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Pigmentation Associated Histopathological Variations in Sympathetic Ophthalmia

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Pigmentation Associated Histopathological Variations in Sympathetic Ophthalmia Br J Ophthalmol: first published as 10.1136/bjo.64.3.220 on 1 March 1980. Downloaded from British Jolarnal of Ophthalmology, 1980, 64, 220-222 Pigmentation associated histopathological variations in sympathetic ophthalmia GEORGE E. MARAK, JR., AND HIROSHI IKUI From the Department of Ophthalmology, Georgetown University, Washington, DC, USA, and the Department of Ophthalmology, Kyishia University, Fukiioka, Japani SUMMARY The severity of inflammation in sympathetic ophthalmia is related to the degree of pigmentation, and the granulomatous response seems to be related to pigmentation. Eosinophilia is also associated with pigmentation, but this association appears to be fortuitous and is a result of the association of eosinophilia with severity of the inflammation. Elsching presented his most confusing pearl to the reasonably be considered intermediate in pigmen- ophthalmological community when he proposed tation between North American black and white that sympathetic ophthalmia represented an autoim- populations. mune response to uveal pigment.12 Recent obser- The magnitude of choroidal thickening by the vations have raised considerable doubts about the inflammatory infiltrate, the intensity of tissue role of uveal pigment as the offending antigenin eosinophilia, and the proportion of the epithelioid sympathetic ophthalmia.34 The function of the uveal cell response in the choroid compared to the melanocytes in sympathetic ophthalmia is not well lymphocytic infiltration were rated by a single understood, but pigmentary disturbances occur observer who was 1 of the 3 independent observers clinically, and some histopathological features of among whom there was essential agreement in all sympathetic ophthalmia appear to be associated cases in the prior study.5 with uveal pigmentation.5 The purpose of this The choroidal inflammatory reaction was rated report is to evaluate the previously described asso- mild if the greatest thickness of the postequatorial http://bjo.bmj.com/ ciation of certain histopathological features of choroid did not exceed half of a 'high-dry' field sympathetic ophthalmia with pigmentation in a new (430 x ), moderate if the choroidal thickness exceeded population. one-half but was less than 1 complete high-dry field, and marked if the thickness of the postequa- Materials and methods torial choroidal inflammation exceeded 1 full high-dry field. Cases were selected for this study from the files on The epithelioid cell response was evaluated by on September 30, 2021 by guest. Protected copyright. sympathetic ophthalmia at Kyushu University, comparing the relative proportion of choroidal Fukuoka, Japan, and from the Armed Forces thickening accounted for by the nests of epithelioid Institute of Pathology (AFIP), USA, that fulfilled cells compared to the lymphocytic infiltrate. Eosino- well established clinical and histopathological phils were considered to be increased if 3 or more criteria for the diagnosis of sympathetic ophthalmia were seen in the choroid in 5 representative high-dry outlined by Easom and Zimmerman.6 fields. This increase was considered heavy if more In the present study 2 groups of patients were than 20 eosinophils were seen in a high-power selected who appeared to be intermediate in pig- field. mentation between the black and white groups of patients described in a previous report.5 One group Results of patients were Japanese and the second group was a heterogeneous collection of Indian subcon- The 2 groups of cases of sympathetic ophtlhalmia tinent, American Indian, Puerto Rican, Middle were chosen because they appeared to represent East, and non-Japanese oriental patients who might degrees of pigmentation intermediate between the white and black patients. The histopatlhological Correspondeince to George E. Marak, Jr., MD, 1451 Belle features of sympathetic ophthalmia that seem to Haven Road, Alexandria, Virginia 22307, USA. be associated with pigment were observed to occupy 220 Br J Ophthalmol: first published as 10.1136/bjo.64.3.220 on 1 March 1980. Downloaded from Pigmenitation associated histopathological variationis ini sympathetic ophthalmiac2221 an intermediate position with respect to the severity ophthalmia. As predicted, patients with pigmenta- of the inflammation, the epithelioid response, and tion intermediate between black and white patients the degree of eosinophilia (Table 1). Although have a form of sympathetic ophthalmia showing increased eosinophilia is associated with increased intermediate intensities of inflammatory reaction. pigmentation (Table 2), this association may be Fuchs originally suggested that the pigment fortuitous and simply reflect the observation