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Bilateral Candida endophthalmitis in a premature infant
Bilateral Candida endophthalmitis in a premature infant Rebecca A. Manning, MD, Joshua N. Carlson, MD, Eric W. Hein, MD, R. Grey Weaver Jr, MD, and Craig M. Greven, MD, FACS Endogenous infantile Candida endophthalmitis is a rare but potentially devastating condition resulting from sequestration of the fungus within the lens after systemic infection. We report the case of a 20-week-old girl with a history of Candida sepsis who presented with bilateral Candida albicans endophthalmitis 15 weeks after completing a 6-week course of intravenous antifungal therapy. Prompt vitrectomy resulted in salvage of the right eye, although a total retinal detachment occurred. Cataract extraction and administration of intravenous and intravitreal amphotericin B preserved vision in the left eye.
Case Report
A
20-week-old African-American girl born at 24 weeks’ gestation (birth weight 570 g) presented at the Wake Forest University Eye Center for a routine retinopathy of prematurity (ROP) follow-up examination 2 weeks after being discharged from the neonatal intensive care unit. Her parents reported that she had developed a “cataract” within the last week. They denied any eye redness, discharge, or behavioral changes. The girl’s medical history was remarkable for grade 3 intraventricular hemorrhage after ventriculoperitoneal shunting, dysphagia after gastrostomy tube placement, and Candida sepsis and Candida meningitis requiring a 6-week course of antifungal treatment with micafungin, amphotericin B, and fluconazole. The girl’s ocular history was significant for ROP that did not require treatment. At the time of discharge, at 40 weeks’ gestational age, the ROP was zone 3, stage 1 bilaterally. Throughout her hospital stay, anterior segment examination was normal, with no evidence of cataract or intraocular involvement of Candida, with the exception of a small, superior, sectoral lens opacity in the left eye and mild chemosis of the right conjunctiva, both noted one day prior to discharge. At the time of this examination, her 13th since initial ROP consultation (performed at 4 weeks’ gestational age) and 13 weeks after completing antifungal therapy, the patient was diagnosed with conjunctivitis and prescribed a 3-day course of a combination Author affiliations: Department of Ophthalmology, Wake Forest Baptist Medical Center, Winston-Salem, North Carolina Submitted July 11, 2012. Revision accepted November 5, 2012. Published online March 25, 2013. Correspondence: Joshua N. Carlson, MD, Wake Forest University Eye Center, Wake Forest Baptist Medical Center, Winston-Salem, NC 27157 (email: [email protected]). J AAPOS 2013;17:206-207. Copyright Ó 2013 by the American Association for Pediatric Ophthalmology and Strabismus. 1091-8531/$36.00 http://dx.doi.org/10.1016/j.jaapos.2012.11.014
206
antibiotic/corticosteroid drop. She failed to appear for her follow-up appointment 3 days later. On ophthalmological examination at presentation 2 weeks later, the conjunctiva of the right eye had trace injection, the anterior chamber was flat, and there was a fibrinous pupillary membrane and a white cataract obscuring the red reflex. The retina of the right eye could not be visualized. Examination of the left eye revealed a clear cornea, deep anterior chamber, mild lens opacity posteriorly with mild anterior vitreous cell, cup/disk ratio of 0.1, formed macula, and zone 3, stage 2 ROP, with no plus disease. No focal retinal inflammatory lesions were noted. The child’s caretakers reported having administered the antibiotic/corticosteroid drop throughout the 2-week period. A B-scan of the right eye revealed an enlarged lens with marked vitreous opacities and traction bands. No definitive retinal detachment was noted (Figure 1). Examination under anesthesia of the left eye revealed a clear cornea, a deep anterior chamber without obvious inflammation, a superior sectoral cataract, and opacities in the anterior vitreous of the left eye. The optic nerve appeared mildly hyperemic, and the vessels were mildly full but without plus disease. No retinal infiltrates were seen, and the ROP remained stable at zone 3, stage 2 (Figure 2). A 23-gauge pars plana lensectomy with vitrectomy was performed in the right eye. Vitreous and anterior chamber samples were sent for bacterial and fungal cultures. Intraoperative findings included a cyclitic membrane, dense vitritis, and extensive necrosis of the retina from the posterior pole to the periphery. Vancomycin, cefepime, and amphotericin B were injected into the vitreous. Cultures obtained from both the anterior chamber and vitreous cavity of the right eye were found to be positive for Candida albicans. The organism was sensitive to amphotericin B, fluconazole, and itraconazole. Intravenous therapy with amphotericin B (1 mg/kg/day) was initiated, and intravitreal injections of amphotericin B were administered in both eyes (5 mg). The patient was monitored biweekly. Intraocular inflammation subsided in the right eye, but a total necrotic retinal detachment occurred. The left eye developed progressive cataract without increased inflammation. A pars plana lensectomy with anterior vitrectomy was performed, and amphotericin B injection was administered without complication. The girl completed an additional 6-week course of intravenous amphotericin B before she was discharged off all antifungal therapy. Culture of aqueous fluid obtained from the left eye at the time of surgery was negative. At her most recent follow-up examination, 2
Journal of AAPOS
Volume 17 Number 2 / April 2013
FIG 1. B-scan of the patient’s right eye at presentation showing an enlarged lens with vitreous opacities and traction bands.
