MASSIVE EXUDATIVE RETINAL DETACHMENT AFTER PHOTODYNAMIC THERAPY FOR PERIPHERAL RETINAL CAPILLARY HEMANGIOMA So Goto, MD, Yusuke Oshima, MD, Motokazu Tsujikawa, MD, Kohji Nishida, MD
Purpose: To report a case requiring emergency surgical intervention to treat a progressive massive retinal detachment after photodynamic therapy for a peripheral retinal capillary hemangioma associated with von Hippel-Lindau disease. Methods: A 38-year-old woman with von Hippel-Lindau disease had a peripheral retinal capillary hemangioma in the left eye. At the initial visit, the best-corrected visual acuity was 20/250 in the left eye. Photodynamic therapy was applied to treat the hemangioma. After 1 day, a massive retinal detachment and vitreous hemorrhage occurred. Three days after photodynamic therapy, vitrectomy was performed to treat the retinal detachment, which progressed with visual deterioration to hand motions. Results: A diagnosis of exudative retinal detachment was made because no retinal breaks were identified. The retina was reattached with external drainage and gas tamponade. One month postoperatively, the best-corrected visual acuity recovered to 20/100 in the left eye, and the vascular activity of the hemangioma stabilized. Conclusion: Photodynamic therapy monotherapy to treat retinal capillary hemangioma might result in a massive exudative retinal detachment requiring surgery. RETINAL CASES & BRIEF REPORTS 7:86–88, 2013
tion. Various therapeutic modalities such as laser photocoagulation, cryotherapy, and vitreoretinal surgery have been reported, with varying and limited success depending on the tumor characteristics.1,2 Although smalland medium-sized RCHs can be treated effectively with laser photocoagulation, cryotherapy, or a combination of both, large and multiple RCHs are often refractory to these conventional treatments. Pars plana vitrectomy with or without direct dissection of such large and multiple RCHs has been considered as the secondary treatment of choice. However, serious vision-threatening complications related to surgery, such as proliferative vitreoretinopathy and tumor recurrence, have been reported.2 Recently, several less invasive alternatives have been used to treat challenging cases, including photodynamic therapy (PDT) with verteporfin3–6 and intravitreal injection of anti–vascular endothelial growth factor.7 Of these, PDT has had dramatic anatomical and functional success for treating peripheral RCH, resulting not only in regression of tumor activity but also in maintenance of the visual acuity with limited complications.3–6
From the Department of Ophthalmology, Osaka University Graduate School of Medicine, Osaka, Japan.
R
etinal capillary hemangioma (RCH) is a benign retinal vascular tumor associated with von HippelLindau disease. However, RCH can sometimes be complicated by a macular edema or a serous retinal detachment at the macula resulting in visual deterioraY. Oshima is an international advisory board member for Alcon Laboratories, Inc, Fort Worth, TX, and a consultant to Topcon Medical Laser Systems, Inc, Santa Clara, CA, and Synergetics, Inc, St. Charles, MO, but he has no proprietary interests in and receives no royalties from any companies and has no financial relationship with any products mentioned in this report. None of other authors have any financial interests in this subject matter. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s Web site (www.retinajournal.com). Reprint requests: Yusuke Oshima, MD, Department of Ophthalmology, Osaka University Graduate School of Medicine, E7, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan; e-mail: yusukeoshima@ gmail.com
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To date, several complications related to PDT for RCH have been reported, including transient decompensation of vascular permeability, occlusion of retinal vessels, and ischemia of the optic nerve.6 However, most of these complications were associated with juxtapapillary RCH. In cases with peripheral RCH, exudative retinal detachment has been reported as a complication of PDT, which resolved spontaneously without the need for surgery.4 In contrast, we describe for the first time a case that required emergency surgery to treat a massive vision-threatening retinal detachment immediately after the application of PDT with verteporfin for peripheral RCH associated with von Hippel-Lindau disease. Case Report A 38-year-old woman presented with peripheral RCH associated with von Hippel-Lindau disease in the left eye; no previous ocular treatment was referred to the Osaka University