- Email: [email protected]
Sympathetic Ophthalmia
SYMPATHETIC O P H T H A L M I A W I L L I A M B. D R E Y E R , J R . , M . D . , H E R N A N D O Z E G A R R A , M.D., Z V E T A N N I C H O L A S ZAKOV, M . D . , AND F R O N C I E A. G U T M A N , M.D.
Cleveland, Ohio
A 29-year-old woman developed severe ocular manifestations of sympathetic ophthalmia on the day after enucleation of a blind, painful eye, and four weeks after a penetrating ocular injury. She was observed for one year with fundus photography, fluorescein angiography, and electrophysiologic tests. Nystagmus, a rare systemic manifestation of sympathetic ophthalmia, was noted early in the course of her disease and was accompanied by vertigo, truncal ataxia, and cerebrospinal fluid pleocytosis. Enucleation and intensive corticosteroid treatment resolved the process; however, she has experienced recurrences in the two-year follow-up period.
Sympathetic ophthalmia is a bilateral diffuse granulomatous uveitis of unknown cause that typically develops after pene trating ocular injury. The systemic mani festations of this disease include poliosis and vitiligo. Central nervous system in volvement has been suggested by meningeal signs (high temperature and headaches), and a few reports have emphasized dysacousia and vertigo as as sociated findings.1"4 Our patient had predominantly poste rior manifestations of sympathetic oph thalmia, including total retinal detach ment. For the past year we have observed the course of her disease with serial fun dus photography, fluorescein angiogra phy, and electrophysiologic tests. Early in the treatment, the patient developed vertigo associated with nystagmus, trun cal ataxia, and cerebrospinal fluid pleocy tosis. To the best of our knowledge this is
From the Cleveland Clinic Foundation, Cleveland Ohio. Reprint requests to Hernando Zegarra, M.D., Cleveland Clinic Foundation, 9500 Euclid Ave., Cleveland, OH 44106. 816
the first report of nystagmus associated with sympathetic ophthalmia. CASE REPORT
On Nov. 14, 1978, a 29-year-old woman sustained a large corneoscleral laceration in her left eye from an explosion in a chemistry laboratory. The lens was removed and the wound was repaired within 24 hours. The eye became increasingly painful and was enucleated on Dec. 18, 1978. On the day after the enucleation the patient reported blurring and photo phobia in her right eye. She was referred to the Retina Service here. External examination disclosed multiple facial scars imbedded with fragments of glass. The left orbit was healing well. Visual acuity was 6/60 (20/200). There was severe ciliary injection. The cornea had fine keratic precipitates, and the anterior chamber had cells and flare but no hypopyon. The iris appeared normal and the lens was clear. There were some vitreous cells. The retina was totally detached with shifting subretinal fluid and no visible retinal breaks. Multiple yellow placoid areas (Fig. 1) suggestive of choroidal infiltrates were pres ent in the posterior pole. A fluorescein angiogram demonstrated multiple sites of choroidal leakage with late coalescence of dye under the detached retina (Fig. 2). The sites of choroidal leakage corresponded to the yellow lesions observed with indirect ophthalmoscopy. The clinical diagnosis was sympathetic ophthalmia. The patient was treated with prednisone orally, 200 mg daily, topical cycloplegics and çoriicosteroids, and periocular corticosteroid injections. Histopathologic examination of the enucleated eye showed an area of healed perforation on the cornea. The anterior chamber was completely obliterated by a dense matrix consisting of inflammatory cells, in-
AMERICAN JOURNAL OF OPHTHALMOLOGY 92:816-823, 1981
VOL. 9 2 , N O . 6
SYMPATHETIC O P H T H A L M I A
817
Fig. 2 (Dreyer and associates). Top left, Early arteriovenous phase of initial angiogram. Top right, Multiple sites of choroidal leakage in recirculation phase. Bottom left, Late coalescence of dye in subret inal space.
eluding epithelioid cells, giant cells, lymphocytes, and other chronic and acute inflammatory cells. Remnants of the lens capsule were surrounded by infiltrates, including some polymorphonuclear leuko cytes. The uveal structures, including the entire ciliary body and choroid, were massively thickened (Fig. 3), and there was evidence of definite granulomatous inflammation with many lymphocytes, epi thelioid cells, and giant cells (Fig. 4). Pigment phag ocytosis, giant cells, and epithelioid cells were prominent. We noted areas of destruction of the choriocapillaris, overlaid with classic Dalen-Fuchs nodules (Fig. 5). Histologie examination of the retina demonstrated artifactious retinal detachment without any evidence of serous retinal detachment. The subretinal space contained loose pigment from the disrupted retinal pigment epithelial cells. The retina
Fig. 3 (Dreyer and associates). Histologie section of the eye, showing severely thickened choroid (hematoxylin and eosin, x 40).
