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Branch retinal artery occlusion associated with photodynamic therapy in a circumscribed choroidal haemangioma
Photodiagnosis and Photodynamic Therapy (2013) 10, 644—646
Available online at www.sciencedirect.com
journal homepage: www.elsevier.com/locate/pdpdt
CASE REPORT/RESEARCH LETTER
Branch retinal artery occlusion associated with photodynamic therapy in a circumscribed choroidal haemangioma夽,夽夽 Yangyan Xiao, Xiaojian Guo PhD ∗, Pingbo Ouyang Department of Opthalmology, Second Xiangya Hospital, Central South University, No.139, Renmin Road, Changsha, China Available online 6 August 2013
KEYWORDS Photodynamic therapy; Branch retinal artery occlusion; Complications
Summary We report a case with retinal arteriole occlusion after a single photodynamic therapy (PDT). A 33-year-old man presented with decreased visual acuity of the right eye, 20/200, for four months. Diagnosed as circumscribed choroidal haemangioma (CCH), he was treated with the PDT. Specifically, 6 mg/m2 of verteporfin was administered intravenously in 10 min. Laser treatment was performed 15 min after the infusion with an exposure of 75 J/cm2 for 125 s. The patient was followed up a week later and then every month for 5 months. Complaining about central visual field defect two days post treatment, he was diagnosed with inferior macular artery occlusion with FA. After three months further treatment, the tumor regressed completely but local retinal atrophy was observed. The best corrected visual acuity (BCVA) was 20/30 with visual field defect. Following this, extensive blood tests were performed, revealing no abnormality. Our result indicates that under certain conditions infarction of retinal arterioles can develop following PDT. © 2013 Elsevier B.V. All rights reserved.
Introduction The circumscribed choroidal hemangioma (CCH) is a benign vascular tumor of the choroid. However, it may lead to total retinal detachment and visual loss in patients. Sev-
夽 All authors have full control of all primary data, and they agree to allow for Graefe’ s Archives for Clinical and Experimental Ophthalmology to review their data upon request. 夽夽 The study was conducted in accordance with the Declaration of Helsinki and was approved by the Medicine Human Ethics Committee of the Second Xiangya Hospital of the Central South University. ∗ Corresponding author. Tel.: +86 13973135320. E-mail addresses: s [email protected], [email protected] (X. Guo).
eral treatment options are available for CCH, including laser coagulation, cryotherapy, external beam radiation, transpupillary thermotherapy and even intravitreal bevacizumab. PDT is an effective method for CCH treatment by inducing photochemical selective occlusion of tumor vessels. Currently, there are several clinical studies for CCH without serious complications both in standard and bolus therapies [1]. However, we report a patient of mine got branch retinal artery occlusion (BRAO) after a single PDT.
Case report A 33-year-old man presented with decreasing visual acuity of the right eye for four months. Best corrected visual acuity (BCVA) of the right eye was 20/200 with refractive
1572-1000/$ — see front matter © 2013 Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.pdpdt.2013.07.004
Circumscribed choroidal haemangioma
645
Fig. 1 The pictures in left row (i—iii) show the OCT change in the same place which is indicated in the infrared imaging in picture (showed in ii) at baseline and after a week and three month. (i) Photograph and OCT at baseline, subfoveal fluid and retinal elevation at the macula secondary to the choroidal tumor. (iv) FA showed angiomatous structures at the early phase before treatment. (ii) A week after treatment, edema and whitening happened in retina underneath the laser spot and a tongue-shape area alongside a retinal arteriole. The change of the retinal artery was showed more clearly in the infrared imaging than the color photograph. The OCT show retinal thickening and increased reflectivity confined to the inner retinal layers decreased reflectivity from the photoreceptor and retinal pigment epithelial layers secondary to a shadowing effect in this area. (v) FA showed non-perfusion of the arteriole starting from arteriovenous crossing indicated by blue arrow and decreased background fluorescence corresponded with laser spot. (iii) Fundus examination showed a circular scar corresponded to the laser spot and local atrophy of outer layer retina confided by the OCT. (vi) Fluorescein angiography displayed late staining of the lesion and uniformed hypofluorescein revealed in ICGA. (vii) Ultrasound demonstrated totally regressed tumor. (viii) Static perimetry showed visual defect three months after treatment.
