Ophthalmologica, Basel 170: 13-21 (1975)
Yeasts in Banal External Ocular Inflammations „ A. R omano, E. Segal, R. Stein and E. E ylan Department of Ophthalmology (Head: Prof. R. Stein ), Chaim Sheba Medical Center, Tel Hashomer, and Department of Human Microbiology (Head: Prof. E. E ylan), Tel Aviv University, Medical School, Tel Aviv
There is ample evidence that in the last decades 'opportunistic' fungal ocular infections have been in a steady ascent. This is best documented in the ever growing number of reports on disastrous fungal corneal affec tions and fungal endophthalmitis. In contrast, reports or surveys on banal affections of the eye and its adnexa in which fungi arc the causative agents, have remained relatively scarce. This may be due to the fact that ophthalmologists are not duly aware of the possible etiological role of fungi in these affections, or that they do not regard a mycological examination as worth while because of the banality of the lesions. An other reason may be that in many places the necessary facilities and expert advice are missing. This is best evidenced by our own experience. Only after the Department of Human Microbiology had shown interest in the ophthalmological problems, and once a micro biological laboratory had been attached directly to the Eye Department, has pertinent information started to accumulate. This report deals with the incidence and etiological significance of yeasts isolated from eyes of patients suffering from various acute, subacute, chronic or recurrent inflammations of the outer eye or its adnexa. The incidence of yeasts in the conjunctival sac and lacrimal pathways of normal healthy eyes of 152 individuals of different age was investigated for com parative purposes.
The material consisted of 313 patients who were referred to the Eye Outpatient Department in the last 2Va years for consultation and eventual treatment. They had suffered for longer periods from inflammations of the outer eye which had not
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Material and Methods
14
R omano/S egal/S tein /E ylan
responded to the usual treatment with antibiotics and/or steroids. They were selected from a pool of patients with similar affections, because their history and the clinical aspect of their affection aroused suspicion of a fungal infection. 517 mycological examinations were done in this sample. At about the same time, a mycological investigation was performed of the con junctival sac and the lacrimal pathways of 304 normal eyes in 12 neonates up to 2 months, and 140 adults in the age of 18-70 years. These investigations fell into the time of the hot summer months. In both groups, material was taken from eyelids, conjunctiva, in cases of keratitis also from the cornea, and from the lacrimal pathways if there were signs of inflam mation. The material taken with sterile swabs was inoculated on Sabourad’s agar, supplemented with 500 mg chloramphenicol (but without cycloheximide). In specificcases, the material was also inoculated on potato dextrose and on yeast extract agar composed of 0.5°/» yeast extract, 3®/o glucose and 2fl/o agar. The cultures were incubated at 28 and at 37 °C. The species of the fungi were identified microscopically in accordance with the standard procedures as described by A jeix o et al. [1], C onant et al. [4], and L odder |9]. In cases of doubt about classification, use was made of other criteria (reproductive and physiological properties). In order to exclude airborne contamination, a finding was recorded only if the same fungus was isolated in more than one culture, and if controls remained sterile. In each case, cultures were made also for possible spontaneous bacterial and viral infections.
Out of a pool of 1,015 patients who suffered from longstanding infec tions of the outer eye and were referred for consultation to the Eye Department, 313 were selected for a mycological investigation because in these cases treatment with antibiotics and steroids had not only failed but had rather aggravated the situation, or bacteriological findings were inconclusive. In 53 of these 313 patients (17%) yeasts, and in 48 molds were iso lated. The molds will not be discussed in this report. The isolated yeasts (table I) were different Candida species in 48, Trichosporon in 2, Rhodotorula species in 2, and Rhodotorula mucilaginosa in one of these cases. This last case of a recalcitrant superficial punctate keratitis has already been reported elsewhere by us [11]. Table II shows that the yeasts were cultivated from various clinical entities and that there is no specific predilection site as far as different yeast species are concerned. Candida albicans was the most frequently encountered Candida species (in 17 of 48 cases). This is in accordance with data from other authors
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Results and Comment
Yeasts in Banal External Ocular Inflammations
15
Species
Number of patients
C. albicans C. guillermondii C. tropicalis C. pseudotropicalis C. krusei C. parapsilosis Rhodotorula mucilaginosa Rltodolorula not defined species Trichosporon not defined species
17 16 7 3 1 4 1 2 2
