of Ophthalmology, Peking University People's Hospital; Key Laboratory of Vision Loss and Restoration, Ministry of Education, Beijing 100044, China (Li Xiaoxin); Beijing Tongren Eye Center, Beijing Institute of Ophthalmology, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, China (Wang Ningli); State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Guangzhou 510060, China (Liang Xiaoling); Department of Ophthalmology, Eye and ENT Hospital of Fudan University, Shanghai 200031, China (Xu Gezhi); Allergan plc, Irvine, CA, USA (Xiao-yan Li, Jenny Jiao, Jean Lou, Yehia Hashad);

Corresponding author：

Li Xiaoxin, Email: dr_lixiaoxin@163.com

Keywords：

Corticosteroids; Drug delivery systems; Intravitreal injections; Macular edema; Retinal vein occlusion; Randomized controlled trial

DOI：

10.3760/cma.j.issn.1005-1015.2018.03.003

Video：

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Objective 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: 34.9%, sham: 11.5%; mean BCVA change from baseline was DEX: 10.6±10.4 letters, sham: 1.7±12.3 letters; and mean CRT change from baseline was DEX: −407±212 μm, sham: −62±224 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 in-creased intraocular pressure (IOP). Increase sin 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.

Citation： Li Xiaoxin, Wang Ningli, Liang Xiaoling, Xu Gezhi, Xiao-yan Li, Jenny Jiao, Jean Lou, Yehia Hashad, China Ozurdexin RVO Study Group. Safety and efficacy of dexamethasone intravitreal implant for treatment of macular edema secondary to retinal vein occlusionin Chinese patients: randomized, sham-controlled, multicenter study. Chinese Journal of Ocular Fundus Diseases, 2018, 34(3): 212-220. doi: 10.3760/cma.j.issn.1005-1015.2018.03.003 Copy

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2.	Rehak M, Wiedemann P. Retinal vein thrombosis: pathogenesis and management[J].J Thromb Haemost, 2010, 8(9):1886-1894. DOI: 10.1111/j.1538-7836.2010.03909.x.
3.	Fujihara-Mino A, Mitamura Y, Inomoto N, et al. Optical coherence tomography parameters predictive of visual outcome after anti-VEGF therapy for retinal vein occlusion[J]. Clin Ophthalmol, 2016, 10:1305-1313. DOI: 10.2147/OPTH.S110793.
4.	Deobhakta A, Chang LK. Inflammation in retinal vein occlusion[J/OL]. Int J Inflam, 2013, 2013:438412[2013-04-03]. https://dx.doi.org/10.1155/2013/438412. DOI: 10.1155/2013/438412.
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6.	Haller JA, Bandello F, Belfort R Jr, et al, Ozurdex GENEVA Study Group. Dexamethasone intravitreal implant in patients with macular edema related to branch or central retinal vein occlusion twelve-month study results[J]. Ophthalmology, 2011, 118(12):2453-2460. DOI: 10.1016/j.ophtha.2011.05.014.
7.	Robinson MR, Whitcup SM. Pharmacologic and clinical profile of dexamethasone intravitreal implant[J]. Expert Rev Clin Pharmacol, 2012, 5(6):629-647. DOI: 10.1586/ecp.12.55.
8.	Haller JA, Dugel P, Weinberg DV, et al. Evaluation of the safety and performance of an applicator for a novel intravitreal dexamethasone drug delivery system for the treatment of macular edema[J].Retina,2009, 29(1):46-51. DOI: 10.1097/IAE.0b013e318188c814.
9.	Chang-Lin JE, Attar M, Acheampong AA, et al. Pharmacokinetics and pharmacodynamics of a sustained-release dexamethasone intravitreal implant[J]. Invest Ophthalmol Vis Sci, 2011, 52(1):80-86. DOI: 10.1167/iovs.10-5285.
