Purpose
To examine the shift in astigmatic error following the use of oral propranolol as first-line treatment for periocular capillary hemangioma.
Design
Retrospective observational study.
Methods
study population: Three healthy infants (1 male) clinically diagnosed with periocular capillary hemangioma. Cycloplegic refraction measurements were obtained at presentation. After a comprehensive clinical evaluation, oral propranolol therapy was starting with a loading dose and titrated up to 2 mg/kg/day under monitoring of heart rate, blood pressure, and blood glucose alterations. Clinical follow-up and repeating cycloplegic refraction measurements were undertaken at the 1-week and 1- and 3-month follow-up visits. intervention: Oral propranolol therapy for infants diagnosed with periocular capillary hemangioma. main outcome measures: Astigmatic refractive errors before and after propranolol treatment.
Results
The infants’ mean age at the initiation of propranolol therapy was 6.3 months (range: 3.0–8.0 months). A rapid therapeutic effect was noticed in all cases, including a major change in lesion size and color. No complications were recorded during or following treatment. The mean astigmatic error decreased from 2.83 diopters before propranolol treatment to 1.33 diopters after 1 month of treatment. The drug was well tolerated by all 3 patients and no side effects were noted.
Conclusions
Infants can benefit from a rapid, meaningful reduction in periocular capillary hemangioma – induced astigmatism following oral propranolol treatment. Propranolol seems to be an effective and safe drug, which can be used as a steroid-sparing first-line treatment modality in this patient population.
Capillary hemangiomas are the most common orbital tumors in childhood. This benign tumor usually appears in the first few months of life, after which it enters the “proliferative phase,” during which there is rapid growth. The lesion stabilizes thereafter and eventually, after a few years, it undergoes involution, which may continue until the end of the first decade of life. Complications occur in up to 80% of untreated or, alternatively, treatment-resistant periocular capillary hemangioma cases. Anisometropic-induced amblyopia, the most significant sequela in terms of frequency, affects up to 60% of this population. This form of amblyopia is usually the result of mass-induced indentation on the infant’s flexible sclera and cornea, causing distortion and astigmatism. Deprivation amblyopia resulting from obstruction of the visual axis by the lesion is an additional potential cause for amblyopia. Further, less common complications of capillary hemangiomas include disfiguring proptosis, exposure keratitis, and optic nerve compression.
Indications for treatment include obstruction of the visual axis, induced astigmatism, strabismus, exposure keratitis, rapid growth, optic nerve compression, and cosmetic factors. While there are numerous treatment modalities for periocular capillary hemangioma, none has a safe and effective therapeutic profile. Systemic corticosteroids are currently the mainstay treatment, with a response rate of only 30% to 60%. Moreover, side effects are numerous and some might even be alarming, such as hypertension and hypertrophic obstructive cardiomyopathy. Intralesional corticosteroid injections, which are used as first-line therapy for small amblyogenic lesions, may lead to superficial eyelid necrosis and transient growth retardation, while devastating complications, such as occlusion of the retinal artery, may also occur. Interferon therapy, which is usually reserved for life-threatening hemangiomas, for orbital lesions, or as second-line therapy, is accompanied by flu-like symptoms, such as fever and muscular pains; and hematologic and hepatic toxicity, hypothyroidism, neurologic effects, and mood alterations have been described in several reports. Excision of the tumor mass may be suitable for selected cases; however, this approach is unpopular and has been found to result in untoward side effects, such as scarring, hemorrhage, incomplete excision, and lash loss.
In 2008, Léauté-Labrèze and associates were the first to report the use of propranolol for hemangiomas of infancy. Two later case reports described improvement in qualitative indices, such as size and color of periocular capillary hemangioma, associated with its use. Our Medline search failed to yield any study on the refractive properties of propranolol treatment in periocular capillary hemangioma patients. We now report an astigmatic reduction effect of propranolol for amblyogenic astigmatic periocular capillary hemangioma in a series of infants.
Patients and Methods
This study is a retrospective interventional case series. The medical records of all patients treated with propranolol (Deralin, Abic, Israel) for periocular capillary hemangioma at the Goldschleger Eye Institute, Sheba Medical Center, Israel, from March 1, 2009 to July 10, 2010 were reviewed. Patients for whom propranolol therapy had followed other therapeutic modality attempts were excluded. All the children diagnosed as having periocular capillary hemangioma and who were eligible for our study were otherwise healthy. The study complied with the policies of the local institutional review board (IRB) and good clinical practice (GCP) rules.
Data on patient demographics, clinical description of the hemangioma, complete eye examination by a pediatric ophthalmologist, age at initiation of propranolol treatment, dosage, side effects associated with therapy, clinical appearance and refractive status before and after initiation of treatment, and follow-up duration were retrieved from our medical records and analyzed. The threshold for treatment was defined as anisometropic astigmatism of 1.5 diopters (D) or more. Cyclopentolate HCl 10 mg/mL (Colircusi Cicloplejico, Alcon, Spain) was instilled twice with a 10-minute interval for cycloplegic refraction, and all measurements were obtained by the same optometrist (C.S.).