relating to findings from eye [8, 12, 15] as well as from other parts of the body [2, 3, 5, 10]. However, the relatively high incidence of Candida guillermondii, which, with 16 cases, occupied the second place was sur prising. Although it has been described as the causative agent of various extraocular diseases [4, 6], isolation of C. guillermondii from eyes was reported only by F rançois and R ysselaere [7] in a case of purulent conjunctivitis in a child, and by Y oshioka [14] in a case of keratomycosis. In our series of 7 patients with dacryocanaliculitis this species of Candida was encountered 5 times. Most of the cases of conjunctivitis alone, or in association with blepha ritis or keratitis, in which C. albicans was found, were characterized by a whitish sticky secretion in the lower fornix. In some of these patients, easily removable pseudomembranes were present. In one case, a small superficial ulcer was seen in the lower fornix. We have never seen the small yellowish spots in the conjunctiva described by F rançois and R ysselaere [7] as characteristic at the onset. But all our patients were late cases, already treated for weeks or months outside of the hospital. Nearly identical forms of conjunctivitis as seen with C. albicans, were found in cases where C. guillermondii or tropicalis were cultivated. The inflammation was of the more banal, catarrhal type in cases where C. subtropicalis or parapsilosis or Trichosporon were apparently the causative agents. In the 3 patients with keratoconjunctivitis, the corneae presented the picture of a superficial keratitis characterized by a diffuse staining of the superficial epithelial layer with fluorescein. These patients complained also of pains and photophobia.
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Table I. Isolated yeast species
R omano/S egal/S tein /E ylan
16
Clinical diagnosis
Species of isolated yeast
Number of patients
Chronic blepharitis
C. albicans C. guillermondii C. pseudotropicalis C. krusei C. parapsilosis
1 3 1 1 1
Chronic blepharoconjunctivitis
C. albicans C. guillermondii C. tropicalis C. pseudotropicalis Trichosporon species
7 4 3 1 2
Subacute, chronic or recurrent conjunctivitis
C. albicans C. guillermondii C. tropicalis C. parapsilosis Rhodotorula species
4 2 3 2 1
Chronic or recurrent keratoconjunctivitis
C. albicans C. tropicalis Rhodotorula species
1 1 1
Superficial punctate epithelial keratitis
C. albicans C. guillermondii C. pseudotropicalis C. parapsilosis Rhodotorula mucilaginosa
2 2 1 1 1
Dacryocanaliculitis
C. albicans C. guillermondii
2 5
The 7 cases of punctate, epithelial keratitis deserve a special mention. In these cases, the conjunctiva was almost not involved. The corneas exhibited lesions reminding those seen in epidemic keratoconjunctivitis or in Thygeson's keratopathy. Fine and coarse, grey epithelial opacities, round, oval or irregular in shape occupied chiefly the central cornea, some of them slightly prominent above the surface, some extending into the underlying Bowman's membrane. This resemblance with the above-men tioned entities explains why these patients were in the beginning treated with steroids. This treatment not only was of no avail but resulted mostly
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Table II. Inflammations of the outer eye in which yeast were isolated
17
in aggravation of the affection. Only after elimination of the yeasts, did the corneas clear up and only where deeper infiltrates had been present, slight nubeculae remained. The 7 cases of blepharitis in which yeasts were found, were of the seborrhoic type with exception of one who presented an ulcerative ble pharitis. The etiological role of the yeasts is open to question since after elimination of the yeasts, the disease relapsed in 6 of these cases though yeasts were no longer present. All patients in this series were in good general health. All were adults with the exception of one with bilateral keratoconjunctivitis who was a child. In no case were yeasts detected in other sites of the body; feces however, were not examined. Even in these more or less banal affections of the outer eye in which yeasts were isolated, treatment with antifungals had to be intensive, fre quent and prolonged in order to eliminate the yeasts, and to attain a cure. The antimycoticals employed in this series, were nystatin (Mycostatin®) and amphotericin B (Fungizone®) in form of eyedrops which were applied 6-8 times a day. Nystatin which has a very low solubility in water, was used as suspension in a concentration of about 1(),()()() U/ml which was increased up to 100,000 U/ml in resistant cases. The suspension has to be prepared every 2 or 3 days because of its low stability. Amphotericin B marketed in vials containing 50 mg of the drug as sterile lyophilized powder plus desoxycholate and a buffer, is dissolved in 10 ml of sterile distilled water - not in saline which causes precipitation - and 5°/o dex trose in water is added to make a final concentration of 0.3 %>. This solu tion is unstable too. The drops may be prepared too from a 3-percent commercial solution. Treatment with 5-fluorocytosin tried only recently, alone and in combination with other antibiotics proved very effective but our experience is still too small. While affections of the conjunctiva alone or associated with keratitis responded relatively fast to the treatment, the cases with punctate epithelial keratitis as described above, proved rather resistant and required a very prolonged treatment even when the concentration of the drugs was in creased. All cases of dacryocanaliculitis in which yeasts were the patho gens reacted favorably to the antimycotic therapy without necessitating curettage of the canaliculus. Only in one case had a concrement to be curetted. Antifungal treatment was stopped in all cases as soon as all clinical signs had disappeared, and at least two cultures had remained sterile.
