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Relationship Between Mycoplasma (PPLO) and Eye Disease
VOL. 64, NO. 2
289
DISSEMINATED COCCIDIOIDOMYCOSIS
8. Levitt, J. M. : Ocular manifestations in coccidioidomycosis. Am. J. Ophth. 31:1626, 1948. 9. Conan, N. J., Jr. and Hyman, G. A. : Dis seminated coccidioidomycosis : Treatment with protoanemonin. Am. J. Med. 9:408, 1950. 10. Lovekin, L. G. : Coccidioidomycosis : Re port of a case with intraocular involvement. Am. J. Ophth. 34:621, 1951. 11. Brown, W. C, Hudson, K. E. and Nisbet, A. A. : Pulmonary coccidioidomycosis associated with Jensen's disease. Am. J. Ophth. 43:965, 1957. 12. Brown, W. C., Kellenberger, R. E. and Hud son, K. E. : Granulomatous uveitis associated with disseminated coccidioidomycosis. Am. J. Ophth. 45:102, 1958. 13. Huntington, R. W. : Personal communication. Errors in clinical diagnosis of fatal coccidioido mycosis, March, 1966. 14. Welch, H. : A Guide to Antibiotic Therapy. New York, Medical Encyclopedia, 1959, p. 11. 15. Skipworth, G. B., Bergin, J. J. and Williams, R. M. : Coccidioidal granulomas of skin and con-
junctiva treated with intravenous amphotericin B. Arch. Dermat. 82:605, 1960. 16. Hinshaw, H. C. and Garland, L. H. : Dis eases of the Chest. Philadelphia, Saunders, 1963, ed. 2, p. 657. 17. Butler, W. T. : Pharmacology, toxicity and therapeutic usefulness of amphotericin B. JAMA, 195:126, 1966. 18. Foster, J. B., Almeda, E., Littman, M. L. and Wilson, M. E. : Some intraocular and conjunctival effects of amphotericin B in man and in the rabbit. Arch. Ophth. 60:555, 1958. 19. Green, W. R., Bennett, J. E. and Goos, R. D. : Ocular penetration of amphotericin B. : A re port of laboratory studies and a case report of postsurgical cephalosporium endophthalmitis. Arch. Ophth. 73 :769, 1965. 20. Faulkner, R. F. : Ocular coccidioidomyco sis: Report of a case of coccidioidal granuloma of the conjunctiva associated with cutaneous coc cidioidomycosis. Am. J. Ophth. 53:822, 1962.
RELATIONSHIP BETWEEN MYCOPLASMA (PPLO) AND EYE
DISEASE
A NEGATIVE REPORT S T E P H E N J. M I L L I A N , P H . D . , I R V I N G H . LEOPOLD, M.D., S.
STANLEY SCHNEIERSON,
AND
M.D.
New York T h e etiology of uveitis, as well as that of a number of other inflammatory ophthalmologic diseases, usually has not been es tablished despite intensive bactériologie, my cologie and virologie investigation. I n an at tempt to elucidate this problem, a study was undertaken to establish or exclude the possi ble contributory role of Mycoplasma (pleuropneumonialike organisms [ P P L O ] ) in this regard, particularly since the human pa thogenic potential of one Mycoplasma has been clearly established in the case of atypi cal pneumonia. T h e existence of some relationship be tween pleuropneumonialike organisms and uveitis was reported by Holland and W o r l ton 1 who obtained seven positive prostatic Mycoplasma cultures in a series of 13 pa tients with uveitis and one with chorioretinFrom the Departments of Microbiology and Ophthalmology, The Mount Sinai Hospital, and the Bureau of Laboratories, New York City De partment of Health.
