Fig. 23.1
Infantile hemangioma . (a) Superficial infantile hemangioma with the bright red appearance typical of epithelial involvement by the hemangioma. (b) Intermediate infantile hemangioma with the purplish-blue discoloration typical of a subdermal infantile hemangioma. (c) This patient has a right-sided deep eyelid and orbital infantile hemangioma, demonstrating a mass effect with no alteration of the skin texture or color
The eyelid infantile hemangioma has some other characteristic features. In the rapidly enlarging superficial skin lesion, the epithelium may become necrotic or ulcerated if the lesion outgrows the local blood supply. Treatment of the lesion may also precipitate devascularization and result in tissue necrosis with ulceration of the skin. The soft tissue mass of the infantile hemangioma lesion is spongy and easily compressible. The lesion blanches with compression. The classic clinical history of an infantile hemangioma predicts that the lesion will initially enlarge over the first 3–6 months of life, followed by spontaneous involution until the age of 9 years. Roughly half of all hemangiomas are no longer clinically visible by age 5 years and the rest by age 9 [3]. When the involution process begins, the previously red lesion may take on a grayish or beige hue, and as involution progresses, patches of normally colored epithelium interdigitate with the purple-gray and red tissue. The epithelium may return to a normal appearance, but larger lesions may cause permanent disruption in the dermal elastic tissue, resulting in thinning of the skin sometimes referred to as a “cigarette paper” appearance (Fig. 23.2).
Fig. 23.2
Texture and pigmentation changes. (a) At age 14, this patient has soft tissue changes in the left upper eyelid and temporal skin that are characteristic of the “cigarette paper” texture that may occur when the infantile hemangioma involutes. (b) An oblique view of the texture and pigmentation changes
Infantile hemangiomas may be present at birth or typically begin in the first few months of life. The lesion is more common in females than males. Without treatment, most lesions will involute, leaving behind little or no evidence of their prior presence. However, a subset of infantile hemangiomas can show dramatic growth over the first 10 months of age that may cause distortions of cosmetic and functional significance (Fig. 23.3). These lesions will also spontaneously involute by 9 years of age, but may require early intervention to prevent permanent sequelae from disruption of function. For the ophthalmologist, this will include monitoring and treatment for deprivational or anisometropic amblyopia. Preliminary evaluation of the pediatric patient with an eyelid infantile hemangioma should include tests of visual function and retinoscopy. Amblyopia may be caused by the eyelid position blocking the visual axis or from astigmatism due to eyelid or orbital pressure effects on the globe. In addition to compression effects on the globe, intraorbital growth can also produce secondary expansion of the bony orbital walls.
Fig. 23.3
Infantile hemangioma : CT scan. (a) Infantile hemangioma of the left upper eyelid and left medial canthal region. (b) CT scan of the same patient with intravenous contrast. Notice the smoothly irregular contour and borders of the hemangioma. On CT, the infantile hemangioma enhances markedly with intravascular contrast material
The nature and extent of an anterior eyelid lesion may be clinically apparent, but in patients where this is not the case, an MRI is a valuable imaging technique for identification and assessment of the extent of an infantile hemangioma. When the goal of the imaging is to help differentiate between an infantile hemangioma and a lymphangioma (venolymphatic malformation), MRI is helpful (Fig. 23.4). MRI better demonstrates the more heterogenous soft tissue structures of the lymphangioma as compared to CT imaging. The MRI scan may also be used to identify blood collections that can produce a “chocolate cyst” that can be found in lymphangioma and is not typical of an infantile hemangioma (see Fig. 23.11). On MRI, an infantile hemangioma will usually show characteristic flow voids or darker areas in the soft tissue structure where higher flow vascular structures are present (Fig. 23.4c). B-scan ultrasound of the infantile hemangioma will show irregular contours, and the A-scan will show variable internal reflectivity in the high to medium range (Fig. 23.5).
