Research
Original Investigation
Prolonged Curvularia Endophthalmitis Due to Organism Sequestration Aleksandra V. Rachitskaya, MD; Ashvini K. Reddy, MD; Darlene Miller, DHSc, MPH; Janet Davis, MD; Harry W. Flynn Jr, MD; William Smiddy, MD; Wilfredo Lara, MD; Selina Lin, MD; Sander Dubovy, MD; Thomas A. Albini, MD
IMPORTANCE Endophthalmitis caused by Curvularia is a rare condition seen after cataract
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surgery and trauma. The clinical course has not been described previously. OBJECTIVE To examine the clinical course of 6 postoperative and trauma-related cases of Curvularia endophthalmitis. DESIGN, SETTING, AND PARTICIPANTS Retrospective case series. We reviewed the archives of the microbiology laboratory of Bascom Palmer Eye Institute, a tertiary referral hospital, from January 1, 1980, through September 30, 2013, to identify cases of Curvularia endophthalmitis. Data collected included demographic information, the cause of endophthalmitis, presenting features, treatment course, the number of recurrences, the area of organism sequestration, and final visual outcome. EXPOSURES Trauma and cataract surgery. MAIN OUTCOMES AND MEASURES Times from the inciting event to presentation of symptoms, diagnosis, and eradication; visual acuity; and identification of the area of sequestration. RESULTS We identified 6 patients with Curvularia endophthalmitis, including 5 who
underwent cataract surgery and 1 after trauma. The diagnosis was established rapidly in the trauma case. In the postoperative cases, the time from the surgery to first symptoms ranged from 2 to 5 months; from the surgery to correct diagnosis, 7 to 24 months; and from the surgery to eradication, 8 to 27 months. Despite aggressive antifungal therapy, eradication of the infection could be achieved only by identification and removal of the nidus of sequestration. The median follow-up was 29.5 months. CONCLUSIONS AND RELEVANCE In cases of endophthalmitis caused by Curvularia, the diagnosis and treatment are often delayed, especially in postoperative cases. The eradication of the organism requires identification and removal of the nidi of sequestration. JAMA Ophthalmol. 2014;132(9):1123-1126. doi:10.1001/jamaophthalmol.2014.1069 Published online June 5, 2014.
C
urvularia is a dematiaceous or darkly pigmented fungus. Endophthalmitis due to Curvularia species is exceedingly rare, with only isolated case reports in the literature.1-6 Large series of endogenous and exogenous fungal endophthalmitis in the United States do not mention Curvularia as a separate causative organism.7-10 The present series of 6 cases of Curvularia endophthalmitis demonstrates the difficulty of timely and proper diagnosis and challenges in the eradication of the microorganism. jamaophthalmology.com
Author Affiliations: Bascom Palmer Eye Institute, Department of Ophthalmology, Miller School of Medicine, University of Miami, Miami, Florida (Rachitskaya, Reddy, Miller, Davis, Flynn, Smiddy, Dubovy, Albini); Department of Ophthalmology, University of Virginia School of Medicine, Charlottesville (Reddy); Retina Macula Specialists of Miami, Miami, Florida (Lara); Kaufman Eye Institute, Zephyrhills, Florida (Lin). Corresponding Author: Thomas A. Albini, MD, Bascom Palmer Eye Institute, Department of Ophthalmology, Miller School of Medicine, University of Miami, 900 NW 17th St, Miami, FL 33136 ([email protected]).
Methods An institutional review board–approved retrospective review of the archives of the microbiology laboratory at Bascom Palmer Eye Institute from January 1, 1980, through September 30, 2013, identified all cultures positive for Curvularia. The substrate (blood agar, chocolate agar, Sabouraud agar, LowensteinJensen agar, or thioglycolate broth) on which Curvularia grew JAMA Ophthalmology September 2014 Volume 132, Number 9
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Table. Clinical Characteristics of Patients With Curvularia Endophthalmitis Curvularia Substrate (Time From Date of To To Plating Surgery/ Trauma Symptoms Diagnosis Specimen to Growth) Time From Inciting Event
Case No./ Age, y Eye
Comorbidities
Cause
1/79
R
DM, hypertension, anemia, possible RA
CE/IOLI November 2006
2/21
L
None
Trauma July 2007
3/76
R
4/67
L
5/84
6/70
VA (Time)
Time From Inciting Event to Presumed Eradication, Area of Sequestration mo
Presentation
Final FU
Vitreous Blood agar, wash of Sabouraud iris lesion agar (3 d)
HM (POM 12)
20/100 (POM 34)
23
Iris lesion
5 mo
12 mo
0
6 wk
Vitreous
Chocolate agar, blood agar, Sabouraud agar, thioglycolate broth (48 h)
2/200 (POW 2)
20/200 (POM 35)
16
Cornea
DM, hypertension, CE/IOLI November hypercholesterolemia 2009
3 mo
7 mo
Vitreous
Chocolate agar, blood agar, Sabouraud agar, thioglycolate broth (3 d)
20/70 (POM 6)
20/60 (POM 31)
14
Ciliary body membranes
DM, hypertension, fibromyalgia, cerebral aneurysm, stroke
CE/IOLI September 2010
2 mo
19 mo
Vitreous
Unknown
20/400 (POM 23)
20/300 (POM 28)
25
Capsule, subretinal abscess
L
COPD, asthma, hypertension, hyperlipidemia
CE/IOLI March 2011
3 mo
7 mo
Vitreous
Chocolate agar (blood agar)
CF (POM 3)
20/400 (POM 11)
8
R
Hypothyroidism, hypertension
CE/IOLI August 2011
2 mo
24 mo
Vitreous
Chocolate agar, blood agar, Sabouraud agar, LowensteinJensen medium (3 d)
1/200 (POM 24)
LP (POM 27)
27
Capsular bag
Unknown
Abbreviations: CE/IOLI, cataract extraction with intraocular lens implantation; CF, counting fingers; COPD, chronic obstructive pulmonary disease; DM, diabetes mellitus; FU, follow-up; HM, hand motions; L, left; LP, light perception; NA, not available; POM, postoperative month; POW, postoperative week; R, right; RA, rheumatoid arthritis; VA, visual acuity.