10.	Haller JA, Bandello F, Belfort R Jr, et al; Ozurdex GENEVA Study Group. Randomized, sham-controlled trial of dexamethasone intravitreal implant in patients with macular edema due to retinal vein occlusion[J]. Ophthalmology, 2010, 117(6):1134-1146. DOI: 10.1016/j.ophtha.2010.03.032.
11.	Kuppermann BD, Haller JA, Bandello F, et al. Onset and duration of visual acuity improvement after dexamethasone intravitreal implant in eyes with macular edema due to retinal vein occlusion[J]. Retina, 2014, 34(9):1743-1749. DOI: 10.1097/IAE.0000000000000167.
12.	Cheng JW, Cheng SW, Ma XY, et al. The prevalence of primary glaucoma in main land China: asystematic review and meta-analysis[J]. J Glaucoma, 2013, 22(4):301-306. DOI: 10.1097/IJG.0b013e31824083ca.
13.	Early Treatment Diabetic Retinopathy Study Research Group. Photocoagulation for diabetic macular edema. Early treatment diabetic retinopathy study report number 1[J]. Arch Ophthalmol, 1985, 103(12):1796-1806.
14.	Chew EY, Kim J, Sperduto RD, et al. Evaluation of the age-related eye disease study clinical lens grading system. AREDS report no. 31[J].Ophthalmology, 2010, 117(11):2112-2119. DOI: 10.1016/j.ophtha.2010.02.033.
15.	Yeh WS, Haller JA, Lanzetta P, et al. Effect of the duration of macular edema on clinical outcomes in retinal vein occlusion treated with dexamethasone intravitreal implant[J]. Ophthalmology, 2012, 119(6):1190-1198. DOI: 10.1016/j.ophtha.2011.12.028.
16.	Jaissle GB, Szurman P, Feltgen N, et al; Retinal Vein Occlusion Study Group. Predictive factors for functional improvement after intravitreal bevacizumab therapy for macular edema due to branch retinal vein occlusion[J]. Graefe’s Arch Clin Exp Ophthalmol, 2011, 249(2): 183-192. DOI: 10.1007/s00417-010-1470-2.
17.	Larsen M, Waldstein SM, Boscia F, et al; CRYSTAL Study Group. Individualized ranibizumab regimen driven by stabilization criteria for central retinal vein occlusion: twelve-month results of the CRYSTAL study[J]. Ophthalmology, 2016, 123(5):1101-1111. DOI: 10.1016/j.ophtha.2016.01.011.
18.	Augustin AJ, Holz FG, Haritoglou C, et al. Retrospective, observational study in patients receiving a dexamethasone intravitreal implant 0.7 mg for macular oedema secondary to retinal vein occlusion[J]. Ophthalmologica, 2015, 233(1):18-26. DOI: 10.1159/000368840.
19.	Singer MA, Capone A Jr, Dugel PU, et al; SHASTA Study Group. Two or more dexamethasone intravitreal implants as mono therapy or in combination therapy for macular edema in retinal vein occlusion: subgroup analysis of a retrospective chart review study[J]. BMC Ophthalmol, 2015, 15:33. DOI: 10.1186/s12886-015-0018-y.
20.	Querques L, Querques G, Lattanzio R, et al. Repeated intravitreal dexamethasone implant (Ozurdex) for retinal vein occlusion[J]. Ophthalmologica, 2013, 229(1):21-25. DOI: 10.1159/000342160.
21.	Eter N, Mohr A, Wachtlin J, et al; German Ozurdex in RVO Real World Study Group. Dexamethasone intravitreal implant in retinal vein occlusion: real-life data from a prospective, multicenter clinical trial[J]. Graefe’s Arch Clin ExpOphthalmol, 2016, 255(1):77-87. DOI: 10.1007/s00417-016-3431-x.
22.	Maturi RK, Pollack A, Uy HS, et al; Ozurdex MEAD Study Group. Intraocular pressure in patients with diabetic macular edema treated with dexamethasone intravitreal implant in the 3-year MEAD study[J]. Retina, 2016, 36(6):1143-1152. DOI: 10.1097/IAE.0000000000001004.
23.	Reid GA, Sahota DS, Sarhan M. Observed complications from dexamethasone intravitreal implant for the treatment of macular edema in retinal vein occlusion over 3 treatment rounds[J].Retina, 2015, 35(8):1647-1655. DOI: 10.1097/IAE.0000000000000524.

