Juxtapapillary retinal capillary hemangioblastomas are vascular, histologically benign lesions that appear on the optic nerve head or within the juxtapapillary region. Although various treatment methods have been described as effective, the treatment of juxtapapillary retinal capillary hemangioblastomas remains a therapeutic dilemma, mainly because of their proximity to the optic disc and major retinal vessels.1
Photodynamic therapy (PDT) with verteporfin was developed to treat choroidal neovascularization associated with age-related macular degeneration. Although retinal capillary hemangioblastomas exhibit normal endothelial cells, basement membranes, and pericytes, their active uptake of acetylated low-density lipoprotein is comparable to that of choroidal neovascularization.2 Selective vascular occlusion without damage to the adjacent neural structures has offered a new mode of therapy for juxtapapillary retinal capillary hemangioblastomas. Single case reports and small series have already shown favorable initial anatomical results, although functional therapeutic effects have been variable. In most of these studies, treatment was performed as per the parameters outlined in the Treatment of Age-related macular degeneration with Photodynamic therapy (TAP) study, using a light-dose of 50 J/cm2.3 The dosimetry of this study (100 J/m2) was adopted to avoid the repetitive treatment approach for papillary angioma.
We report our clinical experience with the use of double-fluence PDT with verteporfin to treat an 8-year-old child with a unilateral juxtapapillary retinal capillary hemangioblastoma.
An 8-year-old girl was admitted to our hospital after a juxtapapillary retinal capillary hemangioblastoma was discovered in her left eye during a routine examination. Her personal and family history for lesions associated with von Hippel–Lindau disease, magnetic resonance imaging of the brain, abdominal sonography, and DNA testing for a mutation of the von Hippel–Lindau disease gene were all negative.
The patient’s visual acuity was hand motions in the affected eye and 20/20 in the right eye. Ophthalmoscopy revealed a swollen optic disc with surrounding serous retinal detachment and severe lipid exudation in the juxtapapillary and papillomacular areas (Figure 1A). Optical coherence tomography (Figure 1D) confirmed cystoid macular edema with a central foveal thickness of 874 μm. Fluorescein angiography (Figures 1B–C) indicated a sessile juxtapapillary retinal capillary hemangioblastoma involving primarily the outer layers of the retina. Early and fast filling of the lesion was observed, as well as extensive leakage of dye into the subretinal space during the late phase. Because the tumor was located around the optic nerve head, a decision was made to treat the lesion with PDT. The parents were involved in the final decision and signed a written consent form. Verteporfin 6 mg/m2 was administered as an intravenous infusion over 10 minutes. Five minutes later, PDT was done using a diode laser (689 nm) to apply a 7,800-μm spot with an intensity of 600 mW/cm2 for 166 seconds (100 J/cm2).
Figure 1. Clinical images before (left) and after (right) treatment. (A) Ophthalmoscopy shows the tumor in the superotemporal side of the optic disc surrounded by serous retinal detachment and abundant lipid exudation (left). Six months later, there is marked shrinkage and increased fibrosis of the tumor, as well as a decrease in exudation (right). (B) Early fluorescein angiography images show early, rapid filling of the lesion (left). Note the decrease in vascular density after treatment (right). (C) Late fluorescein angiography images show extensive late leakage of dye into the subretinal space (left). Note a decrease in leakage of the dye from the tumor after treatment (right). (D) Optical coherence tomography images, which include the central macula.
At the 1-month follow-up visit, visual acuity had improved to 20/200 and the fluorescein angiography (Figures 1B–C) showed decreased early filling of and late leakage from the hemangioblastoma. At the 6-month follow-up visit, best-corrected visual acuity was 20/120 (on the dynamic component). Funduscopy indicated a significant decrease in lipid exudation and fibrotic changes; the presence of residual cystoid macular edema was observed with optical coherence tomography (Figure 1D). The patient is still undergoing part-time patching therapy.
Approximately 50% of solitary retinal capillary hemangioblastomas occur sporadically and not as manifestations of von Hippel–Lindau disease.4 Genetic testing is used to exclude von Hippel–Lindau disease with a high degree of certainty.5 Clinical and angiographic features are usually sufficient to differentiate between a tumor and other retinal pathologies. The morphology and fluorescein angiography in this case were consistent with a juxtapapillary retinal capillary hemangioblastoma. Lesions considered in the differential diagnosis included papillitis, granulomatous disease, and choroidal hemangioma. Fluorescein angiography identified the presence of the underlying angioma, showing a fine capillary network and early and fast filling of the lesion. The amount of lipid present suggested a long evolution of the lesion. The circinate pattern and hyperfluorescence in the early phases of the angiogram were atypical of inflammatory lesions such as granuloma or chorioretinitis. The fluorescein angiography failed to indicate the deep, poorly defined vascular channels, suggesting choroidal hemangioma.
Observation has been proposed as an initial treatment for asymptomatic juxtapapillary retinal capillary hemangioblastomas.6 This recommendation is in line with the findings of previously published reports, which have suggested the long-term stability of juxtapapillary retinal capillary hemangioblastomas relative to extrapapillary retinal capillary hemangioblastomas. Although laser photocoagulation, cryotherapy, and ruthenium brachytherapy have proven successful in treating extrapapillary retinal capillary hemangioblastomas, their use in juxtapapillary retinal capillary hemangioblastomas is limited due to the potential for damage to the nerve fiber layer, resulting in a dense central or arcuate scotoma.7 Better results have been obtained with microsurgical ligation of the feeding vessels and, more recently, with PDT either alone or in combination with intravitreal antiangiogenic agents.8–10
PDT with verteporfin seems to be a safe and effective treatment for vascular lesions in a sensitive neural surrounding.3,9 Optimal treatment settings remain a subject of major debate in reported cases, in which radiant exposure ranges from 50 to 100 J/cm2. It has been suggested that the standard light dose of 50 J/cm2 may not be adequate for treatment of these lesions. Schmidt-Erfurth et al.9 achieved reduced tumor size and exudation in five patients with juxtapapillary retinal capillary hemangioblastomas using laser parameters increased to 100 J/cm2 of light at 692 nm. Sachdeva et al.3 provided further confirmation of the moderate efficacy of PDT using the standard dose of 50 J/cm2 light; 50% of cases required multiple retreatment sessions.
