Acta Ophthalmologica 2014
In conclusion, although rare, AOX should be included in the differential diagnosis of solitary corneoscleral limbal masses in patients of all age groups. Diagnosis should be based on the characteristic clinical and histopathological features, and surgical treatment should be initiated promptly to prevent sight-threatening complications.
3
Department of Cardiology, Gentofte University Hospital, Copenhagen, Denmark; 4Department of Ophtalmology, National Hospital of the Faroe Islands, Queen Alexandrines Teaching Hospital, T orshavn, Faroe Islands doi: 10.1111/aos.12454
Editor,
References Dehner LP (2003): Juvenile xanthogranulomas in the first two decades of life: a clinicopathologic study of 174 cases with cutaneous and extracutaneous manifestations. Am J Surg Pathol 27: 579–593. Fan R & Sun J (2011): Neonatal systemic juvenile xanthogranuloma with an ominous presentation and successful treatment. Clin Med Insights Oncol 5: 157–161. Gartmann H & Tritsch H (1963): Nevoxanthoendothelioma with small and large nodules. Report on 13 cases. Arch Klin Exp Dermatol 215: 409–421. Yanoff M & Perry HD (1995): Juvenile xanthogranuloma of the corneoscleral limbus. Arch Ophthalmol 113: 915–917.
Correspondence: Dr Georgios T. Kontos Department of Ophthalmology Macclesfield District General Hospital Victoria Rd Macclesfield, Cheshire SK10 3BL UK Tel: +44 7973792795 Fax: +44 1625661866 Email: [email protected]
W
hipple’s disease (WD) was described 100 years ago, and the aetiology is the bacillus Tropheryma whipplei (Raoult et al. 2000). The disease is very rare with an estimated incidence of under 0.1/100.000/yrs (Schneider et al. 2008). The classical symptoms of WD involve the gastrointestinal tract, and severe weight loss is pathognomonic (Schneider et al. 2008). WD is also well known to be a rare cause of endocarditis. It is now known that WD can involve many different organs including the central nervous system (Schneider et al. 2008). Ocular involvement has been described (Touitou et al. 2012). A 63-year-old Caucasian male was admitted in September 2011 after a positive test for WD in a vitrectomy sample. In May 2008, he was admitted with diffuse symptoms with malaise, tiredness, limb pain, light weight loss and joint pain in hands, shoulders and legs. A kidney biopsy revealed sarcoidosis. In June 2010, the patient complained of vision problems. An ophtalmological examination revealed bilateral cataracts. The patient had cataract surgery performed in the right eye in October 2010. Five months later,
he complained of blurred vision in the right eye. Mild anterior uveitis and vitritis was found and treatment with topical steroids was initiated. The anterior uveitis disappeared, but the vitritis got worse, and in May 2011, systemic steroids were added. Initially, the vitritis got better, but then worsened again and involved now both eyes. He now developed neurological symptoms with slight paresis of his legs, paraesthesia around his mouth, paraesthesia on his tongue and fingers. In September 2011, he had worsening neurological symptoms. A spinal tap showed no pleocytosis, normal spinal fluid biochemistry. MRI of the brain was normal. A diagnostic vitrectomy of his right eye was performed (Fig. 1). No intravitreal antibiotics were given. The material was sent for a broad-range 16S rRNA examination and the laboratory identified Tropheryma whipplei. A transesophageal echocardiography revealed a 4 9 5 mm vegetation-like structure on the aortic valve. Gastroscopy with duodenal biopsies revealed periodic acid-Schiff-positive macrophages and PCR-positive tests for Tropheryma whipplei. His neurological and eye symptoms improved substantially on treatment with antibiotics. The plan is now to treat with monotherapy doxycycline for at least 2 years (and maybe for life) and then make a new spinal tap and gastroscopy in November 2014. His uveitis has been stable and the vitritis has nearly disappeared. He had cataract surgery performed in the left eye in October 2012 without any worsening of the vitritis. The patient described in this case report is interesting of several reasons.
