The current status and progress of ocriplasmin in treating vitreomacular interface diseases_Chinese Journal of Ocular Fundus Diseases

Authors：

Xie Jiamin ,  Xu Xun

Department of Ophthalmology, The First People’s Hospital Affiliated to Shanghai JiaoTong University, Shanghai 200080, China;

Corresponding author：

Xu Xun, Email: drxuxun@sjtu.edu.cn

Keywords：

Retinal perforations/drug therapy; Fibrinolysin/therapeutic use; Vitreomacular traction syndrome/drug therapy; Review

DOI：

10.3760/cma.j.issn.1005-1015.2017.02.025

Video：

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As a potent collagenase activator, ocriplasmin is a recombinant truncated form of serine protease that retains the protease activity of plasmin. Pre-clinical animal experiments, clinical trials and recent clinical studies all indicated a promising outcome of intravitreal injection of ocriplasmin to treat vitreomacular interface diseases, including vitreomacular adhesion (VMA), vitreomacular traction (VMT) and full-thickness macular hole. Ocriplasmin was approved by the Food and Drug Administration of USA in the management of symptomatic VMA, and by the European Medicines Agency in treating VMT-associated macular hole with less than or equal 400 μm. Further randomized controlled clinical trials are needed for further comprehensive observation and evaluation on its efficiency, safety and other noteworthy issues.

Citation： Xie Jiamin, Xu Xun. The current status and progress of ocriplasmin in treating vitreomacular interface diseases. Chinese Journal of Ocular Fundus Diseases, 2017, 33(2): 203-206. doi: 10.3760/cma.j.issn.1005-1015.2017.02.025 Copy

