Clinical Study Clinical Characteristics of Alternaria KeratitisAlternaria keratitis ( Table...

Clinical StudyClinical Characteristics of Alternaria Keratitis

Ching-Hsi Hsiao,1,2 Lung-Kun Yeh,1,2 Hung-Chi Chen,1,2 Hsin-Chiung Lin,1,2

Phil Y. F. Chen,1,2 David H. K. Ma,1,2 and Hsin-Yuan Tan1,2

1 Department of Ophthalmology, Chang Gung Memorial Hospital, No. 5 Fu-Hsin Road, Kweishan 333, Taoyuan, Taiwan2 College of Medicine, Chang Gung University, Taoyuan, Taiwan

Correspondence should be addressed to Ching-Hsi Hsiao; [email protected] and Hsin-Yuan Tan; [email protected]

Received 3 October 2013; Revised 5 February 2014; Accepted 18 February 2014; Published 20 March 2014

Academic Editor: Terri L. Young

Copyright © 2014 Ching-Hsi Hsiao et al. This is an open access article distributed under the Creative Commons AttributionLicense, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properlycited.

Purpose. Alternaria spp. are an uncommon cause of mycotic keratitis. Previous studies on Alternaria keratitis have generally beenlimited to case reports.We examined the clinical characteristics ofAlternaria keratitis in this study.Methods.Thecharacteristics andoutcomes of 7 patients with culture-proven Alternaria keratitis treated in our hospital were compared with 25 previously reportedcases. Results. The risk factors for Alternaria keratitis were trauma in 5 patients and soft contact lenses in 1 patient. Six patientswith early diagnosis (

2 Journal of Ophthalmology

the same organism on two or more culture media or asgrowth on one medium of organisms seen on stained smearsof corneal scrapings. Fungal identification was based onmorphology.

Medical treatment was considered successful if cornealinfection was resolved during antifungal therapy and didnot recur after topical agents were discontinued. Previouslyreported cases of Alternaria keratitis were identified bysearching the MEDLINE database and then restricting thesearch to corneal infections that had laboratory evidence andoutcome details written in English. Demographic data, riskfactors, and management information were extracted andtabulated. Characteristics of previously reported cases werecompared with the current series by using the Wilcoxonrank-sum test for continuous variables and the Fisher exacttest for categorical variables. A 𝑃 value under 0.05 wasconsidered statistically significant. All statistical analyseswere performed using SPSS software, version 20 (IBM SPSSStatistics, New York, NY, USA).

3. Results

3.1. Clinical Features. Alternaria spp. were isolated from 7patients (3.4%) with fungal keratitis in our hospital duringthe 10-year period. Table 1 summarizes the clinical data.

The median age was 62 years (range 17–76 years). Themean follow-up time was 11 months (range 2–29 months).The patients included 3 women and 4 men. Two ulcersdeveloped in the right eye and 5 in the left eye. Predisposingfactors for keratitis were identified for 6 patients; 5 infectionsfollowed corneal trauma and one was associated with softcontact lenses. One diabetic farmer (Patient 3), who under-went cataract surgery in his left eye 1 month before presen-tation, reported no precipitating factors. Whether Patient 4had used corticosteroids was unclear, but the other 6 patientshad no such history. All of the patients displayed similarmanifestations of pain and redness in the eyes. The durationbetween onset of symptoms and diagnosis ranged from 4to 10 days in 6 patients; Patient 4 was previously treatedelsewhere approximately 4 months and referred to us fordiagnosis. Six patients had centrally located and medium-sized (2–6mm at its greatest dimension) corneal infiltratewith a feathery margin (Figure 1), and Patient 7 had aperipheral 1 × 1mm ulcer.

