Purpose: To investigate the causes of acute spontaneous submacular hemorrhage with indocyanine green angiography (ICGA). Methods: Retrospective observation case series. A total of 51 eyes from 51 patients with newly developed spontaneous submacular hemorrhage were enrolled. Best-corrected visual acuity (BCVA), fundus photography, fluorescein angiography, spectral domain optical coherence tomography (OCT), and ICGA at baseline were analyzed. The extent of hemorrhage using fundus photography, height of hemorrhage, and central foveal thickness measured by OCT was analyzed to compare the diagnostic and nondiagnostic groups. Results: The mean logarithm of the minimum angle of resolution (logMAR) BCVA at presentation was 1.21 ± 0.74 (Snellen equivalent, 20/324); the mean follow-up period was 23.9 ± 23.9 months. The cause of submacular hemorrhage was diagnosed in 43 of 51 eyes (84.3%) based on ICGA at presentation. The initial diagnoses were correct in 93% of eyes. In 3 cases, the initial diagnosis of age-related macular degeneration (AMD) was changed to polypoidal choroidal vasculopathy (PCV) based on follow-up ICGA. The central foveal thickness was significantly greater in the nondiagnostic group (1,102.4 vs. 666.7 μm, respectively; p = 0.008). The most common cause of submacular hemorrhage was neovascular AMD (52.9%), followed by PCV (37.3%), macroaneurysm (5.9%), and lacquer crack (3.9%). The mean final visual acuity was generally worse in patients with submacular hemorrhage with typical AMD (visual acuity 20/618) or PCV (visual acuity 20/240) compared to that in patients with retinal macroaneurysm (visual acuity 20/100) or lacquer crack (visual acuity 20/72). Conclusions: ICGA at initial presentation helps identify causes of submacular hemorrhage, allowing differential treatment approaches that may improve outcomes and safety.

Keywords:
Age-related macular degeneration, Indocyanine green angiography, Lacquer crack, Optical coherence tomography, Polypoidal choroidal vasculopathy, Retinal macroaneurysm, Submacular hemorrhage
1.
Hochman MA, Seery CM, Zarbin MA: Pathophysiology and management of subretinal hemorrhage. Surv Ophthalmol 1997;42:195-213.
2.
el Baba F, Jarrett WH 2nd, Harbin TS Jr, Fine SL, Michels RG, Schachat AP, Green WR: Massive hemorrhage complicating age-related macular degeneration. Clinicopathologic correlation and role of anticoagulants. Ophthalmology 1986;93:1581-1592.
3.
Lewis H, Sloan SH, Foos RY: Massive intraocular hemorrhage associated with anticoagulation and age-related macular degeneration. Graefes Arch Clin Exp Ophthalmol 1988;226:59-64.
4.
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;121:926-935.
5.
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.e1-531.e1.
6.
Tsymanava A, Uhlig CE: Intravitreal recombinant tissue plasminogen activator without and with additional gas injection in patients with submacular haemorrhage associated with age-related macular degeneration. Acta Ophthalmol 2012;90:633-638.
7.
Georgalas I, Papaconstantinou D, Karagiannis D, Ladas I: Pneumatic displacement of acute submacular hemorrhage with and without the use of tPA. Eur J Ophthalmol 2011;21:220, author reply 221.
8.
Bressler NM, Bressler SB, Childs AL, Haller JA, Hawkins BS, Lewis H, MacCumber MW, Marsh MJ, Redford M, Sternberg P Jr, Thomas MA, Williams GA: Surgery for hemorrhagic choroidal neovascular lesions of age-related macular degeneration: ophthalmic findings: SST report No 13. Ophthalmology 2004;111:1993-2006.
9.
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.
10.
Rabb MF, Gagliano DA, Teske MP: Retinal arterial macroaneurysms. Surv Ophthalmol 1988;33:73-96.
11.
Hotchkiss ML, Fine SL: Pathologic myopia and choroidal neovascularization. Am J Ophthalmol 1981;91:177-183.
12.
Hayasaka S, Uchida M, Setogawa T: Subretinal hemorrhages with or without choroidal neovascularization in the maculas of patients with pathologic myopia. Graefes Arch Clin Exp Ophthalmol 1990;228:277-280.
13.
Brinton GS, Aaberg TM, Reeser FH, Topping TM, Abrams GW: Surgical results in ocular trauma involving the posterior segment. Am J Ophthalmol 1982;93:271-278.
14.
Dugan JD Jr, Repke C, Wong T, Eagle RC Jr, Tasman W: Massive spontaneous subretinal hemorrhage from a choroidal metastasis. Am J Ophthalmol 1993;115:677-679.
15.
Brown DM, Sobol WM, Folk JC, Weingeist TA: Retinal arteriolar macroaneurysms: long-term visual outcome. Br J Ophthalmol 1994;78:534-538.
16.
Parodi MB, Iacono P, Ravalico G, Bandello F: Subthreshold laser treatment for retinal arterial macroaneurysm. Br J Ophthalmol 2011;95:534-538.
17.
Battaglia Parodi M, Iacono P, Pierro L, Papayannis A, Kontadakis S, Bandello FM: Subthreshold laser treatment versus threshold laser treatment for symptomatic retinal arterial macroaneurysm. Invest Ophthalmol Vis Sci 2012;53:1783-1786.
18.
Destro M, Puliafito CA: Indocyanine green videoangiography of choroidal neovascularization. Ophthalmology 1989;96:846-853.
