View larger version (47K): [in this window] [in a new window] [as a PowerPoint slide]   Figure 1. Clinical and magnetic resonance images. A, Right axial proptosis in a 4-month-old female infant with fullness of the right upper and lower eyelids. B, Axial magnetic resonance image showing a retrobulbar mass replacing orbital fat and molding to the globe without optic nerve displacement. C, Resolution of axial proptosis 2 months after initiation of treatment with propranolol. D, Axial magnetic resonance image showing complete resolution of the tumor with normal orbital fat.

View larger version (257K): [in this window] [in a new window] [as a PowerPoint slide]   Figure 2. Histological analysis. A, Lobules of hypercellular tissue with some surviving adipocytes separated by fibrous septa (hematoxylin-eosin, original magnification x3). B, Indistinct to small lumina are displayed by the constituent tumor cells (hematoxylin-eosin, original magnification x10). C, Immunostaining with CD34 demonstrates endothelial cells forming vascular channels and nonstaining interstitial pericytic cells (immunoperoxidase reaction, diaminobenzidine chromogen, original magnification x20). D, Glucose transporter isoform 1 staining of endothelial cells confirms infantile hemangioma as the specific diagnosis. Note positive staining of fluid in the lumens (immunoperoxidase reaction, original magnification x20).

Comment
Direct interventional treatments for infantile hemangioma such as local corticosteroid injection, laser therapy, embolization, and surgery, while suitable for superficial and subcutaneous lesions, are sometimes problematic in deep orbital cases primarily because of poor access and risk of injury to the optic nerve and extraocular muscles. Traditional pharmacologic treatment with systemic corticosteroids can be efficacious but may be accompanied by significant systemic adverse effects. Other agents such as vincristine sulfate and cyclophosphamide are less predictable and potentially more dangerous than corticosteroids; we have abandoned interferon alfa altogether in this patient population because of neurotoxicity. Propranolol could represent a new pharmacologic approach to the treatment of deep orbital and/or periocular infantile hemangioma with many potential advantages.

Of 11 patients with infantile hemangioma described by Léauté-Labrèze and colleagues, 7 displayed periocular disease, 1 of whom had orbital involvement. This patient failed to show regression after the earlier administration of systemic corticosteroids (discontinued after 4 months). Within 3 days of the introduction of propranolol, blanching, softening, and early regression of the visible cutaneous lesions occurred. Propranolol was maintained for 3 months in this patient. All of the patients in the series experienced resolution of their hemangiomas without any rebound growth on cessation of propranolol.³

In rare instances, propranolol can cause transient hypoglycemia, bradycardia, and hypotension; bronchospasm can be seen in patients with underlying reactive airway. These risks can be managed anticipatorily by obtaining a pediatric pretherapy evaluation, by monitoring vital signs and blood glucose levels at initiation and throughout therapy, and by maintaining frequent pediatric follow-ups. Doses of propranolol can be administered intravenously or orally. Treatment responses are typically determined by clinical examination, but deep isolated lesions may require repeated magnetic resonance imaging. Discontinuation of therapy through tapering of propranolol over a 2-week period is said to be unnecessary but may minimize the risk of a hyperadrenergic withdrawal response. As exemplified in this case, propranolol is highly promising as an alternative pharmacologic agent and, based on nonophthalmic experience, may emerge as the preferred tool for the treatment of deep orbital and other inaccessible infantile hemangiomas.

AUTHOR INFORMATION
Correspondence: Dr Fay, Massachusetts Eye and Ear Infirmary, 243 Charles St, Boston, MA 02114 (aaron_fay{at}meei.harvard.edu).

Financial Disclosure: None reported.