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Treatment of Progressive Outer Retinal Necrosis With Sorivudine
2. Feiberg NT, Shields JA, Federman JL. Antibody to Toxocara canis in aqueous humor. Arch Ophthalmol 1981;99:1563-4. 3. Goldmann H, Witmer R. Antikörper im kammerwasser. Ophthalmologica 1954;127:323-30. 4. Gillespie SH, Dinning WJ, Voller A, Crowcroft NS. T h e spectrum of ocular toxocariasis. Eye 1993;7:415-8. 5. el Matri L, Ghorbal M, Ayadi A, Ben Naceur B, Triki MF. Localisation oculaire a toxocara canis apparemment bilatérale. J Fr Ophtalmol 1990;13:303-8.
Treatment of Progressive Outer Retinal Necrosis With Sorivudine Michael K. Pinnolis, M.D., Donald Foxworthy, M.D., and Barbara Kemp, R.N. PURPOSE/METHODS: We examined a patient with progressive outer retinal necrosis, which is presumably caused by the varicella-zoster virus in patients with the acquired immunodeficiency syn drome. RESULTS/CONCLUSIONS: The patient was suc cessfully treated with a combination of intravitreal ganciclovir and oral sorivudine. Treatment for progressive outer retinal necrosis has been disap pointing; both acyclovir and ganciclovir have had only limited success. Sorivudine, a new antiviral medication with activity against varicella-zoster virus, may represent an effective alternative treat ment for retinal necrosis.
P
ROGRESSIVE OUTER RETINAL NECROSIS, PRESUMably caused by the varicella-zoster virus, has been well described in patients with the acquired immuno deficiency syndrome (AIDS). 1 ' 3 Although there are isolated instances of successful treatment of acute retinal necrosis with intravenous acyclovir or gan ciclovir, most reports suggest a dismal prognosis.1'5 Affected patients progress rapidly to total visual loss within a few weeks of the onset of the retinitis. We successfully treated a patient with acute retinal necro sis by using a combination of intravitreal ganciclovir and a new experimental antiviral medication BVVisual Services Department (M.K.P.), Internal Medicine Department (D.F.), and Oncology Department (B.K.), Harvard Community Health Plan; and Retina Service, Massachusetts Eye and Ear Infirmary (M.K.P.). Inquiries to Michael Pinnolis, M.D., Retina Service, Massachusetts Eye and Ear Infirmary, 243 Charles St., Boston, MA 02114; fax: (617) 573-3698.
516
araU (sorivudine is equivalent to BV-araU and is available in the United States from Bristol-Myers Squibb, Wallingford, Connecticut). A 48-year-old man with AIDS had complaints of decreasing vision in his left eye associated with a moderate headache in July 1993. Visual acuity was R.E.: 20/20 and LE.: hand motion. There was a left afferent pupillary defect. There was a marked anterior chamber reaction as well as moderate vitreous cells in the left eye. Results of ophthalmoscopic examination of the right eye were normal. However, ophthalmo scopic examination of the left eye showed extensive retinal necrosis in all quadrants extending from the ora serrata posteriorly into the macula. The retinitis involved the outer retina and the pattern was consis tent with varicella-zoster retinitis. Initially, high-dose intravenous acyclovir, 10 mg/kg of body weight three times per day, was given. Two weeks later an area of retinal whitening was noted in the peripheral, nasal retina of the right eye similar in appearance to that in the left eye. A n erythematous, vesicular rash also had developed on the left side of his back consistent with a diagnosis of shingles. Intravenous foscarnet, 60 mg/kg of body weight three times per day, was added to the regimen. The infection, however, continued to progress in both eyes. Intravitreal injections of gan ciclovir, 200 μg two times per week, were initiated. Despite this aggressive therapy, the lesions continued to progress until they involved the entire retina anterior to the equator in the right eye. At this point, all intravenous medication was discontinued and sorivudine, 40 mg orally every day, was begun along with the ganciclovir injections. Within two weeks the retinitis began to improve and rapidly became inactive Over the next few months, two unsuccessful attempts were made to discontinue medication, but the lesions recurred, and treatment was restarted. After five months of therapy, all medication was successfully terminated. The patient has had no recurrence of retinal inflammatory disease for one year. Sorivudine is an arabinofuranosyuracil analog. It is phosphorylated by viral and cellular thymidine kinase to a triphosphate form, which inhibits varicella-zoster virus DNA polymerase. Unlike acyclovir, sorivudine does not appear to be incorporated into viral DNA. Its ability to inhibit varicella-zoster virus in vitro is over 1,000 times greater than that of acyclovir.
