This study compares the anatomical and functional outcomes of two treatments for acute submacular haemorrhage (SMH): pars plana vitrectomy with subretinal recombinant tissue plasminogen activator (tPA) and gas tamponade versus intravitreal tPA and gas injection.
Methods
A retrospective single-centre study was conducted of patients treated for acute SMH at Buckinghamshire Healthcare NHS Trust between January 2016 and December 2022. Patients received either intravitreal tPA and gas ± anti-VEGF (Group A) or pars plana vitrectomy with subretinal tPA and gas tamponade ± anti-VEGF (Group B). The primary outcome was anatomical success, defined as displacement of haemorrhage from the fovea. Secondary outcomes were visual acuity (VA) improvement, central foveal thickness (CFT) reduction, and complication rates.
Results
Eighty eyes from 73 patients (mean age: 79.8 ± 11.5 years; 57.5% female) were analysed, with 53 eyes in Group A and 27 in Group B. Anatomical success was achieved in 71.6% of Group A and 77.8% of Group B. VA improved in 66% of Group A and 63% of Group B. CFT decreased by over 50% in both groups. No statistically significant differences were found between the two treatment groups and in anatomical or functional improvement.
Conclusion
In this real-world study, both approaches effectively displaced SMH and improved vision with comparable outcomes, suggesting that treatment selection may be best determined by patient-specific and logistical factors.
de SilvaSRBindraMS. Early treatment of acute submacular haemorrhage secondary to wet AMD using intravitreal tissue plasminogen activator, C3F8, and an anti-VEGF agent. Eye (Lond)2016; 30: 952–957.
2.
KimuraTArakiTYasukawaT, et al.Differences in clinical characteristics and treatment outcomes of submacular hemorrhage caused by age-related macular degeneration and retinal macroaneurysms: a multicenter survey from the Japan clinical retina study (J-CREST) group. PLoS One2022; 17: e0274508. Published 2022 Sep 29.
3.
KimHLeeSCKimSM, et al.Identification of underlying causes of spontaneous submacular hemorrhage by indocyanine green angiography. Ophthalmologica2015; 233: 146–154.
4.
CasiniGLoiudicePMenchiniM, et al.Traumatic submacular hemorrhage: available treatment options and synthesis of the literature. Int J Retina Vitreous2019; 5: 48. Published 2019 Dec 11.
5.
ChenCYHooperCChiuD, et al.Management of submacular hemorrhage with intravitreal injection of tissue plasminogen activator and expansile gas. Retina2007; 27: 321–328.
6.
IbanezHEWilliamsDFThomasMA, et al.Surgical management of submacular hemorrhage. A series of 47 consecutive cases. Arch Ophthalmol1995; 113: 62–69.
7.
HaupertCLMccuenBWJaffeGJ, et al.Pars plana vitrectomy, subretinal injection of tissue plasminogen activator, and fluid-gas exchange for displacement of thick submacular hemorrhage in age-related macular degeneration. Am J Ophthalmol2001; 131: 208–215.
8.
Stanescu-SegallDBaltaFJacksonTL. Submacular hemorrhage in neovascular age-related macular degeneration: a synthesis of the literature. Surv Ophthalmol2016; 61: 18–32.
9.
HeriotWJIntravitreal gas and TPA: an outpatient procedure for submacular hemorrhage. American Academy of Ophthalmology Annual Vitreoretinal Update. 1996, Chicago.
10.
Al-HityASteelDHYorstonD, et al.Incidence of submacular haemorrhage (SMH) in Scotland: a Scottish ophthalmic surveillance unit (SOSU) study. Eye (Lond)2019; 33: 486–491.
11.
HandwergerBABlodiBAChandraSR, et al.Treatment of submacular hemorrhage with low-dose intravitreal tissue plasminogen activator injection and pneumatic displacement. Arch Ophthalmol2001; 119: 28–32.
12.
HattenbachLOKlaisCKochFH,et al.Intravitreous injection of tissue plasminogen activator and gas in the treatment of submacular hemorrhage under various conditions. Ophthalmology2001; 108: 1485–1492.
13.
MurphyGSPSalehAAyisS, et al.Tissue plasminogen activator or perfluoropropane for submacular hemorrhage in age-related macular degeneration: a factorial randomized clinical trial. JAMA Ophthalmol2024; 142: 1157–1164.
14.
TsaiSCLinJMChenHY. Intravitreous recombinant tissue plasminogen activator and gas to treat submacular hemorrhage in age-related macular degeneration. Kaohsiung J Med Sci2003; 19: 608–616.
