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Intravitreal dexamethasone implant (Ozurdex) and photodynamic therapy for vasoproliferative retinal tumours
CORRESPONDENCE Intravitreal dexamethasone implant (Ozurdex) and photodynamic therapy for vasoproliferative retinal tumours Vasoproliferative retinal tumours (VPRTs) are benign vascular retinal masses that are preferentially located inferotemporally between the equator and ora serrata.1,2 These benign tumours may be primary (idiopathic) or secondary to an ocular cause. Secondary VPRTs have been associated with congenital, inflammatory, vascular, traumatic, dystrophic, and degenerative ocular diseases. Several treatment options have been described for VPRTs, including cryotherapy, plaque brachytherapy, laser photocoagulation, photodynamic therapy (PDT), intravitreal bevacizumab, and pars plana vitrectomy (PPV) with endoresection.3,4 In this article, we report a patient with secondary VPRT successfully treated with the combination of intravitreal dexamethasone implant and PDT. A 41-year-old female was referred to our clinic with a diagnosis of intermediate uveitis in both eyes. Her medical history was relevant, with multiple sclerosis and a vasoproliferative tumour in her right eye. Two years ago in another clinic, she was diagnosed with multiple sclerosis, and she started on interferon-beta 1-b 250 mg subcutaneously every other day. She had been treated with laser photocoagulation and an intravitreal bevacizumab injection to her right eye 3 months before being referred to us. At presentation, visual acuities were 20/25 OD and 20/20 OS. Biomicroscopic findings in both eyes and funduscopy in the left eye were unremarkable. Funduscopy disclosed an elevated, highly vascularized, pink solid lesion located at the 6 o’clock position in the right eye (Fig. 1). The lesion was 3.6 mm in thickness and had a basal diameter of 9.4 mm. There was an intraretinal and subretinal exudation involving the inferior half of the right posterior pole of the fundus. Fluorescein angiography (FA) demonstrated a leakage from the differentiated vasculature of the mass in the late phases.
Fig. 1 — Fundus photograph of the right eye demonstrating a yellow-red elevated lesion located inferiorly surrounded by extensive exudation that threatens the macula.
Based on ophthalmoscopic appearance and angiographic findings, the lesion was diagnosed as secondary VPRT. As a treatment option for VPRT, we chose to perform PDT for the lesion. Because of the lipid exudation that threatened the macula in the right eye and to reduce the inflammatory effect of PDT, we planned to inject a dexamethasone implant intravitreally. With informed consent, she received via injection a single 0.7mg intravitreal dexamethasone implant (Ozurdex) to the right eye as an off-label treatment. One week after the injection, PDT was performed on the right eye using standard parameters at a dosage of 6 mg/m2 body surface area, infused intravenously. Fifteen minutes after beginning the perfusion, 2 overlapping spots (with a size of 7600 mm) were applied to the right eye for 83 seconds, with a laser beam at 689 nm. Subretinal fluid was regressed and exudates gradually disappeared after the PDT. Ophthalmoscopy showed near total involution within 2 months and complete resolution of excessive exudation and pigment epithelial changes in the inferior half of the fundus, leaving fibrotic scar tissue (Figs. 2 and 3). Regression of exudates continued for several months after tumour involution. FA demonstrated fibrotic and avascular scar tissue with no signs of active leakage at the tumour location. Twelve months after the treatment at the final follow-up visit, visual acuity was 20/40 OD with no recurrence. Vision decreased because of posterior subcapsular cataract formation. No adverse effects were observed, and no additional treatment was applied in the combined treated eye during the follow-up period. VPRTs appear as yellow-red retinal masses that arise in the peripheral retina. These benign tumours are classified into 2 types: primary or secondary caused by an ocular disease. Secondary VPRTs more often occur at a young
Fig. 2 — Fundus photography shows the intravitreal implant just anterior the vasoproliferative tumour 2 weeks after photodynamic therapy. CAN J OPHTHALMOL — VOL. ], NO. ], ] 2014
1
Correspondence noninfectious uveitis. We applied an intravitreal dexamethasone implant 1 week before PDT to the eye with macular exudation to prevent macular edema and possible subfoveal migration of hard exudates, and the patient had a successful response to the combined treatment. We considered long-term treatment via dexamethasone implant to attenuate the inflammatory effect after PDT and to reduce the vascular leakage caused by both the tumour and PDT. No further recurrence of exudation was seen through the follow-up period. To our knowledge, this is the first report of VPRT treated with combined intravitreal dexamethasone implant and PDT. Combination therapy seems to be effective in the management of VPRTs.