None had a hypopyon. Topical antifungal agents, occa-sionally used in combination, included natamycin 5% sus-pension and amphotericin B 0.15% for 6 patients.The cultureresult of the corneal scrapings from Patient 3 revealedMycobacterium chelonae in addition toAlternaria spp.; there-fore, amikacin (25mg/cc) and ciprofloxacin 0.3% were addedlater. Patient 7 exhibited a small peripheral soft contact lens-related corneal ulcer, which healed completely after treatmentwith amikacin (25mg/cc) and cefazolin sodium (25mg/cc)for 3 days. Thus, she did not receive antifungal treatmenteven though the culture result later revealed Alternaria spp.No patients received systemic antifungal therapy. All ofthe patients, except Patient 4, responded well to medicalantimicrobial treatment. Two patients (Patients 3 and 4)

underwent superficial keratectomy for debridement andpromotion of the penetration of antimicrobial medication.Patient 4 eventually developed a perforated ulcer; thus apatch graft with a glycerol-preserved cornea was performedand no recrudescent infection developed. All of the patientspreserved useful vision (≥20/200); the limited visual rehabil-itation was primarily caused by central corneal scarring andcataracts if existed.

3.2. Literature Review. Twenty-five previously reported casesof Alternaria keratitis presented surgical or other outcomeinformation (Table 2) [2–23]. These 17 men and 8 womenranged from 26 to 72 years of age.

Risk factors for infections are summarized in Table 3.Nine out of twenty-five (36%) infections followed corneal

trauma; 10 (40%) occurred in the eyes with prior cornealdisease or surgery and 4 (16%) were associated with contactlenses. Fourteen (56%) had a definite history of corticos-teroid usage before diagnosis of fungal keratitis. Topicalantifungal agents, occasionally administered in combina-tion, included natamycin, amphotericin B, miconazole, keto-conazole, voriconazole, flucytosine, fluconazole, and capo-fungin. Some patients also received systemic antifungaltherapy, including oral itraconazole and voriconazole. Twopatients received an intracameral or intrastromal injectionof voriconazole. Seventeen (68%) patients were cured withmedical treatment, but only 5 out of 15 patients, who receivednatamycin or amphotericin B, achieved successful medicaltreatment. Therapeutic keratoplasty was performed on 8patients (32%) (Table 3).

When incorporated with our cases of Alternaria keratitis(𝑛 = 32), 14 (44%) infections followed trauma, 10 (31%) wereassociatedwith preexisting corneal disease or previous ocularsurgery, and 5 (16%) occurred in soft contact lens wearers. Adefinite history of corticosteroid usewas observed in 14 (44%)patients. Successful medical treatment was achieved in 23(72%) patients, including 10 out of 21 eyes (48%) treated withnatamycin and/or amphotericin B. Therapeutic penetratingkeratoplasty was performed in 9 (28%) cases.

4. Discussion

First recognized in 1975 [2],Alternaria spp. are an uncommoncause of corneal infection and account for 3.3% to 8.7% ofmycotic keratitis [24–28].Alternaria spp. were responsible for3.4% of mycotic keratitis over the 10-year interval observedin our hospital. Previous studies of Alternaria keratitis havegenerally been limited to case reports; therefore, this may bethe greatest number of cases of Alternaria keratitis reportedat one institution. Our findings indicate that Alternariakeratitis was generally associated with specific risk factors,including trauma and contact lens usage, and responded wellto conventional antifungal drugs.

The most common risk factors for Alternaria keratitisis trauma (Table 3), considering that 5 out of 7 patientshad a history of trauma in our study. Surgery and preex-isting corneal diseases are also commonly associated withAlternaria keratitis (Table 3), but none of our 6 patients with

Journal of Ophthalmology 3

Table1:Clinicaldataof

patie

ntsw

ithAlternariakeratitis.