Whipple’s disease involving the eye, the brain, the heart and the gut diagnosed through the eye Shahin Gaı¨ ni,1,2 Niels Eske Bruun,3 Rudi Kollslı´ ð,1 Heðin Thomsen,1 Torkil a´ Steig,1 Ka´ri Rubek Nielsen,1 Marija Todorovic Markovic1 and Elin Holm4 1
Department of Internal Medicine, National Hospital of the Faroe Islands, Queen Alexandrines Teaching Hospital, To´rshavn, Faroe Islands; 2Department of Infectious Diseases, Odense University Hospital, Odense, Denmark;
Fig. 1. Photograph of the fundus after diagnostic vitrectomy. Some vitreous is left and within it are characteristic findings of Whipple Disease. The opacities look like clumps of ‘white mulberries’, when looked in high resolution.
e693
Acta Ophthalmologica 2014
He did not have the severe weight loss pathognomonic for classic WD. He was diagnosed with kidney sarcoidosis before the WD diagnosis and was pharmacologically immunosuppressed. After the patient had his first cataract surgery performed, a severe mostly posterior uveitis was diagnosed. It did not respond to neither topical nor systemic immunosuppressive treatment. Case reports have described uveitis after intraocular operations in patients unknown to have WD, only diagnosed later on by vitreous samples. It is uncertain whether it is the operation in itself or the use of post-operative topical steroids that provokes the development of uveitis in these WD patients (Drancourt et al. 2009). In parallel with the eye problems, the patient developed significant neurological symptoms indicating involvement of the brain. WD is a fascinating disease entity with a wide range of clinical manifestations and has been considered to be an extremely rare disease (Raoult et al. 2000). This makes it difficult for clinicians to identify cases, especially the non-classic cases, with more atypical symptoms and findings. New data indicate that Tropheryma whipplei is ubiquitous in the environment (Maiwald et al. 1998). Clinicians treating patients with diffuse symptoms involving the brain and the eyes should not forget about this very rare disease which can be treated effectively with antibiotics.
References Drancourt M, Fenollar F, Denis D & Raoult D (2009): Postoperative panophthalmitis caused by Whipple disease. Emerg Infect Dis 15: 825–827. Maiwald M, Schuhmacher F, Ditton HJ & von Herbay A (1998): Environmental occurrence of the Whipple’s disease bacterium (Tropheryma whippelii). Appl Environ Microbiol 64: 760–762. Raoult D, Birg ML, La Scola B et al. (2000): Cultivation of the bacillus of Whipple’s disease. N Engl J Med 342: 620–625. Schneider T, Moos V, Loddenkemper C, Marth T, Fenollar F & Raoult D (2008): Whipple’s disease: new aspects of pathogenesis and treatment. Lancet Infect Dis 8: 179–190. Touitou V, Fenollar F, Cassoux N, MerleBeral H, LeHoang P, Amoura Z, Drancourt M & Bodaghi B (2012): Ocular Whipple’s disease: therapeutic strategy and long-term follow-up. Ophthalmology 119: 1465–1469.
e694
Correspondance: Elin Holm, MD Department of Ophtalmology National Hospital of the Faroe Islands Queen Alexandrines Teaching Hospital J.C. Svabosgøta 41-49 FO-100 T orshavn, Faroe Islands Tel: +298 304500 Fax: +298 314213 Email: [email protected]
Ozurdex® reduces the retinal thickness in radiation maculopathy refractory to bevacizumab Lisa Tarmann, Gerald Langmann, Christoph Mayer, Martin Weger, Anton Haas and Werner Wackernagel Department of Ophthalmology, Medical University of Graz, Graz, Austria doi: 10.1111/aos.12424
