Middle East African Journal of Ophthalmology

: 2021  |  Volume : 28  |  Issue : 1  |  Page : 6--10

Effect of oral propranolol on periocular infantile capillary hemangioma: Outcomes based on extent of involvement

Kavya M Bejjanki, Kahkashan Akhtar, Arushi P Gupta, Swathi Kaliki 
 Ocular Oncology Serices, The Operation Eyesight Universal Institute for Eye Cancer, L V Prasad Eye Institute, Hyderabad, India

Correspondence Address:
Dr. Swathi Kaliki
The Operation Eyesight Universal Institute for Eye Cancer, L V Prasad Eye Institute, Hyderabad - 500 034, Telangana


PURPOSE: To evaluate the efficacy of oral propranolol in the treatment of periocular infantile capillary hemangioma (CHI) based on the involvement of embryological facial placodes and their extent of anatomical involvement. METHODS: Retrospective study of 27 patients. RESULTS: The mean age at the presentation of periocular CHI was 4 months (median, 3 months; range, <1–14 months). There were 11 (41%) males and 16 (59%) females. Based on embryological facial placodes, the involvement was focal in 16 (59%) cases and segmental in 11 (41%) cases. Based on the anatomical distribution, the lesions were preseptal in 4 (15%), postseptal in 13 (48%), and combined in 10 (37%) cases. The duration of use of oral propranolol was 10 months (median, 10 months; range, 4–16 months). Overall, the mean % resolution of periocular CHI was 78% (median, 90%; range, 20%–100%). The mean percentage resolution of focal lesions was 69% (median, 83%; range, 20%–100%), and segmental lesions were 92% (median, 95%; range, 70%–100%). The mean percentage resolution of preseptal component of lesions was 94% (median, 95%; range, 80%–100%) and postseptal component was 74% (median, 85%; range, 20%–100%) over a mean follow-up period of 16 months (median, 15 months; range, 4–37 months). Four (15%) patients exhibited flare-up of lesion after tapering oral propranolol. CONCLUSION: Oral propranolol is effective in the treatment of periocular CHI. Segmental and preseptal lesions respond better to the treatment compared to focal and postseptal lesions.

How to cite this article:
Bejjanki KM, Akhtar K, Gupta AP, Kaliki S. Effect of oral propranolol on periocular infantile capillary hemangioma: Outcomes based on extent of involvement.Middle East Afr J Ophthalmol 2021;28:6-10

How to cite this URL:
Bejjanki KM, Akhtar K, Gupta AP, Kaliki S. Effect of oral propranolol on periocular infantile capillary hemangioma: Outcomes based on extent of involvement. Middle East Afr J Ophthalmol [serial online] 2021 [cited 2022 Nov 28 ];28:6-10
Available from: http://www.meajo.org/text.asp?2021/28/1/6/315317

Full Text


Infantile capillary hemangiomas (CHI) are common benign vascular tumors of the periocular region in children and are seen in 5%–10% of children.[1] They classically present with an intense proliferative phase followed by spontaneous involution.[2] Hence, close observation is indicated in the uncomplicated cases. However, periocular CHI can infiltrate the soft tissues, resulting in significant functional and cosmetic deformity and can be potentially vision-threatening.[3]

An array of treatment possibilities is popularized for CHI with oral propranolol, a nonselective beta-blocker being introduced into the armamentarium in 2008.[4] The efficacy of this drug on CHI is substantiated in the subsequent studies.[5] The understanding of CHI continues to evolve rapidly with the recognition of subtypes in relation to embryological placodes and anatomical subtypes. Herein, we analyzed the children who received oral propranolol for the management of CHI in the periocular region to assess the efficacy of this compound in relation to demographics, perinatal factors, embryological phenotype, and anatomical subtypes.


This is a retrospective study conducted at the Operation Eyesight Universal Institute for Eye Cancer, L V Prasad Eye Institute, Hyderabad, India. Institutional review board approval was obtained for the study. The medical records of 27 patients with periocular CHI treated with oral propranolol were reviewed. The study period ranged from May 2013 to May 2018. Those with inadequate data or those who were noncomplaint to treatment were excluded from the study. Those with adequate data and known outcome after treatment with oral propranolol were included in the study.