AMERICAN JOURNAL OF OPHTHALMOLOGY
APRIL
1995
Sorivudine is in Phase III trials and is available from Bristol-Myers Squibb on a compassionate use basis. Because we were unwilling to treat this one-eyed patient solely with an experimental drug, it is unclear whether success was primarily attributable to ganciclovir or to sorivudine. However, progression of the retinitis occurred while the patient was receiving ganciclovir injections, suggesting some beneficial therapeutic role for sorivudine. The results in this case demonstrate that therapy for varicella-zoster retinitis must be aggressive and prolonged, and that sorivudine is a new treatment modality that merits further study. REFERENCES 1. Johnston WH, Holland GN, Engstrom RE Jr, Rimmer S. Recurrence of presumed varicella-zoster virus retinopathy in patients with acquired immunodeficiency syndrome. Am J Ophthalmol 1993;116:42-50. 2. Forster DJ, Dugel PU, Frangieh GT, Liggett PE, Rao NA. Rapidly progressive outer retinal necrosis in the acquired immunodeficiency syndrome. Am J Ophthalmol 1990; 110:341-8. 3. Margolis TP, Lowder CY, Holland GN, Spaide RF, Logan AG, Weissman SS, et al. Varicella-zoster virus retinitis in patients with the acquired immunodeficiency syndrome. Am J Ophthalmol 1991;112:119-31. 4. Morley MG, Düker JS, Zacks C. Successful treatment of rapidly progressive outer retinal necrosis in the acquired immunodeficiency syndrome. Am J Ophthalmol 1994; 117:264-5. 5. Laby DM, Nasrallah FP, Butrus SI, Whitmore PV. Treatment of outer retinal necrosis in AIDS patients. Graefes Arch Clin Exp Ophthalmol 1993;231:271-3.
Choroidal and Retinal Detachment in Antineutrophil Cytoplasmic Antibody-Positive Scleritis Dennis M. Marcus, M.D., Albert R. Frederick, Jr., M.D., Michael B. Raizman, M.D., and John W. Shore, M.D. PURPOSE/METHODS: A 72-year-old woman with antineutrophil cytoplasmic antibody-positive vasculitis had a combined detachment of the choroid and retina. This unique initial manifestation was also associated with systemic and orbital manifes tations, including brow ptosis, dacryoadenitis, and pneumonitis. VOL.119,
No. 4
RESULTS/CONCLUSIONS: This patient under went vitrectomy for removal of a dense vitreitis and responded well to systemic cyclophosphamide. This case demonstrates that antineutrophil cyto plasmic antibody testing is useful for the diagnosis and treatment of Wegener's granulomatosis and microscopic polyarteritis-associated scleritis. The distinction between these two entities is often difficult to make.
E
XUDATIVE DETACHMENT OF THE CHOROID AND RETI-
na secondary to scleritis has been infrequently described as a manifestation of Wegener's granuloma tosis1 or microscopic polyarteritis.2 Earlier reports usually demonstrated this manifestation histopathologically after globe perforation. Antineutrophil cyto plasmic antibody testing is useful for diagnosis and treatment of Wegener's granulomatosis and micro scopic polyarteritis-associated scleritis.3 We examined a patient with scleritis-induced combined detach ments and vitreitis caused by antineutrophil cytoplas mic antibody-positive systemic vasculitis. A 72-year-old woman had had eight months of intermittent pain and five months of decreased visual acuity in the right eye. Ocular history was contributo ry for uncomplicated cataract extraction in the right eye. Ocular examination disclosed visual acuity of R.E.: counting fingers at 2 ft and L.E.: 20/30. Slitlamp examination of the right eye disclosed anterior nodular scleritis, anterior chamber flare and cell, and a well-positioned posterior chamber intraocular lens. The vitreous was markedly opacified with a thick, congealed material that obscured fundus examina tion. Orbital magnetic resonance imaging showed contrast enhancement of the sciera with choroidalretinal detachment. The right lacrimal gland was enlarged and enhanced with contrast (Fig. 1). Chest x-ray showed pneumonitis in the right upper lobe. Laboratory studies demonstrated positive indirect immunofluorescence testing for antineutrophil cyto plasmic antibody with a perinuclear staining pattern. Antibodies to myeloperoxidase were positive and
Department of Ophthalmology, Medical College of Georgia (D.M.M.); Ophthalmic Consultants of Boston (A.R.F., J.W.S.); and New En gland Eye Center, Tufts University School of Medicine (M.B.R.). Inquiries to Dennis M. Marcus, M.D., Department of Ophthalmolo gy, Medical College of Georgia, Augusta, GA 30912; fax: (706) 7214012.