Fig. 23.4
Infantile hemangioma : MRI. (a) Infantile hemangioma of the face, upper eyelid, and brow. (b) Sagittal view MRI demonstrating the eyelid and orbital involvement by the infantile hemangioma. (c) Axial MRI scan with gadolinium shows the diffuse increase in signal intensity and the flow voids from vessels in the eyelid
Fig. 23.5
Infantile hemangioma : ultrasound. (a) Clinical appearance of an upper eyelid hemangioma. (b) B-scan ultrasound of the lesion shows the irregular thickening of the eyelid anterior to the globe. (c) The A-scan ultrasound of the infantile hemangioma shows high internal reflectivity
Management of Infantile Hemangiomas
There are numerous treatment options for functionally or cosmetically disruptive infantile hemangiomas [4]. Although the majority of these lesions can be managed conservatively with observation, there is a subset in which the hemangioma may grow rapidly or become very large. In the periocular region, this is particularly problematic because of the resultant effects on the visual system. In one series of 50 patients with infantile hemangiomas of the eyelid followed over 5 years, the complication rate was 80% (60% with amblyopia) [5]. This potentially preventable loss of vision demands careful observation and early intervention. Amblyopia may occur as the result either of changes in refractive error or obscuration of the visual axis [6].
Correction of any significant refractive error and occlusion therapy are medical options for the treatment of early or mild amblyopia. More severe or progressive problems warrant treatment options that focus on techniques to decrease the size of the mass. One study shows that the treatment of anisometropic amblyopia is equally successful with either ocular intervention (spectacle correction/occlusion) or medical intervention (corticosteroids/surgery), but that corticosteroids/surgeries were more successful in the treatment of occlusion amblyopia [7]. Although it is difficult to know in the early phases which infantile hemangiomas will involute without sequelae and which will create functional deficits, the treatment options are less invasive and have fewer risks when the lesion is smaller. For this reason, consideration may be given to more aggressive intervention even for smaller lesions that involve the eyelids.
In 2008 Leaute-Labreze et al. published the first series of patients successfully treated with oral beta blockers for infantile hemangioma [8]. This accidental discovery paved the way for the widespread use of oral and topical beta blockers as a first-line therapy for the treatment of infantile hemangiomas. In a large clinical trial of 460 patients, the beta-blocker propranolol was shown to be an effective treatment at a dose of 3 mg per kilogram per day for 6 months. The known side effects of this beta blocker – hypoglycemia, hypotension, bradycardia, and bronchospasm – were infrequent [9]. This medication is best monitored safely under an inpatient protocol for infants younger than 2 months. For patients over the age of 2 months, outpatient propranolol induction can be acceptably monitored. A meta-analysis of 61 publications involving 5130 participants demonstrated that propranolol was more effective and safer than other therapies in treating infantile hemangioma [10] (Box 23.1).
Currently, the CHOP protocol follows the FDA guideline that children of 45 weeks gestation or older are candidates for outpatient propranolol therapy if they have a normal EKG. Blood pressure and heart rate are monitored for 1–2 h during an initial partial dose administration and again the following week when the full dose is administered. Propranolol appears to have fewer adverse side effects and may even be more effective than steroids in suppressing hemangiomas and causing them to involute more rapidly.
Because propranolol is so effective in the treatment of infantile hemangiomas, systemic steroids are reserved for cases of patient who do not respond to propranolol or as a temporizing therapy for severe cases before beta-blocker induction can be attempted. Some physicians prefer both propranolol and systemic steroids for severe cases of hemangioma that require aggressive treatment.