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Yeasts in Banal External Ocular Inflammations
18
R omano/S egal/S tein /E ylan
Table III. Yeasts in normal eyes
Neonates < 2 months Adults > 1 6 years
Number of eyes
Isolated species
Number of positive cultures
Total
24 280
0 C. albicans C. guillermondii C. parapsilosis Rhodotorula Torulopsis
0 1 2 1 1 2
0
7
In about 30% of the cases, relapses occurred with reappearance of the same yeast species. They were treated in the same way as the primary infections. While in 50% of the 48 patients suffering from similar infections of the outer eye in which molds were the pathogens, also bacteria, mostly Staphylococcus aureus, were present, no such association was detected in the yeast infections with the exception of the case of epithelial keratitis in which Rhodotorula mucilaginosa and Commonas terrigena were present together [11], Table III shows the incidence of yeasts in 304 eyes of 152 healthy individuals. They were present in 5 % of the adults. No significant differ ence was detected between urban and rural population.
If compared with the vast number of genera, species and varieties of existing yeasts as they are enumerated by L o d d e r [9] in his taxonomic study, the species isolated in this investigation from eyes of 313 patients suffering from various banal inflammations of the outer eye and its adnexa, and from 304 normal eyes of 152 healthy individuals, were exclusively members of the genera of asporogenous yeasts not belonging to the sporobolomycetaccae as designated by L odder [9], But also from this big group of 12 genera only three were represented: Candida, Rhodotorula and Trichosporon, if we do not take into account the one case of Torulopsis isolated from a normal eye. Among the isolated yeasts different Candida species were prevailing with C. albicans and C. guillermondii atop. It is
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Discussion
Yeasts in Banal External Ocular Inflammations
19
remarkable that in this series no case of Cryptococcus or Pityrosporon, both known as parasites, saprophytes and potential pathogens in both human general and ocular pathology, was encountered. How far this selective representation by the isolated yeasts is characteristic of the sub tropic climate and the special hygienic conditions prevalent in Israel, or may be due only to the smallness of the sample, remains speculative. Absence of pathognomonic characteristics with which to differentiate fungal infections particularly in their early stages from the more common bacterial and virus infections, is one of the chief reasons of diagnostic failures which are especially liable to occur if the affection is not alarming, and the ophthalmologist is not duly aware of the importance of fungi not only in serious keratomycoses and intraocular infections but also in the more common innocuous affections of the outer eye. This last fact is best exemplified by the isolation of yeasts in 53 (17%), and of molds in 48 (15%) eyes from 313 patients suffering from inflammations of the discussed category. Since in this series mycological investigations were performed only in patients referred to the hospital because of the intrac tability of their ocular affection, and in the hospital were clinically sus pected of a fungal infection, the data on the incidence bear no statistical significance, and appear much too high if compared with the isolation of yeasts in only 94 out of 3,358 ocular affections encountered in the New York area during a period of 30 years [8], Introduction of antibiotics into general and ocular therapy resulting in an upset of the normal symbiosis between bacteria and fungi, as well as indiscriminate use of steroids altering the resistance of the tissues, were inculpated as responsible of the conversion of normally saprophytic fungi into facultative pathogens, and therefore for the increase of fungal infec tions observed in the two last decades. Clinical and experimental data supporting these assumptions have been summarized by F rançois and R issei.aere [7], In accordance with these claims, it seems significant that all the patients of this series in whom yeasts were found, had been at one or the other time, mostly for weeks up to months, treated with steroids alone or in combination with various antibiotics.
In 53 out of 313 patients suffering from longstanding inflammations of the outer eye or dacryocanaliculitis, not yielding to the obligate treatment with antibiotics and steroids, yeasts were isolated and regarded as the causative agents. Among the yeasts.
