- Email: [email protected]
Treatment resistant fungal keratitis caused by Colletotrichum gloeosporioides
ARTICLE IN PRESS a r c h s o c e s p o f t a l m o l . 2 0 1 6;x x x(x x):xxx–xxx
ARCHIVOS DE LA SOCIEDAD ESPAÑOLA DE OFTALMOLOGÍA www.elsevier.es/oftalmologia
Short communication
Treatment resistant fungal keratitis caused by Colletotrichum gloeosporioides夽 J. Lamarca ∗ , F. Vilaplana, J. Nadal, I. García-Barberán, R.I. Barraquer Centro de Oftalmología Barraquer, Barcelona, Spain
a r t i c l e
i n f o
a b s t r a c t
Article history:
Case report: A 56-year-old woman suffered corneal injury from a branch of an orange tree.
Received 11 November 2014
Forty days later she suffered a severe ocular infection, positive to Colletotrichum gloeospori-
Accepted 1 July 2015
oides (C. gloeosporioides). The patient did not respond to traditional treatment or crosslinking,
Available online xxx
and had to be treated with keratoplasty, suffering intraoperative and postoperative complications.
Keywords:
Discussion: Ocular infections due to C. gloeosporioides can occasionally be refractory to tradi-
Fungal keratitis
tional and new treatments, such as crosslinking.
Colletotrichum
˜ © 2015 Sociedad Espanola de Oftalmología. Published by Elsevier España, S.L.U. All rights reserved.
Plant ocular trauma Cross-linking
Queratitis fúngica por Colletotrichum gloeosporioides resistente a tratamiento r e s u m e n Palabras clave:
˜ Caso clínico: Mujer de 56 anos, que sufrió un traumatismo con rama de naranjo en el
Queratitis fúngica
ojo izquierdo. Durante 40 días después desarrolla una infección ocular positiva para
Colletotrichum
Colletotrichum gloeosporioides (C. gloeosporioides). El paciente no respondió al tratamiento
Traumatismo ocular vegetal
clásico ni al cross-linking y tuvo que ser mediante queratoplastia con complicaciones intra-
Cross-linking
operatorias y postoperatorias. Discusión: Las infecciones oculares por Colletotrichum gloeosporioides pueden ser refractarias al tratamiento tradicional así como a nuevas terapias como el cross-linking. ˜ © 2015 Sociedad Espanola de Oftalmología. Publicado por Elsevier España, S.L.U. Todos los derechos reservados.
夽 Please cite this article as: Lamarca J, Vilaplana F, Nadal J, García-Barberán I, Barraquer RI. Queratitis fúngica por Colletotrichum gloeosporioides resistente a tratamiento. Arch Soc Esp Oftalmol. 2016. http://dx.doi.org/10.1016/j.oftal.2015.07.008 ∗ Corresponding author. E-mail address: [email protected] (J. Lamarca). ˜ 2173-5794/© 2015 Sociedad Espanola de Oftalmología. Published by Elsevier España, S.L.U. All rights reserved.
OFTALE-870; No. of Pages 5
ARTICLE IN PRESS 2
a r c h s o c e s p o f t a l m o l . 2 0 1 6;x x x(x x):xxx–xxx
Introduction Colletotrichum gloeosporioides (C. gloeosporioides) is an opportunistic fungus that develops in plant material, particularly citrus. It rarely produces infections in humans and very few articles describe ocular involvement and therapeutic results.1–4 A case is reported below in which this pathogen did not respond to conventional therapy or other therapies such as cross-linking.
