Correspondence coagulation disorders (such as activated protein C resistance or factor V Leiden mutation), immobilization, pregnancy, smoking, medication with corticoids, family disposition, and COCs.3 Underlying conditions that may cause CVST vary, and the etiology is unknown in such cases. Several studies have indicated that COCs and thrombophilia greatly increased the risk of CVST.7 Combined estrogen-progestin oral contraceptives have been associated with an increased risk of venous thromboembolic events. This thrombotic risk was attributed to the estrogen content, which prompted the development of oral contraceptives containing less estrogen. Use of formulations containing lower-dose estrogen still confer about 2fold to 4-fold increased risk of venous thromboembolic events compared with non-use.8 As the most common causes of HH are infarctions, meningiomas, gliomas, and metastatic lesions, these must be kept in mind. However, only a few patients with HH presenting with neurosyphilis, migraine, demyelinating disease, arteriovenous malformation, or neurosarcoidosis have been reported.9 MRI and MRV are the best tools for both the diagnosis and the follow-up of CVST.10 In our case, MRI found right acute occipital lobe infarction (see Fig. 2A-D). MRV showed thrombosis of the right transverse sinus and left internal jugular vein (see Fig. 3A, B). Venous thrombosis has traditionally involved the superficial cerebral venous system,11 as described in our case. To our knowledge, this is the first published case with HH due to CVST associated with COC usage. Available treatment data from the literature offer the use of anticoagulation in patients with CVST.12 Oral anticoagulation is recommended for 3 months in patients with idiopathic CVST and for 3 to 6 months if it is related to pregnancy or oral contraceptives. In patients with hereditary thrombophilia, it is used for 6 to 12 months or longer.4 Anticoagulant therapy was started after the diagnosis of CVST in our patient and continued. Her symptoms improved rapidly, and the visual field defect was much improved in 1 week.
CONCLUSION Homonymous hemianopia is an uncommon vision problem, and our case highlights the importance of imaging techniques to explain unexpected clinical findings. All females must be informed about the increased risk of venous thromboembolism during COC usage. The
Proton beam radiotherapy of progressive pediatric choroidal osteoma: First experience Choroidal osteoma is a rare intraocular tumour predominantly appearing in healthy females in the second or third decade of life.1 Usually, the tumour emerges unilaterally;
other possible diseases should be excluded with detailed clinical history, laboratory findings, and imaging techniques. The most important aspect of this case is the early diagnosis and treatment. Therefore, an accurate and timely diagnosis is important in such cases, and accurate techniques are required for appropriate treatment. Gökçen Çoban, Aylin Karalezli, Bahriye Horasanlı, Nilüfer Yeşilırmak Bas¸kent University Faculty of Medicine, Konya, Turkey Correspondence to: Go¨kc¸en C ¸ oban, MD: [email protected]
REFERENCES 1. Miller NR. Lesions in visual sensory pathway. In: Miller NR, editor. Walsh and Hoyt’s Clinical Neuro-ophthalmology. 4th ed. Baltimore, MD: Williams & Wilkins; 1982: 108-52. 2. Schofield TM, Leff AP. Rehabilitation of hemianopia. Curr Opin Neurol. 2009;22:36-40. 3. van Hylckama Vlieg A, Helmerhors FM, Vandenbroucke JP, et al. The venous thrombotic risk of oral contraceptives, effects of oestrogen dose and progestogen type: results of the MEGA-case control study. BMJ. 2009;339:b2921. 4. Masuhr F, Mehraein S, Einhaupl K. Cerebral venous and sinus thrombosis. J Neurol. 2004;251:11-23. 5. Cheng S, Chng SM, Singh R. Cerebral venous infarction during a high altitude expedition. Singapore Med J. 2009;50:306-8. 6. van den Bergh WM, van der Schaaf I, van Gijn J. The spectrum of presentations of venous infarction caused by deep cerebral vein thrombosis. Neurology. 2005;65:192-6. 7. Martinelli I, Sacchi E, Landi G, Taioli E, Duca F, Mannucci PM. High risk of CVST in carriers of a prothrombinogen mutation and in users of oral contraceptives. N Engl J Med. 1998;338: 1793-7. 8. Helmerhorst FM, Bloemenkamp KW, Rosendaal FR, Vandenbroucke JP. Oral contraceptives and thrombotic disease: risk of venous thromboembolism. Thromb Haemost. 1997;78:327-33. 9. Sattelmeyer VM, Vernet O, Janzer R, de Tribolet N. Neurosarcoidosis presenting as an isolated mass of the quadrigeminal plate. J Clin Neurosci. 1999;6:259-61. 10. Yuh WT, Simonson TM, Wang AM, et al. Venous sinus occlusive disease: MR findings. Am J Neuroradiol. 1994;15:309-16. 11. Fujimaki T, Matsutani M, Asai A, Kohno T, Koike M. Cerebral venous thrombosis due to high-altitude polycythemia. J Neurosurg. 1986;64:148-50. 12. De Bruijn SFTM, Stam J; for the Cerebral Venous Sinus Thrombosis Study Group. Randomized, placebo-controlled trial of anticoagulant treatment with low-molecular-weight heparin for cerebral venous thrombosis. Stroke. 1999;30:484-8. Can J Ophthalmol 2014;49:e119–e123 0008-4182/14/$-see front matter & 2014 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.jcjo.2014.07.006