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Summary
20
R omano/S egal/S tein /E ylan
different Candida species were prevalent, with C. albicans and C. guillennondii at the top. An obstinate, superficial epithelial and subepithelial punctate keratitis appeared to represent an entity pathognomonic of a yeast infection. Eradication of the yeasts and cure of the inflammation was achieved only by intensive prolonged treatment with Mycostatin or amphotericin B.
Zusammenfassung In 53 von 313 Patienten, die an verschiedenen, hartnäckigen Entzündungen des äusseren Auges oder der Tränenkanälchen litten und auf die übliche Behandlung mit Antibiotika und Steroiden nicht reagierten, wurden Hefepilze gezüchtet und als die verantwortlichen Krankheitserreger betrachtet. Unter diesen Pilzen herrschten ver schiedene Candida-Arten vor, mit C. albicans und C. guillennondii an der Spitze. Eine widerspenstige, oberflächliche, epitheliale und subepithelialc, punktförmige Keratitis stellt allem Anschein nach ein Krankheitsbild dar, das für eine Pilzinfektion charakteristisch ist. Eine Ausrottung der Pilze und damit eine Heilung der Ent zündungen wurde nur durch eine intensive, langdauernde Behandlung mit Mykostatin und Amphotericin B erzielt.
Résumé De 313 patients souffrant d’inflammations tenaces de l’œil externe ou de dacryocanaliculite, ne cédant pas au traitement classique d'antibiotiques et stéroides, des levures furent isolées chez 53 et considérées comme l’étiologie. Parmi ces levures prédominaient différentes variétés de Candida, avec C. albicans et C. guillermondi au premier rang. Une kératite ponctuée tenace épithéliale et subépithéliale paraît représenter une entité pathognomonique de l’infection aux levures. L’élimination des levures et la guérison de l’inflammation s’obtiennent seulement par un traitement intensif et prolongé à la mycostatine ou amphotericine B.
1 A jello , L.; G eorg , L. K.; K aplan, W., and K aufman, L.: Laboratory manual for medical mycology (US Government Printing Office, Washington 1966). 2 Barthe, J. et Barthe, M. F.: Levures naturelles chez l’homme. Proc. 5th Congr. lnt. Soc. for Human and Animal Mycology, Paris 1971. 3 Blaschkf.-H f.llmessen , R.: Zum Vorkommen von Hcfcpilzen bei Neugeborenen, Säuglingen und Kleinkindern und ihre pathogenetische Bedeutung als Soorerreger'. Kinderärztl. Praxis (1970). 4 C onant , N. F.; Smith , D. T.; Baker, R. D., and C allaway, J. L.: Manual of clinical mycology (Saunders, London 1971). 5 E mmani, M.; M oshenine , H. et P arvenu, N.: Recherche sur les champignons de l’appareil digestif des jeunes (11-18 ans) en milieu fermé (Maison de charité de
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References
Yeasts in Banal External Ocular Inflammations
7 8 9 10 11 12 13 14 15
Farah Pahleva, Teheran-lran). Proc. 5th Congr. Int. Soc. for Human and Animal Mycology, Paris 1971. E mmons, C. W.; Binford , C. H., and Utz , J. P.: Medical mycology; 2nd ed. (Lea & Fiebiger, Philadelphia 1970). F rançois, J. and R ysselaere, M.: Oculomycoses (Thomas, Springfield 1972). L ocatscher-K horazo, D. and Seegai., B.: Microbiology of the eye (Mosby, St. Louis 1972). L odder , J.: The yeasts. A taxonomic study (North Holland, Amsterdam 1971). M artin, P.; K anarek, D.; Boyd, Z. S., and K oornhof, J. H.: The incidence of fungi in the throat. Mycopath. Mycol. appl. 45: 165-187 (1971). R omano, A.; Segal, E., and B en -T ovim , T.: Epithelial keratitis due to Rhodotorula. Ophthalmologica 166: 353-359 (1973). Suie, T. and Havener, W. H.: Mycology of the eye. A review. Amer. J. Ophthal. 56: 63-77 (1963). W ilson , J. W. and P lunkett , O. A.: The fungcous diseases of man (University of California Press, Berkeley 1970). Y oshioka, H.: Keratomycosis. J. clin. Ophthal., Tokyo 10: 1336-1342 (1956). Z immerman, L. E.: Mycotic keratitis. Lab. Invest. 1H 2: 1151-1160 (1962).