was documented with the time from initial specimen plating to organism growth. We identified a total of 7 patients with vitreous cultures positive for Curvularia. One additional patient had culture-confirmed Curvularia endophthalmitis with a vitreous culture performed at another hospital. Because the patient was treated for her condition at Bascom Palmer Eye Institute and we had access to the patient’s complete medical records, she was included in the study. Thus, we reviewed the records of 8 patients. Two patients were excluded after review of the clinical history because they did not develop clinical endophthalmitis. Therefore, we included a total of 6 cases of Curvularia endophthalmitis, with 2 of these patients previously described in separate reports4,5 (cases 1 and 2 in the Supplement [eAppendix]).
Results A total of 6 patients with endophthalmitis caused by Curvularia species were identified and reviewed in chronological order (Table). In 5 patients (mean age, 75.2 years), endophthalmitis occurred after cataract surgery with intraocular lens implantation; in 1 patient (age, 21 years), endophthalmitis occurred after trauma. The diagnosis was established rapidly at 6 weeks in the trauma case. In the postoperative cases, the time from surgery to the first signs of inflammation ranged from 2 1124
to 5 months. The time from the surgery to correct diagnosis of Curvularia endophthalmitis ranged from 7 to 24 months. The patients with postoperative endophthalmitis were treated with topical corticosteroids (n = 5), sub–Tenon or subconjunctival injection of triamcinolone acetonide (n = 3), or systemic methotrexate sodium and azathioprine sodium (n = 1). These patients underwent a mean of 2 (range, 0-5) intraocular procedures and operations, including anterior chamber culture, vitreous culture, intraocular injection, or pars plana vitrectomy. In 5 postoperative cases, the definitive surgery that established the diagnosis of Curvularia endophthalmitis was pars plana vitrectomy with vitreous cultures, partial or complete capsulectomy or lensectomy, and intravitreal injection of antimicrobials. The time from the inciting event (surgery or trauma) to eradication in all 6 patients ranged from 8 to 27 months. During this time the patients were treated with topical, oral, and, in 1 case, intravenous antifungals. They underwent a mean of 1.8 intraocular procedures, usually with concurrent intravitreal antifungal treatment, with a mean of 6.8 separate intravitreal antifungal injections. Despite aggressive antifungal therapy, eradication of the infection could be achieved only by identification and removal of the nidus of sequestration. This process required the use of imaging studies, such as ultrasonography, and use of endoscopy during the pars plana vitrectomy. The nidi of sequestration included an iris lesion, a corneal endothelial plaque, ciliary body mem-
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Curvularia Endophthalmitis
Original Investigation Research
Figure. Nidi of Sequestration in Curvularia Endophthalmitis A
C
B
D
A, A hypopyon and an iris lesion, representing a nidus of Curvularia sequestration, in a patient with pseudophakia (case 1). B, Corneal laceration repair with corneal infiltrate harboring Curvularia organisms in a trauma patient (case 2). C, Histopathologic photomicrograph of Curvularia organisms in the corneal stroma of the trauma patient (Gomori methenamine silver, original magnification ×100) (case 2). D, Posterior capsular opacity and Curvularia endophthalmitis in a patient with pseudophakia (case 3).
branes, capsular bag, and subretinal abscess (several of these nidi are shown in the Figure). The visual acuity at presentation ranged from 20/70 to hand motions. The median follow-up was 29.5 (range, 11-35) months. The final visual acuity ranged from 20/60 to light perception.
