Treatment of Deep Orbital Hemangiomas of Infancy: Title and subTitle BreakAn Overview

Hemangiomas are the most common benign tumors of infancy and the most common tumors of the orbit and eyelid in childhood. In one series, hemangiomas accounted for 1% of all biopsy specimens of orbital lesions in all age groups and 4% of all biopsy specimens of orbital lesions in children. ^{Article - Article} Ophthalmic terminology often referred to periorbital hemangiomas as capillary hemangiomas; however, current medical literature classifies hemangiomas as superficial, deep, and compound. For periorbital tumors, superficial hemangiomas are anterior to the orbital septum, deep hemangiomas are posterior to the orbital septum and often cause a mass effect, and compound hemangiomas have both a deep and a superficial component. This article reviews the treatment of pediatric deep orbital hemangiomas.

Hemangiomas are benign hamartomatous growths composed of proliferating capillary units and endothelial hyperplasia. They are differentiated from vascular malformations, which are nonproliferating clusters of ectatic aberrant vessels or lymphatic vessels that show normal endothelial turnover. ^Article Hemangiomas typically have a characteristic proliferative phase, a plateau phase, and an involutional phase. Functional and cosmetic sequelae often persist after involution and include both ophthalmic and dermatologic complications.

Haik et al ^Article reported on 101 pediatric periorbital hemangiomas and found that 95% of patients were younger than 6 months and that the female-male patient ratio was 3:2. There was a predominance of upper eyelid and superior orbit involvement, with 75% of patients having orbital signs.

Deep orbital hemangiomas generally are manifested as compressible, fluctuant masses in the eyelids. They are typically unilateral and painless and have a blue-purple tone ( Article ). If the hemangioma is compound, the epidermis has characteristic red vascular channels. Orbital hemangiomas deep in the orbit may not demonstrate eyelid signs. Deep orbital hemangiomas can also mimic other malignant pediatric tumors, including teratoma, lymphangioma, rhabdomyosarcoma, metastatic neuroblastoma, and granulocytic sarcoma. Age at onset, association with other clinical findings, and imaging help to differentiate hemangiomas from other orbital diseases.

B-scan ultrasonograms typically demonstrate an irregularly shaped orbital mass with heterogeneous internal echoes. On computed tomographic scans, hemangiomas appear as well-defined to infiltrating masses with moderate to marked enhancement with contrast medium ( Article ). At magnetic resonance imaging, hemangiomas produce a heterogeneous signal that is hyperintense to muscle and hypointense to fat on T1-weighted images. T2-weighted images produce a heterogeneous signal with areas of both high and low intensity. Gadolinium administration yields diffuse heterogeneous enhancement that is best demonstrated with the fat-suppression algorithm. ^Article

The decision to treat pediatric deep orbital tumors depends on functional and cosmetic factors. Amblyopia is a reduction in the quality of central vision in one or both eyes and results from a disturbance in retinal image formation duringthe first 10 years of life. Hemangiomas can result in amblyopia by induced astigmatism, strabismus, or occlusion of the visual axis. Abnormal visual input caused by induced astigmatism, strabismus, or stimulus deprivation during the critical period of visual system development can result in decreased vision in one or both eyes.

Astigmatism, a defect in vision caused by unequal curvature of one or more refractive surfaces of the eye, can result from an expanding hemangioma causing direct globe deformity. Article shows a hemangioma involving the left upper eyelid with associated astigmatism of the left eye. The astigmatism is thought to be secondary to the hemangioma's direct mechanical effect on the globe. This resulted in unequal curvature of the cornea and associated decreased vision in the affected eye. Strabismus is defined as ocular misalignment. Strabismus can occur with extraocular muscle involvement by the hemangioma. Deprivational amblyopia occurs when there is occlusion of the visual axis. This can result from mechanical ptosis induced by a hemangioma or by direct obscuration of the visual axis by an enlarging hemangioma. In addition to inducing astigmatism, the hemangioma shown in Article demonstrates obscuration of the visual axis. Article shows mechanical ptosis of the left upper eyelid secondary to an orbital hemangioma. Article shows obscuration of the visual axis that can result in severe amblyopia. Other rare ophthalmic indications for treatment include compressive optic neuropathy, significant orbital and ocular dystopia, and corneal exposure secondary to axial globe displacement. ^Article Article shows left axial globe displacement without corneal decompensation secondary to deep orbital hemangioma. Orbital hemangiomas should be treated if there are ophthalmic complications or when a child's self-image is compromised by a disfiguring lesion.

Hemangiomas show a variable trend toward involution. Observation remains a valuable tool in the management of deep orbital hemangiomas. If there are no signs of visual compromise, reevaluation every 4 to 6 weeks is recommended. There may be systemic indications for treatment in the absence of ophthalmic complications.

In addition to treating the hemangioma, amblyopia therapy should be initiated when decreased vision in one eye is suspected. This usually involves optical correction with spectacles and patching of the unaffected eye.