Request reprints from: Dr. A malia R omano, Eye Department, Chaim Sheba Medical Center, Tel Hashomer (Israel)
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6
21
Yeasts in Banal External Ocular Inflammations „ A. R omano, E. Segal, R. Stein and E. E ylan Department of Ophthalmology (Head: Prof. R. Stein ), Chaim Sheba Medical Center, Tel Hashomer, and Department of Human Microbiology (Head: Prof. E. E ylan), Tel Aviv University, Medical School, Tel Aviv
There is ample evidence that in the last decades 'opportunistic' fungal ocular infections have been in a steady ascent. This is best documented in the ever growing number of reports on disastrous fungal corneal affec tions and fungal endophthalmitis. In contrast, reports or surveys on banal affections of the eye and its adnexa in which fungi arc the causative agents, have remained relatively scarce. This may be due to the fact that ophthalmologists are not duly aware of the possible etiological role of fungi in these affections, or that they do not regard a mycological examination as worth while because of the banality of the lesions. An other reason may be that in many places the necessary facilities and expert advice are missing. This is best evidenced by our own experience. Only after the Department of Human Microbiology had shown interest in the ophthalmological problems, and once a micro biological laboratory had been attached directly to the Eye Department, has pertinent information started to accumulate. This report deals with the incidence and etiological significance of yeasts isolated from eyes of patients suffering from various acute, subacute, chronic or recurrent inflammations of the outer eye or its adnexa. The incidence of yeasts in the conjunctival sac and lacrimal pathways of normal healthy eyes of 152 individuals of different age was investigated for com parative purposes.
The material consisted of 313 patients who were referred to the Eye Outpatient Department in the last 2Va years for consultation and eventual treatment. They had suffered for longer periods from inflammations of the outer eye which had not
Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/7/2018 10:55:55 AM
Material and Methods
14
R omano/S egal/S tein /E ylan
responded to the usual treatment with antibiotics and/or steroids. They were selected from a pool of patients with similar affections, because their history and the clinical aspect of their affection aroused suspicion of a fungal infection. 517 mycological examinations were done in this sample. At about the same time, a mycological investigation was performed of the con junctival sac and the lacrimal pathways of 304 normal eyes in 12 neonates up to 2 months, and 140 adults in the age of 18-70 years. These investigations fell into the time of the hot summer months. In both groups, material was taken from eyelids, conjunctiva, in cases of keratitis also from the cornea, and from the lacrimal pathways if there were signs of inflam mation. The material taken with sterile swabs was inoculated on Sabourad’s agar, supplemented with 500 mg chloramphenicol (but without cycloheximide). In specificcases, the material was also inoculated on potato dextrose and on yeast extract agar composed of 0.5°/» yeast extract, 3®/o glucose and 2fl/o agar. The cultures were incubated at 28 and at 37 °C. The species of the fungi were identified microscopically in accordance with the standard procedures as described by A jeix o et al. [1], C onant et al. [4], and L odder |9]. In cases of doubt about classification, use was made of other criteria (reproductive and physiological properties). In order to exclude airborne contamination, a finding was recorded only if the same fungus was isolated in more than one culture, and if controls remained sterile. In each case, cultures were made also for possible spontaneous bacterial and viral infections.
Out of a pool of 1,015 patients who suffered from longstanding infec tions of the outer eye and were referred for consultation to the Eye Department, 313 were selected for a mycological investigation because in these cases treatment with antibiotics and steroids had not only failed but had rather aggravated the situation, or bacteriological findings were inconclusive. In 53 of these 313 patients (17%) yeasts, and in 48 molds were iso lated. The molds will not be discussed in this report. The isolated yeasts (table I) were different Candida species in 48, Trichosporon in 2, Rhodotorula species in 2, and Rhodotorula mucilaginosa in one of these cases. This last case of a recalcitrant superficial punctate keratitis has already been reported elsewhere by us [11]. Table II shows that the yeasts were cultivated from various clinical entities and that there is no specific predilection site as far as different yeast species are concerned. Candida albicans was the most frequently encountered Candida species (in 17 of 48 cases). This is in accordance with data from other authors
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Results and Comment
Yeasts in Banal External Ocular Inflammations
15
Species
Number of patients
C. albicans C. guillermondii C. tropicalis C. pseudotropicalis C. krusei C. parapsilosis Rhodotorula mucilaginosa Rltodolorula not defined species Trichosporon not defined species
17 16 7 3 1 4 1 2 2
