- Email: [email protected]
Aspergillus endophthalmitis following orthotopic heart transplant
Correspondence acid on bradykinin pathways have an effect on the choroidal leakage in CSCR. To our knowledge, this is the first reported case of a patient with CSCR that may be related to underlying INHA. REFERENCES
Fig. 2—(A) Subretinal protein deposits and peripapillary neurosensory retinal detachment. (B–D) Focus of exuberant peripapillary leakage.
Bradykinin mediates vasodilatory effects via stimulation of nitric oxide formation by vascular endothelium. INHA is thought to be perpetuated when the main bradykinin inhibitor, C1Inh, is missing or has reduced function. This has been proposed as one of the causative agents of angioedema. We suggest that choroidal hyperpermeability in CSCR can be explained at least partially by an increase in bradykinin levels in this patient with INHA. It would be interesting to measure bradykinin levels in other patients with CSCR and evaluate whether the antifibrinolytic effects of tranexamic
Aspergillus endophthalmitis following orthotopic heart transplant
O
pportunistic systemic infections with Aspergillus species are common following orthotopic heart transplant (OHT).1 However, ocular infections are rare.1 To date, few cases2–5 of Aspergillus endophthalmitis following OHT have been reported; all showed evidence of disseminated aspergillosis and died within a few days of treatment. We report a patient with invasive Aspergillus endophthalmitis who survived for 16 years. A 70-year-old male presented in 1992 with a 3-day history of a painful left eye associated with blurred vision. He had undergone an OHT 80 days earlier and was immunosuppressed with azathioprine, 75 mg, prednisolone, 12.5 mg, and cyclosporine, 250 mg, daily. Differential white blood count (5.9 u 109/L) showed a neutrophilia (88%) and lymphopenia (10%). Two months previously, he had been investigated for pyrexia and shortness of breath. Chest computerized tomography showed a left lower lobe cavitated lesion, and bronchoalveolar lavage cultured Aspergillus fumigatus. No organism was grown on repeated blood culture, and echocardiography excluded any vegetations. At presentation to the eye department, systemic antifungal treatment included itraconazole, 400
1. Marmor MF, Tan F. Central serous chorioretinopathy: bilateral multifocal electroretinographic abnormalities. Arch Ophthalmol 1999;117:184–8. 2. Spaide RF, Campeas L, Haas A, et al. Central serous chorioretinopathy in younger and older adults. Ophthalmology 1996;103:2070–9; discussion 2079–80. 3. Bouillet L, Ponard D, Drouet C, Massot C. Non-allergic angiodema: update [in French]. Rev Méd Interne 2002;23:533–41. 4. Nussberger J, Cugno M, Amstutz C, Cicardi M, Pellacani A, Agostoni A. Plasma bradykinin in angio-oedema. Lancet 1998;351:1693–97. 5. Pizzimenti J, Daniel KP. Central serous chorioretinopathy after epidural steroid injection. Pharmacotherapy 2005;25:1141–46.
