Korean J Ophthalmol.  2016 Oct;30(5):369-376. 10.3341/kjo.2016.30.5.369.

The Efficacy of Intravitreal Aflibercept in Submacular Hemorrhage Secondary to Wet Age-related Macular Degeneration

• Shin KH
• Lee TG
• Kim JH
• Kim JW
• Kim CG
• Lee DW
• Han JI
• Lew YJ
• Cho HJ

• KMID: 2353830
• DOI: http://doi.org/10.3341/kjo.2016.30.5.369

Abstract

PURPOSE
To evaluate the efficacy of intravitreal aflibercept monotherapy in submacular hemorrhage (SMH) secondary to wet age-related macular degeneration (AMD).
METHODS
This study included 25 eyes in 25 patients with SMH involving the fovea secondary to wet-AMD. All patients were treated with three consecutive monthly intravitreal aflibercept (2.0 mg/0.05 mL) injections, followed by as-needed reinjection. They were followed for at least 6 months. Best-corrected visual acuity (BCVA), central foveal thickness (CFT), and area of SMH were measured at diagnosis, as well as at 3 and 6 months after treatment initiation.
RESULTS
The BCVA significantly improved from 0.79 ± 0.41 logarithm of the minimum angle of resolution (logMAR) at baseline to 0.54 ± 0.41 logMAR at 6 months (p < 0.001). BCVA ≥3 lines and stable vision were observed in 96% of the eyes. The CFT significantly decreased from 560.8 ± 215.3 µm at baseline to 299.8 ± 160.2 µm at 6 months (p < 0.001). The area of SMH significantly decreased from 10.5 ± 7.1 mm² at baseline to 1.8 ± 6.5 mm² at 6 months (p < 0.001). The BCVA, CFT, and area of SMH at baseline, as well as duration of symptoms, all correlated with BCVA at the 6-month follow-up.
CONCLUSIONS
Intravitreal injection of aflibercept is an effective treatment option for patients with SMH secondary to wet-AMD; however, there may be limited efficacy in eyes with large SMH area and cases in which treatment is delayed.

Keyword

Aflibercept; Choroidal hemorrhage; Macular degeneration; Retinal hemorrhage

MeSH Terms

Choroid Hemorrhage
Diagnosis
Follow-Up Studies
Hemorrhage*
Humans
Intravitreal Injections
Macular Degeneration*
Retinal Hemorrhage
Visual Acuity

Figure

• 

  Fig. 1 (A) Changes in best-corrected visual acuity (BCVA) during follow-up after intravitreal aflibercept injection. BCVA improved at 3 months from baseline. The mean BCVA improved from 0.79 ± 0.41 to 0.61 ± 0.46 logarithm of the minimum angle of resolution (logMAR) (p = 0.007), and this overall improvement continued throughout the 3-month follow-up. (B) Changes in central foveal thickness (CFT) with optical coherence tomography during follow-up after intravitreal aflibercept injection. The CFT improved at 3 months from baseline. The mean CFT decreased from 560.8 ± 215.3 to 313.1 ± 189.3 µm (p < 0.001), and this overall decrease continued throughout the 3-month follow-up. (C) Changes in area of the submacular hemorrhage during follow-up after intravitreal aflibercept injection. Area of the submacular hemorrhage decreased at 3 months from baseline. The mean area decreased from 10.5 to 3.9 mm2 (p < 0.001), and this overall decrease continued throughout the 3-month follow-up.

• 

  Fig. 2 At the time of diagnosis, Best-corrected visual acuity (BCVA) and central foveal thickness (CFT) were measured as 1.0 logarithm of the minimum angle of resolution (logMAR) and 493 µm, respectively (A-C). After 3 monthly aflibercept injections, the submacular hemorrhage partially resolved, and BCVA and CFT were 0.52 logMAR and 148 µm, respectively (D-F). At 6 months after the initial aflibercept injection, the submacular hemorrhage completely resolved, and BCVA and CFT improved to 0.42 logMAR and 134 µm, respectively (G-I).

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

3. Toth CA, Morse LS, Hjelmeland LM, Landers MB 3rd. Fibrin directs early retinal damage after experimental subretinal hemorrhage. Arch Ophthalmol. 1991; 109:723–729.

4. Bakri SJ, Nickel J, Yoganathan P, Beer PM. Photodynamic therapy for choroidal neovascularization associated with submacular hemorrhage in age-related macular degeneration. Ophthalmic Surg Lasers Imaging. 2006; 37:278–283.

5. Hassan AS, Johnson MW, Schneiderman TE, et al. Management of submacular hemorrhage with intravitreous tissue plasminogen activator injection and pneumatic displacement. Ophthalmology. 1999; 106:1900–1906.

6. Rosenfeld PJ, Brown DM, Heier JS, et al. Ranibizumab for neovascular age-related macular degeneration. N Engl J Med. 2006; 355:1419–1431.

7. Stifter E, Michels S, Prager F, et al. Intravitreal bevacizumab therapy for neovascular age-related macular degeneration with large submacular hemorrhage. Am J Ophthalmol. 2007; 144:886–892.

8. 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.

9. Altaweel MM, Daniel E, Martin DF, et al. Outcomes of eyes with lesions composed of >50% blood in the comparison of Age-related Macular Degeneration Treatments Trials (CATT). Ophthalmology. 2015; 122:391–398.e5.

10. Stewart MW, Grippon S, Kirkpatrick P. Aflibercept. Nat Rev Drug Discov. 2012; 11:269–270.

11. Heier JS, Brown DM, Chong V, et al. Intravitreal aflibercept (VEGF trap-eye) in wet age-related macular degeneration. Ophthalmology. 2012; 119:2537–2548.

12. Cho H, Shah CP, Weber M, Heier JS. Aflibercept for exudative AMD with persistent fluid on ranibizumab and/or bevacizumab. Br J Ophthalmol. 2013; 97:1032–1035.

13. Kim JH, Chang YS, Kim JW, et al. Intravitreal anti-vascular endothelial growth factor for submacular hemorrhage from choroidal neovascularization. Ophthalmology. 2014; 121:926–935.

14. Inoue M, Arakawa A, Yamane S, Kadonosono K. Short-term efficacy of intravitreal aflibercept in treatment-naive patients with polypoidal choroidal vasculopathy. Retina. 2014; 34:2178–2184.

15. Yamamoto A, Okada AA, Kano M, et al. One-year results of intravitreal aflibercept for polypoidal choroidal vasculopathy. Ophthalmology. 2015; 122:1866–1872.

16. Iacono P, Parodi MB, Introini U, et al. Intravitreal ranibizumab for choroidal neovascularization with large submacular hemorrhage in age-related macular degeneration. Retina. 2014; 34:281–287.

17. 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.e1.