Hospital. At the initial visit, the best-corrected visual acuity was 20/20 in the right eye and 20/250 in the left eye. An indirect ophthalmoscopic fundus examination showed tortuous dilated retinal vessels at the posterior pole connected to a 3.5-mm, fleshy, pink-orange peripheral RCH in the superotemporal quadrant (Figure 1A) of the left eye. Optical coherence tomography showed marked cystoid macular edema (Figure 1B). Fluorescein angiogram showed the afferent feeding retinal arteriole and the draining vein with prominent fluorescein leakage from the RCH (Figure 1C). Because the RCH was large and highly permeable, we chose PDT with verteporfin (Visudyne; QLT Phototherapeutics, Vancouver, Canada) as a less invasive treatment for this case. After providing informed consent, the patient underwent PDT with a spot size of 8,000 mm to the hemangioma for 83 seconds
followed by another laser spot (1,000 mm) to the feeding and draining vessels for another 83 seconds. One day after PDT, the patient reported severe visual impairment in the treated eye; the best-corrected visual acuity was counting fingers. Fundus examination and B-scan echography confirmed an extensive retinal detachment complicated by a vitreous hemorrhage that obscured clear fundus visualization (Figure 1D). Because the retinal detachment progressed with visual deterioration to hand motions 3 days after PDT, the patient underwent a lens-sparing pars plana vitrectomy with a 25-gauge system (see Video, Supplemental Digital Content 1, http://links.lww.com/ICB/A3). After core vitrectomy and peripheral vitreous shaving with scleral indentation, perfluorocarbon liquid (Perfluoron; Alcon Laboratories, Fort Worth, TX) was injected into the vitreous cavity to facilitate easy identification of a Schlieren sign. Because no retinal breaks were identified, the subretinal fluid was drained externally to avoid creating any iatrogenic retinotomies for internal drainage. After fluid-air exchange, cryoretinopexy was applied around the peripheral RCH. The surgery ended with infusion of a nonexpansile concentration of 14% perfluoropropane into the vitreous cavity. The retina was successfully reattached. One month postoperatively, the best-corrected visual acuity improved to 20/100 in the left eye, with complete resolution of the serous retinal detachment at the macula. The RCH was well stabilized (Figure 2) without recurrences during a 12-month postoperative follow-up period, and the bestcorrected visual acuity at the final visit remained 20/100.
Discussion Localized exudative retinal detachment after PDT with verteporfin for RCH is a well-known complication that resolves spontaneously without surgery.4–7 No published reports have described the development of a massive exudative retinal detachment immediately after PDT for RCH. In the current case, we could not
Fig. 1. A. A large RCH is seen at the superotemporal periphery. B. The horizontal optical coherence tomography scan of the left eye obtained through the section indicated by the line in panel A shows marked cystoid macular edema. C. An earlyframe fluorescein angiogram shows tortuous dilated retinal vessels and profuse leakage from the hemangioma. D. Three days after PDT, an extensive retinal detachment with slight vitreous hemorrhage obscures clear fundus visualization.
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application of PDT combined with intravitreal injection of anti–vascular endothelial growth factor drugs effectively stabilizes tumor activities.9,10 This therapeutic option might also prevent the exudative changes induced by PDT. In summary, we report for the first time the need for emergency vitrectomy with external drainage of subretinal fluid to successfully treat a case of a progressively advancing subtotal retinal detachment with vitreous hemorrhage after PDT for a peripheral RCH. Although PDT monotherapy is a promising treatment option for RCH, surgeons should be alert to the possibility of development of a PDT-induced complication, such as an exudative retinal detachment. Because both prevention and treatment strategies for this challenging situation have not yet been fully established, further studies are recommended. Key words: peripheral retinal capillary hemangioma, photodynamic therapy, exudative retinal detachment, pars plana vitrectomy. References Fig. 2. A. A color fundus composite photograph. B. An optical coherence tomography scan obtained through the section indicated by the line in panel A shows that the tumor dimensions have stabilized with decreased intraretinal and subretinal fluid.
