ENDOGENOUS NOCARDIAL CHORIORETINITIS IN AN IMMUNOCOMPETENT PATIENT Zac B. Ravage, MD,* Lawrence J. Singerman, MD, FACS*†
Purpose: To describe the presentation and management of an immunocompetent patient with endogenous Nocardia chorioretinitis. Methods: A previously healthy 55-year-old woman presented with reduced vision and metamorphopsia after accidental inhalation of Nocardia organisms from planting soil. She developed systemic nocardiosis with pulmonary and cerebellar involvement as well as bilateral chorioretinitis. Ocular infection resulted in choroidal neovascularization, which was successfully treated with intravitreal triamcinolone and thermal laser photocoagulation. Discussion: This patient is one of only a few immunocompetent individuals to develop endogenous nocardial chorioretinitis. Systemic antibiotic treatment and local laser therapy for subsequent choroidal neovascularization were effective in management of this case. RETINAL CASES & BRIEF REPORTS 3:27–30, 2009
From the *Department of Ophthalmology, Case Western Reserve University, University Hospitals of Cleveland, and †Retina Associates of Cleveland, Cleveland, Ohio.
has been described after intraocular surgery, with poor outcomes. There are few reports in the English-language medical literature describing ocular nocardiosis in previously healthy patients. We describe an immunocompetent woman who developed bilateral endogenous nocardial chorioretinitis. To our knowledge, this represents only the second case of choroidal neovascularization (CNV) complicating this disease process and the first treated with laser photocoagulation.
N
ocardia asteroides is a Gram-positive, aerobic, soil-borne bacterium with certain fungal characteristics. The organism is typically inhaled, invading the body via the respiratory tract. Nocardia organisms cause localized pulmonary infection, after which hematogenous dissemination to the brain, eyes, and soft tissues may occur. Primary cutaneous infection through traumatic inoculation is also possible. Focal areas of inflammation with suppurative necrosis and abscess formation develop in affected tissues. Most nocardial infections are described in immunocompromised patients, although immunocompetent individuals may also develop localized and disseminated disease. Systemic disease can be associated with high morbidity and mortality rates.1 Development of ocular nocardiosis is extremely rare, occurring in ⬍5% of cases with systemic involvement.1,2 Exogenous nocardial endophthalmitis
Case Report A 55-year-old woman presented to Retina Associates of Cleveland (Cleveland, OH) with a 2-week history of decreased vision and metamorphopsia in the right eye. She had been examined previously by an outside ophthalmologist who referred her for further evaluation of bilateral fundus lesions. She had no other ocular history except for presbyopia. Medical history and review of systems provided the following information. Six months earlier, the patient had accidentally inhaled particulate matter from a recently opened bag of planting soil. Within 4 days, she developed a sore throat and fatigue. A treatment regimen of unspecified oral antibiotics was completed with improvement of the sore throat, but the fatigue persisted. The patient was previously not receiving any medication. Over the next 2 months, she developed a nonproductive cough, right upper chest tightness, and intermittent right subscapular pain. Chest roentgenographic findings were reported as negative at that time. After an additional 2 months of worsening cough and malaise, the patient had an acute onset of severe headache that lasted 3 days. Noncontrast computed
Reprint requests: Lawrence J. Singerman, MD, FACS, Retina Associates of Cleveland, 3401 Enterprise Parkway, Suite 300, Cleveland, OH 44122; e-mail: [email protected]
27
28
RETINAL CASES & BRIEF REPORTSℜ
●
2009
●
VOLUME 3
●
NUMBER 1
species (Fig. 2). Microbiologic culture later confirmed Nocardia asteroides. Laboratory evaluation results were negative for diabetes or lymphoreticular or gastrointestinal malignancy. Human immunodeficiency virus testing was negative. Treatment with intravenous trimethoprim–sulfamethoxazole was started, with gradual improvement in her systemic symptoms. Total hospitalization lasted 2 weeks, after which time she continued to receive intravenous trimethoprim–sulfamethoxazole treatment as an outpatient. At follow-up examination with her primary care physician 1 month after discharge, she described the symptoms of decreased vision and metamorphopsia in the right eye. At ocular examination, uncorrected visual acuity was 20/60 in the right eye and 20/50 in the left eye at distance and 20/30 in both eyes at near with correction. Pupils were 3 mm bilaterally with no relative afferent papillary defect. Intraocular pressure was 13 mmHg in both eyes. Results of anterior segment examination were unremarkable. Funduscopic examination of the right eye revealed a round 2.5-disk-diameter lesion with irregular margins along the inferior arcade, inferotemporal to the fovea. There was an associ-
Fig. 1. Magnetic resonance imaging with contrast showing a ringenhancing lesion (arrow) in the left cerebellum, with significant edema involving much of the cerebellar hemisphere.
