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The effect of initial intravitreal tissue plasminogen activator and gas injection on vision improvement in patients with submacular haemorrhage associated with age-related macular degeneration

Abstract

Purpose

To compare visual improvements between initial intravitreal t-PA with gas injection before anti-vascular endothelial growth factor (VEGF) and anti-VEGF injection monotherapy for submacular haemorrhage (SMH) associated with age-related macular degeneration (AMD).

Methods

We retrospectively reviewed medical records of naive patients treated with intravitreal t-PA with gas injection before anti-VEGF (Group 1) or only with intravitreal anti-VEGF injection (Group 2) for SMH [disc area (DA) ≥ 2] associated with AMD from two institutions. Both groups received 3 monthly loads of anti-VEGF injections followed by injections as needed for AMD treatment. Changes in best-corrected visual acuity (BCVA, logMAR) between the initial visit and after 6 months of treatment were compared between two groups.

Results

A total of 82 patients were enroled. Of these, 32 patients and 50 patients were grouped in Groups 1 and 2, respectively. The mean change in BCVA over 6 months for Group 1 was −0.52 ± 0.88, which was significantly larger (p = 0.044) than the mean change for Group 2 (−0.15 ± 0.58). We compared visual improvements between the two groups based on the following SMH size categories: ≤5, >5, and ≤15, and >15 DA. When the SMH size was ≤5, or >5 and ≤15 DA, the mean change in BCVA was larger for Group 1 than for Group 2, but this difference was not significant. When SMH size was >15 DA, Group 1 patients exhibited a mean visual improvement of −0.79 ± 0.80, which was significantly greater (p = 0.029) than that of Group 2 (−0.06 ± 0.67).

Conclusions

Patients that were primarily treated for SMH associated with AMD using t-PA and gas injection (followed by anti-VEGF injection) exhibited better visual improvement than those treated with anti-VEGF monotherapy, especially in patients exhibiting larger SMH sizes (>15 DA) at the initial visit.

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Fig. 1: Comparison of mean changes in BCVA from the baseline between two treatment groups based on SMH size as follows: ≤5, >5, and ≤15, and >15 DA.
Fig. 2: The representative cases in Groups 1 and 2 with initial SMH size > 15 disc area.

References

  1. Poliner LS, Olk RJ, Burgess D, Gordon ME. Natural history of retinal pigment epithelial detachments in age-related macular degeneration. Ophthalmology. 1986;93:543–51.

    CAS  Article  Google Scholar 

  2. Scupola A, Coscas G, Soubrane G, Balestrazzi E. Natural history of macular subretinal hemorrhage in age-related macular degeneration. Ophthalmologica. 1999;213:97–102. https://doi.org/10.1159/000027400.

    CAS  Article  PubMed  Google Scholar 

  3. Avery RL, Fekrat S, Hawkins BS, Bressler NM. Natural history of subfoveal subretinal hemorrhage in age-related macular degeneration. Retina. 1996;16:183–9.

    CAS  Article  Google Scholar 

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

    CAS  Article  Google Scholar 

  5. Stanescu-Segall D, Balta F, Jackson TL. Submacular hemorrhage in neovascular age-related macular degeneration: a synthesis of the literature. Surv Ophthalmol. 2016;61:18–32. https://doi.org/10.1016/j.survophthal.2015.04.004.

    Article  PubMed  Google Scholar 

  6. Chen CY, Hooper C, Chiu D, Chamberlain M, Karia N, Heriot WJ. Management of submacular hemorrhage with intravitreal injection of tissue plasminogen activator and expansile gas. Retina. 2007;27:321–8. https://doi.org/10.1097/01.iae.0000237586.48231.75.

    Article  PubMed  Google Scholar 

  7. Handwerger BA, Blodi BA, Chandra SR, Olsen TW, Stevens TS. Treatment of submacular hemorrhage with low-dose intravitreal tissue plasminogen activator injection and pneumatic displacement. Arch Ophthalmol. 2001;119:28–32.

