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HPI
This is a 3-month-old female born at 40w3d whose parents noted a lesion growing above the right eyelid at around 11 days of age. Found that it was red/pink in color and without any ulceration or bleeding. The lesion continued to grow causing a mechanical ptosis and prompting her to be evaluated by her dermatologist. She was diagnosed with an infantile hemangioma and presents to your clinic for ophthalmic evaluation.

Past Ocular History
None

Ocular Medications
None

Past Medical History
40-week gestation, normal vaginal delivery, no complications

Surgical History
None

Past Family Ocular History
No history of eye disease, blindness, eye tumors/malignancy

Social History
Lives with mom and dad at home. No siblings. Mother denies smoking, alcohol, recreational drug use during pregnancy.

Medications
PO Propranolol 2 mg/kg/day

Allergies
None

ROS
As per HPI, otherwise negative

Ocular Exam

Visual Acuity (cc)
OD: Central, Steady, Maintained at near without correction
OS: Central, Steady, Maintained at near without correction

IOP (iCare tonometry)
OD: 14
OS: 12

Pupils
OD: 4 mm dark, 2.5 mm light, brisk reaction to light, no relative afferent pupillary defect (rAPD)
OS: 4 mm dark, 2.5 mm light, brisk reaction to light, no rAPD

Extraocular Movements
OD: Full
OS: Full

Confrontational Visual Fields (Toys)
OD: Full
OS: Full

Slit Lamp:

Dilated Fundus Examination:

Imaging/additional tests:
Cycloplegic refraction (retinoscopy)

Diagnosis
Infantile hemangioma

Discussion
Differential Diagnosis
The presentation is most consistent with an infantile hemangioma. Other pathology that may resemble an infantile hemangioma include nevus simplex, port-wine stain, congenital hemangioma, epithelioid hemangioma, pyogenic granuloma, or locally aggressive vascular tumors.¹

Definition
Infantile hemangiomas are a common (4-5% of individuals) benign vascular tumor of infancy mainly composed of endothelial cells. The lesions undergo a natural course consisting of an initial proliferative stage of growth followed by an involutional stage of regression that may take many years to complete. Initial presentation of the lesions may be at birth or within the first month of age. Although their pathogenesis remains unclear, current theories revolve around Vascular Endothelial Growth Factor (VEGF) expression and unregulated growth of hematopoietic stem cells.¹ It is often associated with female infants, those born premature or those with a low birth weight in addition to maternal factors (i.e. multiple gestation, advanced maternal age).² These lesions can be defined by their depth (superficial, deep, or mixed) as well as the extent of their involvement (segmental, localized, multifocal).³ Superficial lesions are characteristically bright red while those that are deep may present with a bluish hue or normal overlying skin. While infantile hemangiomas are benign in nature, they may result in significant disfigurement and/or vision loss secondary to amblyopia.² This primarily occurs through astigmatic anisometropia or vision deprivation and has an incidence ranging between 1/5 to 3/4 of individuals.^{2, 4} Appropriate diagnosis, treatment, and amblyopic screening are necessary to limit morbidity.

Examination
Appropriate examination of an infantile hemangioma is critical in an ophthalmic evaluation. It is important to observe the size of the lesion, as those > 1cm are at increased risk of amblyopia.⁵ In concerning lesions, appropriate vision screening methods (i.e. “central, steady, maintained” beginning at 3 months of age) and cycloplegic refraction (retinoscopy) should be assessed. Pupils and motility should also be assessed to characterize potential motility changes or optic nerve compression.⁶ To better characterize lesions with deep or unusual presentations further imaging via ultrasound, MRI or CT should be considered.⁶ Additional testing that can aid the diagnosis can include a biopsy with GLUT-1 staining (with negative study suggesting an infantile hemangioma is unlikely).⁷

Treatment
Medical observation may be appropriate for individuals without concern for or signs of ocular sequelae. For those in which treatment is indicated, first line options include beta-blockers (classically propranolol), which can be given in oral, topical or intralesional formulations. Of note, special precautions via inpatient initiation should be made when starting oral beta-blockers in infants <5 weeks of age, those with inadequate social support, or those with cardiovascular, respiratory, or neurologic comorbidity.¹ Other treatment options include topical vs intralesional corticosteroids. In individuals without adequate response more invasive measures such as lasers (pulsed dye, Nd-YAG, argon) and/or surgical intervention may be indicated.⁶

1. Amblyopia secondary to an infantile hemangioma most often occurs through which mechanisms?
   A) Refractive error
   B) Astigmatic anisometropia
   C) Vision deprivation
   D) Strabismus
   E) A and B
   F) B and C
   G) C and D
   
   Tavakoli M, Yadegari S, Mosallaei M, Aletaha M, Salour H, Lee WW. Infantile Periocular Hemangioma. J Ophthalmic Vis Res. 2017;12(2):205-211. doi:10.4103/jovr.jovr_66_17
   