Discussion We report the first, to our knowledge, clinical series (6 patients) with intraocular cultures positive for Curvularia species. Curvularia, a widespread septate mold that is black owing to melanin in its hyphae and conidia, is found in tropical climates, lives in the soil and on plants, and is spread by airborne spores.11 In the literature, the number of reports of Curvularia keratitis has increased through the last half of the 20th century, with most of the reports coming from India, the United States, and Asia.11 Nevertheless, fungal keratitis due to Curvularia is less frequent than that due to Candida, Fusarium, or Aspergillus species. 11 Cases of Curvularia endophthalmitis are rare, but reports are increasing. The first reports of Curvularia endophthalmitis are from India in early 2000.3,6,12 Review of the records of the microbiology laboratory at our institution disclosed that the first case of clinically significant Curvularia endophthalmitis was documented in 2006 (case 1; Table). Four large studies focusing on endogenous and exogenous fungal endophthalmitis at our institution spanning 1984 through 199310 and 1990 through 20098 for endogenous and 1969 through 19867 and 1990 through 20069 for exogenous infections did not identify any cases of Curvularia endophthalmitis. jamaophthalmology.com
Curvularia was not documented as a human pathogen until 1959.13 Curvularia species most commonly cause skin infections, invasive sinusitis, and allergic fungal sinusitis.14,15 Cases of pulmonary and cerebral infection and arthritis, osteomyelitis, fungemia, endocarditis, peritonitis, and gastrointestinal tract disease have been reported.14,16-18 Infections with Curvularia do not appear to require an immunosuppressed host, and inhalation and skin inoculation are the main routes of infection.15,18 In the present study, 1 patient was otherwise healthy (case 2). The other patients had several comorbidities such as hypertension, diabetes mellitus, cerebral aneurysm, stroke, anemia, hypothyroidism, and possible rheumatoid arthritis (Table). However, none of them were significantly immunocompromised. In Curvularia keratitis, trauma with plant matter or dirt is the leading cause of infection. 11 In the present traumarelated case of Curvularia endophthalmitis, the trauma was due to nail injury. No unusual exposure was seen in surgeryrelated cases. However, Curvularia species have been isolated in the conjunctival sac of healthy individuals.19 In the trauma-related case of endophthalmitis, the diagnosis was established rapidly because the signs suggestive of infectious endophthalmitis increased the level of suspicion. The patients with Curvularia endophthalmitis after cataract surgery had delayed diagnosis and appropriate therapy. The time from surgery to first symptoms ranged from 2 to 5 months. The time from surgery to correct diagnosis ranged from 7 to 24 months. In fact, 3 of 5 patients were treated with sub-Tenon or subconjunctival injection of corticosteroids in addition to topical corticosteroid application before the appropriate diagnosis, and JAMA Ophthalmology September 2014 Volume 132, Number 9
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1 patient received oral immunosuppressive therapy. Propionibacterium acnes is the most common causative organism of delayed-onset endophthalmitis and presents with similar lowgrade inflammation and a slowly progressive course; a posterior capsular plaque is present in about 65% of patients.20 In Curvularia endophthalmitis, the plaque was seen in 3 of 5 patients who had undergone surgery for cataract. Compared with P acnes, Curvularia infection presented with a variety of locations of sequestration, including an endothelial corneal plaque, the posterior lens capsule, a vitreous fungus ball, membranes on the ciliary body, and the subretinal space. In the present case series, the patients received an aggressive treatment consisting of combined intravitreal, oral, topical, and occasionally intravenous antifungals and surgical intervention. Diagnostic and therapeutic vitrectomy was
ARTICLE INFORMATION Submitted for Publication: November 20, 2013; final revision received February 17, 2014; accepted February 20, 2014. Published Online: June 5, 2014. doi:10.1001/jamaophthalmol.2014.1069. Author Contributions: Dr Albini had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: Rachitskaya, Flynn, Albini. Acquisition, analysis, or interpretation of data: All authors. Drafting of the manuscript: Rachitskaya, Reddy, Lara, Lin. Critical revision of the manuscript for important intellectual content: Rachitskaya, Miller, Davis, Flynn, Smiddy, Lin, Dubovy, Albini. Statistical analysis: Flynn. Administrative, technical, or material support: Rachitskaya, Reddy, Miller, Lara, Albini. Study supervision: Dubovy, Albini. Conflict of Interest Disclosures: None reported. Funding/Support: This study is supported in part by Center Core Grant P30EY014801 from the National Institutes of Health; by an unrestricted grant from Research to Prevent Blindness; and by grant W81XWH-09-1-0675 from the Department of Defense. Role of the Sponsor: The funding sources had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. Previous Presentations: This paper was presented at the Annual Meeting of the Association for Research in Vision and Ophthalmology; May 5, 2013; Seattle, Washington; at the Annual Meeting of the American Society of Retina Specialists; August 25, 2013; Toronto, Ontario, Canada; and at the 47th Annual Meeting of the Ocular
1126
necessary in all cases. All the reported cases clearly demonstrate the importance of identification and elimination of the possible source of sequestered infection. This process may require use of preoperative high-resolution ultrasonography and thorough intraoperative depression or endoscopy to visualize the retinal periphery and the retroirideal space.
