Prevalence and Clinical Features of Orbital Vascular Anomalies in Children

Abstract

Purpose:

To report the prevalence, clinical characteristics and natural history of orbital vascular anomalies diagnosed among children over a 50-year period.

Methods:

The medical records of all patients < 19 years diagnosed with any form of an orbital vascular anomaly at Mayo Clinic, Rochester, Minnesota from January 1, 1966, through December 31, 2015, were retrospectively reviewed.

Results:

A total of 109 children were diagnosed with (OVA) during the 50-year period, of which 24 were from Olmsted County, MN, yielding a birth prevalence of 1 in 4,305 live births. The median age at diagnosis for the 109 patients was 1.2 years (range, 0 to 17.9 years) and 67 (61.5%) were female. Common presenting symptoms included proptosis in 80 (73.4%) patients, abnormalities in skin color in 45 (41.3%) patients, and pain in 18 (16.5%) patients. There were 55 (50.5%) vascular malformations [50 (91%) low-flow lymphatic malformations, 3 (5.5%) high-flow arteriovenous malformations, and 2 (3.5%) low-flow venous malformations] and 54 (49.5%) vascular tumors [53 (98%) capillary hemangiomas and 1 (2%) kaposiform hemangioendothelioma]. During a mean follow up of 5.95 years (range 0 to 27.7 years), amblyopia and/or strabismus were diagnosed in 46 (43.4%) patients.

Conclusions:

Capillary hemangiomas and low-flow lymphatic malformations comprised most of the orbital vascular anomalies in this cohort of children. Amblyopia and strabismus are common sequelae, highlighting the importance of early diagnosis and appropriate management.

Introduction

Orbital vascular anomalies (OVA) are among the most common space-occupying lesions of the orbit,¹ comprising 5.5% to 22% of all orbital disorders in children.^1,2 While controversy in classification exists, these anomalies may be further categorized as vascular tumors (significant component of cellular proliferation) or vascular malformations (anomalous channels of the arterial, venous, capillary, and/or lymphatic vascular system). ^2–5 Orbital vascular malformations may be further divided by flow characteristics into low flow (e.g. venous malformation, lymphatic malformation), high flow (e.g. arteriovenous malformation), and mixed flow (e.g. arteriovenous fistula) categories. ^3,4 Indeed, classification of orbital vascular malformation flow characteristics is particularly useful when planning appropriate treatment.⁴

Although there are numerous publications regarding the incidence and types of orbital lesions from referral-based practices,^6–14 along with reports focused on OVA diagnosis and treatment,^2,15–20 to our knowledge, there are no population-based epidemiologic reports in the literature. The purpose of this study is to report the prevalence, clinical features and natural history of OVA observed in children diagnosed over a 50-year period from a single institution, along with reporting the prevalence among patients who were residents of Olmsted County, Minnesota at the time of their diagnosis.

Subjects and Methods

Institutional review board approval was obtained from Mayo Clinic and Olmsted Medical Group. The medical records of all patients < 19 years of age who were diagnosed at our institution with an OVA from January 1, 1966, through December 31, 2015, were retrospectively reviewed. We also identified pediatric patients who were residents of Olmsted County, Minnesota, when diagnosed with an OVA during the same period. Olmsted County cases were identified by the resources of the Rochester Epidemiology Project, a medical records linkage system designed to capture data on any patient-physician encounter in this county.

OVA was defined in this study as any vascular anomaly involving the orbit (posterior to the orbital septum) with or without periorbital (e.g. eyelid) involvement. A diagnosis was made based on a combination of the clinical exam, imaging (e.g. ultrasound/computed tomography/magnetic resonance) or, in those cases identified prior to the routine use of imaging, with a pathology report following surgical excision. A list of potential cases from the institution, generated by a comprehensive diagnostic code search, identified 2,860 patients. Each record was meticulously reviewed by an ophthalmologist (LATC and BGM) for confirmation of an OVA based on the criteria stated above. Cases were excluded if the vascular anomalies were not located within the orbit (e.g. isolated eyelid capillary hemangioma), were diagnosed outside the time period of this study, or were 19 years or older. Each record was reviewed for demographic information including sex, race, date of diagnosis, as well as perinatal, developmental, medical, and familial histories. Clinical characteristics of the OVA including size, location, treatment, ocular co-morbidities and final outcome were reviewed.