1.	Duker JS, Kaiser PK, Binder S, et al. The International Vitreomacular Traction Study Group classification of vitreomacular adhesion, traction, and macular hole[J]. Ophthalmology, 2013, 120(12): 2611-2619. DOI: 10.1016/j.ophtha.2013.07.042.
2.	Stalmans P, Benz MS, Gandorfer A, et al. Enzymatic vitreolysis with ocriplasmin for vitreomacular traction and macular holes[J]. N Engl J Med, 2012, 367(7): 606-615. DOI: 10.1056/NEJMoa 1110823.
3.	Khan MA, Haller JA. Ocriplasmin for treatment of vitreomacular traction: an update[J]. Ophthalmol Ther, 2016, 5(2): 147-159. DOI: 10.1007/s40123-016-0062-6.
4.	EMA Product information 21/11/2013 Jetrea-EMEA/H/C/002381-IB/0005[EB/OL][2013-11-21]. .
5.	Syed YY, Dhillon S. Ocriplasmin: a review of its use in patients with symptomatic vitreomacular adhesion[J]. Drugs, 2013, 73(14): 1617-1625. DOI: 10.1007/s40265-013-0124-1.
6.	Gandorfer A, Rohleder M, Sethi C, et al. Posterior vitreous detachment induced by microplasmin[J]. Invest Ophthalmol Vis Sci, 2004, 45(2): 641-647.
7.	Sakuma T, Tanaka M, Mizota A, et al. Safety of in vivo pharmacologic vitreolysis with recombinant microplasmin in rabbit eyes[J]. Invest Ophthalmol Vis Sci, 2005, 46(9): 3295-3299. DOI: 10.1167/iovs.04-1517.
8.	Stalmans P, Delaey C, de Smet MD, et al. Intravitreal injection of microplasmin for treatment of vitreomacular adhesion: results of a prospective, randomized, sham-controlled phase Ⅱ trial (the MIVI-ⅡTtrial)[J]. Retina, 2010, 30(7): 1122-1127. DOI: 10.1097/IAE.0b013e3181e0970a.
9.	Benz MS, Packo KH, Gonzalez V, et al. A placebo-controlled trial of microplasmin intravitreous injection to facilitate posterior vitreous detachment before vitrectomy[J]. Ophthalmology, 2010, 117(4): 791-797. DOI: 10.1016/j.ophtha.2009.11.005.
10.	Stalmans P, Girach A. Vitreous levels of active ocriplasmin following intravitreal injection: results of an ascending exposure trial[J]. Invest Ophthalmol Vis Sci, 2013, 54(10): 6620-6627. DOI: 10.1167/iovs.13-11811.
11.	Gandorfer A, Benz MS, Haller JA, et al. Association between anatomical resolution and functional outcomes in the MIVI-TRUST studies using ocriplasmin to treat symptomatic vitreomacular adhesion/vitreomacular traction, including when associated with macular hole[J]. Retina, 2015, 35(6): 1151-1157. DOI: 10.1097/ iae.0000000000000508.
12.	Varma R, Haller JA, Kaiser PK. Improvement in patient-reported visual function after ocriplasmin for vitreomacular adhesion: results of the microplasmin for intravitreous injection-traction release without surgical treatment (MIVI-TRUST) trials[J]. JAMA Ophthalmol, 2015, 133(9): 997-1004. DOI: 10.1001/jamao phthalmol.2015.1746.
13.	Dugel PU, Tolentino M, Feiner L, et al. Results of the 2-year ocriplasmin for treatment for symptomatic vitreomacular adhesion including macular hole (OASIS) randomized trial[J]. Ophthalmology, 2016, 123(10): 2232-2247. DOI: 10.1016/j.ophtha. 2016.06.043.
14.	Haller JA, Stalmans P, Benz MS, et al. Efficacy of intravitreal ocriplasmin for treatment of vitreomacular adhesion: subgroup analyses from two randomized trials[J]. Ophthalmology, 2015, 122(1): 117-122. DOI: 10.1016/j.ophtha.2014.07.045.
15.	Chatziralli I, Theodossiadis G, Xanthopoulou P, et al. Ocriplasmin use for vitreomacular traction and macular hole: a meta-analysis and comprehensive review on predictive factors for vitreous release and potential complications[J]. Graefe’s Arch Clin Exp Ophthalmol, 2016, 254(7): 1247-1256. DOI: 10.1007/s00417-016-3363-5.
16.	Chatziralli I, Theodossiadis G, Parikakis E, et al. Real-life experience after intravitreal ocriplasmin for vitreomacular traction and macular hole: a spectral-domain optical coherence tomography prospective study[J]. Graefe’s Arch Clin Exp Ophthalmol, 2016, 254(2): 223-233. DOI: 10.1007/s00417-015-3031-1.
17.	Nudleman E, Franklin MS, Wolfe JD, et al. Resolution of subretinal fluid and outer retinal changes in patients treated with ocriplasmin[J]. Retina, 2016, 36(4): 738-743. DOI: 10.1097/ iae.0000000000000755.
18.	Heider A, Dimopoulos S, Szurman P, et al. Real-life experience with intravitreal ocriplasmin on vitreomacular traction and full-thickness macular holes[J/OL]. Acta Ophthalmol, 2016: E1[2016-08-08]. . DOI: 10.1111/aos.13199. [published online ahead of print].