Clinical Intervention
All children were evaluated in our institution by a pediatric cardiologist, who inquired for patient medical history, including sensitivity to medication and presence of asthma or other upper reactive airway disease (presence of any of these would contraindicate propranolol treatment), and performed a thorough physical examination. In addition, the children underwent electrocardiographic and echocardiographic examinations prior to initiation of treatment. Propranolol was given at a loading dose of 1 mg/kg/day (divided into 3 doses given 3 times a day), after which the patients were monitored for heart rate, blood pressure, and blood glucose alterations. Propranolol was then titrated by adding 0.5 mg/kg/day every 3 to 4 days, during which the patients’ heart rate was monitored by a pediatrician in an outpatient clinic setting, until reaching an upper limit of 2 mg/kg/day. Two to 3 weeks thereafter the patients were evaluated by an in-house pediatric cardiologist, performing a physical examination and an electrocardiographic examination and inquiring for any complaints on the patients’ behalf. Further in-house follow-up examinations were performed once a month thereafter.
Results
Four children (1 male) presented to our institution with periocular capillary hemangioma and were treated with propranolol from March 1, 2009 to July 10, 2010. One child was excluded from the study since she had received an 8-month course of systemic steroids for her periocular capillary hemangioma prior to initiation of the propranolol therapy.
The mean age at the initiation of propranolol therapy was 6.3 ± 2.9 months (range: 3.0–8.0 months). Clinical data of the 3 study patients are summarized in the Table . They all received propranolol and displayed a rapid therapeutic effect thereafter, including change of color and decrease in lesion mass. The mean astigmatic error decreased from 2.83 D (range: 2.50 to 3.00 D) prior to propranolol treatment to 1.33 D (range: 1.00 to 2.00 D) after 1 month of treatment. There was a noticeably rapid shift of the astigmatic error after 1 week of treatment for Patients 1 and 2 (from 3.00 D to 1.00 D and 0.75 D, respectively). These refractive errors remained stable at the ensuing follow-up evaluations. The third patient missed the 1-week follow-up examination and was evaluated only after 1 and 3 months. In this patient the astigmatic error shifted from 2.50 D prior to treatment to 2.00 D after 1 month of treatment, and with no further reduction in astigmatism at the 3-month follow-up examination.
| Patient | Gender | Eye | Clinical Appearance | Prior to Propranolol Treatment | Propranolol Treatment | Comments | ||
|---|---|---|---|---|---|---|---|---|
| Cycloplegic Refraction: Involved Eye/Fellow Eye | Age of Initiation (Months) | Cycloplegic Refraction (Time After Initiation): Involved Eye/Fellow Eye | Duration of Treatment (Months) | |||||
| 1 | F | Right | Upper nasal lid causing occlusion of visual axis | +3.00@+3.00 × 60/+6.00 | 3 | +4.00@+1.00 × 60/+6.00 (1 wk, 1 mo, 3 mo) | 6 (ongoing) | Visual axis was open after 1 week of treatment |
| 2 | M | Left | Upper temporal lid | −2.00@+3.00 × 50/N/A | 8 | +0.50@+0.75 × 50 (1 wk)−0.50@+1.00 × 50 (1 mo, 3 mo)/N/A | 4 | |
| 3 | F | Right | Upper nasal lid | −2.50@+2.50 × 70/−1.50@+0.50 × 90 | 8 | −2.00@+2.00 × 80 (1 mo) a −2.00@+2.00 × 75 (3 mo)/−1.50@+0.50 × 90 (1 mo, 3 mo) | 3 (ongoing) | |
a The patient did not show up at 1 week after initiation of treatment, and had cycloplegic refraction measurements only at 1 and 3 months of follow-up.
The mean follow-up duration after initiation of the propranolol treatment was 8.3 ± 6.8 months (range: 4–16 months). There have been no complications during treatment or follow-up.
Report of Cases
Case 1
A 3-month-old child presented to our institution with a diagnosed mobile periocular capillary hemangioma in the upper nasal aspect of the right upper eyelid, causing occlusion of the right eye’s visual axis ( Figure 1 , Top). The refractive error was +3.00@+3.00 D × 60 in the involved eye and +6.00 in the fellow eye. The rest of the ophthalmologic examination was unremarkable. The patient was referred for primary treatment with oral propranolol, with the primary indications being visual axis occlusion together with astigmatic anisometropia. Most of the lesion had been absorbed ( Figure 1 , Bottom), the visual axis was open, and the refractive error was +4.00@+1.00 D × 60 at 1 week after initiation of the treatment. The astigmatic refractive error remained stable at the follow-up examinations at 1 and 3 months after initiation of treatment. There was no change in the refraction of the fellow eye during follow-up. There have been no systemic complications during treatment. Currently, the patient is still receiving propranolol therapy concurrent with amblyopia therapy.
Case 2
An 8-month-old child presented to our institution with a nonoccluding left upper lid hemangioma and no further orbital involvement ( Figure 2 , Top). The refractive error was measured as being −2.00@+3.00 D × 50 in the involved eye. Data regarding the refraction status of the fellow eye could not be obtained. The child was given oral propranolol therapy and a rapid absorbance of the lesion together with decrease in the refractive error to +0.50@+0.75 D × 50 was observable at 1 week following therapy initiation ( Figure 2 , Bottom). The child was kept on propranolol therapy for an additional 4 months with no complications. The astigmatic refractive error remained stable at all follow-up examinations. Currently, the child has been off medication for 11 months, with no evidence of lesion regrowth or change in refractive status.