itis. Five of the positive patients were treated with tetracycline, an antibiotic highly active against Mycoplasma, with subsequent eradi cation of the positive prostatic cultures and coincident clinical improvement of the ocu lar disease. I n view of these findings, the authors suggested a possible mechanism of hypersensitivity in nongranulomatous uvei tis, triggered by the release of antigen from P P L O harbored asymptomatically in the genito-urinary tract. Later Holland 2 report ed three positive conjunctival cul-de-sac iso lations of Mycoplasma in 25 patients with simple conjunctivitis as compared to no pos itive isolates in patients seen only for re fractive errors. A r m and associates 3 have recently report ed the double recovery of an undesignated species of Mycoplasma from the eye of a five-year old Chinese child with conjunctivi tis, first in the acute stage and later after the inflammation was no longer present. These Mycoplasma eye isolations, however,
290
AMERICAN JOURNAL OF OPHTHALMOLOGY
do not necessarily indicate etiologic signifi cance since Mycoplasma can be recov ered from the normal oropharynx and genito-urinary tract where they constitute part of the normal flora4 and accidental eye contamination from these sources is well within the realm of probability. MATERIALS AND METHODS
A total of 382 eye cultures, specifically directed toward isolation of Mycoplasma, was performed on a series of 146 patients of one of us (I. H. L.) afflicted with a wide variety of inflammatory and noninflamma tory eye diseases. Included were uveitis (10 patients), conjunctivitis, blepharitis, keratitis, chorioretinitis, glaucoma, diabetic retinopathy, cataracts and refractive errors, as well as a number of other pathologic eye con ditions. Separate cultures were taken from both the involved and uninvolved eye. A num ber of follow-up cultures after subsidence of the acute phase were also included. The culture medium employed, which is specially formulated for the growth of My coplasma, had the following composition : PPLO broth or agar (Baltimore Biological Laboratories) Horse serum, uninactivated 10% yeast extract (Fleischman's Pure Dry Yeast 20-40) Penicillin, 1000 units/ml Thallium Acetate, 1:2000 Amphotericin B, S μg/ml pH adjusted to 7.4
7 parts 2 parts 1 part
Conjunctival swab or sterile platinum loop specimens or corneal scrapings were immersed in a screw-capped tube containing 2.0 ml of P P L O broth and held at 4°C until transported to the laboratory. Elapsed time before subinoculation never exceeded 36 hours. Upon receipt in the laboratory, 0.2 ml of the transport broth, after express ing the swab, was inoculated directly upon the surface of each of two P P L O agar plates. One was placed in a plastic bag to minimize drying and incubated under aero bic conditions, while the other was incubated in an atmosphere containing 5% C 0 2 in air.
AUGUST, 1967
All agar plates were maintained at 35°C and carefully examined microscopically (X100 magnification) for growth at threeto five-day intervals for a period of four weeks. Subcultures of questionable plates were made by agar block transfer onto new plates, which were then similarly incubated and observed for four weeks. The original transport tubes containing the eye swabs in P P L O broth were kept at 35°C for five days and then subcultured upon agar plates as already described. RESULTS
No positive Mycoplasma isolate was ob served in any of the 382 cultures performed as described. Based upon these negative find ings, no direct relationship between Myco plasma and eye disease could be established. The failure to obtain any positive isolates from the uninvolved eyes further indicates that these micro-organisms do not represent a constituent of the normal resident flora of the conjunctiva. The absence of any positive isolations in this study cannot be attributed to defects in any of the batches of medium employed since each batch on preparation was routine ly tested for its capability to support growth of a complete spectrum of prototype Myco plasma strains. Furthermore, the same batches were employed in a study of the va ginal Mycoplasma flora that was being car ried out at the same time, which yielded a large number (30-40%) of positive isolates from the latter source. In an additional effort to assess the possi ble etiologic role of Mycoplasma, paired acute and interval sera were obtained from 10 randomly selected patients, including a number with uveitis. These were titrated for antibodies against a variety of Mycoplasma, including M. hominis 1, M. hominis 2, M. orale, M. salivarium and M. fermentans, by means of the hemagglutination inhibition procedure. No significant rise in titer be tween any of the interval sera against any of the test Mycoplasma species was observed
VOL. 64, NO. 2
MYCOPLASMA AND EYE DISEASE
so that Mycoplasma involvement could not be demonstrated by either sérologie or cul tural means.
