PROGRESSIVE OUTER RETINAL NECROSIS COMPLICATED BY COMBINED CENTRAL RETINAL VEIN AND CENTRAL RETINAL ARTERY OCCLUSIONS Phuong T. Tran, BS, Robert W. Crow, MD, Preston H. Blomquist, MD, Yu-Guang He, MD
Purpose: To describe an uncommon presentation and course of progressive outer retinal necrosis. Methods: A 36-year-old man presented with unilateral optic disk edema with enhancement of the optic nerve sheath shown by magnetic resonance imaging. Intravenous methylprednisolone treatment was initiated. Results: Two days later, he developed multiple discrete areas of outer retinal opacification with areas of confluence in the periphery of the retina. Results of laboratory testing for antibody to human immunodeficiency virus were positive. Therapy for progressive outer retinal necrosis was initiated, and the patient developed combined central retinal vein and central retinal artery occlusions 3 days later. Conclusions: Although usually characterized by a lack of vascular inflammation, progressive outer retinal necrosis may lead to vascular occlusions. RETINAL CASES & BRIEF REPORTS 1:138 –140, 2007
From the Department of Ophthalmology, University of Texas Southwestern Medical Center, Dallas.
(NLP) vision and optic neuritis in one eye. He progressed to develop progressive outer retinal necrosis in both eyes and combined central retinal vein occlusion (CRVO) and central retinal artery occlusion (CRAO) in his left eye.
P
rogressive outer retinal necrosis is a necrotizing herpetic retinopathy seen in patients with acquired immunodeficiency syndrome (AIDS) or other immunocompromised states.1 In contrast to acute retinal necrosis (ARN), which is characterized by an occlusive vasculopathy, patients with progressive outer retinal necrosis have minimal intraocular inflammation, and only about one-fifth have retinal vasculopathy. We report the case of a patient with undiagnosed AIDS who initially presented with no light perception
Case Report A 36-year-old man presented with sudden loss of vision in the right eye associated with pain on eye movement for 3 days. The past medical history was unremarkable. Review of systems revealed a generalized weakness for the past 2 to 3 weeks. On examination, visual acuity was NLP in the right eye and 20/20 in the left. A 4⫹ afferent pupillary defect was present in the right eye, and severe disk edema without retinal lesions was found on ophthalmoscopic examination of the right eye. Examination of the left eye was unremarkable, and neither eye had anterior segment or vitreous inflammation. Magnetic resonance imaging revealed enhancement of right optic nerve sheath to level of the orbital apex consistent with optic neuritis. The patient was started on 1 g daily of intravenous methylprednisolone. Two days later the patient developed multiple discrete areas of outer retinal opacification with areas of confluence in the periphery of his right eye (Figures 1 and 2).
Supported in part by an unrestricted research grant from Research to Prevent Blindness, Inc., New York, New York. The authors have no proprietary or financial interest in the material discussed in this article. Reprint requests: Preston H. Blomquist, MD, Department of Ophthalmology, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390-9057; e-mail: [email protected]
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Fig. 1. Color fundus photograph of right eye at time of diagnosis of progressive outer retinal necrosis. Note the disk edema with hemorrhages on disk (arrow) and multifocal outer retinal white lesions (arrowhead) sparing the macula.
Fig. 3. Color fundus photograph of right eye at time of development of central retinal artery occlusion/central retinal vein occlusion. In addition to the outer retinal lesions there are widespread retinal hemorrhages and ischemia with arterial vascular occlusions.
Laboratory testing was positive for HIV antibody, and the CD4 cell count was 32 ⫻ 106/L. Testing for syphilis, tuberculosis, and necrotizing vasculitis was negative. Methylprednisolone was discontinued, and intravenous ganciclovir (5 mg/kg) was initiated twice daily. Highly active antiretroviral therapy (HAART) using lamivudine/zidovudine and lopinavir/ritonavir combination therapy was also begun. Three days later, the patient developed retinal hemorrhages, venous engorgement, poor filling of arterial vessels, and diffuse retinal ischemia consistent with combined CRVO and CRAO (Figures 3 and 4). Visual acuity remained NLP in the right eye. Three weeks later the left eye developed progressive outer retinal necrosis but without vascular occlusions. Prophylactic peripheral laser retinopexy was performed in the left eye, and his visual acuity in that eye remains 20/20.