Editor, adiation retinopathy and maculopathy are common side-effects of radiotherapy for posterior uveal melanoma, occurring in up to 84% of cases (Haas et al. 2002). Recently, the administration of dexamethasone intravitreal implant (Ozurdexâ) has been approved by the U.S. Food and Drug Administration for the treatment of retinal oedema in retinal vein occlusion and non-infectious posterior uveitis (London et al. 2011; Bezatis et al. 2013; Matonti et al. 2013). This dexamethasone ‘drug delivery system’ (DDS) has been developed for a sustained drug release and longlasting effect up to 3–6 months, for superior dose consistency, and shows a favourable safety profile (London et al. 2011). We report the effect of dexamethasone DDS on retinal thickness and visual acuity after ineffective bevacizumab therapy in patients with radiation maculopathy. Institutional review board (IRB) approval was obtained for a retrospective evaluation of clinical records. All patients developed a radiation maculopathy with cystoid macular oedema,
R
between 15 months and 4 years after radiotherapy for uveal melanoma (Table 1). All 4 patients had previously been treated with intravitreal bevacizumab (Avastinâ), and one patient had received adjunct panretinal laser coagulation followed by an intravitreal triamcinolone. For the measurement of retinal thickness optical coherent tomography (OCT, Cirrus Operator; Zeiss, Oberkochen) five-line raster, evaluating the thickest horizontal retinal cross-sectional image directly in the perifoveolar area was used. Macular oedema: 2–4 weeks after treatment with dexamethasone, all patients showed a reduction in macular oedema; 14–17 weeks after injection retinal thickness increased to almost pretreatment values (Table 1). Visual acuity: Two patients showed a vision improvement of two or more Snellen lines within the first month of observation after treatment. Persistent improvement of vision was found in only one patient (14–17 weeks after treatment). Side-effects: An elevation of intraocular pressure was measured in one patient 2 months postoperatively (27 mmHg), which was treated by topical antiglaucomatous therapy. No infections or haemorrhages were seen after injection. Local tumour recurrence was not recorded during follow-up. Currently used off-label therapies for radiation maculopathy are as follows: periocular and intravitreal triamcinolone, intravitreal antivascular endothelial growth factor agents (anti-VEGF), photodynamic therapy and panretinal and central laser photocoagulation. Recently, intravitreal injection of antiVEGF has been published to reduce macular oedema, stabilize retinal vessels and reduce leakage after radiotherapy (Wen & McCannel 2009). Anatomical and functional results were promising; however, drug effect was not long lasting and frequent injections were necessary for continued response. In our study, we used the intravitreal Ozurdexâ as salvage treatment for radiation induced macular oedema, unresponsive to bevacizumab. Among the corticosteroids, dexamethasone is known to be one of the most potent substances, and due to its polymer structure of dexamethasone DDS, the drug effect lasts longer with consistent levels of drug release (London et al. 2011).
In conclusion, although rare, AOX should be included in the differential diagnosis of solitary corneoscleral limbal masses in patients of all age groups. Diagnosis should be based on the characteristic clinical and histopathological features, and surgical treatment should be initiated promptly to prevent sight-threatening complications.
3
Department of Cardiology, Gentofte University Hospital, Copenhagen, Denmark; 4Department of Ophtalmology, National Hospital of the Faroe Islands, Queen Alexandrines Teaching Hospital, T orshavn, Faroe Islands doi: 10.1111/aos.12454
Editor,
References Dehner LP (2003): Juvenile xanthogranulomas in the first two decades of life: a clinicopathologic study of 174 cases with cutaneous and extracutaneous manifestations. Am J Surg Pathol 27: 579–593. Fan R & Sun J (2011): Neonatal systemic juvenile xanthogranuloma with an ominous presentation and successful treatment. Clin Med Insights Oncol 5: 157–161. Gartmann H & Tritsch H (1963): Nevoxanthoendothelioma with small and large nodules. Report on 13 cases. Arch Klin Exp Dermatol 215: 409–421. Yanoff M & Perry HD (1995): Juvenile xanthogranuloma of the corneoscleral limbus. Arch Ophthalmol 113: 915–917.