291
resident microbial flora of the normal con junctiva. Fifth Avenue and 100th Street (10029)
SUMMARY
REFERENCES
Special cultures for Mycoplasma per formed upon 382 specimens obtained from involved and uninvolved eyes of patients with a wide variety of inflammatory and noninflammatory ocular diseases failed to yield a single positive isolate. Failure to ob tain positive Mycoplasma cultures from any of the uninvolved eyes is an indication that these organisms are not constituents of the
1. Holland, M. C. and Worlton, J. T., J r : Relation ship of pleuropneumonialike organisms and uveitis. Am. J. Ophth. 43:597, 1957. 2. Holland, M. C. : Uveitis and pleuropneumo nialike organisms. Ann N. Y. Acad. Sei. 79:646, 1960. 3. Arm, H. G., Woolridge, R. L., Cheng, K-H. and Chang, I-H. Isolation of Mycoplasma orga nisms (PPLO) from the human eye. Am. J. Ophth. 62:1125, 1966. 4. Hayflick, L. and Chanock, R. M. : Mycoplas ma species of man. Bact. Rev. 29:185, 1965.
F U R T H E R E X P E R I E N C E W I T H P O S T E R I O R LAMELLAR RESECTION O F T H E CORNEA FOR E P I T H E L I A L I M P L A N T A T I O N CYST H.
SAUL SUGAR,
M.D.
Detroit, Michigan
In 1962, a method of removal of epithelial implantation cysts after cataract extraction was described and its successful use in one case was reported.1 Since then two similar cases have been seen and were successfully treated surgically. A fourth case, following a perforating injury of the cornea in a phakic eye, resulted in an expulsive hemor rhage immediately before completion of ex cision of the cyst attached to the posterior corneoscleral layer. It was found that the cyst might have been incompletely removed. The purpose of this paper is to report these cases and suggest the possible usefulness of the operative technique in removal of small tumors of the iris or ciliary body and in early epithelial downgrowth, as well as to point out the absence of significant epithelial edema and bullous keratopathy in the area of lamellar corneal resections in the cases in which the technique has been successfully used. Many instances of successful treatment of epithelial implantation cyst by other
means have been reported, including a con siderable number removed by iridectomy.1 Some of these have recurred; others have been removed in fragments. Maumenee2'3 and Tjanides and associates4 successfully combined iridectomy and curettage of the involved cornea in epithelial downgrowth following cataract extraction. X-ray therapy of these cysts has been de scribed as arresting the continual growth of
From Wayne State University School of Medicine and Sinai Hospital of Detroit.
Fig. 1 (Sugar). Case 1. Cyst in iris as it appeared in 1961.
289
DISSEMINATED COCCIDIOIDOMYCOSIS
8. Levitt, J. M. : Ocular manifestations in coccidioidomycosis. Am. J. Ophth. 31:1626, 1948. 9. Conan, N. J., Jr. and Hyman, G. A. : Dis seminated coccidioidomycosis : Treatment with protoanemonin. Am. J. Med. 9:408, 1950. 10. Lovekin, L. G. : Coccidioidomycosis : Re port of a case with intraocular involvement. Am. J. Ophth. 34:621, 1951. 11. Brown, W. C, Hudson, K. E. and Nisbet, A. A. : Pulmonary coccidioidomycosis associated with Jensen's disease. Am. J. Ophth. 43:965, 1957. 12. Brown, W. C., Kellenberger, R. E. and Hud son, K. E. : Granulomatous uveitis associated with disseminated coccidioidomycosis. Am. J. Ophth. 45:102, 1958. 13. Huntington, R. W. : Personal communication. Errors in clinical diagnosis of fatal coccidioido mycosis, March, 1966. 14. Welch, H. : A Guide to Antibiotic Therapy. New York, Medical Encyclopedia, 1959, p. 11. 15. Skipworth, G. B., Bergin, J. J. and Williams, R. M. : Coccidioidal granulomas of skin and con-
junctiva treated with intravenous amphotericin B. Arch. Dermat. 82:605, 1960. 16. Hinshaw, H. C. and Garland, L. H. : Dis eases of the Chest. Philadelphia, Saunders, 1963, ed. 2, p. 657. 17. Butler, W. T. : Pharmacology, toxicity and therapeutic usefulness of amphotericin B. JAMA, 195:126, 1966. 18. Foster, J. B., Almeda, E., Littman, M. L. and Wilson, M. E. : Some intraocular and conjunctival effects of amphotericin B in man and in the rabbit. Arch. Ophth. 60:555, 1958. 19. Green, W. R., Bennett, J. E. and Goos, R. D. : Ocular penetration of amphotericin B. : A re port of laboratory studies and a case report of postsurgical cephalosporium endophthalmitis. Arch. Ophth. 73 :769, 1965. 20. Faulkner, R. F. : Ocular coccidioidomyco sis: Report of a case of coccidioidal granuloma of the conjunctiva associated with cutaneous coc cidioidomycosis. Am. J. Ophth. 53:822, 1962.
