Korean J Ophthalmol.  2016 Jun;30(3):192-197. 10.3341/kjo.2016.30.3.192.

Management of Acute Submacular Hemorrhage with Intravitreal Injection of Tenecteplase, Anti-vascular Endothelial Growth Factor and Gas

• Lee JP
• Park JS
• Kwon OW
• You YS
• Kim SH

• KMID: 2373974
• DOI: http://doi.org/10.3341/kjo.2016.30.3.192

Abstract

PURPOSE
To evaluate the visual and anatomical outcomes for neovascular age-related macular degeneration with submacular hemorrhage after intravitreal injections of tenecteplase (TNK), anti-vascular endothelial growth factor (VEGF) and expansile gas.
METHODS
This study was a retrospective clinical case series following 25 eyes of 25 patients. All patients received a triple injection using 0.05 mL TNK (50 µg), 0.05 mL anti-VEGF and 0.3 mL of perfluoropropane gas. Retreatment with anti-VEGF was performed as needed. Preoperative and postoperative best-corrected visual acuity and central retinal thickness were analyzed.
RESULTS
The mean logarithm of the minimum angle of resolution of best-corrected visual acuity improved significantly from 1.09 ± 0.77 at baseline to 0.52 ± 0.60 at 12 months (p < 0.001). The mean central retinal thickness also improved significantly from 545 ± 156 at baseline to 266 ± 107 at 12 months (p < 0.001). A visual improvement of 0.3 logarithm of the minimum angle of resolution unit or more was achieved in 15 eyes (60%). During the 12 postoperative months, an average of 4.04 intravitreal anti-VEGF injections was applied.
CONCLUSIONS
A triple injection of TNK, anti-VEGF, and a gas appears to be safe and effective for the treatment of submacular hemorrhage secondary to neovascular age-related macular degeneration.

Keyword

Anti-vascular endothelial growth factor; Expansile gas; Intravitreal injection; Submacular hemorrhage; Tenecteplase

MeSH Terms

Acute Disease
Aged
Aged, 80 and over
Female
Fibrinolytic Agents/administration & dosage
Fluorescein Angiography
Fluorocarbons/*administration & dosage
Follow-Up Studies
Fundus Oculi
Humans
Intravitreal Injections
Macula Lutea/*diagnostic imaging
Male
Middle Aged
Retinal Hemorrhage/diagnosis/*drug therapy
Retrospective Studies
Tissue Plasminogen Activator/*administration & dosage
Tomography, Optical Coherence
Treatment Outcome
Vascular Endothelial Growth Factor A/antagonists & inhibitors
Visual Acuity
Fibrinolytic Agents
Fluorocarbons
Tissue Plasminogen Activator
Vascular Endothelial Growth Factor A

Figure

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  Fig. 1 Preoperative and 12 months postoperative fundus photographs and optical coherence tomography images of patient 4 (A,B) and patient 12 (C,D).

Reference

1. Avery RL, Fekrat S, Hawkins BS, Bressler NM. Natural history of subfoveal subretinal hemorrhage in age-related macular degeneration. Retina. 1996; 16:183–189.

2. Bennett SR, Folk JC, Blodi CF, Klugman M. Factors prognostic of visual outcome in patients with subretinal hemorrhage. Am J Ophthalmol. 1990; 109:33–37.

3. Hochman MA, Seery CM, Zarbin MA. Pathophysiology and management of subretinal hemorrhage. Surv Ophthalmol. 1997; 42:195–213.

4. Schulze SD, Hesse L. Tissue plasminogen activator plus gas injection in patients with subretinal hemorrhage caused by age-related macular degeneration: predictive variables for visual outcome. Graefes Arch Clin Exp Ophthalmol. 2002; 240:717–720.

5. Cakir M, Cekic O, Yilmaz OF. Pneumatic displacement of acute submacular hemorrhage with and without the use of tissue plasminogen activator. Eur J Ophthalmol. 2010; 20:565–571.

6. Mizutani T, Yasukawa T, Ito Y, et al. Pneumatic displacement of submacular hemorrhage with or without tissue plasminogen activator. Graefes Arch Clin Exp Ophthalmol. 2011; 249:1153–1157.

7. Bressler NM, Bressler SB, Childs AL, et al. Surgery for hemorrhagic choroidal neovascular lesions of age-related macular degeneration: ophthalmic findings. SST report no. 13. Ophthalmology. 2004; 111:1993–2006.

8. Hohn F, Mirshahi A, Hattenbach LO. Combined intravitreal injection of bevacizumab and SF6 gas for treatment of submacular hemorrhage secondary to age-related macular degeneration. Ophthalmologe. 2010; 107:328–332.

9. Meyer CH, Scholl HP, Eter N, et al. Combined treatment of acute subretinal haemorrhages with intravitreal recombined tissue plasminogen activator, expansile gas and bevacizumab: a retrospective pilot study. Acta Ophthalmol. 2008; 86:490–494.

10. Kwan AS, Vijayasekaran S, McAllister IL, et al. A study of retinal penetration of intravitreal tenecteplase in pigs. Invest Ophthalmol Vis Sci. 2006; 47:2662–2667.

11. Rowley SA, Vijayasekaran S, Yu PK, et al. Retinal toxicity of intravitreal tenecteplase in the rabbit. Br J Ophthalmol. 2004; 88:573–578.

12. McAllister IL, Vijayasekaran S, Khong CH, Yu DY. Investigation of the safety of tenecteplase to the outer retina. Clin Experiment Ophthalmol. 2006; 34:787–793.

13. Davydov L, Cheng JW. Tenecteplase: a review. Clin Ther. 2001; 23:982–997.

14. McAllister IL, Chen SD, Patel JI, et al. Management of submacular haemorrhage in age-related macular degeneration with intravitreal tenecteplase. Br J Ophthalmol. 2010; 94:260–261.

15. Heriot W, editor. Intravitreal gas and tPA: an outpatient procedure for subretinal haemorrhage. Proceedings of Vail Vitrectomy Meeting. Vail: American Society of Retina Specialists;1996.

16. Chen CY, Hooper C, Chiu D, et al. Management of submacular hemorrhage with intravitreal injection of tissue plasminogen activator and expansile gas. Retina. 2007; 27:321–328.

17. Chen SN, Yang TC, Ho CL, et al. Retinal toxicity of intravitreal tissue plasminogen activator: case report and literature review. Ophthalmology. 2003; 110:704–708.

18. Fujikawa M, Sawada O, Miyake T, et al. Comparison of pneumatic displacement for submacular hemorrhages with gas alone and gas plus tissue plasminogen activator. Retina. 2013; 33:1908–1914.

19. Kwon YH, Lim SJ, Jeung WJ, et al. Subretinal tenecteplase injection in a submacular hemorrhage from polypoidal choroidal vasculopathy: a case report. Retin Cases Brief Rep. 2012; 6:400–405.

20. Shienbaum G, Garcia Filho CA, Flynn HW Jr, et al. Management of submacular hemorrhage secondary to neovascular age-related macular degeneration with anti-vascular endothelial growth factor monotherapy. Am J Ophthalmol. 2013; 155:1009–1013.

21. Cho HJ, Koh KM, Kim HS, et al. Anti-vascular endothelial growth factor monotherapy in the treatment of submacular hemorrhage secondary to polypoidal choroidal vasculopathy. Am J Ophthalmol. 2013; 156:524–531.el.

22. Cho HJ, Koh KM, Kim JH, et al. Intravitreal ranibizumab injections with and without pneumatic displacement for treating submacular hemorrhage secondary to neovascular age-related macular degeneration. Retina. 2015; 35:205–212.