Manning et al
207
presentation of endogenous Candida endophthalmitis in premature infants due to sequestration of the fungus in the lens.1-7 The infants, predisposed to systemic fungal infection as the result of their immunocompromised status, often present after resolution of systemic candidemia. This is currently thought to be due to regression of the hyaloidal artery system between 24 and 32 weeks’ gestational age, which allows the fungus to become sequestered in the lens.8 Without perfusion of the lens, the antifungal medications would presumably be unable to reach the nidus of infection, allowing the fungus to grow and present as either a cataract or, as in our case, fulminant fungal endophthalmitis. The clinical course in our patient’s left eye supports this proposed mechanism because the cataract and anterior vitreous haze were clearly present without any associated chorioretinal findings on examination. It is important to recognize the late presentation of fungal endophthalmitis in premature infants and to recognize that a new-onset cataract may, in fact, be a fungal abscess presenting in the eye. Because the infection becomes isolated from antifungal therapy, it is necessary to remove the lens. In this case, a fulminant endophthalmitis and subsequent retinal detachment in the right eye occurred within 3 weeks of a dilated ROP examination in the setting of topical corticosteroid use. However, as the result of aggressive antifungal therapy with both systemic and local therapy, the infection was confined to the lens and anterior vitreous in the left eye. After a period of stabilization of the left eye, the lens was successfully removed without reactivation of Candida in the vitreoretinal space. References
FIG 2. Color fundus photograph of the patient’s left eye at presentation demonstrating anterior vitreous opacities; no retinal infiltrates were seen.
weeks after discharge, she blinked to light in the left eye, had a quiet anterior chamber, and was aphakic. Her vitreous was clear and her retina remained stable.
Discussion We present a case of bilateral Candida endophthalmitis proven on culture of the right eye and treated in the left eye based on clinical findings suggestive of infection. In the literature, there have been 8 reported cases of delayed
Journal of AAPOS
1. Hill H, Mitchell TG, Matsen JM, Quie PG. Recovery from disseminated candidiasis in a premature neonate. Pediatrics 1974;53:748-52. 2. Clinch TE, Duker JS, Eagle RC, et al. Infantile endogenous Candida endophthalmitis presenting as a cataract. Surv Ophthalmol 1989;34: 107-12. 3. Shah CK, Vander J, Eagle RC. Intralenticular Candida species abscess in a premature infant. Am J Ophthalmol 2000;123:390-91. 4. Johnston TW, Cogen MS. Systemic candidiasis with cataract formation in a premature infant. J AAPOS 2000;4:386-8. 5. Stern JH, Calvano C, Simon JW. Recurrent endogenous candidal endophthalmitis in a premature infant. J AAPOS 2001;5:50-51. 6. Drohan L, Colby CE, Brindle ME, Sansilo S, Ariagno R. Candida (amphotericin-sensitive) lens abscess associated with decreasing arterial blood flow in a very low birth weight preterm infant. Pediatrics 2002;110:e65. 7. Singh-Parikshak R, Bothun ED, Superstein R, Del Monte M, Archer S, Johnson MW. Sequestration and late activation of lenticular Candida abscess in premature infants. Arch Ophthalmol 2004;122:1393-5. 8. Baley JE, Ellis FJ. Neonatal candidiasis: Ophthalmologic infection. Semin Perinatol 2003;27:401-5.
