Brit. J. Ophthal. (1976) 6o, 614

Unsuspected fungal endophthalmitis diagnosedin vitrectomy specimen

BARBARA PERINA, GEORGE H. KURZ, AND RAINER N. MITTLFrom the Department of Ophthalmology, New York University Medical Center

Mycotic infections of the eye, as in other areas ofthe body, have been increasing. Nearly I00 differentfungal species have been reported in ocular infection(Jones, 1975). This trend has been attributed tomany factors including the use of corticosteroidsand antibiotics and also to conditions causingdecreased host resistance (Anderson, Roberts,Gonzalez, and Chick, I959; Veirs and Davis, I958;Rheins, Suie, Van Winkle, and Havener, I966;Ley and Sanders, I956; Fran9ois and Rysselaere,1972; Wolter, I962).The observation of multiple septate hyphae in

the microscopical examination of a vitrectomyspecimen from a patient in whom endophthalmitiswas not suspected before surgery prompted thepresent report. To our knowledge this is the firstaccount of mycotic endophthalmitis diagnosed frommaterial obtained by vitrectomy.

Report of a caseA 47-year-old White man with diabetes mellitus andmild congestive heart failure had an ocular historywhich included advanced diabetic retinopathy, recentvitreous haemorrhage, and neovascular glaucoma. Theglaucoma was controlled medically and with penetratingcyclodiathermy of the left eye in November I972. A mildanterior segment reaction followed this procedure andwas treated intermittently with topical corticosteroidsuntil January 1974.On examination in January I974, the vision was

right eye: hand movements, and left eye: perception oflight with projection. The right eye had rubeosis iridisand proliferative diabetic retinopathy. In the left eyethere were minor areas of rubeosis, cataractous changesof the lens, and a dense vitreous haemorrhage. Thefundus could not be seen. Ultrasound study of the lefteye revealed relatively dense opacities and membraneswithin the vitreous. Vitrectomy was suggested for theleft eye and performed in July 1974, using the roto-extractor (Douvas, I975).During the procedure a peculiar dense-white rubbery

substance was encountered in multiple areas of thevitreous cavity. Some of this material was submitted tothe pathology laboratory. Microscopical examinationrevealed patches of proteinaceous exudate with large

Address for reprints: Barbara Perina, MD, Department of Oph-thalmology, New York University-Bellevue Medical Center,New York, New York xooI6, USA

numbers of closely packed septate fungal hyphae(Figs I and 2). A few mycotic granules were observed(Figs I and 3). These were considered suggestive, but notdiagnostic of coccidioidomycosis. Scattered lymphocyteswere noted in some areas in association with the hyphae(Figs 2 and 4). Cultures for fungi were not done.

After this unexpected finding, the patient was put inhospital for a complete medical examination. He deniedhaving any systemic symptoms, and his diabetes andcongestive failure were well under control. He deniedpast or present ocular pain and the general physicalexamination was unremarkable except for moderateobesity. On examination of the eyes the vision was righteye: perception of light; left eye: no perception of light.Intraocular pressure was right eye I6 and left eye zeroby applanation. The right eye had otherwise remainedessentially unchanged since January 1974. In the lefteye the lids and adnexa were normal. There was markedinjection of the conjunctiva, mild microcystic oedemaof the comea, and an organizing haemorrhage involvingapproximately go per cent of the anterior chamber.These findings had been present since the vitrectomy.The blood in the anterior chamber prevented furtherexamination of the eye.

In an attempt to find a possible source of the fungalinfection, extensive laboratory studies were done inaddition to the medical examination. Complete bloodcount, urine analysis, and blood cultures were negative.Serum profile was normal except for a raised level ofglucose. Conjunctival cultures were negative for fungi.Anterior chamber and vitreous taps were not done. Skintests for histoplasmosis and coccidioidomycosis werenegative. Chest, skull, and sinus x-rays showed noabnormalities. A liver scan revealed an enlarged spleenfor which no explanation was found. Microscopical slidesfrom the vitrectomy were reviewed by several mycolo-gists, but the species of fungus could not be positivelyidentified.During the patient's stay in hospital no evidence of

fungal infection could be found elsewhere in the bodyand two years later he was healthy without systemiccomplaints. The left eye was phthisical. A follow-upmedical examination failed to reveal any coccidioidallesions.The patient's record for the two years before the

vitrectomy showed no sign of endophthalmitis, althoughhe had been examined by numerous ophthalmologistsduring the period. An infection of the extemal ocularstructures, specifically corneal ulcer, was never present.There was no history of accidental trauma. The cyclodia-thermy, which was followed by a mild anterior segment

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Unsuspected fungal endophthalmitis 6x5

FIG. I Matted hyphae (H),surrounding patches of proteinaceousexudate (E). Mycotic granule (G).Haematoxylin and eosin. x 35

FIG. 2 Densely packed septatehyphae with scattered lymphocytesExudate (E).Haematoxylin and eosin. X 224

reaction, preceded the vitrectomy by 2o months. Fungalendophthalmitis after cyclodiathermy has not beenreported to our knowledge. We believe it unlikely,although not inconceivable, that the fungi gainedentrance to the eye at the time of the cyclodiathermy inthis case.