Progressive outer retinal necrosis is generally seen in immunocompromised individuals and is most often
caused by varicella zoster virus.1 Rarely the disease may present with optic nerve involvement.2 In Engstrom and coworkers’ series of 38 HIV-positive patients with progressive outer retinal necrosis, 17% had optic nerve involvement at the time of diagnosis.1 Our patient presented with unilateral optic disk swelling, but did not develop the retinal lesions characteristic of progressive outer retinal necrosis until after treatment with systemic methylprednisolone. Nakamoto et al reported two immunocompromised patients presenting with isolated optic neuropathy whose examination and visual acuity worsened after systemic corticosteroid treatment and developed retinal findings of progressive outer retinal necrosis.2 Benz et al described two immunocompetent patients who developed progressive outer retinal necrosis after corticosteroid
Fig. 2. Color fundus photograph of right eye at time of diagnosis of progressive outer retinal necrosis. Note the confluence of the outer retinal white lesions in the nasal periphery of the fundus.
Fig. 4. Color fundus photograph of right eye at time of development of central retinal artery occlusion/central retinal vein occlusion. Nasal retina is shown with extensive hemorrhages and retinal opacification.
Discussion
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treatment for optic neuropathy,3 but it is unknown how initial treatment with corticosteroids affects both the course of the disease and the final outcome. Our patient presented with NLP vision in the affected eye, and the fellow eye has retained 20/20 visual acuity. Two days after the appearance of the typical multifocal lesions of deep retinal opacification in the periphery with areas of confluence in his right eye and the beginning of treatment for progressive outer retinal necrosis, our patient developed a combined CRVO and CRAO. This may represent the first case reported to demonstrate combined central arterial and venous retinal occlusions with progressive outer retinal necrosis, a disease usually characterized by a lack of vascular inflammation. Engstrom and colleagues noted that only 21% of eyes with progressive outer retinal necrosis had vascular involvement, of which 54% had vascular sheathing and 46% vascular occlusion.1 Optic neuritis has been reported with secondary retinal venous stasis, but visual outcomes paralleled that of optic neuritis alone.4 A patient with HIV infection and no other risk factors for hypercoagulability, increased blood viscosity, or vasculitis was reported by Wen et al to develop bilateral CRVO with artery occlusions.5 The authors suggested that HIV infection may have several effects on retinal vasculature that predispose to occlusion. In addition to direct endothelial damage by the virus itself, HIV infection leads to elevation of many cytokines including tumor necrosis factor alpha, which has been shown in vitro to indirectly increase
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thrombin formation by decreasing fibrinolytic potential.5 The cause for our patient’s combined CRVO and CRAO is unclear. Patients who receive empirical systemic corticosteroid treatment for acute, unexplained vision loss should receive a thorough examination of the periphery of the retina before management with corticosteroids is initiated and be periodically reassessed with a dilated fundus examination.3 Patients should be assessed for risk factors for immunodeficiency, and testing ordered as appropriate. For HIV-positive patients it is unknown how HAART therapy affects the course of progressive outer retinal necrosis. References 1.
2.
3.
4.
5.
Engstrom RE Jr, Holland GN, Margolis TP, et al. The progressive outer retinal necrosis syndrome: a variant of necrotizing herpetic retinopathy in patients with AIDS. Ophthalmology 1994;101:1488–1502. Nakamoto BK, Dorotheo EU, Biousse V, et al. Progressive outer retinal necrosis presenting with isolated optic neuropathy. Neurology 2004;63:2423–2425. Benz MS, Glaser MS, Davis JL. Progressive outer retinal necrosis in immunocompetent patients treated initially for optic neuropathy with systemic corticosteroids. Am J Ophthalmol 2003;135:551–553. Duker JS, Sergott RC, Savino PJ, Bosley TM. Optic neuritis with secondary retinal venous stasis. Ophthalmology 1989;96: 475–480. Wen F, Chen X, Liao R. Bilateral central retinal vein occlusions in a Chinese patient with HIV-infection. Int Ophthalmol 2001;24:173–175.