Case Report
A
20-week-old African-American girl born at 24 weeks’ gestation (birth weight 570 g) presented at the Wake Forest University Eye Center for a routine retinopathy of prematurity (ROP) follow-up examination 2 weeks after being discharged from the neonatal intensive care unit. Her parents reported that she had developed a “cataract” within the last week. They denied any eye redness, discharge, or behavioral changes. The girl’s medical history was remarkable for grade 3 intraventricular hemorrhage after ventriculoperitoneal shunting, dysphagia after gastrostomy tube placement, and Candida sepsis and Candida meningitis requiring a 6-week course of antifungal treatment with micafungin, amphotericin B, and fluconazole. The girl’s ocular history was significant for ROP that did not require treatment. At the time of discharge, at 40 weeks’ gestational age, the ROP was zone 3, stage 1 bilaterally. Throughout her hospital stay, anterior segment examination was normal, with no evidence of cataract or intraocular involvement of Candida, with the exception of a small, superior, sectoral lens opacity in the left eye and mild chemosis of the right conjunctiva, both noted one day prior to discharge. At the time of this examination, her 13th since initial ROP consultation (performed at 4 weeks’ gestational age) and 13 weeks after completing antifungal therapy, the patient was diagnosed with conjunctivitis and prescribed a 3-day course of a combination Author affiliations: Department of Ophthalmology, Wake Forest Baptist Medical Center, Winston-Salem, North Carolina Submitted July 11, 2012. Revision accepted November 5, 2012. Published online March 25, 2013. Correspondence: Joshua N. Carlson, MD, Wake Forest University Eye Center, Wake Forest Baptist Medical Center, Winston-Salem, NC 27157 (email: [email protected]). J AAPOS 2013;17:206-207. Copyright Ó 2013 by the American Association for Pediatric Ophthalmology and Strabismus. 1091-8531/$36.00 http://dx.doi.org/10.1016/j.jaapos.2012.11.014
206
antibiotic/corticosteroid drop. She failed to appear for her follow-up appointment 3 days later. On ophthalmological examination at presentation 2 weeks later, the conjunctiva of the right eye had trace injection, the anterior chamber was flat, and there was a fibrinous pupillary membrane and a white cataract obscuring the red reflex. The retina of the right eye could not be visualized. Examination of the left eye revealed a clear cornea, deep anterior chamber, mild lens opacity posteriorly with mild anterior vitreous cell, cup/disk ratio of 0.1, formed macula, and zone 3, stage 2 ROP, with no plus disease. No focal retinal inflammatory lesions were noted. The child’s caretakers reported having administered the antibiotic/corticosteroid drop throughout the 2-week period. A B-scan of the right eye revealed an enlarged lens with marked vitreous opacities and traction bands. No definitive retinal detachment was noted (Figure 1). Examination under anesthesia of the left eye revealed a clear cornea, a deep anterior chamber without obvious inflammation, a superior sectoral cataract, and opacities in the anterior vitreous of the left eye. The optic nerve appeared mildly hyperemic, and the vessels were mildly full but without plus disease. No retinal infiltrates were seen, and the ROP remained stable at zone 3, stage 2 (Figure 2). A 23-gauge pars plana lensectomy with vitrectomy was performed in the right eye. Vitreous and anterior chamber samples were sent for bacterial and fungal cultures. Intraoperative findings included a cyclitic membrane, dense vitritis, and extensive necrosis of the retina from the posterior pole to the periphery. Vancomycin, cefepime, and amphotericin B were injected into the vitreous. Cultures obtained from both the anterior chamber and vitreous cavity of the right eye were found to be positive for Candida albicans. The organism was sensitive to amphotericin B, fluconazole, and itraconazole. Intravenous therapy with amphotericin B (1 mg/kg/day) was initiated, and intravitreal injections of amphotericin B were administered in both eyes (5 mg). The patient was monitored biweekly. Intraocular inflammation subsided in the right eye, but a total necrotic retinal detachment occurred. The left eye developed progressive cataract without increased inflammation. A pars plana lensectomy with anterior vitrectomy was performed, and amphotericin B injection was administered without complication. The girl completed an additional 6-week course of intravenous amphotericin B before she was discharged off all antifungal therapy. Culture of aqueous fluid obtained from the left eye at the time of surgery was negative. At her most recent follow-up examination, 2
Journal of AAPOS
Volume 17 Number 2 / April 2013
FIG 1. B-scan of the patient’s right eye at presentation showing an enlarged lens with vitreous opacities and traction bands.
