Bevacizumab and External Beam Radiation Therapy for Diffuse Choroidal Hemangioma in Sturge-Weber Syndrome: A Case Report

Sturge-Weber syndrome is a congenital disorder consisting of vascular malformations of the skin, leptomeninges, and eyes. It is associated with diffuse choroidal hemangiomas, which may occur spontaneously or following glaucoma filtering surgery. There have been several reports published in the literature describing treatments for diffuse choroidal hemangioma including radiation therapy, beta-blocker therapy, argon laser therapy, and photodynamic therapy with varying levels of success [1‒3]. Treatments for choroidal hemangiomas focus on treatments of complications and manifestations of the underlying etiology. Here, we present a patient with Sturge-Weber syndrome who has a hemangioma-associated exudative retinal detachment treated with a combination of bevacizumab intravitreal injection and external beam radiation therapy (EBRT) with successful resolution of the exudative retinal detachment.

A 37-year-old male with a history of glaucoma in both eyes associated with Sturge-Weber syndrome status-post trabeculectomies as a child presented with an acute-onset decrease in vision in the right eye. Best-corrected visual acuity at presentation was 20/400 in the right eye and 20/30-2 in the left. Fundus examination revealed a macula-off exudative retinal detachment as well as an orange-red hue of the fundus in the right eye (Fig. 1a) and normal examination on the left. Intraocular pressure (IOP) was 8 mm Hg for the right eye and 9 mm Hg for the left eye. B-scan ultrasonography of the right eye was notable for a total, bullous, folded retinal detachment without evidence of a tractional component or retinal tear or break with 360-degree choroidal thickening extending anteriorly to the ciliary body, consistent with diffuse choroidal hemangioma (Fig. 2a). Fluorescein angiogram demonstrated late hyperfluorescent staining of the tissue adjacent to the area of exudative detachment in the far nasal and temporal periphery (Fig. 3).

The patient was treated with a single injection of anti-vascular endothelial growth factor (anti-VEGF) agent bevacizumab (1.25 mg/0.05 mL) in the right eye. He then underwent EBRT of the right eye, starting 4 weeks after the anti-VEGF injection. Radiation treatment consisted of 2,000 centigray (cGy) in 10 fractions at 200 cGy per fraction over a 2-week duration. Follow-up examination 6 months later revealed decreased subretinal fluid and decreased size of choroidal hemangioma on B-scan (Fig. 1b, 2b). IOP was 10 mm Hg for the right eye. Follow-up examination at 17 months demonstrated complete resolution of subretinal fluid and no evidence of choroidal elevation on B-scan (Fig. 2c). IOP was 6 mm Hg at this follow-up visit. The final best-corrected visual acuity in the right eye was 20/1,000. Informed consent was obtained from the patient for the use of patient data and images and consent for publication.

Sturge-Weber syndrome is a rare neurocutaneous disorder characterized by the presence of facial port-wine stains, leptomeningeal angiomas, and ocular abnormalities. The ocular manifestations of Sturge-Weber include increased risk of glaucoma, retinal pigment epithelial atrophy, iris hypoplasia and atrophy, retinal vascular abnormalities, and choroidal hemangiomas [4]. We report a case of choroidal hemangioma and associated exudative retinal detachment which resolved over several months following bevacizumab injection and EBRT. The current mainstay of treatment in diffuse choroidal hemangioma is radiation therapy, including EBRT, plaque brachytherapy, proton beam therapy, and gamma knife surgery [3]. Photodynamic therapy has also been used successfully as monotherapy in the treatment of diffuse choroidal hemangioma [1, 5]. To our knowledge, this is the first report of simultaneous treatment with EBRT and bevacizumab in the treatment of diffuse choroidal hemangioma and associated exudative retinal detachment.

The rationale for anti-VEGF therapy in this setting is that the exudative detachment in choroidal hemangioma is in part due to vascular permeability presumably regulated by VEGF. Anti-VEGF therapy has been used successfully in the treatment of exudative retinal detachments in other vascular tumors. A combination of laser photocoagulation and pegaptanib and bevacizumab resulted in gradual anatomic resolution and improvement of visual acuity in the setting of retinal angioma [6]. Bevacizumab has also been shown to hasten the recovery of visual acuity in circumscribed choroidal hemangioma [7, 8]. There is no standardized regimen for anti-VEGF therapy in vascular tumors. In our case, a single initial injection was performed and was deferred subsequently given the patient’s clinical improvement. Repeat bevacizumab injections were performed years later to treat cystoid macular edema in the setting of radiation retinopathy. Published case reports generally use a single injection or injections on an as-needed schedule based on the clinical course [6‒9].

A drawback of our report is that the patient received bevacizumab and EBRT concurrently, making it difficult to discern a clear temporal association between bevacizumab treatment and resolution of the exudative detachment. There is one previous report in the literature on the use of the anti-VEGF agent pegaptanib, resulting in rapid resolution of a persistent exudative retinal detachment associated with EBRT-treated choroidal hemangioma [9]. This complete resolution of the exudative detachment over 1 month was preceded by 6 months of minimal change after EBRT alone. In contrast, our case demonstrated gradual resolution of both the choroidal hemangioma and the associated exudative retinal detachment over several months following therapy. Unfortunately, this patient’s vision remained poor following the resolution of the choroidal hemangioma and associated subretinal fluid. Previous studies examining the use of radiation therapy in the treatment of diffuse choroidal hemangiomas with exudative detachments have reported only modest benefits in improving visual acuity. Further studies are indicated to report on the safety profile of anti-VEGF in this patient population.

This case report discusses a case of choroidal hemangioma and associated exudative retinal detachment which resolved over several months following bevacizumab injection and EBRT. Follow-up examination at 17 months demonstrated complete resolution of subretinal fluid and no evidence of choroidal elevation on B-scan. Moving forward, investigators may wish to intervene early in the course of the disease with anti-VEGF agents in addition to EBRT in order to determine whether they may assist in preventing visual decline. The CARE Checklist has been completed by the authors for this case report, attached as online supplementary material (for all online suppl. material, see https://doi.org/10.1159/000539655).

Ethical approval is not required for this study in accordance with local or national guidelines. Written informed consent was obtained from the patient for publication of the details of their medical case and any accompanying images.

The authors declare that they have no competing interests.

This report was sponsored by the National Eye Institute (Grant No. 1K08EY027458), Fight for Sight-International Retinal Research Foundation (Grant No. FFSGIA16002), and Alcon Research Institute Young Investigator and received generous support from the Helmut F. Stern Career Development Professorship in Ophthalmology and Visual Sciences. Unrestricted departmental support was also provided by Research to Prevent Blindness and the University of Michigan Department of Ophthalmology and Visual Sciences.

J.J.Y. analyzed and interpreted the patient data and was a major contributor to the writing of the manuscript. D.B. aided in the collection and interpretation of patient data and was a major contributor to the writing of the manuscript. Y.M.P. analyzed and interpreted the patient data and was a major contributor to the writing of the manuscript. All authors read and approved the final manuscript.

The data that support the findings of this study are not publicly available due to their containing information that could compromise the privacy of research participants but are available from J.Y. upon reasonable request.