Retinal hemorrhage has been described in many proanemic conditions, such as juvenile and adult pernicious anemias, iron deficiency, acute leukemias, malaria, aplastic anemia, and autoimmune hemolytic anemia.1,2 More rarely, bleeding may affect the macula or the premacular retrohyaloid space.3 Although surgical4 or Nd:YAG laser treatment is often performed for these vision-threatening conditions,5,6 this study evaluates the clinical and spectral-domain optical coherence tomography (SD-OCT) findings during follow-up of two untreated patients.
To the best of our knowledge, this is the first report on the natural history of premacular hemorrhage associated with acute anemia studied with SD-OCT.
A 36-year-old man presented to the emergency department complaining of bilateral poor vision, worsening fatigue, and exertional dyspnea. Of note, he was a heavy smoker and had been a chronic alcohol abuser for at least 15 years. Laboratory analysis revealed severe megaloblastic anemia with thrombocytopenia and vitamin B12 and folate deficiencies.
Visual acuity was 20/100 in the right eye and 20/160 in the left eye. Pupillary reactions, ocular motility, and IOP were bilaterally normal. Fundus examination showed disk swelling, widespread cotton wool spots, and multiple intraretinal hemorrhages associated with a wide premacular hemorrhage (Figures 1A and 1E). Fluorescein angiography showed dilated tortuous retinal veins and staining of the optic disc. SD-OCT showed a large hyper-reflective, dome-shaped area in the macular region with a posterior shadowing effect due to the preretinal blood (Figures 1B and 1F). The patient was immediately transfused with three blood units. He refused any surgical or laser treatment for the premacular hemorrhage. After commencing daily supplementation with 100 μg vitamin B12 and 5 mg folate, he was discharged.
Case 1. (A, E) At the time of presentation, fundus photographs of the first patient showed multiple intraretinal hemorrhages in both eyes associated with a wide premacular hemorrhage. (B, F) The corresponding SD-OCT scans revealed a large hyper-reflective, dome-shaped area in the macular region with a posterior shadowing effect and a fluid level caused by the gravitational settling of the blood. (C) Two months later, a small round hemorrhage over the fovea was still visible in a fundus photograph of the right eye. (G) In the left eye, a peanut-shaped hemorrhage next to the fovea remained. SD-OCT revealed a more pronounced cavity topped with some hyper-reflective material in the right eye (D) and a small hyper-reflective spot with posterior shadowing in the left eye (H). Resolution of clinical findings was observed in the right eye at 4 months with the same OCT aspect as the other eye (not shown).
One month later, most of the retinal hemorrhages had disappeared, and the premacular hemorrhages were smaller and well delimited. Visual acuity was 20/80 in the right eye and 20/125 left eye.
After 2 months, all the retinal hemorrhages disappeared, except for a small round hemorrhage over the right fovea (Figure 1C) and a peanut-shaped hemorrhage next to the left fovea (Figure 1G). The disc appeared normal. Visual acuity was 20/32 in the right eye and 20/25 in the left eye. SD-OCT revealed a small residual hyporeflective cavity above the fovea in the right eye delimited by internal limiting membrane (ILM), while in the left eye it showed a minute residual hyper-reflective premacular thickening next to the fovea with a posterior shadowing effect (Figures 1D and 1H). Four months later, visual acuity was 20/20 in both eyes, with a complete resolution of clinical findings in the right eye, which had the same OCT aspect as the left eye.
A 38-year-old man with Hodgkin’s lymphoma, Kaposi’s sarcoma, HHV8+, and a known deficit in CD4 cells presented to the emergency department complaining of weakness, fever, sickness, jaundice, and blurred vision in the left eye. Autoimmune hemolytic anemia was diagnosed, probably caused by a viral infection and/or by recent IL-2 therapy.
On ophthalmic examination, visual acuity was 20/25 in the right eye and 20/40 in the left eye, with normal IOP and pupillary reactions in both eyes. Fundus examination revealed a small macular hemorrhage in the left eye and numerous cotton wool spots in both eyes along the vascular arcades and around the optic disc (Figure 2A). Fluorescein angiography showed a hypo-fluorescent spot in the left fovea caused by the hemorrhage. The same spot appeared on SD-OCT as a small dome-shaped area with a fluid level (Figure 2B).
Case 2. (A) In the second patient, a fundus photograph of the left eye showed a small macular hemorrhage and numerous cotton wool spots. (C) These findings disappeared after 1 month. (B) A corresponding SD-OCT scan at presentation revealed a dome-shaped elevated area just above the fovea. (D) One month later, a small hyper-reflective spot similar to the one described in the first case was visible (Figure 1D,H).
Blood transfusions and systemic corticosteroids stabilized the patient’s hematologic status.
No Nd:YAG laser treatment was necessary because the hemorrhage resolved spontaneously after just 1 month (Figure 1C), and visual acuity in both eyes improved to 20/20.
Below the left eye foveal depression, a small hyper-reflective spot with a small posterior shadowing effect was visible on SD-OCT (Figure 2D), similar to the one noted in case 1.
Concomitant thrombocytopenia or platelet dysfunction in patients with severe anemia may be a contributing factor for the development of retinal hemorrhages.7 Conversely, premacular hemorrhages are quite rare.3,8 This is the first report of premacular sub-ILM hemorrhages secondary to severe acute anemia monitored through its natural evolution by SD-OCT. It has been hypothesized that in severe anemia, the retinal endothelial cell integrity is compromised by ischemia, vessel wall dilatation (stretch), and increased blood flow (shear stress), facilitating seepage of red blood cells through inter-endothelial junctions when platelets that act as endothelial plugs are deficient.9 The exact location of the premacular hemorrhage is not well ascertained in the literature. Some authors suggest a cleavage plane under the ILM, whereas others note a pooling of blood under the posterior hyaloid.5,10 In the cases presented here, the blood is clearly pooled under the ILM. Our observations agree with a prior time-domain OCT study of two cases of preretinal hemorrhage secondary to Valsalva retinopathy, treated by laser or surgical approach.11
We report two cases that differ in terms of anemia etiology and hemorrhage size at presentation. Notwithstanding, the hemorrhages in both cases resolved well without treatment. While the functional outcomes were optimal, the anatomical restoration was not complete. A case of a spontaneous resolution of subhyaloid hemorrhage associated with anemia secondary to idiopathic thrombocytopenic purpura was recently reported, with a similar favorable outcome; however, no OCT imaging was conducted in this study.3 We could find no other reports of untreated patients to compare with our OCT findings, but interestingly some authors12,13 report a similar OCT pattern after laser treatment in premacular cases due to Valsalva retinopathy. They attribute the residual hyper-reflective spot to a thickening of the ILM due to the laser scar, but we believe this is just the natural evolution of blood adsorption, leaving a small cavity under the ILM filled with blood remnants.
In conclusion, the SD-OCT follow-up of two untreated patients has enabled us to report the natural history of premacular hemorrhage secondary to severe acute anemia. Even if etiology, clinical presentation, and anatomical features are initially different, we demonstrate a common final outcome.
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