Submacular hemorrhage is a serious problem that can cause devastating visual loss. It can occur due to choroidal neovascularization (CNV), retinal arterial macroaneurysms, and trauma. It is more common in patients on anticoagulants, particularly those on warfarin and clopidogrel. There is no formal consensus on the management of submacular hemorrhage, as it very difficult to perform clinical trials in this area.
Submacular hemorrhages are classified by location relative to the fovea and retinal pigment epithelium (RPE) (i.e., subretinal or sub-RPE), size, and thickness. A small subretinal hemorrhage approximates a few disc areas around the fovea, a medium-sized hemorrhage reaches the arcades, and a massive subretinal hemorrhage (also known as a hemorrhagic retinal detachment) involves the retinal periphery. Thin subretinal hemorrhages are usually less than 500 microns thick, and thick hemorrhages are greater than 500 microns thick. It is also important to ascertain the duration of the hemorrhage as this is important in the management decision.
Subretinal hemorrhage may cause retinal damage through a number of mechanisms: toxicity due to iron from hemoglobin, impairment of metabolic exchange between photoreceptors and RPE, and fibrin-mediated damage to the outer retina due to clot contraction.1 At about 3-14 days, retinal degeneration over areas of dense fibrin occurs.2 This underlies the importance of early management of subretinal hemorrhage.
For small thin submacular hemorrhages, or those not involving the fovea, I initiate treatment with anti-VEGF therapy. For medium-sized submacular hemorrhage, reaching the arcades, I offer surgical displacement by vitrectomy, subretinal tissue plasminogen activator and air fluid exchange. However, in order to be a candidate for the surgery, the hemorrhage should be thick and involve the fovea, and look fresh or have occurred within approximately 2 weeks. If not a surgical candidate, I may treat with anti-VEGF therapy depending on several factors (including chronicity, visual potential). Massive subretinal hemorrhage with hemorrhagic retinal detachment involving the fovea represents a difficult challenge. In patients on warfarin, it is important to check that the INR is within recommended range. In some cases, I may offer patients retinal surgery with vitrectomy, 180 degree peripheral retinectomy, removal of the CNV, and silicone oil tamponade. It is important to note that, in these patients, the peripheral visual field and the scotoma density may improve, but anatomically the best result is often central geographic atrophy and an attached retina.
There are a variety of other reported therapeutic options for medium-sized subretinal hemorrhage. These include office-based pneumatic displacement with or without intravitreal tissue plasminogen activator, and surgery as in the Submacular Surgery Trials3 (SST), which includes vitrectomy with removal of the CNV and blood, rather than hemorrhage displacement. Pneumatic displacement without liquefaction of the blood may cause shearing of the photoreceptors, and intravitreal tissue plasminogen activator has been shown not to penetrate the retina4,5. Surgery, as performed in the SST, was not associated with an increased likelihood of stable or improved visual acuity and was associated with a high risk of rhegmatogenous retinal detachment, but reduced the risk of severe visual loss. The SST was performed before anti-VEGF agents were available.
Postoperative management depends on the cause of the subretinal hemorrhage. If due to CNV, postoperative treatment after hemorrhage displacement includes imaging with fluorescein angiography and optical coherence tomography, and treatment of the CNV with currently available agents, including anti-VEGF agents, photodynamic therapy, and steroids, or combination therapies. It is important to remember that intravitreal drugs clear rapidly in vitrectomized eyes.
The outcome can be difficult to ascertain preoperatively. It depends on the status of the macula before the hemorrhage occurred (i.e., presence of geographic atrophy, fibrosis), the duration of the hemorrhage, and the cause. For example, subretinal hemorrhages due to retinal arterial macroaneurysm tend to have better outcomes than those due to CNV associated with age-related macular degeneration, and patients with good vision just before the hemorrhage occurred, and with a short duration of hemorrhage, may do well.
Glatt H, Machemer R. Experimental subretinal hemorrhage in rabbits. Am J Ophthalmol. 1982 Dec;94(6):762-73.
Toth CA, Benner JD, Hjelmeland LM, Landers MB 3rd, Morse LS. Ultramicrosurgical removal of subretinal hemorrhage in cats. Am J Ophthalmol. 1992 Feb 15;113(2):175-82
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; Submacular Surgery Trials (SST) Research Group. Surgery for hemorrhagic choroidal neovascular lesions of age-related macular degeneration: ophthalmic findings: SST report no. 13. Ophthalmology. 2004 Nov;111(11):1993-2006.
Kamei M, Misono K, Lewis H. A study of the ability of tissue plasminogen activator to diffuse into the subretinal space after intravitreal injection in rabbits. Am J Ophthalmol. 1999 Dec;128(6):739-46.
Pulido JS, Bakri SJ, Valyi-Nagy T, Shukla D. Rituximab penetrates full-thickness retina in contrast to tissue plasminogen activator control. Retina. 2007 Oct;27(8):1071-3
About our author(s):
Sophie J. Bakri, MD
Associate Professor of Ophthalmology