1. Jonas JB, Xu L, Wang YX. The Beijing eye study[J]. Acta Ophthalmol, 2009, 87(3):247-261. DOI: 10.1111/j.1755-3768.2008.01385.x.
2. Rehak M, Wiedemann P. Retinal vein thrombosis: pathogenesis and management[J].J Thromb Haemost, 2010, 8(9):1886-1894. DOI: 10.1111/j.1538-7836.2010.03909.x.
3. Fujihara-Mino A, Mitamura Y, Inomoto N, et al. Optical coherence tomography parameters predictive of visual outcome after anti-VEGF therapy for retinal vein occlusion[J]. Clin Ophthalmol, 2016, 10:1305-1313. DOI: 10.2147/OPTH.S110793.
4. Deobhakta A, Chang LK. Inflammation in retinal vein occlusion[J/OL]. Int J Inflam, 2013, 2013:438412[2013-04-03]. https://dx.doi.org/10.1155/2013/438412. DOI: 10.1155/2013/438412.
5. Jonas JB. Intravitreal triamcinolone acetonide for treatment of intraocular oedematous and neovascular diseases[J].Acta Ophthalmol Scand, 2005, 83(6):645-663. DOI: 10.1111/j.1600-0420.2005.00592.x.
6. Haller JA, Bandello F, Belfort R Jr, et al, Ozurdex GENEVA Study Group. Dexamethasone intravitreal implant in patients with macular edema related to branch or central retinal vein occlusion twelve-month study results[J]. Ophthalmology, 2011, 118(12):2453-2460. DOI: 10.1016/j.ophtha.2011.05.014.
7. Robinson MR, Whitcup SM. Pharmacologic and clinical profile of dexamethasone intravitreal implant[J]. Expert Rev Clin Pharmacol, 2012, 5(6):629-647. DOI: 10.1586/ecp.12.55.
8. Haller JA, Dugel P, Weinberg DV, et al. Evaluation of the safety and performance of an applicator for a novel intravitreal dexamethasone drug delivery system for the treatment of macular edema[J].Retina,2009, 29(1):46-51. DOI: 10.1097/IAE.0b013e318188c814.
9. Chang-Lin JE, Attar M, Acheampong AA, et al. Pharmacokinetics and pharmacodynamics of a sustained-release dexamethasone intravitreal implant[J]. Invest Ophthalmol Vis Sci, 2011, 52(1):80-86. DOI: 10.1167/iovs.10-5285.
10. Haller JA, Bandello F, Belfort R Jr, et al; Ozurdex GENEVA Study Group. Randomized, sham-controlled trial of dexamethasone intravitreal implant in patients with macular edema due to retinal vein occlusion[J]. Ophthalmology, 2010, 117(6):1134-1146. DOI: 10.1016/j.ophtha.2010.03.032.
11. Kuppermann BD, Haller JA, Bandello F, et al. Onset and duration of visual acuity improvement after dexamethasone intravitreal implant in eyes with macular edema due to retinal vein occlusion[J]. Retina, 2014, 34(9):1743-1749. DOI: 10.1097/IAE.0000000000000167.
12. Cheng JW, Cheng SW, Ma XY, et al. The prevalence of primary glaucoma in main land China: asystematic review and meta-analysis[J]. J Glaucoma, 2013, 22(4):301-306. DOI: 10.1097/IJG.0b013e31824083ca.
13. Early Treatment Diabetic Retinopathy Study Research Group. Photocoagulation for diabetic macular edema. Early treatment diabetic retinopathy study report number 1[J]. Arch Ophthalmol, 1985, 103(12):1796-1806.
14. Chew EY, Kim J, Sperduto RD, et al. Evaluation of the age-related eye disease study clinical lens grading system. AREDS report no. 31[J].Ophthalmology, 2010, 117(11):2112-2119. DOI: 10.1016/j.ophtha.2010.02.033.
15. Yeh WS, Haller JA, Lanzetta P, et al. Effect of the duration of macular edema on clinical outcomes in retinal vein occlusion treated with dexamethasone intravitreal implant[J]. Ophthalmology, 2012, 119(6):1190-1198. DOI: 10.1016/j.ophtha.2011.12.028.
16. Jaissle GB, Szurman P, Feltgen N, et al; Retinal Vein Occlusion Study Group. Predictive factors for functional improvement after intravitreal bevacizumab therapy for macular edema due to branch retinal vein occlusion[J]. Graefe’s Arch Clin Exp Ophthalmol, 2011, 249(2): 183-192. DOI: 10.1007/s00417-010-1470-2.
17. Larsen M, Waldstein SM, Boscia F, et al; CRYSTAL Study Group. Individualized ranibizumab regimen driven by stabilization criteria for central retinal vein occlusion: twelve-month results of the CRYSTAL study[J]. Ophthalmology, 2016, 123(5):1101-1111. DOI: 10.1016/j.ophtha.2016.01.011.
18. Augustin AJ, Holz FG, Haritoglou C, et al. Retrospective, observational study in patients receiving a dexamethasone intravitreal implant 0.7 mg for macular oedema secondary to retinal vein occlusion[J]. Ophthalmologica, 2015, 233(1):18-26. DOI: 10.1159/000368840.
19. Singer MA, Capone A Jr, Dugel PU, et al; SHASTA Study Group. Two or more dexamethasone intravitreal implants as mono therapy or in combination therapy for macular edema in retinal vein occlusion: subgroup analysis of a retrospective chart review study[J]. BMC Ophthalmol, 2015, 15:33. DOI: 10.1186/s12886-015-0018-y.
20. Querques L, Querques G, Lattanzio R, et al. Repeated intravitreal dexamethasone implant (Ozurdex) for retinal vein occlusion[J]. Ophthalmologica, 2013, 229(1):21-25. DOI: 10.1159/000342160.
21. Eter N, Mohr A, Wachtlin J, et al; German Ozurdex in RVO Real World Study Group. Dexamethasone intravitreal implant in retinal vein occlusion: real-life data from a prospective, multicenter clinical trial[J]. Graefe’s Arch Clin ExpOphthalmol, 2016, 255(1):77-87. DOI: 10.1007/s00417-016-3431-x.
22. Maturi RK, Pollack A, Uy HS, et al; Ozurdex MEAD Study Group. Intraocular pressure in patients with diabetic macular edema treated with dexamethasone intravitreal implant in the 3-year MEAD study[J]. Retina, 2016, 36(6):1143-1152. DOI: 10.1097/IAE.0000000000001004.
23. Reid GA, Sahota DS, Sarhan M. Observed complications from dexamethasone intravitreal implant for the treatment of macular edema in retinal vein occlusion over 3 treatment rounds[J].Retina, 2015, 35(8):1647-1655. DOI: 10.1097/IAE.0000000000000524.

Chinese Journal of Ocular Fundus Diseases

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

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