only in 20% to 25% of cases is choroidal osteoma bilateral.1 It is typically located in the juxtapapillary or peripapillary region.1 Funduscopically, choroidal osteoma presents as a yellow-white to orange-red lesion.1 Ultrasonography reveals an elevated choroidal lesion with high reflectivity and a typical acoustic shadowing.1 Visual
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Correspondence prognosis is unpredictable, but 56% to 58% of patients end up with poor visual acuity (VA) at 10 years (20/200 or worse).2,3 Complications occurring with choroidal osteoma resulting in VA deterioration include tumour growth, decalcification, and choroidal neovascularization (CNV). Despite its benign nature, choroidal osteoma may grow in about 51% of cases by 10 years.2 Decalcification is seen in 46%, and CNV may develop in 31% by 10 years.2 No standard therapy for choroidal osteoma has yet been established. The lack of such a standard especially affects the management of pediatric osteoma in young children.
CASE REPORT In April 2008, a 4-year-old female presented with a subretinal tumour of unknown origin in the left eye on the
occasion of retinoscopy. At the first examination, the VA in both eyes was 20/20. An amelanotic prominent juxtapapillary tumour, nasal and inferior to the fovea, 2.5 disc diameters in dimension, and orange-red, was seen (Fig. 1A). On optical coherence tomography, no accompanying exudation was detectable. However, a subretinal tumour mass with a bulging elevation of the retina was visible. Ultrasonography found a hyperreflective lesion with an acoustic shadow consistent with a calcified tumour (Fig. 2). The patient’s brother had died at age 13 years because of an extraosseous Ewing sarcoma (primitive neuroectodermal tumour [PNET]), a fact that prompted further work-up of the child to exclude choroidal metastasis of Ewing sarcoma. After PNET was excluded using whole-body magnetic resonance imaging, the diagnosis of a choroidal osteoma was made.4 Sclerochoroidal calcification as a differential diagnosis could be ruled out, given
Fig. 1 — Funduscopic photograph and optical coherence tomography scan of the choroidal tumour nasal and inferior to the optic disc in April 2008 (A). Six months later, in October 2008, the osteoma had progressed clearly (B). Nineteen months after proton beam radiotherapy, the tumour had regressed, showing discrete retinal pigment epithelium alterations at the edges. The foveal architecture was intact, with visual acuity of 20/22 (C).
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Correspondence DISCUSSION
Fig. 2 — Ultrasonography shows a hyperreflective mass in the left eye with an acoustic shadow.
that it usually occurs in elderly patients, is often associated with electrolyte imbalance, and presents a different clinical picture with regard to the location, number, and shape of the lesions. During the following months, the tumour increased progressively in size, approaching the fovea (see Fig. 1B). To date, no standard treatment for choroidal osteoma has been established. To stop tumour growth we decided to perform low-dose proton beam radiation as used for exudative choroidal hemangioma, a benign intraocular choroidal tumour with secondary visual loss on long-term follow-up.5 In January 2009, proton beam radiation was performed with a total dose of 20 cobalt gray equivalent (CGE) in 4 fractions of 5 CGE on 4 consecutive days. In the fully anaesthetized patient, the eye was deflected with a special suction system to place a frontal 68 MeV fixed proton beam. This technique led to a complete sparing of the cornea, the anterior chamber, and the bony orbit. The 90% isodose covered the target with an additional safety margin of 1.5 mm defined. In the following months the tumour regressed, and discrete retinal pigment epithelium (RPE) alterations appeared at the edges of the tumour (see Fig. 1C). VA remained at 20/22. In February 2011, VA decreased to 20/50. There were hemorrhages at the central border of the osteoma; subretinal fluid was seen on optical coherence tomography; and fluorescence angiography found CNV (Fig. 3A). Intravitreal injection of bevacizumab (1.25 mg/0.05 mL) was conducted based on reports of the effectiveness of anti–vascular endothelial growth factor (anti-VEGF) therapy with respect to CNV secondary to choroidal osteoma.6,7 A CNV recurrence in July 2011 resulted in a second treatment, and a further recurrence in May 2013 was treated by a third injection. The VA at the most recent examination (in July 2013) was 20/400. The choroidal osteoma remained in a regressed state, and the CNV was inactive (see Fig. 3B). Reduction of VA was due to secondary foveal atrophy.