Results

One hundred nine new cases of childhood OVA were diagnosed during the 50-year study period. The median age at diagnosis was 1.2 years (range, 0 to 17.9 years), and 67 (61.5%) were female. Of the 61 (55.9%) patients reporting race, 52 (85.2%) were Caucasian, 6 (9.8%) reported a mixed race, 2 (3.3%) were Asian, and 1 (1.6%) was Native Hawaiian. A history of premature birth occurred in 9 (8.3%) patients. The mean maternal and paternal ages recorded at childbirth for each patient were 27.8 and 29.9 years, respectively. A positive family history of vascular anomalies not isolated to the orbit was reported in 3 (2.8%) patients. Table 1 shows the demographic characteristics of the 109 study patients. Twenty-four (22%) of the one hundred nine patients resided in Olmsted County, Minnesota at the time of their diagnosis, yielding a birth prevalence of 1 in 4,305 live births. There were ten (9.2%) with vascular malformations and fourteen (12.8 %) with vascular tumors.

TABLE-1.

Demographic Characteristics of 109 Children Diagnosed with Orbital Vascular Anomalies over a 50-year period.

Characteristic	No. of Patients (%)
Males (%)/Females (%)	42(38.5)/67(61.5)
Race n= 61
Caucasian	52 (85.2)
More than one race	6 (9.8)
Asian	2 (3.3)
Native Hawaiian	1 (1.6)
Premature birth*(%)	9 (8.3)
Mean maternal age at birth in years (range), n=60	27.77 (17-42)
Mean paternal age at birth in years (range), n=59	29.89 (18-51)
Family history of vascular malformations	3 (2.8)
Median age at diagnosis (range)	1.2 (0-17.9)
Location
Right (%)/Left orbit (%)	56 (51.4)/53 (48.6)
Associated structural ocular abnormalities	3 (2.6)

^*Born at < 37 weeks gestation

The most common presenting symptoms of the 109 subjects were proptosis in 80 patients (73.4%), change in skin color (e.g. blue or purple tinge) in 45 (41.3%) patients, pain in 18 (16.5%) patients, and ulceration or dry “crepey” skin in 17 (15.6%) patients. Fifty-five (50.5%) of the 109 patients had a vascular malformation [50 (91%) low-flow lymphatic malformations, 3 (5.5%) high-flow arteriovenous malformations, and 2 (3.5%) low-flow venous malformations], while 54 (49.5%) patients had a vascular tumor [53 (98%) orbital hemangiomas and 1 (2%) case of kapasiform hemangioendothelioma]. The right and the left orbits were equally affected (51.4% vs 48.6%).

Sixty-four (58.7%) patients received treatment, characteristic of the particular time of diagnosis during the 50-year study period. Forty-five (41%) were treated with surgical excision, 12 (11%) with intralesional steroids, 11 (10.1%) with CO2 laser, 10 (9.2%) with systemic steroids, five (4.6%) with radiation, 2 (1.8%) with sclerosis and 1 (1%) with systemic propranolol, while the remaining 45 patients were observed. Twenty-five (22.9%) patients required combined treatment modalities. Table 2 shows the treatment characteristics of the 109 study patients during this 50-year period. Of the 64 patients that received treatment, 9 (14.1%) developed treatment related complications: 4 (5.9%) developed a hematoma, 2 (2.9%) presented with symblepharon, 1 (1.5%) developed optic nerve atrophy, 1 (1.5%) suffered from lateral rectus muscle injury and 1 (1.5%) developed persistent hypotension.

TABLE-2.

Treatment characteristics

Characteristic	No. of Patients (%)
Observation	45 (41.3%)
Treatment	64 (58.7%)
Surgical excision	45 (41%)
Intralesional steroids	12 (11%)
CO2 laser	11 (10.1%)
Systemic steroids	10 (9.2%)
Radiation	5 (4.6%)
Sclerosis	2 (1.8%)
Systemic propranolol	1 (1%)
Combined treatment	25 (22.9%)

During a mean follow-up of 5.95 years (range 0 to 27.7 years), 46 (42.2%) patients were diagnosed with amblyopia at the initial visit. Strabismus was present in 46 (43.4%) patients, with exotropia occurring in 17 (36.9%) patients. At the final follow-up visit, sixty-two (56.9%) patients had documented decrease in the size of the lesion, 26 (23.9%) were lost to follow-up, 19 (17.4%) were unchanged and 2 (1.8%) patients were noted to have lesion growth. Amblyopia persisted in 29 (26.6%) patients from the total cohort (n=109) despite treatment.

Discussion

In this population-based cohort of children diagnosed over a 50-year period, orbital vascular anomalies occurred in 1 in 4,305 live births. Etiologies were equally divided between vascular malformations and vascular tumors. The most common presenting symptoms were proptosis, abnormalities in skin color, and pain. Amblyopia and strabismus occurred in approximately half of the patients and nearly 60% underwent treatment during the follow-up period.

Ocular complications from orbital vascular anomalies, such as proptosis and optic nerve compression, are due to the space-occupying effects on a fixed orbital volume. ^21,22 Vascular anomalies may additionally lead to soft tissue changes (e.g. eyelid involvement with orbital capillary hemangiomas), resulting in ptosis and deprivation amblyopia. Because of the potential to develop these complications, close ophthalmic clinic follow-up along with serial imaging in select patients, is recommended.