19.
Guyer DR, Puliafito CA, Mones JM, Friedman E, Chang W, Verdooner SR: Digital indocyanine-green angiography in chorioretinal disorders. Ophthalmology 1992;99:287-291.
20.
Panzardi G, Donati MC, Longobardi G, Poggi P: Choroidal angiography with indocyanine green dye: absorption and fluorescence techniques. Eur J Ophthalmol 1992;2:83-85.
21.
Cohen SY, Dubois L, Quentel G, Gaudric A: Is indocyanine green angiography still relevant? Retina 2011;31:209-221.
22.
Flower RW, Csaky KG, Murphy RP: Disparity between fundus camera and scanning laser ophthalmoscope indocyanine green imaging of retinal pigment epithelium detachments. Retina 1998;18:260-268.
23.
Ruiz-Medrano J, Flores-Moreno I, Pena-Garcia P, Montero JA, Duker JS, Ruiz-Moreno JM: Macular choroidal thickness profile in a healthy population measured by swept-source optical coherence tomography. Invest Ophthalmol Vis Sci 2014;55:3532-3542.
24.
Hassan AS, Johnson MW, Schneiderman TE, Regillo CD, Tornambe PE, Poliner LS, Blodi BA, Elner SG: Management of submacular hemorrhage with intravitreous tissue plasminogen activator injection and pneumatic displacement. Ophthalmology 1999;106:1900-1906, discussion 1906-1907.
25.
Sandhu SS, Manvikar S, Steel DH: Displacement of submacular hemorrhage associated with age-related macular degeneration using vitrectomy and submacular tPA injection followed by intravitreal ranibizumab. Clin Ophthalmol 2010;4:637-642.
26.
Papavasileiou E, Steel DH, Liazos E, McHugh D, Jackson TL: Intravitreal tissue plasminogen activator, perfluoropropane (C3F8), and ranibizumab or photodynamic therapy for submacular hemorrhage secondary to wet age-related macular degeneration. Retina 2013;33:846-853.
27.
Yannuzzi LA, Wong DW, Sforzolini BS, Goldbaum M, Tang KC, Spaide RF, Freund KB, Slakter JS, Guyer DR, Sorenson JA, Fisher Y, Maberley D, Orlock DA: Polypoidal choroidal vasculopathy and neovascularized age-related macular degeneration. Arch Ophthalmol 1999;117:1503-1510.
28.
Sho K, Takahashi K, Yamada H, Wada M, Nagai Y, Otsuji T, Nishikawa M, Mitsuma Y, Yamazaki Y, Matsumura M, Uyama M: Polypoidal choroidal vasculopathy: incidence, demographic features, and clinical characteristics. Arch Ophthalmol 2003;121:1392-1396.
29.
Yoon JS, Lee J, Lee SC, Koh HJ, Kim SS, Kwon OW: Polypoidal choroidal vasculopathy in Korean patients with large submacular hemorrhage. Yonsei Med J 2007;48:225-232.
30.
Koh AH, Chen LJ, Chen SJ, Chen Y, Giridhar A, Iida T, Kim H, Yuk Yau Lai T, Lee WK, Li X, Han Lim T, Ruamviboonsuk P, Sharma T, Tang S, Yuzawa M: Polypoidal choroidal vasculopathy: evidence-based guidelines for clinical diagnosis and treatment. Retina 2013;33:686-716.
31.
Chan WM, Lam DS, Lai TY, Liu DT, Li KK, Yao Y, Wong TH: Photodynamic therapy with verteporfin for symptomatic polypoidal choroidal vasculopathy: one-year results of a prospective case series. Ophthalmology 2004;111:1576-1584.
32.
Kokame GT, Yeung L, Lai JC: Continuous anti-VEGF treatment with ranibizumab for polypoidal choroidal vasculopathy: 6-month results. Br J Ophthalmol 2010;94:297-301.
33.
Gomi F, Sawa M, Wakabayashi T, Sasamoto Y, Suzuki M, Tsujikawa M: Efficacy of intravitreal bevacizumab combined with photodynamic therapy for polypoidal choroidal vasculopathy. Am J Ophthalmol 2010;150:48.e1-54.e1.
34.
Koh A, Lee WK, Chen LJ, Chen SJ, Hashad Y, Kim H, Lai TY, Pilz S, Ruamviboonsuk P, Tokaji E, Weisberger A, Lim TH: EVEREST study: efficacy and safety of verteporfin photodynamic therapy in combination with ranibizumab or alone versus ranibizumab monotherapy in patients with symptomatic macular polypoidal choroidal vasculopathy. Retina 2012;32:1453-1464.
35.
Ahmad S, Bearelly S, Stinnett SS, Cooney MJ, Fekrat S: Photodynamic therapy for predominantly hemorrhagic lesions in neovascular age-related macular degeneration. Am J Ophthalmol 2008;145:1052-1057.
36.
Townsend-Pico WA, Meyers SM, Lewis H: Indocyanine green angiography in the diagnosis of retinal arterial macroaneurysms associated with submacular and preretinal hemorrhages: a case series. Am J Ophthalmol 2000;129:33-37.
37.
Ohno-Matsui K, Ito M, Tokoro T: Subretinal bleeding without choroidal neovascularization in pathologic myopia. A sign of new lacquer crack formation. Retina 1996;16:196-202.
© 2015 S. Karger AG, Basel
2015
Copyright / Drug Dosage / Disclaimer
Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.
You do not currently have access to this content.