Therapeutic experiences with choroidal osteoma are rare because of its infrequence. It is a benign tumour of the choroid whose etiology and pathogenesis are not well understood. Choroidal osteoma in a child is even rarer than in adults. There are only a few case reports of choroidal osteoma appearing in a child.8–11 In our case, the tumour showed progressive growth within 8 months of follow-up. As the spontaneous course was difficult to predict, and because of the family history of extraosseous Ewing sarcoma in the brother, we discussed with the parents possible options to stop tumour growth and to keep the best possible vision. Choroidal osteoma is made up of osseous tissue. During bone growth, proliferating mesenchymal precursor cells differentiate into osteoblasts that produce ground substance that accompanies an increase in capillary density. Radiotherapy aims at destroying these proliferating mesenchymal precursor cells and the proliferating endothelial cells of the capillary vessels, resulting in cessation of osteoma growth or even tumour regression. Low-dose proton beam radiotherapy succeeded in tumour control; however, during the follow-up, secondary CNV occurred with foveal involvement, resulting in foveal atrophy, reduced vision, and eccentric fixation at the end. No radiation optic neuropathy was evident at the last visit, despite the juxtapapillary location of the osteoma. We believe that the development of CNV was caused by RPE alterations arising after radiation during regression of the tumour as an indirect effect of the radiotherapy and not by radiation retinopathy.12–14 AntiVEGF-treatment (as off-label therapy) was effective to inactivate the CNV and recurrences occurring at long intervals, as reported by other authors.6,7 Visual loss associated with choroidal osteoma is often caused by decalcification of the osteoma and secondary pigment epithelial atrophy in the foveal area resulting in photoreceptor atrophy.15 In 46% of cases, decalcification has taken place after an observation time of 10 years.2 Another possible reason for visual impairment is the development of a CNV, occurring in 31% of patients at 10 years.2 Shields et al.2,11 have observed that tumour growth was arrested in decalcified choroidal osteomas and that tumour growth occurred only at the site opposite the decalcified area of a partially decalcified osteoma. Hence, targeted decalcification as a therapeutic approach using laser photocoagulation or photodynamic therapy was discussed in this context. However, in our case, laser photocoagulation of the central part of the osteoma to prevent further growth onto the fovea would have resulted in significant visual field defects and immediate deterioration of VA. Photodynamic therapy was used only in single pediatric patients until now to treat other diseases.16 It would not have been possible in the present case because of reduced cooperation of the child. A further idea to maintain calcification of choroidal osteoma and to preserve vision was calcium supplementation.11 However, the exact role
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Fig. 3 — Two years after proton beam radiotherapy, a subretinal hemorrhage occurred at the border of the regressed osteoma. In the optical coherence tomography scan, the subretinal bleeding together with subretinal fluid was evident. Early-phase and late-phase fluorescence angiography found a choroidal neovascularization (CNV) (A). After 3 intravitreal injections of bevacizumab (1.25 mg/0.05 mL), the CNV was inactive, without any hemorrhages on the funduscopic photograph. Optical coherence tomography found foveal atrophy without intraretinal or subretinal fluid. Fluorescence angiography did not find any evidence for active CNV (B).
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Correspondence of calcium supplementation in this context is unclear, and data are still lacking.
CONCLUSION Choroidal osteoma can show an aggressive course even in young children. To the best of our knowledge, the management of the present case marked the first time that proton beam radiotherapy was used for the treatment of choroidal osteoma. Low-dose proton beam radiotherapy may be an option to stop tumour growth and to prevent visual loss. However, the possibility of tumour-associated or radiation-associated complications (or both) during the clinical course still has to be considered. Long-term regular follow-up is mandatory in these young patients. Daniela Süsskind, * Elke K. Altpeter, * Lutz Moser, ‡ Michael H. Foerster, *,† Sabine Aisenbrey *
Karls University, Tübingen, Germany; †Augenklinik DRK Kliniken Berlin Westend, Berlin, Germany; and ‡Charite´, Campus Benjamin Franklin, Berlin, Germany
*Eberhard
Correspondence to: Daniela Su¨sskind, MD: daniela.suesskind@med. uni-tuebingen.de REFERENCES 1. Shields C, Shields JA, Augsburger JJ. Choroidal osteoma. Surv Ophthalmol. 1988;33:17-27. 2. Shields CL, Sun H, Demirci H, Shields JA. Factors predictive of tumor growth, tumor decalcification, choroidal neovascularization, and visual outcome in 74 eyes with choroidal osteoma. Arch Ophthalmol. 2005;123:1658-66. 3. Aylward GW, Chang TS, Pautler SE, Gass JDM. A long-term follow-up of choroidal osteoma. Arch Ophthalmol. 1998;116: 1337-41.