Kourosh Edalati, Marian Theresa Roesch, Michael L. Buchanan, Miriah Teeter, David Alan Maberley University of British Columbia, Vancouver, B.C. Correspondence to David Alan Maberley, MD: [email protected] Can J Ophthalmol 2009;44:606–7 doi:10.3129/i09-105
mg, intravenous amphotericin B, 200 mg, and nebulized amphotericin. His visual acuity was 6/5 right and hand movements left. Examination revealed left iridocyclitis with hypopyon restricting posterior segment view. A provisional diagnosis of endogenous endophthalmitis was made, urgent vitreous biopsy was performed, and intravitreal amphotericin, 5 Pg, miconazole, 10 Pg, gentamicin, 0.1 mg, and vancomycin, 1 mg, were administered. A large white retinal exudate was observed superotemporally; however, the retina was attached. Light microscopy of the vitreous aspirate identified neutrophils but no organisms. Subsequent cultures were negative. Electron microscopy revealed organisms measuring 2 to 4 Pm, with features suggestive of either Aspergillus or Candida (Fig. 1). Unfortunately, the patient’s left eye became blind and painful, requiring enucleation 1 month after presentation. The enucleation specimen showed a vitreous abscess, adjacent choroidal thickening, and retinal detachment (Fig. 1A). Histological examination confirmed a vitreous abscess (Fig. 1B) containing necrotic fungal elements centrally, with viable septate branching organisms peripherally. Mycological assessment confirmed A. fumigatus. Fungal hyphae penetrated the internal limiting membrane of the detached retina and invaded the inner nuclear layer. The retina was necrotic at the equator because of thrombosis of peripheral retinal vessels. Subretinal CAN J OPHTHALMOL—VOL. 44, NO. 5, 2009
607
Correspondence fungal hyphae invaded Bruch’s membrane through to the inner choroid (Figs. 1C and 1D). A massive inflammatory cell infiltration destroyed the choriocapillaris. The use of new selective immunosuppressive drugs has enabled the long-term survival of transplanted organs,3 while creating an increasing patient population at risk for invasive infections. Invasive aspergillosis is the most important cause of life-threatening fungal infection, affecting up to 13% of OHT recipients.1 A. fumigatus causes up to 90% of invasive aspergillosis in OHT recipients; Aspergillus flavus and Aspergillus niger are rare. A. fumigatus can bind specifically to different host tissue components, releases toxins that have a significant generalized immunosuppressive effect on host defences, and produces proteolytic enzymes that seem to be the main factor responsible for tissue invasion.6 The lungs are the main portal of entry. Once tissue infection develops, invasion of blood vessels ensues, resulting in tissue infarction and dissemination with metastatic seeding, which is almost uniformly fatal.7 Ocular complications following OHT are well described;3,5 however, endophthalmitis is rare and is usually associated with disseminated infection. Previous reports2–5 describe patients who had preceding aspergillus pneumonia or infective
Fig. 1—(A) Macroscopic picture of enucleation specimen showing dense vitreous abscess (arrowhead), retinal detachment (RD), and choroidal thickening (*). The lens is normal. (B) Photomicrograph of inflamed retina with surface granulation tissue (arrowheads) and edge of vitreous abscess (a) (hematoxylin and eosin; original magnification u40). (C) Photomicrograph showing numerous Aspergillus sp. in the subretinal space (arrowheads) (hematoxylin and eosin; original magnification u40). (D) Photomicrograph showing fungal hyphae in the subretinal space and penetrating the retinal pigment epithelium (RPE) and Bruch’s membrane (arrowheads) with necrosis of the choriocapillaris (CC) (periodic acid-Schiff; original magnification u400). (E) Transmission electron microscopy showing a septate branching hypha characteristic of Aspergillus sp.