error of +5.0D, and that of the left eye was 20/20. Fundus examination showed an orange-colored minimally elevated paramacular lesion located at lower vascular arcade (Fig. 1i). The lesion presented angiomatous structures from the early phase and extensive vascular leakage in the late phases in fluorescein angiography (FA) (Heidelberg, Germany) (Fig. 1iv) optical coherence tomography (OCT) (Spectralis; Heidelberg, Germany) demonstrated serous retinal detachment involving the fovea angiomatous structures from the early phase, and B-scan ultrasonography showed a choroidal tumor with the largest basal diameter
of 5.58 mm and the height of the 3.25 mm. Based on the above clinical manifestation, this patient was diagnosed as CCH. After carefully communicating with patients about risks and benefits of all available treatment options, photodynamic therapy (PDT) with verteporfin (Visudyne, Novartis Ophthalmics, Switzerland) was recommended. Due to the neoplastic nature of the CCH, it may be not enough with the standard PDT for neovascular lesion in the age related degeneration. Therefore, 6 mg/m2 of verteporfin was administered intravenously in 10 min under the control of an injection pump (Syringe pump SP6000, Switzerland), and
646
Y. Xiao et al.
laser treatment at 698 nm was performed 15 min after the end of the infusion, with an exposure of 75 J/cm2 for 125 s (Quantel, France). The diameter of the treatment spot was calculated based on the lesion size measured on the pretreatment fluorescein angiogram. The treatment with one exposure and a diameter of 7800 m, The treatment spot was set to cover the greatest linear dimension of the lesion, with an additional 500 m covering the borders on each side. A week later, the patient came to the hospital for regular checks and complained of sudden decreased vision two days after treatment Dilated fundus examination revealed a tongue-shape white elevated area alongside a retinal arteriole of inferotemporal arcade (Fig. 1ii and v). Retrobulbar injection of Anisodamine and sublingual nitroglycerin were executed at once and further medicine was taken to dredge the blood vessel and restore neural function. And he was asked to come back for checkup every month. After three months medication treatment, his visual acuity was 20/200 accompanied with visual field defect which was showed in static perimetry (Fig. 1viii). The refractive error was—1D with a corresponding BCVA of 20/30. With the same refractive system, this change was mainly caused by shortened visual length. Fundus examination showed that a circular scar corresponded to the laser spot used in the PDT treatment (Fig. 1iii). FA showed complete nonvisualization of all retinal arterioles and capillaries within the treated area but enhanced background fluorescein (Fig. 1vi). And the ICGA showed hypofluorescence in this area but persistent dye in the large choroidal vessels (Fig. 1vi). The CCH regressed mostly but leaving local atrophy of outer layer retina confided by ultrasound and OCT (Fig. 1vii). In his last examination 5 months after treatment, the circular retinal atrophy remained stable in size. The patient refused any further examination. Therefore, static perimetry, OCT, FA and ICGA could not be obtained.
treatment at 5 min; 100 J/cm2 ;166 s) in the treatment of symptomatic CCH. The complications in this study include RPE hyperplasia, besides, subretinal fibrosis and macular pucker with retinal traction both of which happened only in bolus PDT. They concluded that both therapies were effective, but Bolus PDT might more likely cause RPE and retinal changes associated with reduced retinal sensitivity [1]. BRAO as an ophthalmic emergency usually presents with sudden loss of visual field, and mainly caused by emboli. Other causes are arteries, vasospasm, angioslerosis and so on. The reperfusion should be performed within 8 h.This patient got tumor flattened which was certified by the B-scan ultrasonography and the refractive error change. Indeed, the BRAO happened in this patient remains to be explained. However, technical malfunctions could be excluded. For this perimacular CCH, the recommended dose is 75 J/cm2 . We were able to confirm that the rate of infusion and laser settings were accurate at the time of the treatment. After BRAO happened, the patient was given blood investigations including complete blood count with Erythrocyte sedimentation rate (ESR), peripheral blood smear, platelet count, Prothrombin/Activated Partial Thromboplastin time, serum lipids, and hypercoagulability testing. All of these tests showed results within normal ranges. It is even more intriguing that the arteriole and capillary within the laser spot that got occlusion and the venule sill could be seen in FA after the PDT. It seems that the thrombosis happened in the place of the arteriovenous crossing (Fig. 1). So far, no documents have ever reported such kind of retinal artery occlusion corresponding to the irradiated area following PDT. In summary, our results suggest that retinal arteriole occlusion can develop following PDT. And the highly selective mechanism of the PDT needs more studies.