Conclusions Curvularia infection represents a rare cause of endophthalmitis. The diagnosis and treatment are often delayed, especially in the postoperative cases. The eradication of the organism requires identification and removal of the nidus of sequestration.
Microbiology and Immunology Group; November 15, 2013; New Orleans, Louisiana.
endogenous fungal endophthalmitis. Ophthalmic Surg Lasers. 1997;28(3):185-194.
REFERENCES
11. Wilhelmus KR, Jones DB. Curvularia keratitis. Trans Am Ophthalmol Soc. 2001;99:111-132.
1. Ehlers JP, Chavala SH, Woodward JA, Postel EA. Delayed recalcitrant fungal endophthalmitis secondary to Curvularia. Can J Ophthalmol. 2011;46 (2):199-200.
12. Chakrabarti A, Shivaprakash MR, Singh R, et al. Fungal endophthalmitis: fourteen years’ experience from a center in India. Retina. 2008;28(10): 1400-1407.
2. Berbel RF, Casella AM, de Freitas D, Höfling-Lima AL. Curvularia lunata endophthalmitis. J Ocul Pharmacol Ther. 2011;27(5):535-537.
13. Baylet J, Camain R, Segretain G. Identification of the agents of maduromycoses of Senegal and Mauritania: description of a new species [in French]. Bull Soc Pathol Exot Filiales. 1959;52:448-477.
3. Kaushik S, Ram J, Chakrabarty A, Dogra MR, Brar GS, Gupta A. Curvularia lunata endophthalmitis with secondary keratitis. Am J Ophthalmol. 2001;131 (1):140-142.
14. Silveira F, Nucci M. Emergence of black moulds in fungal disease: epidemiology and therapy. Curr Opin Infect Dis. 2001;14(6):679-684.
4. Pathengay A, Miller DM, Flynn HW Jr, Dubovy SR. Curvularia endophthalmitis following open globe injuries. Arch Ophthalmol. 2012;130(5): 652-654.
15. Brandt ME, Warnock DW. Epidemiology, clinical manifestations, and therapy of infections caused by dematiaceous fungi. J Chemother. 2003;15 (suppl 2):36-47.
5. Sisk RASW, Dubovy SR, Miller D. Chronic Curvularia lunata endophthalmitis following cataract extraction. Retinal Cases Brief Rep. 2009;3(4): 438-439.
16. Varughese S, David VG, Mathews MS, Tamilarasi V. A patient with amphotericin-resistant Curvularia lunata peritonitis. Perit Dial Int. 2011;31(1):108-109.
6. Pathengay A, Shah GY, Das T, Sharma S. Curvularia lunata endophthalmitis presenting with a posterior capsular plaque. Indian J Ophthalmol. 2006;54(1):65-66. 7. Pflugfelder SC, Flynn HW Jr, Zwickey TA, et al. Exogenous fungal endophthalmitis. Ophthalmology. 1988;95(1):19-30. 8. Lingappan A, Wykoff CC, Albini TA, et al. Endogenous fungal endophthalmitis: causative organisms, management strategies, and visual acuity outcomes. Am J Ophthalmol. 2012;153(1): 162-166.e1. doi:10.1016/j.ajo.2011.06.020. 9. Wykoff CC, Flynn HW Jr, Miller D, Scott IU, Alfonso EC. Exogenous fungal endophthalmitis: microbiology and clinical outcomes. Ophthalmology. 2008;115(9):1501-1507.e2. doi:10.1016/j.ophtha.2008 .02.027.
17. Berg D, Garcia JA, Schell WA, Perfect JR, Murray JC. Cutaneous infection caused by Curvularia pallescens: a case report and review of the spectrum of disease. J Am Acad Dermatol. 1995;32 (2, pt 2):375-378. 18. Carter E, Boudreaux C. Fatal cerebral phaeohyphomycosis due to Curvularia lunata in an immunocompetent patient. J Clin Microbiol. 2004;42(11):5419-5423. 19. Sehgal SC, Dhawan S, Chhiber S, Sharma M, Talwar P. Frequency and significance of fungal isolations from conjunctival sac and their role in ocular infections. Mycopathologia. 1981;73(1):17-19. 20. Shirodkar AR, Pathengay A, Flynn HW Jr, et al. Delayed- versus acute-onset endophthalmitis after cataract surgery. Am J Ophthalmol. 2012;153(3): 391-398.e2. doi:10.1016/j.ajo.2011.08.029.
