The efficacy of intravitreal injection of tissue plasminogen activator, ranibizumab and C<sub>3</sub>F<sub>8</sub> in the treatment of early submacular hemorrhage induce to polypoid choroid vasculopathy _Chinese Journal of Ocular Fundus Diseases

Authors：

Zhang Shuang , Zhang Jie , Xu Xinyan , Gao Rongyu , Wu Peng , Han Haitao ,  Sun Xianyong , Huang Xudong

Department of Ophthalmology, The Weifang Eye Hospital, Weifang 261041, China (Zhang Shuang, postgraduate student in Weifang Medical University);

Corresponding author：

Sun Xianyong, Email: Xianyongs1968@aliyun.com

Keywords：

Choroid diseases/therapy; Submacular hemorrhage; Tissue plasminogen activator/therapeutic use; Angiogenesis inhibitors/therapeutic use; Noble gases/therapeutic use

DOI：

10.3760/cma.j.issn.1005-1015.2018.05.007

Video：

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ObjectiveTo observe the clinical effect of intravitreal injection of tissue plasminogen activator (t-PA), ranibizumab and C₃F₈ in the treatment of early submacular hemorrhage (SMH) induce to polypoid choroidal vasculopathy (PCV).MethodsThe clinical data of 20 eyes of 20 patients with early SMH induce to PCV were enrolled in this study. The duration of bleeding in the eye was 7 to 28 days, and the mean duration of bleeding was 14.8±5.6 days. All eyes are measured using the Snellen chart best corrected visual acuity (BCVA), logarithm of the minimum angle of resolution (logMAR) was used to calculate visual acuity. Measure central retinal thickness (CRT) and central retinal pigment epithelial detachment (PED) thickness using frequency-domain optical coherence tomography. The average logMAR BCVA of eyes was 1.73±0.91; the mean CRT was 620.0±275.8 μm; the average central PED thickness was 720.3±261.9 μm. All eyes receive intravitreal injection of t-PA, ranibizumab and C₃F₈. The intravitreal injection of ranibizumab was administered once a month for 3 consecutive months, followed by an on-demand treatment plan. Mean follow-up time was 9.9±3.6 months. The changes in BCVA, CRT, central PED thickness and clearance degree of SMH at 6 months after treatment were observed.ResultsOn the 6 months after treatment, the average logMAR BCVA, CRT and central PED thickness of the eyes were respectively 0.42±0.37, 290.2±97.4 μm and 41.6±78.1 μm. Compared with baseline, the after treatment BCVA was significantly increased (F=38.14, P=0.000), but the CRT and central PED were significantly decreased (F=7.48, 75.94; P=0.000, 0.000). Among the 20 eyes, 16 eyes of SMH was completely cleared, accounting for 80%;4 eyes was partially cleared, accounting for 20%. No recurrence and systemic or local complications occurred during follow-up of all eyes.ConclusionIntravitreal injection of t-PA, ranibizumab, and C₃F₈ in the treatment of early SMH induce to PCV can effectively remove SMH, improve vision, reduce CRT and central thickness of PED.

Citation： Zhang Shuang, Zhang Jie, Xu Xinyan, Gao Rongyu, Wu Peng, Han Haitao, Sun Xianyong, Huang Xudong. The efficacy of intravitreal injection of tissue plasminogen activator, ranibizumab and C₃F₈ in the treatment of early submacular hemorrhage induce to polypoid choroid vasculopathy . Chinese Journal of Ocular Fundus Diseases, 2018, 34(5): 448-452. doi: 10.3760/cma.j.issn.1005-1015.2018.05.007 Copy