confidently exclude the presence of a rhegmatogenous retinal detachment because the subtotal retinal detachment developed rapidly within 3 days after the application of PDT. Therefore, early vitrectomy was performed to explore the etiology of the retinal detachment, rhegmatogenous or exudative. Another reason for performing early vitrectomy was to remove the vitreous hemorrhage, which is a well-known risk factor for the development of proliferative vitreoretinopathy. Ultimately, the retinal detachment was presumed to be an exudative response induced by PDT because no breaks were identified intraoperatively and subretinal fluid did not recur postoperatively. Photodynamic therapy, applied to a large hemangioma, might induce a spike in secretion of vascular endothelial growth factor and other inflammatory cytokines and increase vascular permeability and leakage from the hemangioma.8 Similar to age-related macular degeneration, vascular endothelial growth factor plays an important role in RCH. Because the capillary hemangioma itself is a large vascularized tissue, it is easy to understand that the severity of the leakage from the hemangioma after PDT will be much more prominent than that from a small choroidal neovascular network observed in the age-related macular degeneration cases. Several studies have reported that the
1. Singh AD, Nouri M, Shields CL, et al. Treatment of retinal capillary hemangioma. Ophthalmology 2002;109:1799–1806. 2. Gaudric A, Krivosic V, Duquid G, et al. Vitreoretinal surgery for severe retinal capillary hemangiomas in Von Hippel-Lindau disease. Ophthalmology 2011;118:142–149. 3. Aaberg TM Jr, Aaberg TM Sr, Martin DF, et al. Three cases of large retinal capillary hemangiomas treated with verteporfin and photodynamic therapy. Arch Ophthalmol 2005;123:328–332. 4. Wong YM, Jalil A, Mathews J, Stanga PE. Exudative retinal detachment following photodynamic therapy for retinal capillary hemangioma. Can J Ophthalmol 2010;45:299–300. 5. Sachdeva R, Dadgostar H, Kaiser PK, et al. Verteporfin photodynamic therapy of six eyes with retinal capillary haemangioma. Acta Ophthalmol 2010;88:334–340. 6. Schmidt-Erfurth UM, Kusserow C, Barbazetto IA, Lagua H. Benefits and complications of photodynamic therapy of papillary capillary hemangiomas. Ophthalmology 2002;109:1256– 1266. 7. Wong WT, Liang KJ, Hammel K, et al. Intravitreal ranibizumab therapy for retinal capillary hemangioblastoma related to von Hippel-Lindau disease. Ophthalmology 2008;115:1957–1964. 8. Schmidt-Erfurth U, Schlötzer-Schrehard U, Cursiefen C, et al. 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;44:4473–4480. 9. Ziemssen F, Voelker M, Inhoffen W, et al. Combined treatment of a juxtapapillary retinal capillary haemangioma with intravitreal bevacizumab and photodynamic therapy. Eye (Lond) 2007;21:1125–1126. 10. Mennel S, Meyer CH, Callizo J. Combined intravitreal antivascular endothelial growth factor (Avastin) and photodynamic therapy to treat retinal juxtapapillary capillary haemangioma. Acta Ophthalmol 2010;88:610–613.
Purpose: To report a case requiring emergency surgical intervention to treat a progressive massive retinal detachment after photodynamic therapy for a peripheral retinal capillary hemangioma associated with von Hippel-Lindau disease. Methods: A 38-year-old woman with von Hippel-Lindau disease had a peripheral retinal capillary hemangioma in the left eye. At the initial visit, the best-corrected visual acuity was 20/250 in the left eye. Photodynamic therapy was applied to treat the hemangioma. After 1 day, a massive retinal detachment and vitreous hemorrhage occurred. Three days after photodynamic therapy, vitrectomy was performed to treat the retinal detachment, which progressed with visual deterioration to hand motions. Results: A diagnosis of exudative retinal detachment was made because no retinal breaks were identified. The retina was reattached with external drainage and gas tamponade. One month postoperatively, the best-corrected visual acuity recovered to 20/100 in the left eye, and the vascular activity of the hemangioma stabilized. Conclusion: Photodynamic therapy monotherapy to treat retinal capillary hemangioma might result in a massive exudative retinal detachment requiring surgery. RETINAL CASES & BRIEF REPORTS 7:86–88, 2013
tion. Various therapeutic modalities such as laser photocoagulation, cryotherapy, and vitreoretinal surgery have been reported, with varying and limited success depending on the tumor characteristics.1,2 Although smalland medium-sized RCHs can be treated effectively with laser photocoagulation, cryotherapy, or a combination of both, large and multiple RCHs are often refractory to these conventional treatments. Pars plana vitrectomy with or without direct dissection of such large and multiple RCHs has been considered as the secondary treatment of choice. However, serious vision-threatening complications related to surgery, such as proliferative vitreoretinopathy and tumor recurrence, have been reported.2 Recently, several less invasive alternatives have been used to treat challenging cases, including photodynamic therapy (PDT) with verteporfin3–6 and intravitreal injection of anti–vascular endothelial growth factor.7 Of these, PDT has had dramatic anatomical and functional success for treating peripheral RCH, resulting not only in regression of tumor activity but also in maintenance of the visual acuity with limited complications.3–6
From the Department of Ophthalmology, Osaka University Graduate School of Medicine, Osaka, Japan.