RELATIONSHIP BETWEEN MYCOPLASMA (PPLO) AND EYE
DISEASE
A NEGATIVE REPORT S T E P H E N J. M I L L I A N , P H . D . , I R V I N G H . LEOPOLD, M.D., S.
STANLEY SCHNEIERSON,
AND
M.D.
New York T h e etiology of uveitis, as well as that of a number of other inflammatory ophthalmologic diseases, usually has not been es tablished despite intensive bactériologie, my cologie and virologie investigation. I n an at tempt to elucidate this problem, a study was undertaken to establish or exclude the possi ble contributory role of Mycoplasma (pleuropneumonialike organisms [ P P L O ] ) in this regard, particularly since the human pa thogenic potential of one Mycoplasma has been clearly established in the case of atypi cal pneumonia. T h e existence of some relationship be tween pleuropneumonialike organisms and uveitis was reported by Holland and W o r l ton 1 who obtained seven positive prostatic Mycoplasma cultures in a series of 13 pa tients with uveitis and one with chorioretinFrom the Departments of Microbiology and Ophthalmology, The Mount Sinai Hospital, and the Bureau of Laboratories, New York City De partment of Health.
itis. Five of the positive patients were treated with tetracycline, an antibiotic highly active against Mycoplasma, with subsequent eradi cation of the positive prostatic cultures and coincident clinical improvement of the ocu lar disease. I n view of these findings, the authors suggested a possible mechanism of hypersensitivity in nongranulomatous uvei tis, triggered by the release of antigen from P P L O harbored asymptomatically in the genito-urinary tract. Later Holland 2 report ed three positive conjunctival cul-de-sac iso lations of Mycoplasma in 25 patients with simple conjunctivitis as compared to no pos itive isolates in patients seen only for re fractive errors. A r m and associates 3 have recently report ed the double recovery of an undesignated species of Mycoplasma from the eye of a five-year old Chinese child with conjunctivi tis, first in the acute stage and later after the inflammation was no longer present. These Mycoplasma eye isolations, however,
290
AMERICAN JOURNAL OF OPHTHALMOLOGY
do not necessarily indicate etiologic signifi cance since Mycoplasma can be recov ered from the normal oropharynx and genito-urinary tract where they constitute part of the normal flora4 and accidental eye contamination from these sources is well within the realm of probability. MATERIALS AND METHODS
A total of 382 eye cultures, specifically directed toward isolation of Mycoplasma, was performed on a series of 146 patients of one of us (I. H. L.) afflicted with a wide variety of inflammatory and noninflamma tory eye diseases. Included were uveitis (10 patients), conjunctivitis, blepharitis, keratitis, chorioretinitis, glaucoma, diabetic retinopathy, cataracts and refractive errors, as well as a number of other pathologic eye con ditions. Separate cultures were taken from both the involved and uninvolved eye. A num ber of follow-up cultures after subsidence of the acute phase were also included. The culture medium employed, which is specially formulated for the growth of My coplasma, had the following composition : PPLO broth or agar (Baltimore Biological Laboratories) Horse serum, uninactivated 10% yeast extract (Fleischman's Pure Dry Yeast 20-40) Penicillin, 1000 units/ml Thallium Acetate, 1:2000 Amphotericin B, S μg/ml pH adjusted to 7.4
7 parts 2 parts 1 part
Conjunctival swab or sterile platinum loop specimens or corneal scrapings were immersed in a screw-capped tube containing 2.0 ml of P P L O broth and held at 4°C until transported to the laboratory. Elapsed time before subinoculation never exceeded 36 hours. Upon receipt in the laboratory, 0.2 ml of the transport broth, after express ing the swab, was inoculated directly upon the surface of each of two P P L O agar plates. One was placed in a plastic bag to minimize drying and incubated under aero bic conditions, while the other was incubated in an atmosphere containing 5% C 0 2 in air.