Isolated lesions or predominantly smaller, flat hemangiomas can be treated with topical beta blocker effectively. The dose of 0.5% timolol gel-forming solution is typically used [11]. In a CHOP study, we found that 0.25% timolol gel-forming solution to be equally effective. This dosage can be used for small infants 4 months or younger [12]. In the past, treatment options that have been employed to decrease the mass of eyelid infantile hemangioma included intralesional corticosteroids, systemic corticosteroids, topical corticosteroids, superficial laser ablation, CO2 laser debulking, surgical debulking, systemic α-interferon, and radiotherapy. Radiation therapy is generally avoided because of the potential for significant scarring and atrophy (Fig. 23.6). Intralesional steroid injections were once popular but were a concern for potential central retinal artery occlusion (Fig. 23.7). In life-threatening cases, the use of α-interferon was reported as a therapeutic option [13–15]. There may be serious systemic side effects, however, including fever, neutropenia, hemodynamic changes at the onset of use, anorexia, and neurologic toxicity [16–18]. All of these modalities are now considered second-line therapies for patients who either fail beta-blocker therapy or in whom the treatment is contraindicated, such as in PHACES.
Fig. 23.6
Infantile hemangioma: radiation therapy . (a) Skin changes demonstrating scarring and atrophy following radiation therapy for infantile hemangioma of the left periocular region, cheek and neck. (b) Sagittal view of the soft tissue changes. This was treated with tissue expansion and sequential excision of the scar
Fig. 23.7
Infantile hemangioma: corticosteroid treatment . (a) A lower eyelid infantile hemangioma extending up into the pupillary axis. (b) Intralesional injection of corticosteroid into the infantile hemangioma. (c) After injection, the infantile hemangioma is gradually shrinking out of the line of the visual axis
Vision-threatening hemangiomas of the eyelids may also be debulked surgically. Surgical intervention may be challenging because of the growth pattern of the infantile hemangioma. In some circumstances, imaging and clinical examination identify an anteriorly placed and well-circumscribed hemangioma. This pattern of growth is amenable to surgical excision. Eyelid lesions that are deep to the epithelium but anteriorly placed in the orbit and well circumscribed are also ideal for surgical removal. More commonly, however, the hemangioma will interdigitate with and become indistinguishable from the normal structures of the eyelid. This affects the surgeon’s ability to distinguish the normal planes and surgical landmarks. When the lesion involves the epithelium, it will also be difficult to dissect a plane and not disrupt the circulation to the skin. Recognizing these limitations, it may still be valuable to surgically alter the eyelids in order to create a functional visual axis by decreasing the mechanical mass effect of the tumor (Fig. 23.8). The surgical CO2 laser has been beneficial to use as a tool to simultaneously vaporize and cauterize the tissue. The insulated point tip cautery can also be effective for removing an eyelid lesion. Consideration should be given to preoperative blood type and cross match if there is any concern for significant intraoperative blood loss. Postoperatively, these patients often have prolonged edema and may develop areas of tissue necrosis from alteration in the vascular supply to the lesion. These problems do not preclude a good cosmetic result as the child matures and the infantile hemangioma continues to involute.
Fig. 23.8
Infantile hemangioma: CO2 laser debulking . (a) Infantile hemangioma of the left upper eyelid. (b) The same patient following intralesional injection of corticosteroid. The palpebral fissure is improved, but the upper eyelid still covers the central visual axis. (c) The lesion is debulked using the CO2 laser for hemostasis. (d) The patient’s immediate postoperative appearance. (e) One month following debulking surgery, the surrounding tissue necrosis and ulceration of the devascularized lid skin are seen. (f) At 5 years of age, there is still some thickening of the upper eyelid, but the skin is well healed, and the superficial components of the infantile hemangioma have undergone involution. (g) At 8 years of age, the mass effect of the hemangioma has resolved, but there are some residual skin changes and a ptosis of the upper eyelid. (h) The patient at 11 years of age following ptosis repair and removal of a small amount of skin in the upper eyelid to create a more symmetrical lid crease
Additional surgical options may be necessary when the child has completed the spontaneous involution or treatment process and is left with significant residual changes in the soft tissue. Smaller lesions or excess skin may be excised, but larger areas may require skin grafts or tissue expansion to replace the abnormal tissue with normal expanded skin from a nearby region (see Chap. 7).