Clinic case report Patient, 56, visited the emergency department complaining of pain and reddening in the left eye (LE). Forty days earlier she suffered a traumatism with an orange tree branch that was treated with occlusion and the following eye drops: moxifloxacine 5 mg/ml every 2 h, atropin 1% every 12 h and medroxyprogesterone acetate 20 mg/1 ml with tetrizoline hydrochloride 0.5 mg/1 ml every 4 h. The patient was administered moxifloxacin orally 400 mg every 24 h. The visual examination of the affected eye exhibited luminous localization without improvement with correction. Biomicroscopy revealed conjunctival hyperemia without secretions, inferotemporal corneal de-epithelization, deep and whitish stromal plastron in contact with the lens and a size of 5 mm × 5 mm. Hypopion of 1 mm and Tyndall +++. The
posterior segment could not be seen due to opacity although anatomically correct according to the ecograph (Fig. 1). Treatment for filamentous fungus was initiated (demonstrated with culture and Gram staining), including natamycin 50 mg/ml eyedrops and voriconazole 1%, alternating every hour, including oral voriconazole 400 mg every 24 h. Deepithelization was performed daily to facilitate penetration of the treatment. Due to persistence of the corneal ulcer and 2 mm and hypopion during 11 days, samples were taken in the surgery room for conventional culture and PCR, in addition to administering an intrastromal injection of voriconazole 100 g/0.1 m in 0.1 ml and anterior chamber cleansing. The results were positive for C. gloeosporioides, sensitive to natamycin and voriconazole, for which reason the therapeutic treatment was not modified (Fig. 2). Due to worsening of the patient condition in the following days, corneal cross-linking5 was performed, prescribing eyedrops recommended in the literature3 for this pathogen, i.e., amphotericin B 0.5 mg/ml every 2 h, voriconazole 1% every 2 h and tobramycin 3 mg/ml every 4 h. Despite the treatment in subsequent days, the condition progressively deteriorated (Fig. 3), including vitritis confirmed by ecograph. Due to the poor evolution of the condition (Fig. 4) penetrating keratoplasty was performed with lensectomy, anterior vitrectomy and sector iridectomy, after which expansive hemorrhage occurred contained with temporal Landers
Fig. 1 – corneal ulcer (4 mm), hypopion (1 mm) and plastron in the anterior chamber in contact with the lens.
ARTICLE IN PRESS a r c h s o c e s p o f t a l m o l . 2 0 1 6;x x x(x x):xxx–xxx
Fig. 2 – Corneal ulcer (3 mm) with surrounding edema and hypopion (3 mm).
Fig. 3 – De-epithelization (6.5 mm) and hypopion (5 mm). Persistent ulcer.
Fig. 4 – Hypopion as a de-structured mass without level. Persistent ulcer.
3
ARTICLE IN PRESS 4
a r c h s o c e s p o f t a l m o l . 2 0 1 6;x x x(x x):xxx–xxx
Fig. 5 – Penetrating keratoplasty. Hypopion not observed.
penetrating keratoplasty which caused temporal retina detachment (RD) and choroidal detachment (CD) comprising over half the chamber in superior quadrants. For this reason, drainage was performed with sclerotomies and 8.5 mm corneal graft. Prescribing prednisolone acetate 10 mg/1 ml every 4 h, moxifloxacin 5 mg/ml 5 times a day and amphotericin B 0.5 mg/ml 5 times a day. Five days post-surgery, echography revealed hemorrhagic CD in the 4 quadrants. CD was drained, carrying out posterior vitrectomy, peripheral retinectomy, laser photocoagulation and silicone 5000 cSt. A combination of dexamethasone 1 mg and tobramycin 3 mg every 6 h in eyedrops were added to the fungostatic treatment. Moxifloxacin 5 mg/ml was suspended.
The following day, treatment was initiated with oral prednisolone 30 mg every 24 h, voriconazole 200 mg every 24 h and omeprazol 20 mg every 24 h (Fig. 5). Examination 3 months after the surgery did not reveal signs of infection. However, anterior synechiae, hyphema (Fig. 6) and RD were observed. In this situation, pupiloplasty, VPP preand retro-retinal peeling, retinotomy-retinectomy, laser and silicone were performed. Signs of infection were not observed in the following months and the retina remains adhered. After 9 months, treatment with 10 mg/1 ml prednisolone acetate was reduced to twice a day (Fig. 6). One year later, corrected visual acuity is of 0.03.
Fig. 6 – Upper images: 3 months after keratoplasty, well adapted graft and hyphema can be observed. Lower images: 5 days after retina detachment relapse, graft is well adapted and anterior chamber is clear.
ARTICLE IN PRESS a r c h s o c e s p o f t a l m o l . 2 0 1 6;x x x(x x):xxx–xxx
Discussion The present case is one of the few published cases in Spain of demonstrated C. gloeosporioides.2,3 Resistance to amphotericin B eyedrops, natamycin and voriconazole was evident, as in other cases.2,6,7 The contribution to existing literature involves the fact that the use of cross-linking was not effective, probably due to the highly evolved condition. Fungal keratitis due to Colletotrichum is exceptional,3,6 slowly progressive and identifiable by means of microbiological techniques.2,3 There is consensus in that rapid identification and immediate treatment is crucial to avoid complications.6–9
Conflict of interests No conflict of interests was declared by the authors.
references
1. Yamamoto N, Matsumoto T, Ishibashi Y. Fungal keratitis caused by Colletotrichum gloeosporioides. Cornea. 2001;20:902–3.