15.
SobolewskaBUtebeyEBartz-SchmidtKU,et al.Long-term visual outcome and its predictive factors following treatment of acute submacular hemorrhage with intravitreous injection of tissue plasminogen factor and gas. J Ocul Pharmacol Ther2014; 30: 567–572.
16.
KaramitsosAPapastavrouVIvanovaT, et al.Management of acute submacular hemorrhage using intravitreal injection of tissue plasminogen activator and gas: a case series. SAGE Open Med Case Rep2020; 8: 2050313X20970337. Published 2020 Nov 13.
17.
HassanASJohnsonMWSchneidermanTE, et al.Management of submacular hemorrhage with intravitreous tissue plasminogen activator injection and pneumatic displacement. Ophthalmology1999; 106: 1900–1907.
18.
PapavasileiouESteelDHLiazosE, et al.Intravitreal tissue plasminogen activator, perfluoropropane (C3F8), and ranibizumab or photodynamic therapy for submacular hemorrhage secondary to wet age-related macular degeneration. Retina2013; 33: 846–853.
19.
ChangWGargSJMaturiR, et al.Management of thick submacular hemorrhage with subretinal tissue plasminogen activator and pneumatic displacement for age-related macular degeneration. Am J Ophthalmol2014; 157: 1250–1257.
20.
AbboudMBenzerrougMMilazzoS. Traitement des hématomes maculaires compliquant la DMLA par vitrectomie, injection sous-rétinienne r-TPA, injection intravitréenne de bévacizumab associé à un tamponnement par gaz : à propos de 4 cas [treatment of macular hematoma complicating AMD by vitrectomy, subretinal r-TPA injection, intravitreal injection of bevacizumab combined with gas tamponade: report of 4 cases]. J Fr Ophtalmol2017; 40: 133–137.
21.
KadonosonoKArakawaAYamaneS, et al.Displacement of submacular hemorrhages in age-related macular degeneration with subretinal tissue plasminogen activator and air. Ophthalmology2015; 122: 123–128.
22.
HesseLSchmidtJKrollP. Management of acute submacular hemorrhage using recombinant tissue plasminogen activator and gas. Graefes Arch Clin Exp Ophthalmol1999; 237: 273–277.
23.
KreplerKKrugerATittlM, et al.Intravitreal injection of tissue plasminogen activator and gas in subretinal hemorrhage caused by age-related macular degeneration. Retina2000; 20: 251–256.
24.
OzkayaAErdoganGTarakciogluHN. Submacular hemorrhage secondary to age-related macular degeneration managed with vitrectomy, subretinal injection of tissue plasminogen activator, hemorrhage displacement with liquid perfluorocarbon, gas tamponade, and face-down positioning. Saudi J Ophthalmol2018; 32: 269–274.
25.
Ali SaidYDewildeEStalmansP. Visual outcome after vitrectomy with subretinal tPA injection to treat submacular hemorrhage secondary to age-related macular degeneration or macroaneurysm. J Ophthalmol2021; 2021: 3160963. Published 2021 Dec 30.
26.
de JongJHvan ZeeburgEJTCeredaMG, et al.Intravitreal versus subretinal administration of recombinant tissue plasminogen activator combined with gas for acute submacular hemorrhages due to age-related macular degeneration: an exploratory prospective study. Retina2016; 36: 914–925.
27.
GabriellePHDelyferMNGlacet-BernardA, et al.Surgery, tissue plasminogen activator, antiangiogenic agents, and age-related macular degeneration study: a randomized controlled trial for submacular hemorrhage secondary to age-related macular degeneration. Ophthalmology2023; 130: 947–957.
28.
ConfalonieriFHertzbergSNWDziedzicKA, et al.Cost-Effectiveness of alternative treatment strategies of subretinal macular hemorrhage. Healthcare (Basel)2025; 13: 1550. Published 2025 Jun 29.
29.
KimJHChangYSKimJW, et al.Intravitreal anti-vascular endothelial growth factor for submacular hemorrhage from choroidal neovascularization. Ophthalmology2014; 121: 926–935.
30.
JacksonTLBunceCDesaiR, et al.Vitrectomy, subretinal tissue plasminogen activator and intravitreal gas for submacular haemorrhage secondary to exudative age-related macular degeneration (TIGER): study protocol for a phase 3, pan-European, two-group, non-commercial, active-control, observer-masked, superiority, randomised controlled surgical trial. Trials2022; 23: 99.
