From the Department of Ophthalmology, Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, Florida.
Supported by grant EY014801 from the National Eye Institute, National Institutes of Health, Bethesda, Maryland, and by Research to Prevent Blindness, Inc., New York, New York.
The authors have no financial or proprietary interest in the materials presented herein.
Address correspondence to Sara Tullis Wester, MD, Bascom Palmer Eye Institute, 900 NW 17th St., Miami, FL 33136. E-mail: Swester2@med.miami.edu
Infantile periocular capillary hemangiomas occur in 1% to 2% of neonates and have significant visual and cosmetic morbidity. The tumors can cause amblyopia by occlusion of the visual axis or induced astigmatism.1 Past treatments have been limited to systemic or intralesional steroids, surgical excision, and other experimental modalities. A recent report demonstrated that systemic propranolol was found to have a dramatic effect on decreasing the size of these tumors.2 The mechanism of action of this non-selective beta blocker in periocular capillary hemangiomas is not completely understood, but may be secondary to decreased vascular endothelial growth factor and bFGF gene expression or effects on apoptosis.2
This case report was designed to document quantitative changes in the size of a periocular capillary hemangioma using sequential echography in a patient receiving off-label treatment with systemic propranolol.
A 5-week-old female infant presented to an outside ophthalmologist with right eyelid swelling. At presentation, examination disclosed right upper eyelid swelling due to a violaceous mass causing occlusion of the visual axis. The patient was referred to the oculoplastics service at 7 weeks of age. At that visit, she was noted to have 2 mm of right upper eyelid ptosis and a soft, violaceous mass in her right upper eyelid (Fig. 1A).
Figure 1. (A) Photograph Prior to Initiation of Propranolol Treatment. (B) Photograph 6 Days After Initiation of Propranolol Treatment. (C) Photograph 6½ Weeks After Initiation of Propranolol Treatment.
Extraocular movements were full and she grimaced to light in both eyes with equal red reflexes. Quantitative A-scan ultrasound documented a well-outlined, compressible lesion involving the anterior superotemporal orbit with a maximal depth of 22.3 mm (Fig. 2A). The mass was slightly irregularly structured with marked vascularity, consistent with a capillary hemangioma. After the risks, benefits, and alternatives of treatment with intralesional corticosteroid injection, surgical excision, and off-label systemic propranolol were discussed with the patient’s parents, they decided to proceed with propranolol treatment. Treatment was initiated (beginning at 0.5 mg/kg/day and increased over several weeks to 2 mg/kg/day divided in twice-daily doses) under the care of a pediatric cardiologist who performed an echocardiogram and electrocardiogram prior to the initiation of therapy. Six days later, the patient was noted to have significant improvement in the size and external appearance of the eyelid lesion, and displayed only 1 mm of ptosis (Fig. 1B). Two weeks later, there was echographic documentation of continued improvement with the lesion measuring 20.0 mm in maximal depth (Fig. 2B). Six and ½ weeks after initiation of propranolol therapy, the patient demonstrated no ptosis and the lesion was not grossly visible (Fig. 1C). Quantitative A-scan ultrasound demonstrated that the tumor size had decreased to 16.0 mm in maximum depth (Fig. 2C). Approximately 10 months after starting therapy, the lesion was undetectable both clinically and by ultrasonographic examination. The patient continued to take propranolol until approximately 1 year of age, at which time it was tapered. Two months after beginning the taper, the lesion was undetectable clinically and by ultrasonographic examination.
Figure 2. (A) A-Scan Ultrasound Prior to Initiation of Propranolol Documented a Lesion with a Maximal Depth of 22.3 mm. The Arrows Correlate to the Anterior and Posterior Aspects of the Lesion. The Line Shows Sound Attenuation (angle Kappa) Through the Lesion. (B) A-Scan Ultrasound 2 Weeks After Initiation of Treatment Documented a Lesion with a Maximal Depth of 20 mm. The Arrows Correlate to the Anterior and Posterior Aspects of the Lesion, Which Has Clearly Reduced in Size. (C) A-Scan Ultrasound 6½ Weeks After Initiation of Treatment Documented a Lesion with a Maximal Depth of 16 mm. The Arrows Mark the Anterior and Posterior Reflectivity Spikes in the Area of the Previous Lesion, Which now Is Significantly Reduced in Size and Looks More Similar to the Normal Periocular Pattern.
Current treatment for vision-threatening periocular capillary hemangiomas includes systemic, topical, or intralesional corticosteroids, interferon alfa-2b, radiation, and surgery. Systemic steroids have a low response rate, with only 30% of life- or vision-threatening hemangiomas responding with marked regression,3 and hemangiomas larger than 20 cm2 have been documented to have a poorer response. According to Chowdri et al.3 and Kushner,4 intralesional steroids result in a higher response rate (80% and 84%, respectively). This modality has significant risks,5 including optic neuropathy, subcutaneous deposits, tissue atrophy, eyelid necrosis, adrenal suppression, retrograde embolization, and central retinal artery occlusion.
Although measures to avoid the complication of retinal embolization lower the risk of central retinal artery occlusion,6 this potentially blinding consequence is often feared by patients’ families and practitioners. Therefore, other treatment modalities have been investigated. Hastings et al.7 studied the use of interferon alfa-2b in the treatment of 40 children 3 years old or younger with life- or vision-threatening hemangiomas, 35 of whom had no response to oral or intralesional steroids. Treatment with interferon alfa-2b resulted in an average regression of 82%, as measured by computed tomography. However, this therapy required daily subcutaneous injections over 3 months and had risks including fever, neutropenia, increased liver function tests, and intercurrent mild illnesses.