19.	Chaudhary K, Mak MY, Gizicki R, et al. Proportion of patients with macular hole surgery who would have been favorable ocriplasmin candidates: a retrospective analysis[J]. Retina, 2017, 37(1): 76-79. DOI: 10.1097/iae.0000000000001143.
20.	Singh RP, Li A, Bedi R, et al. Anatomical and visual outcomes following ocriplasmin treatment for symptomatic vitreomacular traction syndrome[J]. Br J Ophthalmol, 2014, 98(3): 356-360. DOI: 10.1136/bjophthalmol-2013-304219.
21.	Itoh Y, Kaiser PK, Singh RP, et al. Assessment of retinal alterations after intravitreal ocriplasmin with spectral-domain optical coherence tomography[J]. Ophthalmology, 2014, 121(12): 2506-2507. DOI: 10.1016/j.ophtha.2014.07.044.
22.	Quezada-Ruiz C, Pieramici DJ, Nasir M, et al. Outer retina reflectivity changes on SD-OCT after intravitreal ocriplasmin for vitreomacular traction and macular hole[J]. Retina, 2015, 35(6): 1144-1150. DOI: 10.1097/iae.0000000000000544.
23.	Chatziralli IP, Theodossiadis GP, Parikakis E, et al. Complications of intravitreal ocriplasmin for vitreomacular traction and macular hole: a prospective spectral-domain optical coherence tomography study[J]. Cutan Ocul Toxicol, 2015: 1-7. DOI: 10.3109/155 69527.2015.1096941.
24.	Fahim AT, Khan NW, Johnson MW. Acute panretinal structural and functional abnormalities after intravitreous ocriplasmin injection[J]. JAMA Ophthalmol, 2014, 132(4): 484-486. DOI: 10.1001/ jamaophthalmol.2013.8142.
25.	Tibbetts MD, Reichel E, Witkin AJ. Vision loss after intravitreal ocriplasmin: correlation of spectral-domain optical coherence tomography and electroretinography[J]. JAMA Ophthalmol, 2014, 132(4): 487-490. DOI: 10.1001/jamaophthalmol.2013.8258.
26.	Margo JA, Schocket LS, Klima K, et al. Persistent retinal changes after intravitreal ocriplasmin[J]. Retin Cases Brief Rep, 2016, 10(1): 48-51. DOI: 10.1097/icb.0000000000000175.
27.	Birch DG, Benz MS, Miller DM, et al. Evaluation of full-field electroretinogram reductions after ocriplasmin treatment: results of the OASIS trial ERG substudy[J/OL]. Retina, 2017: E1[2017-02-14]. . DOI: 10.1097/iae.0000000000001536. [published online ahead of print].
28.	Thanos A, Hernandez-Siman J, Marra KV, et al. Reversible vision loss and outer retinal abnormalities after intravitreal ocriplasmin injection[J]. Retin Cases Brief Rep, 2014, 8(4): 330-332. DOI: 10.1097/icb.0000000000000061.
29.	Genics T. Safety and efficacy study of intravitreal ocriplasmin in subjects with amd with focal vitreomacular adhesion (MIVI-5)[EB/OL](2009-06-02)[2014-12-02]. .
30.	Genics T. A multicenter study to compare multiple doses of intravitreal microplasmin versus sham injection for treatment of patients with diabetic macular edema (DME) (MIVI-Ⅱ)[EB/OL][2007-09-15]. .
31.	Warrow DJ, Lai MM, Patel A, et al. Treatment outcomes and spectral-domain optical coherence tomography findings of eyes with symptomatic vitreomacular adhesion treated with intravitreal ocriplasmin[J]. Am J Ophthalmol, 2015, 159(1): 20-30. DOI: 10.1016/j.ajo.2014.09.015.
32.	Kim BT, Schwartz SG, Smiddy WE, et al. Initial outcomes following intravitreal ocriplasmin for treatment of symptomatic vitreomacular adhesion[J]. Ophthalmic Surg Lasers Imaging Retina, 2013, 44(4): 334-343. DOI: 10.3928/23258160-20130715-05.
33.	Dimopoulos S, Bartz-Schmidt KU, Gelisken F, et al. Rate and timing of spontaneous resolution in a vitreomacular traction group: should the role of watchful waiting be re-evaluated as an alternative to ocriplasmin therapy?[J]. Br J Ophthalmol, 2015, 99(3): 350-353. DOI: 10.1136/bjophthalmol-2014-304961.
34.	John VJ, Flynn HW Jr, Smiddy WE, et al. Clinical course of vitreomacular adhesion managed by initial observation[J]. Retina, 2014, 34(3): 442-446. DOI: 10.1097/IAE.0b013e3182a15f8b.
35.	Morescalchi F, Gambicorti E, Duse S, et al. From the analysis of pharmacologic vitreolysis to the comprehension of ocriplasmin safety[J]. Expert Opin Drug Saf, 2016, 15(9): 1267-1278. DOI: 10.1080/14740338.2016.1208169.
36.	Rodrigues IA, Stangos AN, McHugh DA, et al. Intravitreal injection of expansile perfluoropropane (C₃F₈) for the treatment of vitreomacular traction[J]. Am J Ophthalmol, 2013, 155(2): 270-276. DOI: 10.1016/j.ajo.2012.08.018.
37.	Yu G, Duguay J, Marra KV, et al. Efficacy and safety of treatment options for vitreomacular traction: a case series and meta-analysis[J]. Retina, 2016, 36(7): 1260-1270. DOI: 10.1097/iae.0000000000000909.

