Evaluation of intra-lesional corticosteroids in the treatment of peri-ocular haemangioma of infancy: still an alternative besides propranolol
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- Janmohamed, S.R., Madern, G.C., Nieuwenhuis, K. et al. Pediatr Surg Int (2012) 28: 393. doi:10.1007/s00383-011-3037-7
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Haemangioma of infancy (HOI) is the most frequently occurring benign tumour of infancy. Alarming HOI require treatment. Current therapy is empirically based; corticosteroids are often administered but in recent publications propranolol was reported to be more effective. Peri-ocular HOI are highly sensitive to corticosteroids. Our goal was to evaluate the effectiveness of intra-lesional corticosteroids in the treatment of peri-ocular HOI.
We selected all patients with peri-ocular HOI who had only been treated with intra-lesional corticosteroids at our hospital from 1993 until 2009. Treatment was standardized according to a prospective protocol.
A total of n = 34 patients were included. There were no complications at all after therapy. A second intra-lesional injection was necessary in five patients. At follow-up after 6 and 12 months after injection, 94 and 91% of the patients, respectively, had regression of the HOI. Astigmatism, Haemangioma Activity Score and global assessments all had improved after therapy.
This study shows that intra-lesional therapy with corticosteroids is very safe in the treatment of peri-ocular HOI. It remains a good and safe alternative besides propranolol or when propranolol therapy is not possible (e.g. asthma, PHACE syndrome, and certain cardiac diseases).
Haemangioma of infancy (HOI)  is the most common, benign, self-limiting tumour of infancy [2, 3] and therefore needs no treatment . It is commonly located on the face . However, HOI may cause severe complications , generally because of extensive growth or location, leading to (besides psychological problems) life-threatening or disabling complications  (e.g. compression of the airways, heart failure, ulceration and visual problems). Amblyopia or reduced vision in the affected eye, secondary to astigmatism or visual deprivation affects 43–60% of the children with peri-ocular HOI . Of course, such HOI require treatment. However, the current therapy in HOI is empirically based. Systemic or intra-lesional corticosteroid treatment is often administered . Peri-ocular HOI are particularly sensitive to corticosteroids. In recent publications, propranolol [8, 9] was reported to be either more or at least equally effective in treating proliferative HOI. Other alternatives among others are  laser therapy, intravenous vincristine, cyclophosphamide and recombinant interferon alfa  (high risk for adverse events), local/intra-lesional imiquimod, becaplermin (recombinant platelet-derived growth factor) and bleomycin. Apart from waiting for involution or surgical resection, treatment aims at inducing or accelerating the natural involution process . Although there is extensive literature, objective measures of astigmatism and anisometropia before and after treatment are limited. In this article we evaluate the effectiveness of intra-lesional corticosteroids in the treatment of peri-ocular HOI.
Study design and patient selection
Patients with alarming (threatening) peri-ocular HOI who needed treatment, e.g. because they were (at risk of) developing amblyopia, were treated according to a WEVAR protocol including ultrasonography of the peri-ocular region and eye examinations prior to therapy. These eye examinations (cycloplegic refractions of both eyes) were also protocolized and performed by a paediatric ophthalmologist. Patients received one drop of a solution containing 2.5% phenylephrine and 0.5% tropicamide in each eye. After 15–20 min this was repeated. The examination started 15–20 min after the second drops were administered to the patients. Spherical and cylindrical abnormalities were assessed using skiascopy. All patients were awake during the eye examinations.
Inclusion and exclusion criteria
All of the patients with alarming peri-ocular HOI (i.e. the eye was at risk because of such threatening HOI) who were treated with intra-lesional corticosteroids from 1993 until 2009 were included in this study. Patients who were treated with both systemic and intra-lesional corticosteroids were excluded, as were patients with HOI at another location than peri-ocular. Patients with intra-orbital HOI are not treated with intra-lesional therapy. Data was obtained by investigating the patients’ medical dossiers. Photographs that had been taken were assessed.
The effect of treatment was evaluated by the Haemangioma Activity Score (HAS) . This scoring system focuses on the (disease) proliferative activity of a HOI at a certain time point. Scores at multiple time points of one HOI in one patient can be compared with each other.
HAS before and after treatment was calculated at t = 0, 6 and 12 months from the photographs. We searched all patients’ medical dossiers for complications. The global assessments at the check-ups on the size of the HOI were collected as were the ophthalmic measurements made by the ophthalmologist.
