Serologic Studies of Presumed Histoplasmic Choroiditis1

RETINAL HOLES AND TEARS

1059

REFERENCES

1. Schepens, C. L., and Marden, D. : Data on the natural history of retinal detachment: 1. Age and sex relationships. Arch. Ophth., 66:631-642 (Nov.) 1961. 2. Duke-Elder, S. : Textbook of Ophthalmology. London, Kimpton, 1947, v. 3, pp. 2864-2921. 3. Dunnington, J. EL, and Macnie, T. P. : Detachment of the retina : Operative results in 164 cases. Arch. Ophth., 18:532-539, (Oct.) 1937. 4. Huerkamp, B., Leidig, L., and Klomp, G. : Bedeutung der Begleitsymptome bei ein-und beidseitiger Ablatio retinae. Graefes Arch. Ophth., 155 :556-566, 1954. 5. Schiff-Wertheimer, S., Jonqueres, J., and Jarry, C. : Le décollement rétinien des jeunes myopes: Symptomatologie et prognostic. Ann. Oculist. (Paris), 182:13-23 (Jan.) 1949. 6. Fundar, W. : Das 'Schicksal der einseitig an Netzhautabhebung Erblindeten. Klin. Mbl. Augenh., 129 :330-335, 1956. 7. Everett, W. G. : The fellow eye syndrome in retinal detachment. Am. J. Ophth., 56:739-748 (Nov.) 1963. 8. Lister, A. : Scierai resection in the treatment of retinal detachment. Trans, ophth. Soc. Aust, 11 : 57-77, 1952. 9. Arruga, H. : Symposium on Retinal Detachments : Home Study Course. Am. Acad. Ophth. Otolaryng., 1955. 10. Colyear, B. H., Jr., and Piscbel, D. K. : Clinical tears in the retina without detachment. Am. J. Ophth., 41:773 (May) 1956. 11. Smith, T. R., and Pierce, L. H. : Idiopathic detachment of the retina: Analysis of results. Arch. Ophth., 49:36-44 (Jan.) 1953. 12. McDonald, P. R. : Retinal detachment surgery. Am. J. Ophth., 50:1247 (Dec.) 1960.

SEROLOGIC STUDIES OF PRESUMED HISTOPLASMIC T E D S U I E , P H . D . , M E L V I N S. R H E I N S , P H . D . ,

A N D T O R R E N C E A.

CHOROIDITIS* MAKLEY, JR.,

M.D.

Columbus, Ohio I n recent years Histoplasma capsulatum has been incriminated as a causative agent of naturally occurring chorioretinitis on the basis of circumstantial and clinical evidence. 1 T h e typical appearance of the peripheral and central fundus lesions, 2 positive histoplasmin skin test and calcifications in the lung field have been used as the criteria for clinically diagnosing this type of chorioretinitis as being caused by this organism (table 1 ) . Most of these individuals also show an anergy to tuberculin. W h e t h e r the pathogenesis is dependent upon an infectious mechanism or a hypersensitivity (or both) is not known. T h e organism has never been isolated from the eye nor demonstrated in histopathologic sections of the uveal tract. In an attempt to gain additional information on this problem we have inves* From the Department of Ophthalmology, Ohio State University. This investigation was supported in part by a grant from the Ohio Tuberculosis and Health Association.

tigated the sérologie aspects of this inflammation. M A T E R I A L AND M E T H O D S

Sera from individuals with clinically diagnosed histoplasmic chorioretinitis, as well as from patients having other uveal tract disease, were obtained prior to skin testing with histoplasmin and other antigens used in our uveitis survey. T h e two immunologie procedures employed were (1) the complement-fixation test utilizing both the yeastphase antigen and the histoplasmin antigen and (2) the collodion agglutination test. 3 RESULTS

Table 2 presents the findings of the complement-fixation test. It is interesting to note that with the yeast-phase antigen approximately the same number of individuals from both groups, that is, the histoplasmic cases and the nonhistoplasmic cases, showed the same percentage of reactive and non-

1060

TED SUIE, MF.LVTN S. RTIETNS AND TORRENCE Λ. MAKLEY, JR. TABLE 1 COMPARATIVE DATA OF CLINICAL FINDINGS IN INDIVIDUALS WITH PRESUMED HISTOPLASMIC CHORIORETINITIS WITH THOSE HAVING OTHER UVEAL TRACT DISEASE Typical Histoplasmic Chorioretinal Lesion

Presumed histoplasmic chorioretinitis (79 cases)

100%

Uveal tract disease excluding presumed histoplasmic chorioretinitis (109 cases)

0%

( + + +to+ + + + )

Calcifications in Lung Fields

100% (94%)*

81% (90%)

36% (25%)

56% (54%)

Histoplasmin Skin Reactivity

* Figures in parentheses included to compare our findings with those obtained by Van Metre and Maumenee.5 Thirty percent of the consecutively studied patients with uveal tract disease were diagnosed as5 having presumed histoplasmic chorioretinitis; this compares with 25% found by Van Metre and Maumenee from a total of 251 consecutively studied patients with uveal disease. reactive results. However, with the histoplasmin antigen there was a definite increase in the number of positive titers in the histoplasmic group as compared with the control or nonhistoplasmic individuals. Table 4 shows the results with the collodion agglutination tests. Only four patients in the histoplasmic group showed suspicious or positive titers as compared with only six individuals in the control group. DISCUSSION

