Author Affiliations: Ophthalmic Plastic and Reconstructive Surgery Division (Drs Fay and Nguyen) and Cogan Ophthalmic Pathology Laboratory (Dr Jakobiec), Harvard Medical School, Massachusetts Eye and Ear Infirmary, Boston; Center for Vascular Malformation in Children, St Joseph Hospital, Berlin, Germany (Dr Meyer-Junghaenel); and Vascular Birthmark Institute of New York, St Luke’s/Roosevelt Hospital Center, New York (Dr Waner). Dr Nguyen is now with the Department of Ophthalmology, Robert C. Byrd Health Science Center, West Virginia University School of Medicine, Morgantown.
Infantile hemangioma is the most common benign solid tumor of the ocular adnexa of children, causing significant functional and cosmetic deformity, with a 43% to 60% incidence of astigmatic or occlusion amblyopia when either the eyelid or orbit is affected.1,2 In cases involving the orbit, there can be proptosis, displacement of the globe, exposure keratopathy, compressive optic neuropathy, and strabismic amblyopia.2 Numerous modalities have been used to treat infantile hemangioma, but no single uniformly safe and effective method has yet been found. Léauté-Labrèze et al3 recently discovered that propranolol can inhibit growth and cause regression of segmental infantile hemangioma without any serious adverse effects. We report the successful use of systemic propranolol in an infant who had an isolated, extensive, and deep orbital infantile hemangioma.
A healthy 4-month-old female infant had experienced progressive painless protrusion of the right eye for 3 months. Examination revealed axial proptosis of the right globe along with fullness of the eyelids (Figure 1A). A relative afferent pupillary defect was not detected. Magnetic resonance imaging revealed a predominantly intraconal mass replacing the orbital fat, pushing the globe forward but not distorting the optic nerve (Figure 1B). A biopsy was obtained through an inferior transconjunctival orbitotomy. A hypercellular tumor was composed of variably sized lobules replacing most of the orbital fat except for a scattering of surviving adipocytes (Figure 2A and B). Immunostaining with CD34 for endothelial cells highlighted the capillary nature of the proliferation with nonstaining interstitial pericytic cells (Figure 2C); the endothelial cells also expressed glucose transporter isoform 1, a marker for infantile hemangioma (Figure 2D). Propranolol treatment was initiated at a dosage of 2 mg/kg/d intravenously for 5 days and then continued at home at the same dosage by oral administration. At the 6-week follow-up visit, there was no obvious proptosis (Figure 1C). Repeated magnetic resonance imaging at the 3-month visit revealed complete resolution of the orbital tumor with restoration of an unremarkable retrobulbar fat pattern (Figure 1D). Our patient was treated with propranolol until 1 year of age (treatment for 8 months). Propranolol was then tapered over a 1-month period, and the patient experienced no adverse effects or regrowth at the 9-month follow-up.
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.
Histological analysis. A, Lobules of hypercellular tissue with some surviving adipocytes separated by fibrous septa (hematoxylin-eosin, original magnification ×3). B, Indistinct to small lumina are displayed by the constituent tumor cells (hematoxylin-eosin, original magnification ×10). C, Immunostaining with CD34 demonstrates endothelial cells forming vascular channels and nonstaining interstitial pericytic cells (immunoperoxidase reaction, diaminobenzidine chromogen, original magnification ×20). 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 ×20).
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.
Correspondence: Dr Fay, Massachusetts Eye and Ear Infirmary, 243 Charles St, Boston, MA 02114 (firstname.lastname@example.org).
Financial Disclosure: None reported.
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