1. Duker JS, Kaiser PK, Binder S, et al. The International Vitreomacular Traction Study Group classification of vitreomacular adhesion, traction, and macular hole[J]. Ophthalmology, 2013, 120(12): 2611-2619. DOI: 10.1016/j.ophtha.2013.07.042.
2. Stalmans P, Benz MS, Gandorfer A, et al. Enzymatic vitreolysis with ocriplasmin for vitreomacular traction and macular holes[J]. N Engl J Med, 2012, 367(7): 606-615. DOI: 10.1056/NEJMoa 1110823.
3. Khan MA, Haller JA. Ocriplasmin for treatment of vitreomacular traction: an update[J]. Ophthalmol Ther, 2016, 5(2): 147-159. DOI: 10.1007/s40123-016-0062-6.
4. EMA Product information 21/11/2013 Jetrea-EMEA/H/C/002381-IB/0005[EB/OL][2013-11-21]. .
5. Syed YY, Dhillon S. Ocriplasmin: a review of its use in patients with symptomatic vitreomacular adhesion[J]. Drugs, 2013, 73(14): 1617-1625. DOI: 10.1007/s40265-013-0124-1.
6. Gandorfer A, Rohleder M, Sethi C, et al. Posterior vitreous detachment induced by microplasmin[J]. Invest Ophthalmol Vis Sci, 2004, 45(2): 641-647.
7. Sakuma T, Tanaka M, Mizota A, et al. Safety of in vivo pharmacologic vitreolysis with recombinant microplasmin in rabbit eyes[J]. Invest Ophthalmol Vis Sci, 2005, 46(9): 3295-3299. DOI: 10.1167/iovs.04-1517.
8. Stalmans P, Delaey C, de Smet MD, et al. Intravitreal injection of microplasmin for treatment of vitreomacular adhesion: results of a prospective, randomized, sham-controlled phase Ⅱ trial (the MIVI-ⅡTtrial)[J]. Retina, 2010, 30(7): 1122-1127. DOI: 10.1097/IAE.0b013e3181e0970a.
9. Benz MS, Packo KH, Gonzalez V, et al. A placebo-controlled trial of microplasmin intravitreous injection to facilitate posterior vitreous detachment before vitrectomy[J]. Ophthalmology, 2010, 117(4): 791-797. DOI: 10.1016/j.ophtha.2009.11.005.
10. Stalmans P, Girach A. Vitreous levels of active ocriplasmin following intravitreal injection: results of an ascending exposure trial[J]. Invest Ophthalmol Vis Sci, 2013, 54(10): 6620-6627. DOI: 10.1167/iovs.13-11811.
11. Gandorfer A, Benz MS, Haller JA, et al. Association between anatomical resolution and functional outcomes in the MIVI-TRUST studies using ocriplasmin to treat symptomatic vitreomacular adhesion/vitreomacular traction, including when associated with macular hole[J]. Retina, 2015, 35(6): 1151-1157. DOI: 10.1097/ iae.0000000000000508.
12. Varma R, Haller JA, Kaiser PK. Improvement in patient-reported visual function after ocriplasmin for vitreomacular adhesion: results of the microplasmin for intravitreous injection-traction release without surgical treatment (MIVI-TRUST) trials[J]. JAMA Ophthalmol, 2015, 133(9): 997-1004. DOI: 10.1001/jamao phthalmol.2015.1746.
13. Dugel PU, Tolentino M, Feiner L, et al. Results of the 2-year ocriplasmin for treatment for symptomatic vitreomacular adhesion including macular hole (OASIS) randomized trial[J]. Ophthalmology, 2016, 123(10): 2232-2247. DOI: 10.1016/j.ophtha. 2016.06.043.