1.	Cho JH, Na KR, Cho KH, et al. Incidence rate of massive submacular hemorrhage and its risk factors in polypoidalchoroidal vasculopathy[J]. Am J Ophthalmol, 2016, 169: 79-88. DOI: 10.1016/j.ajo.2016.06.014.
2.	Fine HF, Iranmanesh R, Del Priore LV, et al. Surgical outcomes after massive subretinal hemorrhage secondary to age-related macular degeneration[J]. Retina, 2010, 30(10): 1588-1594. DOI: 10.1097/IAE.0b013e3181e2263c.
3.	Ahmad S, Bearelly S, Stinnett SS, et al. Photodynamic therapy for predominantly hemorrhagic lesions in neovascular age-related macular degeneration[J]. Am J Ophthalmol, 2008, 145(6): 1052-1057. DOI: 10.1016/j.ajo.2008.02.008.
4.	Haupert CL, McCuen BW, Jaffe GJ, et al. Pars plana vitrectomy, subretinal injection of tissue plasminogen activator, and fluid-gas exchange for displacement of thick submacular hemorrhage in age-related macular degeneration[J]. Am J Ophthalmol, 2001, 131(2): 208-215.
5.	Hassan AS, Johnson MW, Schneiderman TE, et al. Management of submacular hemorrhage with intravitreous tissue plasminogen activator injection and pneumatic displacement[J]. Ophthalmology, 1999, 106(10): 1900-1907. DOI: 10.1016/S0161-6420(99)90399-8.
6.	Chawla S, Misra V. Pneumatic displacement and intravitreal bevacizumab: a new approach for management of submacular hemorrhage in choroidal neovascular membrane[J]. Indian J Ophthalmol, 2009, 57(2): 155-157.
7.	Waizel M, Todorova MG, Rickmann A, et al. Efficacy of vitrectomy combined with subretinal rtpa injection with gas or air tamponade[J]. Klin Monbl Augenheilkd, 2017, 234(4): 487-492. DOI: 10.1055/s-0042-121575.
8.	Cheung CM, Bhargava M, Xiang L, et al. Six-month visual prognosis in eyes with submacular hemorrhage secondary to age-related macular degeneration or polypoidal choroidal vasculopathy[J]. Graefe’s Arch Clin Exp Ophthalmol, 2013, 251(1): 19-25. DOI: 10.1007/s00417-012-2029-1.
9.	Yuzawa M, Mori R. The origins of polypoidal choroidal vasculopathy[J]. Br J Ophthalmol 2005, 89(5): 602-607. DOI: 10.1136/bjo.2004.049296.
10.	Koizumi H, Yamagishi T, Yamazaki T. Relationship between clinical characteristics of polypoidal choroidal vasculopathy and choroidal vascular hyperpermeability[J]. Am J Ophthalmol, 2013, 155(2): 305-313. DOI: 10.1016/j.ajo.2012.07.018.
11.	Yang LH, Jonas JB. Optical coherence tomographic enhanced depth imaging of polypoidal choroidal vasculopathy[J]. Retina, 2013, 33(8): 1584-1589. DOI: 10.1097/IAE.0b013e318285cbb3.
12.	De Salvo G, Vaz-Pereira S, Keane PA, et al. Sensitivity and specificity of spectral-domain optical coherence tomography in detecting idiopathic polypoidal choroidal vasculopathy[J]. Am J Ophthalmol, 2014, 158(6): 1228-1238. DOI: 10.1016/j.ajo.2014.08.025.
13.	Kawamura A, Yuzawa M, Mori R, et al. Indocyanine green angiographic and optical coherence tomographic findings support classification of polypoidal choroidal vasculopathy into two types[J]. Acta Ophthalmol, 2013, 91(6): 474-481. DOI: 10.1111/aos.12110.
14.	Sacu S, Stifter E, Vécsei-Marlovits PV, et al. Management of extensive subfoveal haemorrhage secondary to neovascular age-related macular degeneration[J]. Eye (Lond), 2009, 23(6): 1404-1410. DOI: 10.1038/eye.2008.267.
15.	Zhao PQ, Wang WJ, Song HY, et al. The application of t-PA in ophthalmology[J]. Foreign Journal of Medical Ophthalmology, 1993, 17(2): 65-71.
16.	Mayer WJ, Hakim I, Haritoglou C, et al. Efficacy and safety of recombinant tissue plasminogen activator and gas versus bevacizumab and gas for subretinal haemorrhage[J]. Acta Ophthalmol, 2013, 91(3): 274-278. DOI: 10.1111/j.1755-3768.2011.02264.x.
17.	Guthoff R, Guthoff T, Meigen T. Intravitreous injection of bevacizumab, tissue plasminogen activator, and gas in the treatment of submacular hemorrhage in age-related macular degeneration[J]. Retina, 2011, 31(1): 36-40. DOI: 10.1097/IAE.0b013e3181e37884.
18.	Kitagawa Y, Shimada H, Mori R, et al. Intravitreal tissue plasminogen activator, ranibizumab, and gas injection for submacular hemorrhage in polypoidal choroidal vasculopathy[J]. Ophthalmology, 2016, 123(6): 1278-1286. DOI: 10.1016/j.ophtha.2016.01.035.
19.	Scupola A, Coscas G, Soubrane G. Natural history of macular subretinal hemorrhage in age-related macular degeneration[J]. Ophthalmologica, 1999, 213(2): 97-102. DOI: 10.1159/000027400.
20.	Treumer F, Roider J. Long-term outcome of subretinal coapplication of rtPA and bevacizumab followed by repeated intravitreal anti-VEGF injections for neovascular AMD with submacular haemorrhage[J]. Br J Ophthalmol, 2012, 96(5): 708-713. DOI: 10.1136/bjophthalmol-2011-300655.
21.	Hattenbach LO, Klais C, Koch FH. Intravitreous injection of tissue plasminogen activator and gas in the treatment of submacular hemorrhage under various conditions[J]. Ophthalmology, 2001, 108(8): 1485-1492.
22.	Schulze SD. Tissue plasminogen activator plus gas injection in patients with subretinal hemorrhage caused by age-related macular degeneration: predictive variables for visual outcome[J]. Graefe’s Arch Clin Exp Ophthalmol, 2002, 240(9): 717-720. DOI: 10.1007/s00417-002-0516-5.
23.	Lewis H, Resnick SC, Flannery JG. Tissue plasminogen activator treatment of experimental subretinal hemorrhage[J]. Am J Ophthalmol, 1991, 111(2): 197-204.
24.	Toth CA, Morse LS, Hjelmeland LM. Fibrin directs early retinal damage after experimental subretinal hemorrhage[J]. Arch Ophthalmol, 1991, 109(5): 723-729.
25.	Benner JD, Hay A, Landers MB, et al. Fibrinolytic-assisted removal of experimental subretinal hemorrhage within seven days reduces outer retinal degeneration[J]. Ophthalmology, 1994, 101(4): 672-681.
26.	Sternberg P, Aguilar HE, Drews C. The effect of tissue plasminogen activator on retinal bleeding[J]. Arch Ophthalmol, 1990, 108(5): 720-722.
27.	Hawkins BS, Bressler NM, Miskala PH, et al. Surgery for subfoveal choroidal neovascularization in age-related macular degeneration: ophthalmic findings: SST report No. 11[J]. Ophthalmology, 2004, 111(11): 1967-1980. DOI: 10.1016/j.ophtha.2004.07.021.