10. Essman TF, Flynn HW Jr, Smiddy WE, et al. Treatment outcomes in a 10-year study of
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Original Investigation
Prolonged Curvularia Endophthalmitis Due to Organism Sequestration Aleksandra V. Rachitskaya, MD; Ashvini K. Reddy, MD; Darlene Miller, DHSc, MPH; Janet Davis, MD; Harry W. Flynn Jr, MD; William Smiddy, MD; Wilfredo Lara, MD; Selina Lin, MD; Sander Dubovy, MD; Thomas A. Albini, MD
IMPORTANCE Endophthalmitis caused by Curvularia is a rare condition seen after cataract
Supplemental content at jamaophthalmology.com
surgery and trauma. The clinical course has not been described previously. OBJECTIVE To examine the clinical course of 6 postoperative and trauma-related cases of Curvularia endophthalmitis. DESIGN, SETTING, AND PARTICIPANTS Retrospective case series. We reviewed the archives of the microbiology laboratory of Bascom Palmer Eye Institute, a tertiary referral hospital, from January 1, 1980, through September 30, 2013, to identify cases of Curvularia endophthalmitis. Data collected included demographic information, the cause of endophthalmitis, presenting features, treatment course, the number of recurrences, the area of organism sequestration, and final visual outcome. EXPOSURES Trauma and cataract surgery. MAIN OUTCOMES AND MEASURES Times from the inciting event to presentation of symptoms, diagnosis, and eradication; visual acuity; and identification of the area of sequestration. RESULTS We identified 6 patients with Curvularia endophthalmitis, including 5 who
underwent cataract surgery and 1 after trauma. The diagnosis was established rapidly in the trauma case. In the postoperative cases, the time from the surgery to first symptoms ranged from 2 to 5 months; from the surgery to correct diagnosis, 7 to 24 months; and from the surgery to eradication, 8 to 27 months. Despite aggressive antifungal therapy, eradication of the infection could be achieved only by identification and removal of the nidus of sequestration. The median follow-up was 29.5 months. CONCLUSIONS AND RELEVANCE In cases of endophthalmitis caused by Curvularia, the diagnosis and treatment are often delayed, especially in postoperative cases. The eradication of the organism requires identification and removal of the nidi of sequestration. JAMA Ophthalmol. 2014;132(9):1123-1126. doi:10.1001/jamaophthalmol.2014.1069 Published online June 5, 2014.
C
urvularia is a dematiaceous or darkly pigmented fungus. Endophthalmitis due to Curvularia species is exceedingly rare, with only isolated case reports in the literature.1-6 Large series of endogenous and exogenous fungal endophthalmitis in the United States do not mention Curvularia as a separate causative organism.7-10 The present series of 6 cases of Curvularia endophthalmitis demonstrates the difficulty of timely and proper diagnosis and challenges in the eradication of the microorganism. jamaophthalmology.com
Author Affiliations: Bascom Palmer Eye Institute, Department of Ophthalmology, Miller School of Medicine, University of Miami, Miami, Florida (Rachitskaya, Reddy, Miller, Davis, Flynn, Smiddy, Dubovy, Albini); Department of Ophthalmology, University of Virginia School of Medicine, Charlottesville (Reddy); Retina Macula Specialists of Miami, Miami, Florida (Lara); Kaufman Eye Institute, Zephyrhills, Florida (Lin). Corresponding Author: Thomas A. Albini, MD, Bascom Palmer Eye Institute, Department of Ophthalmology, Miller School of Medicine, University of Miami, 900 NW 17th St, Miami, FL 33136 ([email protected]).
Methods An institutional review board–approved retrospective review of the archives of the microbiology laboratory at Bascom Palmer Eye Institute from January 1, 1980, through September 30, 2013, identified all cultures positive for Curvularia. The substrate (blood agar, chocolate agar, Sabouraud agar, LowensteinJensen agar, or thioglycolate broth) on which Curvularia grew JAMA Ophthalmology September 2014 Volume 132, Number 9
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Curvularia Endophthalmitis
Table. Clinical Characteristics of Patients With Curvularia Endophthalmitis Curvularia Substrate (Time From Date of To To Plating Surgery/ Trauma Symptoms Diagnosis Specimen to Growth) Time From Inciting Event
Case No./ Age, y Eye
Comorbidities
Cause
1/79
R
DM, hypertension, anemia, possible RA
CE/IOLI November 2006
2/21
L
None
Trauma July 2007
3/76
R
4/67
L
5/84
6/70
VA (Time)
Time From Inciting Event to Presumed Eradication, Area of Sequestration mo
Presentation
Final FU
Vitreous Blood agar, wash of Sabouraud iris lesion agar (3 d)
HM (POM 12)
20/100 (POM 34)
23
Iris lesion
5 mo
12 mo
0
6 wk
Vitreous
Chocolate agar, blood agar, Sabouraud agar, thioglycolate broth (48 h)
2/200 (POW 2)
20/200 (POM 35)
16
Cornea
DM, hypertension, CE/IOLI November hypercholesterolemia 2009
3 mo
7 mo
Vitreous
Chocolate agar, blood agar, Sabouraud agar, thioglycolate broth (3 d)
20/70 (POM 6)
20/60 (POM 31)
14
Ciliary body membranes
DM, hypertension, fibromyalgia, cerebral aneurysm, stroke
CE/IOLI September 2010
2 mo
19 mo
Vitreous
Unknown
20/400 (POM 23)
20/300 (POM 28)
25
Capsule, subretinal abscess
L
COPD, asthma, hypertension, hyperlipidemia
CE/IOLI March 2011
3 mo
7 mo
Vitreous
Chocolate agar (blood agar)
CF (POM 3)
20/400 (POM 11)
8
R
Hypothyroidism, hypertension
CE/IOLI August 2011
2 mo
24 mo
Vitreous
Chocolate agar, blood agar, Sabouraud agar, LowensteinJensen medium (3 d)
1/200 (POM 24)
LP (POM 27)
27
Capsular bag
Unknown
Abbreviations: CE/IOLI, cataract extraction with intraocular lens implantation; CF, counting fingers; COPD, chronic obstructive pulmonary disease; DM, diabetes mellitus; FU, follow-up; HM, hand motions; L, left; LP, light perception; NA, not available; POM, postoperative month; POW, postoperative week; R, right; RA, rheumatoid arthritis; VA, visual acuity.
