To assess the efficacy and safety of systemic propranolol for infantile capillary hemangiomas of the eyelid.
Prospective, interventional cases series.
All patients with eyelid infantile capillary hemangiomas at risk of developing amblyopia seen between January 2009 and January 2012 at the University Federico II, Naples, Italy, were treated with systemic propranolol (2 mg/kg body weight per day). Maximum length of treatment was 4 months, and propranolol was suspended when complete regression of lesions was obtained or in case of collateral effects. Minimum follow-up was 6 months.
Of 17 patients with eyelid infantile capillary hemangiomas, 3 were excluded for asthma and 14 (7 males, 7 females; mean age, 20.85 ± 29.7 months; range, 1 to 72 months) underwent treatment with systemic propranolol. Capillary hemangiomas involved the upper eyelid in 10 cases and the lower eyelid in 4 cases. Propranolol was stopped in 1 case for hypotension and in 1 case for allergy. Treatment was administered over a mean of 2.5 ± 1.3 months (range, 1 to 4 months); the mean follow-up was 10.64 ± 8.7 months (range, 6 to 39 months). Ten patients were younger than 1 year and demonstrated complete regression. Two patients older than 5 years also benefited from treatment. In 4 cases, amblyogenic astigmatism was present and decreased from 1.25 ± 0.5 diopters before treatment to 0.25 ± 0.2 diopters after treatment. No regrowth was observed.
Four months of treatment with oral propranolol for eyelid infantile capillary hemangiomas led to complete regression of the lesion in patients younger than 1 year. No major collateral effects were observed. Treatment also may be considered in patients older than 5 years to reduce astigmatism and for aesthetic purposes.
Infantile capillary hemangiomas are the most common tumors of the eyelid in infancy. They appear shortly after birth and usually begin to involute spontaneously in early childhood. Many involuted lesions do not need to be treated using corrective surgery, but in some cases, treatment is necessary because of vision loss secondary to amblyopia induced by astigmatism, ptosis, or globe displacement. Therapeutic options include intralesional, topical, or systemic corticosteroids as a first line of treatment, and interferon α, vincristine, cyclophosphamide, topical imiquimod, focal laser photocoagulation, and surgical excision as secondary therapeutic options. In 2008, the successful effect of oral propranolol therapy on severe infantile hemangiomas was reported by Léauté-Labrèze and associates in patients treated for high-output cardiac failure. In this study, we evaluated the efficacy and adverse effects of oral propranolol treatment in patients with eyelid infantile capillary hemangiomas.
In this prospective interventional study, we included all patients with eyelid infantile capillary hemangiomas at risk of occlusive or refractive amblyopia. Recruitment was conducted at the Pediatric Ophthalmology Department and in the Pediatric Department of the University Federico II, Naples, Italy, between January 2009 and January 2012. The main inclusion criterion was the presence of an eyelid hemangioma that could determine occlusive or refractive amblyopia because of its position and size. Exclusion criteria for treatment were the presence of an intraconic lesion, congestive cardiac failure, asthma, and obstructive pulmonary disease. Informed consent was obtained in accordance with institutional review board approval. Before initiation of treatment, 2 visits within 1 month were scheduled to exclude spontaneous improvement of the lesion. All children included in the study were given propranolol at a dose of 2 mg/kg body weight per day. Treatment was suspended when a complete flattening of the hemangioma was obtained or in case of adverse effect. Treatment was administered during a maximum period of 4 months to obtain an antiamblyopic effect by minimizing the risk of collateral effects. All patients underwent a cardiology evaluation (including electrocardiography and echocardiography) before treatment. The unwanted general effects of β-blockers were monitored carefully monthly by a general pediatrician (A.D.M.) under ambulatory conditions (rhythm cardiac monitoring, pulmonary sounding, blood pressure monitoring, research of acrocyanosis, nightmares, drowsiness, irritability, and gastric acid backward flow). In case of blood hypotension or rhythm cardiac abnormalities, a heart echography was scheduled.
