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Show f. Clin. Neuro-ophthalmol. 3: 101-104, 1983. Recurrent Bilateral Optic Neuropathy in Mixed Connective Tissue Disease MICHAEL G. GRESSEL, M.D. ROBERT L. TOMSAK, M.D., Ph.D. Abstract Multiple attacks of optic neuropathy occurred in a young woman suffering from mixed connective tissue disease despite maintenance therapy with corticosteroids and cytotoxic agents. Introduction There has been considerable interest generated by recent reports 1 - ., of autoimmune disease as a cause of acute optic neuritis. Most of the patients reported have been young to middle-aged females in whom serologic abnormalities were initially more striking than classic clinical signs and symptoms of systemic lupus erythematosus or related diseases. In some cases, optic neuritis has been the first sign of the systemic disease. A common theme among these reports has been recurrent attacks of optic neuritis in one or both eyes, not infrequently causing, in some degree, permanent visual deficit. The importance of early diagnosis and treatment in prevention of blindness has been emphasized by Dutton et al. l Other authors~·4 have noted visual improvement following treatment with corticosteroids and/or cytotoxic agents. We have recently seen such a patient who experienced recurrent attacks of optic neuritis in both eyes and developed signs of progressive optic nerve damage despite aggressive treatment. Case Report The patient is a 21-year-old woman who had been well until the age of 8 years when a febrile illness was followed by recurrent bouts of polyarthritis involving predominantly the wrists, ankles, and left shoulder. She was treated intermittently with intramuscular gold and oral aspirin, which controlled her joint disease. In July 1980, she developed fever, a severe head- From the Department of Ophthalmology, Cleveland Clinic Foundation. Cleveland. Ohio. June 1983 ache, and blurred vision in both eyes, followed by transient urinary retention and diminished sensation below the waist. Visual acuity was 20/40 with the right eye and 20/25 with the left eye with reportedly normal-appearing optic discs. A computed tomographic scan of the head was normal. Lumbar puncture revealed cerebrospinal fluid with 35 white blood cells/mm;l (100% lymphocytes), glucose = 43 mg/dt and protein = 118 mg/dl. Cerebrospinal fluid IgG/albumin ratio was 28.5 (normal 1.3 to 10.4). The patient's serum was positive for antinuclear antibodies (speckled pattern) at a titer of >1: 256 and for antiribonucleoprotein (RNP) at a titer of 1: 40,960. Antismooth-muscle antibodies were absent. Vision improved over several weeks of oral prednisone. She was known to have experienced acute episodes of decreased vision in the right eye to hand motions in December 1980 and in the left eye to 20/80 in January 1981, each time with improvement on systemic corticosteroids. Attempts to taper prednisone dosage below 40 mg/day were followed repeatedly by visual deterioration, particularly in the left eye. Systemic azathioprine (lmuran) therapy was instituted in April 1981. By September 1981, optic atrophy was apparent in both eyes, although visual acuity was recorded at 20/20-1 with the right eye and 20/20-3 with the left eye. In November 1981, she developed a severe bifrontal headache and awakened the next day with complete loss of vision in both eyes. She was admitted to a hospital where treatment with 1 g of methylprednisolone intravenously per day for I week was followed by moderate improvement in right-eye vision. Limited change. however, was noted in the left eye. At the time of transfer to the Cleveland Clinic Hospital, best-corrected visual acuities were 20/60 on the right and 10/200 on the left with an afferent pupillary defect in the left eye. Color vision was moderately decreased in the right eye and severely decreased in the left. Visual fields were as illustrated in Figure 1. Mild central posterior subcapsular lens opacities were present in both eyes. Marked pallor of the optic discs and narrowing of the retinal arterioles were noted in both eyes 101 Optic Neuropathy <lnci Tissue Disease "" LUT 10/200 RIGHT 20/60 Figure 1. Goldmann visual fields showing cecocent ra I scotoma in the right eye and complete loss of nasal field in the left eye. la I Figures 2" and 2b. Severe bil.lter.,1 optic atrophy. right and left eyes (Ncwember 10SI). (Fig. 2). General physical examination was remarkable for a Cushingoid body habitus and sclerodactylous changes in the fingers. Serologic studies confirmed the presence of antinuclear and extremely high titers of anti ribonucleoprotein antibodies as well as the absence of antismooth-muscle and anti-Sjogren syndrome B-antibodies. The diagnosis of mixed connective tissue disease was made. The patient was treated with oral prednisone (60 mg/day) and intravenous nitrogen mustard (2 mg/day for 6 days), with gradual visual improvement. She was discharged on oral prednisone, 55 mg/day, and cyclophosphamide (Cytoxan), 100 mg/day. Three weeks later, her vision had improved to 20/30 (right eye) and 20/50 (left eye). Another episode of visual loss in the left eye 102 occurred in March 1982 after tapering of prednisone to IS mg/day. Because of leukopenia and hematuria, cyclophosphamide was discontinued in April 1982 and substituted with chlorambucil (Leukeran), 2 mg twice daily, supplemented with the minimum amount of prednisone possible. In June 1982, the patient experienced an episode of sudden visual loss to hand