was documented with the time from initial specimen plating to organism growth. We identified a total of 7 patients with vitreous cultures positive for Curvularia. One additional patient had culture-confirmed Curvularia endophthalmitis with a vitreous culture performed at another hospital. Because the patient was treated for her condition at Bascom Palmer Eye Institute and we had access to the patient’s complete medical records, she was included in the study. Thus, we reviewed the records of 8 patients. Two patients were excluded after review of the clinical history because they did not develop clinical endophthalmitis. Therefore, we included a total of 6 cases of Curvularia endophthalmitis, with 2 of these patients previously described in separate reports4,5 (cases 1 and 2 in the Supplement [eAppendix]).
Results A total of 6 patients with endophthalmitis caused by Curvularia species were identified and reviewed in chronological order (Table). In 5 patients (mean age, 75.2 years), endophthalmitis occurred after cataract surgery with intraocular lens implantation; in 1 patient (age, 21 years), endophthalmitis occurred after trauma. The diagnosis was established rapidly at 6 weeks in the trauma case. In the postoperative cases, the time from surgery to the first signs of inflammation ranged from 2 1124
to 5 months. The time from the surgery to correct diagnosis of Curvularia endophthalmitis ranged from 7 to 24 months. The patients with postoperative endophthalmitis were treated with topical corticosteroids (n = 5), sub–Tenon or subconjunctival injection of triamcinolone acetonide (n = 3), or systemic methotrexate sodium and azathioprine sodium (n = 1). These patients underwent a mean of 2 (range, 0-5) intraocular procedures and operations, including anterior chamber culture, vitreous culture, intraocular injection, or pars plana vitrectomy. In 5 postoperative cases, the definitive surgery that established the diagnosis of Curvularia endophthalmitis was pars plana vitrectomy with vitreous cultures, partial or complete capsulectomy or lensectomy, and intravitreal injection of antimicrobials. The time from the inciting event (surgery or trauma) to eradication in all 6 patients ranged from 8 to 27 months. During this time the patients were treated with topical, oral, and, in 1 case, intravenous antifungals. They underwent a mean of 1.8 intraocular procedures, usually with concurrent intravitreal antifungal treatment, with a mean of 6.8 separate intravitreal antifungal injections. Despite aggressive antifungal therapy, eradication of the infection could be achieved only by identification and removal of the nidus of sequestration. This process required the use of imaging studies, such as ultrasonography, and use of endoscopy during the pars plana vitrectomy. The nidi of sequestration included an iris lesion, a corneal endothelial plaque, ciliary body mem-
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Original Investigation Research
Figure. Nidi of Sequestration in Curvularia Endophthalmitis A
C
B
D
A, A hypopyon and an iris lesion, representing a nidus of Curvularia sequestration, in a patient with pseudophakia (case 1). B, Corneal laceration repair with corneal infiltrate harboring Curvularia organisms in a trauma patient (case 2). C, Histopathologic photomicrograph of Curvularia organisms in the corneal stroma of the trauma patient (Gomori methenamine silver, original magnification ×100) (case 2). D, Posterior capsular opacity and Curvularia endophthalmitis in a patient with pseudophakia (case 3).
branes, capsular bag, and subretinal abscess (several of these nidi are shown in the Figure). The visual acuity at presentation ranged from 20/70 to hand motions. The median follow-up was 29.5 (range, 11-35) months. The final visual acuity ranged from 20/60 to light perception.