Minimum length of follow-up was 6 months. All children were examined at baseline, at 1 week after initiation of treatment, at 1 month, and then at monthly intervals until total regression and after therapy ended. Ophthalmologic examinations included assessment of visual fixation preference, eyelid function and ptosis, extraocular motility, anterior segment, dilated funduscopy, and cycloplegic refraction. To obtain the astigmatic difference, the cylinder measurement in the affected eye was subtracted from the cylinder measurement in the unaffected eye. A difference of 1.50 diopters or more in astigmatism (in accordance with the preferred practice pattern of the American Academy of Ophthalmology ), ptosis, eyelid contour changes at risk of causing occlusion, strabismus, or globe displacement were considered to be significant amblyogenic factors. Demographic information, age at first visit to clinic, age at start of treatment, duration of treatment, and indication for treatment were recorded.
Size of the hemangioma was documented by B-scan echography, by clinical examination, and by photography at treatment onset, throughout treatment, and at the conclusion of treatment. The visual analog scale was used to compare the response to treatment because it was used in previous studies evaluating the response of infantile capillary hemangiomas to corticosteroids and propranolol treatment. Two expert ophthalmologists (P.V., R.F.), blinded to the patients, independently assessed the efficacy of the therapy by analyzing the clinical photographs at baseline and at 6 months. The clinical score for the overall change in the infantile capillary hemangiomas used a 100-mm VAS with a range from −100 to +100. An assessment between −100 mm and 0 reflected a deterioration of the infantile capillary hemangiomas, and an assessment between 0 and +100 mm reflected an improvement of the infantile capillary hemangiomas. Doubling in size was recorded as −100 mm, absence of change was recorded as 0, and complete resolution was recorded as +100 mm. The percentage of change from baseline then was translated by determining the distance on the VAS from point 0, with each 5 mm equaling a 5% change from baseline. Side effects of therapy were evaluated at each follow-up visit. The main outcome measure was posttreatment regression of lesions measured by the visual analog scale and echography. Secondary outcome measures were improvement in astigmatism, amblyopia, and visual acuity and the safety of therapy.
All analyses were performed with the SPSS software version 18 (SPSS, Inc, Chicago, Illinois, USA). Continuous variables, such as age, duration of ophthalmologic follow-up, and VAS, were described using mean, standard deviation, and median values in the studied patients. The agreement between the 2 evaluators of VAS was measured using the intraclass correlation coefficient and respective P values ( P < .05 was considered significant).
Three patients with intraconic hemangioma and 17 patients with eyelid hemangioma were seen in the recruitment period. Of 17 patients with eyelid hemangioma, 3 were excluded because of a history of asthma and 14 (7 males, 7 females) underwent treatment with systemic propranolol. Treatment was initiated at an age of 20.85 ± 29.7 months (range, 2 to 96 months; mean, 5.3 ± 2.3 months if 1 23-month-old child, 1 72-month-old child, 1 96-month-old child, and 1 48-month-old child are excluded). A summary of patient characteristics and outcomes is reported in Table 1 . Lesion characteristics at baseline and at the 6-month visit are shown in Table 2 .
|Patient No.||Sex||Age at Treatment Onset, (mos)||Treatment Duration (mos)||Site||Type of Hemangioma||Lesion Progression||Visual Acuity (Snellen)||Pretreatment Astigmatism (Diopters)||Posttreatment Astigmatism (Diopters)||Pretreatment Amblyopia||Cause of Amblyopia||Posttreatment Amblyopia||Side Effects||Follow-up (mos)|
|7||F||72||4||UE||Involving elevator muscle||Stable||32/25||+1||+0.25||Yes||Astigmatism, Ptosis||No||NA||6|
|Patient No.||Size on Baseline Photography (Height/Width), cm||Thickness on Baseline Echography, cm||Size on Photography at Last Visit (Height/Width), cm||Thickness on Echography at Last Visit, cm||VAS Results at 6-Month Visit (Evaluator 1/Evaluator 2)|