Patie

ntRisk

factors

Locatio

nandsiz

eMedicaltre

atment

Surgery

InitialVA

FinalV

AF/U(m

onths)

Others

1Trauma

C,4×3mm

Natam

ycin

+Amph

otericin

BCF

20/200

22

Trauma

C,2×2mm

Amph

otericin

B20/200

20/10

010

3Unk

nown,

DM

C,4×4.4mm

Natam

ycin

+am

ikacin

+ciprofl

oxacin

Superficialkeratectom

y20/200

20/70

16

(i)Ca

taractop

eration1m

onth

ago

(ii)A

farm

er(iii)Coinfectio

nwith

M.ch

elona

e

4Trauma

C,3.6×3mm

Natam

ycin

Superficialkeratectom

y,patchgraft

CF20/200

15PK

P+EC

CE+IO

L5

mon

thslater

5Trauma

C,3×4mm

Natam

ycin

CF20/10

029

6Trauma

C,2×2mm

Natam

ycin

+am

photericin

B20/400

20/10

04

7SC

LP,1×1mm

Cefazolin

+am

ikacin

20/25

20/20

2DM:diabetesm

ellitus,SCL

:soft

contactlens,C:

central,P:

perip

heral,CF

:cou

ntingfin

gers,F/U

:follow-up,PK

P:penetratingkeratoplasty,E

CCE:

extracapsularc

ataractextraction,

andIO

L:intraocularlens.


Table2:Previouslyrepo

rted

caseso

fAlternariakeratitis.

Reference,repo

rtyear

Age/sex

Risk

factor

Antifu

ngalmedication

Surgery

Others

Azare

tal.,1975

[2]

53/M

HSV

keratitis

Topicaln

atam

ycin

PKP

And

oandTakatori,

1987

[3]

53/F

PKP

Topicalthimerosal,pim

aricin,flucytosine

Changetal.,1994

[4]

55/M

Trauma

Topicalm

icon

azole,flu

conazole

PKP

Com

binedendo

phthalmitis

Arresee

tal.,1996

[5]

46/M

Syste

micste

roids

Itracon

azole

PKP

Danieletal.,1997

[6]

45/M

Trauma

Topicalketocon

azole

Koce

tal.,1997

[7]

82/M

ECCE

Topicalfl

ucon

azole

Ferrer

etal.,2002

[8]

50/M

Trauma

Syste

micste

roids

Topicalamph

otericin

B,flu

conazole

PKP

Zahrae

tal.,2002

[9]

55/M

Trauma,DM

Topicalamph

otericin

BFerrer

etal.,2003

[10]

66/M

Trauma

Topicalamph

otericin

B,flu

conazole

Com

binedwith

endo

phthalmitis

Verm

aetal.,2005

[11]

29/F

LASIK

—PK

PDiagn

osisaft

erPK

P

Ozbek

etal.,2006

[12]

69/M

Trauma

Topicaln

atam

ycin,amph

oterin

B→

topicaland

oralvoric

onazole

Barnes

etal.,2007

[13]

59/M

KPro

Topicalamph

otericin

BBu

nyae

tal.,2007

[14]

69/M

Topicalamph

otericin

B,natamycin→

topicaland

oralvoric

onazole

Kocaturk

etal.,2007

[15]

46/F

LASIK

Topicalamph

otericin

B+natamycin

+oralitracon

azole

PKP

PKPaft

erresolutio

nof

infection

Tu,200

9[16]

39/M

SCL

Topicalvoricon

azole→

oralvoric

onazole+

topicaln

atam

ycin→

intrastro

malinjectionof

voric

onazole+

topicalcaspo

fung

inTu

,200

9[16]

45/M

Trauma

Topicaln

atam

ycin

+oralitracon

azole→

topicalfl

ucon

azole

Tu,200

9[16]

70/M

COAG

DM

Topicalfl

ucon

azole

Usuietal.,2009

[17]

55/M

Glau

coma

Topicalfl

ucon

azole+

micon

azole→

topicalamph

otericin

BShen

etal.,2010

[18 ]

62/F

Trauma

Topicaln

atam

ycin

+oralketoconazole→

intracam

eralvoric

onazole

Com

binedendo

phthalmitis

Ursea

etal.,2010

[19]

72/F

RGPlens

Old

PKP

Topicaln

atam

ycin

andam

photericin

BPK

P

Yildizetal.,2010

[20]

41/F

SCL

Topicaln

atam

ycin→

topicaland

oralvoric

onazole

Yildizetal.,2010

[20]