Discussion
The authors have no financial interest or conflicts of interest for this work.
To date, there are a number of studies confirming that PDT appears to be a safe and effective approach to the treatment of symptomatic CCH [2]. These studies with parameter of 50—100 J/cm2 resulted in improvement or stabilization of visual acuity, regression of macular edema, and tumor flattening were observed with side effects no more than RPE change [1,2]. The PDT has also been recommended as the first line treatment for patients with macular CCH [2,3]. However, in a phase 1 and 2 study of PDT, the regimen using a double verteporfin dose (12 mg/m2 ) and a triple light dose (150 J/cm2 ) with the light application 30 min after initiation of infusion induced retinal occlusions of both branch retinal arterioles and venules in one patient [4]. Histological examinations of human eyes after experimental PDT have revealed such a dose dependent effect on choroidal vessels and the RPE [5]. Additionally, specific PDT protocols for the treatment of CCH have never been standardized. Elisabetta Pilotto and others compared the standard PDT with bolus PDT (6 mg/m2 verteporfin infusion bolus in 1 min;
Conflict of interest
References [1] Pilotto E, et al. Standard versus bolus photodynamic therapy in circumscribed choroidal hemangioma: functional outcomes. European Journal of Ophthalmology 2011;21(4):452—8. [2] Jurklies B, Bornfeld N. The role of photodynamic therapy in the treatment of symptomatic choroidal hemangioma. Graefe’s Archive for Clinical and Experimental Ophthalmology 2005;243(5):393—6. [3] Zhang Y, et al. Photodynamic therapy for symptomatic circumscribed macular choroidal hemangioma in Chinese patients. American Journal of Ophthalmology 2010;150(5):710—5.e1. [4] Schmidt-Erfurth U, et al. Photodynamic therapy with verteporfin for choroidal neovascularization caused by age-related macular degeneration: results of retreatments in a phase 1 and 2 study. Archives of Ophthalmology 1999;117(9):1177—87. [5] Schmidt-Erfurth U, et al. Histopathological changes following photodynamic therapy in human eyes. Archives of Ophthalmology 2002;120(6):835—44.
Available online at www.sciencedirect.com
journal homepage: www.elsevier.com/locate/pdpdt
CASE REPORT/RESEARCH LETTER
Branch retinal artery occlusion associated with photodynamic therapy in a circumscribed choroidal haemangioma夽,夽夽 Yangyan Xiao, Xiaojian Guo PhD ∗, Pingbo Ouyang Department of Opthalmology, Second Xiangya Hospital, Central South University, No.139, Renmin Road, Changsha, China Available online 6 August 2013
KEYWORDS Photodynamic therapy; Branch retinal artery occlusion; Complications
Summary We report a case with retinal arteriole occlusion after a single photodynamic therapy (PDT). A 33-year-old man presented with decreased visual acuity of the right eye, 20/200, for four months. Diagnosed as circumscribed choroidal haemangioma (CCH), he was treated with the PDT. Specifically, 6 mg/m2 of verteporfin was administered intravenously in 10 min. Laser treatment was performed 15 min after the infusion with an exposure of 75 J/cm2 for 125 s. The patient was followed up a week later and then every month for 5 months. Complaining about central visual field defect two days post treatment, he was diagnosed with inferior macular artery occlusion with FA. After three months further treatment, the tumor regressed completely but local retinal atrophy was observed. The best corrected visual acuity (BCVA) was 20/30 with visual field defect. Following this, extensive blood tests were performed, revealing no abnormality. Our result indicates that under certain conditions infarction of retinal arterioles can develop following PDT. © 2013 Elsevier B.V. All rights reserved.
Introduction The circumscribed choroidal hemangioma (CCH) is a benign vascular tumor of the choroid. However, it may lead to total retinal detachment and visual loss in patients. Sev-
夽 All authors have full control of all primary data, and they agree to allow for Graefe’ s Archives for Clinical and Experimental Ophthalmology to review their data upon request. 夽夽 The study was conducted in accordance with the Declaration of Helsinki and was approved by the Medicine Human Ethics Committee of the Second Xiangya Hospital of the Central South University. ∗ Corresponding author. Tel.: +86 13973135320. E-mail addresses: s [email protected], [email protected] (X. Guo).
eral treatment options are available for CCH, including laser coagulation, cryotherapy, external beam radiation, transpupillary thermotherapy and even intravitreal bevacizumab. PDT is an effective method for CCH treatment by inducing photochemical selective occlusion of tumor vessels. Currently, there are several clinical studies for CCH without serious complications both in standard and bolus therapies [1]. However, we report a patient of mine got branch retinal artery occlusion (BRAO) after a single PDT.