    CAS  PubMed  Google Scholar 

  8. Hattenbach LO, Klais C, Koch FH, Gumbel HO. Intravitreous injection of tissue plasminogen activator and gas in the treatment of submacular hemorrhage under various conditions. Ophthalmology. 2001;108:1485–92.

    CAS  Article  Google Scholar 

  9. Chang MA, Do DV, Bressler SB, Cassard SD, Gower EW, Bressler NM. Prospective one-year study of ranibizumab for predominantly hemorrhagic choroidal neovascular lesions in age-related macular degeneration. Retina. 2010;30:1171–6. https://doi.org/10.1097/IAE.0b013e3181dd6d8a.

    Article  PubMed  Google Scholar 

  10. Iacono P, Parodi MB, Introini U, La Spina C, Varano M, Bandello F. Intravitreal ranibizumab for choroidal neovascularization with large submacular hemorrhage in age-related macular degeneration. Retina. 2014;34:281–7. https://doi.org/10.1097/IAE.0b013e3182979e33.

    CAS  Article  PubMed  Google Scholar 

  11. Shienbaum G, Garcia Filho CA, Flynn HW Jr, Nunes RP, Smiddy WE, Rosenfeld PJ. Management of submacular hemorrhage secondary to neovascular age-related macular degeneration with anti-vascular endothelial growth factor monotherapy. Am J Ophthalmol. 2013;155:1009–13. https://doi.org/10.1016/j.ajo.2013.01.012.

    CAS  Article  PubMed  Google Scholar 

  12. Stifter E, Michels S, Prager F, Georgopoulos M, Polak K, Hirn C, et al. Intravitreal bevacizumab therapy for neovascular age-related macular degeneration with large submacular hemorrhage. Am J Ophthalmol. 2007;144:886–92. https://doi.org/10.1016/j.ajo.2007.07.034.

    CAS  Article  PubMed  Google Scholar 

  13. Hassan AS, Johnson MW, Schneiderman TE, Regillo CD, Tornambe PE, Poliner LS, et al. Management of submacular hemorrhage with intravitreous tissue plasminogen activator injection and pneumatic displacement. Ophthalmology. 1999;106:1900–6. https://doi.org/10.1016/S0161-6420(99)90399-8.

    CAS  Article  PubMed  Google Scholar 

  14. Johnson MW. Pneumatic displacement of submacular hemorrhage. Curr Opin Ophthalmol. 2000;11:201–6.

    CAS  Article  Google Scholar 

  15. Kokame GT. Vitreous hemorrhage after intravitreal tissue plasminogen activator (t-PA) and pneumatic displacement of submacular hemorrhage. Am J Ophthalmol. 2000;129:546–7.

    CAS  Article  Google Scholar 

  16. Wu TT, Kung YH, Hong MC. Vitreous hemorrhage complicating intravitreal tissue plasminogen activator and pneumatic displacement of submacular hemorrhage. Retina. 2011;31:2071–7. https://doi.org/10.1097/IAE.0b013e31822528c8.

    Article  PubMed  Google Scholar 

  17. Fujikawa M, Sawada O, Miyake T, Kakinoki M, Sawada T, Kawamura H, et al. Comparison of pneumatic displacement for submacular hemorrhages with gas alone and gas plus tissue plasminogen activator. Retina. 2013;33:1908–14. https://doi.org/10.1097/IAE.0b013e318287d99d.

    CAS  Article  PubMed  Google Scholar 

  18. 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.

    CAS  Article  Google Scholar 

  19. Wu TT, Sheu SJ. Intravitreal tissue plasminogen activator and pneumatic displacement of submacular hemorrhage secondary to retinal artery macroaneurysm. J Ocul Pharmacol Therapeutics. 2005;21:62–67. https://doi.org/10.1089/jop.2005.21.62.

    CAS  Article  Google Scholar 

  20. Cho HJ, Koh KM, Kim HS, Lee TG, Kim CG, Kim JW. Anti-vascular endothelial growth factor monotherapy in the treatment of submacular hemorrhage secondary to polypoidal choroidal vasculopathy. Am J Ophthalmol. 2013;156:524–31. e521. https://doi.org/10.1016/j.ajo.2013.04.029.