Peripheral retinal ischemia after intravenous tissue plasminogen activator for central retinal artery occlusion Central retinal artery occlusion (CRAO) is most commonly caused by emboli, 74% of which are composed of cholesterol originating from atherosclerotic plaques in the carotid artery.1 CRAO is an ophthalmic emergency typically associated with severe visual loss, but there is no evidence-based guideline for treatment.2 Given the similar mechanism of nonarteritic CRAO and cerebral stroke, there is growing interest in the use of tissue plasminogen activator (tPA) as an acute intervention for this condition.3–5 Thrombolytic agents such as tPA are designed to break up fibrinoplatelet occlusions. In our patient, it is possible that such treatment may have led to distalization of the retinal vascular emboli and development of a sharply demarcated zone of peripheral retinal ischemia with more posterior intervening zones that remained perfused.
4. Altpeter EK, Süsskind D, Bartz-Schmidt KU, Foerster MH, Aisenbrey S. Unclear parapapillary tumor in childhood [published online May 18, 2013]. Ophthalmologe. 5. Höcht S, Wachtlin J, Bechrakis NE, et al. Proton or photon irradiation for hemangiomas of the choroid? A retrospective comparison. Int J Radiat Oncol Biol Phys. 2006;66:345-51. 6. Kubota-Taniai M, Oshitari T, Handa M, Baba T, Yotsukura J, Yamamoto S. Long-term success of intravitreal bevacizumab for choroidal neovascularization associated with choroidal osteoma. Clin Ophthalmol. 2011;5:1051-5. 7. Wu ZHY, Wong MYY, Lai TYY. Long-term follow-up of intravitreal ranibizumab for the treatment of choroidal neovascularization due to choroidal osteoma. Case Rep Ophthalmol. 2012;3:200-4. 8. Fava GE, Brown GC, Shields JA, Broocker G. Choroidal osteoma in a 6-year-old child. J Pediatr Ophthalmol Strabismus. 1980;17:203-5. 9. Cunha SL. Osseous choristoma of the choroid: a familial disease. Arch Ophthalmol. 1984;102:1052-4. 10. Mizota A, Tanabe R, Adachi-Usami E. Rapid enlargement of choroidal osteoma in a 3-year-old girl. Arch Ophthalmol. 1998;116: 1128-9. 11. Voluck MR, Say EA, Shields CL. Progressive growth of bilateral choroidal osteomas in a child. J Pediatr Ophthalmol Strabismus. 2011;48:e66-8. 12. Spaide RF, Borodoker N, Shah V. Atypical choroidal neovascularization in radiation retinopathy. Am J Ophthalmol. 2002;133:709-11. 13. Berker N, Aslan O, Batman C, Elgin U, Ozkan SS. Choroidal neovascular membrane in radiation retinopathy. Clin Experiment Ophthalmol. 2006;34:625-6. 14. Ghauri A-J, Musadiy M, Sha Y, Elsherbiny S. Late onset of subfoveal choroidal neovascularisation following cerebral radiotherapy. BMJ Case Rep. 2010;2010:bcr0520091825. 15. Shields CL, Perez B, Materin M, Mehta S, Shields JA. Optical coherence tomography of choroidal osteoma in 22 cases: evidence for photoreceptor atrophy over the decalcified portion of the tumor. Ophthalmology. 2007;114:e53-8. 16. Lipski A, Bornfeld N, Jurklies B. Photodynamic therapy with verteporfin in paediatric and young adult patients: long-term treatment results of choroidal neovascularisations. Br J Ophthalmol. 2008;92:655-60. Can J Ophthalmol 2014;49:e123–e127 0008-4182/14/$-see front matter & 2014 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.jcjo.2014.07.009
A 63-year-old male presented to the emergency department with a 2-hour history of sudden painless vision loss of the right eye and a visual acuity (VA) of hand motions. He was diagnosed with an acute CRAO and emergently treated with intravenous (IV) tPA (9 mg bolus with an additional 81 mg administered over 1 hour). One week later, vision was subjectively improved in the right eye but measured only count fingers. Colour fundus photography and fluorescein angiography (FA) performed 1 week after treatment showed a cherry red spot with cilioretinal sparing and a Hollenhorst embolus at the origin of the inferior hemiretinal artery (Fig. 1). Although the retina was perfused in the midperiphery, a well-demarcated region of peripheral whitening (Fig. 2) corresponding to inferotemporal zones of retinal ischemia and nonperfusion on FA could be appreciated (Fig. 3). Distalized intraarterial (IA) embolic plaques were identified in the inferotemporal periphery (Fig. 4). Interestingly, the arteriolar blood columns distal to these emboli were dark