tomography of the brain showed left-sided cerebellar hemorrhage. The patient was admitted to the hospital for further evaluation. Magnetic resonance imaging with contrast disclosed a 2.5-cmdiameter left cerebellar, ring-enhancing lesion with significant edema involving much of the cerebellar hemisphere (Fig. 1). Systemic evaluation revealed a 2.3 ⫻ 2.7-cm paraspinous mass at the level of the lowermost trachea and carina with extension into the right upper lobe. No cavitation was noted. Results of biopsy of the pulmonary mass were indeterminate on two attempts. Given the possibility of malignancy, surgical resection of the cerebellar lesion was performed. Pathologic examination of the tissue with hematoxylin– eosin staining showed acute and chronic inflammation with extensive necrosis and abscess formation. Grocott–Gomori methenamine–silver nitrate staining identified filamentous microorganisms consistent with Nocardia
Fig. 2. Stained specimen showing filamentous microorganisms (arrow) consistent with Nocardia species.
Fig. 3. Fundus photography showing lesions in the right eye (A) and the left eye (B).
29
NOCARDIAL CHORIORETINITIS IN AN IMMUNOCOMPETENT PATIENT
acuity was 20/40 in the right eye and 20/50 in the left eye. The juxtafoveal lesion in the left macula appeared less well defined, with greater subretinal fluid and angiographic evidence of CNV. Intravitreal triamcinolone acetonide (1 mg) was given, followed 4 days later by argon laser photocoagulation to the lesion by Dr. Gitter (Fig. 4). Treatment resulted in lesion stabilization and resolution of subretinal fluid. At the most recent examination, four months after treatment, the patient’s vision remained stable at 20/50 in the left eye.
Discussion
Fig. 4. Fluorescein angiograms before (A) and after (B) treatment of choroidal neovascularization (photograph courtesy Dr. Kurt Gitter).
ated area of intraretinal hemorrhage at the nasal margin of the lesion. Subretinal fluid and associated striae were seen extending to the temporal margin of the fovea (Fig. 3A). Examination of the left eye showed a round, flat, 0.5-disk-diameter, temporal juxtafoveal lesion (Fig. 3B); there were two lesions, similar in appearance to that seen in the right eye, in the superonasal periphery (data not shown). All lesions appeared to represent chorioretinal scars. There was no vitreous cell in either eye. Fluorescein angiography showed hyperfluorescence of the lesion in the right eye with minimal leakage. The lesions in the left eye had patterns of staining without active leakage. Indocyanine green angiography showed hypofluorescence of all lesions in both eyes. No evidence of CNV was noted. Optical coherence tomography confirmed a small serous retinal detachment in the macula of the right eye. Follow-up examinations 2 weeks and 3 weeks after the initial visit revealed a less defined foveal lesion in the left eye, although fluorescein angiography indicated no significant leakage and visual acuity in both eyes remained unchanged. Treatment had been switched to oral trimethoprim–sulfamethoxazole 2 days after the first visit. The patient planned to return to her home in the Gulf Coast region and was referred to a retinal specialist (Kurt Gitter, MD) who saw her for follow-up 2 weeks after she left Cleveland. Visual