Box 23.1: Inpatient Admission Protocol
Admit to appropriate unit or ward. Optional: peripheral IV placement at the discretion of the on-service attending.
Baseline vital signs including temperature, HR, BP, with cardiorespiratory and oximeter monitor placement. In ICU, vital signs are monitored continuously. On inpatient ward, baseline vital signs are taken and then q2h vital signs × 2 following initial dose and subsequent dose escalations, then standard q4h vital signs.
Day 1
Initiation of beta-blocker (propranolol) therapy as ORAL dose:
<1 month of age: 0.5 mg/kg/day divided q8h × 3 doses
≥1 month of age: 1 mg/kg/day divided q8h × 3 doses
Blood glucose measurement: OPTIONAL unless patient symptomatic. If elected, can be performed 1 h following each of first 2 doses at each dose range
For critical values, hold dose, repeat measurement, and contact front-line physician if abnormal values persist or if patient is symptomatic:
Bradycardia: HR <80 bpm
Hypotension: <70 mm Hg (systolic) in infants [<5th percentile] or <30 mm Hg (diastolic) in infants
Hypoglycemia: <70 mg/dL [normal 60–105 mg/dL]
Day 2
Beta-blocker (propranolol) therapy as ORAL dose at:
<1 month of age: 1 mg/kg/day divided q8h × 3 doses
≥1 month of age: 2 mg/kg/day divided q8h × 3 doses
Blood glucose measurement: OPTIONAL unless patient symptomatic. If elected, can be performed 1 h following each of first 2 doses at each dose range
For critical values, hold dose, repeat measurement, and contact front-line physician if abnormal values persist or if patient is symptomatic:
Bradycardia: HR <80 bpm
Hypotension: <70 mm Hg (systolic) in infants [<5th percentile] or <30 mm Hg (diastolic) in infants
Hypoglycemia: <70 mg/dL [normal 60–105 mg/dL]
Day 3 (ONLY needed for those <1 month of age who initiated dosing at 0.5 mg/kg/day divided q8h)
Initiation of beta-blocker (propranolol) therapy as ORAL dose at 2 mg/kg/day divided q8h x 3 doses
Blood glucose measurement: OPTIONAL unless patient symptomatic. If elected, can be performed 1 h following each of first 2 doses at each dose range
For critical values, hold dose, repeat measurement, and contact front-line physician if abnormal values persist or if patient is symptomatic:
Bradycardia: HR <80 bpm
Hypotension: <70 mm Hg (systolic) in infants [<5th percentile] or <30 mm Hg (diastolic) in infants
Hypoglycemia: <70 mg/dL [normal 60–105 mg/dL]
If symptomatic concerns arise, doses lower than 2 mg/kg/day may be used.
If suboptimal or partial results are obtained for complicated problems, doses may be escalated to 3–5 mg/kg/day in 0.5 or 1 mg/kg increments at the clinician’s discretion as tolerated by the patient.
Post-admission Monitoring Visits
Once the target dose has been achieved, ambulatory heart rate and blood pressure monitoring is recommended monthly either at their primary care clinician’s office or at the prescribing physician’s office.
At follow-up visits once a month, dose adjustments may need to be made to accommodate the infant’s interval weight gain or if warranted due to clinical changes in the hemangioma.
Closer follow-up may be necessary if systemic corticosteroids are being tapered while still on beta-blocker therapy.
Anticipation is that beta-blocker therapy may be necessary for approximately 6–12 months, or until the child is 12–18 months of age due to the proliferative nature of infantile hemangiomas but can be adjusted to individual patient needs. Topical timolol may be added during the taper of beta-blocker or following discontinuation to help prevent recrudescence.
