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Letters to the Editor 6. Acera A, Rocha G, Vecino E, Lema I, Duran JA. Inflammatory markers in the tears of patients with ocular surface disease. Ophthalmic Res 2008; 40: 315–21. 7. Schafers M, Sommer C. Anticytokine therapy in neuropathic pain management. Expert Rev Neurother 2007; 7: 1613–27.
Subacute visual loss as the sole presenting feature in progressive multifocal leukoencephalopathy We report on a rare case of progressive multifocal leukoencephalopathy (PML), with only bilateral visual loss as the initial presenting symptom. PML usually causes a myriad of neurologic deficits, but our case demonstrates that initial presentation may exclusively consist of ocular signs. Ophthalmologists should thus be aware of this entity in patients with unexplained visual loss and impaired immunity, especially in light of the increasing use of biologicals. A 65-year-old male was referred to our clinic because of a 3-month history of progressive, painless visual loss. He had a 16-year history of B-cell type chronic lymphatic
599 leukaemia (B-CLL), for which he had received intermittent chlorambucil therapy until 3 years ago. Chemoimmunotherapy (fludarabine, cyclophosphamide and rituximab) was then given with complete remission after 6 cycles. Subsequently, high-dosed rituximab was used in a clinical trial setting in order to prolong the remission period. Best-corrected visual acuity at presentation was 6/10 on the right eye and 7/10 on the left. Anterior and posterior segments were unremarkable, as were the pupillary reactions. Ocular movements were full. Visual field examination showed bilateral defects (Fig. 1a). Due to the unexplained visual features, patient underwent cerebral magnetic resonance imaging (MRI). This revealed bilateral subcortical white matter lesions, predominantly in the occipital lobes (Fig. 2). Further diagnostic work-up included a neurologic examination – that showed no abnormalities – and lumbar puncture. He was also human immunodeficiency virus negative. Lumbar puncture demonstrated presence of John Cunningham (JC) virus DNA by polymerase chain reaction. Based upon clinical, radiologic and laboratory findings, diagnosis of PML was made. Ophthalmic examination 2 months later showed vision of hand motions on both eyes (Fig. 1b). Despite attempted treatment with cidofovir, mirtazapine and intravenous immunoglobulins, the patient’s condition rapidly deteriorated with right-sided hemiplegia and cognitive impairment. He died three months after diagnosis.
Figure 1. (a) Visual field testing (Octopus 123, Central 30°, HaagStreit, Germany) at presentation shows central and inferior scotoma in both eyes. (b) Repeat visual field examination 2 months later reveals near total loss of visual fields.
Conflict of interest: None. Funding sources: None. © 2015 Royal Australian and New Zealand College of Ophthalmologists
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Letters to the Editor Figure 2. Magnetic resonance imaging (MRI) shows T1-weighted hypointensities (a), T2-weighted (b) and fluid-attenuated inversion recovery (FLAIR) (c) hyperintensities, predominantly located in the occipital lobes. These white matter lesions in the subcortical and deep areas are present in the absence of a focal mass, mass effect or contrast enhancement.
PML is a rare demyelinating disease of the central nervous system (CNS) caused by JC virus, a human DNA polyomavirus.1 About 90% of adults are seropositive for this ubiquitous virus.2 However, PML affects almost exclusively patients with impaired cell-mediated immunity.3 In the last decades, PML has gained importance due to acquired immune deficiency syndrome (AIDS) and the increased use of immunosuppressive drugs, especially monoclonal antibodies.4 B-CLL itself predisposes to PML in absence of a specific immunosuppressive agent.5 The underlying conditions in this patient were his background of long B-CLL history in synopsis with multiple immunosuppressive treatments, most notably fludarabine and rituximab, which had caused impaired function and very low counts of B and T cells.5,6 Absolute confirmation of PML requires brain biopsy with demonstration of JC viral particles in the nuclei of oligodendrocytes.2 However, authorities regard appropriate clinical and radiologic features coupled with demonstration of JC viral DNA sufficient for PML diagnosis.5 Overall, apart from combined antiretroviral therapy in AIDS patients, treatment options are scarce and prognosis is extremely poor.2,5 PML manifests as focal neurologic deficits, rapidly progressing over weeks to months.1 Some of the common clinical features include motor weakness, cognitive deficits, dysphasia and incoordination.1,5 Vision loss is seen in up to 50% of PML cases and ranges from very mild to cortical blindness, depending on the extent of occipital lobe involvement.2 Visual symptoms without associated neurologic signs are infrequent.1 This patient initially presented with a 3-month history of moderate bilateral vision loss as the sole clinical manifestation of bilateral occipital lobe demyelination. It took several weeks for other neurological symptoms to appear, even though the initial MRI showed scattered white matter lesions outside the occipital lobes. Unexplained visual loss in immunosuppressed patients should thus call attention to CNS complications and necessitates neuroimaging, even in the absence of other focal neurologic deficits.