Systemic, intralesional, and topical routes of corticosteroid administration can accelerate the involutional process of hemangiomas. Proposed mechanisms of action include the ability to increase vascular sensitivity to systemic vasoconstricting agents, production of antianabolic effects on immature vascular tissue, and inhibition of angiogenesis. ^{Article - Article}

Zarem and Edgerton ^Article demonstrated the effect of oral corticosteroid therapy on hemangiomas. The most common recommended oral corticosteroid dose is 1.5 to 2.5 mg/kg given over 2 to 4 weeks with titration downward depending on response. ^Article Most lesions show dramatic reduction in the first 2 weeks. Potential complications from systemic administration of corticosteroids include increased frequency of infections, cushingoid facies, failure to thrive, adrenal gland suppression, increased appetite, and irritability. ^{Article - Article}

Intralesional corticosteroid injections are commonly used in the treatment of deep orbital hemangiomas. This treatment was popularized by Kushner in 1982 as a viable alternative to systemic administration of corticosteroids. Although the amount and type of corticosteroid used varies among series, most authors prefer 1 to 2 mL of a 50:50 mixture of betamethasone sodium phosphate, 6 mg/mL, and triamcinolone acetate, 40 mg/mL, injected into the hemangioma. ^Article Computed tomography and ultrasonography can be used to help guide injections into deep orbital hemangiomas. ^Article Most deep orbital hemangiomas respond favorably after a single injection, and shrinkage of the tumor occurs most rapidly during the first 2 weeks. Most often the reduction is moderate; however, dramatic reduction with almost total disappearance of the lesion can occur. If there is suboptimal reduction of the hemangioma, repeated injections can be given 3 to 4 times with 4 to 6 weeks between injections. Complications of intralesional injection of corticosteroids include eyelid necrosis, eyelid depigmentation, linear fat atrophy, adrenal gland suppression, failure to thrive, and growth retardation. A devastating complication of intralesional corticosteroid injection into periorbital hemangiomas is central retinal artery occlusion. This results from retrograde travel of corticosteroid deposit in the ocular circulation. Indirect ophthalmoscopy is recommended for all periorbital injections. If a central artery occlusion occurs, a lateral canthotomy may relieve the pressure that caused intravascular retrograde flow, and anterior chamber aspiration may enable the embolus to travel to a more peripheral vessel. Carbon dioxide inhalation may dilate the blood vessels and also enable the embolus to move to a more peripheral vessel. ^Article

Topical corticosteroid agents have been used in the treatment of eyelid hemangiomas. Studies have shown that, although there was a measurable decrease in the size of the hemangiomas, there was a slower response to treatment. ^{Article - Article} This treatment method would be considered only in the setting of compound hemangioma with a significant portion of the hemangioma anterior to the orbital septum. Because of the slower rate of response to topical corticosteroid agents, rarely would they be used to treat amblyopia. Topical steroid treatment would not be considered for deep orbital hemangiomas.

Interferon alfa has infrequently been used to treat vision-threatening deep hemangiomas of the orbit. Interferon alfa has been shown to inhibit angiogenesis. Ezekowitz et al ^Article showed a slow but positive reduction response to interferon alfa-2a. Hastings et al ^Article demonstrated effective reduction in hemangiomas treated with recombinant interferon alfa-2b; however, one third of the treated patients had residual amblyopia. Reported adverse effects of interferon alfa therapy include elevation of liver enzyme concentrations, low-grade fever, neurotoxicity, retinal vasculopathy, motor developmental disturbance, and spastic diplegia. ^{Article - Article} Spastic diplegia is particularly worrisome because it can be potentially irreversible. When interferon alfa is administered, neurologic status should be carefully monitored. Despite positive clinical results, treatment of deep orbital hemangiomas with interferon alfa should be reserved for life-threatening or sight-threatening lesions unresponsive to other treatments, including corticosteroid therapy and excision.

Several medical lasers that demonstrate vascular specificity have been used to treat hemangiomas. The pulsed-dye laser is considered the most effective laser for treating superficial periorbital hemangiomas because it does not cause epidermal damage. However, because of its minimal depth of penetration (1-2 mm), deep orbital hemangiomas do not benefit from pulsed-dye laser therapy. ^Article Despite early intervention, pulsed-dye laser therapy may not prevent the proliferative growth of compound hemangiomas. ^Article Although the superficial component of a compound hemangioma may benefit from pulsed-dye laser therapy, the deeper orbital component is usually managed with corticosteroid agents or excision.

Excision of deep orbital hemangiomas is a viable treatment option in selected clinical circumstances, including significant threat to vision with failure to respond to oral or intralesional corticosteroid therapy, rebound during corticosteroid withdrawal, serious adverse reactions to corticosteroid agents, and severe proptosis. A lesion that is well defined and isolated that causes functional deficits can effectively be treated with excision. ^Article Article shows a hemangioma that is anterior, well defined, and isolated, which makes it a good candidate for excision. Careful preoperative imaging, meticulous surgical technique, and careful avoidance of critical orbital structures can result in successful management of orbital hemangiomas. Surgical technique involves a transconjunctival approach or incision in the natural eyelid crease. Both sharp and blunt dissection are used to isolate the hemangioma, with care to avoid entry into the lobular portion of the tumor. Feeding vessels are gently cauterized, and extreme care is used to prevent damage to normal orbital structures. Surgical debulking with injection of a corticosteroid under direct visualization is a valuable option when complete removal cannot be achieved. Several studies have reported good surgical outcomes with no recurrences, resolution of astigmatism, and good postoperative cosmesis. ^{Article - Article} Excision is not appropriate for all hemangiomas of the orbit, for example, lesions with large areas of cutaneous involvement with extension into the dermis. Complications of excision of hemangiomas with large areas of skin involvement include skin necrosis and wound dehiscence. ^{Article - Article}

There are many options for treatment of deep orbital hemangiomas of infancy including observation, pharmacologic therapy, radiotherapy, and excision. It is important for the practitioner to understand both functional and cosmetic indications for treatment. The risks and benefits of each treatment must be carefully reviewed. Because the natural history of deep orbital hemangiomas of infancy is variable, therapy should be individualized for each patient.

Correspondence: Vikram D. Durairaj, MD, Department of Ophthalmology, Oculoplastic and Orbital Surgery, Rocky Mountain Lions Eye Institute, 1675 N Ursula St, Campus Box F-731, PO Box 6510, Aurora, CO 80045-0510 (vikram.durairaj@uchsc.edu).

Accepted for Publication: November 7, 2005.