5
2. Navalpotro Rodríguez D, Martinez-Macias O, Domínguez-Márquez V, Burgos Teruel A. Severe corneal infection by Colletotrichum gloeosporioides in a farmer. Med Clin (Barc). 2014;142:138–9. 3. Morcillo Guardiola M, Hurtado Montalbán N, Martínez Morales JA, Villegas Pérez MP, Miralles de Imperal Mora Figueroa J. Queratitis fúngica por Colletotrichum spp. A propósito de un caso, Murcia. Arch Soc Esp Oftalmol. 2014;89:110–2. 4. Fernandez V, Dursun D, Miller M, Alfonso EC. Colletotrichum keratitis. Am J Ophthalmol. 2002;134:435–8. 5. Shiraishi A, Araki-Sasaki K, Mitani A, Miyamoto H, Sunada A, Ueda A, et al. Clinical characteristics of keratitis due to Colletotrichum gloeosporioides. J Ocul Pharmacol Ther. 2011;27:487–91. 6. Ammermann C, Cursiefen C, Hermann M. Corneal cross-linking in microbial keratitis to prevent à chaudkeratoplasty: a retrospective case series. Klin Monatsbl Augenheilkd. 2014;231:619–25. 7. Shivaprakash MR, Appannanavar SB, Dhaliwal M, Gupta A, Gupta S, Gupta A, et al. Colletotrichum truncatum: an unusual pathogen causing mycotic keratitis and endophthalmitis. J Clin Microbiol. 2011;49:2894–8. 8. Rosa RH, Miller D, Alfonso EC. The changing spectrum of fungal keratitis in South Florida. Ophthalmology. 1994;101: 1005–13. 9. Tanure MAG, Cohen EJ, Sudes S, Capuano CJ, Laibson PR. Spectrum of fungal keratitis at Wills eye hospital, Philadelphia, Pennsylvania. Cornea. 2000;19:307–12.
ARCHIVOS DE LA SOCIEDAD ESPAÑOLA DE OFTALMOLOGÍA www.elsevier.es/oftalmologia
Short communication
Treatment resistant fungal keratitis caused by Colletotrichum gloeosporioides夽 J. Lamarca ∗ , F. Vilaplana, J. Nadal, I. García-Barberán, R.I. Barraquer Centro de Oftalmología Barraquer, Barcelona, Spain
a r t i c l e
i n f o
a b s t r a c t
Article history:
Case report: A 56-year-old woman suffered corneal injury from a branch of an orange tree.
Received 11 November 2014
Forty days later she suffered a severe ocular infection, positive to Colletotrichum gloeospori-
Accepted 1 July 2015
oides (C. gloeosporioides). The patient did not respond to traditional treatment or crosslinking,
Available online xxx
and had to be treated with keratoplasty, suffering intraoperative and postoperative complications.
Keywords:
Discussion: Ocular infections due to C. gloeosporioides can occasionally be refractory to tradi-
Fungal keratitis
tional and new treatments, such as crosslinking.
Colletotrichum
˜ © 2015 Sociedad Espanola de Oftalmología. Published by Elsevier España, S.L.U. All rights reserved.
Plant ocular trauma Cross-linking
Queratitis fúngica por Colletotrichum gloeosporioides resistente a tratamiento r e s u m e n Palabras clave:
˜ Caso clínico: Mujer de 56 anos, que sufrió un traumatismo con rama de naranjo en el
Queratitis fúngica
ojo izquierdo. Durante 40 días después desarrolla una infección ocular positiva para
Colletotrichum
Colletotrichum gloeosporioides (C. gloeosporioides). El paciente no respondió al tratamiento
Traumatismo ocular vegetal
clásico ni al cross-linking y tuvo que ser mediante queratoplastia con complicaciones intra-
Cross-linking
operatorias y postoperatorias. Discusión: Las infecciones oculares por Colletotrichum gloeosporioides pueden ser refractarias al tratamiento tradicional así como a nuevas terapias como el cross-linking. ˜ © 2015 Sociedad Espanola de Oftalmología. Publicado por Elsevier España, S.L.U. Todos los derechos reservados.