Purpose: To describe an uncommon presentation and course of progressive outer retinal necrosis. Methods: A 36-year-old man presented with unilateral optic disk edema with enhancement of the optic nerve sheath shown by magnetic resonance imaging. Intravenous methylprednisolone treatment was initiated. Results: Two days later, he developed multiple discrete areas of outer retinal opacification with areas of confluence in the periphery of the retina. Results of laboratory testing for antibody to human immunodeficiency virus were positive. Therapy for progressive outer retinal necrosis was initiated, and the patient developed combined central retinal vein and central retinal artery occlusions 3 days later. Conclusions: Although usually characterized by a lack of vascular inflammation, progressive outer retinal necrosis may lead to vascular occlusions. RETINAL CASES & BRIEF REPORTS 1:138 –140, 2007
From the Department of Ophthalmology, University of Texas Southwestern Medical Center, Dallas.
(NLP) vision and optic neuritis in one eye. He progressed to develop progressive outer retinal necrosis in both eyes and combined central retinal vein occlusion (CRVO) and central retinal artery occlusion (CRAO) in his left eye.
P
rogressive outer retinal necrosis is a necrotizing herpetic retinopathy seen in patients with acquired immunodeficiency syndrome (AIDS) or other immunocompromised states.1 In contrast to acute retinal necrosis (ARN), which is characterized by an occlusive vasculopathy, patients with progressive outer retinal necrosis have minimal intraocular inflammation, and only about one-fifth have retinal vasculopathy. We report the case of a patient with undiagnosed AIDS who initially presented with no light perception
Case Report A 36-year-old man presented with sudden loss of vision in the right eye associated with pain on eye movement for 3 days. The past medical history was unremarkable. Review of systems revealed a generalized weakness for the past 2 to 3 weeks. On examination, visual acuity was NLP in the right eye and 20/20 in the left. A 4⫹ afferent pupillary defect was present in the right eye, and severe disk edema without retinal lesions was found on ophthalmoscopic examination of the right eye. Examination of the left eye was unremarkable, and neither eye had anterior segment or vitreous inflammation. Magnetic resonance imaging revealed enhancement of right optic nerve sheath to level of the orbital apex consistent with optic neuritis. The patient was started on 1 g daily of intravenous methylprednisolone. Two days later the patient developed multiple discrete areas of outer retinal opacification with areas of confluence in the periphery of his right eye (Figures 1 and 2).
Supported in part by an unrestricted research grant from Research to Prevent Blindness, Inc., New York, New York. The authors have no proprietary or financial interest in the material discussed in this article. Reprint requests: Preston H. Blomquist, MD, Department of Ophthalmology, University of Texas Southwestern Medical Center, 5323 Harry Hines Blvd., Dallas, TX 75390-9057; e-mail: [email protected]
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Fig. 1. Color fundus photograph of right eye at time of diagnosis of progressive outer retinal necrosis. Note the disk edema with hemorrhages on disk (arrow) and multifocal outer retinal white lesions (arrowhead) sparing the macula.
Fig. 3. Color fundus photograph of right eye at time of development of central retinal artery occlusion/central retinal vein occlusion. In addition to the outer retinal lesions there are widespread retinal hemorrhages and ischemia with arterial vascular occlusions.
Laboratory testing was positive for HIV antibody, and the CD4 cell count was 32 ⫻ 106/L. Testing for syphilis, tuberculosis, and necrotizing vasculitis was negative. Methylprednisolone was discontinued, and intravenous ganciclovir (5 mg/kg) was initiated twice daily. Highly active antiretroviral therapy (HAART) using lamivudine/zidovudine and lopinavir/ritonavir combination therapy was also begun. Three days later, the patient developed retinal hemorrhages, venous engorgement, poor filling of arterial vessels, and diffuse retinal ischemia consistent with combined CRVO and CRAO (Figures 3 and 4). Visual acuity remained NLP in the right eye. Three weeks later the left eye developed progressive outer retinal necrosis but without vascular occlusions. Prophylactic peripheral laser retinopexy was performed in the left eye, and his visual acuity in that eye remains 20/20.