Preretinal neovascularization after bevacizumab injections in a patient with von Hippel-Lindau syndrome
V
on Hippel-Lindau (VHL) syndrome is a rare, autosomal dominant, multisystemic, neoplastic syndrome. Retinal capillary hemangioblastomas (RCHs) are found in more than 50% of patients with VHL syndrome.1
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CAN J OPHTHALMOL—VOL. 44, NO. 5, 2009
endocarditis and died within a few days despite treatment.2,4,5 Retinal and choroidal vascular invasion with thrombosis and subsequent infarction is a predominant feature in Aspergillus endophthalmitis.2 Mycelia extend through the vessel walls and accumulate in tissue spaces,2 characteristically the subretinal and subretinal pigment epithelial spaces, which may explain why vitreous biopsy yielded no growth. Endogenous Aspergillus endophthalmitis is a rare, sightthreatening complication following OHT, typically associated with systemic infection and high mortality.2–5 Physicians managing transplant recipients should be aware of the risk and implications of fungal endophthalmitis and seek urgent ophthalmic assessment of any patient with visual symptoms because prompt systemic treatment may reduce morbidity and mortality. REFERENCES 1. Grossi P, Claudio F, Fiocchi R, Dalla Gasperina D. Prevalence and outcome of invasive fungal infections in 1,963 thoracic organ transplant recipients: a multicenter retrospective study. Transplantation 2000;70:112–6. 2. Bodoia RD, Kinyoun JL, Lou QL, Bunt-Milam AH. Aspergillus necrotizing retinitis. A clinic-pathological study and review. Retina 1989;9:226–31. 3. Ng P, McCluskey P, McCaughan G, Glanville A, MacDonald P, Keogh A. Ocular complications of heart, lung, and liver transplantation. Br J Ophthalmol 1998;82:423–8. 4. Garcia-Diaz JB, Dismukes WE, Pankey GA. A heart transplant patient with a scotoma. Infect Med 1998;15:827–31. 5. Sherman-Weber S, Axelrod P, Suh B, et al. Infective endocarditis following orthotopic heart transplantation: 10 cases and a review of the literature. Transpl Infect Dis 2004;6:165–70. 6. Tomee JF, Kauffman HF. Putative virulence factors of Aspergillus fumigatus. Clin Exp Allergy 2000;30:476–84. 7. Hibberd PL, Rubin RH. Clinical aspects of fungal infection in organ transplant recipients. Clin Infect Dis 1994;19:S33–40.
Maria Elena Gregory,* Clifford R. Weir,* Fiona Roberts,† Benjamin H. Browne‡ *Tennent Institute of Ophthalmology, Gartnavel General Hospital, † Western Infirmary, and ‡Glasgow Royal Infirmary, Glasgow, United Kingdom Correspondence to Maria Elena Gregory, MD: [email protected] Can J Ophthalmol 2009;44:607–8 doi:10.3129/i09-121
RCHs occur most commonly in the peripheral retina, but 11%–15% arise in a juxtapapillary location.2 Juxtapapillary RCHs are often located on the temporal side of the disc and chronic leakage can reduce visual acuity.3 Additionally, their location complicates treatment. Up-regulation of ocular vascular endothelial growth factor (VEGF) has been found in patients with VHL syndrome, although retinal and preretinal neovascularization
Fig. 2—(A) Subretinal protein deposits and peripapillary neurosensory retinal detachment. (B–D) Focus of exuberant peripapillary leakage.
Bradykinin mediates vasodilatory effects via stimulation of nitric oxide formation by vascular endothelium. INHA is thought to be perpetuated when the main bradykinin inhibitor, C1Inh, is missing or has reduced function. This has been proposed as one of the causative agents of angioedema. We suggest that choroidal hyperpermeability in CSCR can be explained at least partially by an increase in bradykinin levels in this patient with INHA. It would be interesting to measure bradykinin levels in other patients with CSCR and evaluate whether the antifibrinolytic effects of tranexamic
Aspergillus endophthalmitis following orthotopic heart transplant
O
pportunistic systemic infections with Aspergillus species are common following orthotopic heart transplant (OHT).1 However, ocular infections are rare.1 To date, few cases2–5 of Aspergillus endophthalmitis following OHT have been reported; all showed evidence of disseminated aspergillosis and died within a few days of treatment. We report a patient with invasive Aspergillus endophthalmitis who survived for 16 years. A 70-year-old male presented in 1992 with a 3-day history of a painful left eye associated with blurred vision. He had undergone an OHT 80 days earlier and was immunosuppressed with azathioprine, 75 mg, prednisolone, 12.5 mg, and cyclosporine, 250 mg, daily. Differential white blood count (5.9 u 109/L) showed a neutrophilia (88%) and lymphopenia (10%). Two months previously, he had been investigated for pyrexia and shortness of breath. Chest computerized tomography showed a left lower lobe cavitated lesion, and bronchoalveolar lavage cultured Aspergillus fumigatus. No organism was grown on repeated blood culture, and echocardiography excluded any vegetations. At presentation to the eye department, systemic antifungal treatment included itraconazole, 400
1. Marmor MF, Tan F. Central serous chorioretinopathy: bilateral multifocal electroretinographic abnormalities. Arch Ophthalmol 1999;117:184–8. 2. Spaide RF, Campeas L, Haas A, et al. Central serous chorioretinopathy in younger and older adults. Ophthalmology 1996;103:2070–9; discussion 2079–80. 3. Bouillet L, Ponard D, Drouet C, Massot C. Non-allergic angiodema: update [in French]. Rev Méd Interne 2002;23:533–41. 4. Nussberger J, Cugno M, Amstutz C, Cicardi M, Pellacani A, Agostoni A. Plasma bradykinin in angio-oedema. Lancet 1998;351:1693–97. 5. Pizzimenti J, Daniel KP. Central serous chorioretinopathy after epidural steroid injection. Pharmacotherapy 2005;25:1141–46.
