Timolol Gel Effective for Infantile Capillary Hemangiomas

Caroline Helwick

November 19, 2012

CHICAGO — For treatment of cutaneous infantile capillary hemangiomas that are not visually threatening, topical timolol maleate gel 0.25% is safe and effective, researchers reported at the American Academy of Ophthalmology (AAO) 2012 Annual Meeting.

"This treatment can be considered for both superficial and mixed lesions, but other treatment options must be considered for deep lesions," said lead investigator Christopher B. Chambers, MD, of Northwestern University Feinberg School of Medicine, Chicago.

Capillary hemangiomas account for 5.6% of all pediatric orbital tumors. They resolve in about one half of patients by age 5 years and in nearly three quarters by age 7 years. Long-term complications include amblyopia, strabismus, cutaneous changes, residual proptosis, ocular dystropia, and several rare conditions.

Timolol may be appropriate for superficial hemangiomas (which have a red dimpled appearance) and mixed superficial and deep lesions, though not deep lesions (which may be space-occupying and compressible and may lack external features).

In the past 5 years, systemic propranolol gained favor as a treatment for capillary hemangiomas. Treatment, which reduces the size of the lesion within 24 hours, is believed to be due to a triple mechanism of action: vasoconstriction, reduction in proangiogenic signals, and induction of apoptosis.

"Like propranolol, timolol maleate is a nonselective beta blocker, and it is commonly used to treat infantile glaucoma," Dr. Chambers said.

A 0.5% solution and a 0.5% gel have been shown to be effective in treating hemangiomas, but a 0.25% gelling solution is also available that reduces the systemic absorption below that of the ophthalmic solution. This is important because side effects, including bradycardia and hypotension, have been reported with 0.5% timolol for glaucoma, he said.

"While the safety profile of timolol is good, if a lower concentration in a gelling solution is effective, it would theoretically decrease the systemic absorption and therefore be prudent," Dr. Chambers explained.

Study of 23 Infants

Dr. Chambers and colleagues performed a study evaluating timolol 0.25% gelling solution in consecutive patients with non-vision-threatening hemangiomas, defined as the absence of visually significant ptosis or induced astigmatism. Patients treated with systemic steroids or propranolol were excluded.

The study was a retrospective, nonrandomized, comparative single-masked cohort study. Parents chose twice-daily topical 0.25% timolol gel (n = 13) or observation (n = 10). Mean age at presentation was approximately 4 months.

The treatment was tapered beginning at 1 year of age over a 1-week period. The primary outcome was response to treatment at 2 months. The secondary outcome was response at latest follow-up visit.

Photographs were taken at each visit, reviewed by a masked examiner, and evaluated for lesion size, color, and thickness. Response to treatment was categorized as good (lesion decrease > 50%), moderate (lesion stable or decreased < 50%), or poor (lesion caused visually significant ptosis, induced astigmatism, or increased in size).

At 2 months, response was significantly better in the treated group (P = .001), of which 61.5% were classified "good," 30.8% were "moderate," and 7.7% were "poor." In the observation group, these responses were observed in 0%, 10%, and 90%, respectively, Dr. Chambers reported.

In the timolol group, 100% of superficial lesions were deemed to have a good response. For mixed lesions, 43% had a good response, and 57% had a moderate response. The 1 patient with a deep hemangioma had a poor response. In the observation group, there were no good responses for any lesion type. Altogether, 75% to 100%, depending on classification, had a poor response.

Graded responses at 2 months remained in the same category at all follow-up visits except for 1 patient with a mixed lesion who had a good response but discontinued treatment at 5 months of age. The lesion increased in size, but involution resumed within 1 month after treatment was reinitiated.

"All treated patients demonstrated an improvement in cutaneous hue, whereas all in the observation group worsened," Dr. Chambers added.

He said future studies should compare timolol 0.25% gel with 0.5% gel and should measure lesion thickness to test whether this predicts success.

Moderator of the session, Jill S. Melicher Larson, MD, of Minnesota Eye Consultants in Minneapolis, commented on the results.

"The data look excellent," she said. "Timolol gel is now commercially available, and as an ocular plastic surgeon, I probably will tailor my practice based on this study. Their thought is there is less systemic absorption with the gel, and I think that has been shown in the literature. For these hemangiomas, which are non-vision-threatening but create aesthetic and cosmetic changes in the eyelid, this could be an excellent treatment."

Dr. Chambers and Dr. Melicher Larson have disclosed no relevant financial relationships.

American Academy of Ophthalmology (AAO) 2012 Annual Meeting. Presented November 13, 2012.