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CONCLUSION Homonymous hemianopia is an uncommon vision problem, and our case highlights the importance of imaging techniques to explain unexpected clinical findings. All females must be informed about the increased risk of venous thromboembolism during COC usage. The
Proton beam radiotherapy of progressive pediatric choroidal osteoma: First experience Choroidal osteoma is a rare intraocular tumour predominantly appearing in healthy females in the second or third decade of life.1 Usually, the tumour emerges unilaterally;
other possible diseases should be excluded with detailed clinical history, laboratory findings, and imaging techniques. The most important aspect of this case is the early diagnosis and treatment. Therefore, an accurate and timely diagnosis is important in such cases, and accurate techniques are required for appropriate treatment. Gökçen Çoban, Aylin Karalezli, Bahriye Horasanlı, Nilüfer Yeşilırmak Bas¸kent University Faculty of Medicine, Konya, Turkey Correspondence to: Go¨kc¸en C ¸ oban, MD: [email protected]
REFERENCES 1. Miller NR. Lesions in visual sensory pathway. In: Miller NR, editor. Walsh and Hoyt’s Clinical Neuro-ophthalmology. 4th ed. Baltimore, MD: Williams & Wilkins; 1982: 108-52. 2. Schofield TM, Leff AP. Rehabilitation of hemianopia. Curr Opin Neurol. 2009;22:36-40. 3. van Hylckama Vlieg A, Helmerhors FM, Vandenbroucke JP, et al. The venous thrombotic risk of oral contraceptives, effects of oestrogen dose and progestogen type: results of the MEGA-case control study. BMJ. 2009;339:b2921. 4. Masuhr F, Mehraein S, Einhaupl K. Cerebral venous and sinus thrombosis. J Neurol. 2004;251:11-23. 5. Cheng S, Chng SM, Singh R. Cerebral venous infarction during a high altitude expedition. Singapore Med J. 2009;50:306-8. 6. van den Bergh WM, van der Schaaf I, van Gijn J. The spectrum of presentations of venous infarction caused by deep cerebral vein thrombosis. Neurology. 2005;65:192-6. 7. Martinelli I, Sacchi E, Landi G, Taioli E, Duca F, Mannucci PM. High risk of CVST in carriers of a prothrombinogen mutation and in users of oral contraceptives. N Engl J Med. 1998;338: 1793-7. 8. Helmerhorst FM, Bloemenkamp KW, Rosendaal FR, Vandenbroucke JP. Oral contraceptives and thrombotic disease: risk of venous thromboembolism. Thromb Haemost. 1997;78:327-33. 9. Sattelmeyer VM, Vernet O, Janzer R, de Tribolet N. Neurosarcoidosis presenting as an isolated mass of the quadrigeminal plate. J Clin Neurosci. 1999;6:259-61. 10. Yuh WT, Simonson TM, Wang AM, et al. Venous sinus occlusive disease: MR findings. Am J Neuroradiol. 1994;15:309-16. 11. Fujimaki T, Matsutani M, Asai A, Kohno T, Koike M. Cerebral venous thrombosis due to high-altitude polycythemia. J Neurosurg. 1986;64:148-50. 12. De Bruijn SFTM, Stam J; for the Cerebral Venous Sinus Thrombosis Study Group. Randomized, placebo-controlled trial of anticoagulant treatment with low-molecular-weight heparin for cerebral venous thrombosis. Stroke. 1999;30:484-8. Can J Ophthalmol 2014;49:e119–e123 0008-4182/14/$-see front matter & 2014 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.jcjo.2014.07.006
only in 20% to 25% of cases is choroidal osteoma bilateral.1 It is typically located in the juxtapapillary or peripapillary region.1 Funduscopically, choroidal osteoma presents as a yellow-white to orange-red lesion.1 Ultrasonography reveals an elevated choroidal lesion with high reflectivity and a typical acoustic shadowing.1 Visual
CAN J OPHTHALMOL — VOL. 49, NO. 5, OCTOBER 2014
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Correspondence prognosis is unpredictable, but 56% to 58% of patients end up with poor visual acuity (VA) at 10 years (20/200 or worse).2,3 Complications occurring with choroidal osteoma resulting in VA deterioration include tumour growth, decalcification, and choroidal neovascularization (CNV). Despite its benign nature, choroidal osteoma may grow in about 51% of cases by 10 years.2 Decalcification is seen in 46%, and CNV may develop in 31% by 10 years.2 No standard therapy for choroidal osteoma has yet been established. The lack of such a standard especially affects the management of pediatric osteoma in young children.
