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Brit. J. Ophthal. (1975) 59, 372 Dematiaceous fungal keratitis Clinical isolates and management RICHARD K. FORSTER, GERBERT REBELL, AND LOUIS A. WILSON* From the Bascom Palmer Eye Institute, University of Miami, Florida, and the University of Georgia, Augusta, Georgia* Dematiaceous fungi are darkly pigmented, filament- ary moulds and are common in the environment as plant saprophytes and pathogens. Incidental reports of corneal ulcers that have been caused by species of this group have appeared in the literature, but the relative importance of this species as potential comeal pathogens has not been appre- ciated. As a group, second to Fusarium solani and other moniliaceous fungi, we find that dematiaceous fungi comprise the next most common cause of fungal ulcers in south Florida. The successful treatment of Fusarium solani keratitis with Natamycin (Pimaricin) has been reported by Jones, Forster, and Rebell (1972), and we have examined the management of other non-Fusarium solani moniliaceous fungal ulcers. The purpose of this communication is to report our study of I 6 isolates of dematiaceous fungal keratitis, their features, and management including nine cases that were treated with Natamycin, and to stress their relative clinical importance. Material and methods PATIENTS We have studied i6 cases of keratitis caused by dematia- ceous fungi. Ten cases were referred to the Bascom Palmer Eye Institute; three were examined before I969 and reported by Jones, Sexton, and Rebell (i969), and seven were included in the 53 isolates seen during the last 4i years. Three cases were examined in Augusta, Georgia, by one of us (LAW) and the isolates were identified and studied at the Bascom Palmer Eye Institute. Three ad- ditional isolates from Florida were sent to us; two of the patients received Natamycin, and a third was treated with topical Amphotericin B and was examined by us on completion of treatment. Address for reprints: Richard K. Forster MD, Department of Oph- thalmology, University of Miami, School of Medicine, P.O. Box 875, Biscayne Annex, Miami, Florida 33152 Supported in part by: Public Health Services Grant No. 5 ROI EY00674-02, from the National Eye Institute; Fight for Sight Grant No. G-457; United Health Foundation of Dade County Grant; The Florida Lions Eye Bank; and The Flournory and Mae Knight Clark Research Fund. CLINICAL-LABORATORY DIAGNOSIS All the patients had scrapings performed; microscopical examination by KOH preparation, Gram or Giemsa stains; and positive cultures on at least one medium including Sabouraud's agar, blood agar at 260C and 370C, and liquid brain-heart infusion (BHI). In one case keratoplasty fragments were cultured on Sabouraud's agar, and histopathology performed by Gomori's methen- amine silver nitrate technique (GMS), periodic acid- Schiff (PAS) reaction, and haematoxylin-eosin stain (H and E). Isolates were identified and speciated by sporulation from the original or lyophilized cultures. Ten of the I6 isolates were confirmed taxonomically by Dr M. B. Ellis, at the Commonwealth Mycological Institute, and the others by Ellis's manual (I97I) and Von Arx (1970). MANAGEMENT Nine patients were treated topically with Natamycin (Pimaricin) 5 per cent suspension. Two received only Gentamicin topically. One was treated with topical Amphotericin B. A patient seen before I 969 received topical Amphotericin B, Thiabendazole, and Merthiolate and later required a conjunctival flap operation. Two other patients seen before I 969 received topical Amphotericin B, including Case 3, who also received topical Natamycin ointment and Thiabendazole. A therapeutic keratoplasty was necessary in a patient whose eye perforated before fungal diagnosis. Results IDENTIFICATION Before I969, three of 38 isolates at the Bascom Palmer Eye Institute were identified as dematiaceous fungi. These included a Curvularia sp. (originally identified as C. lunata, but not confirmed), a case of Phialophora verrucosa reported by Wilson, Sexton, and Aheam (I966), and a Lasiodiplodia theobromae, previously diagnosed and reported as Macrophoma sp. by Jones and others (I969) (Table I: Cases I, 2, and 3). In 53 casesof fungal keratitiswhichhavebeenperson- ally examined by the author (RKF) since I969, seven have been identified as dematiaceous fungi. These include Curvularia jenegalensis (2); C. pallescens, and a non-speciated Curvularia; and one each Drechslera on March 15, 2020 by guest. Protected by copyright. http://bjo.bmj.com/ Br J Ophthalmol: first published as 10.1136/bjo.59.7.372 on 1 July 1975. Downloaded from

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Brit. J. Ophthal. (1975) 59, 372

Dematiaceous fungal keratitisClinical isolates and management

RICHARD K. FORSTER, GERBERT REBELL, AND LOUIS A. WILSON*From the Bascom Palmer Eye Institute, University of Miami, Florida, and the University of Georgia, Augusta, Georgia*

Dematiaceous fungi are darkly pigmented, filament-ary moulds and are common in the environment asplant saprophytes and pathogens.