818
AMERICAN JOURNAL OF OPHTHALMOLOGY
DECEMBER, 1981
Fig. 4 (Dreyer and associates). Histologie section of choroid show ing granulomatous inflammation with lymphocytes, epithelioid cells, giant cells, and pigment phagocyto sis (hematoxylin and eosin, x 400).
itself was well preserved with some degenerative changes in the photoreceptor layer; the other retinal layers were completely intact. The only abnormality was some perivascular cuffing intraretinally by ma ture lymphocytes and occasional eosinophils. There was no evidence, however, of any granulomatous inflammation within the retina. By the sixth day of hospitalization, the patient showed dramatic improvement. Her visual acuity was 6/18 (20/60) and the anterior chamber was clear. As the subretinal fluid absorbed superiorly, many small (one-third disk diameter) yellow-white subret
inal lesions became visible along the arcade (Fig. 6). On the eighth day, multiple yellow-white subretinal lesions (one-fourth disk diameter) were observed in the midperiphery (Fig. 7), but the retina was totally attached. By the 12th day, the dosage of prednisone was decreased to 40 mg/day. On the 13th day, the patient complained of verti go. She had horizontal jerk nystagmus (fast compo nent to the left) with a rotary component. Neurologic examination confirmed the presence of truncal ataxia and lumbar puncture showed 70 WBC/mm3 with 95% lymphocytes, a blood glucose level of
Fig. 5 (Dreyer and associates). Destruction of the choriocapillaris with overlying Dalen-Fuchs nod ules. Section of the choroid (hema toxylin and eosin, X 400).
VOL. 92, NO. 6
SYMPATHETIC OPHTHALMIA
73 mg/100 ml, and a protein level of 24 mg/100 ml. Routine cultures were negative. Other studies were performed in an attempt to determine the cause of the nystagmus. Urine culture of virus in MRC-5 embryonic lung cells was negative. Acute and convalescent sera for echovirus, coxsackie virus B types 1 to 6, herpes simplex, and cytomegaloviruses were normal. Toxoplasmosis titer was less than 1:16. Computed tomography of the head was also normal. The patient's symptoms gradually re solved over the next three days. After 23 days in the hospital, her visual acuity was 6/9 (20/30). Although minimal nystagmus remained, she was asymptomatic and was discharged from the hospital. Medication prescribed at discharge includ ed prednisone, 40 mg every other day, and corticosteroid drops topically. The fluorescein angiogram had normal choroidal and retinal phases, with mild leakage from the optic nerve on late phases (Fig. 8). The corticosteroid dosage was gradually reduced. On May 16, 1979, her visual acuity was 6/6 (20/20) and the Goldmann visual field was normal. The white lesions in the midperiphery had disappeared, al though the yellow lesions along the arcades persist ed. Left horizontal nystagmus with a rotary compo nent was present under closed eyelids, but absent with the eyelids open. Neurologic evaluation was repeated to localize the lesion causing the nystag mus. Repeat lumbar puncture showed 5 WBC/mm , all lymphocytes. The glucose level was 50 mg/100 ml, and the protein level was 14 mg/100 ml. Viral cultures of the cerebrospinal fluid MRC-5 embryonic lung cells were negative, as were routine bacterial fungal cultures. Audiometry and auditory-evoked potentials were also normal, but electronystag-
819
mography documented the spontaneous left beating horizontal nystagmus, as well as severely diminished caloric responses in the right ear. On June 22, 1979, the patient noted blurred vision and her best corrected visual acuity was 6/9 (20/30). On examination 1 + posterior vitreous cells could be seen with the Hruby lens. Prednisone dosage was increased to 40 mg every other day and gradually tapered over the next three weeks. On July 20, the patient's best visual acuity was 6/12 (20/40). Ophthalmoscopic examination showed yellow lesions along the arcades as before and a geographic area of sharply demarcated retinal pigment epithelial disturbance in the posterior pole (Fig. 9). Electrophysiologic testing was performed. The light rise and the dark trough were absent in the electro-oculogram. The electroretinogram demon strated a 50% reduction in the cone b-wave ampli tude (photopic) and 75% reduction of the rod b-wave (scotopic). Dark adaptometry (Goldmann-Weekers) demonstrated increased thresholds of four standard deviations for Both rods and cones. The results of the Farnsworth-Munsell 100-hue test showed average discrimination. By Sept. 21, 1979, the patient's visual acuity improved to 6/9 (20/30) and there were no cells in the aqueous or vitreous. Prednisone dosage was tapered to 15 mg every other day. On Jan. 31, 1980, visual acuity was 6/9 (20/30). She was maintained on a regimen of prednisone, 15 mg every other day. An electroretinogram demonstrated increased ampli tude of the scotopic b-wave (rods), showing only a 50% reduction. On April 10, 1980, after the prednisone dosage had been tapered to 10 mg every other day, the patient had another recurrence of uveitis; her visual acuity remained at 6/9 (20/30). The anterior chamber showed mild cells and flare, and the vitreous showed 1+ cells. Results of the ophthalmoscopic examination were unchanged. The patient was treated again by increasing the prednisone dosage to 40 mg/day for one week and then tapering. DISCUSSION
Fig. 8 (Dreyer and associates). Fluorescein angio gram shows only mild leakage from the optic nerve on the 23rd day of hospitalization.