Progressive outer retinal necrosis is generally seen in immunocompromised individuals and is most often
caused by varicella zoster virus.1 Rarely the disease may present with optic nerve involvement.2 In Engstrom and coworkers’ series of 38 HIV-positive patients with progressive outer retinal necrosis, 17% had optic nerve involvement at the time of diagnosis.1 Our patient presented with unilateral optic disk swelling, but did not develop the retinal lesions characteristic of progressive outer retinal necrosis until after treatment with systemic methylprednisolone. Nakamoto et al reported two immunocompromised patients presenting with isolated optic neuropathy whose examination and visual acuity worsened after systemic corticosteroid treatment and developed retinal findings of progressive outer retinal necrosis.2 Benz et al described two immunocompetent patients who developed progressive outer retinal necrosis after corticosteroid
Fig. 2. Color fundus photograph of right eye at time of diagnosis of progressive outer retinal necrosis. Note the confluence of the outer retinal white lesions in the nasal periphery of the fundus.
Fig. 4. Color fundus photograph of right eye at time of development of central retinal artery occlusion/central retinal vein occlusion. Nasal retina is shown with extensive hemorrhages and retinal opacification.
Discussion
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treatment for optic neuropathy,3 but it is unknown how initial treatment with corticosteroids affects both the course of the disease and the final outcome. Our patient presented with NLP vision in the affected eye, and the fellow eye has retained 20/20 visual acuity. Two days after the appearance of the typical multifocal lesions of deep retinal opacification in the periphery with areas of confluence in his right eye and the beginning of treatment for progressive outer retinal necrosis, our patient developed a combined CRVO and CRAO. This may represent the first case reported to demonstrate combined central arterial and venous retinal occlusions with progressive outer retinal necrosis, a disease usually characterized by a lack of vascular inflammation. Engstrom and colleagues noted that only 21% of eyes with progressive outer retinal necrosis had vascular involvement, of which 54% had vascular sheathing and 46% vascular occlusion.1 Optic neuritis has been reported with secondary retinal venous stasis, but visual outcomes paralleled that of optic neuritis alone.4 A patient with HIV infection and no other risk factors for hypercoagulability, increased blood viscosity, or vasculitis was reported by Wen et al to develop bilateral CRVO with artery occlusions.5 The authors suggested that HIV infection may have several effects on retinal vasculature that predispose to occlusion. In addition to direct endothelial damage by the virus itself, HIV infection leads to elevation of many cytokines including tumor necrosis factor alpha, which has been shown in vitro to indirectly increase
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2007
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VOLUME 1
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thrombin formation by decreasing fibrinolytic potential.5 The cause for our patient’s combined CRVO and CRAO is unclear. Patients who receive empirical systemic corticosteroid treatment for acute, unexplained vision loss should receive a thorough examination of the periphery of the retina before management with corticosteroids is initiated and be periodically reassessed with a dilated fundus examination.3 Patients should be assessed for risk factors for immunodeficiency, and testing ordered as appropriate. For HIV-positive patients it is unknown how HAART therapy affects the course of progressive outer retinal necrosis. References 1.
2.
3.
4.
5.
Engstrom RE Jr, Holland GN, Margolis TP, et al. The progressive outer retinal necrosis syndrome: a variant of necrotizing herpetic retinopathy in patients with AIDS. Ophthalmology 1994;101:1488–1502. Nakamoto BK, Dorotheo EU, Biousse V, et al. Progressive outer retinal necrosis presenting with isolated optic neuropathy. Neurology 2004;63:2423–2425. Benz MS, Glaser MS, Davis JL. Progressive outer retinal necrosis in immunocompetent patients treated initially for optic neuropathy with systemic corticosteroids. Am J Ophthalmol 2003;135:551–553. Duker JS, Sergott RC, Savino PJ, Bosley TM. Optic neuritis with secondary retinal venous stasis. Ophthalmology 1989;96: 475–480. Wen F, Chen X, Liao R. Bilateral central retinal vein occlusions in a Chinese patient with HIV-infection. Int Ophthalmol 2001;24:173–175.
