CYTOMEGALOVIRUS RETINITIS: AN UNUSUAL PRESENTATION AS VITREOUS HEMORRHAGE Soon Wai Ch’ng, MBChB, Alexander Brent, MBChB, Somnath Banerjee, FRCSEd
Purpose: The purpose of this report is to describe an unusual presentation of vitreous hemorrhage (VH) in a patient with an immunosuppressive condition. Methods: Retrospective case report. Results: A 72-year-old woman with known T-cell prolymphocytic leukemia treated with a course of alemtuzumab presented to our department with a VH in her left eye after a fall. An initial diagnosis of hemorrhagic posterior vitreous detachment was made. However, as the VH was resolving, she was found to have underlying vitritis, occlusive vasculitis, and a pale optic nerve head. Vitreous biopsy confirmed cytomegalovirus retinitis. Despite treatment with intravenous foscarnet and oral valganciclovir, her vision continued to remain poor because of the severe damage from the retinal vasculitis and residual VH. Conclusion: As indications for immunosuppression increase, the incidence of cytomegalovirus retinitis in non-HIV–immunosuppressed patients is expected to rise. Therefore, in this subgroup of patients, we should be aware of any underlying retinitis especially in cases with an unusual presentation of VH. RETINAL CASES & BRIEF REPORTS 8:50–51, 2014
fingers. The VH was resolving but revealed underlying vitritis, occlusive vasculitis, and a pale optic nerve head (Figure 1). Fundus fluorescein angiogram showed a venous phase with leakage at the optic nerve head, absent filling of the peripheral blood vessels, and scattered blot hemorrhages (Figure 2). We made a provisional diagnosis of panuveitis with occlusive vasculitis secondary to lymphocytic infiltrate or infective uveitis. Therefore, she was admitted for 4 pulses of intravenous methylprednisolone (500 mg) but reported no improvement. An anterior chamber and vitreous biopsy was performed. The vitreous polymerase chain reaction samples confirmed 1,400 copies per milliliter of cytomegalovirus (CMV) but no evidence of neoplastic cells. It was also negative for bacterial growth, Epstein–Barr virus, varicella zoster virus, herpes simplex virus, adenoviral DNA, and toxoplasma. The anterior chamber samples were negative. Serological sample was positive for CMV DNA. HIV tests were negative. The intravenous methylprednisolone was stopped and she was commenced on intravenous foscarnet (90 mg/kg). After 1 week, she was discharged on 900 mg oral valganciclovir once a day. However, her visual acuity remained at counting fingers because of the severe retinal damage from the vasculitis and residual VH.
From the Department of Ophthalmology, University Hospitals of Leicester, Leicester Royal Infirmary, Leicester, United Kingdom. Case Report A 72-year-old woman presented to our department with a 3-day history of left photopsia and a “net-like curtain” effect in her vision after a fall. Her visual acuity was 20/30. Examination revealed a left vitreous hemorrhage (VH) precluding a clear fundal view. Ultrasound B-scan confirmed the VH without any evidence of retinal tears or detachment. Before presentation, she had no relevant ophthalmic history. Her medical history included hypertension and T-cell prolymphocytic leukemia. She had recently completed a 14week course of alemtuzumab (Campath; Genzyme, Cambridge, MA). Her leukocyte count, neutrophils, and platelet counts were normal. However, her CD4 counts were markedly reduced at 0.04 · 109/L (reference range: 0.49–1.67 · 109/L). After an observation period of 2 months, her visual acuity had deteriorated to counting Paper presented at the third Kettering Eye Meeting at Kettering Park Hotel, United Kingdom, March15, 2013. Won the first prize for the presentation of this case. None of the authors have any financial/conflicting interests to disclose. Reprint requests: Soon Wai Ch’ng, MBChB, Department of Ophthalmology, University Hospitals of Leicester, Leicester Royal Infirmary, Infirmary Square, Leicester LE1 5WW, United Kingdom; e-mail: [email protected]
Discussion Cytomegalovirus is part of the herpes family of viruses that causes opportunistic infection especially in patients with HIV, hematological malignancy, and organ transplantation.1–3 Cytomegalovirus retinitis 50
51
CMV RETINITIS AS VITREOUS HEMORRHAGE
Fig. 1. Left fundal examination revealing a pale optic nerve head, occlusive vasculitis, and VH.