Kourosh Edalati, Marian Theresa Roesch, Michael L. Buchanan, Miriah Teeter, David Alan Maberley University of British Columbia, Vancouver, B.C. Correspondence to David Alan Maberley, MD: [email protected] Can J Ophthalmol 2009;44:606–7 doi:10.3129/i09-105
mg, intravenous amphotericin B, 200 mg, and nebulized amphotericin. His visual acuity was 6/5 right and hand movements left. Examination revealed left iridocyclitis with hypopyon restricting posterior segment view. A provisional diagnosis of endogenous endophthalmitis was made, urgent vitreous biopsy was performed, and intravitreal amphotericin, 5 Pg, miconazole, 10 Pg, gentamicin, 0.1 mg, and vancomycin, 1 mg, were administered. A large white retinal exudate was observed superotemporally; however, the retina was attached. Light microscopy of the vitreous aspirate identified neutrophils but no organisms. Subsequent cultures were negative. Electron microscopy revealed organisms measuring 2 to 4 Pm, with features suggestive of either Aspergillus or Candida (Fig. 1). Unfortunately, the patient’s left eye became blind and painful, requiring enucleation 1 month after presentation. The enucleation specimen showed a vitreous abscess, adjacent choroidal thickening, and retinal detachment (Fig. 1A). Histological examination confirmed a vitreous abscess (Fig. 1B) containing necrotic fungal elements centrally, with viable septate branching organisms peripherally. Mycological assessment confirmed A. fumigatus. Fungal hyphae penetrated the internal limiting membrane of the detached retina and invaded the inner nuclear layer. The retina was necrotic at the equator because of thrombosis of peripheral retinal vessels. Subretinal CAN J OPHTHALMOL—VOL. 44, NO. 5, 2009
607
Correspondence fungal hyphae invaded Bruch’s membrane through to the inner choroid (Figs. 1C and 1D). A massive inflammatory cell infiltration destroyed the choriocapillaris. The use of new selective immunosuppressive drugs has enabled the long-term survival of transplanted organs,3 while creating an increasing patient population at risk for invasive infections. Invasive aspergillosis is the most important cause of life-threatening fungal infection, affecting up to 13% of OHT recipients.1 A. fumigatus causes up to 90% of invasive aspergillosis in OHT recipients; Aspergillus flavus and Aspergillus niger are rare. A. fumigatus can bind specifically to different host tissue components, releases toxins that have a significant generalized immunosuppressive effect on host defences, and produces proteolytic enzymes that seem to be the main factor responsible for tissue invasion.6 The lungs are the main portal of entry. Once tissue infection develops, invasion of blood vessels ensues, resulting in tissue infarction and dissemination with metastatic seeding, which is almost uniformly fatal.7 Ocular complications following OHT are well described;3,5 however, endophthalmitis is rare and is usually associated with disseminated infection. Previous reports2–5 describe patients who had preceding aspergillus pneumonia or infective
Fig. 1—(A) Macroscopic picture of enucleation specimen showing dense vitreous abscess (arrowhead), retinal detachment (RD), and choroidal thickening (*). The lens is normal. (B) Photomicrograph of inflamed retina with surface granulation tissue (arrowheads) and edge of vitreous abscess (a) (hematoxylin and eosin; original magnification u40). (C) Photomicrograph showing numerous Aspergillus sp. in the subretinal space (arrowheads) (hematoxylin and eosin; original magnification u40). (D) Photomicrograph showing fungal hyphae in the subretinal space and penetrating the retinal pigment epithelium (RPE) and Bruch’s membrane (arrowheads) with necrosis of the choriocapillaris (CC) (periodic acid-Schiff; original magnification u400). (E) Transmission electron microscopy showing a septate branching hypha characteristic of Aspergillus sp.