夽 Please cite this article as: Lamarca J, Vilaplana F, Nadal J, García-Barberán I, Barraquer RI. Queratitis fúngica por Colletotrichum gloeosporioides resistente a tratamiento. Arch Soc Esp Oftalmol. 2016. http://dx.doi.org/10.1016/j.oftal.2015.07.008 ∗ Corresponding author. E-mail address: [email protected] (J. Lamarca). ˜ 2173-5794/© 2015 Sociedad Espanola de Oftalmología. Published by Elsevier España, S.L.U. All rights reserved.
OFTALE-870; No. of Pages 5
ARTICLE IN PRESS 2
a r c h s o c e s p o f t a l m o l . 2 0 1 6;x x x(x x):xxx–xxx
Introduction Colletotrichum gloeosporioides (C. gloeosporioides) is an opportunistic fungus that develops in plant material, particularly citrus. It rarely produces infections in humans and very few articles describe ocular involvement and therapeutic results.1–4 A case is reported below in which this pathogen did not respond to conventional therapy or other therapies such as cross-linking.
Clinic case report Patient, 56, visited the emergency department complaining of pain and reddening in the left eye (LE). Forty days earlier she suffered a traumatism with an orange tree branch that was treated with occlusion and the following eye drops: moxifloxacine 5 mg/ml every 2 h, atropin 1% every 12 h and medroxyprogesterone acetate 20 mg/1 ml with tetrizoline hydrochloride 0.5 mg/1 ml every 4 h. The patient was administered moxifloxacin orally 400 mg every 24 h. The visual examination of the affected eye exhibited luminous localization without improvement with correction. Biomicroscopy revealed conjunctival hyperemia without secretions, inferotemporal corneal de-epithelization, deep and whitish stromal plastron in contact with the lens and a size of 5 mm × 5 mm. Hypopion of 1 mm and Tyndall +++. The
posterior segment could not be seen due to opacity although anatomically correct according to the ecograph (Fig. 1). Treatment for filamentous fungus was initiated (demonstrated with culture and Gram staining), including natamycin 50 mg/ml eyedrops and voriconazole 1%, alternating every hour, including oral voriconazole 400 mg every 24 h. Deepithelization was performed daily to facilitate penetration of the treatment. Due to persistence of the corneal ulcer and 2 mm and hypopion during 11 days, samples were taken in the surgery room for conventional culture and PCR, in addition to administering an intrastromal injection of voriconazole 100 g/0.1 m in 0.1 ml and anterior chamber cleansing. The results were positive for C. gloeosporioides, sensitive to natamycin and voriconazole, for which reason the therapeutic treatment was not modified (Fig. 2). Due to worsening of the patient condition in the following days, corneal cross-linking5 was performed, prescribing eyedrops recommended in the literature3 for this pathogen, i.e., amphotericin B 0.5 mg/ml every 2 h, voriconazole 1% every 2 h and tobramycin 3 mg/ml every 4 h. Despite the treatment in subsequent days, the condition progressively deteriorated (Fig. 3), including vitritis confirmed by ecograph. Due to the poor evolution of the condition (Fig. 4) penetrating keratoplasty was performed with lensectomy, anterior vitrectomy and sector iridectomy, after which expansive hemorrhage occurred contained with temporal Landers
Fig. 1 – corneal ulcer (4 mm), hypopion (1 mm) and plastron in the anterior chamber in contact with the lens.
ARTICLE IN PRESS a r c h s o c e s p o f t a l m o l . 2 0 1 6;x x x(x x):xxx–xxx
Fig. 2 – Corneal ulcer (3 mm) with surrounding edema and hypopion (3 mm).
Fig. 3 – De-epithelization (6.5 mm) and hypopion (5 mm). Persistent ulcer.
Fig. 4 – Hypopion as a de-structured mass without level. Persistent ulcer.