Case report A 33-year-old man presented with decreasing visual acuity of the right eye for four months. Best corrected visual acuity (BCVA) of the right eye was 20/200 with refractive
1572-1000/$ — see front matter © 2013 Elsevier B.V. All rights reserved. http://dx.doi.org/10.1016/j.pdpdt.2013.07.004
Circumscribed choroidal haemangioma
645
Fig. 1 The pictures in left row (i—iii) show the OCT change in the same place which is indicated in the infrared imaging in picture (showed in ii) at baseline and after a week and three month. (i) Photograph and OCT at baseline, subfoveal fluid and retinal elevation at the macula secondary to the choroidal tumor. (iv) FA showed angiomatous structures at the early phase before treatment. (ii) A week after treatment, edema and whitening happened in retina underneath the laser spot and a tongue-shape area alongside a retinal arteriole. The change of the retinal artery was showed more clearly in the infrared imaging than the color photograph. The OCT show retinal thickening and increased reflectivity confined to the inner retinal layers decreased reflectivity from the photoreceptor and retinal pigment epithelial layers secondary to a shadowing effect in this area. (v) FA showed non-perfusion of the arteriole starting from arteriovenous crossing indicated by blue arrow and decreased background fluorescence corresponded with laser spot. (iii) Fundus examination showed a circular scar corresponded to the laser spot and local atrophy of outer layer retina confided by the OCT. (vi) Fluorescein angiography displayed late staining of the lesion and uniformed hypofluorescein revealed in ICGA. (vii) Ultrasound demonstrated totally regressed tumor. (viii) Static perimetry showed visual defect three months after treatment.
error of +5.0D, and that of the left eye was 20/20. Fundus examination showed an orange-colored minimally elevated paramacular lesion located at lower vascular arcade (Fig. 1i). The lesion presented angiomatous structures from the early phase and extensive vascular leakage in the late phases in fluorescein angiography (FA) (Heidelberg, Germany) (Fig. 1iv) optical coherence tomography (OCT) (Spectralis; Heidelberg, Germany) demonstrated serous retinal detachment involving the fovea angiomatous structures from the early phase, and B-scan ultrasonography showed a choroidal tumor with the largest basal diameter
of 5.58 mm and the height of the 3.25 mm. Based on the above clinical manifestation, this patient was diagnosed as CCH. After carefully communicating with patients about risks and benefits of all available treatment options, photodynamic therapy (PDT) with verteporfin (Visudyne, Novartis Ophthalmics, Switzerland) was recommended. Due to the neoplastic nature of the CCH, it may be not enough with the standard PDT for neovascular lesion in the age related degeneration. Therefore, 6 mg/m2 of verteporfin was administered intravenously in 10 min under the control of an injection pump (Syringe pump SP6000, Switzerland), and
646
Y. Xiao et al.
laser treatment at 698 nm was performed 15 min after the end of the infusion, with an exposure of 75 J/cm2 for 125 s (Quantel, France). The diameter of the treatment spot was calculated based on the lesion size measured on the pretreatment fluorescein angiogram. The treatment with one exposure and a diameter of 7800 m, The treatment spot was set to cover the greatest linear dimension of the lesion, with an additional 500 m covering the borders on each side. A week later, the patient came to the hospital for regular checks and complained of sudden decreased vision two days after treatment Dilated fundus examination revealed a tongue-shape white elevated area alongside a retinal arteriole of inferotemporal arcade (Fig. 1ii and v). Retrobulbar injection of Anisodamine and sublingual nitroglycerin were executed at once and further medicine was taken to dredge the blood vessel and restore neural function. And he was asked to come back for checkup every month. After three months medication treatment, his visual acuity was 20/200 accompanied with visual field defect which was showed in static perimetry (Fig. 1viii). The refractive error was—1D with a corresponding BCVA of 20/30. With the same refractive system, this change was mainly caused by shortened visual length. Fundus examination showed that a circular scar corresponded to the laser spot used in the PDT treatment (Fig. 1iii). FA showed complete nonvisualization of all retinal arterioles and capillaries within the treated area but enhanced background fluorescein (Fig. 1vi). And the ICGA showed hypofluorescence in this area but persistent dye in the large choroidal vessels (Fig. 1vi). The CCH regressed mostly but leaving local atrophy of outer layer retina confided by ultrasound and OCT (Fig. 1vii). In his last examination 5 months after treatment, the circular retinal atrophy remained stable in size. The patient refused any further examination. Therefore, static perimetry, OCT, FA and ICGA could not be obtained.