AUGUST, 1967
All agar plates were maintained at 35°C and carefully examined microscopically (X100 magnification) for growth at threeto five-day intervals for a period of four weeks. Subcultures of questionable plates were made by agar block transfer onto new plates, which were then similarly incubated and observed for four weeks. The original transport tubes containing the eye swabs in P P L O broth were kept at 35°C for five days and then subcultured upon agar plates as already described. RESULTS
No positive Mycoplasma isolate was ob served in any of the 382 cultures performed as described. Based upon these negative find ings, no direct relationship between Myco plasma and eye disease could be established. The failure to obtain any positive isolates from the uninvolved eyes further indicates that these micro-organisms do not represent a constituent of the normal resident flora of the conjunctiva. The absence of any positive isolations in this study cannot be attributed to defects in any of the batches of medium employed since each batch on preparation was routine ly tested for its capability to support growth of a complete spectrum of prototype Myco plasma strains. Furthermore, the same batches were employed in a study of the va ginal Mycoplasma flora that was being car ried out at the same time, which yielded a large number (30-40%) of positive isolates from the latter source. In an additional effort to assess the possi ble etiologic role of Mycoplasma, paired acute and interval sera were obtained from 10 randomly selected patients, including a number with uveitis. These were titrated for antibodies against a variety of Mycoplasma, including M. hominis 1, M. hominis 2, M. orale, M. salivarium and M. fermentans, by means of the hemagglutination inhibition procedure. No significant rise in titer be tween any of the interval sera against any of the test Mycoplasma species was observed
VOL. 64, NO. 2
MYCOPLASMA AND EYE DISEASE
so that Mycoplasma involvement could not be demonstrated by either sérologie or cul tural means.
291
resident microbial flora of the normal con junctiva. Fifth Avenue and 100th Street (10029)
SUMMARY
REFERENCES
Special cultures for Mycoplasma per formed upon 382 specimens obtained from involved and uninvolved eyes of patients with a wide variety of inflammatory and noninflammatory ocular diseases failed to yield a single positive isolate. Failure to ob tain positive Mycoplasma cultures from any of the uninvolved eyes is an indication that these organisms are not constituents of the
1. Holland, M. C. and Worlton, J. T., J r : Relation ship of pleuropneumonialike organisms and uveitis. Am. J. Ophth. 43:597, 1957. 2. Holland, M. C. : Uveitis and pleuropneumo nialike organisms. Ann N. Y. Acad. Sei. 79:646, 1960. 3. Arm, H. G., Woolridge, R. L., Cheng, K-H. and Chang, I-H. Isolation of Mycoplasma orga nisms (PPLO) from the human eye. Am. J. Ophth. 62:1125, 1966. 4. Hayflick, L. and Chanock, R. M. : Mycoplas ma species of man. Bact. Rev. 29:185, 1965.
F U R T H E R E X P E R I E N C E W I T H P O S T E R I O R LAMELLAR RESECTION O F T H E CORNEA FOR E P I T H E L I A L I M P L A N T A T I O N CYST H.
SAUL SUGAR,
M.D.
Detroit, Michigan
In 1962, a method of removal of epithelial implantation cysts after cataract extraction was described and its successful use in one case was reported.1 Since then two similar cases have been seen and were successfully treated surgically. A fourth case, following a perforating injury of the cornea in a phakic eye, resulted in an expulsive hemor rhage immediately before completion of ex cision of the cyst attached to the posterior corneoscleral layer. It was found that the cyst might have been incompletely removed. The purpose of this paper is to report these cases and suggest the possible usefulness of the operative technique in removal of small tumors of the iris or ciliary body and in early epithelial downgrowth, as well as to point out the absence of significant epithelial edema and bullous keratopathy in the area of lamellar corneal resections in the cases in which the technique has been successfully used. Many instances of successful treatment of epithelial implantation cyst by other
means have been reported, including a con siderable number removed by iridectomy.1 Some of these have recurred; others have been removed in fragments. Maumenee2'3 and Tjanides and associates4 successfully combined iridectomy and curettage of the involved cornea in epithelial downgrowth following cataract extraction. X-ray therapy of these cysts has been de scribed as arresting the continual growth of
From Wayne State University School of Medicine and Sinai Hospital of Detroit.
Fig. 1 (Sugar). Case 1. Cyst in iris as it appeared in 1961.