Child’s Treatment-Refractory Hemangioma Threatens His Vision

Child’s Treatment-Refractory Hemangioma Threatens His Vision

July 18, 2022 0 By Jennifer Walker

What could be done to prevent loss of vision in this young child with a lazy left eye, associated with a persistent hemangioma on his left cheek? That’s the challenge described by Catherine Y. Liu, MD, PhD, of Shiley Eye Institute at the University of California San Diego, and colleagues in JAMA Ophthalmology.

The 3-year-old boy presented to the clinic with his parents, who were concerned that in addition to the persistent lesion on his cheek and left eye socket, his left eye was protruding and turned inwards and upwards. Clinicians noted that the boy had dense amblyopia, large-angle monocular esotropia and hypertropia, and proptosis of the left eye. On assessment, they found that his left eye was unable to abduct beyond the midline.

An MRI series revealed the presence of persistent orbital involvement causing medial displacement of the lateral rectus muscle and mass effect on the globe.

His parents explained that a flat, pink macule had been present on his left cheek at birth, and it had become raised and increasingly discolored over the following 3 to 4 weeks. The patient’s medical history included diagnosis of a capillary hemangioma on his left cheek. At 1 month of age, he had been started on treatment with propranolol and received increasing dosages as the size of the lesion continued to increase.

This was followed by a trial of topical timolol, with no response to treatment. Oral prednisolone was effective in reducing the size of the hemangioma, but treatment was not well-tolerated and was discontinued.

Ophthalmic assessment at another hospital revealed anisohypermetropia, greater on the left, as well as a left esotropia and hypertropia, raising concerns of amblyopia.

MRI findings included an orbital mass surrounding the left lateral rectus muscle with mass effect on the globe and extension into the eyelid, pterygopalatine fossa, and cheek. In an effort to address potential development of amblyopia, two embolization and debulking procedures were performed on the affected areas of the cheek and eye socket. Pathology findings were positive for glucose transporter 1. Unfortunately, the second procedure was followed by abrupt worsening of the eye’s inward turn.

Various treatment options could be considered in this case, including another trial of oral prednisolone, radiological embolization and debulking of the lesion, pulsed dye laser therapy, and oral sirolimus.

The child’s poor tolerance of oral steroid therapy precluded that option, and lack of response to the embolization and debulking made that option less than ideal.

Pulse dye laser therapy, which is often used as an adjunctive treatment, provides the best results when used for superficial lesions less than 1.3-mm deep.

Clinicians decided on a trial of sirolimus, an emerging treatment for vascular tumors and malformations that demonstrated efficacy and safety in treating complicated vascular anomalies in a phase II clinical trial, and effectiveness in infantile hemangiomas that are resistant to alternative therapies.

After 3 months of treatment, the patient’s left eye abduction had improved by 50%, the hypertropia and proptosis were also reduced, and his cheek mass had softened.

After 4 months of treatment, MRI confirmed a decrease in the size and enhancement of the lesion’s cheek and orbital components. The patient was prescribed eyeglasses with full cycloplegic refraction; his right eye was kept covered. Ongoing treatment with sirolimus and propranolol continues to be well tolerated.

Discussion

Clinicians reported this case to raise clinicians’ awareness of sirolimus as a treatment option to consider for persistent, unresectable vascular anomalies such as infantile hemangioma. As an mTOR inhibitor, sirolimus produces antiangiogenic effects by regulating mechanisms that drive cellular growth and proliferation in hemangiomas, authors explained.

Infantile hemangioma is a benign vascular tumor occurring in 5% of infants worldwide, the group noted. Typically, the endothelial cells proliferate rapidly in the first 3 months of life and then shrink gradually when growth is completed, which occurs by 5 months of age in most cases.

Their rapid clinical course and glucose transporter 1 positivity differentiates infantile hemangiomas from other vascular tumors, Liu’s group noted. While surveillance is all that is needed in many cases, they added, medical treatment is recommended when the eyelid or orbit is involved, with risk for “visually significant ptosis, strabismus, astigmatism, and amblyopia.”

The guideline-recommended first-line therapy for problematic infantile hemangiomas, propranolol, is thought to have its effect by constricting blood vessels and slowing angiogenic growth, case authors noted. According to a meta-analysis by the American Academy of Pediatrics, propranolol treatment of infantile hemangiomas had a mean clearance rate of 95%.

For those hemangiomas that are unresponsive or intolerant to propranolol, clinicians should consider steroids, previously considered the criterion standard, case authors noted.

Prednisolone or prednisone can be administered orally or via intralesional injection for well-localized lesions, they wrote, while cautioning that these are associated with potential adverse effects such as growth retardation, mood changes, and development of Cushingoid features.

Embolization and debulking is generally used for treatment of children at age 3 to 4 years, when most infantile hemangiomas are no longer involute, but the procedures may be considered for younger patients with hemangiomas that obstruct vital structures, such as the orbit.

Case authors noted that adverse effects associated with sirolimus at levels used for treating hemangioma include:

  • Bone marrow suppression (27%)
  • Mucositis (10%)
  • Hypercholesterolemia (3%)
  • Elevated liver enzymes (3%)

Thus, they recommended that clinicians should monitor patients’ comprehensive metabolic panel and hematology during treatment. Clinicians should be aware that sirolimus is a possible treatment option for persistent vascular anomalies such as infantile hemangioma, authors concluded.

Disclosures

Liu reported a research grant from Horizon Therapeutics.