The demographic details (age and gender) and perinatal factors (birth weight and gestational age) were reviewed. All the children underwent a comprehensive eye examination including cycloplegic refraction and dilated fundus evaluation using indirect ophthalmoscopy before the initiation of treatment. The recorded clinical features included presenting complaints, duration of symptoms (months), location, and extent of hemangioma. Photographic documentation (done in each follow-up visit) and imaging (computed tomography/magnetic resonance imaging of the orbit) of all children were reviewed. Based on the anatomical location, the lesions were classified into preseptal hemangioma, postseptal hemangiomas, and combined (both preseptal and postseptal hemangiomas) and based on the pattern of distribution in relation to embryological placodes, they were classified as focal (discrete hemangiomas occur along the lines of fusion between embryological facial placodes) and segmental (large plaque-like hemangiomas overlying individual or multiple facial placodes) [Figure 1] and [Figure 2].{Figure 1}{Figure 2}

Comprehensive assessment of systemic condition, including cardiovascular and respiratory status, was performed for all children before the initiation of the treatment. All children were also examined to rule out any systemic associations such as PHACE (posterior fossa anomalies, hemangioma, arterial anomalies, cardiac anomalies, and eye anomalies) syndrome, Kasabach-Merritt syndrome. All children received oral propranolol after obtaining medical clearance from the physician. The tablet form of propranalol was used. Parents were directed to administer the medication as oral suspension by mixing the powdered tablet in water or milk. Patients were started on 1 mg per kg body weight dose initially followed by escalating to 2 mg per kg body weight dose after 1 week if there were no unfavorable side effects to the primary dose. Each patient was reviewed after 1 week and then at 1 month, 3 months, 6 months, and 1 year. The children were also asked to review every fortnight with pediatrician locally to monitor any adverse events to the drug during the course of treatment. Children showing a significant decrease (clearance of the visual axis and/or correction of refractive error) or complete resolution of the lesion clinically and/or radiologically were advised to taper oral propranolol over a period of 3 months and then stop the medication subsequently. The response to oral propranolol was also analyzed in relation to the percentage of decrease in the size of the lesion (excellent, >90%; good, 75% to 90%; fair, 50% to 75%; poor <50%) based on serial photographs and orbital imaging in cases with orbital extension of the lesion. All patients were monitored for the change in visual acuity or any signs of amblyopia. The vision was recorded by assessing if the child is able to fix and follow light (if child was <6 months of age), Teller Acuity Charts (if the age is 7 months to 3 years) or Kay picture charts or Snellen's visual acuity charts (if the child is >3 years of age). Cycloplegic retinoscopy was repeated during each visit. Anisometropic amblyopia was defined as the difference in refraction between both eyes of more than 1.5D. Amblyopia treatment was initiated accordingly.


The present study included 27 children with periocular CHI including 16 (59%) females and 11 (41%) males. The mean age at the presentation of patients with CHI was 4 months (median, 3 months; range, <1–14 months). Infants with low-birth weight were 19% (n = 5), both preterm and low-birth weight were 15% (n = 4), normal birth weight and full-term babies were 67% (n = 18). There was no history of parental consanguinity. There was no history of atopic allergy or bronchial asthma or eczema in any patient. One child had tetralogy of Fallot and cardiologist clearance was obtained before initiation of oral propranolol. None of them had systemic associations such as PHACE syndrome or Kasabach-Merritt syndrome.

Of the 27 patients, 23 (85%) patients had ptosis, 3 (11%) had proptosis, and 1 (4%) had both proptosis and ptosis. The lesion was focal in 16 (59%) and segmental in 11 (41%) patients. Based on the anatomical distribution, the lesions were preseptal in 4 (15%), postseptal in 13 (48%), and combined in 10 (37%) cases. Vision-threatening ptosis (n = 19, 70%) was the most common indication for the treatment. The other indications included cosmetic blemish (n = 4, 15%), rapidly growing lesion (n = 2, 7%), and amblyopia (n = 2, 7%).