BRIEF REPORTS
517
Treatment of Progressive Outer Retinal Necrosis With Sorivudine Michael K. Pinnolis, M.D., Donald Foxworthy, M.D., and Barbara Kemp, R.N. PURPOSE/METHODS: We examined a patient with progressive outer retinal necrosis, which is presumably caused by the varicella-zoster virus in patients with the acquired immunodeficiency syn drome. RESULTS/CONCLUSIONS: The patient was suc cessfully treated with a combination of intravitreal ganciclovir and oral sorivudine. Treatment for progressive outer retinal necrosis has been disap pointing; both acyclovir and ganciclovir have had only limited success. Sorivudine, a new antiviral medication with activity against varicella-zoster virus, may represent an effective alternative treat ment for retinal necrosis.
P
ROGRESSIVE OUTER RETINAL NECROSIS, PRESUMably caused by the varicella-zoster virus, has been well described in patients with the acquired immuno deficiency syndrome (AIDS). 1 ' 3 Although there are isolated instances of successful treatment of acute retinal necrosis with intravenous acyclovir or gan ciclovir, most reports suggest a dismal prognosis.1'5 Affected patients progress rapidly to total visual loss within a few weeks of the onset of the retinitis. We successfully treated a patient with acute retinal necro sis by using a combination of intravitreal ganciclovir and a new experimental antiviral medication BVVisual Services Department (M.K.P.), Internal Medicine Department (D.F.), and Oncology Department (B.K.), Harvard Community Health Plan; and Retina Service, Massachusetts Eye and Ear Infirmary (M.K.P.). Inquiries to Michael Pinnolis, M.D., Retina Service, Massachusetts Eye and Ear Infirmary, 243 Charles St., Boston, MA 02114; fax: (617) 573-3698.
516
araU (sorivudine is equivalent to BV-araU and is available in the United States from Bristol-Myers Squibb, Wallingford, Connecticut). A 48-year-old man with AIDS had complaints of decreasing vision in his left eye associated with a moderate headache in July 1993. Visual acuity was R.E.: 20/20 and LE.: hand motion. There was a left afferent pupillary defect. There was a marked anterior chamber reaction as well as moderate vitreous cells in the left eye. Results of ophthalmoscopic examination of the right eye were normal. However, ophthalmo scopic examination of the left eye showed extensive retinal necrosis in all quadrants extending from the ora serrata posteriorly into the macula. The retinitis involved the outer retina and the pattern was consis tent with varicella-zoster retinitis. Initially, high-dose intravenous acyclovir, 10 mg/kg of body weight three times per day, was given. Two weeks later an area of retinal whitening was noted in the peripheral, nasal retina of the right eye similar in appearance to that in the left eye. A n erythematous, vesicular rash also had developed on the left side of his back consistent with a diagnosis of shingles. Intravenous foscarnet, 60 mg/kg of body weight three times per day, was added to the regimen. The infection, however, continued to progress in both eyes. Intravitreal injections of gan ciclovir, 200 μg two times per week, were initiated. Despite this aggressive therapy, the lesions continued to progress until they involved the entire retina anterior to the equator in the right eye. At this point, all intravenous medication was discontinued and sorivudine, 40 mg orally every day, was begun along with the ganciclovir injections. Within two weeks the retinitis began to improve and rapidly became inactive Over the next few months, two unsuccessful attempts were made to discontinue medication, but the lesions recurred, and treatment was restarted. After five months of therapy, all medication was successfully terminated. The patient has had no recurrence of retinal inflammatory disease for one year. Sorivudine is an arabinofuranosyuracil analog. It is phosphorylated by viral and cellular thymidine kinase to a triphosphate form, which inhibits varicella-zoster virus DNA polymerase. Unlike acyclovir, sorivudine does not appear to be incorporated into viral DNA. Its ability to inhibit varicella-zoster virus in vitro is over 1,000 times greater than that of acyclovir.
