By: Barton L. Blackorby, MD; Anjali Shah; and Gaurav K. Shah, MD
Submacular hemorrhage (SMHs) is a visually debilitating condition that may be associated with a variety of underlying etiologies. Long-term visual loss can occur secondary to the toxic effects of blood and iron on the photoreceptors, prolonged separation of the photoreceptors from the retinal pigment epithelium (RPE), sheering forces of the fibrin clot on the photoceptors or creation of scar tissue.1,2 SMHs is most commonly associated with age-related macular degeneration (AMD) but may also be observed in various other pathologies associated with choroidal neovascularization (CNV) such as myopia, polypoidal choroidal vasculopathy (PCV), trauma, presumed ocular histoplasmosis and angioid streaks.1 SMHs may also present as a complication of laser photocoagulation or scleral buckle surgery. Treatment options vary and are tailored to characteristics of the SMHs. Small SMHs can typically be observed, medium SMHs are typically amenable to treatment and large SMHs often have a poor prognosis regardless of treatment.1 This paper will provide a brief overview of current treatment options, patient selection and outcomes.
Observation alone may be associated with variable visual acuity outcomes. Factors associated with a poor visual prognosis include the presence of CNV, thick SMH, SMH secondary to AMD,3 and large SMH.4 Cases appropriate for observation include patients with small and thin SMH,1 hemorrhages in areas of RPE atrophy,5 SMH secondary to choroidal rupture,3 and SMH secondary to retinal artery macroaneurysms (RAM).6
In-clinic management options include photodynamic therapy (PDT), pneumatic displacement and monotherapy with anti-vascular endothelial growth factor (anti-VEGF) drugs. Advantages of these procedures are that they can be performed in the clinic and are minimally invasive. PDT may have a role in treating SMH secondary to AMD but, to our knowledge, no head-to-head studies comparing PDT to other treatment modalities have been published to date.
Pneumatic displacement, like PDT, has the advantage of being an in-clinic procedure. Ideal candidates for this procedure are those with recent (less than three weeks old) thick SMH that involve the fovea, large SMH, SMH inferior to the fovea or SMH secondary to trauma; AMD; or RAM.1,7 Intravitreal tissue plasminogen activator (tPA) may be combined with pneumatic displacement in order to facilitate clot liquefaction. Use of tPA along with pneumatic displacement has been reported to be beneficial in cases of SMH secondary to AMD or those associated with vitreous hemorrhage.1 Potential complications of this procedure include vitreous hemorrhage, endophthalmitis, retinal detachment, suprachoroidal gas placement, glaucoma and recurrent hemorrhage.2
Surgical approaches to management of SMH typically involve pars plana vitrectomy (PPV) with clot evacuation or displacement. Clot evacuation is generally performed through large retinotomies after PPV has been performed. The retinotomies result in focal RPE and photoreceptor atrophy and carry a risk of rhegmatogenous retinal detachment.2 Removal of the clot also carries the risk of damaging the overlying photoreceptors through mechanical forces. This approach was evaluated in the Submacular Surgery Trial, which compared observation versus clot evacuation in patients with SMH secondary to neovascular AMD. The results demonstrated that although clot evacuation was associated with prevention of severe vision loss, there was no associated improvement in quality of life.8 Combined with the risk of retinal detachment, this approach lost popularity and has been largely replaced by attempts to displace, rather than evacuate, the clot.2 An alternative to the original clot evacuation technique is the addition of tPA and air or gas in cases in which the hemorrhage can be displaced away from the fovea. With this approach, a smaller retinotomy can be created to facilitate insertion of the tPA which allows the blood to liquefy and then eventually be displaced away from the fovea with gas or air (see video). This approach has been attempted in patients with SMH secondary to AMD, PCV or choroidal rupture. Visual acuity outcomes vary by the underlying disease process and are generally worse when associated with neovascular AMD, longer duration of SMH, massive SMH or SMH associated with hemorrhagic RPE detachment.9
An alternative surgical intervention is macular translocation. This approach is associated with variable visual acuity outcomes and may be complicated by the development of proliferative vitreoretinopathy, CNV, cataract and retinal detachment.10 This approach may be of benefit for patients with severe vision loss secondary to large SMH when alternative methods have not yielded satisfactory outcomes.
The addition of intravitreal anti-VEGF therapy to the above approaches has gained popularity as the majority of SMH is secondary to a neovascular process, such as neovascular AMD. Supplementation of PPV and pneumatic displacement with anti-VEGF therapy has been reported to be associated with improved visual acuity outcomes.11 Additionally, anti-VEGF monotherapy alone has been reported to be an effective treatment of SMH of varying sizes and thicknesses compared to observation while avoiding the risks associated with vitrectomy.12,13
Subretinal anti-VEGF therapy has also been investigated as a treatment option for SMH since intravitreal administration of anti-VEGF therapy in a post-vitrectomized eye may not allow for the sustained anti-VEGF therapy, which may be needed for adequate diffusion into the SMH. In a report of two patients, both underwent displacement of SMH secondary to AMD along with placement of subretinal tPA and subretinal anti-VEGF. In one patient, the combination with subretinal anti-VEGF therapy was associated with improvement of visual acuity to the patient’s baseline acuity and reduction in CNV activity noted on IVFA on postoperative day four.14 The patient did not require additional anti-VEGF therapy until six weeks postoperatively for a new subretinal hemorrhage. The other patient underwent monthly anti-VEGF therapy after surgery for persistent subretinal fluid but experienced moderate visual acuity improvement from 20/125 preoperatively to 20/60 at seven months postoperatively. At nine months postoperatively, the latter patient developed an RPE tear.14
In sum, management of SMH depends on the size, chronicity and thickness of the SMH. Knowledge of the underlying disease process can also help tailor management by addition of anti-VEGF or tPA therapy. With appropriate and timely management, many patients with SMH are able to achieve some improvement in visual acuity, but ongoing therapy with intravitreal chemotherapeutics may be necessary to maintain the initial visual acuity gains.
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About our author(s):
Dr. Blackorby received his medical education from the University of Oklahoma College of Medicine and his ophthalmology education from Madigan Army Medical Center. He is currently the Chief of Ophthalmology at General Leonard Wood Army Community Hospital and began his vitreoretinal fellowship at The Retina Institute of St. Louis in July 2018.
Anjali Shah is a sophomore in high school.
Dr. Shah is director of the vitreoretinal fellowship program at The Retina Institute in St. Louis, Missouri.