Nocardiosis is a multisystem infection that typically affects immunocompromised individuals. Delay in diagnosis greatly increases the risk of morbidity and mortality. The patient described here had no history suggestive of immunodeficiency. Results of lung imaging and biopsies had been nondiagnostic. The diagnosis was not made until brain surgery was undertaken for suspected malignancy. Earlier diagnosis and treatment might have limited the systemic dissemination,3 but such a diagnosis would have required a high index of suspicion. Thorough medical evaluation failed to uncover a predisposing medical condition in our patient. The development of systemic bacterial disease in this otherwise healthy person was likely due to the large amount of inoculum inhaled. Upon extensive review of the English-language literature, we identified only one case of ocular nocardiosis in a previously healthy patient.4 In two other reported cases, the medical histories were incomplete; therefore, we were unable to determine the patients’ immunologic status.2 Since we submitted this report, one additional case of endogenous nocardial endophthalmitis in an immunocompetent person has been reported.5 The patient described was positive for antibody to hepatitis C virus; however, this fact does not necessarily imply an immunocompromised state. Chorioretinitis with subretinal abscess formation is the hallmark of endogenous ocular nocardial infection.3 Our patient had bilateral chorioretinal lesions that appeared minimally active at our initial examination. Chorioretinal scarring in the left eye led to CNV, which was treated successfully with intravitreal triamcinolone acetonide and argon laser photocoagulation. Although treatment with an anti–vascular endothelial growth factor agent might have been considered, we concur with the choice made by the treating physician. This patient’s CNV preceded US Food & Drug Administration approval of ranibizumab, her insurance did not cover treatment with pegaptanib, and bevacizumab was not as widely used as it is currently. With the rarity of this etiology of CNV, there is still no clear evidence as to the best treatment. Steroid therapy treated the inflammatory process underlying the CNV, and laser photocoagulation was
30
RETINAL CASES & BRIEF REPORTSℜ
an appropriate choice for treatment of a juxtafoveal lesion. Long-term therapy for 6 months to 12 months with systemic antibiotics is recommended to treat chronic systemic nocardial infection. With development of frank endophthalmitis, intravitreal antibiotic administration and pars plana vitrectomy may be considered, although recommendations are uncertain given limited experience.6 Development of CNV secondary to ocular infection is rare, and management is uncertain. The juxtafoveal lesion in this case stabilized clinically and angiographically after thermal laser treatment. To our knowledge, there has been one previous report of CNV after nocardial endophthalmitis; the CNV treated with submacular surgery.7 This patient represents one of only a few immunocompetent individuals to develop endogenous nocardial chorioretinitis. Systemic antibiotic treatment and local laser therapy for subsequent CNV were effective in management of this case.
●
2009
●
VOLUME 3
●
NUMBER 1
Key words: Nocardia asteroides, chorioretinitis, endophthalmitis. References 1.
2. 3. 4. 5.
6.
7.
Bullock JD. Endogenous ocular nocardiosis: a clinical and experimental study. Trans Am Ophthalmol Soc 1983;81:451– 531. Lakosha H, Pavlin CJ, Lipton J. Subretinal abscess due to Nocardia farcinica infection. Retina 2000;20:269–274. Jampol LM, Strauch BS, Albert DM. Intraocular nocardiosis. Am J Ophthalmol 1973;76:568–573. Meyer SL, Font RL, Shaver RP. Intraocular nocardiosis. Report of three cases. Arch Ophthalmol 1970;83:536–541. de Silva T, Evans C, Mudhar HS, et al. Isolated endogenous endophthalmitis secondary to Nocardia spp in an immunocompetent adult. Clin Pathol 2006;59:1226. Ng EW, Zimmer-Galler IE, Green WR. Endogenous Nocardia asteroides endophthalmitis. Arch Ophthalmol 2002;120:210– 213. Moshfeghi DM, Sears JE, Lewis H. Submacular surgery for choroidal neovascularization following nocardial endophthalmitis. Retina 2004;24:161–164.