Discussion We report the first, to our knowledge, clinical series (6 patients) with intraocular cultures positive for Curvularia species. Curvularia, a widespread septate mold that is black owing to melanin in its hyphae and conidia, is found in tropical climates, lives in the soil and on plants, and is spread by airborne spores.11 In the literature, the number of reports of Curvularia keratitis has increased through the last half of the 20th century, with most of the reports coming from India, the United States, and Asia.11 Nevertheless, fungal keratitis due to Curvularia is less frequent than that due to Candida, Fusarium, or Aspergillus species. 11 Cases of Curvularia endophthalmitis are rare, but reports are increasing. The first reports of Curvularia endophthalmitis are from India in early 2000.3,6,12 Review of the records of the microbiology laboratory at our institution disclosed that the first case of clinically significant Curvularia endophthalmitis was documented in 2006 (case 1; Table). Four large studies focusing on endogenous and exogenous fungal endophthalmitis at our institution spanning 1984 through 199310 and 1990 through 20098 for endogenous and 1969 through 19867 and 1990 through 20069 for exogenous infections did not identify any cases of Curvularia endophthalmitis. jamaophthalmology.com
Curvularia was not documented as a human pathogen until 1959.13 Curvularia species most commonly cause skin infections, invasive sinusitis, and allergic fungal sinusitis.14,15 Cases of pulmonary and cerebral infection and arthritis, osteomyelitis, fungemia, endocarditis, peritonitis, and gastrointestinal tract disease have been reported.14,16-18 Infections with Curvularia do not appear to require an immunosuppressed host, and inhalation and skin inoculation are the main routes of infection.15,18 In the present study, 1 patient was otherwise healthy (case 2). The other patients had several comorbidities such as hypertension, diabetes mellitus, cerebral aneurysm, stroke, anemia, hypothyroidism, and possible rheumatoid arthritis (Table). However, none of them were significantly immunocompromised. In Curvularia keratitis, trauma with plant matter or dirt is the leading cause of infection. 11 In the present traumarelated case of Curvularia endophthalmitis, the trauma was due to nail injury. No unusual exposure was seen in surgeryrelated cases. However, Curvularia species have been isolated in the conjunctival sac of healthy individuals.19 In the trauma-related case of endophthalmitis, the diagnosis was established rapidly because the signs suggestive of infectious endophthalmitis increased the level of suspicion. The patients with Curvularia endophthalmitis after cataract surgery had delayed diagnosis and appropriate therapy. The time from surgery to first symptoms ranged from 2 to 5 months. The time from surgery to correct diagnosis ranged from 7 to 24 months. In fact, 3 of 5 patients were treated with sub-Tenon or subconjunctival injection of corticosteroids in addition to topical corticosteroid application before the appropriate diagnosis, and JAMA Ophthalmology September 2014 Volume 132, Number 9
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Research Original Investigation
Curvularia Endophthalmitis
1 patient received oral immunosuppressive therapy. Propionibacterium acnes is the most common causative organism of delayed-onset endophthalmitis and presents with similar lowgrade inflammation and a slowly progressive course; a posterior capsular plaque is present in about 65% of patients.20 In Curvularia endophthalmitis, the plaque was seen in 3 of 5 patients who had undergone surgery for cataract. Compared with P acnes, Curvularia infection presented with a variety of locations of sequestration, including an endothelial corneal plaque, the posterior lens capsule, a vitreous fungus ball, membranes on the ciliary body, and the subretinal space. In the present case series, the patients received an aggressive treatment consisting of combined intravitreal, oral, topical, and occasionally intravenous antifungals and surgical intervention. Diagnostic and therapeutic vitrectomy was
ARTICLE INFORMATION Submitted for Publication: November 20, 2013; final revision received February 17, 2014; accepted February 20, 2014. Published Online: June 5, 2014. doi:10.1001/jamaophthalmol.2014.1069. Author Contributions: Dr Albini had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Study concept and design: Rachitskaya, Flynn, Albini. Acquisition, analysis, or interpretation of data: All authors. Drafting of the manuscript: Rachitskaya, Reddy, Lara, Lin. Critical revision of the manuscript for important intellectual content: Rachitskaya, Miller, Davis, Flynn, Smiddy, Lin, Dubovy, Albini. Statistical analysis: Flynn. Administrative, technical, or material support: Rachitskaya, Reddy, Miller, Lara, Albini. Study supervision: Dubovy, Albini. Conflict of Interest Disclosures: None reported. Funding/Support: This study is supported in part by Center Core Grant P30EY014801 from the National Institutes of Health; by an unrestricted grant from Research to Prevent Blindness; and by grant W81XWH-09-1-0675 from the Department of Defense. Role of the Sponsor: The funding sources had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication. Previous Presentations: This paper was presented at the Annual Meeting of the Association for Research in Vision and Ophthalmology; May 5, 2013; Seattle, Washington; at the Annual Meeting of the American Society of Retina Specialists; August 25, 2013; Toronto, Ontario, Canada; and at the 47th Annual Meeting of the Ocular
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necessary in all cases. All the reported cases clearly demonstrate the importance of identification and elimination of the possible source of sequestered infection. This process may require use of preoperative high-resolution ultrasonography and thorough intraoperative depression or endoscopy to visualize the retinal periphery and the retroirideal space.