Fig. 3 — Regression of the tumour, leaving a fibrotic, scar tissue, and retinal pigment changes after resolution of exudation.
age, bilaterally and multifocally. Macular exudation, cystoid macular edema, vitreous hemorrhage, tractional retinal detachment, and epiretinal membrane related to the effect of the tumour can cause visual loss.2 Differential diagnosis includes angiomas (capillary hemangiomas), eccentric choroidal neovascularization, and amelanotic melanomas.5 Lack of feeder vessels helps to differentiate VPRTs from capillary hemangiomas and eccentric choroidal neovascularization. FA and ultrasonography usually assist in distinguishing amelanotic melanomas from VPRTs in difficult cases. Management for VPRTs depends on location and related complications, and includes observation for asymptomatic lesions, cryotherapy, plaque brachytherapy, laser photocoagulation, PDT, intravitreal bevacizumab, and PPV with endoresection.3,4 The angio-occlusive effect of PDT has been shown in secondary VPRTs with successful regressions of the tumours.6,7 However, persistence of macular edema after PDT can cause poor vision. Blasi et al.6 reported 2 and Osman et al.7 reported 1 secondary VPRT treated with PDT. Although the tumours were dissolved, all of the reported cases have ongoing intraretinal and subretinal exudation after 1 year. In addition, increased exudation has been reported after PDT for choroidal neovascular membrane and some intraocular tumours.8,9 PDT increases the vascular permeability with possible mechanisms of vascular injury, subsequent inflammation immediately after PDT, and also VEGF expression increases after the procedure.10 In addition, VPRT tissue itself strongly shows immunoreactivity for VEGF.11 Dexamethasone is a known potent steroid with good anti-inflammatory and anti-VEGF properties. Intravitreal injection of dexamethasone inhibits the leukostasis, improves blood–retina barrier breakdown, and reduces vascular leakage.12 Dexamethasone 0.7-mg implant (Ozurdex) is a favorable treatment option in patients with macular edema after retinal vein occlusion and
2
CAN J OPHTHALMOL — VOL. ], NO. ], ] 2014
Zafer Cebeci, Merih Oray, Samuray Tuncer, Ilknur Tugal Tutkun, Nur Kir Istanbul University, Istanbul Faculty of Medicine, Ophthalmology Department, Istanbul, Turkey Correspondence to: Zafer Cebeci, MD: [email protected] REFERENCES 1. Shields CL, Shields JA, Barrett J, De Potter P. Vasoproliferative tumors of the ocular fundus. Classification and clinical manifestations in 103 patients. Arch Ophthalmol. 1995;113:615-23. 2. Shields CL, Kaliki S, Al-Dahmash S, et al. Retinal vasoproliferative tumors: comparative clinical features of primary vs secondary tumors in 334 cases. JAMA Ophthalmol. 2013;131:328-34. 3. Turell ME, Singh AD. Vascular tumors of the retina and choroid: diagnosis and treatment. Middle East Afr J Ophthalmol. 2010;17:191-200. 4. Yeh S, Wilson DJ. Pars plana vitrectomy and endoresection of a retinal vasoproliferative tumor. Arch Ophthalmol. 2010;128:1196-9. 5. Rennie IG. Retinal vasoproliferative tumours. Eye (Lond). 2010;24:468-71. 6. Blasi MA, Scupola A, Tiberti AC, Sasso P, Balestrazzi E. Photodynamic therapy for vasoproliferative retinal tumors. Retina. 2006;26:404-9. 7. Osman SA, Aylin Y, Arikan G, Celikel H. Photodynamic treatment of a secondary vasoproliferative tumour associated with sector retinitis pigmentosa and Usher syndrome type I. Clin Experiment Ophthalmol. 2007;35:191-3. 8. Holz ER, Linares L, Mieler WF, Weinberg DV. Exudative complications after photodynamic therapy. Arch Ophthalmol. 2003;121:1649-52. 9. Mashayekhi A, Shields CL, Shields JA. Transient increased exudation after photodynamic therapy of intraocular tumors. Middle East Afr J Ophthalmol. 2013;20:83-6. 10. Schmidt-Erfurth U, Schlötzer-Schrehard U, Cursiefen C, Michels S, Beckendorf A, Naumann GO. Influence of photodynamic therapy on expression of vascular endothelial growth factor (VEGF), VEGF receptor 3, and pigment epithelium-derived factor. Invest Ophthalmol Vis Sci. 2003;44:4473-80. 11. Saito W, Kase S, Fujiya A, Dong Z, Noda K, Ishida S. Expression of vascular endothelial growth factor and intravitreal Anti-VEGF therapy with bevacizumab in vasoproliferative retinal tumors. Retina. 2013;33:1959-67. 12. Tamura H, Miyamoto K, Kiryu J, et al. Intravitreal injection of corticosteroid attenuates leukostasis and vascular leakage in experimental diabetic retina. Invest Ophthalmol Vis Sci. 2005;46:1440-4. Can J Ophthalmol 2014;]:]]]–]]] 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.2014.04.006
Fig. 1 — Fundus photograph of the right eye demonstrating a yellow-red elevated lesion located inferiorly surrounded by extensive exudation that threatens the macula.