Purpose: To describe the presentation and management of an immunocompetent patient with endogenous Nocardia chorioretinitis. Methods: A previously healthy 55-year-old woman presented with reduced vision and metamorphopsia after accidental inhalation of Nocardia organisms from planting soil. She developed systemic nocardiosis with pulmonary and cerebellar involvement as well as bilateral chorioretinitis. Ocular infection resulted in choroidal neovascularization, which was successfully treated with intravitreal triamcinolone and thermal laser photocoagulation. Discussion: This patient is one of only a few immunocompetent individuals to develop endogenous nocardial chorioretinitis. Systemic antibiotic treatment and local laser therapy for subsequent choroidal neovascularization were effective in management of this case. RETINAL CASES & BRIEF REPORTS 3:27–30, 2009
From the *Department of Ophthalmology, Case Western Reserve University, University Hospitals of Cleveland, and †Retina Associates of Cleveland, Cleveland, Ohio.
has been described after intraocular surgery, with poor outcomes. There are few reports in the English-language medical literature describing ocular nocardiosis in previously healthy patients. We describe an immunocompetent woman who developed bilateral endogenous nocardial chorioretinitis. To our knowledge, this represents only the second case of choroidal neovascularization (CNV) complicating this disease process and the first treated with laser photocoagulation.
N
ocardia asteroides is a Gram-positive, aerobic, soil-borne bacterium with certain fungal characteristics. The organism is typically inhaled, invading the body via the respiratory tract. Nocardia organisms cause localized pulmonary infection, after which hematogenous dissemination to the brain, eyes, and soft tissues may occur. Primary cutaneous infection through traumatic inoculation is also possible. Focal areas of inflammation with suppurative necrosis and abscess formation develop in affected tissues. Most nocardial infections are described in immunocompromised patients, although immunocompetent individuals may also develop localized and disseminated disease. Systemic disease can be associated with high morbidity and mortality rates.1 Development of ocular nocardiosis is extremely rare, occurring in ⬍5% of cases with systemic involvement.1,2 Exogenous nocardial endophthalmitis
Case Report A 55-year-old woman presented to Retina Associates of Cleveland (Cleveland, OH) with a 2-week history of decreased vision and metamorphopsia in the right eye. She had been examined previously by an outside ophthalmologist who referred her for further evaluation of bilateral fundus lesions. She had no other ocular history except for presbyopia. Medical history and review of systems provided the following information. Six months earlier, the patient had accidentally inhaled particulate matter from a recently opened bag of planting soil. Within 4 days, she developed a sore throat and fatigue. A treatment regimen of unspecified oral antibiotics was completed with improvement of the sore throat, but the fatigue persisted. The patient was previously not receiving any medication. Over the next 2 months, she developed a nonproductive cough, right upper chest tightness, and intermittent right subscapular pain. Chest roentgenographic findings were reported as negative at that time. After an additional 2 months of worsening cough and malaise, the patient had an acute onset of severe headache that lasted 3 days. Noncontrast computed
Reprint requests: Lawrence J. Singerman, MD, FACS, Retina Associates of Cleveland, 3401 Enterprise Parkway, Suite 300, Cleveland, OH 44122; e-mail: [email protected]
27
28
RETINAL CASES & BRIEF REPORTSℜ
●
2009
●
VOLUME 3
●
NUMBER 1
species (Fig. 2). Microbiologic culture later confirmed Nocardia asteroides. Laboratory evaluation results were negative for diabetes or lymphoreticular or gastrointestinal malignancy. Human immunodeficiency virus testing was negative. Treatment with intravenous trimethoprim–sulfamethoxazole was started, with gradual improvement in her systemic symptoms. Total hospitalization lasted 2 weeks, after which time she continued to receive intravenous trimethoprim–sulfamethoxazole treatment as an outpatient. At follow-up examination with her primary care physician 1 month after discharge, she described the symptoms of decreased vision and metamorphopsia in the right eye. At ocular examination, uncorrected visual acuity was 20/60 in the right eye and 20/50 in the left eye at distance and 20/30 in both eyes at near with correction. Pupils were 3 mm bilaterally with no relative afferent papillary defect. Intraocular pressure was 13 mmHg in both eyes. Results of anterior segment examination were unremarkable. Funduscopic examination of the right eye revealed a round 2.5-disk-diameter lesion with irregular margins along the inferior arcade, inferotemporal to the fovea. There was an associ-
Fig. 1. Magnetic resonance imaging with contrast showing a ringenhancing lesion (arrow) in the left cerebellum, with significant edema involving much of the cerebellar hemisphere.