SPSS version 15.0.0 was used for the database and statistical measures. Differences in astigmatism, in matters of refractive cylindrical value, and HAS between the three time points were assessed using Friedman’s test.
Demographics and baseline characteristics of n = 34 patients with peri-ocular HOI treated only with intra-lesional therapy
Rx/intra-lesional corticosteroids (n = 34)
Gestational age (%)
>37 weeks: 82
Median age of development of HOI
0.4 months (10th percentile = 0.0; 90th percentile = 1.75)
Median number of HOI per patient
1 (10th percentile = 1; 90th percentile = 4)
Size of HOI (assessed by ultrasonography) (%)
<3 cm: 71
3–10 cm: 26
>10 cm: 3
Median age at start intra-lesional therapy
3.8 months (10th percentile = 2; 90th percentile = 9)
Outcomes of intra-lesional corticosteroid therapy in n = 34 patients with alarming peri-ocular haemangioma of infancy (HOI) at t = 0 (baseline, just before intra-lesional therapy), 6 and 12 (6 and 12 months after injection)
t = 0
t = 6 months
t = 12 months
3.0 (SD 1.3)
2.1 (SD 0.9)
1.6 (SD 0.7)*
Refraction: mean astigmatism (diopters)
2.57 (SD 1.49)
1.84 (SD 1.01)
1.44 (SD 1.26)**
Occlusion therapy (for amblyopia) (%)
Therapy effect (evaluation by the doctor) (%)
Plastic surgery required until 2009? (%)
This study showed that intra-lesional therapy with corticosteroids is a very safe alternative in the treatment of (peri-ocular) HOI as no complications were observed by us. HAS, eye examinations, and clinical appearance all improved after intra-lesional therapy. Since HOI is a self-limiting tumour, the expectation is that HAS and clinical appearance would eventually improve, but we were able to demonstrate that when an eye is at risk of visual impairment, intra-lesional therapy is highly effective: all eye examinations (especially cylindrical abnormalities) improved after treatment.
In 9% of our cases, plastic surgery was indicated in a later stage. However, this did not mean that intra-lesional therapy was not effective. The HOI did regress faster. We think that without the intra-lesional therapy or with another therapy, a scar would have eventually developed that required plastic surgery. It is possible that this percentage may have been higher because some patients could have gone to another hospital or may require plastic surgery in the future.
Our results of the treatment with intra-lesional corticosteroids for peri-ocular HOI are excellent with a success rate of 85% after one injection and 100% after two injections, without any adverse events. These percentages are somewhat higher than those reported in the literature. 50% of HOI respond after therapy with corticosteroids, peri-ocular HOI are more sensitive, with rates up to 64% [10, 14, 15]. These differences are probably attributed to other measures of effect and success. Often, the amount of corticosteroids that were administered in those cases is also difficult to establish. We treated all patients in a standardized manner.
Furthermore, female to male ratio is slightly high in our study, but agrees with the reported findings that HOI is more common in girls . We also observed that most patients had a small (<3 cm) HOI.
Advantages and disadvantages of intra-lesional corticosteroid treatment and propranolol treatment of peri-ocular haemangioma of infancy (HOI)
Often just one injection, instead of long-term administration of medicine
Seems to work at least as good as intra-lesional corticosteroids without the side effects of intra-lesional therapy
Good response on peri-ocular HOI
A lot of experience with this therapy: not many side effects
Can be given when propranolol fails, or in PHACE syndrome
Anaesthesia is recommended to minimize side effects
Other HOI than peri-ocular have a success rate of only 50%
Side effects have not yet been properly investigated at this age (watch out: do not give in patients with PHACE. Several published case reports with hypoglycaemia). Blue coloured hands and feet
1 day hospitalization, limited ultrasound evaluation
1 day hospitalization, expensive multiple ultrasound pre-treatment evaluation
Sometimes the therapy has to be repeated later on (with another narcosis)
Doses and duration of therapy is still unknown. Additional investigations are necessary
When administered by non-experienced physicians: retinal occlusion/optic nerve compression is a rare complication
Contra-indicated in vascular malformations of internal organs and PHACE syndrome 
Conflicts of interest
The authors declare that they have no conflict of interest.
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