CASE REPORT In April 2008, a 4-year-old female presented with a subretinal tumour of unknown origin in the left eye on the
occasion of retinoscopy. At the first examination, the VA in both eyes was 20/20. An amelanotic prominent juxtapapillary tumour, nasal and inferior to the fovea, 2.5 disc diameters in dimension, and orange-red, was seen (Fig. 1A). On optical coherence tomography, no accompanying exudation was detectable. However, a subretinal tumour mass with a bulging elevation of the retina was visible. Ultrasonography found a hyperreflective lesion with an acoustic shadow consistent with a calcified tumour (Fig. 2). The patient’s brother had died at age 13 years because of an extraosseous Ewing sarcoma (primitive neuroectodermal tumour [PNET]), a fact that prompted further work-up of the child to exclude choroidal metastasis of Ewing sarcoma. After PNET was excluded using whole-body magnetic resonance imaging, the diagnosis of a choroidal osteoma was made.4 Sclerochoroidal calcification as a differential diagnosis could be ruled out, given
Fig. 1 — Funduscopic photograph and optical coherence tomography scan of the choroidal tumour nasal and inferior to the optic disc in April 2008 (A). Six months later, in October 2008, the osteoma had progressed clearly (B). Nineteen months after proton beam radiotherapy, the tumour had regressed, showing discrete retinal pigment epithelium alterations at the edges. The foveal architecture was intact, with visual acuity of 20/22 (C).
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Correspondence DISCUSSION
Fig. 2 — Ultrasonography shows a hyperreflective mass in the left eye with an acoustic shadow.
that it usually occurs in elderly patients, is often associated with electrolyte imbalance, and presents a different clinical picture with regard to the location, number, and shape of the lesions. During the following months, the tumour increased progressively in size, approaching the fovea (see Fig. 1B). To date, no standard treatment for choroidal osteoma has been established. To stop tumour growth we decided to perform low-dose proton beam radiation as used for exudative choroidal hemangioma, a benign intraocular choroidal tumour with secondary visual loss on long-term follow-up.5 In January 2009, proton beam radiation was performed with a total dose of 20 cobalt gray equivalent (CGE) in 4 fractions of 5 CGE on 4 consecutive days. In the fully anaesthetized patient, the eye was deflected with a special suction system to place a frontal 68 MeV fixed proton beam. This technique led to a complete sparing of the cornea, the anterior chamber, and the bony orbit. The 90% isodose covered the target with an additional safety margin of 1.5 mm defined. In the following months the tumour regressed, and discrete retinal pigment epithelium (RPE) alterations appeared at the edges of the tumour (see Fig. 1C). VA remained at 20/22. In February 2011, VA decreased to 20/50. There were hemorrhages at the central border of the osteoma; subretinal fluid was seen on optical coherence tomography; and fluorescence angiography found CNV (Fig. 3A). Intravitreal injection of bevacizumab (1.25 mg/0.05 mL) was conducted based on reports of the effectiveness of anti–vascular endothelial growth factor (anti-VEGF) therapy with respect to CNV secondary to choroidal osteoma.6,7 A CNV recurrence in July 2011 resulted in a second treatment, and a further recurrence in May 2013 was treated by a third injection. The VA at the most recent examination (in July 2013) was 20/400. The choroidal osteoma remained in a regressed state, and the CNV was inactive (see Fig. 3B). Reduction of VA was due to secondary foveal atrophy.