Elke O Kreps MD,1 Achiel Van Hoof MD2 and Rudolf Reyniers MD3 1 Department of Ophthalmology, Ghent University Hospital, University of Ghent, Ghent, Departments of 2 Haematology and 3Ophthalmology, General Hospital St Jan Bruges, Bruges, Belgium
Received 20 January 2015; accepted 28 January 2015.
REFERENCES 1. Jeyaraman VA, Sudharshan S, Selvakumar A et al. Isolated cortical blindness without simultaneous neurological involvement in progressive multifocal leukoencephalopathy in a patient with human immune deficiency virus infection. J Ophthalmic Inflamm Infect 2013; 3: 3. 2. Diller R, Thompson K. Visual loss secondary to acquired immunodeficiency virus-related progressive multifocal leukoencephalopathy demonstrating clinical improvement with highly active antiretroviral therapy. Optometry 2007; 78: 63–70. 3. Kiewe P, Seyfert S, Körper S, Rieger K, Thiel E, Knauf W. Progressive multifocal leukoencephalopathy with detection of JC virus in a patient with chronic lymphocytic leukemia parallel to onset of fludarabine therapy. Leuk Lymphoma 2003; 44: 1815–8. 4. Herold TR, Jaki V, Graser A, Eibl-Lindner K. Hemianopia and visual loss due to progressive multifocal leukoencephalopathy in natalizumab-treated multiple sclerosis. Clin Ophthalmol 2012; 6: 1131–3. 5. Berger JR, Aksamit AJ, Clifford DB et al. PML diagnostic criteria. Consensus statement from the AAN Neuroinfectious Disease Section. Neurology 2013; 80: 1430–8. 6. Chahin S, Berger JR. A risk classification for immunosuppressive treatment-associated progressive multifocal leukoencephalopathy. J Neurovirol 2014; doi: 10.1007/ s13365-014-0303-1. [Epub ahead of print].
Biometric and refractive changes in a patient with persistent traumatic hypotony Chronic ocular hypotony may cause decreased vision, shallowing of the anterior chamber. When conservative medical treatment fails, a cyclodialysis cleft may be successfully managed with non-invasive argon laser photocoConflict of interest: None declared. Funding sources: None declared.
© 2015 Royal Australian and New Zealand College of Ophthalmologists
Letters to the Editor 6. Acera A, Rocha G, Vecino E, Lema I, Duran JA. Inflammatory markers in the tears of patients with ocular surface disease. Ophthalmic Res 2008; 40: 315–21. 7. Schafers M, Sommer C. Anticytokine therapy in neuropathic pain management. Expert Rev Neurother 2007; 7: 1613–27.
Subacute visual loss as the sole presenting feature in progressive multifocal leukoencephalopathy We report on a rare case of progressive multifocal leukoencephalopathy (PML), with only bilateral visual loss as the initial presenting symptom. PML usually causes a myriad of neurologic deficits, but our case demonstrates that initial presentation may exclusively consist of ocular signs. Ophthalmologists should thus be aware of this entity in patients with unexplained visual loss and impaired immunity, especially in light of the increasing use of biologicals. A 65-year-old male was referred to our clinic because of a 3-month history of progressive, painless visual loss. He had a 16-year history of B-cell type chronic lymphatic
599 leukaemia (B-CLL), for which he had received intermittent chlorambucil therapy until 3 years ago. Chemoimmunotherapy (fludarabine, cyclophosphamide and rituximab) was then given with complete remission after 6 cycles. Subsequently, high-dosed rituximab was used in a clinical trial setting in order to prolong the remission period. Best-corrected visual acuity at presentation was 6/10 on the right eye and 7/10 on the left. Anterior and posterior segments were unremarkable, as were the pupillary reactions. Ocular movements were full. Visual field examination showed bilateral defects (Fig. 1a). Due to the unexplained visual features, patient underwent cerebral magnetic resonance imaging (MRI). This revealed bilateral subcortical white matter lesions, predominantly in the occipital lobes (Fig. 2). Further diagnostic work-up included a neurologic examination – that showed no abnormalities – and lumbar puncture. He was also human immunodeficiency virus negative. Lumbar puncture demonstrated presence of John Cunningham (JC) virus DNA by polymerase chain reaction. Based upon clinical, radiologic and laboratory findings, diagnosis of PML was made. Ophthalmic examination 2 months later showed vision of hand motions on both eyes (Fig. 1b). Despite attempted treatment with cidofovir, mirtazapine and intravenous immunoglobulins, the patient’s condition rapidly deteriorated with right-sided hemiplegia and cognitive impairment. He died three months after diagnosis.