motions in the left eye while on prednisone (35 mg/day) and chlorambucil (4 mg/day). Visual acuity in the right eye was 20/25. She was hospitalized and treated with oral prednisone, intravenous methylprednisolone, and nitrogen mustard. No objective improvement in central visual acuity occurred, and further loss of visual field in the left eye was documented (Fig. 3). Journal of Clinical Neuro-ophthalmology LUT HM 6·4'82 "" RIGHT 20/25 Figure 3. Goldmdnn vlsudl field, showong progressIOn "f v"udl field It", In the left eye. Discussion Mixed connective tissue disease is a syndrome combining clinical features of systemic lupus erythematosus, progressive systemic sclerosis (scleroderma), and polymyositis6 ,; High titers of antiribonucleoprotein antibodies are the most character: istic serologic finding. Bennett and O'Connell' found a relatively high (11/20) incidence of neuropsychiatric disorders in their patients with this syndrome. These took the form of aseptic meningitis, psychosis, febrile headaches, peripheral and trigeminal neuropathies, and convulsions. By contrast, Sharp" states that even mild neurologic abnormalities are found in only 10% of patients with mixed connective tissue disease. To the best of our knowledge, there has been only one previously reported patient with mixed connective tissue disease and optic neuritis. I The present case illustrates several important points. First, optic neuropathy was unquestionably the most severe and debilitating aspect of our patient's disease. She was markedly Cushingoid as a result of attempts to preserve her vision. Second, although her vision was responsive to corticosteroids (even dependent on high-maintenance doses), she continued to experience severe episodes of visual loss despite aggressive treatment with prednisone and a variety of cytotoxic agents. Although pulsed intravenous methylprednIsolone and nitrogen mustard therapy appeared somewhat beneficial in improving central vision, her visual fields suggest that permanent optic nerve damage occurred with these episodes. Our patient's optic discs were examined multiple times both before and after optIC atrophy supervened. At no time was papillitis observed. We believe that our patient's disease process has beer:t, a retrobulbar optic neuritis. Klingele and Burde have observed both papillitis and retrobulbar neu- June 1983 ritis in their series of presumed autoimmune optic neuritis. The pathophysiology of optic neuropathy in autoimmune diseases is unresolved. Histopathologic evidence of demyelination in the optic nerves has been reported in three cases of systemic lupus erythematosus associated with symptoms of spinal cord disease and optic neuropathy.H.Y.IIl Crompton et aLII have reported an elderly patient with anterior ischemic optic neuropathy and rheumatoid arthritis who at autopsy showed evidence of posterior ciliary arthritis. Our patient's stuttering course of visual loss, apparently precipitated at times by attempts to taper prednisone, seems more suggestive of vasculitis than of primary demyelinating disease. However, her cerebrospinal fluid pleocytosis with elevation of protein and IgG does not serve to differentiate between a vasculitic and a demyelinating process. Whether common mechanisms underlie optic neuropathy in the various autoimmune diseases remains to be determined. We agree with Dutton et aLI that early diagnosis and treatment of autoimmune optic neuritis is necessary to prevent visual loss. However, the present case illustrates the fact that the visual prognosis of this group of disorders can be poor in spite of aggressive treatment. References 1. Dutton, rl., Burde. RM" Jnd Klingele, T.G. Autoimmune retrobulbar optic neuritis. Am. T. Ophthalmol. 94: 11-17, 1qg2. 2. Cinefro, RI, and Frenl..el, M.: Systemic lupus erythematosus presenting as optic neuritis. Ann, Ophthdlmol. 10: SSq-So3, IQ78, 3. HJckett, E.R., M,Htinez, RD., Ldrson, P.F., dnd Pdddison, R.M.: Optic neuritis in systemic lupus erythemdtosus. Arch. Neural. 31: 9-11, 1974. 4. Zduel, D.W, Goodell, R.C., Wilson, r.M., Sr, dnd 103 Optic Neuropathy and Tissue Disease Julian, K.G.: Acute bilateral ischemic optic neuropathy. Presented at American Academy of Ophthalmology Annual Meeting, Atlanta, 1981. 5. Klingele, T.G., and Burde, R.M.: A.N.A. positive optic neuritis. Presented at the annual Walsh Society Meeting, 1982, Los Angeles, California. b. Sharp, C.c.: Mixed connective tissue disease. In Arthritis and Allied Conditions (9th ed.), D.l. McCarthy, Ed. Lea & Febiger, Philadelphia, 1979, Chap. 51, pp. 737-741. 7. Bennett, R.M., and O'Connell, D,J.: Mixed connective tissue disease: A clinicopathologic study of 20 cases. Semin. Arthritis Rheum. 10: 25-51, 1980. 8. April, R.S., and Vansonnenberg, E.: A case of neuromyelitis optica (Devic's syndrome) in systemic lupus erythematosus. Neurology 26: 1066-1070, 1976. 104 9. Kinney, E.L., Berdoff, R.L., Rao, N.5., and Fox, L.M.: Devic's syndrome and systemic lupus erythematosus. Arch. Neural. 36: 643-644, 1979. 10. Shepherd, D.I., Downie, A.W., and Best, P.V.: Systemic lupus erythematosus and multiple sclerosis. (Abstract.) Arch. Neural. 30: 423, 1974. 11. Crompton, l.L., Iyer, P., and Begg, M.W.: Vasculitis and ischemic optic neuropathy associated with rheumatoid arthritis. Aust. f. Ophthalmol. 8: 219-230, 1980. Write for reprints to: Robert L. Tomsak, MD., Department of Ophthalmology, Cleveland Clinic Foundation, 9500 Euclid Avenue, Cleveland, Ohio 44106. Journal of Clinical Neuro-ophthalmology |