26/F

SCL

Topicaln

atam

ycin→

topicalvoricon

azole

Martone

etal.,2011[21]

68/M

Trauma

Topical+

oralvoric

onazole

Neohetal.,2011[22]

67/M

Bullo

uskeratopathy

Topicaland

intrastro

malvoric

onazole+

caspofun

gin

PKP

Konidaris

etal.,2013

[23]

66/F

PKP

Topicaland

oralvoric

onazole+

topicalamph

otericin

BPK

PM:m

ale,F:female,HSV

:herpessim

plex

virus,PK

P:penetra

tingkeratoplasty,E

CCE:

extracapsularc

ataractextraction,

DM:d

iabetesm

ellitus,L

ASIK:

laser-assis

tedin

situkeratomileusis,

Kpro:keratop

rosthesis

,SC

L:softcontactlens,CO

AG:chron

icop

enangleg

laucom

a,andRG

P:rig

idgasp

ermeablelens.


(a) (b)

Figure 1: Alternaria keratitis presenting as a central corneal infiltrate with feathery margin. (a) Patient 3, coinfected with Mycobacteriumchelonae. (b) Patient 5.

Table 3: Clinical features of Alternaria keratitis.

Characteristics Previous cases (𝑛 = 25) Current cases (𝑛 = 7) 𝑃 valueAge, median year (range) 56 (26 to 72) 62 (17 to 76) 0.21Gender, number of males (%) 17 (68%) 4 (57%) 0.32Risk factor, number (%)

Trauma 9 (36%) 5 (72%) 0.06Preexisting corneal disease or surgery 10 (40%) 0


[29]. All of these cases were diagnosed at an early stage,presented with small, superficial, paracentral, or peripherallesions, similar to our case. Host immunoresponsiveness, adecrease in organism loading after corneal scrapings, and thepossible antifungal effects of certain antibiotics [32] are likelyassociated with the solution of infection in these cases.

Two of our patients (Patients 3 and 4) underwent super-ficial keratectomy. Superficial keratectomy may aid in themedical management of fungal keratitis by increasing drugpenetration, removing infected corneal tissue, and subse-quently reducing themicrobial load. However, the increase ofcorneal perforation after early keratectomy is concerning. Linet al. studied treatment outcome, cost of care, and long-termcomplications in patients with moderate Fusarium keratitiswho received early keratectomy compared with those treatedmedically and observed that the early keratectomy grouphad a shorter hospital stay, shorter disease duration, lowerhospitalization costs, and lower rates of corneal perforationthan the medical therapy group did [33]. Topical natamycinsolution was prescribed for our Patient 4, having receivedchronic keratitis treatment elsewhere for 4 months, andsuperficial keratectomy was performed on the day afteradmission, based on a presumed diagnosis of fungal keratitis.Unfortunately, perforation occurred 5 days later; thus, a patchgraft with a glycerol-preserved cornea was performed. Theprogressive and perforated ulcer in this patient was partiallycaused by inadequate medical treatment, because previousreports indicated that Alternaria spp. appeared to be largelyresistant to natamycin clinically [12, 16]; however, in ourstudy, 2 other patients responded well to natamycin solely.Superficial keratectomymight be at least partially responsiblefor perforation in this case. How to judge which caseswith Alternaria keratitis would benefit from early superficialkeratectomy is critical and requires further investigation.

Our patients appeared to respond well to medical treat-ment and presented more favorable outcomes when com-pared with previous case reports. Although some reportingbias may exist, early diagnosis (


[14] V. Y. Bunya, K. M. Hammersmith, C. J. Rapuano, B. D. Ayres,and E. J. Cohen, “Topical and oral voriconazole in the treatmentof fungal keratitis,”American Journal of Ophthalmology, vol. 143,no. 1, pp. 151–153, 2007.

[15] T. Kocaturk, R. Pineda II, L. K. Green, and D. T. Azar, “Post-LASIK epithelial dendritic defect associated with Alternaria,”Cornea, vol. 26, no. 9, pp. 1144–1146, 2007.