Conclusions Curvularia infection represents a rare cause of endophthalmitis. The diagnosis and treatment are often delayed, especially in the postoperative cases. The eradication of the organism requires identification and removal of the nidus of sequestration.
Microbiology and Immunology Group; November 15, 2013; New Orleans, Louisiana.
endogenous fungal endophthalmitis. Ophthalmic Surg Lasers. 1997;28(3):185-194.
REFERENCES
11. Wilhelmus KR, Jones DB. Curvularia keratitis. Trans Am Ophthalmol Soc. 2001;99:111-132.
1. Ehlers JP, Chavala SH, Woodward JA, Postel EA. Delayed recalcitrant fungal endophthalmitis secondary to Curvularia. Can J Ophthalmol. 2011;46 (2):199-200.
12. Chakrabarti A, Shivaprakash MR, Singh R, et al. Fungal endophthalmitis: fourteen years’ experience from a center in India. Retina. 2008;28(10): 1400-1407.
2. Berbel RF, Casella AM, de Freitas D, Höfling-Lima AL. Curvularia lunata endophthalmitis. J Ocul Pharmacol Ther. 2011;27(5):535-537.
13. Baylet J, Camain R, Segretain G. Identification of the agents of maduromycoses of Senegal and Mauritania: description of a new species [in French]. Bull Soc Pathol Exot Filiales. 1959;52:448-477.
3. Kaushik S, Ram J, Chakrabarty A, Dogra MR, Brar GS, Gupta A. Curvularia lunata endophthalmitis with secondary keratitis. Am J Ophthalmol. 2001;131 (1):140-142.
14. Silveira F, Nucci M. Emergence of black moulds in fungal disease: epidemiology and therapy. Curr Opin Infect Dis. 2001;14(6):679-684.
4. Pathengay A, Miller DM, Flynn HW Jr, Dubovy SR. Curvularia endophthalmitis following open globe injuries. Arch Ophthalmol. 2012;130(5): 652-654.
15. Brandt ME, Warnock DW. Epidemiology, clinical manifestations, and therapy of infections caused by dematiaceous fungi. J Chemother. 2003;15 (suppl 2):36-47.
5. Sisk RASW, Dubovy SR, Miller D. Chronic Curvularia lunata endophthalmitis following cataract extraction. Retinal Cases Brief Rep. 2009;3(4): 438-439.
16. Varughese S, David VG, Mathews MS, Tamilarasi V. A patient with amphotericin-resistant Curvularia lunata peritonitis. Perit Dial Int. 2011;31(1):108-109.
6. Pathengay A, Shah GY, Das T, Sharma S. Curvularia lunata endophthalmitis presenting with a posterior capsular plaque. Indian J Ophthalmol. 2006;54(1):65-66. 7. Pflugfelder SC, Flynn HW Jr, Zwickey TA, et al. Exogenous fungal endophthalmitis. Ophthalmology. 1988;95(1):19-30. 8. Lingappan A, Wykoff CC, Albini TA, et al. Endogenous fungal endophthalmitis: causative organisms, management strategies, and visual acuity outcomes. Am J Ophthalmol. 2012;153(1): 162-166.e1. doi:10.1016/j.ajo.2011.06.020. 9. Wykoff CC, Flynn HW Jr, Miller D, Scott IU, Alfonso EC. Exogenous fungal endophthalmitis: microbiology and clinical outcomes. Ophthalmology. 2008;115(9):1501-1507.e2. doi:10.1016/j.ophtha.2008 .02.027.
17. Berg D, Garcia JA, Schell WA, Perfect JR, Murray JC. Cutaneous infection caused by Curvularia pallescens: a case report and review of the spectrum of disease. J Am Acad Dermatol. 1995;32 (2, pt 2):375-378. 18. Carter E, Boudreaux C. Fatal cerebral phaeohyphomycosis due to Curvularia lunata in an immunocompetent patient. J Clin Microbiol. 2004;42(11):5419-5423. 19. Sehgal SC, Dhawan S, Chhiber S, Sharma M, Talwar P. Frequency and significance of fungal isolations from conjunctival sac and their role in ocular infections. Mycopathologia. 1981;73(1):17-19. 20. Shirodkar AR, Pathengay A, Flynn HW Jr, et al. Delayed- versus acute-onset endophthalmitis after cataract surgery. Am J Ophthalmol. 2012;153(3): 391-398.e2. doi:10.1016/j.ajo.2011.08.029.
10. Essman TF, Flynn HW Jr, Smiddy WE, et al. Treatment outcomes in a 10-year study of
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