treatment at 5 min; 100 J/cm2 ;166 s) in the treatment of symptomatic CCH. The complications in this study include RPE hyperplasia, besides, subretinal fibrosis and macular pucker with retinal traction both of which happened only in bolus PDT. They concluded that both therapies were effective, but Bolus PDT might more likely cause RPE and retinal changes associated with reduced retinal sensitivity [1]. BRAO as an ophthalmic emergency usually presents with sudden loss of visual field, and mainly caused by emboli. Other causes are arteries, vasospasm, angioslerosis and so on. The reperfusion should be performed within 8 h.This patient got tumor flattened which was certified by the B-scan ultrasonography and the refractive error change. Indeed, the BRAO happened in this patient remains to be explained. However, technical malfunctions could be excluded. For this perimacular CCH, the recommended dose is 75 J/cm2 . We were able to confirm that the rate of infusion and laser settings were accurate at the time of the treatment. After BRAO happened, the patient was given blood investigations including complete blood count with Erythrocyte sedimentation rate (ESR), peripheral blood smear, platelet count, Prothrombin/Activated Partial Thromboplastin time, serum lipids, and hypercoagulability testing. All of these tests showed results within normal ranges. It is even more intriguing that the arteriole and capillary within the laser spot that got occlusion and the venule sill could be seen in FA after the PDT. It seems that the thrombosis happened in the place of the arteriovenous crossing (Fig. 1). So far, no documents have ever reported such kind of retinal artery occlusion corresponding to the irradiated area following PDT. In summary, our results suggest that retinal arteriole occlusion can develop following PDT. And the highly selective mechanism of the PDT needs more studies.
Discussion
The authors have no financial interest or conflicts of interest for this work.
To date, there are a number of studies confirming that PDT appears to be a safe and effective approach to the treatment of symptomatic CCH [2]. These studies with parameter of 50—100 J/cm2 resulted in improvement or stabilization of visual acuity, regression of macular edema, and tumor flattening were observed with side effects no more than RPE change [1,2]. The PDT has also been recommended as the first line treatment for patients with macular CCH [2,3]. However, in a phase 1 and 2 study of PDT, the regimen using a double verteporfin dose (12 mg/m2 ) and a triple light dose (150 J/cm2 ) with the light application 30 min after initiation of infusion induced retinal occlusions of both branch retinal arterioles and venules in one patient [4]. Histological examinations of human eyes after experimental PDT have revealed such a dose dependent effect on choroidal vessels and the RPE [5]. Additionally, specific PDT protocols for the treatment of CCH have never been standardized. Elisabetta Pilotto and others compared the standard PDT with bolus PDT (6 mg/m2 verteporfin infusion bolus in 1 min;
Conflict of interest
References [1] Pilotto E, et al. Standard versus bolus photodynamic therapy in circumscribed choroidal hemangioma: functional outcomes. European Journal of Ophthalmology 2011;21(4):452—8. [2] Jurklies B, Bornfeld N. The role of photodynamic therapy in the treatment of symptomatic choroidal hemangioma. Graefe’s Archive for Clinical and Experimental Ophthalmology 2005;243(5):393—6. [3] Zhang Y, et al. Photodynamic therapy for symptomatic circumscribed macular choroidal hemangioma in Chinese patients. American Journal of Ophthalmology 2010;150(5):710—5.e1. [4] Schmidt-Erfurth U, et al. Photodynamic therapy with verteporfin for choroidal neovascularization caused by age-related macular degeneration: results of retreatments in a phase 1 and 2 study. Archives of Ophthalmology 1999;117(9):1177—87. [5] Schmidt-Erfurth U, et al. Histopathological changes following photodynamic therapy in human eyes. Archives of Ophthalmology 2002;120(6):835—44.