Figure 1. (a) Visual field testing (Octopus 123, Central 30°, HaagStreit, Germany) at presentation shows central and inferior scotoma in both eyes. (b) Repeat visual field examination 2 months later reveals near total loss of visual fields.
Conflict of interest: None. Funding sources: None. © 2015 Royal Australian and New Zealand College of Ophthalmologists
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600
Letters to the Editor Figure 2. Magnetic resonance imaging (MRI) shows T1-weighted hypointensities (a), T2-weighted (b) and fluid-attenuated inversion recovery (FLAIR) (c) hyperintensities, predominantly located in the occipital lobes. These white matter lesions in the subcortical and deep areas are present in the absence of a focal mass, mass effect or contrast enhancement.
PML is a rare demyelinating disease of the central nervous system (CNS) caused by JC virus, a human DNA polyomavirus.1 About 90% of adults are seropositive for this ubiquitous virus.2 However, PML affects almost exclusively patients with impaired cell-mediated immunity.3 In the last decades, PML has gained importance due to acquired immune deficiency syndrome (AIDS) and the increased use of immunosuppressive drugs, especially monoclonal antibodies.4 B-CLL itself predisposes to PML in absence of a specific immunosuppressive agent.5 The underlying conditions in this patient were his background of long B-CLL history in synopsis with multiple immunosuppressive treatments, most notably fludarabine and rituximab, which had caused impaired function and very low counts of B and T cells.5,6 Absolute confirmation of PML requires brain biopsy with demonstration of JC viral particles in the nuclei of oligodendrocytes.2 However, authorities regard appropriate clinical and radiologic features coupled with demonstration of JC viral DNA sufficient for PML diagnosis.5 Overall, apart from combined antiretroviral therapy in AIDS patients, treatment options are scarce and prognosis is extremely poor.2,5 PML manifests as focal neurologic deficits, rapidly progressing over weeks to months.1 Some of the common clinical features include motor weakness, cognitive deficits, dysphasia and incoordination.1,5 Vision loss is seen in up to 50% of PML cases and ranges from very mild to cortical blindness, depending on the extent of occipital lobe involvement.2 Visual symptoms without associated neurologic signs are infrequent.1 This patient initially presented with a 3-month history of moderate bilateral vision loss as the sole clinical manifestation of bilateral occipital lobe demyelination. It took several weeks for other neurological symptoms to appear, even though the initial MRI showed scattered white matter lesions outside the occipital lobes. Unexplained visual loss in immunosuppressed patients should thus call attention to CNS complications and necessitates neuroimaging, even in the absence of other focal neurologic deficits.
Elke O Kreps MD,1 Achiel Van Hoof MD2 and Rudolf Reyniers MD3 1 Department of Ophthalmology, Ghent University Hospital, University of Ghent, Ghent, Departments of 2 Haematology and 3Ophthalmology, General Hospital St Jan Bruges, Bruges, Belgium
Received 20 January 2015; accepted 28 January 2015.
REFERENCES 1. Jeyaraman VA, Sudharshan S, Selvakumar A et al. Isolated cortical blindness without simultaneous neurological involvement in progressive multifocal leukoencephalopathy in a patient with human immune deficiency virus infection. J Ophthalmic Inflamm Infect 2013; 3: 3. 2. Diller R, Thompson K. Visual loss secondary to acquired immunodeficiency virus-related progressive multifocal leukoencephalopathy demonstrating clinical improvement with highly active antiretroviral therapy. Optometry 2007; 78: 63–70. 3. Kiewe P, Seyfert S, Körper S, Rieger K, Thiel E, Knauf W. Progressive multifocal leukoencephalopathy with detection of JC virus in a patient with chronic lymphocytic leukemia parallel to onset of fludarabine therapy. Leuk Lymphoma 2003; 44: 1815–8. 4. Herold TR, Jaki V, Graser A, Eibl-Lindner K. Hemianopia and visual loss due to progressive multifocal leukoencephalopathy in natalizumab-treated multiple sclerosis. Clin Ophthalmol 2012; 6: 1131–3. 5. Berger JR, Aksamit AJ, Clifford DB et al. PML diagnostic criteria. Consensus statement from the AAN Neuroinfectious Disease Section. Neurology 2013; 80: 1430–8. 6. Chahin S, Berger JR. A risk classification for immunosuppressive treatment-associated progressive multifocal leukoencephalopathy. J Neurovirol 2014; doi: 10.1007/ s13365-014-0303-1. [Epub ahead of print].
Biometric and refractive changes in a patient with persistent traumatic hypotony Chronic ocular hypotony may cause decreased vision, shallowing of the anterior chamber. When conservative medical treatment fails, a cyclodialysis cleft may be successfully managed with non-invasive argon laser photocoConflict of interest: None declared. Funding sources: None declared.
© 2015 Royal Australian and New Zealand College of Ophthalmologists