relating to findings from eye [8, 12, 15] as well as from other parts of the body [2, 3, 5, 10]. However, the relatively high incidence of Candida guillermondii, which, with 16 cases, occupied the second place was sur prising. Although it has been described as the causative agent of various extraocular diseases [4, 6], isolation of C. guillermondii from eyes was reported only by F rançois and R ysselaere [7] in a case of purulent conjunctivitis in a child, and by Y oshioka [14] in a case of keratomycosis. In our series of 7 patients with dacryocanaliculitis this species of Candida was encountered 5 times. Most of the cases of conjunctivitis alone, or in association with blepha ritis or keratitis, in which C. albicans was found, were characterized by a whitish sticky secretion in the lower fornix. In some of these patients, easily removable pseudomembranes were present. In one case, a small superficial ulcer was seen in the lower fornix. We have never seen the small yellowish spots in the conjunctiva described by F rançois and R ysselaere [7] as characteristic at the onset. But all our patients were late cases, already treated for weeks or months outside of the hospital. Nearly identical forms of conjunctivitis as seen with C. albicans, were found in cases where C. guillermondii or tropicalis were cultivated. The inflammation was of the more banal, catarrhal type in cases where C. subtropicalis or parapsilosis or Trichosporon were apparently the causative agents. In the 3 patients with keratoconjunctivitis, the corneae presented the picture of a superficial keratitis characterized by a diffuse staining of the superficial epithelial layer with fluorescein. These patients complained also of pains and photophobia.
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Table I. Isolated yeast species
R omano/S egal/S tein /E ylan
16
Clinical diagnosis
Species of isolated yeast
Number of patients
Chronic blepharitis
C. albicans C. guillermondii C. pseudotropicalis C. krusei C. parapsilosis
1 3 1 1 1
Chronic blepharoconjunctivitis
C. albicans C. guillermondii C. tropicalis C. pseudotropicalis Trichosporon species
7 4 3 1 2
Subacute, chronic or recurrent conjunctivitis
C. albicans C. guillermondii C. tropicalis C. parapsilosis Rhodotorula species
4 2 3 2 1
Chronic or recurrent keratoconjunctivitis
C. albicans C. tropicalis Rhodotorula species
1 1 1
Superficial punctate epithelial keratitis
C. albicans C. guillermondii C. pseudotropicalis C. parapsilosis Rhodotorula mucilaginosa
2 2 1 1 1
Dacryocanaliculitis
C. albicans C. guillermondii
2 5
The 7 cases of punctate, epithelial keratitis deserve a special mention. In these cases, the conjunctiva was almost not involved. The corneas exhibited lesions reminding those seen in epidemic keratoconjunctivitis or in Thygeson's keratopathy. Fine and coarse, grey epithelial opacities, round, oval or irregular in shape occupied chiefly the central cornea, some of them slightly prominent above the surface, some extending into the underlying Bowman's membrane. This resemblance with the above-men tioned entities explains why these patients were in the beginning treated with steroids. This treatment not only was of no avail but resulted mostly
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Table II. Inflammations of the outer eye in which yeast were isolated
17
in aggravation of the affection. Only after elimination of the yeasts, did the corneas clear up and only where deeper infiltrates had been present, slight nubeculae remained. The 7 cases of blepharitis in which yeasts were found, were of the seborrhoic type with exception of one who presented an ulcerative ble pharitis. The etiological role of the yeasts is open to question since after elimination of the yeasts, the disease relapsed in 6 of these cases though yeasts were no longer present. All patients in this series were in good general health. All were adults with the exception of one with bilateral keratoconjunctivitis who was a child. In no case were yeasts detected in other sites of the body; feces however, were not examined. Even in these more or less banal affections of the outer eye in which yeasts were isolated, treatment with antifungals had to be intensive, fre quent and prolonged in order to eliminate the yeasts, and to attain a cure. The antimycoticals employed in this series, were nystatin (Mycostatin®) and amphotericin B (Fungizone®) in form of eyedrops which were applied 6-8 times a day. Nystatin which has a very low solubility in water, was used as suspension in a concentration of about 1(),()()() U/ml which was increased up to 100,000 U/ml in resistant cases. The suspension has to be prepared every 2 or 3 days because of its low stability. Amphotericin B marketed in vials containing 50 mg of the drug as sterile lyophilized powder plus desoxycholate and a buffer, is dissolved in 10 ml of sterile distilled water - not in saline which causes precipitation - and 5°/o dex trose in water is added to make a final concentration of 0.3 %>. This solu tion is unstable too. The drops may be prepared too from a 3-percent commercial solution. Treatment with 5-fluorocytosin tried only recently, alone and in combination with other antibiotics proved very effective but our experience is still too small. While affections of the conjunctiva alone or associated with keratitis responded relatively fast to the treatment, the cases with punctate epithelial keratitis as described above, proved rather resistant and required a very prolonged treatment even when the concentration of the drugs was in creased. All cases of dacryocanaliculitis in which yeasts were the patho gens reacted favorably to the antimycotic therapy without necessitating curettage of the canaliculus. Only in one case had a concrement to be curetted. Antifungal treatment was stopped in all cases as soon as all clinical signs had disappeared, and at least two cultures had remained sterile.