All low-birth weight and/or preterm children (n = 8, 89%) had excellent response to oral propranolol except one (11%) low-birth weight child with the focal pattern of lesion distribution and deeper component who had a poor response to treatment. In full-term children with normal birth weight (n = 18), excellent response was seen in 8 (44%), good response in 4 (22%), and fair to poor response in 6 (33%) patients. All patients with fair to poor response were associated with the focal pattern of lesion distribution and had postseptal lesions.

Of the 11 patients with segmental involvement of hemangioma with the lesion overlying multiple facial placodes, 9 (82%) patients had excellent response, 2 (18%) had good response, and none of them showed fair or poor response [Figure 3]. Of the 16 lesions with focal involvement of hemangioma along the lines of fusion between embryological facial placodes, 6 (38%) had excellent response, 4 (25%) had good response, 3 (19%) had fair response, and 3 (19%) patients had poor response. In the group of patients showing an excellent to good response to treatment, the average duration of the treatment required for focal lesions was 9 months and for segmental lesions was 14 months. All preseptal lesions (n = 4, 100%) had excellent response to oral propranolol. Of the 13 postseptal lesions, 6 (46%) had excellent response, 2 (15%) had good response, 2 (15%) had fair response, and 3 (23%) had poor response. Of the 10 patients with combined lesions, 5 (50%) had excellent response, 2 (20%) had good response, 2 (20%) had fair response, and one (10%) had poor response. The child with poor response had excellent resolution of preseptal component and poor response of postseptal component. Overall, the mean % resolution of preseptal component of lesions was 94% (median, 95%; range, 80%–100%) and postseptal component was 74% (median, 85%; range, 20%–100%) over a mean follow-up period of 16 months (median, 15 months; range, 4–37 months). Four (15%) patients exhibited flare-up of the lesion after tapering oral propranolol, necessitating restarting of treatment in two patients. The other two patients had mild flare-up, not threatening vision, which resolved spontaneously on close observation.{Figure 3}

Anisometric amblyopia was noted in 10 (37%) children, 8 with eyelid component, and 2 with deep orbital component. After the pupillary axis was cleared during the course of treatment, amblyopia was managed by patching the normal eye for 2 hours/day in all ten patients, resulting in the recovery of vision after 3 months of oral propranolol. None of the patients developed side effects of oral propranolol during the treatment.


Infantile CHI is a common vascular lesion affecting 10% of children below 1 year of age.[6] CHI is 2–5 times more common in females compared to males and is also common in preterm babies.[6] In our study, 59% were females and 15% were preterm infants. The mean age at the presentation of CHI was 4 months in our study.

Children with CHI typically display rapid proliferation of the lesion over a period of time (proliferative phase) followed by spontaneous regression (involution phase) in the first decade. Treatment for ICH is recommended for lesions causing adverse consequences locally.[6],[7] The lesions could be small and asymptomatic or large and disfiguring, causing ocular morbidity.[8],[9] The most common indication of oral propranolol in this study was vision-threatening ptosis (89%). Periocular CHI can cause amblyopia in 43%–60% of cases.[6] In this study, amblyopia was noted in 37% children. With the increasing size of the lesion, the risk of complications including ptosis, visual axis obstruction, and astigmatic errors increase causing amblyopia. Amblyopia can also occur secondary to the direct mechanical effect of lesion on the extraocular muscles and strabismus.[10],[11] Apart from the functional impairment, these lesions can cause significant cosmetic deformity. In orbitopalpebral CHI, it is important to treat the infants early to prevent subsequent consequences of the disease, especially amblyopia.[12],[13]

The various treatment options of CHI include oral and topical propranolol, corticosteroids, immunomodulators (interferon and vincristine), sclerosants (bleomycin), embolization, CO2 laser, and surgical excision.[14],[15] Until recently, corticosteroids were used as the first line of management, but various adverse reactions have been reported with its usage, particularly in infants. Immunomodulators were found to be associated with neurologic toxicity.[14] Currently, oral propranolol is the first-line management of ICH since its introduction in 2008.[4]

In our study, oral propranolol displayed excellent to good response in nearly 80% of children. Based on our study, we noted that perinatal factors, the pattern of arrangement of lesion in relation to embryological facial placodes, and anatomical location of the lesion influence the treatment outcome. Excellent to good response to oral propranolol was noted in children with a history of low birth weight and preterm delivery, those with segmental hemangioma involving multiple facial placodes and with the superficial location of the lesion.