Incidental reports of corneal ulcers that have beencaused by species of this group have appeared in theliterature, but the relative importance of this speciesas potential comeal pathogens has not been appre-ciated.As a group, second to Fusarium solani and other

moniliaceous fungi, we find that dematiaceous fungicomprise the next most common cause of fungalulcers in south Florida.The successful treatment of Fusarium solani keratitis

with Natamycin (Pimaricin) has been reported byJones, Forster, and Rebell (1972), and we haveexamined the management of other non-Fusariumsolani moniliaceous fungal ulcers. The purpose of thiscommunication is to report our study of I 6 isolates ofdematiaceous fungal keratitis, their features, andmanagement including nine cases that were treatedwith Natamycin, and to stress their relative clinicalimportance.

Material and methods

PATIENTS

We have studied i6 cases of keratitis caused by dematia-ceous fungi. Ten cases were referred to the Bascom PalmerEye Institute; three were examined before I969 andreported by Jones, Sexton, and Rebell (i969), and sevenwere included in the 53 isolates seen during the last 4iyears. Three cases were examined in Augusta, Georgia,by one of us (LAW) and the isolates were identified andstudied at the Bascom Palmer Eye Institute. Three ad-ditional isolates from Florida were sent to us; two of thepatients received Natamycin, and a third was treated withtopical Amphotericin B and was examined by us oncompletion of treatment.

Address for reprints: Richard K. Forster MD, Department of Oph-thalmology, University of Miami, School of Medicine, P.O. Box 875,Biscayne Annex, Miami, Florida 33152

Supported in part by: Public Health Services Grant No. 5 ROIEY00674-02, from the National Eye Institute; Fight for Sight GrantNo. G-457; United Health Foundation of Dade County Grant; TheFlorida Lions Eye Bank; and The Flournory and Mae Knight ClarkResearch Fund.

CLINICAL-LABORATORY DIAGNOSIS

All the patients had scrapings performed; microscopicalexamination by KOH preparation, Gram or Giemsastains; and positive cultures on at least one mediumincluding Sabouraud's agar, blood agar at 260C and370C, and liquid brain-heart infusion (BHI). In one casekeratoplasty fragments were cultured on Sabouraud'sagar, and histopathology performed by Gomori's methen-amine silver nitrate technique (GMS), periodic acid-Schiff (PAS) reaction, and haematoxylin-eosin stain(H and E).

Isolates were identified and speciated by sporulationfrom the original or lyophilized cultures. Ten of theI6 isolates were confirmed taxonomically by Dr M. B.Ellis, at the Commonwealth Mycological Institute, andthe others by Ellis's manual (I97I) and Von Arx (1970).

MANAGEMENT

Nine patients were treated topically with Natamycin(Pimaricin) 5 per cent suspension. Two received onlyGentamicin topically. One was treated with topicalAmphotericin B. A patient seen before I 969 received topicalAmphotericin B, Thiabendazole, and Merthiolate andlater required a conjunctival flap operation. Two otherpatients seen before I 969 received topical Amphotericin B,including Case 3, who also received topical Natamycinointment and Thiabendazole. A therapeutic keratoplastywas necessary in a patient whose eye perforated beforefungal diagnosis.

Results

IDENTIFICATION

Before I969, three of 38 isolates at the Bascom PalmerEye Institute were identified as dematiaceous fungi.These included a Curvularia sp. (originally identifiedas C. lunata, but not confirmed), a case of Phialophoraverrucosa reported by Wilson, Sexton, and Aheam(I966), and a Lasiodiplodia theobromae, previouslydiagnosed and reported as Macrophoma sp. by Jonesand others (I969) (Table I: Cases I, 2, and 3).