Vascular Malformations
Vascular malformations of the eyelid and periorbital tissue may be venous, lymphatic, or arterial in nature. The term lymphangioma has typically been used to describe a mass that contains lymphatic and often venous channels. This term has since been replaced by venolymphatic malformation by the International Society of the Study of Vascular Anomalies (ISSVA) and updated to be lymphatic-venous malformation (LVM) [19]. Lymphatic-venous malformations that are visible on the eyelid typically extend into the orbit and are covered in greater detail in Chap. 35.
When there is a soft tissue component in the eyelids, LVM and other vascular malformations present with painless, compressible enlargement of the eyelid that may be accompanied by displacement of the globe (Fig. 23.9). Ocular motility may be impaired and the mass may demonstrate a Valsalva increase with crying or straining. There may be red or blue discoloration of the eyelid (Fig. 23.10). Some clinical features that help to distinguish the LVM from other periorbital lesions of childhood include a tendency for the lesion to increase in size with respiratory infections and the potential for sudden hemorrhage into a cystic space, which can result in an acute painful proptosis (Fig. 23.11). The presence of beaded cystic structures in the conjunctiva or on the roof of the mouth is also a feature that points toward the diagnosis of LVM . When the LVM involves the epithelium, the mass has the appearance of dilated lymphatic channels characterized by a beaded cystic architecture. Deeper lesions may take on a purple or blue hue, especially when the potential spaces fill with blood. A growth spurt at the time of puberty may also occur. This probably represents an enlargement of the spaces rather than a true proliferation of cells. These lesions can also extend along the under surface of the skin into the forehead.
Fig. 23.9
Lymphangioma of the left upper eyelid
Fig. 23.10
Lymphangioma of the eyelid, conjunctiva, and superficial left orbit. (a) The upper eyelid margin. (b) The eyelids are separated to expose the lesion in the temporal conjunctiva. (c) A close-up of the conjunctiva shows the blood-filled cystic structures. In other patients, the conjunctival lesions may be filled with clear fluid rather than blood, but the texture is similar. (d) A coronal CT scan of this patient shows the soft tissue infiltration in the left lateral eyelids and orbit. (e) The axial CT scan shows a soft tissue thickening in the left lateral lid and conjunctiva. The soft tissue changes in this eyelid lymphangioma are quite homogenous. Orbital or larger lymphangiomas tend to have less distinct borders and may be more heterogeneous with cystic spaces
Fig. 23.11
Superonasal cyst : MRI. (a–c) This 12-year-old woman presented with an acute onset of left periocular pain and proptosis. She had no previous history of any ophthalmic problems. The clinical photos demonstrate the downward displacement of her left globe and the proptosis. (d) The axial MRI scan shows the presence of some irregular soft tissue and a large cystic structure in the retrobulbar space. (e) The coronal MRI shows the superonasal cystic structure with heterogenous soft tissue and the resultant downward displacement of the globe. (f) The T 2-weighted MRI shows the high-intensity material within the cyst. (g) The patient is in a prone position, and careful inspection of the cyst shows a layering of the red blood cells and plasma within the hemorrhagic “chocolate cyst.” (h) Twenty-four hours later, the acute hemorrhage is visible with anterior dissection of the blood into the lids and conjunctiva
CT imaging will delineate the size and location of the vascular malformations, but MRI is more useful to help to differentiate between infantile hemangioma and lymphangioma. On CT an LVM may show less enhancement with contrast than the typical infantile hemangioma. MRI better documents the internal structure of the LVM , which is typically more heterogenous than an infantile hemangioma, and may show areas of hemorrhage that are hyperintense on T 1-weighted images. The margins of the lesions are typically irregular and do not follow the usual compartmental planes of the orbit. In addition, cystic spaces of an LVM help to differentiate macrocystic LVM, which are cysts larger than 10 mm from microcystic (<10 mm). This treatment of these lesions is covered in Chap. 35.