Low birth weight and preterm delivery are considered as the predisposing factors for the development of CHI. However, the association of these peri-natal factors with oral propranolol has not been reported in the literature. In this study, excellent to good response was seen in all patients with a history of low birth weight and preterm delivery except one patient who had a poor response. When the other associated factors were studied for these children, it was found that all the children with low birth weight and preterm delivery had the segmental pattern of arrangement of CHI except one with poor response who had the focal pattern of distribution of lesion. In the segmental pattern of distribution, the deposition of hemangioma precursor cells occurs as an earlier event.[16] The infants with low birth weight and preterm delivery are more predisposed for the segmental pattern of distribution of these lesions.

Waner et al. described the pattern of distribution of facial infantile hemangiomas, as focal type and diffuse or segmental type based on their relation to the fusion of embryonic sutures.[10] In our study, there were 16 (59%) focal lesions and 11 (41%) segmental lesions, and all (100%) segmental lesions showed excellent to good response to oral propranolol. As the segmental lesions develop in relation to neuromesenchyme,[17] it can be postulated that the angioblasts involved may contain more beta receptors in comparison to that of focal lesions. It can also be explained by the fact that the drug is more concentrated in the segmental pattern of the lesion because of a larger area of involvement. The effect of oral propranolol on angioblasts of segmental placodes is thus more efficacious. Although a better response rate was noted in patients with segmental lesions, they required longer duration of treatment compared to focal lesions.

Preseptal lesions are intensely red in color (strawberry-like). Postseptal is not associated with any skin discoloration, while the combined lesions including both deep and superficial tumors are dark blue or purple in color and involve both pre-and postseptal tissues.[11] In our case series, 15% patients had superficial lesions, 48% had deep lesions, and 37% had combined lesions. The preseptal component of hemangiomas showed a better response to oral propranolol compared to postseptal component (mean percentage reduction of the lesion was 94% vs. 74%, respectively). This can be postulated by the rich vascular supply of preseptal component of the lesion resulting in increased availability of the drug.

In our study, the mean age at presentation to the clinic was 4 months of age which is the crucial age for the development of the sensory function of vision thus increasing the risk of amblyopia.[12],[13] CHI in the palpebral and orbital region can cause anisometropia.[18] Stigmar et al. found an increased risk of anisometropia with deeper lesions, whereas Schwartz et al. noted an increased risk of refractive error with lesions >1 cm.[11] In our study, all children had lesions >1 cm in maximal tumor diameter and astigmatism was noted in 8 children with preseptal involvement and 2 with postseptal lesions. In all these cases with astigmatism, the refractive error resolved within 3 months of starting oral propranolol therapy, which was comparable to previous studies.[19],[20]

Beta-blockers have been used safely in infants and children for various other conditions, with no reports of associated death or severe cardiovascular morbidity. None of the patients in our study displayed any significant side effects of oral propranolol.


The limitations of the study included the retrospective nature of the study and a small sample size. In conclusion, our study results are encouraging with the excellent response of oral propranolol, especially in lesions with segmental involvement, lesions involving preseptal tissue planes, and in infants having a history of low birth weight and preterm delivery. Oral propranolol provides promising results with a good safety profile. Amblyopia management should be provided along with the treatment of oral propranolol when indicated.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient (s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initial s will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

This study was financially supported by the Operation Eyesight Universal Institute for Eye Cancer (SK) and Hyderabad Eye Research Foundation (SK), Hyderabad, India. The funders had no role in the preparation, review, or approval of the manuscript.

Conflicts of interest

There are no conflicts of interest.


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