title: Topical Timolol Maleate Treatment of Infantile Hemangiomas.
abstract: BACKGROUND
  There has been a dramatic increase in the off-label use of ophthalmic timolol maleate, a β-blocker used for infantile hemangioma (IH) treatment as a topical counterpart to oral propranolol. Its safety and efficacy in a pediatric population with IH have not been evaluated in a large cohort. Our goal was to retrospectively assess timolol's effectiveness, discern characteristics associated with response, and document reported adverse events.
  
  
  METHODS
  A multicenter retrospective cohort study of 731 patients treated with topical timolol was completed at 9 centers. Inclusion required an IH suitable for timolol in the treating physician's judgment and access to clinical details including photographs. Logistic regression analysis and descriptive statistics were performed. Primary outcome measures were efficacy assessed by using visual analog scales for color and for size, extent, and volume from review of digital photographs taken as standard of care.
  
  
  RESULTS
  Most IHs were localized (80.1%) and superficial (55.3%). Risk of disfigurement was the most common indication for therapy (74.3%). Duration of therapy (P < .0001), initial thinness (P = .008), and subtype (P = .031) were significant predictors of response. Best response occurred in superficial IHs <1 mm thick. Fifty-three (7.3%) required subsequent therapy with systemic β-blocker. Adverse events were mild, occurring in 25 (3.4%) patients. No cardiovascular side effects were documented.
  
  
  CONCLUSIONS
  Timolol seems to be a well-tolerated, safe treatment option with moderate to good effectiveness, demonstrating best response in thin, superficial IHs regardless of pretreatment size. Timolol can be recommended as an alternative to systemic β-blockers and watchful waiting for many patients.
authors.affiliation: Johns Hopkins School of Medicine, Baltimore, Maryland; kateputtgen@jhmi.edu.
authors.forename: Katherine
authors.initials: K
authors.lastname: Püttgen
authors.affiliation: Cincinnati Children's Hospital, Cincinnati, Ohio;
authors.forename: Anne
authors.initials: A
authors.lastname: Lucky
authors.affiliation: Cincinnati Children's Hospital, Cincinnati, Ohio;
authors.forename: Denise
authors.initials: D
authors.lastname: Adams
authors.affiliation: Hospital for Sick Children, Toronto, Ontario, Canada;
authors.forename: Elena
authors.initials: E
authors.lastname: Pope
authors.affiliation: Sainte-Justine Hospital, Montréal, Québec, Canada;
authors.forename: Catherine
authors.initials: C
authors.lastname: McCuaig
authors.affiliation: Sainte-Justine Hospital, Montréal, Québec, Canada;
authors.forename: Julie
authors.initials: J
authors.lastname: Powell
authors.affiliation: University of California, San Francisco, San Francisco, California;
authors.forename: Dana
authors.initials: D
authors.lastname: Feigenbaum
authors.affiliation: Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland;
authors.forename: Yulia
authors.initials: Y
authors.lastname: Savva
authors.affiliation: Hospital de la Santa Creu i Sant Pau, Barcelona, Spain;
authors.forename: Eulalia
authors.initials: E
authors.lastname: Baselga
authors.affiliation: Medical College of Wisconsin, Milwaukee, Wisconsin;
authors.forename: Kristen
authors.initials: K
authors.lastname: Holland
authors.affiliation: Medical College of Wisconsin, Milwaukee, Wisconsin;
authors.forename: Beth
authors.initials: B
authors.lastname: Drolet
authors.affiliation: Medical College of Wisconsin, Milwaukee, Wisconsin;
authors.forename: Dawn
authors.initials: D
authors.lastname: Siegel
authors.affiliation: Columbia University, New York, New York;
authors.forename: Kimberly D
authors.initials: KD
authors.lastname: Morel
authors.affiliation: Columbia University, New York, New York;
authors.forename: Maria C
authors.initials: MC
authors.lastname: Garzon
authors.affiliation: University of California, San Francisco, San Francisco, California;
authors.forename: Erin
authors.initials: E
authors.lastname: Mathes
authors.affiliation: Columbia University, New York, New York;
authors.forename: Christine
authors.initials: C
authors.lastname: Lauren
authors.affiliation: Children's Mercy Hospital, Kansas City, Missouri; and.
authors.forename: Amy
authors.initials: A
authors.lastname: Nopper
authors.affiliation: Children's Mercy Hospital, Kansas City, Missouri; and.
authors.forename: Kimberly
authors.initials: K
authors.lastname: Horii
authors.affiliation: Children's Mercy Hospital, Kansas City, Missouri; and.
authors.forename: Brandon
authors.initials: B
authors.lastname: Newell
authors.affiliation: Children's Hospital of Fudan University, Shanghai, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Song
authors.affiliation: University of California, San Francisco, San Francisco, California;
authors.forename: Ilona
authors.initials: I
authors.lastname: Frieden
mesh_terms: D000284:Administration, Oral; D000287:Administration, Topical; D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage* / Q000009:adverse effects; D015331:Cohort Studies; D005260:Female; D006391:Hemangioma / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D056687:Off-Label Use; D011433:Propranolol / Q000627:therapeutic use; D012189:Retrospective Studies; D012878:Skin Neoplasms / Q000188:drug therapy* / Q000473:pathology; D013999:Timolol / Q000008:administration & dosage* / Q000009:adverse effects; D064232:Visual Analog Scale
chemical_list: D000319:Adrenergic beta-Antagonists; D013999:Timolol; D011433:Propranolol