The clinical findings in sympathetic ophthalmia are dominated by severe granulomatous anterior uveitis. The pos terior form of the disease is dominated by inflammation of the optic nerve, choroid, and ciliary body, and is sometimes ac companied by mild iritis. 2,5 Although ear lier reports suggest that the posterior form of the disease occurs in only 5% of all cases of sympathetic ophthalmia, 2 in a recent clinicopathologic review by Lubin, Albert, and Weinstein, 6 58% of
820
AMERICAN JOURNAL OF OPHTHALMOLOGY
the patients described had signs of retinal detachment. Only four fiuorescein angiograms have been reported in cases of sympathe tic ophthalmia. Our fiuorescein angio graphie findings were similar to those of Segawa and Matsuoka, 7 and Spitznas, 8 who found multiple focal areas of choroidal fluorescence that coalesced in the late phases of the angiogram. In contrast, Lewis, Gass, and Spencer 9 and Shimizu, Yokochi, and Kobayashi 10 noted a pattern of early blocking and late fluorescence simulating the angiogram seen in acute posterior multifocal placoid pigment epitheliopathy. In our case the yellow plac oid areas underneath the detached retina at initial examination seemed to corre spond to the areas of late staining on fiuorescein angiography. Accepted management of sympathetic ophthalmia consists of suppressing in flammation with corticosteroids and avoiding synechiae with mydriatics. Our patient responded dramatically to high doses of oral, periocular, and topical cor ticosteroids. Most researchers agree that early enucleation will prevent the devel opment of sympathetic ophthalmia. Re ports from the era before corticosteroids suggest that enucleation does not im prove the chance of retaining good vision in the sympathizing eye. 11,12 It has been suggested that enucleation may improve the course of the posterior form of sympa thetic ophthalmia. 2 The recent retrospective series report ed by Lubin, Albert, and Weinstein 6 sug gests that enucleation may play a protec tive role if performed within two weeks of the development of symptoms in the sympathizing eye. In this case, early enu cleation and corticosteroids have been associated with a benign clinical course. In Makley and Azar's 13 review of 14 patients and in Lubin, Albert, and Weinstein's 6 review of 18 patients, all treated
DECEMBER, 1981
with corticosteroids, at least 65% of pa tients retained final visual acuities of 6/18 (20/60) or better in the sympathizing eye. Unfortunately, relapses are common. Fully 30% of patients had relapses within six months, and one patient had a relapse after 13 years. 13 Therefore, the prognosis for our patient is difficult to predict. Ferry 2 has pointed out that melanin is present not only in the skin, but also in such related structures as the méninges, cochlea, and vestibular apparatus. Re sults of skin tests with uveal prepara tions, abnormal lymphocyte transforma tion test, 14 leukocyte migration test, 15 and ultrastructural studies 16 support his con clusion that hypersensitivity to uveal pigment plays an important role in sympathetic ophthalmia. In our patient, the inflammatory proc ess associated with sympathetic oph thalmia appears to have involved the méninges, producing cerebrospinal fluid pleocytosis. Focal involvement of the ves tibular apparatus may explain the nystag mus and absent caloric responses. The negative computed tomography scan, auditory-evoked response, and audiogram with abnormal electronystagmography support this conclusion. There are many similarities between sympathetic ophthalmia and Vogt-Koyanagi-Harada syndrome, including the pathologic findings6,17 and the fiuorescein angiographie pattern. 1 8 Also, meningoencephalitis, which occurs only rarely in sympathetic ophthalmia, is seen com monly in Vogt-Koyanagi-Harada syn drome.19"24 The difference between these two entities is established clinically. In our case the diagnosis of sympathetic ophthalmia was made on the basis that anterior and posterior uveitis followed a severe penetrating injury to the opposite eye. The histopathologic results in the enucleated eye were consistent with the diagnosis.
