Blinding Anemia: A Case of Bilateral Sequential Nonarteritic Ischemic Optic Neuropathy Secondary to Warm Autoimmune Hemolytic Anemia

We present the case of a 54-year-old man who presented with a 1-day history of visual loss of the inferior aspect of his left visual field with associated photopsia.

Clinical Correspondence Section Editors: Robert Avery, DO Karl C. Golnik, MD Caroline Froment, MD, PhD An-Guor Wang, MD Blinding Anemia: A Case of Bilateral Sequential Nonarteritic Ischemic Optic Neuropathy Secondary to Warm Autoimmune Hemolytic Anemia Benjamin O’Keeffe, MB ChB, Neil Avery, MBChB, FRANZCO, Neil Aburn, MBChB, FRANZCO W e present the case of a 54-year-old man who presented with a 1-day history of visual loss of the inferior aspect of his left visual field with associated photopsia. He had no underlying medical conditions (including no history of diabetes mellitus, hypertension, or renal disease), was a nonsmoker, and was on no regular medications. On examination, best visual acuity was 6/6 in the right eye (RE) and 6/18 in the left eye (LE). There was a left relative afferent pupillary defect and absent left color vision (pseudoisochromatic plates). Visual field testing showed a left inferior altitudinal defect, with nonspecific changes in the RE (Fig. 1). Fundus examination revealed optic disc hemorrhages and optic nerve swelling in the left eye with no other abnormal features. Examination of the right eye revealed a ‟disc at risk,” without swelling or hemorrhage. Full physical examination performed by the physicians was normal with no other features of autoimmune or lymphoproliferative disease. Importantly, the patient had no symptoms of other autoimmune disease or giant cell arteritis. Routine blood screening was performed and revealed an anemia with hemoglobin 73 g/L (normal 130–175 g/L), Erythrocyte sedimentation rate was 120 mm/h (normal 0–30 mm/h), and platelets were 275 · 109/L (normal 150–400 · 109/L). C reactive protein was mildly elevated at 6 mg/mL (normal 0–5 mg/mL). Review of the blood film revealed spherocytes and a leukoerythroblastic pattern consistent with hemolysis. The patient was immediately admitted to hospital by the hematology team and received a red blood cell (RBC) transfusion of 2 units, thiamine replacement, and was started on high-dose oral prednisone 1 mg/ kg. Subsequent investigations revealed an antinuclear antibody of 1:640 and a homogenous pattern (of note, no other signs or symptoms of systemic lupus erythematosus were present), and a positive direct antiglobulin test (positive immunoglobulin [IgG] and negative C3d). Other results Ophthalmology Department, Capital and Coast District Health Board, Wellington, New Zealand. The authors report no conflicts of interest. Address correspondence to Neil Avery, Wellington Hospital, Riddiford Street, Newtown 6021, Wellington, New Zealand; E-mail: [e-mail] e574 of interest included normal double stranded deoxyribonucleic acid, negative extractable nuclear antigen antibodies, negative cardiolipin, and negative antineutrophil cytoplasmic antibody, and complement classical pathway activity was elevated at 141% (normal 70%–130%), but all other complement test were within normal limits. Bone marrow biopsy histology revealed erythroid hyperplasia consistent with hemolytic anemia. Flow cytometry of the marrow revealed no lymphoid infiltrate, and computed tomography of the chest, abdomen, and pelvis confirmed no occult lymphadenopathy. Temporal artery biopsy was considered but not performed because of the patient’s lack of symptoms and alternative explanations for elevated inflammatory markers. Subsequent review at day 8 showed objective worsening of best visual acuity of the RE to 6/9 and of the LE to hand movements. Fundus examination revealed new optic disc swelling and hemorrhages at the right optic disc and early pallor of the left optic disc. A diagnosis of bilateral sequential nonarteritic anterior ischemic optic neuropathy (NAION) was made; at this point, repeat blood tests revealed a hemoglobin of 92 g/L, Erythrocyte sedimentation rate 80 mm/Hr, C reactive protein 10 mg/mL, and platelets 237 · 109/L. Successful medical treatment with prednisone and weekly rituximab infusions improved his hemoglobin to 120 g/L, and a slow tapering course of prednisone was completed. While tapering prednisone, his hemoglobin, vision, and visual fields were monitored closely, and there was no change in his visual disturbance. Unfortunately, his direct antiglobulin test remained positive, and on tapering prednisone, his anemia worsened and he required a splenectomy (histology of which revealed no malignancy and was consistent with hemolytic anemia). Subsequently, the hemoglobin remained