1. Cho JH, Na KR, Cho KH, et al. Incidence rate of massive submacular hemorrhage and its risk factors in polypoidalchoroidal vasculopathy[J]. Am J Ophthalmol, 2016, 169: 79-88. DOI: 10.1016/j.ajo.2016.06.014.
2. Fine HF, Iranmanesh R, Del Priore LV, et al. Surgical outcomes after massive subretinal hemorrhage secondary to age-related macular degeneration[J]. Retina, 2010, 30(10): 1588-1594. DOI: 10.1097/IAE.0b013e3181e2263c.
3. Ahmad S, Bearelly S, Stinnett SS, et al. Photodynamic therapy for predominantly hemorrhagic lesions in neovascular age-related macular degeneration[J]. Am J Ophthalmol, 2008, 145(6): 1052-1057. DOI: 10.1016/j.ajo.2008.02.008.
4. Haupert CL, McCuen BW, Jaffe GJ, et al. Pars plana vitrectomy, subretinal injection of tissue plasminogen activator, and fluid-gas exchange for displacement of thick submacular hemorrhage in age-related macular degeneration[J]. Am J Ophthalmol, 2001, 131(2): 208-215.
5. Hassan AS, Johnson MW, Schneiderman TE, et al. Management of submacular hemorrhage with intravitreous tissue plasminogen activator injection and pneumatic displacement[J]. Ophthalmology, 1999, 106(10): 1900-1907. DOI: 10.1016/S0161-6420(99)90399-8.
6. Chawla S, Misra V. Pneumatic displacement and intravitreal bevacizumab: a new approach for management of submacular hemorrhage in choroidal neovascular membrane[J]. Indian J Ophthalmol, 2009, 57(2): 155-157.
7. Waizel M, Todorova MG, Rickmann A, et al. Efficacy of vitrectomy combined with subretinal rtpa injection with gas or air tamponade[J]. Klin Monbl Augenheilkd, 2017, 234(4): 487-492. DOI: 10.1055/s-0042-121575.
8. Cheung CM, Bhargava M, Xiang L, et al. Six-month visual prognosis in eyes with submacular hemorrhage secondary to age-related macular degeneration or polypoidal choroidal vasculopathy[J]. Graefe’s Arch Clin Exp Ophthalmol, 2013, 251(1): 19-25. DOI: 10.1007/s00417-012-2029-1.
9. Yuzawa M, Mori R. The origins of polypoidal choroidal vasculopathy[J]. Br J Ophthalmol 2005, 89(5): 602-607. DOI: 10.1136/bjo.2004.049296.
10. Koizumi H, Yamagishi T, Yamazaki T. Relationship between clinical characteristics of polypoidal choroidal vasculopathy and choroidal vascular hyperpermeability[J]. Am J Ophthalmol, 2013, 155(2): 305-313. DOI: 10.1016/j.ajo.2012.07.018.
11. Yang LH, Jonas JB. Optical coherence tomographic enhanced depth imaging of polypoidal choroidal vasculopathy[J]. Retina, 2013, 33(8): 1584-1589. DOI: 10.1097/IAE.0b013e318285cbb3.
12. De Salvo G, Vaz-Pereira S, Keane PA, et al. Sensitivity and specificity of spectral-domain optical coherence tomography in detecting idiopathic polypoidal choroidal vasculopathy[J]. Am J Ophthalmol, 2014, 158(6): 1228-1238. DOI: 10.1016/j.ajo.2014.08.025.
13. Kawamura A, Yuzawa M, Mori R, et al. Indocyanine green angiographic and optical coherence tomographic findings support classification of polypoidal choroidal vasculopathy into two types[J]. Acta Ophthalmol, 2013, 91(6): 474-481. DOI: 10.1111/aos.12110.
14. Sacu S, Stifter E, Vécsei-Marlovits PV, et al. Management of extensive subfoveal haemorrhage secondary to neovascular age-related macular degeneration[J]. Eye (Lond), 2009, 23(6): 1404-1410. DOI: 10.1038/eye.2008.267.
15. Zhao PQ, Wang WJ, Song HY, et al. The application of t-PA in ophthalmology[J]. Foreign Journal of Medical Ophthalmology, 1993, 17(2): 65-71.