Correspondence: Dr Georgios T. Kontos Department of Ophthalmology Macclesfield District General Hospital Victoria Rd Macclesfield, Cheshire SK10 3BL UK Tel: +44 7973792795 Fax: +44 1625661866 Email: [email protected]
W
hipple’s disease (WD) was described 100 years ago, and the aetiology is the bacillus Tropheryma whipplei (Raoult et al. 2000). The disease is very rare with an estimated incidence of under 0.1/100.000/yrs (Schneider et al. 2008). The classical symptoms of WD involve the gastrointestinal tract, and severe weight loss is pathognomonic (Schneider et al. 2008). WD is also well known to be a rare cause of endocarditis. It is now known that WD can involve many different organs including the central nervous system (Schneider et al. 2008). Ocular involvement has been described (Touitou et al. 2012). A 63-year-old Caucasian male was admitted in September 2011 after a positive test for WD in a vitrectomy sample. In May 2008, he was admitted with diffuse symptoms with malaise, tiredness, limb pain, light weight loss and joint pain in hands, shoulders and legs. A kidney biopsy revealed sarcoidosis. In June 2010, the patient complained of vision problems. An ophtalmological examination revealed bilateral cataracts. The patient had cataract surgery performed in the right eye in October 2010. Five months later,
he complained of blurred vision in the right eye. Mild anterior uveitis and vitritis was found and treatment with topical steroids was initiated. The anterior uveitis disappeared, but the vitritis got worse, and in May 2011, systemic steroids were added. Initially, the vitritis got better, but then worsened again and involved now both eyes. He now developed neurological symptoms with slight paresis of his legs, paraesthesia around his mouth, paraesthesia on his tongue and fingers. In September 2011, he had worsening neurological symptoms. A spinal tap showed no pleocytosis, normal spinal fluid biochemistry. MRI of the brain was normal. A diagnostic vitrectomy of his right eye was performed (Fig. 1). No intravitreal antibiotics were given. The material was sent for a broad-range 16S rRNA examination and the laboratory identified Tropheryma whipplei. A transesophageal echocardiography revealed a 4 9 5 mm vegetation-like structure on the aortic valve. Gastroscopy with duodenal biopsies revealed periodic acid-Schiff-positive macrophages and PCR-positive tests for Tropheryma whipplei. His neurological and eye symptoms improved substantially on treatment with antibiotics. The plan is now to treat with monotherapy doxycycline for at least 2 years (and maybe for life) and then make a new spinal tap and gastroscopy in November 2014. His uveitis has been stable and the vitritis has nearly disappeared. He had cataract surgery performed in the left eye in October 2012 without any worsening of the vitritis. The patient described in this case report is interesting of several reasons.
Whipple’s disease involving the eye, the brain, the heart and the gut diagnosed through the eye Shahin Gaı¨ ni,1,2 Niels Eske Bruun,3 Rudi Kollslı´ ð,1 Heðin Thomsen,1 Torkil a´ Steig,1 Ka´ri Rubek Nielsen,1 Marija Todorovic Markovic1 and Elin Holm4 1
Department of Internal Medicine, National Hospital of the Faroe Islands, Queen Alexandrines Teaching Hospital, To´rshavn, Faroe Islands; 2Department of Infectious Diseases, Odense University Hospital, Odense, Denmark;
Fig. 1. Photograph of the fundus after diagnostic vitrectomy. Some vitreous is left and within it are characteristic findings of Whipple Disease. The opacities look like clumps of ‘white mulberries’, when looked in high resolution.
e693
Acta Ophthalmologica 2014
He did not have the severe weight loss pathognomonic for classic WD. He was diagnosed with kidney sarcoidosis before the WD diagnosis and was pharmacologically immunosuppressed. After the patient had his first cataract surgery performed, a severe mostly posterior uveitis was diagnosed. It did not respond to neither topical nor systemic immunosuppressive treatment. Case reports have described uveitis after intraocular operations in patients unknown to have WD, only diagnosed later on by vitreous samples. It is uncertain whether it is the operation in itself or the use of post-operative topical steroids that provokes the development of uveitis in these WD patients (Drancourt et al. 2009). In parallel with the eye problems, the patient developed significant neurological symptoms indicating involvement of the brain. WD is a fascinating disease entity with a wide range of clinical manifestations and has been considered to be an extremely rare disease (Raoult et al. 2000). This makes it difficult for clinicians to identify cases, especially the non-classic cases, with more atypical symptoms and findings. New data indicate that Tropheryma whipplei is ubiquitous in the environment (Maiwald et al. 1998). Clinicians treating patients with diffuse symptoms involving the brain and the eyes should not forget about this very rare disease which can be treated effectively with antibiotics.
