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de Jong, Jan H. MD; van Zeeburg, Elsbeth J. T. MD, PhD; Cereda, Matteo G. MD; van Velthoven, Mirjam E. J. MD, PhD; Faridpooya, Koorosh MD; Vermeer, Koenraad A. MSc, PhD; van Meurs, Jan C. MD, PhD

doi: 10.1097/IAE.0000000000000954
Original Study

Purpose: Current management of submacular hemorrhage (SMH) favors vitrectomy and gas with subretinal administration of recombinant tissue plasminogen activator (rtPA) over mere intravitreal rtPA injections and gas. In this study, we aimed to compare the effectiveness of both treatment modalities to displace submacular blood.

Methods: Twenty-four patients with SMH secondary to age-related macular degeneration were included. The SMH had to exist ≤14 days at time of surgery and SMH thickness had to be between 250 μm and 1,250 μm. Patients were randomized to either intravitreal injections of rtPA, perfluoropropane (C3F8) gas, and bevacizumab (n = 12) or vitrectomy with subretinal rtPA administration, intravitreal C3F8 gas, and bevacizumab (n = 12). The SMH volume change was measured on spectral domain optical coherence tomography postoperatively within a 2.5-mm cylinder centered at the fovea.

Results: Median relative volume reduction of subretinal blood at 6 weeks postoperatively was 97% (95% confidence interval: 91–99%) in the intravitreal rtPA group and 100% (95–100%) in the subretinal rtPA group and did not differ significantly between groups (P = 0.56).

Conclusion: Both treatment modalities effectively displaced SMH in this exploratory clinical trial. To more definitely study the noninferiority of intravitreal rtPA with gas to subretinal rtPA, vitrectomy with gas, a larger clinical trial would be necessary.

Supplemental Digital Content is Available in the Text.In this exploratory randomized controlled trial, the authors used spectral domain optical coherence tomography (SD-OCT) to demonstrate the effective and similar displacement of acute submacular hemorrhages owing to age-related macular degeneration treated with intravitreal rtPA with gas or subretinal rtPA, vitrectomy with gas.

*The Rotterdam Eye Hospital, Rotterdam, the Netherlands;

Rotterdam Ophthalmic Institute, Rotterdam, the Netherlands;

Eye Clinic, Department of Clinical and Biomedical Science “Luigi Sacco,” Sacco Hospital, University of Milan, Milan, Italy; and

§Department of Ophthalmology, Erasmus University Rotterdam, Rotterdam, the Netherlands.

Reprint requests: Jan H. de Jong, MD, Rotterdam Ophthalmic Institute, Schiedamse Vest 160, 3011BH Rotterdam, the Netherlands; e-mail:

Financial support: Stichting MaculaFonds, Utrecht, the Netherlands; Grant number: Uitzicht 2012-38. Stichting Oogfonds Nederland, Utrecht, the Netherlands; Grant number: Uitzicht 2012-38. Stichting Coolsingel, Rotterdam, the Netherlands; Grant number: project 175. The funding organizations had no role in the design or conduct of this research.

Paper presented at EURETINA Congress, London, United Kingdom, September 11, 2014. NOG Jaarcongres, Groningen, the Netherlands, March 25, 2015. ARVO Annual Meeting, Denver, May 5, 2015.

None of the authors have any conflicting interests to disclose.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Web site (

J. H. de Jong and E. J. T. van Zeeburg Joint principal authorship.

© 2016 by Ophthalmic Communications Society, Inc.