Therapeutic experiences with choroidal osteoma are rare because of its infrequence. It is a benign tumour of the choroid whose etiology and pathogenesis are not well understood. Choroidal osteoma in a child is even rarer than in adults. There are only a few case reports of choroidal osteoma appearing in a child.8–11 In our case, the tumour showed progressive growth within 8 months of follow-up. As the spontaneous course was difficult to predict, and because of the family history of extraosseous Ewing sarcoma in the brother, we discussed with the parents possible options to stop tumour growth and to keep the best possible vision. Choroidal osteoma is made up of osseous tissue. During bone growth, proliferating mesenchymal precursor cells differentiate into osteoblasts that produce ground substance that accompanies an increase in capillary density. Radiotherapy aims at destroying these proliferating mesenchymal precursor cells and the proliferating endothelial cells of the capillary vessels, resulting in cessation of osteoma growth or even tumour regression. Low-dose proton beam radiotherapy succeeded in tumour control; however, during the follow-up, secondary CNV occurred with foveal involvement, resulting in foveal atrophy, reduced vision, and eccentric fixation at the end. No radiation optic neuropathy was evident at the last visit, despite the juxtapapillary location of the osteoma. We believe that the development of CNV was caused by RPE alterations arising after radiation during regression of the tumour as an indirect effect of the radiotherapy and not by radiation retinopathy.12–14 AntiVEGF-treatment (as off-label therapy) was effective to inactivate the CNV and recurrences occurring at long intervals, as reported by other authors.6,7 Visual loss associated with choroidal osteoma is often caused by decalcification of the osteoma and secondary pigment epithelial atrophy in the foveal area resulting in photoreceptor atrophy.15 In 46% of cases, decalcification has taken place after an observation time of 10 years.2 Another possible reason for visual impairment is the development of a CNV, occurring in 31% of patients at 10 years.2 Shields et al.2,11 have observed that tumour growth was arrested in decalcified choroidal osteomas and that tumour growth occurred only at the site opposite the decalcified area of a partially decalcified osteoma. Hence, targeted decalcification as a therapeutic approach using laser photocoagulation or photodynamic therapy was discussed in this context. However, in our case, laser photocoagulation of the central part of the osteoma to prevent further growth onto the fovea would have resulted in significant visual field defects and immediate deterioration of VA. Photodynamic therapy was used only in single pediatric patients until now to treat other diseases.16 It would not have been possible in the present case because of reduced cooperation of the child. A further idea to maintain calcification of choroidal osteoma and to preserve vision was calcium supplementation.11 However, the exact role
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Fig. 3 — Two years after proton beam radiotherapy, a subretinal hemorrhage occurred at the border of the regressed osteoma. In the optical coherence tomography scan, the subretinal bleeding together with subretinal fluid was evident. Early-phase and late-phase fluorescence angiography found a choroidal neovascularization (CNV) (A). After 3 intravitreal injections of bevacizumab (1.25 mg/0.05 mL), the CNV was inactive, without any hemorrhages on the funduscopic photograph. Optical coherence tomography found foveal atrophy without intraretinal or subretinal fluid. Fluorescence angiography did not find any evidence for active CNV (B).
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Correspondence of calcium supplementation in this context is unclear, and data are still lacking.
CONCLUSION Choroidal osteoma can show an aggressive course even in young children. To the best of our knowledge, the management of the present case marked the first time that proton beam radiotherapy was used for the treatment of choroidal osteoma. Low-dose proton beam radiotherapy may be an option to stop tumour growth and to prevent visual loss. However, the possibility of tumour-associated or radiation-associated complications (or both) during the clinical course still has to be considered. Long-term regular follow-up is mandatory in these young patients. Daniela Süsskind, * Elke K. Altpeter, * Lutz Moser, ‡ Michael H. Foerster, *,† Sabine Aisenbrey *
Karls University, Tübingen, Germany; †Augenklinik DRK Kliniken Berlin Westend, Berlin, Germany; and ‡Charite´, Campus Benjamin Franklin, Berlin, Germany
*Eberhard
Correspondence to: Daniela Su¨sskind, MD: daniela.suesskind@med. uni-tuebingen.de REFERENCES 1. Shields C, Shields JA, Augsburger JJ. Choroidal osteoma. Surv Ophthalmol. 1988;33:17-27. 2. Shields CL, Sun H, Demirci H, Shields JA. Factors predictive of tumor growth, tumor decalcification, choroidal neovascularization, and visual outcome in 74 eyes with choroidal osteoma. Arch Ophthalmol. 2005;123:1658-66. 3. Aylward GW, Chang TS, Pautler SE, Gass JDM. A long-term follow-up of choroidal osteoma. Arch Ophthalmol. 1998;116: 1337-41.