14. Haller JA, Stalmans P, Benz MS, et al. Efficacy of intravitreal ocriplasmin for treatment of vitreomacular adhesion: subgroup analyses from two randomized trials[J]. Ophthalmology, 2015, 122(1): 117-122. DOI: 10.1016/j.ophtha.2014.07.045.
15. Chatziralli I, Theodossiadis G, Xanthopoulou P, et al. Ocriplasmin use for vitreomacular traction and macular hole: a meta-analysis and comprehensive review on predictive factors for vitreous release and potential complications[J]. Graefe’s Arch Clin Exp Ophthalmol, 2016, 254(7): 1247-1256. DOI: 10.1007/s00417-016-3363-5.
16. Chatziralli I, Theodossiadis G, Parikakis E, et al. Real-life experience after intravitreal ocriplasmin for vitreomacular traction and macular hole: a spectral-domain optical coherence tomography prospective study[J]. Graefe’s Arch Clin Exp Ophthalmol, 2016, 254(2): 223-233. DOI: 10.1007/s00417-015-3031-1.
17. Nudleman E, Franklin MS, Wolfe JD, et al. Resolution of subretinal fluid and outer retinal changes in patients treated with ocriplasmin[J]. Retina, 2016, 36(4): 738-743. DOI: 10.1097/ iae.0000000000000755.
18. Heider A, Dimopoulos S, Szurman P, et al. Real-life experience with intravitreal ocriplasmin on vitreomacular traction and full-thickness macular holes[J/OL]. Acta Ophthalmol, 2016: E1[2016-08-08]. . DOI: 10.1111/aos.13199. [published online ahead of print].
19. Chaudhary K, Mak MY, Gizicki R, et al. Proportion of patients with macular hole surgery who would have been favorable ocriplasmin candidates: a retrospective analysis[J]. Retina, 2017, 37(1): 76-79. DOI: 10.1097/iae.0000000000001143.
20. Singh RP, Li A, Bedi R, et al. Anatomical and visual outcomes following ocriplasmin treatment for symptomatic vitreomacular traction syndrome[J]. Br J Ophthalmol, 2014, 98(3): 356-360. DOI: 10.1136/bjophthalmol-2013-304219.
21. Itoh Y, Kaiser PK, Singh RP, et al. Assessment of retinal alterations after intravitreal ocriplasmin with spectral-domain optical coherence tomography[J]. Ophthalmology, 2014, 121(12): 2506-2507. DOI: 10.1016/j.ophtha.2014.07.044.
22. Quezada-Ruiz C, Pieramici DJ, Nasir M, et al. Outer retina reflectivity changes on SD-OCT after intravitreal ocriplasmin for vitreomacular traction and macular hole[J]. Retina, 2015, 35(6): 1144-1150. DOI: 10.1097/iae.0000000000000544.
23. Chatziralli IP, Theodossiadis GP, Parikakis E, et al. Complications of intravitreal ocriplasmin for vitreomacular traction and macular hole: a prospective spectral-domain optical coherence tomography study[J]. Cutan Ocul Toxicol, 2015: 1-7. DOI: 10.3109/155 69527.2015.1096941.
24. Fahim AT, Khan NW, Johnson MW. Acute panretinal structural and functional abnormalities after intravitreous ocriplasmin injection[J]. JAMA Ophthalmol, 2014, 132(4): 484-486. DOI: 10.1001/ jamaophthalmol.2013.8142.
25. Tibbetts MD, Reichel E, Witkin AJ. Vision loss after intravitreal ocriplasmin: correlation of spectral-domain optical coherence tomography and electroretinography[J]. JAMA Ophthalmol, 2014, 132(4): 487-490. DOI: 10.1001/jamaophthalmol.2013.8258.