Based on ophthalmoscopic appearance and angiographic findings, the lesion was diagnosed as secondary VPRT. As a treatment option for VPRT, we chose to perform PDT for the lesion. Because of the lipid exudation that threatened the macula in the right eye and to reduce the inflammatory effect of PDT, we planned to inject a dexamethasone implant intravitreally. With informed consent, she received via injection a single 0.7mg intravitreal dexamethasone implant (Ozurdex) to the right eye as an off-label treatment. One week after the injection, PDT was performed on the right eye using standard parameters at a dosage of 6 mg/m2 body surface area, infused intravenously. Fifteen minutes after beginning the perfusion, 2 overlapping spots (with a size of 7600 mm) were applied to the right eye for 83 seconds, with a laser beam at 689 nm. Subretinal fluid was regressed and exudates gradually disappeared after the PDT. Ophthalmoscopy showed near total involution within 2 months and complete resolution of excessive exudation and pigment epithelial changes in the inferior half of the fundus, leaving fibrotic scar tissue (Figs. 2 and 3). Regression of exudates continued for several months after tumour involution. FA demonstrated fibrotic and avascular scar tissue with no signs of active leakage at the tumour location. Twelve months after the treatment at the final follow-up visit, visual acuity was 20/40 OD with no recurrence. Vision decreased because of posterior subcapsular cataract formation. No adverse effects were observed, and no additional treatment was applied in the combined treated eye during the follow-up period. VPRTs appear as yellow-red retinal masses that arise in the peripheral retina. These benign tumours are classified into 2 types: primary or secondary caused by an ocular disease. Secondary VPRTs more often occur at a young
Fig. 2 — Fundus photography shows the intravitreal implant just anterior the vasoproliferative tumour 2 weeks after photodynamic therapy. CAN J OPHTHALMOL — VOL. ], NO. ], ] 2014
1
Correspondence noninfectious uveitis. We applied an intravitreal dexamethasone implant 1 week before PDT to the eye with macular exudation to prevent macular edema and possible subfoveal migration of hard exudates, and the patient had a successful response to the combined treatment. We considered long-term treatment via dexamethasone implant to attenuate the inflammatory effect after PDT and to reduce the vascular leakage caused by both the tumour and PDT. No further recurrence of exudation was seen through the follow-up period. To our knowledge, this is the first report of VPRT treated with combined intravitreal dexamethasone implant and PDT. Combination therapy seems to be effective in the management of VPRTs.
Fig. 3 — Regression of the tumour, leaving a fibrotic, scar tissue, and retinal pigment changes after resolution of exudation.