[16] E. Y. Tu, “Alternaria keratitis: clinical presentation and resolu-tion with topical fluconazole or intrastromal voriconazole andtopical caspofungin,” Cornea, vol. 28, no. 1, pp. 116–119, 2009.

[17] T. Usui, Y. Misawa, N. Honda, A. Tomidokoro, S. Yam-agami, and S. Amano, “Nontraumatic keratomycosis caused byAlternaria in a glaucoma patient,” International Ophthalmology,vol. 29, no. 6, pp. 529–531, 2009.

[18] Y.-C. Shen, C.-Y. Wang, H.-Y. Tsai, and H.-N. Lee, “Intra-cameral voriconazole injection in the treatment of fungalendophthalmitis resulting from keratitis,” American Journal ofOphthalmology, vol. 149, no. 6, pp. 916–921, 2010.

[19] R. Ursea, L. A. Tavares, M. T. Feng, A. Z. McColgin, R. W. Sny-der, and D. M.Wolk, “Non-traumatic Alternaria keratomycosisin a rigid gas-permeable contact lens patient,” British Journal ofOphthalmology, vol. 94, no. 3, pp. 389–390, 2010.

[20] E. H. Yildiz, H. Ailani, K. M. Hammersmith, R. C. Eagle Jr.,C. J. Rapuano, and E. J. Cohen, “Alternaria and paecilomyceskeratitis associated with soft contact lens wear,” Cornea, vol. 29,no. 5, pp. 564–568, 2010.

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[23] V. Konidaris, A. Mersinoglou, T. A. Vyzantiadis, D.Papadopoulou, K. G. Boboridis, and P. Ekonomidis, “Cornealtransplant infection due to Alternaria alternata: a case report,”Case Reports in Ophthalmological Medicine, vol. 2013, ArticleID 589620, 3 pages, 2013.

[24] J. Chander and A. Sharma, “Prevalence of fungal corneal ulcersin Northern India,” Infection, vol. 22, no. 3, pp. 207–209, 1994.

[25] M. A. Tanure, E. J. Cohen, S. Sudesh, C. J. Rapuano, and P. R.Laibson, “Spectrum of fungal keratitis at Wills Eye Hospital,Philadelphia, Pennsylvania,” Cornea, vol. 19, no. 3, pp. 307–312,2000.

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[27] U. Jurkunas, I. Behlau, and K. Colby, “Fungal keratitis: changingpathogens and risk factors,” Cornea, vol. 28, no. 6, pp. 638–643,2009.

[28] L.Wang, S. Sun, Y. Jing, L.Han,H. Zhang, and J. Yue, “Spectrumof fungal keratitis in central China,” Clinical & ExperimentalOphthalmology, vol. 37, no. 8, pp. 763–771, 2009.

[29] W.-B. Khor, T. Aung, S.-M. Saw et al., “An outbreak of Fusariumkeratitis associated with contact lens wear in Singapore,” TheJournal of the American Medical Association, vol. 295, no. 24,pp. 2867–2873, 2006.

[30] A.M. Brooks,M.G. Lazarus, and J.M.Weiner, “Soft contact lenscontamination by Alternaria alternata,” The Medical Journal ofAustralia, vol. 140, no. 8, pp. 490–491, 1984.

[31] I. Pujol, C. Aguilar, J. Gene, and J. Guarro, “In vitro antifungalsusceptibility of Alternaria spp. and Ulocladium spp.,” TheJournal of Antimicrobial Chemotherapy, vol. 46, no. 2, pp. 337–338, 2000.

[32] S. Day, P. Lalitha, S. Haug et al., “Activity of antibiotics againstFusarium and Aspergillus,” British Journal of Ophthalmology,vol. 93, no. 1, pp. 116–119, 2009.

[33] H. C. Lin, J. L. Lin, D. T. Lin-Tan, H. K. Ma, and H. C. Chen,“Early keratectomy in the treatment of moderate FusariumKeratitis,” PLoS ONE, vol. 7, no. 8, Article ID e42126, 2012.

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