   2. The expected natural course of an infantile hemangioma is?
   A) Malignant transformation
   B) Spontaneous involution and regression
   C) Persistence through adulthood
   D) Cycling growth and regression throughout childhood
   
   Tavakoli M, Yadegari S, Mosallaei M, Aletaha M, Salour H, Lee WW. Infantile Periocular Hemangioma. J Ophthalmic Vis Res. 2017;12(2):205-211. doi:10.4103/jovr.jovr_66_17
   
   3. An infant is brought to your office with a lesion above the right eyelid characterized by a slight bluish hue with a trace periocular bulge. Appropriate work up confirms an infantile hemangioma. How would you characterize the lesion?
   A) Mixed
   B) Superficial
   C) Deep
   D) Ischemic
   
   Chiller KG, Passaro D, Frieden IJ. Hemangiomas of infancy: clinical characteristics, morphologic subtypes, and their relationship to race, ethnicity, and sex. Arch Dermatol. 2002 Dec;138(12):1567-76. doi: 10.1001/archderm.138.12.1567. PMID: 12472344.
   
   4. An infant with a bright red periocular lesion presents to your clinic for evaluation. After appropriate examination and work-up a diagnosis of infantile hemangioma is made. Discussion surrounding the initiation of propranolol and potential need for inpatient admission is considered. Which of the following factors would suggest the need for inpatient initiation?
   A) Age >10 weeks
   B) Inadequate social support
   C) Cardiovascular/respiratory comorbidity
   D) All of the above
   E) A, B
   F) B, C
   
   Pahl KS, McLean TW. Infantile Hemangioma: A Current Review. J Pediatr Hematol Oncol. 2022 Mar 1;44(2):31-39. doi: 10.1097/MPH.0000000000002384. PMID: 34966091.

1. Amblyopia secondary to an infantile hemangioma most often occurs through which mechanisms?

F) B and C
The most often associated contributors of amblyopia secondary to an infantile hemangioma are astigmatic anisometropia and visual deprivation. Infantile hemangiomas, especially deep lesions, can be associated with strabismus but are not seen as a major cause of amblyopia in these cases.

2. The expected natural course of an infantile hemangioma is?
B) Spontaneous involution and regression
The natural course of an infantile hemangioma has a proliferative phase characterized by growth and an involutional phase characterized by tumor regression. The involutional phase may take several years to complete without intervention.

3. An infant is brought to your office with a slight bluish hue and an associated trace periocular bulge. You are concerned for an infantile hemangioma. How would you characterize the lesion?
C) Deep
Superficial lesions have a characteristic bright red appearance, while deeper lesions may present with bluish hue or normal skin appearance depending on the depth. Ischemic changes are unlikely to present in this manner.

4. An infant with a bright red periocular lesion presents to your clinic for evaluation. After appropriate examination and work-up a diagnosis of infantile hemangioma is made. Discussion surrounding the initiation of propranolol and potential need for inpatient admission is considered. Which of the following factors would suggest the need for inpatient initiation?
F) B, C
When initiating oral propranolol, inpatient initiation is recommended for infants with the following factors:

• 5 weeks of age,
• neurologic, cardiac, or pulmonary risk factors
• poor social support

References/Resources:

1) Pahl KS, McLean TW. Infantile Hemangioma: A Current Review. J Pediatr Hematol Oncol. 2022 Mar 1;44(2):31-39. doi: 10.1097/MPH.0000000000002384. PMID: 34966091.

2) Tavakoli M, Yadegari S, Mosallaei M, Aletaha M, Salour H, Lee WW. Infantile Periocular Hemangioma. J Ophthalmic Vis Res. 2017;12(2):205-211. doi:10.4103/jovr.jovr_66_17

3) Chiller KG, Passaro D, Frieden IJ. Hemangiomas of infancy: clinical characteristics, morphologic subtypes, and their relationship to race, ethnicity, and sex. Arch Dermatol. 2002 Dec;138(12):1567-76. doi: 10.1001/archderm.138.12.1567. PMID: 12472344.

4) Alniemi ST, Griepentrog GJ, Diehl N, Mohney BG. Rate of Amblyopia in Periocular Infantile Hemangiomas. Arch Ophthalmol. 2012;130(7):943–944. doi:10.1001/archophthalmol.2012.664

5) Schwartz SR, Blei F, Ceisler E, Steele M, Furlan L, Kodsi S. Risk factors for amblyopia in children with capillary hemangiomas of the eyelids and orbit. J AAPOS. 2006 Jun;10(3):262-8. doi: 10.1016/j.jaapos.2006.01.210. PMID: 16814181.

6) https://www.aao.org/oculoplastics-center/infantile-hemangioma

7) van Vugt LJ, van der Vleuten CJM, Flucke U, Blokx WAM. The utility of GLUT1 as a diagnostic marker in cutaneous vascular anomalies: A review of literature and recommendations for daily practice. Pathol Res Pract. 2017 Jun;213(6):591-597. doi: 10.1016/j.prp.2017.04.023. Epub 2017 Apr 27. PMID: 28552538.