In 53 casesof fungal keratitiswhichhavebeenperson-ally examined by the author (RKF) since I969, sevenhave been identified as dematiaceous fungi. Theseinclude Curvularia jenegalensis (2); C. pallescens, and anon-speciated Curvularia; and one each Drechslera

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Dematiaceousfungal keratitis 373

halodes, Altemnaria state of Pleospora infectoria, andLasiodiplodia theobromae (Table I: Cases 4-IO).One of us (LAW) diagnosed three dematiaceous

fungal ulcers in Augusta, Georgia, including Alternariaaltemnata, Drechslera state of Cochliobulus specifer, andCladosporium oxysporium (Table I: Cases I I-I3). Threeother Florida isolates included two Curvularia senegalen-sis and a case of Curvularia verrucolosa which was

examined by us after treatment (Table I: Cases I4-I 6), see Figs I to 5.

CLINICAL-LABORATORY DIAGNOSIS

The characteristic features of fungal ulcers in a group

of 53 cases have been described, and this series ofdematiaceous fungal ulcers was not significantlydifferent (Table i). Ages ranged from 7 to 64 years;

Io of i6 had sustained definite foreign body trauma;and 7 of I 6 had already been treated, two withantibiotics alone, and five with antibiotics andsteroids.The severity varied, some of the ulcers were super-

ficial and mild (Fig. 6), but others were deep (Fig. 7).One needed keratoplasty because of perforation,(Case 6).

Microscopical examination of scrapings or cornealfragments was positive for fungal elements in tencases on one or more preparations using KOH,Gram, Giemsa, or histopathological stains. Theseincluded five positive KOH preparations, four positiveGiemsa stains, and one positive Gram stain. Cornealfragments were positive histopathologically in Case 6.

Sixteen positive isolates grew on one or more mediaincluding 14 on Sabouraud's, two on blood agar at26°C, four on blood agar at 370C, and five on BHIliquid broth.

MEDICAL AND SURGICAL MANAGEMENT

Seven of i6 cases retained a visual acuity of 20/40or better; four were 20/50 to 20/70; three 'healed' withno final vision determined; and two resulted in20/400 acuity (Table II).Nine of I6 cases were treated with Natamycin,

Table I Dematiaceousfungal keratitis

Earlier treatment

Case Isolate

I Curvularia sp.2 Phialophora

verrucosa

3 Lasiodiplodiatheobromae

4 Curvularia sp.5 Alternaria state of

Pleospora infectoria6 Curvularia senegalensis7 Curvularia

pallescens8 Lasiodiplodia

theobromae9 Drechslera

halodes10 Curvularia

senegalensisI I Alternaria

alternataI2 Drechslera-state of

Cochliobulus speciferI 3 Cladosporium

oxysporumI4 Curvularia

senegalensis15 Curvularia

senegalensisi6 Curvularia

verruculosa

Trauma* Antibiotics Steroids Management**

+ NI o Amphotericin B+ + + Amphotericin B

Other, Conj. flap+ 0 0 Amphotericin B

Other, Pimaricin oint+ o o Natamycin0 0 0 Natamycin

+ + + TPKNI 0 0 Gentamicin

+ + 0 Natamycin

0 o o Gentamicin

0 0 0 Natamycin

+ + + Natamycin

+ +

Post- +keratoplastyNI o

0 Natamycin

+ Amphotericin B,Natamycin

0 Natamycin

+ 0 0 Natamycinand Steroids

+ + + Amphotericin B

Viscual acuity

Initial Final

NI 20/7020/30 20/400

NI 20/30+

20/40 20/20

CF I.5 m 20/70

HM 20/40+20/200 20/50

20/25+ 20/25+

20/15

20/70

'Healed'

'Healed'

20/400 20/400***

20/400 20/40+ 2

20/400

20/20

20/30

NI

20/40+2

20/20

'Healed'

20/60

* + = positive, o = negative, NI = not indicated** TPK-therapeutic penetrating keratoplasty*** Cornea clinically better than 20/400

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374 British Journal of Ophthalmology5_ _Xjt tbKSS bi- Qw1|1 '1D 81bi JL.5.i s.

An ...:v).._ ...S

_.r;;;r_x..... : e': .:X'9Etss

u@::@S:

FIG. I Conidia of Curvularia senegalensis (Case I5).x43o

FIG. 4x 430

Conidia of Cladosporium oxysporium (Case i3).