usually occurs as a result of hematogenous spread of the virus to the retina after systemic reactivation of a latent infection or in patients with severe deficiency of cell-mediated immunity. In adult hematopoietic malignancies without stem cell transplantation, the incidence of CMV retinitis is more common in lymphoid malignancies (13.6%) compared with myeloid malignancies (3.9%).4,5 Typically, CMV retinitis presents as a necrotizing retinitis with a characteristic appearance. However, in our case, the unusual pre-
Fig. 2. Venous phase of the fundus fluorescein angiogram showing leakage at the optic nerve head, shutdown of the peripheral blood vessels with absence filling, and scattered blot hemorrhages.
sentation of VH masked the underlying retinitis delaying the final diagnosis. To our knowledge, this is the first reported case of CMV retinitis in T-cell prolymphocytic leukemia. T-cell prolymphocytic leukemia is a very rare and aggressive form of leukemia in the elderly characterized by the proliferation of small-to-medium sized prolymphocytes with a mature postthymic T cell.6,7 Alemtuzumab is a humanized monoclonal antibody against the CD52 antigen in the T cell. In a single center study, it has been reported that the rate of CMV reactivation over a 5-year period was especially high in patients receiving alemtuzumab (50%).5 In our case, we suspect the use of alemtuzumab may have been the triggering factor for her CMV retinitis. First-line treatment of CMV retinitis often involves oral valganciclovir or intravenous ganciclovir administration. Local therapy with intravitreal injection or implant may be considered in cases without any systemic involvement.8 As indications for immunosuppression increase, the incidence of CMV retinitis in non-HIV–immunosuppressed patients is expected to rise. Therefore, in this subgroup of patients, we should be aware of any underlying retinitis especially in cases with an unusual presentation of VH. Key words: cytomegalovirus retinitis, T-cell prolymphocytic leukemia, vitreous hemorrhage. References 1. Ng P, McCluskey P, McCaughan G, et al. Ocular complications of heart, lung and liver transplantation. Br J Ophthalmol 1998;82:423–428. 2. Okamoto T, Okada M, Mori A, et al. Successful treatment of severe cytomegalovirus retinitis with foscarnet and intraocular injection of ganciclovir in a myelosuppressed unrelated bone marrow transplant patient. Bone Marrow Transplant 1997;20:801–803. 3. Kuo I, Kempen JH, Dunn JP, et al. Clincial characteristics and outcomes of cytomegalovirus retinitis in persons without human immunodeficiency virus infection. Am J Ophthalmol 2004;138:338–346. 4. Guyotat D, Gibert R, Chomel J, et al. Incidence and prognosis of cytomegalovirus infections following allogenic bone marrow transplantation. J Med Virol 1987;23:393–399. 5. Ng AP, Worth L, Chen L, et al. Cytomegalovirus DNAemia antignenemia and disease: incidence, natural history and management in settings other than allogenic stem cell transplantation. Haematologica 2005;90:1672–1679. 6. Graham RL, Cooper B, Krause JR. T-cell prolymphocytic leukemia. Proc (Bayi Univ Med Cent) 2013;26:19–21. 7. Swerdlow SH, Campo E, Harris NL, et al. WHO Classification of Tumours, Tumours of Haematopoietic and Lymphoid Tissues. 4th ed. Lyon, France: IARC; 2008. 8. Libby E, Movva S, Quintana D. Cytomegalovirus retinitis during chemotherapy with rituximab plus hyperfractionated cyclophosphamide, vincristine, doxorubicin and dexamethasone. J Clin Oncol 2010;28:661–662.