Our case demonstrates the efficacy of PDT in the treatment of juxtapapillary retinal capillary hemangioblastomas in a young patient. Tumor shrinkage was observed after just one PDT session, along with improved visual acuity. The dosimetry in this study was the same as that used by Schmidt-Erfurth et al.9 The better functional results achieved in our case might be explained by the younger age of the patient, which has been associated with reduced gliosis and therefore a higher susceptibility of the tumor to PDT. We believe that large juxtapapillary retinal capillary hemangioblastomas should be treated with a higher PDT dose of 100 J/cm2, because the depth of vascular occlusion depends on the total dose delivered. No damage to the neurosensory structure or to normal vessels was observed with a light dose below 150 J/cm2 in the case of choroidal neovascularization or choroidal hemangiomas. The dosage chosen for the PDT therefore seems to be safe and effective.
A combination of PDT with anti-vascular endothelial growth factor (VEGF) may offer another therapeutic option for juxtapapillary retinal capillary hemangioblastomas, and its successful use in adults has already been reported by several authors.10 Bevacizumab also showed promising results in several retinal and choroidal vascular diseases in children.11 The theoretical possibility of interference with the patient’s vascular and neurological development can be limited by local administration of a VEGF inhibitor. We did not recommend anti-VEGF therapy for our patient because we believe that the vasculature of large retinal hemangiomas is mature and thus less dependent on VEGF for growth or maintenance. This belief is consistent with other reports, which have failed to show tumor regression after the administration of anti-VEGF therapy.12 Anti-angiogenics could be used as a second-line treatment in cases of tumor recurrence.
Monotherapy of juxtapapillary retinal capillary hemangioblastomas with double-fluence verteporfin PDT can be a safe and effective treatment for the management of juxtapapillary retinal capillary hemangioblastomas.
- McCabe CM, Flynn HW Jr, Shields CL, et al. Juxtapapillary capillary hemangiomas: clinical features and visual acuity outcomes. Ophthalmology. 2000;107:2240–2248. doi:10.1016/S0161-6420(00)00422-X [CrossRef]
- Gass JD, Braunstein R. Sessile and exophytic capillary angiomas of the juxtapapillary retina and optic nerve head. Arch Ophthalmol. 1980;98:1790–1797. doi:10.1001/archopht.1980.01020040642011 [CrossRef]
- Sachdeva R, Dadgostar H, Kaiser PK, Sears JE, Singh AD. Verteporfin photodynamic therapy of six eyes with retinal capillary haemangioma. Acta Ophthalmol. 2010;88:e334–e340. doi:10.1111/j.1755-3768.2010.02008.x [CrossRef]
- Singh AD, Shields JA, Shields CL. Solitary retinal capillary hemangioma: hereditary (von Hippel-Lindau disease) or non hereditary?Arch Ophthalmol. 2001;119:232–234.
- Singh AD, Ahmad NN, Shields CL, Shields JA. Solitary retinal capillary hemangioma: lack of genetic evidence for von Hippel-Lindau disease. Ophthalmic Genet. 2002;23:21–27. doi:10.1076/opge.18.104.22.1681 [CrossRef]
- Singh AD, Nouri M, Shields CL, Shields JA, Perez N. Treatment of retinal capillary hemangioma. Ophthalmology. 2002;109:1799–1806. doi:10.1016/S0161-6420(02)01177-6 [CrossRef]
- Kreusel KM, Bornfeld N, Lommatzsch A, Wessing A, Foerster MH. Ruthenium-106 brachytherapy for peripheral retinal capillary hemangioma. Ophthalmology. 1998;105:1386–1392. doi:10.1016/S0161-6420(98)98017-4 [CrossRef]
- Nadal J, Abreu R, Barraquer R. Surgical treatment of a juxtapapillary retinal hemangioma. Retina. 2008;28:900–903. doi:10.1097/IAE.0b013e3181723d7d [CrossRef]
- Schmidt-Erfurth UM, Kusserow C, Barbazetto IA, Laqua H. Benefits and complications of photodynamic therapy of papillary capillary hemangiomas. Ophthalmology. 2002;109:1256–1266. doi:10.1016/S0161-6420(02)01059-X [CrossRef]
- Mennel S, Meyer CH, Callizo J. Combined intravitreal anti-vascular endothelial growth factor (Avastin) and photodynamic therapy to treat retinal juxtapapillary capillary haemangioma. Acta Ophthalmol. 2010;88:610–613.
- Sisk RA, Berrocal AM, Albini TA, Murray TG. Bevacizumab for the treatment of pediatric retinal and choroidal diseases. Ophthalmic Surg Lasers Imaging. 2010;41:582–92. doi:10.3928/15428877-20100830-03 [CrossRef]
- Wong WT, Liang KJ, Hammel K, Coleman HR, Chew EY. Intravitreal ranibizumab therapy for retinal capillary hemangioblastoma related to von Hippel-Lindau disease. Ophthalmology. 2008;115:1957–1964. doi:10.1016/j.ophtha.2008.04.033 [CrossRef]