Léauté-Labrèze et al. reported 11 children with capillary hemangiomas treated with systemic propranolol exhibiting a dramatic improvement in their tumors.2 The study was initiated after two children treated with propranolol for myocardiopathy were found to have dramatic incidental changes in their hemangiomas. Nine additional patients were treated and within 24 hours all of the lesions changed from intense red to purple and softened. The patients continued to improve until the lesions were nearly flat with only residual skin telangiectasias.2 Several other reports have also documented significant improvement in cutaneous and laryngotracheal hemangiomas treated with propranolol.8–11
The most common dosage for treatment is 2 to 3 mg/kg/day divided in twice-daily dosing. Some studies advocate using a protocol with baseline cardiac ultrasonography, cardiologic examination, and monitoring of blood glucose levels during the first 48 hours of treatment, while initiating propranolol at 0.16 mg/kg/8 h and increasing to a maximum of 2 mg/kg/day.8 Our patient initiated propranolol at 0.5 mg/kg/day and increased to 2 mg/kg/day over several weeks. She had baseline cardiac ultrasonography and cardiologic examination and had no side effects throughout the treatment. Treatment was tapered after age 1 year with no relapse of the hemangioma.
This case report highlights the change in size of a periocular capillary hemangioma as documented by sequential echography after treatment with propranolol. Although echography is not used in many centers for orbital lesions, in the hands of experienced echographers, this technique may be extremely useful. Other imaging modalities in children have inherent disadvantages: radiation exposure with computed tomography and the need for sedation with both computed tomography and magnetic resonance imaging. No adverse side effects were noted throughout this patient’s treatment course. However, it is important to note that bronchospasm and congestive heart failure have been reported coincident with the administration of propranolol in pediatric patients. In addition, there have been recent reports of occult hypoglycemia and bradycardia associated with propranolol treatment for hemangioma of infancy.12 As previously mentioned, several treatment protocols have been developed to optimize safety given the risks of bradycardia, hypotension, and occult hypoglycemia with this therapy.8,12 In summary, systemic propranolol therapy appears to be a promising new therapy for periocular capillary hemangiomas when administered with appropriate monitoring and quantitative A-scan echography is an excellent modality for documenting the regression of these tumors during treatment.
- Rosca T, Pop M, Curca M, et al. Vascular tumors in the orbit: capillary and cavernous hemangiomas. Ann Diagn Pathol. 2006;10:13–19. doi:10.1016/j.anndiagpath.2005.07.008 [CrossRef]
- Léauté-Labrèze C, Dumas de la Roque E, Hubiche T, Boralevi F, Thambo J-B, Taïeb A. Propranolol for severe hemangiomas of infancy. N Eng J Med. 2008;358:2649–2651. doi:10.1056/NEJMc0708819 [CrossRef]
- Chowdri NA, Darzi MA, Fazili Z, Iqbal S. Intralesional corticosteroid therapy for childhood cutaneous hemangiomas. Ann Plast Surg. 1994;33:46–51. doi:10.1097/00000637-199407000-00009 [CrossRef]
- Kushner BJ. Intralesional corticosteroid injection for infantile adnexal hemangioma. Am J Ophthalmol. 1982;93:496–506.
- Siegfried E, Keenan W, Al-Jureidini S. More on propranolol for hemangiomas of infancy. N Engl J Med. 2008;358:2846–2847.
- Egbert JE, Paul S, Engel WK, Summers CG. High injection pressure during intralesional injection of corticosteroids into capillary hemangiomas. Arch Ophthalmol. 2001;119:677–683.
- Hastings MM, Milot J, Barsoum-Homsy M, Hershon L, Dubois J, Leclerc JM. Recombinant interferon alfa-2b in the treatment of vision-threatening capillary hemangiomas in childhood. J AAPOS. 1997;1:226–230. doi:10.1016/S1091-8531(97)90042-2 [CrossRef]
- Denoyelle F, Leboulanger N, Enjolras O, Harris R, Roger G, Garabedian E. Role of propranolol in the therapeutic strategy of infantile laryngotracheal hemangioma. Int J Pediatr Otorhinolaryngol. 2009;73:1168–1172. doi:10.1016/j.ijporl.2009.04.025 [CrossRef]
- Zimmerman AP, Wiegand S, Werner JA, Eivazi B. Propranolol therapy for infantile haemangiomas: review of the literature. Int J Pediatr Otorhinolaryngol. 2010;74:338–342. doi:10.1016/j.ijporl.2010.01.001 [CrossRef]
- Taban M, Goldberg RA. Propranolol for orbital hemangioma. Ophthalmology. 2010;117:195–195. doi:10.1016/j.ophtha.2009.08.040 [CrossRef]
- Sans V, Dumas de la Roque E, Berge J, et al. Propranolol for severe infantile hemangiomas: follow-up report. Pediatrics. 2009;124:e423–e431. doi:10.1542/peds.2008-3458 [CrossRef]
- Lawley LP, Siegfried E, Todd JL. Propranolol treatment for hemangioma of infancy: risks and recommendations. Pediatr Dermatol. 2009;26:610–614. doi:10.1111/j.1525-1470.2009.00975.x [CrossRef]