Eyelid and Periocular Dermoid Cysts
The dermoid cyst is believed to originate when a portion of the embryologic ectoderm becomes inadvertently buried along the suture lines of moving fetal growth plates. The clinical presentation of the lesion [20] is divided into 2 groups that have different characteristics: anterior lesions and posterior lesions. The anterior cysts occur along the frontozygomatic, frontolacrimal, and frontoethmoidal sutures. The deeper dermoids develop along the lines of the sphenozygomatic and sphenoethmoidal sutures. The more anterior lesions become obvious at a younger age than the deeper orbital lesions.(Refer to Chap. 35 for a more detailed discussion of the orbital dermoid.)
The typical anterior dermoid cyst presents as a smooth, rounded, firm, non-tender mass (Fig. 23.12). The mass is not attached to the skin and is often adherent to the periosteum along the suture line. These cysts enlarge very slowly unless the cyst wall becomes disrupted. Exposure of the contents of the cyst to the immune system results in an acute inflammatory reaction with edema, erythema, and pain. The most common location for the cysts is the lateral brow, followed by the superonasal medial canthal region. On occasion, these cysts can fistulize to the skin and present as an isolated skin lesion which spontaneously drains a keratin-rich exudate.
Fig. 23.12
Dermoid Cyst . (a) Clinical appearance of a dermoid cyst located in the supero-lateral eyelid. (b) The axial CT demonstrates a small, well-defined, subcutaneous mass (arrows). The dermoid causes slight flattening of the bone on which it lies. (c) The coronal CT shows the dermoid (arrows) with a denser capsule. The black arrow indicates the flattened bone, which is in contact with the dermoid cyst
The dermoid cyst has a characteristic appearance on CT scan. The CT shows an oval, smooth lesion with well-demarcated borders that may have some rim enhancement and lower central absorption with intravenous (IV) contrast. The surrounding bone may show molding or pressure changes. For anterior lateral dermoid cysts, CT is necessary only for an atypical lesion or a lesion that appears fixed and may possibly extend into the orbit. The CT will help in assessing the posterior extent of the cyst. Anterior medial lesions may be scanned to help differentiate the dermoid cyst from encephalocele, infantile hemangioma, or a lacrimal mass (Fig. 23.13). In general, while it is reasonable to image most lesions suspected to be dermoids, the classic firm, but non-fixed, lesion of the temporal brow need not be imaged. In any other location, however, imaging is indicated to rule out bony extension into a neighboring cavity. In the case of superomedial lesions, dermoids may be compressed by advancing bones and become dumbbelled into the nasal space as well as the external orbit. This can also occur temporally. In cases of a temporal lesion that is palpable and firm, but not moveable, imaging should always be ordered to rule out extension into the orbit or skull base.
Fig. 23.13
Medial upper lid masses . (a) Clinical photograph of a left medial cystic structure. (b) Axial CT scan demonstrating a rounded and well-circumscribed mass at the frontonasal suture line consistent with a dermoid cyst. (c) Appearance of the same dermoid cyst after removal, a round, yellowish mass with surrounding fibrous tissue. (d) Another child also presents with a right medial upper lid mass. (e) An MRI scan shows an elliptical lesion in the medial orbit with a slightly heterogenous soft tissue nature. In this case the findings are compatible with an infantile hemangioma rather than a dermoid cyst
The treatment for dermoid cysts is surgical excision. This is an elective procedure, but may be considered around 12 months of age for the anterior lesions and at the time of diagnosis for posterior lesions. Anterior lesions should be removed before the child becomes sufficiently mobile so as to be at risk for traumatic rupture of the dermoid cyst. The resultant inflammatory response can cause tissue fibrosis and scarring. When the lesion is removed, care is taken not to spill the cyst contents in the operative site for the same reason. A lid crease incision may be used to remove even very large dermoid cysts (Fig. 23.14). The eyelid crease incision creates the most cosmetically acceptable scar and provides access to superonasal as well as temporal dermoid cysts. If necessary, a sub- or suprabrow incision may be considered (Fig. 23.15). Often as a child grows, the brow cilia will thicken and obscure the scar, but this is not a reliable feature of brow incisions.