R
etinal capillary hemangioma (RCH) is a benign retinal vascular tumor associated with von HippelLindau disease. However, RCH can sometimes be complicated by a macular edema or a serous retinal detachment at the macula resulting in visual deterioraY. Oshima is an international advisory board member for Alcon Laboratories, Inc, Fort Worth, TX, and a consultant to Topcon Medical Laser Systems, Inc, Santa Clara, CA, and Synergetics, Inc, St. Charles, MO, but he has no proprietary interests in and receives no royalties from any companies and has no financial relationship with any products mentioned in this report. None of other authors have any financial interests in this subject matter. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s Web site (www.retinajournal.com). Reprint requests: Yusuke Oshima, MD, Department of Ophthalmology, Osaka University Graduate School of Medicine, E7, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan; e-mail: yusukeoshima@ gmail.com
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MASSIVE RETINAL DETACHMENT AFTER PDT
To date, several complications related to PDT for RCH have been reported, including transient decompensation of vascular permeability, occlusion of retinal vessels, and ischemia of the optic nerve.6 However, most of these complications were associated with juxtapapillary RCH. In cases with peripheral RCH, exudative retinal detachment has been reported as a complication of PDT, which resolved spontaneously without the need for surgery.4 In contrast, we describe for the first time a case that required emergency surgery to treat a massive vision-threatening retinal detachment immediately after the application of PDT with verteporfin for peripheral RCH associated with von Hippel-Lindau disease. Case Report A 38-year-old woman presented with peripheral RCH associated with von Hippel-Lindau disease in the left eye; no previous ocular treatment was referred to the Osaka University Hospital. At the initial visit, the best-corrected visual acuity was 20/20 in the right eye and 20/250 in the left eye. An indirect ophthalmoscopic fundus examination showed tortuous dilated retinal vessels at the posterior pole connected to a 3.5-mm, fleshy, pink-orange peripheral RCH in the superotemporal quadrant (Figure 1A) of the left eye. Optical coherence tomography showed marked cystoid macular edema (Figure 1B). Fluorescein angiogram showed the afferent feeding retinal arteriole and the draining vein with prominent fluorescein leakage from the RCH (Figure 1C). Because the RCH was large and highly permeable, we chose PDT with verteporfin (Visudyne; QLT Phototherapeutics, Vancouver, Canada) as a less invasive treatment for this case. After providing informed consent, the patient underwent PDT with a spot size of 8,000 mm to the hemangioma for 83 seconds
followed by another laser spot (1,000 mm) to the feeding and draining vessels for another 83 seconds. One day after PDT, the patient reported severe visual impairment in the treated eye; the best-corrected visual acuity was counting fingers. Fundus examination and B-scan echography confirmed an extensive retinal detachment complicated by a vitreous hemorrhage that obscured clear fundus visualization (Figure 1D). Because the retinal detachment progressed with visual deterioration to hand motions 3 days after PDT, the patient underwent a lens-sparing pars plana vitrectomy with a 25-gauge system (see Video, Supplemental Digital Content 1, http://links.lww.com/ICB/A3). After core vitrectomy and peripheral vitreous shaving with scleral indentation, perfluorocarbon liquid (Perfluoron; Alcon Laboratories, Fort Worth, TX) was injected into the vitreous cavity to facilitate easy identification of a Schlieren sign. Because no retinal breaks were identified, the subretinal fluid was drained externally to avoid creating any iatrogenic retinotomies for internal drainage. After fluid-air exchange, cryoretinopexy was applied around the peripheral RCH. The surgery ended with infusion of a nonexpansile concentration of 14% perfluoropropane into the vitreous cavity. The retina was successfully reattached. One month postoperatively, the best-corrected visual acuity improved to 20/100 in the left eye, with complete resolution of the serous retinal detachment at the macula. The RCH was well stabilized (Figure 2) without recurrences during a 12-month postoperative follow-up period, and the bestcorrected visual acuity at the final visit remained 20/100.
Discussion Localized exudative retinal detachment after PDT with verteporfin for RCH is a well-known complication that resolves spontaneously without surgery.4–7 No published reports have described the development of a massive exudative retinal detachment immediately after PDT for RCH. In the current case, we could not
Fig. 1. A. A large RCH is seen at the superotemporal periphery. B. The horizontal optical coherence tomography scan of the left eye obtained through the section indicated by the line in panel A shows marked cystoid macular edema. C. An earlyframe fluorescein angiogram shows tortuous dilated retinal vessels and profuse leakage from the hemangioma. D. Three days after PDT, an extensive retinal detachment with slight vitreous hemorrhage obscures clear fundus visualization.