tomography of the brain showed left-sided cerebellar hemorrhage. The patient was admitted to the hospital for further evaluation. Magnetic resonance imaging with contrast disclosed a 2.5-cmdiameter left cerebellar, ring-enhancing lesion with significant edema involving much of the cerebellar hemisphere (Fig. 1). Systemic evaluation revealed a 2.3 ⫻ 2.7-cm paraspinous mass at the level of the lowermost trachea and carina with extension into the right upper lobe. No cavitation was noted. Results of biopsy of the pulmonary mass were indeterminate on two attempts. Given the possibility of malignancy, surgical resection of the cerebellar lesion was performed. Pathologic examination of the tissue with hematoxylin– eosin staining showed acute and chronic inflammation with extensive necrosis and abscess formation. Grocott–Gomori methenamine–silver nitrate staining identified filamentous microorganisms consistent with Nocardia
Fig. 2. Stained specimen showing filamentous microorganisms (arrow) consistent with Nocardia species.
Fig. 3. Fundus photography showing lesions in the right eye (A) and the left eye (B).
29
NOCARDIAL CHORIORETINITIS IN AN IMMUNOCOMPETENT PATIENT
acuity was 20/40 in the right eye and 20/50 in the left eye. The juxtafoveal lesion in the left macula appeared less well defined, with greater subretinal fluid and angiographic evidence of CNV. Intravitreal triamcinolone acetonide (1 mg) was given, followed 4 days later by argon laser photocoagulation to the lesion by Dr. Gitter (Fig. 4). Treatment resulted in lesion stabilization and resolution of subretinal fluid. At the most recent examination, four months after treatment, the patient’s vision remained stable at 20/50 in the left eye.
Discussion
Fig. 4. Fluorescein angiograms before (A) and after (B) treatment of choroidal neovascularization (photograph courtesy Dr. Kurt Gitter).
ated area of intraretinal hemorrhage at the nasal margin of the lesion. Subretinal fluid and associated striae were seen extending to the temporal margin of the fovea (Fig. 3A). Examination of the left eye showed a round, flat, 0.5-disk-diameter, temporal juxtafoveal lesion (Fig. 3B); there were two lesions, similar in appearance to that seen in the right eye, in the superonasal periphery (data not shown). All lesions appeared to represent chorioretinal scars. There was no vitreous cell in either eye. Fluorescein angiography showed hyperfluorescence of the lesion in the right eye with minimal leakage. The lesions in the left eye had patterns of staining without active leakage. Indocyanine green angiography showed hypofluorescence of all lesions in both eyes. No evidence of CNV was noted. Optical coherence tomography confirmed a small serous retinal detachment in the macula of the right eye. Follow-up examinations 2 weeks and 3 weeks after the initial visit revealed a less defined foveal lesion in the left eye, although fluorescein angiography indicated no significant leakage and visual acuity in both eyes remained unchanged. Treatment had been switched to oral trimethoprim–sulfamethoxazole 2 days after the first visit. The patient planned to return to her home in the Gulf Coast region and was referred to a retinal specialist (Kurt Gitter, MD) who saw her for follow-up 2 weeks after she left Cleveland. Visual