Downloaded by: Univ. of California Santa Barbara 128.111.121.42 - 3/7/2018 10:55:55 AM
Yeasts in Banal External Ocular Inflammations
18
R omano/S egal/S tein /E ylan
Table III. Yeasts in normal eyes
Neonates < 2 months Adults > 1 6 years
Number of eyes
Isolated species
Number of positive cultures
Total
24 280
0 C. albicans C. guillermondii C. parapsilosis Rhodotorula Torulopsis
0 1 2 1 1 2
0
7
In about 30% of the cases, relapses occurred with reappearance of the same yeast species. They were treated in the same way as the primary infections. While in 50% of the 48 patients suffering from similar infections of the outer eye in which molds were the pathogens, also bacteria, mostly Staphylococcus aureus, were present, no such association was detected in the yeast infections with the exception of the case of epithelial keratitis in which Rhodotorula mucilaginosa and Commonas terrigena were present together [11], Table III shows the incidence of yeasts in 304 eyes of 152 healthy individuals. They were present in 5 % of the adults. No significant differ ence was detected between urban and rural population.
If compared with the vast number of genera, species and varieties of existing yeasts as they are enumerated by L o d d e r [9] in his taxonomic study, the species isolated in this investigation from eyes of 313 patients suffering from various banal inflammations of the outer eye and its adnexa, and from 304 normal eyes of 152 healthy individuals, were exclusively members of the genera of asporogenous yeasts not belonging to the sporobolomycetaccae as designated by L odder [9], But also from this big group of 12 genera only three were represented: Candida, Rhodotorula and Trichosporon, if we do not take into account the one case of Torulopsis isolated from a normal eye. Among the isolated yeasts different Candida species were prevailing with C. albicans and C. guillermondii atop. It is
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Discussion
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remarkable that in this series no case of Cryptococcus or Pityrosporon, both known as parasites, saprophytes and potential pathogens in both human general and ocular pathology, was encountered. How far this selective representation by the isolated yeasts is characteristic of the sub tropic climate and the special hygienic conditions prevalent in Israel, or may be due only to the smallness of the sample, remains speculative. Absence of pathognomonic characteristics with which to differentiate fungal infections particularly in their early stages from the more common bacterial and virus infections, is one of the chief reasons of diagnostic failures which are especially liable to occur if the affection is not alarming, and the ophthalmologist is not duly aware of the importance of fungi not only in serious keratomycoses and intraocular infections but also in the more common innocuous affections of the outer eye. This last fact is best exemplified by the isolation of yeasts in 53 (17%), and of molds in 48 (15%) eyes from 313 patients suffering from inflammations of the discussed category. Since in this series mycological investigations were performed only in patients referred to the hospital because of the intrac tability of their ocular affection, and in the hospital were clinically sus pected of a fungal infection, the data on the incidence bear no statistical significance, and appear much too high if compared with the isolation of yeasts in only 94 out of 3,358 ocular affections encountered in the New York area during a period of 30 years [8], Introduction of antibiotics into general and ocular therapy resulting in an upset of the normal symbiosis between bacteria and fungi, as well as indiscriminate use of steroids altering the resistance of the tissues, were inculpated as responsible of the conversion of normally saprophytic fungi into facultative pathogens, and therefore for the increase of fungal infec tions observed in the two last decades. Clinical and experimental data supporting these assumptions have been summarized by F rançois and R issei.aere [7], In accordance with these claims, it seems significant that all the patients of this series in whom yeasts were found, had been at one or the other time, mostly for weeks up to months, treated with steroids alone or in combination with various antibiotics.
In 53 out of 313 patients suffering from longstanding inflammations of the outer eye or dacryocanaliculitis, not yielding to the obligate treatment with antibiotics and steroids, yeasts were isolated and regarded as the causative agents. Among the yeasts.