DiscussionThe hyphae encountered in the microscopical

sections are believed to reflect the true diseaserather than a contaminant for the following reasons:their presence on all slides of this case; theirintimate association with the eosinophilic exudate;their large number; absence of fungal contamina-tion of other cases concurrently processed in thelaboratory; the presence of mycotic granules; thepresence of lymphocytes, and the unusual densityand difficulty cutting the membranes encountered

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6i6 British Yournal of Ophthalmology

FIG. 3 Mycotic granule (G) amidmultiple septate hyphae.Haematoxylin and eosin. X 224

FIG. 4 Scattered lymphocytes inproteinaceous exudate. Smallnumber of hyphae (H).Haematoxylin and eosin. X 224

during surgery, making the procedure much longerthan anticipated.

Intraocular infections caused by fungus (McClean,I963) may result from:

i. Direct invasion of the external ocular struc-tures with resulting fungal conjunctivitis,fungal keratitis, and fungi in the lacrimalpassages. Infection may then spread to deepertissues.

2. Extension from neighbouring areas, such asthe skin of the face, nasopharynx or sinus,extending into the orbit.

3.Exogenous route: or direct introduction intra-ocularly, either traumatic or surgical, mostcommonly after cataract surgery.

4. Endogenous route: or haematogenous route.This may be considered in cases in whichthere is no infection of the cornea or adnexa

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Unsuspected fungal endophthalmitis 617

and there is no history of ocular surgery ortrauma. It may be subdivided into two types:A. Ocular involvement with an overt source.B. Ocular involvement with an occult source.

Oculomycosis, as a complication of intraocularsurgery (Theodore, Littman, and Almeda, I96I;I962) and traumatic injury (Fine and Zimmerman,I959), is being recognized with increasing fre-quency. Endogenous endophthalmitis is lessfrequently recognized (Bonatti, Jaeger, and Frayer,I963; Harley and Mishler, I959). Our case appearsto fall into the last category: endogenous intraocularinfection without apparent systemic involvement.

Intraocular infections caused by coccidioido-mycoses have been reported as cases of uveitis andchorioretinitis (Francois and Rysselaere, 1972). In1958, a case was presented of a patient with general-ized coccidioidomycosis with a granulomatous uveitis(Brown, Kellenberger, and Hudson, 1958). Histo-pathological examination revealed granulomatousinflammatory nodules in the iris and ciliary body.These nodules contained giant cells with spherules,surrounded by an infiltrate of lymphocytes, plasmacells, and epithelioid cells. Another interesting caseof iridocyclitis with iris nodules was reported inI967 (Pettit, Learn, and Foos, I967). Cultures ofaqueous grew Coccidioides immitis. Of note in thiscase is that there was no evidence of disseminatedcoccidioidomycosis.

Iris nodules were not noted clinically in ourpatient before the vitrectomy. After that procedurethe patient had almost a total hyphaema, and theiris could not be visualized.Endogenous intraocular infection due to fungi

was considered very rare I5 to 20 years ago. Harleyand Mishler (I959) pointed out that only I4 suchcases had been reported in the literature and addedone case of their own. Fungi were grown from a

systemic site in only one of these cases. In morerecent years these infections are being reportedmore frequently. Freeman, Davis, and Maclean(I974) reviewed the literature on Candida endoph-thalmitis. There were 49 cases and all were reportedduring the io-year period I962-72. Systemicinvolvement was found in I4 patients and wasquestionable in 5; 30 had no evidence of systemicfungal involvement. Ocular symptoms were presentin most of the cases. Naidoff and Green (1975)reviewed the literature on I7 patients reported withendogenous Aspergillus endophthalmitis. Fourteenof i6 on whom this information was available hadsome underlying predisposing disease. Ocularsymptoms were present in most of the patients.The most common cause of endogenous fungal

endophthalmitis today are the Candida species,followed by the genus Aspergillus. Some patientswith infections secondary to Candida, Aspergillus,or other mycotic organisms do not have rapidlyfatal diseases and may even be asymptomatic. Aspointed out recently in the literature, some of theearlier reported cases in which no systemic sourcewas identified, as well as our present case, un-doubtedly fit into this category.

Summary

A vitrectomy specimen obtained with the roto-extractor from a diabetic patient with vitreoushaemorrhage revealed fungal endophthalmitis onmicroscopical examination. Endophthalmitis wasnot suspected before the procedure. Extensivemedical examinations failed to reveal any evidenceof systemic fungal disease. The case exemplifiesendogenous mycotic endophthalmitis of occultorigin, the first of its kind, we believe, to bediagnosed in this manner.

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SpringfieldFREEMAN, J. B., DAVIS, P. L., and MACLEAN, L. D. (1974) Arch. Surg., I08, 237HARLEY, R. D., and MISHLER, J. E. (I959) Trans. Amer. Acad. Ophthal. Otolaryng., 63, 264JONES, B. R. (I975) Ibid., 79, I5LEY, A. P., and SANDERS, T. E. (1956) Arch. Ophthal., 56, 257MCCLEAN, J. M. (1963) Amer. Y. Ophthal., 56, 537NAIDOFF, M. A., and GREEN, W. G. (1975) Ibid., 79, 502PETTIT, T. H., LEARN, R. N., and FOOS, R. Y. (1967) Arch. Ophthal., 77, 655RHEINS, M. S., SUIE, T., VAN WINKLE, M. G., and HAVENER, W. H. (1966) Brit. J. Ophthal., 50, 533THEODORE, F. H., LITTMAN, M. L., and ALMEDA, E. (1961) Arch. Ophthal., 66, 163

I -, and (I962) Amer. J. OP/hthal, 53, 35VEIRS, E. R., and DAVIS, C. T. (I958) Arch. Ophthal., 59, 172WOLTER, J. R. (I962) Ibid., 68, 337

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