Nocardiosis is a multisystem infection that typically affects immunocompromised individuals. Delay in diagnosis greatly increases the risk of morbidity and mortality. The patient described here had no history suggestive of immunodeficiency. Results of lung imaging and biopsies had been nondiagnostic. The diagnosis was not made until brain surgery was undertaken for suspected malignancy. Earlier diagnosis and treatment might have limited the systemic dissemination,3 but such a diagnosis would have required a high index of suspicion. Thorough medical evaluation failed to uncover a predisposing medical condition in our patient. The development of systemic bacterial disease in this otherwise healthy person was likely due to the large amount of inoculum inhaled. Upon extensive review of the English-language literature, we identified only one case of ocular nocardiosis in a previously healthy patient.4 In two other reported cases, the medical histories were incomplete; therefore, we were unable to determine the patients’ immunologic status.2 Since we submitted this report, one additional case of endogenous nocardial endophthalmitis in an immunocompetent person has been reported.5 The patient described was positive for antibody to hepatitis C virus; however, this fact does not necessarily imply an immunocompromised state. Chorioretinitis with subretinal abscess formation is the hallmark of endogenous ocular nocardial infection.3 Our patient had bilateral chorioretinal lesions that appeared minimally active at our initial examination. Chorioretinal scarring in the left eye led to CNV, which was treated successfully with intravitreal triamcinolone acetonide and argon laser photocoagulation. Although treatment with an anti–vascular endothelial growth factor agent might have been considered, we concur with the choice made by the treating physician. This patient’s CNV preceded US Food & Drug Administration approval of ranibizumab, her insurance did not cover treatment with pegaptanib, and bevacizumab was not as widely used as it is currently. With the rarity of this etiology of CNV, there is still no clear evidence as to the best treatment. Steroid therapy treated the inflammatory process underlying the CNV, and laser photocoagulation was
30
RETINAL CASES & BRIEF REPORTSℜ
an appropriate choice for treatment of a juxtafoveal lesion. Long-term therapy for 6 months to 12 months with systemic antibiotics is recommended to treat chronic systemic nocardial infection. With development of frank endophthalmitis, intravitreal antibiotic administration and pars plana vitrectomy may be considered, although recommendations are uncertain given limited experience.6 Development of CNV secondary to ocular infection is rare, and management is uncertain. The juxtafoveal lesion in this case stabilized clinically and angiographically after thermal laser treatment. To our knowledge, there has been one previous report of CNV after nocardial endophthalmitis; the CNV treated with submacular surgery.7 This patient represents one of only a few immunocompetent individuals to develop endogenous nocardial chorioretinitis. Systemic antibiotic treatment and local laser therapy for subsequent CNV were effective in management of this case.
●
2009
●
VOLUME 3
●
NUMBER 1
Key words: Nocardia asteroides, chorioretinitis, endophthalmitis. References 1.
2. 3. 4. 5.
6.
7.
Bullock JD. Endogenous ocular nocardiosis: a clinical and experimental study. Trans Am Ophthalmol Soc 1983;81:451– 531. Lakosha H, Pavlin CJ, Lipton J. Subretinal abscess due to Nocardia farcinica infection. Retina 2000;20:269–274. Jampol LM, Strauch BS, Albert DM. Intraocular nocardiosis. Am J Ophthalmol 1973;76:568–573. Meyer SL, Font RL, Shaver RP. Intraocular nocardiosis. Report of three cases. Arch Ophthalmol 1970;83:536–541. de Silva T, Evans C, Mudhar HS, et al. Isolated endogenous endophthalmitis secondary to Nocardia spp in an immunocompetent adult. Clin Pathol 2006;59:1226. Ng EW, Zimmer-Galler IE, Green WR. Endogenous Nocardia asteroides endophthalmitis. Arch Ophthalmol 2002;120:210– 213. Moshfeghi DM, Sears JE, Lewis H. Submacular surgery for choroidal neovascularization following nocardial endophthalmitis. Retina 2004;24:161–164.