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application of PDT combined with intravitreal injection of anti–vascular endothelial growth factor drugs effectively stabilizes tumor activities.9,10 This therapeutic option might also prevent the exudative changes induced by PDT. In summary, we report for the first time the need for emergency vitrectomy with external drainage of subretinal fluid to successfully treat a case of a progressively advancing subtotal retinal detachment with vitreous hemorrhage after PDT for a peripheral RCH. Although PDT monotherapy is a promising treatment option for RCH, surgeons should be alert to the possibility of development of a PDT-induced complication, such as an exudative retinal detachment. Because both prevention and treatment strategies for this challenging situation have not yet been fully established, further studies are recommended. Key words: peripheral retinal capillary hemangioma, photodynamic therapy, exudative retinal detachment, pars plana vitrectomy. References Fig. 2. A. A color fundus composite photograph. B. An optical coherence tomography scan obtained through the section indicated by the line in panel A shows that the tumor dimensions have stabilized with decreased intraretinal and subretinal fluid.
confidently exclude the presence of a rhegmatogenous retinal detachment because the subtotal retinal detachment developed rapidly within 3 days after the application of PDT. Therefore, early vitrectomy was performed to explore the etiology of the retinal detachment, rhegmatogenous or exudative. Another reason for performing early vitrectomy was to remove the vitreous hemorrhage, which is a well-known risk factor for the development of proliferative vitreoretinopathy. Ultimately, the retinal detachment was presumed to be an exudative response induced by PDT because no breaks were identified intraoperatively and subretinal fluid did not recur postoperatively. Photodynamic therapy, applied to a large hemangioma, might induce a spike in secretion of vascular endothelial growth factor and other inflammatory cytokines and increase vascular permeability and leakage from the hemangioma.8 Similar to age-related macular degeneration, vascular endothelial growth factor plays an important role in RCH. Because the capillary hemangioma itself is a large vascularized tissue, it is easy to understand that the severity of the leakage from the hemangioma after PDT will be much more prominent than that from a small choroidal neovascular network observed in the age-related macular degeneration cases. Several studies have reported that the
1. Singh AD, Nouri M, Shields CL, et al. Treatment of retinal capillary hemangioma. Ophthalmology 2002;109:1799–1806. 2. Gaudric A, Krivosic V, Duquid G, et al. Vitreoretinal surgery for severe retinal capillary hemangiomas in Von Hippel-Lindau disease. Ophthalmology 2011;118:142–149. 3. Aaberg TM Jr, Aaberg TM Sr, Martin DF, et al. Three cases of large retinal capillary hemangiomas treated with verteporfin and photodynamic therapy. Arch Ophthalmol 2005;123:328–332. 4. Wong YM, Jalil A, Mathews J, Stanga PE. Exudative retinal detachment following photodynamic therapy for retinal capillary hemangioma. Can J Ophthalmol 2010;45:299–300. 5. Sachdeva R, Dadgostar H, Kaiser PK, et al. Verteporfin photodynamic therapy of six eyes with retinal capillary haemangioma. Acta Ophthalmol 2010;88:334–340. 6. Schmidt-Erfurth UM, Kusserow C, Barbazetto IA, Lagua H. Benefits and complications of photodynamic therapy of papillary capillary hemangiomas. Ophthalmology 2002;109:1256– 1266. 7. Wong WT, Liang KJ, Hammel K, et al. Intravitreal ranibizumab therapy for retinal capillary hemangioblastoma related to von Hippel-Lindau disease. Ophthalmology 2008;115:1957–1964. 8. Schmidt-Erfurth U, Schlötzer-Schrehard U, Cursiefen C, et al. 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;44:4473–4480. 9. Ziemssen F, Voelker M, Inhoffen W, et al. Combined treatment of a juxtapapillary retinal capillary haemangioma with intravitreal bevacizumab and photodynamic therapy. Eye (Lond) 2007;21:1125–1126. 10. Mennel S, Meyer CH, Callizo J. Combined intravitreal antivascular endothelial growth factor (Avastin) and photodynamic therapy to treat retinal juxtapapillary capillary haemangioma. Acta Ophthalmol 2010;88:610–613.