Purpose: The purpose of this report is to describe an unusual presentation of vitreous hemorrhage (VH) in a patient with an immunosuppressive condition. Methods: Retrospective case report. Results: A 72-year-old woman with known T-cell prolymphocytic leukemia treated with a course of alemtuzumab presented to our department with a VH in her left eye after a fall. An initial diagnosis of hemorrhagic posterior vitreous detachment was made. However, as the VH was resolving, she was found to have underlying vitritis, occlusive vasculitis, and a pale optic nerve head. Vitreous biopsy confirmed cytomegalovirus retinitis. Despite treatment with intravenous foscarnet and oral valganciclovir, her vision continued to remain poor because of the severe damage from the retinal vasculitis and residual VH. Conclusion: As indications for immunosuppression increase, the incidence of cytomegalovirus retinitis in non-HIV–immunosuppressed patients is expected to rise. Therefore, in this subgroup of patients, we should be aware of any underlying retinitis especially in cases with an unusual presentation of VH. RETINAL CASES & BRIEF REPORTS 8:50–51, 2014
fingers. The VH was resolving but revealed underlying vitritis, occlusive vasculitis, and a pale optic nerve head (Figure 1). Fundus fluorescein angiogram showed a venous phase with leakage at the optic nerve head, absent filling of the peripheral blood vessels, and scattered blot hemorrhages (Figure 2). We made a provisional diagnosis of panuveitis with occlusive vasculitis secondary to lymphocytic infiltrate or infective uveitis. Therefore, she was admitted for 4 pulses of intravenous methylprednisolone (500 mg) but reported no improvement. An anterior chamber and vitreous biopsy was performed. The vitreous polymerase chain reaction samples confirmed 1,400 copies per milliliter of cytomegalovirus (CMV) but no evidence of neoplastic cells. It was also negative for bacterial growth, Epstein–Barr virus, varicella zoster virus, herpes simplex virus, adenoviral DNA, and toxoplasma. The anterior chamber samples were negative. Serological sample was positive for CMV DNA. HIV tests were negative. The intravenous methylprednisolone was stopped and she was commenced on intravenous foscarnet (90 mg/kg). After 1 week, she was discharged on 900 mg oral valganciclovir once a day. However, her visual acuity remained at counting fingers because of the severe retinal damage from the vasculitis and residual VH.
From the Department of Ophthalmology, University Hospitals of Leicester, Leicester Royal Infirmary, Leicester, United Kingdom. Case Report A 72-year-old woman presented to our department with a 3-day history of left photopsia and a “net-like curtain” effect in her vision after a fall. Her visual acuity was 20/30. Examination revealed a left vitreous hemorrhage (VH) precluding a clear fundal view. Ultrasound B-scan confirmed the VH without any evidence of retinal tears or detachment. Before presentation, she had no relevant ophthalmic history. Her medical history included hypertension and T-cell prolymphocytic leukemia. She had recently completed a 14week course of alemtuzumab (Campath; Genzyme, Cambridge, MA). Her leukocyte count, neutrophils, and platelet counts were normal. However, her CD4 counts were markedly reduced at 0.04 · 109/L (reference range: 0.49–1.67 · 109/L). After an observation period of 2 months, her visual acuity had deteriorated to counting Paper presented at the third Kettering Eye Meeting at Kettering Park Hotel, United Kingdom, March15, 2013. Won the first prize for the presentation of this case. None of the authors have any financial/conflicting interests to disclose. Reprint requests: Soon Wai Ch’ng, MBChB, Department of Ophthalmology, University Hospitals of Leicester, Leicester Royal Infirmary, Infirmary Square, Leicester LE1 5WW, United Kingdom; e-mail: [email protected]
Discussion Cytomegalovirus is part of the herpes family of viruses that causes opportunistic infection especially in patients with HIV, hematological malignancy, and organ transplantation.1–3 Cytomegalovirus retinitis 50
51
CMV RETINITIS AS VITREOUS HEMORRHAGE
Fig. 1. Left fundal examination revealing a pale optic nerve head, occlusive vasculitis, and VH.