Peripheral retinal ischemia after intravenous tissue plasminogen activator for central retinal artery occlusion Central retinal artery occlusion (CRAO) is most commonly caused by emboli, 74% of which are composed of cholesterol originating from atherosclerotic plaques in the carotid artery.1 CRAO is an ophthalmic emergency typically associated with severe visual loss, but there is no evidence-based guideline for treatment.2 Given the similar mechanism of nonarteritic CRAO and cerebral stroke, there is growing interest in the use of tissue plasminogen activator (tPA) as an acute intervention for this condition.3–5 Thrombolytic agents such as tPA are designed to break up fibrinoplatelet occlusions. In our patient, it is possible that such treatment may have led to distalization of the retinal vascular emboli and development of a sharply demarcated zone of peripheral retinal ischemia with more posterior intervening zones that remained perfused.
4. Altpeter EK, Süsskind D, Bartz-Schmidt KU, Foerster MH, Aisenbrey S. Unclear parapapillary tumor in childhood [published online May 18, 2013]. Ophthalmologe. 5. Höcht S, Wachtlin J, Bechrakis NE, et al. Proton or photon irradiation for hemangiomas of the choroid? A retrospective comparison. Int J Radiat Oncol Biol Phys. 2006;66:345-51. 6. Kubota-Taniai M, Oshitari T, Handa M, Baba T, Yotsukura J, Yamamoto S. Long-term success of intravitreal bevacizumab for choroidal neovascularization associated with choroidal osteoma. Clin Ophthalmol. 2011;5:1051-5. 7. Wu ZHY, Wong MYY, Lai TYY. Long-term follow-up of intravitreal ranibizumab for the treatment of choroidal neovascularization due to choroidal osteoma. Case Rep Ophthalmol. 2012;3:200-4. 8. Fava GE, Brown GC, Shields JA, Broocker G. Choroidal osteoma in a 6-year-old child. J Pediatr Ophthalmol Strabismus. 1980;17:203-5. 9. Cunha SL. Osseous choristoma of the choroid: a familial disease. Arch Ophthalmol. 1984;102:1052-4. 10. Mizota A, Tanabe R, Adachi-Usami E. Rapid enlargement of choroidal osteoma in a 3-year-old girl. Arch Ophthalmol. 1998;116: 1128-9. 11. Voluck MR, Say EA, Shields CL. Progressive growth of bilateral choroidal osteomas in a child. J Pediatr Ophthalmol Strabismus. 2011;48:e66-8. 12. Spaide RF, Borodoker N, Shah V. Atypical choroidal neovascularization in radiation retinopathy. Am J Ophthalmol. 2002;133:709-11. 13. Berker N, Aslan O, Batman C, Elgin U, Ozkan SS. Choroidal neovascular membrane in radiation retinopathy. Clin Experiment Ophthalmol. 2006;34:625-6. 14. Ghauri A-J, Musadiy M, Sha Y, Elsherbiny S. Late onset of subfoveal choroidal neovascularisation following cerebral radiotherapy. BMJ Case Rep. 2010;2010:bcr0520091825. 15. Shields CL, Perez B, Materin M, Mehta S, Shields JA. Optical coherence tomography of choroidal osteoma in 22 cases: evidence for photoreceptor atrophy over the decalcified portion of the tumor. Ophthalmology. 2007;114:e53-8. 16. Lipski A, Bornfeld N, Jurklies B. Photodynamic therapy with verteporfin in paediatric and young adult patients: long-term treatment results of choroidal neovascularisations. Br J Ophthalmol. 2008;92:655-60. Can J Ophthalmol 2014;49:e123–e127 0008-4182/14/$-see front matter & 2014 Canadian Ophthalmological Society. Published by Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.jcjo.2014.07.009
A 63-year-old male presented to the emergency department with a 2-hour history of sudden painless vision loss of the right eye and a visual acuity (VA) of hand motions. He was diagnosed with an acute CRAO and emergently treated with intravenous (IV) tPA (9 mg bolus with an additional 81 mg administered over 1 hour). One week later, vision was subjectively improved in the right eye but measured only count fingers. Colour fundus photography and fluorescein angiography (FA) performed 1 week after treatment showed a cherry red spot with cilioretinal sparing and a Hollenhorst embolus at the origin of the inferior hemiretinal artery (Fig. 1). Although the retina was perfused in the midperiphery, a well-demarcated region of peripheral whitening (Fig. 2) corresponding to inferotemporal zones of retinal ischemia and nonperfusion on FA could be appreciated (Fig. 3). Distalized intraarterial (IA) embolic plaques were identified in the inferotemporal periphery (Fig. 4). Interestingly, the arteriolar blood columns distal to these emboli were dark
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