26. Margo JA, Schocket LS, Klima K, et al. Persistent retinal changes after intravitreal ocriplasmin[J]. Retin Cases Brief Rep, 2016, 10(1): 48-51. DOI: 10.1097/icb.0000000000000175.
27. Birch DG, Benz MS, Miller DM, et al. Evaluation of full-field electroretinogram reductions after ocriplasmin treatment: results of the OASIS trial ERG substudy[J/OL]. Retina, 2017: E1[2017-02-14]. . DOI: 10.1097/iae.0000000000001536. [published online ahead of print].
28. Thanos A, Hernandez-Siman J, Marra KV, et al. Reversible vision loss and outer retinal abnormalities after intravitreal ocriplasmin injection[J]. Retin Cases Brief Rep, 2014, 8(4): 330-332. DOI: 10.1097/icb.0000000000000061.
29. Genics T. Safety and efficacy study of intravitreal ocriplasmin in subjects with amd with focal vitreomacular adhesion (MIVI-5)[EB/OL](2009-06-02)[2014-12-02]. .
30. Genics T. A multicenter study to compare multiple doses of intravitreal microplasmin versus sham injection for treatment of patients with diabetic macular edema (DME) (MIVI-Ⅱ)[EB/OL][2007-09-15]. .
31. Warrow DJ, Lai MM, Patel A, et al. Treatment outcomes and spectral-domain optical coherence tomography findings of eyes with symptomatic vitreomacular adhesion treated with intravitreal ocriplasmin[J]. Am J Ophthalmol, 2015, 159(1): 20-30. DOI: 10.1016/j.ajo.2014.09.015.
32. Kim BT, Schwartz SG, Smiddy WE, et al. Initial outcomes following intravitreal ocriplasmin for treatment of symptomatic vitreomacular adhesion[J]. Ophthalmic Surg Lasers Imaging Retina, 2013, 44(4): 334-343. DOI: 10.3928/23258160-20130715-05.
33. Dimopoulos S, Bartz-Schmidt KU, Gelisken F, et al. Rate and timing of spontaneous resolution in a vitreomacular traction group: should the role of watchful waiting be re-evaluated as an alternative to ocriplasmin therapy?[J]. Br J Ophthalmol, 2015, 99(3): 350-353. DOI: 10.1136/bjophthalmol-2014-304961.
34. John VJ, Flynn HW Jr, Smiddy WE, et al. Clinical course of vitreomacular adhesion managed by initial observation[J]. Retina, 2014, 34(3): 442-446. DOI: 10.1097/IAE.0b013e3182a15f8b.
35. Morescalchi F, Gambicorti E, Duse S, et al. From the analysis of pharmacologic vitreolysis to the comprehension of ocriplasmin safety[J]. Expert Opin Drug Saf, 2016, 15(9): 1267-1278. DOI: 10.1080/14740338.2016.1208169.
36. Rodrigues IA, Stangos AN, McHugh DA, et al. Intravitreal injection of expansile perfluoropropane (C₃F₈) for the treatment of vitreomacular traction[J]. Am J Ophthalmol, 2013, 155(2): 270-276. DOI: 10.1016/j.ajo.2012.08.018.
37. Yu G, Duguay J, Marra KV, et al. Efficacy and safety of treatment options for vitreomacular traction: a case series and meta-analysis[J]. Retina, 2016, 36(7): 1260-1270. DOI: 10.1097/iae.0000000000000909.

Chinese Journal of Ocular Fundus Diseases

The current status and progress of ocriplasmin in treating vitreomacular interface diseases

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