I . '...

I,

F I G. 2 Conidia ofAlternaria-state ofPleospora infectoria(Case 5). x 43o

I

FIG. 5 Pycno conidia of Lasiodiplodia theobromae (Case8). X 250

F I G. 3 Conidia of Drechslera-state of Cochliobulusspecifer (Case I2). X 430

including five of the seven with 20/40 or better visualacuity.Only one patient required therapeutic keratoplasty.

A 46-year-old woman sustained a mild injury from a

splinter of old wood while redecorating the inside of

her home, and was treated with a multitude ofmedications including topical steroid-antibioticsbefore referral with a perforated cornea, 2j monthsafter injury. She did not receive Natamycin, but shehad culture and histology positive corneal fragments,and after keratoplasty the visual acuity was 20/40 +(Case 6).Two patients were treated with only topical

Gentamicin 3 mg/ml; one attained 20/50 vision, and

Table II Visual results in i6 cases ofdematiaceousfungalkeratitis

Therapy

Final visual acuity Natamycin Other Total

20/40 or better 5 2 720/50-20/70 I 3 4'Healed' 2 I 320/400 I I 2Total cases 9 7 I6

as*.w*-Ms / |,8r..... .. . zt : Z| ::w ...| ibF f. 4-: !, s

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Dematiaceousfungal keratitis 375

F I G. 6 Dematiaceous.fungalulcer due to Curvularia species(Case 4)

F I G . 7 Dematiaceousfungalulcer due to a Drechslera species(Case 12).

the other 'healed' without returning for a final test ofvisual acuity. In both cases scrapings were negativeon microscopical examination, and after 36 hours,when the cultures were positive for Curvularia pallescensand Drechslera halodes, the ulcers had improved, andtherefore, Gentamicin was continued without institut-ing Natamycin (Cases 7 and 9).Case i 6 was treated with Amphotericin B, 2 mg/ml

topically, and achieved a cure and a visual acuity of20/60.The three additional cases were seen before i969.

Case i attained 20/70 vision with Amphotericin Btreatment, and Case 3 attained 20/30 + visual acuityafter topical Amphotericin B, Thiabendazole, andNatamycin ointment. A final case due to Phialophora

verrucosa (Case 2) reported by Wilson and others(I966) was treated with Amphotericin B (0o3 percent), thiabendazole (0o3 per cent), thiomersal, andsubsequently required a conjunctival flap operation.

Discussion

The term dematiaceous fungi is a convenient de-signation for the major pigmented fungi implicated inkeratitis, including the Dematiaceous Hyphomycetes(Moniliales) and other pigmented isolates such asLasiodiplodia theobromae (Sphaeropsidales).

Case reports of keratitis caused by these fungi areinfrequent, and vary in clinical presentation andcourse. Keratitis caused by Curvularia species has been

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376 British Journal of Ophthalmology

reported in single cases by Nityananda, Sivasu-bramaniam, and Ajello (i 962, I964) (2 species),Anderson, Roberts, Gonzalez, and Chick (959),Anderson and Chick (I963), Georg (I964), Llamozas,Suprani, and De Albornoz (I966), Salceda, Nievera,and Abendanio (I969), and Wind and Polack (I970).Alternaria species have been reported by Orlow (I 914),and Halde and Okumoto (i 966). Drechslera andHelminthosporium case reports are probably lacking.There are reports of Phialophora verrucosa by Wilsonand others (I966), of P. gougerotii and Lasiodiplodiatheobromae by Laverde, Vera, Moncada, Restrepo,and Diaz (1972), Laverde, Moncada, Restrepo, andVera (I973), and Puttanna (I967), and of Clado-sporium (Hormodendrum) by Suie and Havener (I963),and Francois and Rysselaera (1972).

Whereas, keratitis due to Fusarium solani has beenrecognized as progressive and destructive, thedematiaceous ulcers are more variable and lesspredictable. If neglected or augmented by steroidsthe ulcers may become deep and lead to perforationsuch as Case 6. On the other hand, debridement aloneor treatment with non-antifungal antibiotics maylead to a self-limited infection and healing, such as inCases 7 and 9.