AMERICAN JOURNAL OF OPHTHALMOLOGY
APRIL
1995
Sorivudine is in Phase III trials and is available from Bristol-Myers Squibb on a compassionate use basis. Because we were unwilling to treat this one-eyed patient solely with an experimental drug, it is unclear whether success was primarily attributable to ganciclovir or to sorivudine. However, progression of the retinitis occurred while the patient was receiving ganciclovir injections, suggesting some beneficial therapeutic role for sorivudine. The results in this case demonstrate that therapy for varicella-zoster retinitis must be aggressive and prolonged, and that sorivudine is a new treatment modality that merits further study. REFERENCES 1. Johnston WH, Holland GN, Engstrom RE Jr, Rimmer S. Recurrence of presumed varicella-zoster virus retinopathy in patients with acquired immunodeficiency syndrome. Am J Ophthalmol 1993;116:42-50. 2. Forster DJ, Dugel PU, Frangieh GT, Liggett PE, Rao NA. Rapidly progressive outer retinal necrosis in the acquired immunodeficiency syndrome. Am J Ophthalmol 1990; 110:341-8. 3. Margolis TP, Lowder CY, Holland GN, Spaide RF, Logan AG, Weissman SS, et al. Varicella-zoster virus retinitis in patients with the acquired immunodeficiency syndrome. Am J Ophthalmol 1991;112:119-31. 4. Morley MG, Düker JS, Zacks C. Successful treatment of rapidly progressive outer retinal necrosis in the acquired immunodeficiency syndrome. Am J Ophthalmol 1994; 117:264-5. 5. Laby DM, Nasrallah FP, Butrus SI, Whitmore PV. Treatment of outer retinal necrosis in AIDS patients. Graefes Arch Clin Exp Ophthalmol 1993;231:271-3.
Choroidal and Retinal Detachment in Antineutrophil Cytoplasmic Antibody-Positive Scleritis Dennis M. Marcus, M.D., Albert R. Frederick, Jr., M.D., Michael B. Raizman, M.D., and John W. Shore, M.D. PURPOSE/METHODS: A 72-year-old woman with antineutrophil cytoplasmic antibody-positive vasculitis had a combined detachment of the choroid and retina. This unique initial manifestation was also associated with systemic and orbital manifes tations, including brow ptosis, dacryoadenitis, and pneumonitis. VOL.119,
No. 4
RESULTS/CONCLUSIONS: This patient under went vitrectomy for removal of a dense vitreitis and responded well to systemic cyclophosphamide. This case demonstrates that antineutrophil cyto plasmic antibody testing is useful for the diagnosis and treatment of Wegener's granulomatosis and microscopic polyarteritis-associated scleritis. The distinction between these two entities is often difficult to make.
E
XUDATIVE DETACHMENT OF THE CHOROID AND RETI-
na secondary to scleritis has been infrequently described as a manifestation of Wegener's granuloma tosis1 or microscopic polyarteritis.2 Earlier reports usually demonstrated this manifestation histopathologically after globe perforation. Antineutrophil cyto plasmic antibody testing is useful for diagnosis and treatment of Wegener's granulomatosis and micro scopic polyarteritis-associated scleritis.3 We examined a patient with scleritis-induced combined detach ments and vitreitis caused by antineutrophil cytoplas mic antibody-positive systemic vasculitis. A 72-year-old woman had had eight months of intermittent pain and five months of decreased visual acuity in the right eye. Ocular history was contributo ry for uncomplicated cataract extraction in the right eye. Ocular examination disclosed visual acuity of R.E.: counting fingers at 2 ft and L.E.: 20/30. Slitlamp examination of the right eye disclosed anterior nodular scleritis, anterior chamber flare and cell, and a well-positioned posterior chamber intraocular lens. The vitreous was markedly opacified with a thick, congealed material that obscured fundus examina tion. Orbital magnetic resonance imaging showed contrast enhancement of the sciera with choroidalretinal detachment. The right lacrimal gland was enlarged and enhanced with contrast (Fig. 1). Chest x-ray showed pneumonitis in the right upper lobe. Laboratory studies demonstrated positive indirect immunofluorescence testing for antineutrophil cyto plasmic antibody with a perinuclear staining pattern. Antibodies to myeloperoxidase were positive and
Department of Ophthalmology, Medical College of Georgia (D.M.M.); Ophthalmic Consultants of Boston (A.R.F., J.W.S.); and New En gland Eye Center, Tufts University School of Medicine (M.B.R.). Inquiries to Dennis M. Marcus, M.D., Department of Ophthalmolo gy, Medical College of Georgia, Augusta, GA 30912; fax: (706) 7214012.
BRIEF REPORTS
517