References Drancourt M, Fenollar F, Denis D & Raoult D (2009): Postoperative panophthalmitis caused by Whipple disease. Emerg Infect Dis 15: 825–827. Maiwald M, Schuhmacher F, Ditton HJ & von Herbay A (1998): Environmental occurrence of the Whipple’s disease bacterium (Tropheryma whippelii). Appl Environ Microbiol 64: 760–762. Raoult D, Birg ML, La Scola B et al. (2000): Cultivation of the bacillus of Whipple’s disease. N Engl J Med 342: 620–625. Schneider T, Moos V, Loddenkemper C, Marth T, Fenollar F & Raoult D (2008): Whipple’s disease: new aspects of pathogenesis and treatment. Lancet Infect Dis 8: 179–190. Touitou V, Fenollar F, Cassoux N, MerleBeral H, LeHoang P, Amoura Z, Drancourt M & Bodaghi B (2012): Ocular Whipple’s disease: therapeutic strategy and long-term follow-up. Ophthalmology 119: 1465–1469.
e694
Correspondance: Elin Holm, MD Department of Ophtalmology National Hospital of the Faroe Islands Queen Alexandrines Teaching Hospital J.C. Svabosgøta 41-49 FO-100 T orshavn, Faroe Islands Tel: +298 304500 Fax: +298 314213 Email: [email protected]
Ozurdex® reduces the retinal thickness in radiation maculopathy refractory to bevacizumab Lisa Tarmann, Gerald Langmann, Christoph Mayer, Martin Weger, Anton Haas and Werner Wackernagel Department of Ophthalmology, Medical University of Graz, Graz, Austria doi: 10.1111/aos.12424
Editor, adiation retinopathy and maculopathy are common side-effects of radiotherapy for posterior uveal melanoma, occurring in up to 84% of cases (Haas et al. 2002). Recently, the administration of dexamethasone intravitreal implant (Ozurdexâ) has been approved by the U.S. Food and Drug Administration for the treatment of retinal oedema in retinal vein occlusion and non-infectious posterior uveitis (London et al. 2011; Bezatis et al. 2013; Matonti et al. 2013). This dexamethasone ‘drug delivery system’ (DDS) has been developed for a sustained drug release and longlasting effect up to 3–6 months, for superior dose consistency, and shows a favourable safety profile (London et al. 2011). We report the effect of dexamethasone DDS on retinal thickness and visual acuity after ineffective bevacizumab therapy in patients with radiation maculopathy. Institutional review board (IRB) approval was obtained for a retrospective evaluation of clinical records. All patients developed a radiation maculopathy with cystoid macular oedema,
R
between 15 months and 4 years after radiotherapy for uveal melanoma (Table 1). All 4 patients had previously been treated with intravitreal bevacizumab (Avastinâ), and one patient had received adjunct panretinal laser coagulation followed by an intravitreal triamcinolone. For the measurement of retinal thickness optical coherent tomography (OCT, Cirrus Operator; Zeiss, Oberkochen) five-line raster, evaluating the thickest horizontal retinal cross-sectional image directly in the perifoveolar area was used. Macular oedema: 2–4 weeks after treatment with dexamethasone, all patients showed a reduction in macular oedema; 14–17 weeks after injection retinal thickness increased to almost pretreatment values (Table 1). Visual acuity: Two patients showed a vision improvement of two or more Snellen lines within the first month of observation after treatment. Persistent improvement of vision was found in only one patient (14–17 weeks after treatment). Side-effects: An elevation of intraocular pressure was measured in one patient 2 months postoperatively (27 mmHg), which was treated by topical antiglaucomatous therapy. No infections or haemorrhages were seen after injection. Local tumour recurrence was not recorded during follow-up. Currently used off-label therapies for radiation maculopathy are as follows: periocular and intravitreal triamcinolone, intravitreal antivascular endothelial growth factor agents (anti-VEGF), photodynamic therapy and panretinal and central laser photocoagulation. Recently, intravitreal injection of antiVEGF has been published to reduce macular oedema, stabilize retinal vessels and reduce leakage after radiotherapy (Wen & McCannel 2009). Anatomical and functional results were promising; however, drug effect was not long lasting and frequent injections were necessary for continued response. In our study, we used the intravitreal Ozurdexâ as salvage treatment for radiation induced macular oedema, unresponsive to bevacizumab. Among the corticosteroids, dexamethasone is known to be one of the most potent substances, and due to its polymer structure of dexamethasone DDS, the drug effect lasts longer with consistent levels of drug release (London et al. 2011).