Antibodies detected by the complementfixation test tend to rise slowly during the early stages of infection and remain elevated usually for months or even several years. The antibodies detected by the collo-

dion agglutination test, on the other hand, often rise rapidly during the early phases of the infection, but frequently return to low titers by the third month of the disease. Generally, the yeast-phase antigen used in the complement-fixation test reacts to a high titer with serum from a new or very active disease as contrasted to the histoplasmin antigen used in the same test which generally reacts with higher titers during a chronic or waning disease. Table 2 shows the distribution of reactive titers using the complementfixation test according to the test antigens. W i t h the yeast-phase antigen, the titers were fairly evenly distributed in both groups of patients, while with the histoplasmin antigen the majority of the reactive

TABLE 2 RESULTS OF HISTOPLASMA COMPLEMENT FIXATION TESTS

Yeast-Phase Antigen Titers Suspected histoplasmic chorioretinitis (34 cases)

Uveal tract disease excluding histoplasmic uveitis (78 cases)

1:128 or above (practically diagnostic) (0/34)0%

1:4 or below (nonreactive)

1:8 or 1:16 (suggestive)

(17/34)50%

(15/34)44%

1:32 or 1:64 (highly suggestive) (2/34)6%

(51/78)65%

(27/78)35%

(0/34) 0 %

(0/34)0%

Histoplasmin Antigen Suspected histoplasmic chorioretinitis (34 cases)

(17/34)50%

(15/34)44%

(2/34) 6 %

(0/34)0%

Uveal tract disease excluding h istoplasmic uveitis ( 78 cases )

(74/78)95%

(4/78)5%

(0/78)0%

(0/34)0%

HISTOPLASMIC

CHOROIDITIS

1061

TABLE 3 COMPLEMENT-FIXATION RESULTS INDICATING REACTIVITY WITH EITHER YEAST-PHASE ANTIGEN OR HISTOPLASMIN ANTIGEN

Nonreactive (0 to 1/4 titer)

Reactive (1/8 or above titer)

Presumed histoplasmic chorioretinitis (35 patients)

(11/34)32%

(23/34)68%

Uveal tract disease excluding presumed histoplasmic chorioretinitis (78 patients)

(48/78)62%

(30/78) 38%

titers occurred with sera tested from individuals with pesumed histoplasmic chorioretinitis. The significance of these findings in relationship to uveal tract disease is unknown as yet. If one considers reactive titers obtained with the complement-fixation test and disregards the antigen employed, then 68% of the presumed histoplasmic group showed reactive titers in their sera as compared to 38% of the control group (table 3). The collodion agglutination test for histoplasmosis was negative for 97% of the suspected cases of histoplasmic choroiditis and for 99% of those having other uveal tract disease. This finding would indicate that TABLE 4 RESULTS OF HISTOPLASMA COLLODION AGGLUTINATION TEST

39 cases of suspected histoplasmic chorioretinitis Negative 35 (88%) Suspicious 3 (9%) Positive _ 1 (3%) 164 cases of uveal tract disease excluding suspected histoplasmic chorioretinits Negative 158(97%) Suspicious 4 ( 2%) Positive 2 (1%)

this sérologie test would not be useful as a diagnostic procedure for this ocular inflammation. This might suggest that this ocular inflammation does not represent an acute or recent histoplasmic disease. Other possible explanations of these findings require further investigations. In summation, the data would indicate that, based on our group of patients, the best sérologie diagnostic procedure for presumed histoplasmic chorioretinitis at present would be the complement-fixation test using histoplasmin antigen. It must be stressed, however, that even in the individuals whose sera showed reactive titers, although generally low (1/8 to 1/16), this test only can be considered, at best, as supportive evidence for the disease. It is of interest to note that Falls and Giles4 reporting on the effects of amphotericin-B for the treatment of presumed histoplasmic choroiditis, found that individuals having insignificant histoplasmic complement fixation titers showed little response to this drug as compared to those patients having positive titers. 410 West 10th Avenue

(43210).

REFERENCES

1. Woods, A. C. : Endogenous Inflammations of the Uveal Tract. Baltimore, Williams & Wilkins, 1961, pp. 99-109. 2. Makley, T. A., Long, J. W., Suie, T., and Stephan, J. D. : Presumed histoplasmic chorioretinitis with special emphasis on present modes of therapy. T r . Am. Acad. Ophth. Otolaryng., in press. 3. Saslaw, S., and Carlisle, H. N. : Histoplasmin-latex agglutination test : II. Results with human sera. Proc. Soc. Exp. Biol. Med., 105:76, 1960. 4. Giles, C. L., and Falls, H . F. : Further evaluation of amphotericin-B in presumptive histoplasmosis chorioretinitis. Am. J. Ophth., 51 :S88-S98 (Apr.) 1961. 5. Van Metre, T. E., and Maumenee, E. A. : Specific ocular uveal lesions in patients with evidence of histoplasmosis. Arch. Ophth., 71:314-324 (Mar.) 1964.