Preretinal neovascularization after bevacizumab injections in a patient with von Hippel-Lindau syndrome
V
on Hippel-Lindau (VHL) syndrome is a rare, autosomal dominant, multisystemic, neoplastic syndrome. Retinal capillary hemangioblastomas (RCHs) are found in more than 50% of patients with VHL syndrome.1
608
CAN J OPHTHALMOL—VOL. 44, NO. 5, 2009
endocarditis and died within a few days despite treatment.2,4,5 Retinal and choroidal vascular invasion with thrombosis and subsequent infarction is a predominant feature in Aspergillus endophthalmitis.2 Mycelia extend through the vessel walls and accumulate in tissue spaces,2 characteristically the subretinal and subretinal pigment epithelial spaces, which may explain why vitreous biopsy yielded no growth. Endogenous Aspergillus endophthalmitis is a rare, sightthreatening complication following OHT, typically associated with systemic infection and high mortality.2–5 Physicians managing transplant recipients should be aware of the risk and implications of fungal endophthalmitis and seek urgent ophthalmic assessment of any patient with visual symptoms because prompt systemic treatment may reduce morbidity and mortality. REFERENCES 1. Grossi P, Claudio F, Fiocchi R, Dalla Gasperina D. Prevalence and outcome of invasive fungal infections in 1,963 thoracic organ transplant recipients: a multicenter retrospective study. Transplantation 2000;70:112–6. 2. Bodoia RD, Kinyoun JL, Lou QL, Bunt-Milam AH. Aspergillus necrotizing retinitis. A clinic-pathological study and review. Retina 1989;9:226–31. 3. Ng P, McCluskey P, McCaughan G, Glanville A, MacDonald P, Keogh A. Ocular complications of heart, lung, and liver transplantation. Br J Ophthalmol 1998;82:423–8. 4. Garcia-Diaz JB, Dismukes WE, Pankey GA. A heart transplant patient with a scotoma. Infect Med 1998;15:827–31. 5. Sherman-Weber S, Axelrod P, Suh B, et al. Infective endocarditis following orthotopic heart transplantation: 10 cases and a review of the literature. Transpl Infect Dis 2004;6:165–70. 6. Tomee JF, Kauffman HF. Putative virulence factors of Aspergillus fumigatus. Clin Exp Allergy 2000;30:476–84. 7. Hibberd PL, Rubin RH. Clinical aspects of fungal infection in organ transplant recipients. Clin Infect Dis 1994;19:S33–40.
Maria Elena Gregory,* Clifford R. Weir,* Fiona Roberts,† Benjamin H. Browne‡ *Tennent Institute of Ophthalmology, Gartnavel General Hospital, † Western Infirmary, and ‡Glasgow Royal Infirmary, Glasgow, United Kingdom Correspondence to Maria Elena Gregory, MD: [email protected] Can J Ophthalmol 2009;44:607–8 doi:10.3129/i09-121
RCHs occur most commonly in the peripheral retina, but 11%–15% arise in a juxtapapillary location.2 Juxtapapillary RCHs are often located on the temporal side of the disc and chronic leakage can reduce visual acuity.3 Additionally, their location complicates treatment. Up-regulation of ocular vascular endothelial growth factor (VEGF) has been found in patients with VHL syndrome, although retinal and preretinal neovascularization