16. Mayer WJ, Hakim I, Haritoglou C, et al. Efficacy and safety of recombinant tissue plasminogen activator and gas versus bevacizumab and gas for subretinal haemorrhage[J]. Acta Ophthalmol, 2013, 91(3): 274-278. DOI: 10.1111/j.1755-3768.2011.02264.x.
17. Guthoff R, Guthoff T, Meigen T. Intravitreous injection of bevacizumab, tissue plasminogen activator, and gas in the treatment of submacular hemorrhage in age-related macular degeneration[J]. Retina, 2011, 31(1): 36-40. DOI: 10.1097/IAE.0b013e3181e37884.
18. Kitagawa Y, Shimada H, Mori R, et al. Intravitreal tissue plasminogen activator, ranibizumab, and gas injection for submacular hemorrhage in polypoidal choroidal vasculopathy[J]. Ophthalmology, 2016, 123(6): 1278-1286. DOI: 10.1016/j.ophtha.2016.01.035.
19. Scupola A, Coscas G, Soubrane G. Natural history of macular subretinal hemorrhage in age-related macular degeneration[J]. Ophthalmologica, 1999, 213(2): 97-102. DOI: 10.1159/000027400.
20. Treumer F, Roider J. Long-term outcome of subretinal coapplication of rtPA and bevacizumab followed by repeated intravitreal anti-VEGF injections for neovascular AMD with submacular haemorrhage[J]. Br J Ophthalmol, 2012, 96(5): 708-713. DOI: 10.1136/bjophthalmol-2011-300655.
21. Hattenbach LO, Klais C, Koch FH. Intravitreous injection of tissue plasminogen activator and gas in the treatment of submacular hemorrhage under various conditions[J]. Ophthalmology, 2001, 108(8): 1485-1492.
22. Schulze SD. Tissue plasminogen activator plus gas injection in patients with subretinal hemorrhage caused by age-related macular degeneration: predictive variables for visual outcome[J]. Graefe’s Arch Clin Exp Ophthalmol, 2002, 240(9): 717-720. DOI: 10.1007/s00417-002-0516-5.
23. Lewis H, Resnick SC, Flannery JG. Tissue plasminogen activator treatment of experimental subretinal hemorrhage[J]. Am J Ophthalmol, 1991, 111(2): 197-204.
24. Toth CA, Morse LS, Hjelmeland LM. Fibrin directs early retinal damage after experimental subretinal hemorrhage[J]. Arch Ophthalmol, 1991, 109(5): 723-729.
25. Benner JD, Hay A, Landers MB, et al. Fibrinolytic-assisted removal of experimental subretinal hemorrhage within seven days reduces outer retinal degeneration[J]. Ophthalmology, 1994, 101(4): 672-681.
26. Sternberg P, Aguilar HE, Drews C. The effect of tissue plasminogen activator on retinal bleeding[J]. Arch Ophthalmol, 1990, 108(5): 720-722.
27. Hawkins BS, Bressler NM, Miskala PH, et al. Surgery for subfoveal choroidal neovascularization in age-related macular degeneration: ophthalmic findings: SST report No. 11[J]. Ophthalmology, 2004, 111(11): 1967-1980. DOI: 10.1016/j.ophtha.2004.07.021.

Chinese Journal of Ocular Fundus Diseases

The efficacy of intravitreal injection of tissue plasminogen activator, ranibizumab and C₃F₈ in the treatment of early submacular hemorrhage induce to polypoid choroid vasculopathy

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Chinese Journal of Ocular Fundus Diseases

The efficacy of intravitreal injection of tissue plasminogen activator, ranibizumab and C3F8 in the treatment of early submacular hemorrhage induce to polypoid choroid vasculopathy

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The efficacy of intravitreal injection of tissue plasminogen activator, ranibizumab and C₃F₈ in the treatment of early submacular hemorrhage induce to polypoid choroid vasculopathy