The most common presenting symptom/sign in this cohort was proptosis, occurring in 73.4% of the patients, similar to that described by prior investigators.^6,15,21 Other classic orbit lesion presentations including a history of upper respiratory infections preceding lymphangioma enlargement or bruits in AV malformations, were encountered in 15.6% and 0% of patients, respectively.^6,18,21 We report a high incidence of strabismus (43.4%), similar to Kodsi and co-authors previous report in which they reported that 42% of their cohort presented with a form of eye misalignment.⁷ In addition, we report an incidence of amblyopia of 42.2% at the initial visit; Tavakoli et al previously reviewed the incidence of amblyopia ranging from 76% in older reports to 21% in recent studies.²³ During a mean follow-up of almost 6 years, amblyopia improved in 15.6% of these patients with appropriate therapy, highlighting the importance of timely diagnosis and treatment.

Capillary hemangiomas were the most common type of OVA in this cohort, similar to the findings of the large referral-based retrospective case series of Bonavolonta et al ⁹ of 2,840 lesions in patients of all ages between the years 1976 to 2011. Other retrospective case series have reported lymphangioma as the most common anomaly.^8,10 We previously reported the incidence of periocular infantile hemangiomas in all patients living in Olmsted County, Minnesota, between 1965 and 2004.²⁴ None of the previously reported cases qualified for inclusion in the current study as they were primarily involving the lid and periocular structures. The second most frequent lesion in this cohort was lymphangioma, accounting for 46.5% of the cases, followed by AV malformation in 3.5%, varix in 1.8% and hemangioendothelioma in 0.9% of the patients. These numbers differ slightly from what was observed by Bonavolontà and coauthors,⁹ who reported a higher frequency of varix (15%) and a lower frequency of AV malformations (<1%).

Most cases of orbital hemangiomas were diagnosed within the first year of life, similar to a study by Rao et al and Speranta et al.^15,25 Stacey and coauthors reported that lymphangiomas are generally present at birth,⁴ which differs from the current report and a previous review by Rao et al ¹⁵ in which the onset occurred around 2 years of age. Schick and coauthors found an association between lymphangioma and the presence of palatal cysts and intracranial venous anomalies,¹⁸ an association that was not observed in the current study. In this cohort, premature birth (8.3%), associated structural ocular abnormalities (2.6%) and a positive family history of vascular malformations (2.8%) were associated with the development of an OVA, particularly hemangiomas, as previously described by other authors like Topilow et al in their review ^21,26; however, our numbers were too small to assess for a significant association.

The diagnosis and therapy of OVA have been challenging because these lesions vary in their clinical presentation and making an accurate diagnosis can be difficult.²⁶ Historically, total excision of the lesion or partial removal with pathologic analysis was the only means for accurate diagnosis. However, the advent radiological techniques such as computed tomography, magnetic resonance imaging and interventional radiographic techniques have helped in accurately diagnosing without the need of an invasive procedure.^22,27 We observerd this trend during the years studied; in the earlier years surgical procedures were mostly performed, until the commonplace clinical use of CT and MRI. More recently, computed tomography angiography and magnetic resonance angiography have added additional sensitivity and specificity to the radiologic diagnosis of OVA.

Management of OVA includes observation, however treatment is required when there is a risk of amblyopia or progressively worsening symptoms develop.²¹ More than half of the patients (58.7%) in our study received treatment. Until recently, surgical resection was the standard of care for these lesions.^12,27 However, newer diagnostic techniques, medical treatments and refined surgical techniques have transformed the treatment of select OVA over the past decades.²⁷ An individualized approach should be considered that may involve a multi-disciplinary team including an oculoplastic specialist, pediatric ophthalmologist and neurosurgeon.^22. In addition, non-surgical management of select OVA have gained wider use. For example, systemic propranolol therapy has displaced corticosteroids and surgery as first line of treatment for hemangiomas, and sclerosing agents have gained importance in treatment of arteriovenous malformations. ^23,28

There are several limitations to the findings of this study. Its retrospective design is limited by incomplete data and irregular follow-up. Space-occupying lesions within the orbit are notoriously variable and shape-shifting, with smaller or non-progressive lesions never coming to an examiner’s attention. Such potential selection bias affects both the overall cohort as well as the Olmsted County incidence cohort. Finally, our ability to generalize the findings of 24 Olmsted County residents to other populations is limited by the small sample size and the relatively homogenous semi-urban white demographics of the study population.

In this, the largest series of pediatric orbital vascular anomalies reported to date, we observed a prevalence of approximately 1 in 4305 births. Capillary hemangiomas and low-flow lymphatic malformations comprised more than 90% of the orbital vascular anomalies and significant ocular sequelae, including amblyopia and strabismus, were common in this cohort.