age, bilaterally and multifocally. Macular exudation, cystoid macular edema, vitreous hemorrhage, tractional retinal detachment, and epiretinal membrane related to the effect of the tumour can cause visual loss.2 Differential diagnosis includes angiomas (capillary hemangiomas), eccentric choroidal neovascularization, and amelanotic melanomas.5 Lack of feeder vessels helps to differentiate VPRTs from capillary hemangiomas and eccentric choroidal neovascularization. FA and ultrasonography usually assist in distinguishing amelanotic melanomas from VPRTs in difficult cases. Management for VPRTs depends on location and related complications, and includes observation for asymptomatic lesions, cryotherapy, plaque brachytherapy, laser photocoagulation, PDT, intravitreal bevacizumab, and PPV with endoresection.3,4 The angio-occlusive effect of PDT has been shown in secondary VPRTs with successful regressions of the tumours.6,7 However, persistence of macular edema after PDT can cause poor vision. Blasi et al.6 reported 2 and Osman et al.7 reported 1 secondary VPRT treated with PDT. Although the tumours were dissolved, all of the reported cases have ongoing intraretinal and subretinal exudation after 1 year. In addition, increased exudation has been reported after PDT for choroidal neovascular membrane and some intraocular tumours.8,9 PDT increases the vascular permeability with possible mechanisms of vascular injury, subsequent inflammation immediately after PDT, and also VEGF expression increases after the procedure.10 In addition, VPRT tissue itself strongly shows immunoreactivity for VEGF.11 Dexamethasone is a known potent steroid with good anti-inflammatory and anti-VEGF properties. Intravitreal injection of dexamethasone inhibits the leukostasis, improves blood–retina barrier breakdown, and reduces vascular leakage.12 Dexamethasone 0.7-mg implant (Ozurdex) is a favorable treatment option in patients with macular edema after retinal vein occlusion and
2
CAN J OPHTHALMOL — VOL. ], NO. ], ] 2014
Zafer Cebeci, Merih Oray, Samuray Tuncer, Ilknur Tugal Tutkun, Nur Kir Istanbul University, Istanbul Faculty of Medicine, Ophthalmology Department, Istanbul, Turkey Correspondence to: Zafer Cebeci, MD: [email protected] REFERENCES 1. Shields CL, Shields JA, Barrett J, De Potter P. Vasoproliferative tumors of the ocular fundus. Classification and clinical manifestations in 103 patients. Arch Ophthalmol. 1995;113:615-23. 2. Shields CL, Kaliki S, Al-Dahmash S, et al. Retinal vasoproliferative tumors: comparative clinical features of primary vs secondary tumors in 334 cases. JAMA Ophthalmol. 2013;131:328-34. 3. Turell ME, Singh AD. Vascular tumors of the retina and choroid: diagnosis and treatment. Middle East Afr J Ophthalmol. 2010;17:191-200. 4. Yeh S, Wilson DJ. Pars plana vitrectomy and endoresection of a retinal vasoproliferative tumor. Arch Ophthalmol. 2010;128:1196-9. 5. Rennie IG. Retinal vasoproliferative tumours. Eye (Lond). 2010;24:468-71. 6. Blasi MA, Scupola A, Tiberti AC, Sasso P, Balestrazzi E. Photodynamic therapy for vasoproliferative retinal tumors. Retina. 2006;26:404-9. 7. Osman SA, Aylin Y, Arikan G, Celikel H. Photodynamic treatment of a secondary vasoproliferative tumour associated with sector retinitis pigmentosa and Usher syndrome type I. Clin Experiment Ophthalmol. 2007;35:191-3. 8. Holz ER, Linares L, Mieler WF, Weinberg DV. Exudative complications after photodynamic therapy. Arch Ophthalmol. 2003;121:1649-52. 9. Mashayekhi A, Shields CL, Shields JA. Transient increased exudation after photodynamic therapy of intraocular tumors. Middle East Afr J Ophthalmol. 2013;20:83-6. 10. Schmidt-Erfurth U, Schlötzer-Schrehard U, Cursiefen C, Michels S, Beckendorf A, Naumann GO. Influence of photodynamic therapy on expression of vascular endothelial growth factor (VEGF), VEGF receptor 3, and pigment epithelium-derived factor. Invest Ophthalmol Vis Sci. 2003;44:4473-80. 11. Saito W, Kase S, Fujiya A, Dong Z, Noda K, Ishida S. Expression of vascular endothelial growth factor and intravitreal Anti-VEGF therapy with bevacizumab in vasoproliferative retinal tumors. Retina. 2013;33:1959-67. 12. Tamura H, Miyamoto K, Kiryu J, et al. Intravitreal injection of corticosteroid attenuates leukostasis and vascular leakage in experimental diabetic retina. Invest Ophthalmol Vis Sci. 2005;46:1440-4. Can J Ophthalmol 2014;]:]]]–]]] 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.2014.04.006