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Summary
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R omano/S egal/S tein /E ylan
different Candida species were prevalent, with C. albicans and C. guillennondii at the top. An obstinate, superficial epithelial and subepithelial punctate keratitis appeared to represent an entity pathognomonic of a yeast infection. Eradication of the yeasts and cure of the inflammation was achieved only by intensive prolonged treatment with Mycostatin or amphotericin B.
Zusammenfassung In 53 von 313 Patienten, die an verschiedenen, hartnäckigen Entzündungen des äusseren Auges oder der Tränenkanälchen litten und auf die übliche Behandlung mit Antibiotika und Steroiden nicht reagierten, wurden Hefepilze gezüchtet und als die verantwortlichen Krankheitserreger betrachtet. Unter diesen Pilzen herrschten ver schiedene Candida-Arten vor, mit C. albicans und C. guillennondii an der Spitze. Eine widerspenstige, oberflächliche, epitheliale und subepithelialc, punktförmige Keratitis stellt allem Anschein nach ein Krankheitsbild dar, das für eine Pilzinfektion charakteristisch ist. Eine Ausrottung der Pilze und damit eine Heilung der Ent zündungen wurde nur durch eine intensive, langdauernde Behandlung mit Mykostatin und Amphotericin B erzielt.
Résumé De 313 patients souffrant d’inflammations tenaces de l’œil externe ou de dacryocanaliculite, ne cédant pas au traitement classique d'antibiotiques et stéroides, des levures furent isolées chez 53 et considérées comme l’étiologie. Parmi ces levures prédominaient différentes variétés de Candida, avec C. albicans et C. guillermondi au premier rang. Une kératite ponctuée tenace épithéliale et subépithéliale paraît représenter une entité pathognomonique de l’infection aux levures. L’élimination des levures et la guérison de l’inflammation s’obtiennent seulement par un traitement intensif et prolongé à la mycostatine ou amphotericine B.
1 A jello , L.; G eorg , L. K.; K aplan, W., and K aufman, L.: Laboratory manual for medical mycology (US Government Printing Office, Washington 1966). 2 Barthe, J. et Barthe, M. F.: Levures naturelles chez l’homme. Proc. 5th Congr. lnt. Soc. for Human and Animal Mycology, Paris 1971. 3 Blaschkf.-H f.llmessen , R.: Zum Vorkommen von Hcfcpilzen bei Neugeborenen, Säuglingen und Kleinkindern und ihre pathogenetische Bedeutung als Soorerreger'. Kinderärztl. Praxis (1970). 4 C onant , N. F.; Smith , D. T.; Baker, R. D., and C allaway, J. L.: Manual of clinical mycology (Saunders, London 1971). 5 E mmani, M.; M oshenine , H. et P arvenu, N.: Recherche sur les champignons de l’appareil digestif des jeunes (11-18 ans) en milieu fermé (Maison de charité de
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References
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Farah Pahleva, Teheran-lran). Proc. 5th Congr. Int. Soc. for Human and Animal Mycology, Paris 1971. E mmons, C. W.; Binford , C. H., and Utz , J. P.: Medical mycology; 2nd ed. (Lea & Fiebiger, Philadelphia 1970). F rançois, J. and R ysselaere, M.: Oculomycoses (Thomas, Springfield 1972). L ocatscher-K horazo, D. and Seegai., B.: Microbiology of the eye (Mosby, St. Louis 1972). L odder , J.: The yeasts. A taxonomic study (North Holland, Amsterdam 1971). M artin, P.; K anarek, D.; Boyd, Z. S., and K oornhof, J. H.: The incidence of fungi in the throat. Mycopath. Mycol. appl. 45: 165-187 (1971). R omano, A.; Segal, E., and B en -T ovim , T.: Epithelial keratitis due to Rhodotorula. Ophthalmologica 166: 353-359 (1973). Suie, T. and Havener, W. H.: Mycology of the eye. A review. Amer. J. Ophthal. 56: 63-77 (1963). W ilson , J. W. and P lunkett , O. A.: The fungcous diseases of man (University of California Press, Berkeley 1970). Y oshioka, H.: Keratomycosis. J. clin. Ophthal., Tokyo 10: 1336-1342 (1956). Z immerman, L. E.: Mycotic keratitis. Lab. Invest. 1H 2: 1151-1160 (1962).
Request reprints from: Dr. A malia R omano, Eye Department, Chaim Sheba Medical Center, Tel Hashomer (Israel)
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