Dematiaceous fungal keratitis presented in similarage groups to those ulcers due to moniliaceous fungi;were usually preceded by outdoor trauma; and oftenoccurred as primary infections, not necessarilyaggravated by topical steroids or antibiotics. Three ofthe five cases that had already been treated withsteroids, however, had the most complicated course(Cases 2, 6, and i I). Case I5, due to Curvulariasenegalensis, had the same fungus cultured from a pieceof garden plant, from which the injurious foreignbody came.

This series serves to alert the ophthalmologist to the

relative frequency of keratitis due to pigmentedfungi, and it stresses the importance of prompt,careful diagnostic, and therapeutic debridement oftheulcer. If recognized early and not aggravated bysteroids, the diagnosis should not be so discouragingas it has been with most fungal keratitis. However, itshould be noted that one of the fungi, Phialophoraverrucosa, is a recognized pathogen causing chromo-mycosis. Prompt therapy with available antifungals,particularly Natamycin, should be instituted uponculture identification.Although many variables alter the reproduceability

of antifungal sensitivity studies, I 2 stains of demati-aceous fungi tested in vitro have in general been moresensitive to antifungals such as Natamycin and Am-photericin B than I9 strains of Fusarium solani tested.

Summary

Clinical and laboratory features of I 6 cases of keratitisthat were caused by dematiaceous pigmented fungiare reported. Management, including the treatmentof nine cases with Natamycin (Pimaricin), resulted incorneal healing in 14 cases, and therapeutic surgeryin two cases.

We should like to acknowledge the help of M.B. EllisPhD, Principal Mycologist, Commonwealth MycologicalInstitute, Kew, for identifying many of these fungalisolates.We should like to thank Roy Bresky MD, ofPompano, andRaymond Sever MD, of Tampa, for their co-operation onCases 14 and 15.We should also like to thank Maria Suerio and Mary G.Wirta for their technical assistance, and FernandoGonzalez, RSP, FBPA,Joe Goren, and Barbara French forphotography.

ReferencesANDERSON, B., and CHICK, E. w. (I963) Sth. med. J., 56, 270

, ROBERTS, S. S., GONZALEZ, c., and CHICK, E. W. (1959) Arch. Ophthal. (Chicago), 62, I69ELLIS, M. B. (1971) 'Dematiaceous Hyphomycetes', Commonwealth Mycological Institute, KewFRAN9OIS, j., and RYSSELAERA, M. (1972) 'Oculomycoses'. Thomas, Springfield, Ill.GEORG, L. K. (I964) J. med. Ass. Ala, 33, 234HALDE, c., and OKUMOTO, M. (I966) XX Concilium Ophthal. Germania, p. 705. Excerpta med. (Amst.)JONES, D. B., FORSTER, R. K., and REBELL, G. (1972) Arch. Ophthal. (Chicago), 88, 147

, SEXTON, R. R., and REBELL, G. (I969) Trans. ophthal. Soc. U.K., 89, 78ILAVERDE, S., MONCADA, L.H., RESTREPO, A., and vERA, C.L. (I973) Sabouraudia, II, I I9

, VERA, C., MONCADA, L. H. RESTREPO, A., and DIAZ, V. F. (1972) Rev. Soc. colomb. Oftal., 3, 175LLAMOZAS, P., SUPRANI, v., and DE ALBORNOZ, V. (I966) Acta med. venez., 13, 178NITYANANDA, K., SIVASUBRAMANIAM, P., and AJELLO, L. (I962) Sabouraudia, 2, 35

, - , (I964) Arch. Ophthal. (Chicago), 71, 456ORLOW, K. (I9I4) Klin. Mbl. Augenheilk., 52, 326PUTTANNA, S. T., (I967) J. All-India ophthal. Soc., I5, I ISALCEDA, S. R., NIEVERA, L-F., and ABENDANO, R. (I969) Philipp. J. Ophthal. Otolaryng., Is 31SUIE, T., and HAVENER, W. H. (I963) Amer. J. Ophthal., 56, 63VON ARX, J. A. (1970) 'The Genera of Fungi Sporulating in Pure Culture'. Cramer, LehreWILSON, L. A., SEXTON, R. R., and AHEARN, D. (I966) Arch. Ophthal. (Chicago), 76, 8I IWIND, C. A., and POLACK, F. M. (1970) Ibid., 84, 694

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