3
ARTICLE IN PRESS 4
a r c h s o c e s p o f t a l m o l . 2 0 1 6;x x x(x x):xxx–xxx
Fig. 5 – Penetrating keratoplasty. Hypopion not observed.
penetrating keratoplasty which caused temporal retina detachment (RD) and choroidal detachment (CD) comprising over half the chamber in superior quadrants. For this reason, drainage was performed with sclerotomies and 8.5 mm corneal graft. Prescribing prednisolone acetate 10 mg/1 ml every 4 h, moxifloxacin 5 mg/ml 5 times a day and amphotericin B 0.5 mg/ml 5 times a day. Five days post-surgery, echography revealed hemorrhagic CD in the 4 quadrants. CD was drained, carrying out posterior vitrectomy, peripheral retinectomy, laser photocoagulation and silicone 5000 cSt. A combination of dexamethasone 1 mg and tobramycin 3 mg every 6 h in eyedrops were added to the fungostatic treatment. Moxifloxacin 5 mg/ml was suspended.
The following day, treatment was initiated with oral prednisolone 30 mg every 24 h, voriconazole 200 mg every 24 h and omeprazol 20 mg every 24 h (Fig. 5). Examination 3 months after the surgery did not reveal signs of infection. However, anterior synechiae, hyphema (Fig. 6) and RD were observed. In this situation, pupiloplasty, VPP preand retro-retinal peeling, retinotomy-retinectomy, laser and silicone were performed. Signs of infection were not observed in the following months and the retina remains adhered. After 9 months, treatment with 10 mg/1 ml prednisolone acetate was reduced to twice a day (Fig. 6). One year later, corrected visual acuity is of 0.03.
Fig. 6 – Upper images: 3 months after keratoplasty, well adapted graft and hyphema can be observed. Lower images: 5 days after retina detachment relapse, graft is well adapted and anterior chamber is clear.
ARTICLE IN PRESS a r c h s o c e s p o f t a l m o l . 2 0 1 6;x x x(x x):xxx–xxx
Discussion The present case is one of the few published cases in Spain of demonstrated C. gloeosporioides.2,3 Resistance to amphotericin B eyedrops, natamycin and voriconazole was evident, as in other cases.2,6,7 The contribution to existing literature involves the fact that the use of cross-linking was not effective, probably due to the highly evolved condition. Fungal keratitis due to Colletotrichum is exceptional,3,6 slowly progressive and identifiable by means of microbiological techniques.2,3 There is consensus in that rapid identification and immediate treatment is crucial to avoid complications.6–9
Conflict of interests No conflict of interests was declared by the authors.
references
1. Yamamoto N, Matsumoto T, Ishibashi Y. Fungal keratitis caused by Colletotrichum gloeosporioides. Cornea. 2001;20:902–3.
5
2. Navalpotro Rodríguez D, Martinez-Macias O, Domínguez-Márquez V, Burgos Teruel A. Severe corneal infection by Colletotrichum gloeosporioides in a farmer. Med Clin (Barc). 2014;142:138–9. 3. Morcillo Guardiola M, Hurtado Montalbán N, Martínez Morales JA, Villegas Pérez MP, Miralles de Imperal Mora Figueroa J. Queratitis fúngica por Colletotrichum spp. A propósito de un caso, Murcia. Arch Soc Esp Oftalmol. 2014;89:110–2. 4. Fernandez V, Dursun D, Miller M, Alfonso EC. Colletotrichum keratitis. Am J Ophthalmol. 2002;134:435–8. 5. Shiraishi A, Araki-Sasaki K, Mitani A, Miyamoto H, Sunada A, Ueda A, et al. Clinical characteristics of keratitis due to Colletotrichum gloeosporioides. J Ocul Pharmacol Ther. 2011;27:487–91. 6. Ammermann C, Cursiefen C, Hermann M. Corneal cross-linking in microbial keratitis to prevent à chaudkeratoplasty: a retrospective case series. Klin Monatsbl Augenheilkd. 2014;231:619–25. 7. Shivaprakash MR, Appannanavar SB, Dhaliwal M, Gupta A, Gupta S, Gupta A, et al. Colletotrichum truncatum: an unusual pathogen causing mycotic keratitis and endophthalmitis. J Clin Microbiol. 2011;49:2894–8. 8. Rosa RH, Miller D, Alfonso EC. The changing spectrum of fungal keratitis in South Florida. Ophthalmology. 1994;101: 1005–13. 9. Tanure MAG, Cohen EJ, Sudes S, Capuano CJ, Laibson PR. Spectrum of fungal keratitis at Wills eye hospital, Philadelphia, Pennsylvania. Cornea. 2000;19:307–12.