    CAS  Article  PubMed  Google Scholar 

  21. Guthoff R, Guthoff T, Meigen T, Goebel W. Intravitreous injection of bevacizumab, tissue plasminogen activator, and gas in the treatment of submacular hemorrhage in age-related macular degeneration. Retina. 2011;31:36–40. https://doi.org/10.1097/IAE.0b013e3181e37884.

    CAS  Article  PubMed  Google Scholar 

  22. Kung YH, Wu TT, Hong MC, Sheu SJ. Intravitreal tissue plasminogen activator and pneumatic displacement of submacular hemorrhage. J Ocul Pharmacol Therapeutics. 2010;26:469–74. https://doi.org/10.1089/jop.2010.0066.

    CAS  Article  Google Scholar 

  23. Peyman GA, Nelson NC Jr, Alturki W, Blinder KJ, Paris CL, Desai UR, et al. Tissue plasminogen activating factor assisted removal of subretinal hemorrhage. Ophthalmic Surg. 1991;22:575–82.

    CAS  PubMed  Google Scholar 

  24. Gopalakrishan M, Giridhar A, Bhat S, Saikumar SJ, Elias A,NS. Pneumatic displacement of submacular hemorrhage: safety, efficacy, and patient selection. Retina. 2007;27:329–34. https://doi.org/10.1097/01.iae.0000231544.43093.40.

    Article  PubMed  Google Scholar 

  25. Krepler K, Kruger A, Tittl M, Stur M, Wedrich A. Intravitreal injection of tissue plasminogen activator and gas in subretinal hemorrhage caused by age-related macular degeneration. Retina. 2000;20:251–6.

    CAS  Article  Google Scholar 

  26. Cho HJ, Koh KM, Kim JH, Kim HS, Han JI, Lew YJ, et al. Intravitreal ranibizumab injections with and without pneumatic displacement for treating submacular hemorrhage secondary to neovascular age-related macular degeneration. Retina. 2015;35:205–12. https://doi.org/10.1097/IAE.0000000000000295.

    CAS  Article  PubMed  Google Scholar 

  27. Sacu S, Stifter E, Vecsei-Marlovits PV, Michels S, Schutze C, Prunte C, et al. Management of extensive subfoveal haemorrhage secondary to neovascular age-related macular degeneration. Eye. 2009;23:1404–10. https://doi.org/10.1038/eye.2008.267.

    CAS  Article  PubMed  Google Scholar 

  28. Shin JY, Lee JM, Byeon SH. Anti-vascular endothelial growth factor with or without pneumatic displacement for submacular hemorrhage. Am J Ophthalmol. 2015;159:904–14. e901. https://doi.org/10.1016/j.ajo.2015.01.024.

    CAS  Article  PubMed  Google Scholar 

  29. Kim JH, Chang YS, Kim JW, Kim CG, Yoo SJ, Cho HJ. Intravitreal anti-vascular endothelial growth factor for submacular hemorrhage from choroidal neovascularization. Ophthalmology. 2014;121:926–35. https://doi.org/10.1016/j.ophtha.2013.11.004.

    Article  PubMed  Google Scholar 

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Acknowledgements

This work was supported by Chungnam National University Sejong Hospital Research Fund, 2020.

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Design of study (JYK and KYN); analysis and interpretation of data (SHL, SJL, HBL, YSH, KYN); collection of data (SHL, SJL, YIS, HBL, JYK, KYN); draft of manuscript (SHL and KYN) and critical review of article (SJL, YSH, HBL, KYN); and approval of final version of manuscript (SHL and KYN).

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Correspondence to Ki Yup Nam.

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Lee, S.H., Lee, S.J., Shin, Y.I. et al. The effect of initial intravitreal tissue plasminogen activator and gas injection on vision improvement in patients with submacular haemorrhage associated with age-related macular degeneration. Eye 35, 3064–3070 (2021). https://doi.org/10.1038/s41433-020-01383-z

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