September 2013, Issue 61

Management of Submacular Hemorrhage Associated with Neovascular Age-Related Macular Degeneration

Christopher J. Brady, MD and Carl D. Regillo, MD Retina Service, Wills Eye Institute, MidAtlantic Retina Philadelphia, PA

Hemorrhage under the center of the macula is one of the dreaded manifestations of neovascular age-related macular degeneration (AMD). Natural history studies have shown that a large submacular hemorrhage (SMH) portends a very poor prognosis, with most patients presenting with poor vision, and then worsening in up to 80% of cases without treatment.¹ Despite the recent therapeutic advances of targeted therapies against vascular endothelial growth factor (VEGF), the optimal management of SMH associated with AMD is poorly defined.^2,3 This is due, in part, to the fact that patients with SMH were excluded from the major pivotal AMD trials testing the various anti-VEGF therapeutics. Some information from a randomized clinical trial on management of this condition is provided by the Submacular Surgery Trials (SST)⁴ in which surgery to remove the choroidal neovascular complex in conjunction with evacuation of the hemorrhage prevented severe vision loss compared with observation although it did not stabilize or improve vision. Further guidance is limited to smaller, uncontrolled published series.⁵

The decision to manage AMD-related SMH with a hemorrhage displacement procedure (in addition to anti-VEGF therapy) is based mainly on the location, size and thickness of hemorrhage. In the authors' opinion, patients with small, thin SMH, especially if the blood is mostly outside the foveal center, are best managed by medical therapy (anti-VEGF) alone. Patients with larger hemorrhages (> 6 disc areas) that are relatively thick and centered in the macula may be considered for a pneumatic displacement procedure, especially if the hemorrhage is less than 3 weeks in duration and if there was reasonably good vision before the acute hemorrhage. Displacing a SMH can be done in the office with an intravitreal injection of an expansile gas with or without an intravitreal injection of tissue plasminogen activator (tPA) or in the operating room with a pars plana vitrectomy (PPV), subretinal tPA injection and fluid-gas exchange.^5,6 In the authors' experience, the surgical approach produces a more reliable, complete displacement of the SMH away from the macula, and is the preferred technique.

Known poor vision prior to SMH development is a relative contraindication to surgical intervention. Patients with massive subretinal hemorrhage, such as hemorrhages that extend significantly into the peripheral retina, are not good candidates for hemorrhage displacement. Individuals with severe or uncontrolled systemic conditions may not be good surgical candidates.

If the decision is made to proceed with surgery, perioperative anti-VEGF therapy should be considered. Small-incision vitrectomy (23- or 25-gauge) with valved cannulas is the authors' current standard procedure. A core PPV is performed and the posterior hyaloid is separated from the posterior pole if there is not a preexisting posterior vitreous detachment. To allow a self-sealing retinotomy, a 39- or 41- gauge needle is then used to inject tPA at a concentration of 25 mcg/0.1 ml directly into the SMH. To ensure a good postoperative displacement, it is best to create a generous size bleb of subretinal fluid that extends beyond the borders of the SMH, particularly inferiorly (there is no attempt to evacuate the subretinal blood directly or remove the neovascular complex). A 75-80% fluid-air exchange is then performed. The air may, in turn, be exchanged with 20% SF6 gas if a longer lasting tamponade is desired. Patients are instructed to maintain face-down positioning for 24-48 hours, and are followed closely for complications. Customary postoperative topical therapy (steroid and antibiotic drops) is used.

Postoperative retinal tears, retinal detachment and proliferative vitreoretinopathy are potential complications (these complications are more common with older surgical approaches that utilized larger retinotomies to evacuate the hemorrhage directly). Endophthalmitis is a potential rare complication of PPV. Vitreous hemorrhage, macular hole, recurrent SMH, and retinal pigment epithelium (RPE) tear formation have all been reported following PPV with tPA for SMH displacement.

Level 1 evidence in support of the efficacy of any intervention for AMD-related, large SMH is not available, but because the natural history is so poor, any evidence to suggest a favorable effect compared to the natural history is encouraging.⁷ Most series which used small needles or microcannulas to create a self-sealing retinotomy have reported mean improvements in vision postoperatively, with one series reporting some visual improvement in 73% (8 of 11) of eyes with a mean follow-up of 6.5 months.⁸ Olivier et al reported greater than or equal to two lines of vision gained in 68% (17 of 25) of eyes at 3 months follow-up.⁹ More recently, Sandhu and colleagues reported 83% of patients reaching the same ≥2-line improvement endpoint at 6 months.¹⁰

In the authors' experience, attention to several aspects of the care of patients with SMH may help to improve outcomes. A generous amount of tPA solution injected under the retina in and around the hemorrhage helps to maximize the postoperative hemorrhage displacement success. Anti-VEGF therapy should continue after surgery to minimize the risk of neovascular growth and progressive exudation due to recurrent bleeding. After a PPV, drugs injected intravitreally are cleared faster compared to non-vitrectomized eyes and, thus, anti-VEGF therapy may need to be delivered on a regular and frequent basis to keep the neovascular process in check and maximize long-term visual outcomes.

References:
1. Scupola A, Coscas G, Soubrane G, Balestrazzi E. Natural history of macular subretinal hemorrhage in age-related macular degeneration. Ophthalmologica 1999;213:97-102.
2. Tennant MT, Borrillo JL, Regillo CD. Management of submacular hemorrhage. Ophthalmol Clin North Am 2002;15:445-52, vi.
3. Steel DH, Sandhu SS. Submacular haemorrhages associated with neovascular age-related macular degeneration. Br J Ophthalmol 2011;95:1051-7.
4. Bressler NM, Bressler SB, Childs AL, et al. Surgery for hemorrhagic choroidal neovascular lesions of age-related macular degeneration: ophthalmic findings: SST report no. 13. Ophthalmology 2004;111:1993-2006.
5. Shultz RW, Bakri SJ. Treatment for submacular hemorrhage associated with neovascular age-related macular degeneration. Semin Ophthalmol 2011;26:361-71.
6. Hassan AS, Johnson MW, Schneiderman TE, et al. Management of submacular hemorrhage with intravitreous tissue plasminogen activator injection and pneumatic displacement. Ophthalmology 1999;106:1900-6; discussion 6-7.
7. van Zeeburg EJ, van Meurs JC. Literature review of recombinant tissue plasminogen activator used for recent-onset submacular hemorrhage displacement in age-related macular degeneration. Ophthalmologica 2013;229:1-14.
8. Haupert CL, McCuen BW, 2nd, Jaffe GJ, 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 Ophthalmol 2001;131:208-15.
9. Olivier S, Chow DR, Packo KH, MacCumber MW, Awh CC. Subretinal recombinant tissue plasminogen activator injection and pneumatic displacement of thick submacular hemorrhage in Age-Related macular degeneration. Ophthalmology 2004;111:1201-8.
10. 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;4:637-42.