usually occurs as a result of hematogenous spread of the virus to the retina after systemic reactivation of a latent infection or in patients with severe deficiency of cell-mediated immunity. In adult hematopoietic malignancies without stem cell transplantation, the incidence of CMV retinitis is more common in lymphoid malignancies (13.6%) compared with myeloid malignancies (3.9%).4,5 Typically, CMV retinitis presents as a necrotizing retinitis with a characteristic appearance. However, in our case, the unusual pre-
Fig. 2. Venous phase of the fundus fluorescein angiogram showing leakage at the optic nerve head, shutdown of the peripheral blood vessels with absence filling, and scattered blot hemorrhages.
sentation of VH masked the underlying retinitis delaying the final diagnosis. To our knowledge, this is the first reported case of CMV retinitis in T-cell prolymphocytic leukemia. T-cell prolymphocytic leukemia is a very rare and aggressive form of leukemia in the elderly characterized by the proliferation of small-to-medium sized prolymphocytes with a mature postthymic T cell.6,7 Alemtuzumab is a humanized monoclonal antibody against the CD52 antigen in the T cell. In a single center study, it has been reported that the rate of CMV reactivation over a 5-year period was especially high in patients receiving alemtuzumab (50%).5 In our case, we suspect the use of alemtuzumab may have been the triggering factor for her CMV retinitis. First-line treatment of CMV retinitis often involves oral valganciclovir or intravenous ganciclovir administration. Local therapy with intravitreal injection or implant may be considered in cases without any systemic involvement.8 As indications for immunosuppression increase, the incidence of CMV retinitis in non-HIV–immunosuppressed patients is expected to rise. Therefore, in this subgroup of patients, we should be aware of any underlying retinitis especially in cases with an unusual presentation of VH. Key words: cytomegalovirus retinitis, T-cell prolymphocytic leukemia, vitreous hemorrhage. References 1. Ng P, McCluskey P, McCaughan G, et al. Ocular complications of heart, lung and liver transplantation. Br J Ophthalmol 1998;82:423–428. 2. Okamoto T, Okada M, Mori A, et al. Successful treatment of severe cytomegalovirus retinitis with foscarnet and intraocular injection of ganciclovir in a myelosuppressed unrelated bone marrow transplant patient. Bone Marrow Transplant 1997;20:801–803. 3. Kuo I, Kempen JH, Dunn JP, et al. Clincial characteristics and outcomes of cytomegalovirus retinitis in persons without human immunodeficiency virus infection. Am J Ophthalmol 2004;138:338–346. 4. Guyotat D, Gibert R, Chomel J, et al. Incidence and prognosis of cytomegalovirus infections following allogenic bone marrow transplantation. J Med Virol 1987;23:393–399. 5. Ng AP, Worth L, Chen L, et al. Cytomegalovirus DNAemia antignenemia and disease: incidence, natural history and management in settings other than allogenic stem cell transplantation. Haematologica 2005;90:1672–1679. 6. Graham RL, Cooper B, Krause JR. T-cell prolymphocytic leukemia. Proc (Bayi Univ Med Cent) 2013;26:19–21. 7. Swerdlow SH, Campo E, Harris NL, et al. WHO Classification of Tumours, Tumours of Haematopoietic and Lymphoid Tissues. 4th ed. Lyon, France: IARC; 2008. 8. Libby E, Movva S, Quintana D. Cytomegalovirus retinitis during chemotherapy with rituximab plus hyperfractionated cyclophosphamide, vincristine, doxorubicin and dexamethasone. J Clin Oncol 2010;28:661–662.
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