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Figure 1.
Photographs of a 3-month-old infant with facial hemangiomas before and after treatment with topical timolol solution. A, A 3-month-old girl had a large capillary hemangioma of her right upper eyelid that induced marked blepharoptosis and covered the pupil. B, Two drops of timolol maleate, 0.5%, solution were applied to the surface of the hemangioma twice daily. After 3 and a half months, her hemangioma almost completely resolved and the visual axis cleared. Her palpebral fissure height improved from approximately 2 mm to 9 mm and the margin-reflex distance improved from a negative value to +3 mm.

Photographs of a 3-month-old infant with facial hemangiomas before and after treatment with topical timolol solution. A, A 3-month-old girl had a large capillary hemangioma of her right upper eyelid that induced marked blepharoptosis and covered the pupil. B, Two drops of timolol maleate, 0.5%, solution were applied to the surface of the hemangioma twice daily. After 3 and a half months, her hemangioma almost completely resolved and the visual axis cleared. Her palpebral fissure height improved from approximately 2 mm to 9 mm and the margin-reflex distance improved from a negative value to +3 mm.

Figure 2.
Photographs of a 16-month-old girl with a diffuse hemangioma. A, A 16-month-old girl had a diffuse hemangioma on the right upper face involving the right upper eyelid. B, The hemangioma significantly improved after 4 weeks of treatment with 3 drops of timolol maleate, 0.5%, solution applied twice daily onto the surface of the hemangioma.

Photographs of a 16-month-old girl with a diffuse hemangioma. A, A 16-month-old girl had a diffuse hemangioma on the right upper face involving the right upper eyelid. B, The hemangioma significantly improved after 4 weeks of treatment with 3 drops of timolol maleate, 0.5%, solution applied twice daily onto the surface of the hemangioma.

1.
Drolet  BAEsterly  NBFrieden  IJ Hemangiomas in children. N Engl J Med 1999;341 (3) 173- 181
PubMedArticle
2.
Schwartz  SRBlei  FCeisler  ESteele  MFurlan  LKodsi  S Risk factors for amblyopia in children with capillary hemangiomas of the eyelids and orbit. J AAPOS 2006;10 (3) 262- 268
PubMedArticle
3.
Léauté-Labrèze  CDumas de la Roque  EHubiche  TBoralevi  FThambo  JBTaïeb  A Propranolol for severe hemangiomas of infancy. N Engl J Med 2008;358 (24) 2649- 2651
PubMedArticle
4.
Guo  SNi  N Topical treatment for capillary hemangioma of the eyelid using β-blocker solution. Arch Ophthalmol 2010;128 (2) 255- 256
PubMedArticle
5.
Siegfried  ECKeenan  WJAl-Jureidini  S More on propranolol for hemangiomas of infancy. N Engl J Med 2008;359 (26) 2846
PubMedArticle
6.
Sommers Smith  SKSmith  DM Beta blockade induces apoptosis in cultured capillary endothelial cells. In Vitro Cell Dev Biol Anim 2002;38 (5) 298- 304
PubMedArticle
Research Letters
March 2011

Topical Timolol for Periocular Hemangioma: Report of Further Study

Author Affiliations

Author Affiliations: Yale University School of Medicine, New Haven, Connecticut (Ms Ni); and The Eye Institute of Ophthalmology and Visual Science, New Jersey Medical School, Newark (Drs Langer, Wagner, and Guo).

Arch Ophthalmol. 2011;129(3):373-379. doi:10.1001/archophthalmol.2011.24

Childhood superficial capillary hemangiomas of the eyelid may lead to amblyopia or anisometropia.1,2 Although benign, such tumors can cause irreversible visual loss if not treated promptly. Treatment options for infantile hemangioma include both systemic and intralesional corticosteroids, interferon alfa, laser, embolization, immunomodulators, surgery, and, most recently, propanolol.1,3 Guo and Ni4 first reported successful outcomes for a 4-month-old infant with superficial capillary hemangioma of the eyelid using topical timolol maleate application. We now report a series of 7 children in whom significant reductions of periocular and facial capillary hemangiomas occurred following topical application of timolol maleate, 0.5%, solution.