Manning et al
207
presentation of endogenous Candida endophthalmitis in premature infants due to sequestration of the fungus in the lens.1-7 The infants, predisposed to systemic fungal infection as the result of their immunocompromised status, often present after resolution of systemic candidemia. This is currently thought to be due to regression of the hyaloidal artery system between 24 and 32 weeks’ gestational age, which allows the fungus to become sequestered in the lens.8 Without perfusion of the lens, the antifungal medications would presumably be unable to reach the nidus of infection, allowing the fungus to grow and present as either a cataract or, as in our case, fulminant fungal endophthalmitis. The clinical course in our patient’s left eye supports this proposed mechanism because the cataract and anterior vitreous haze were clearly present without any associated chorioretinal findings on examination. It is important to recognize the late presentation of fungal endophthalmitis in premature infants and to recognize that a new-onset cataract may, in fact, be a fungal abscess presenting in the eye. Because the infection becomes isolated from antifungal therapy, it is necessary to remove the lens. In this case, a fulminant endophthalmitis and subsequent retinal detachment in the right eye occurred within 3 weeks of a dilated ROP examination in the setting of topical corticosteroid use. However, as the result of aggressive antifungal therapy with both systemic and local therapy, the infection was confined to the lens and anterior vitreous in the left eye. After a period of stabilization of the left eye, the lens was successfully removed without reactivation of Candida in the vitreoretinal space. References
FIG 2. Color fundus photograph of the patient’s left eye at presentation demonstrating anterior vitreous opacities; no retinal infiltrates were seen.
weeks after discharge, she blinked to light in the left eye, had a quiet anterior chamber, and was aphakic. Her vitreous was clear and her retina remained stable.
Discussion We present a case of bilateral Candida endophthalmitis proven on culture of the right eye and treated in the left eye based on clinical findings suggestive of infection. In the literature, there have been 8 reported cases of delayed
Journal of AAPOS
1. Hill H, Mitchell TG, Matsen JM, Quie PG. Recovery from disseminated candidiasis in a premature neonate. Pediatrics 1974;53:748-52. 2. Clinch TE, Duker JS, Eagle RC, et al. Infantile endogenous Candida endophthalmitis presenting as a cataract. Surv Ophthalmol 1989;34: 107-12. 3. Shah CK, Vander J, Eagle RC. Intralenticular Candida species abscess in a premature infant. Am J Ophthalmol 2000;123:390-91. 4. Johnston TW, Cogen MS. Systemic candidiasis with cataract formation in a premature infant. J AAPOS 2000;4:386-8. 5. Stern JH, Calvano C, Simon JW. Recurrent endogenous candidal endophthalmitis in a premature infant. J AAPOS 2001;5:50-51. 6. Drohan L, Colby CE, Brindle ME, Sansilo S, Ariagno R. Candida (amphotericin-sensitive) lens abscess associated with decreasing arterial blood flow in a very low birth weight preterm infant. Pediatrics 2002;110:e65. 7. Singh-Parikshak R, Bothun ED, Superstein R, Del Monte M, Archer S, Johnson MW. Sequestration and late activation of lenticular Candida abscess in premature infants. Arch Ophthalmol 2004;122:1393-5. 8. Baley JE, Ellis FJ. Neonatal candidiasis: Ophthalmologic infection. Semin Perinatol 2003;27:401-5.