Fig. 1 (Dreyer and associates). Total retinal detachment with underlying areas suggestive of choroidal infiltrates.
Fig. 6 (Dreyer and associates). Yellowish-white lesions noted along the arcades on hospital day 6.
Fig. 7 (Dreyer and associates). Multiple yellowishwhite lesions in the midperiphery noted on hospital day 8.
Fig. 9 (Dreyer and associates). Geographic area of sharply demarcated retinal pigment epithelium distur bance in the posterior pole.
VOL. 92, NO. 6
SYMPATHETIC OPHTHALMIA
REFERENCES
1. Duke-Elder, S., and Leigh, A. G.: Diseases of the Uveal Tract. In Duke-Elder, S. (ed.): System of Ophthalmology, vol. 9. St. Louis, C. V. Mosby, 1966, pp. 558-589. 2. Ferry, A., in discussion of McPherson, S. D., Jr., and Dalton, H. T.: Posterior form sympathetic ophthalmia. Trans. Am. Ophthalmol. Soc. 73:251, 1976. 3. Nirankari, M. S., Khanna, K. K., Chawla, G. D., and Mathur, R. P. : Sympathetic ophthalmitis with total deafness (a case report). J. India Ophthal mol. Soc. 18:29, 1970. 4. Wilson, P.: Sympathetic ophthalmitis simulat ing Harada's disease. Br. J. Ophthalmol. 46:626, 1962. 5. Woods, A. C : Sympathetic ophthalmia. Part I. Am. J. Ophthalmol. 19:9, 1936. 6. Lubin, J. R., Albert, D. M., and Weinstein, M.: Sixty-five years of sympathetic ophthalmia. Oph thalmology 87:109, 1980. 7. Segawa, K., and Matsuoka, N.: Sympathetic ophthalmia. A comparative fluorographic and elec tron microscopic study. Jpn. J. Ophthalmol. 15:81, 1971. 8. Spitznas, M.: Fluoreszenzangiographie der sympathischen Ophthalmie. Klin. Monatsbl. Augenheilkd. 169:195, 1976. 9. Lewis, M. L., Gass, J. D. M., and Spencer, W. H.: Sympathetic uveitis after trauma and vitrectomy. Arch. Ophthalmol. 96:263, 1978. 10. Shimizu, K., Yokochi, K., and Kobayashi, Y. : Inflammations of the choroid. Doc. Ophthalmol. 9:385, 1976. 11. Irvine, R.: Sympathetic ophthalmia. A clin ical review of 63 cases. Arch. Ophthalmol. 24:149, 1940. 12. Joy, H. H. : A survey of cases of sympathetic
823
ophthalmia occuring in New York State. N. Y. State J. Med. 36:85, 1936. 13. Makley, T. A., Jr., and Azar, A. : Sympathetic ophthalmia, a long-term follow-up. Arch. Ophthal mol. 96:257, 1978. 14. Wong, V. G., Anderson, R., and O'Brien, P. J. : Sympathetic ophthalmia and lymphocyte trans formation. Am. J. Ophthalmol. 72:960, 1971. 15. Hammer, H.: Cellular hypersensitivity to uveal pigment confirmed by leukocyte migration tests in sympathetic ophthalmia and Vogt-KoyanagiHarada syndrome. Br. J. Ophthalmol. 58:773, 1974. 16. Matsuda, H.: Electron microscopic studies on Vogt-Koyanagi-Harada syndrome and sympathetic ophthalmia with special reference to the melanocyte. Acta Soc. Ophthalmol. Jpn. 74:1107, 1970. 17. Yanoff, M., and Fine, B. M.: Ocular Patholo gy. New York, Harper and Row, 1975, p. 104. 18. Kanter, P. J., and Goldberg, M. F.: Bilateral uveitis with exudative retinal detachment. Arch. Ophthalmol. 91:13, 1974. 19. Cowper, A. R.: Harada's disease and VogtKoyanagi syndrome (uveoencephalitis). Arch. Oph thalmol. 45:367, 1951. 20. Bruno, M. G., and McPherson, S. D., Jr.: Harada's disease. Am. J. Ophthalmol. 32:513, 1949. 21. Perry, H. D., and Font, R. L.: Clinical and histopathologic observations in severe VogtKoyanagi-Harada syndrome. Am. J. Ophthalmol. 83:242, 1977. 22. Yuge, T. : The relation between Vogt-Koyanagi syndrome and sympathetic ophthalmia. Report of a case of Vogt-Koyanagi syndrome. Am J. Ophthalmol. 43:735, 1957. 23. Wilson, P. : Sympathetic ophthalmitis simulat ing Harada's disease. Br. J. Ophthalmol. 46:626, 1962. 24. Swartz, E. A.: Vogt-Koyanagi-Harada syn drome. Am. J. Ophthalmol. 39:488, 1955.
Cleveland, Ohio
A 29-year-old woman developed severe ocular manifestations of sympathetic ophthalmia on the day after enucleation of a blind, painful eye, and four weeks after a penetrating ocular injury. She was observed for one year with fundus photography, fluorescein angiography, and electrophysiologic tests. Nystagmus, a rare systemic manifestation of sympathetic ophthalmia, was noted early in the course of her disease and was accompanied by vertigo, truncal ataxia, and cerebrospinal fluid pleocytosis. Enucleation and intensive corticosteroid treatment resolved the process; however, she has experienced recurrences in the two-year follow-up period.
Sympathetic ophthalmia is a bilateral diffuse granulomatous uveitis of unknown cause that typically develops after pene trating ocular injury. The systemic mani festations of this disease include poliosis and vitiligo. Central nervous system in volvement has been suggested by meningeal signs (high temperature and headaches), and a few reports have emphasized dysacousia and vertigo as as sociated findings.1"4 Our patient had predominantly poste rior manifestations of sympathetic oph thalmia, including total retinal detach ment. For the past year we have observed the course of her disease with serial fun dus photography, fluorescein angiogra phy, and electrophysiologic tests. Early in the treatment, the patient developed vertigo associated with nystagmus, trun cal ataxia, and cerebrospinal fluid pleocy tosis. To the best of our knowledge this is
From the Cleveland Clinic Foundation, Cleveland Ohio. Reprint requests to Hernando Zegarra, M.D., Cleveland Clinic Foundation, 9500 Euclid Ave., Cleveland, OH 44106. 816
the first report of nystagmus associated with sympathetic ophthalmia. CASE REPORT
On Nov. 14, 1978, a 29-year-old woman sustained a large corneoscleral laceration in her left eye from an explosion in a chemistry laboratory. The lens was removed and the wound was repaired within 24 hours. The eye became increasingly painful and was enucleated on Dec. 18, 1978. On the day after the enucleation the patient reported blurring and photo phobia in her right eye. She was referred to the Retina Service here. External examination disclosed multiple facial scars imbedded with fragments of glass. The left orbit was healing well. Visual acuity was 6/60 (20/200). There was severe ciliary injection. The cornea had fine keratic precipitates, and the anterior chamber had cells and flare but no hypopyon. The iris appeared normal and the lens was clear. There were some vitreous cells. The retina was totally detached with shifting subretinal fluid and no visible retinal breaks. Multiple yellow placoid areas (Fig. 1) suggestive of choroidal infiltrates were pres ent in the posterior pole. A fluorescein angiogram demonstrated multiple sites of choroidal leakage with late coalescence of dye under the detached retina (Fig. 2). The sites of choroidal leakage corresponded to the yellow lesions observed with indirect ophthalmoscopy. The clinical diagnosis was sympathetic ophthalmia. The patient was treated with prednisone orally, 200 mg daily, topical cycloplegics and çoriicosteroids, and periocular corticosteroid injections. Histopathologic examination of the enucleated eye showed an area of healed perforation on the cornea. The anterior chamber was completely obliterated by a dense matrix consisting of inflammatory cells, in-
AMERICAN JOURNAL OF OPHTHALMOLOGY 92:816-823, 1981
VOL. 9 2 , N O . 6
SYMPATHETIC O P H T H A L M I A
817
Fig. 2 (Dreyer and associates). Top left, Early arteriovenous phase of initial angiogram. Top right, Multiple sites of choroidal leakage in recirculation phase. Bottom left, Late coalescence of dye in subret inal space.
eluding epithelioid cells, giant cells, lymphocytes, and other chronic and acute inflammatory cells. Remnants of the lens capsule were surrounded by infiltrates, including some polymorphonuclear leuko cytes. The uveal structures, including the entire ciliary body and choroid, were massively thickened (Fig. 3), and there was evidence of definite granulomatous inflammation with many lymphocytes, epi thelioid cells, and giant cells (Fig. 4). Pigment phag ocytosis, giant cells, and epithelioid cells were prominent. We noted areas of destruction of the choriocapillaris, overlaid with classic Dalen-Fuchs nodules (Fig. 5). Histologie examination of the retina demonstrated artifactious retinal detachment without any evidence of serous retinal detachment. The subretinal space contained loose pigment from the disrupted retinal pigment epithelial cells. The retina
Fig. 3 (Dreyer and associates). Histologie section of the eye, showing severely thickened choroid (hematoxylin and eosin, x 40).
818
AMERICAN JOURNAL OF OPHTHALMOLOGY
DECEMBER, 1981
Fig. 4 (Dreyer and associates). Histologie section of choroid show ing granulomatous inflammation with lymphocytes, epithelioid cells, giant cells, and pigment phagocyto sis (hematoxylin and eosin, x 400).
itself was well preserved with some degenerative changes in the photoreceptor layer; the other retinal layers were completely intact. The only abnormality was some perivascular cuffing intraretinally by ma ture lymphocytes and occasional eosinophils. There was no evidence, however, of any granulomatous inflammation within the retina. By the sixth day of hospitalization, the patient showed dramatic improvement. Her visual acuity was 6/18 (20/60) and the anterior chamber was clear. As the subretinal fluid absorbed superiorly, many small (one-third disk diameter) yellow-white subret
inal lesions became visible along the arcade (Fig. 6). On the eighth day, multiple yellow-white subretinal lesions (one-fourth disk diameter) were observed in the midperiphery (Fig. 7), but the retina was totally attached. By the 12th day, the dosage of prednisone was decreased to 40 mg/day. On the 13th day, the patient complained of verti go. She had horizontal jerk nystagmus (fast compo nent to the left) with a rotary component. Neurologic examination confirmed the presence of truncal ataxia and lumbar puncture showed 70 WBC/mm3 with 95% lymphocytes, a blood glucose level of
Fig. 5 (Dreyer and associates). Destruction of the choriocapillaris with overlying Dalen-Fuchs nod ules. Section of the choroid (hema toxylin and eosin, X 400).
VOL. 92, NO. 6
SYMPATHETIC OPHTHALMIA
73 mg/100 ml, and a protein level of 24 mg/100 ml. Routine cultures were negative. Other studies were performed in an attempt to determine the cause of the nystagmus. Urine culture of virus in MRC-5 embryonic lung cells was negative. Acute and convalescent sera for echovirus, coxsackie virus B types 1 to 6, herpes simplex, and cytomegaloviruses were normal. Toxoplasmosis titer was less than 1:16. Computed tomography of the head was also normal. The patient's symptoms gradually re solved over the next three days. After 23 days in the hospital, her visual acuity was 6/9 (20/30). Although minimal nystagmus remained, she was asymptomatic and was discharged from the hospital. Medication prescribed at discharge includ ed prednisone, 40 mg every other day, and corticosteroid drops topically. The fluorescein angiogram had normal choroidal and retinal phases, with mild leakage from the optic nerve on late phases (Fig. 8). The corticosteroid dosage was gradually reduced. On May 16, 1979, her visual acuity was 6/6 (20/20) and the Goldmann visual field was normal. The white lesions in the midperiphery had disappeared, al though the yellow lesions along the arcades persist ed. Left horizontal nystagmus with a rotary compo nent was present under closed eyelids, but absent with the eyelids open. Neurologic evaluation was repeated to localize the lesion causing the nystag mus. Repeat lumbar puncture showed 5 WBC/mm , all lymphocytes. The glucose level was 50 mg/100 ml, and the protein level was 14 mg/100 ml. Viral cultures of the cerebrospinal fluid MRC-5 embryonic lung cells were negative, as were routine bacterial fungal cultures. Audiometry and auditory-evoked potentials were also normal, but electronystag-
819
mography documented the spontaneous left beating horizontal nystagmus, as well as severely diminished caloric responses in the right ear. On June 22, 1979, the patient noted blurred vision and her best corrected visual acuity was 6/9 (20/30). On examination 1 + posterior vitreous cells could be seen with the Hruby lens. Prednisone dosage was increased to 40 mg every other day and gradually tapered over the next three weeks. On July 20, the patient's best visual acuity was 6/12 (20/40). Ophthalmoscopic examination showed yellow lesions along the arcades as before and a geographic area of sharply demarcated retinal pigment epithelial disturbance in the posterior pole (Fig. 9). Electrophysiologic testing was performed. The light rise and the dark trough were absent in the electro-oculogram. The electroretinogram demon strated a 50% reduction in the cone b-wave ampli tude (photopic) and 75% reduction of the rod b-wave (scotopic). Dark adaptometry (Goldmann-Weekers) demonstrated increased thresholds of four standard deviations for Both rods and cones. The results of the Farnsworth-Munsell 100-hue test showed average discrimination. By Sept. 21, 1979, the patient's visual acuity improved to 6/9 (20/30) and there were no cells in the aqueous or vitreous. Prednisone dosage was tapered to 15 mg every other day. On Jan. 31, 1980, visual acuity was 6/9 (20/30). She was maintained on a regimen of prednisone, 15 mg every other day. An electroretinogram demonstrated increased ampli tude of the scotopic b-wave (rods), showing only a 50% reduction. On April 10, 1980, after the prednisone dosage had been tapered to 10 mg every other day, the patient had another recurrence of uveitis; her visual acuity remained at 6/9 (20/30). The anterior chamber showed mild cells and flare, and the vitreous showed 1+ cells. Results of the ophthalmoscopic examination were unchanged. The patient was treated again by increasing the prednisone dosage to 40 mg/day for one week and then tapering. DISCUSSION
Fig. 8 (Dreyer and associates). Fluorescein angio gram shows only mild leakage from the optic nerve on the 23rd day of hospitalization.
The clinical findings in sympathetic ophthalmia are dominated by severe granulomatous anterior uveitis. The pos terior form of the disease is dominated by inflammation of the optic nerve, choroid, and ciliary body, and is sometimes ac companied by mild iritis. 2,5 Although ear lier reports suggest that the posterior form of the disease occurs in only 5% of all cases of sympathetic ophthalmia, 2 in a recent clinicopathologic review by Lubin, Albert, and Weinstein, 6 58% of
820
AMERICAN JOURNAL OF OPHTHALMOLOGY
the patients described had signs of retinal detachment. Only four fiuorescein angiograms have been reported in cases of sympathe tic ophthalmia. Our fiuorescein angio graphie findings were similar to those of Segawa and Matsuoka, 7 and Spitznas, 8 who found multiple focal areas of choroidal fluorescence that coalesced in the late phases of the angiogram. In contrast, Lewis, Gass, and Spencer 9 and Shimizu, Yokochi, and Kobayashi 10 noted a pattern of early blocking and late fluorescence simulating the angiogram seen in acute posterior multifocal placoid pigment epitheliopathy. In our case the yellow plac oid areas underneath the detached retina at initial examination seemed to corre spond to the areas of late staining on fiuorescein angiography. Accepted management of sympathetic ophthalmia consists of suppressing in flammation with corticosteroids and avoiding synechiae with mydriatics. Our patient responded dramatically to high doses of oral, periocular, and topical cor ticosteroids. Most researchers agree that early enucleation will prevent the devel opment of sympathetic ophthalmia. Re ports from the era before corticosteroids suggest that enucleation does not im prove the chance of retaining good vision in the sympathizing eye. 11,12 It has been suggested that enucleation may improve the course of the posterior form of sympa thetic ophthalmia. 2 The recent retrospective series report ed by Lubin, Albert, and Weinstein 6 sug gests that enucleation may play a protec tive role if performed within two weeks of the development of symptoms in the sympathizing eye. In this case, early enu cleation and corticosteroids have been associated with a benign clinical course. In Makley and Azar's 13 review of 14 patients and in Lubin, Albert, and Weinstein's 6 review of 18 patients, all treated
DECEMBER, 1981
with corticosteroids, at least 65% of pa tients retained final visual acuities of 6/18 (20/60) or better in the sympathizing eye. Unfortunately, relapses are common. Fully 30% of patients had relapses within six months, and one patient had a relapse after 13 years. 13 Therefore, the prognosis for our patient is difficult to predict. Ferry 2 has pointed out that melanin is present not only in the skin, but also in such related structures as the méninges, cochlea, and vestibular apparatus. Re sults of skin tests with uveal prepara tions, abnormal lymphocyte transforma tion test, 14 leukocyte migration test, 15 and ultrastructural studies 16 support his con clusion that hypersensitivity to uveal pigment plays an important role in sympathetic ophthalmia. In our patient, the inflammatory proc ess associated with sympathetic oph thalmia appears to have involved the méninges, producing cerebrospinal fluid pleocytosis. Focal involvement of the ves tibular apparatus may explain the nystag mus and absent caloric responses. The negative computed tomography scan, auditory-evoked response, and audiogram with abnormal electronystagmography support this conclusion. There are many similarities between sympathetic ophthalmia and Vogt-Koyanagi-Harada syndrome, including the pathologic findings6,17 and the fiuorescein angiographie pattern. 1 8 Also, meningoencephalitis, which occurs only rarely in sympathetic ophthalmia, is seen com monly in Vogt-Koyanagi-Harada syn drome.19"24 The difference between these two entities is established clinically. In our case the diagnosis of sympathetic ophthalmia was made on the basis that anterior and posterior uveitis followed a severe penetrating injury to the opposite eye. The histopathologic results in the enucleated eye were consistent with the diagnosis.
Fig. 1 (Dreyer and associates). Total retinal detachment with underlying areas suggestive of choroidal infiltrates.
Fig. 6 (Dreyer and associates). Yellowish-white lesions noted along the arcades on hospital day 6.
Fig. 7 (Dreyer and associates). Multiple yellowishwhite lesions in the midperiphery noted on hospital day 8.
Fig. 9 (Dreyer and associates). Geographic area of sharply demarcated retinal pigment epithelium distur bance in the posterior pole.
VOL. 92, NO. 6
SYMPATHETIC OPHTHALMIA
REFERENCES
1. Duke-Elder, S., and Leigh, A. G.: Diseases of the Uveal Tract. In Duke-Elder, S. (ed.): System of Ophthalmology, vol. 9. St. Louis, C. V. Mosby, 1966, pp. 558-589. 2. Ferry, A., in discussion of McPherson, S. D., Jr., and Dalton, H. T.: Posterior form sympathetic ophthalmia. Trans. Am. Ophthalmol. Soc. 73:251, 1976. 3. Nirankari, M. S., Khanna, K. K., Chawla, G. D., and Mathur, R. P. : Sympathetic ophthalmitis with total deafness (a case report). J. India Ophthal mol. Soc. 18:29, 1970. 4. Wilson, P.: Sympathetic ophthalmitis simulat ing Harada's disease. Br. J. Ophthalmol. 46:626, 1962. 5. Woods, A. C : Sympathetic ophthalmia. Part I. Am. J. Ophthalmol. 19:9, 1936. 6. Lubin, J. R., Albert, D. M., and Weinstein, M.: Sixty-five years of sympathetic ophthalmia. Oph thalmology 87:109, 1980. 7. Segawa, K., and Matsuoka, N.: Sympathetic ophthalmia. A comparative fluorographic and elec tron microscopic study. Jpn. J. Ophthalmol. 15:81, 1971. 8. Spitznas, M.: Fluoreszenzangiographie der sympathischen Ophthalmie. Klin. Monatsbl. Augenheilkd. 169:195, 1976. 9. Lewis, M. L., Gass, J. D. M., and Spencer, W. H.: Sympathetic uveitis after trauma and vitrectomy. Arch. Ophthalmol. 96:263, 1978. 10. Shimizu, K., Yokochi, K., and Kobayashi, Y. : Inflammations of the choroid. Doc. Ophthalmol. 9:385, 1976. 11. Irvine, R.: Sympathetic ophthalmia. A clin ical review of 63 cases. Arch. Ophthalmol. 24:149, 1940. 12. Joy, H. H. : A survey of cases of sympathetic
823
ophthalmia occuring in New York State. N. Y. State J. Med. 36:85, 1936. 13. Makley, T. A., Jr., and Azar, A. : Sympathetic ophthalmia, a long-term follow-up. Arch. Ophthal mol. 96:257, 1978. 14. Wong, V. G., Anderson, R., and O'Brien, P. J. : Sympathetic ophthalmia and lymphocyte trans formation. Am. J. Ophthalmol. 72:960, 1971. 15. Hammer, H.: Cellular hypersensitivity to uveal pigment confirmed by leukocyte migration tests in sympathetic ophthalmia and Vogt-KoyanagiHarada syndrome. Br. J. Ophthalmol. 58:773, 1974. 16. Matsuda, H.: Electron microscopic studies on Vogt-Koyanagi-Harada syndrome and sympathetic ophthalmia with special reference to the melanocyte. Acta Soc. Ophthalmol. Jpn. 74:1107, 1970. 17. Yanoff, M., and Fine, B. M.: Ocular Patholo gy. New York, Harper and Row, 1975, p. 104. 18. Kanter, P. J., and Goldberg, M. F.: Bilateral uveitis with exudative retinal detachment. Arch. Ophthalmol. 91:13, 1974. 19. Cowper, A. R.: Harada's disease and VogtKoyanagi syndrome (uveoencephalitis). Arch. Oph thalmol. 45:367, 1951. 20. Bruno, M. G., and McPherson, S. D., Jr.: Harada's disease. Am. J. Ophthalmol. 32:513, 1949. 21. Perry, H. D., and Font, R. L.: Clinical and histopathologic observations in severe VogtKoyanagi-Harada syndrome. Am. J. Ophthalmol. 83:242, 1977. 22. Yuge, T. : The relation between Vogt-Koyanagi syndrome and sympathetic ophthalmia. Report of a case of Vogt-Koyanagi syndrome. Am J. Ophthalmol. 43:735, 1957. 23. Wilson, P. : Sympathetic ophthalmitis simulat ing Harada's disease. Br. J. Ophthalmol. 46:626, 1962. 24. Swartz, E. A.: Vogt-Koyanagi-Harada syn drome. Am. J. Ophthalmol. 39:488, 1955.