Report of Cases

We treated 7 children with superficial periocular hemangiomas without previous intervention. This study was approved by the institutional review board of our institution. All parents were instructed to apply and gently spread 2 to 3 drops of timolol maleate, 0.5%, solution (liquid) topically onto the surface of the hemangioma using a fingertip twice daily. In all 7 children, the tumors decreased in size and volume and faded in color. Response times ranged from 4 to 8 weeks following timolol treatment. All children continued receiving topical timolol until their last office visits, ranging from 1 to 6 months. Among these 7 children, the reduction in hemangioma size and volume varied from 55% to 95% with follow-up for 1 to 6 months after treatment. All 7 patients showed a fade in hemangioma color from bright red to light pink or normal skin tone following timolol application. All patients were monitored by their pediatricians during the course of treatment. We also checked the patients' heart rates before and after timolol application during their office visits. All mothers were instructed to check pulse rates at home. No significant changes in heart rate and no local or systemic adverse effects were observed or reported in any children. Two illustrative cases are presented in Figure 1 and Figure 2.

Comment

All currently available treatment modalities are associated with adverse local or systemic effects.1,2 Intralesional corticosteroids are associated with disfiguring eyelid changes, elevated intraocular pressure, and central retinal artery occlusion, while oral steroids cause increased risk of hypertension, adrenal cortical insufficiency, delay of growth, immunosuppression, gastrointestinal bleeding, and behavioral changes. Surgical excision is associated with potential hemorrhage. Immunomodulators may cause myelosuppression, hepatotoxic effects, and neurotoxic effects.

Recently, propranolol, a β-blocker, was reported to successfully treat severe hemangiomas in infants when administered orally.3 However, use of oral propranolol is associated with systemic adverse effects, including bronchospasm, heart block, hypotension, severe bradycardia, congestive heart failure, and hypoglycemia.5 Children treated with oral propranolol must be monitored closely and frequently by the pediatrician.5

Our findings suggest that application of topical timolol, another β-blocker, provides a safe and effective alternative treatment for superficial periocular hemangiomas and may have fewer systemic effects. While the mechanism(s) by which timolol reduces hemangiomas is unclear, β-blockade–mediated vasoconstriction, decreased vascular endothelial growth factor expression, and endothelial cell apoptosis may all be contributory.3,6 Further studies on the use of topical β-blockers for the treatment of infantile hemangiomas, including close monitoring for potential adverse effects, are ongoing at our institution.

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Article Information

Correspondence: Dr Guo, The Eye Institute of Ophthalmology and Visual Science, New Jersey Medical School, 90 Bergen St, DOC 6100, Newark, NJ 07101 (guos1@umdnj.edu).

Financial Disclosure: Dr Guo has filed a patent for the use of topical β-blockers in cutaneous hemangioma.

References
1.
Drolet  BAEsterly  NBFrieden  IJ Hemangiomas in children. N Engl J Med 1999;341 (3) 173- 181
PubMedArticle
2.
Schwartz  SRBlei  FCeisler  ESteele  MFurlan  LKodsi  S Risk factors for amblyopia in children with capillary hemangiomas of the eyelids and orbit. J AAPOS 2006;10 (3) 262- 268
PubMedArticle
3.
Léauté-Labrèze  CDumas de la Roque  EHubiche  TBoralevi  FThambo  JBTaïeb  A Propranolol for severe hemangiomas of infancy. N Engl J Med 2008;358 (24) 2649- 2651
PubMedArticle
4.
Guo  SNi  N Topical treatment for capillary hemangioma of the eyelid using β-blocker solution. Arch Ophthalmol 2010;128 (2) 255- 256
PubMedArticle
5.
Siegfried  ECKeenan  WJAl-Jureidini  S More on propranolol for hemangiomas of infancy. N Engl J Med 2008;359 (26) 2846
PubMedArticle
6.
Sommers Smith  SKSmith  DM Beta blockade induces apoptosis in cultured capillary endothelial cells. In Vitro Cell Dev Biol Anim 2002;38 (5) 298- 304
PubMedArticle
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