that containing epithelioid cells in sympathetic ophthal- eosinophilia is a function of the severity of disease mia may represent modified uveal melanocytes.7 in all groups studied (Table 3). The epithelioid This possibility has been discussed in some detail response appeared to be more closely related pig- by Hogan and Zimmerman, who point out8 that mentation. In severe cases in whites the epithelioid there is insufficient tissue necrosis in sympathetic response is not as predominant as in black patients, ophthalmia to account for the amount of apparent though the degree of epithelioid response is difficult pigment 'phacocytosis'. to quantitate. Current evidence suggests an alternative to the belief that the pigment-containing epithelioid cells Discussion have phagocytosed the alleged offending uveal pig- ment. The hypothesis that pigment-containing Our observations confirm the previously described epithelioid cells represent modified uveal melano- association between degree of pigmentation and the cytes is supported by several studies. Various inter- intensity of uveal inflammation in sympathetic mediate stages between melanocytes and the so- called pigment-containing epithelioid cells have been observed.9 10 Autophagy of melanosomes by Table I Degree of inflammatory thickening of the pigment-containing cells has been described.1" There choroid in sympathetic ophthalmia has been a detailed demonstration that the epithe- Choroi(lal thickening (per cent) lioid cells of Dalen-Fuchs nodules are modified Pigm1ientation No. of retinal pigment epithelial cells.'2 13 patients Milci moderate Servere A recent observation on the association of an Caucasians 218 60 24 16 experimental form of sympathetic ophthalmia with inflammation of the pineal gland suggests that a Mixecd group 19 21 37 42 disturbance in melantonin metabolism may provide Japanese 25 24 28 48 a link between the uveal inflammation and pigmen- Black 34 1 1 29 60 tary disturbances.'4 The association of eosinophilia with pigmentation http://bjo.bmj.com/ appears to be fortuitous, as there are no known mechanisms of association. This appears to be a Table 2 Eosinophilia in the choroid of sympathetic reflection of the correlation between eosinophilia ophthalmia and the severity of the inflammation. The associa- No. of Percentage with tion of eosinophilia with severe inflammation and Pijgm71entation patients Eosinophilia the relative concentration of eosinophils in the Negro 34 39 inner choroid have important immunological impli- on September 30, 2021 by guest. Protected copyright. cations. In experimental sympathetic ophthalmia Mixed grouip 19 23 eosinophils occur only in the more severe forms of Japanese 25 24 disease, are associated an increase in antibodies to Caucasians 218 9 the sympathogenic antigen, and may be suppressed by the C3 inactivator factor of cobra venom (which depletes complement and interferes with immune complex disease). These observations suggest that as a Table 3 Eosiniophilia function of imiflamnnation an immune complex mechanism of pathogenesis Eosinophitia* Milht ( %) MAolerate ( ,) Seere(rr may participate in very severe forms of disease, though the basic pathogenic mechanism appears to Negroes (13) 15 15 70 involve cell mediated hypersensitivity.15 Japanese (7) 0 43 57 The preferential localisation of eosinophils in Mixed (5) 20 20 60 the inner choroid in both human and experimental sympathetic ophthalmia may be a reflection of the Caucasian (19) 10 15 75 site at which the immunological surveillance system *Three or more eosinophils in the chor-oid in 5 representative first encounters the sympathogenic antigen, which high-dry fields. is presumably released from the immunologically Br J Ophthalmol: first published as 10.1136/bjo.64.3.220 on 1 March 1980. Downloaded from 222 George E. Marak, Jr., and Hiroshi Ikui privileged site between the middle limiting mem- 4Wacker WB, Rao NA, Marak GE. Experimental Sympa- thetic Ophthalmia. In: Silverstein A, O'Connor R, eds. brane of the retina and Bruch's membrane as a Immunology and Immunopathology of the Eye. New York: result of the digestion of outer segment containing Masson, 1979. phagosomes by the retinal pigment epithelium.34 5Marak GE, Font RL, Zimmerman LE. Histologic variations Our understanding of the pathogenesis of the related to race in sympathetic ophthalmia. Am J Ophthalmol pigment-containing cells in 1974;78:935-38. epithelioid sympathetic 6Easom HA, Zimmerman LE. Sympathetic ophthalmia and ophthalmia is uncertain. Recent evidence suggests bilateral phacoanaphylaxis. Arch Ophthalmol (1964) ;72: that the hypothesis that the pigment-containing 9-15. epithelioid cells in sympathetic ophthalmia represent 7Fuchs T. Concerning sympathetic ophthalmia (including modified uveal melanocytes may be considered remarks about serous traumatic iritis). Albrecht von as Graefes Arch Klin Ophthalmol
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