stable without ongoing medical treatment, and he was discharged from medical followup with stable hemoglobin and no further evidence of hemolysis. At 40 months, the best visual acuity was 6/6 in the RE and 6/60 in the LE. Visual fields remained stable with no documented recurrence or progression of NAION in either eye (Fig. 1). Hemolytic anemia is an anemia due to premature destruction (hemolysis) of red blood cells (RBCs). Diagnostic features include reduced RBC indices and a peripheral blood film showing immature RBCs (reticulocytes). Autoimmune hemolytic anemia (AHA) is the O’Keeffe et al: J Neuro-Ophthalmol 2022; 42: e574-e576 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Clinical Correspondence FIG. 1. Visual fields on presentation, Day 15, and 39 months follow-up. clinical condition in which immunoglobulin (IgG and IgM) antibodies bind to RBC surface antigens and cause hemolysis through the complement system and the reticuloendothelial system; in warm autoimmune hemolytic anemias (WAIHAs), these autoantibodies react most strongly near 37°C and exhibit decreased affinity at lower temperatures. WAIHA is responsible for 48%– 70% of AHA, with incidence increasing from age 40. It may be isolated or associated with diseases including postviral infections, connective tissue diseases, immune deficiency diseases, posttransplantation, and malignancies (1). O’Keeffe et al: J Neuro-Ophthalmol 2022; 42: e574-e576 NAION is likely caused by occlusion or impaired blood flow in the short posterior ciliary arteries resulting in partial or total infarction of the optic nerve head. Common risk factors for NAION include structural crowding of the optic nerve head, hypertension, diabetes mellitus and hyperlipidemia, hypotensive episodes, and immune-related disorders (2,3). Although most cases of NAION can be attributable to the aforementioned risk factors, NAION is welldocumented in anemic patients, particularly postoperative patients. It is important to note that risks factors for NAION in these patients are not isolated to anemia and pathogenesis may be multifactorial (2,3). There are also case e575 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Clinical Correspondence reports of NAION in patients with anemia secondary to renal failure, hemoglobinopathies, and iron deficiency anemia (4). Of note, AHA is associated with a prothrombotic state and an increased risk of both venous and arterial thrombosis. This is another potential mechanism by which AHA may precipitate NAION (5). Despite this, there have not been any previously reported cases of warm hemolytic anemia presenting with bilateral NAION. This case illustrates the importance of the gold standard routine blood workup for NAION including FBC, Erythrocyte sedimentation rate, and C reactive protein. Further testing can then be directed to the individual case. The nature of the sequential involvement in this case shows the importance of aggressive treatment of anemia in patients with NAION to attempt to prevent the recurrence or involvement of the fellow eye. It also illustrates despite aggressive treatment and correction of anemia, patients may develop sequential involvement of the fellow eye. For both this reason and the systemic thrombotic risk, systemic anticoagulant therapy should be considered in these patients because of the elevated risk of both venous and arterial thrombotic events (5). e576 STATEMENT OF AUTHORSHIP Category 1: a. Conception and design: N. Avery, N. Aburn, and B. O’Keeffe; b. Acquisition of data: N. Avery and N. Aburn; c. Analysis and interpretation of data: N. Avery, Neil Aburn, and O’Keeffe. Category 2: a. Drafting the manuscript: N. Avery, N. Aburn, and O’Keeffe; b. Revising it for intellectual content: N. Avery, N. Aburn, and O’Keeffe. Category 3: a. Final approval of the completed manuscript: N. Avery, Neil Aburn, and O’Keeffe. REFERENCES 1. Hoffman PC. Immune hemolytic anemia—selected topics. Hematology Am Soc Hematol Educ Program. 2009;10:80–86. 2. McCulley TJ, Lam BL, Feuer WJ. A comparison of risk factors for postoperative and spontaneous nonarteritic anterior ischemic optic neuropathy. J Neuroophthalmol. 2005;25:22–24. 3. Ho SF, Dhar-Munshi S. Nonarteritic anterior ischaemic optic neuropathy. Curr Opin Ophthalmol. 2008;19:461–467. 4. Hattenbach LO, Horle S, Scharrer I, Kroll P, Koch F. Central retinal vein occlusion and nonarteritic ischemic optic neuropathy in 2 patients with mild iron deficiency anemia. Kacer Ophthalmologica. 2001;215:128–131. 5. Rugeri M, Rodeghiero F. Thrombotic risk in patients with haemolytic anaemia. Br J Haematol. 2016;172:131–146. O’Keeffe et al: J Neuro-Ophthalmol 2022; 42: e574-e576 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited.