Chapter 11 Intraocular Tumors
While rare in comparison to other forms of ocular disease, intraocular tumors in particular require precise and accurate characterization utilizing ocular imaging techniques. Intraocular tumors comprise a heterogeneous group ranging from benign asymptomatic lesions to vision and life threatening malignancies. Ophthalmic ultrasonography has long been utilized as a powerful, non-invasive, and economical tool for characterizing and following the clinical course of intraocular tumors. Ophthalmic ultrasonography, in combination with computed tomography (CT), magnetic resonance imaging (MRI), and optical coherence tomography (OCT) provide a ready means for determining overall tumor dimensions, configuration, location, presence of extraocular extension, and associated features such as retinal detachment or calcification. The key in differentiating one tumor type from another based upon ultrasonographic features lies in the variable histopathologic compositions of each entity. These differences can be elucidated using both one-dimensional reflectivity analysis (A-scan) and two-dimensional acoustic sectioning techniques (B-scan). Combining information regarding reflectivity and sound attenuation provides useful information about the acoustic internal texture of intraocular tumors. Furthermore, ultrasonography provides an important means by which to follow tumor progression or stability over time and is critical in formulating management strategies. The following chapter provides a review of the ultrasonographic and clinicopathologic features of many of the more commonly encountered intraocular tumors seen in ophthalmic practice.
Retinoblastoma is the most common intraocular malignancy of childhood and occurs with a frequency of approximately one in 14,000 to 20,000 live births.1 Ninety percent of cases are diagnosed in children under the age of 3 years. Ultrasonography along with other forms of imaging is invaluable in establishing the diagnosis of retinoblastoma.
While leukocoria is the most common presenting symptom of retinoblastoma, strabismus, decreased vision, ocular inflammation, and other rarer symptoms have also been observed.1 In general, the presentation varies with the stage of the disease at the time of diagnosis. In its earliest clinical stage, retinoblastoma appears as a flat transparent to slightly whitish colored lesion in the sensory retina. Dilated and tortuous feeding retinal vessels may be evident. As the tumor enlarges, it loses its transparency and takes on a creamy yellow to whitish coloration with foci of chalk-like calcification. As it grows beyond the boundary of the sensory retina, retinoblastoma will typically follow either an endophytic or exophytic growth pattern (Figure 11.1). Other growth patterns including mixed and diffuse infiltrative forms (Figure 11.2) are less commonly observed. Necrosis may be a significant component of the tumor. Endophytic retinoblastomas grow from the retina inward towards the vitreous cavity. Vitreous seeding from these friable tumors as well as anterior chamber involvement can simulate endophthalmitis and other inflammatory conditions. In contrast, exophytic retinoblastomas grow from the retina outward into the subretinal space and can cause exudative retinal detachment, sometimes displacing the retina anteriorly behind the lens. Advanced retinoblastoma can present with neovascular glaucoma, corneal edema, spontaneous hyphema, vitreous hemorrhage, pseudohypopyon, and vitreitis.
Figure 11.1 Classic presentation of retinoblastoma. External photograph showing right-sided leukocoria (A), slit lamp photograph (B), B-scan revealing an intraocular calcified mass (C), gross photograph of globe with retinoblastoma (D).
Figure 11.2 Diffuse variant of retinoblastoma. External photograph demonstrating the appearance of diffuse retinoblastoma (A), B-scan ultrasonography revealed irregularly thickened retinal detachment with vitreous cells (B). Typical features of retinoblastoma including intraocular mass and intraocular calcification were not present. Magnetic resonance imaging confirmed enhancing thickened retina (C). Enucleated globe with diffuse infiltrating retinoblastoma (D).
Ultrasonography is helpful in confirming the diagnosis of retinoblastoma and in differentiating the disease from other causes of leukocoria. This is particularly valuable when funduscopic examination is limited in advanced cases. On A-scan, the internal reflectivity of these lesions varies in accordance to the degree of calcification within the tumor. Non-calcified tumors exhibit low to medium internal reflectivity, whereas calcified lesions demonstrate high internal reflectivity. When a significant degree of calcification is present, shadowing of the adjacent sclera and orbit occurs. B-scan ultrasonography typically displays a rounded or irregular intraocular mass. It should be noted that mildly elevated and diffuse lesions have also been reported.2,3 Other associated ultrasonographic findings may include retinal detachment and vitreous opacities. When extraocular extension is present in cases of retinoblastoma, invasion of the optic nerve is the most common route. In cases where extensive calcification is present, tumor involvement of the optic nerve and extraocular extension can be difficult to detect secondary to the shadowing effect. CT and MRI imaging of the orbits should be used in combination with ultrasonography when optic nerve or extraocular invasion is suspected (Figure 11.2). MRI of the optic nerve, orbits, and brain is preferred as this modality offers superior soft tissue resolution and avoids potentially harmful exposure to radiation.
The diagnosis of retinoblastoma can generally be suspected based upon the clinical findings observed in a complete ophthalmic examination in the office or an examination performed under anesthesia. The most commonly observed finding is an elevated intraocular mass with characteristic calcification demonstrating either an endophytic or exophytic growth pattern. Other causes of intraocular calcification are listed in Box 11.1.
Box 11.1 Conditions associated with intraocular calcification
There are several pediatric ocular conditions that can cause leukocoria and should be considered in the differential diagnosis of retinoblastoma. The conditions that most commonly present a diagnostic challenge include retinopathy of prematurity (ROP), persistent fetal vasculature (PFV), Coats’ disease, toxocariasis, and medulloepithelioma (Table 11.1).
ROP occurs in the setting of known risk factors including: prematurity, low birth weight, and exposure to supplemental oxygenation in the neonatal period. While both ROP and retinoblastoma can present with leukocoria, in ROP the absence of the red reflex is caused by retinal dragging toward fibrovascular tissue in the retinal periphery. Eyes that develop retinoblastoma are usually of normal axial length. In contrast, in ROP it is more common for eyes to have some degree of the axial length shortening. Additionally, ROP is typically a bilateral condition whereas retinoblastoma can be either unilateral or bilateral. In the most advanced cases of ROP, the retina is detached in a funnel-like configuration, resulting in a hyper-reflective retrolental membrane on B-scan. The peripheral retina frequently exhibits a loop or trough-like appearance as a result of traction by the retrolental membrane (Figure 11.3).
PFV, formerly known as persistent hyperplastic primary vitreous (PHPV), is a congenital condition that usually presents during the first few days to weeks of life. In contrast, retinoblastoma typically presents months to years after birth. In nearly all cases, PFV is a unilateral condition that occurs in association with a number of other congenital ocular anomalies including: microphthalmos, a shallow or flat anterior chamber, a hypoplastic iris with prominent blood vessels, and a retrolental fibrovascular mass that causes the ciliary body processes to rotate inwards. On ophthalmic examination, a stalk-like structure connecting the optic nerve to the posterior lens capsule may be visualized. Ultrasonography can be used to confirm the diagnosis. On B-scan, persistent hyaloid remnants arising from the optic nerve are observed. The vitreous band may be extremely thin, and its entire course may not be visualized. Some vitreous bands can be extremely thick simulating a tightly closed, funnel-shaped retinal detachment.
The lens is often thin with irregularities in the posterior capsule (Figure 11.4). Eyes usually have some degree of axial length shortening. Calcification may be present, however in contrast to retinoblastoma, there is no discrete mass visualized clinically or with ultrasonography.
Reproduced with permission from: Fu EX, Hayden BC, Singh AD. Intraocular tumors. Ultrasound Clin 2008; 3:229–244.
Coats’ disease is a retinal vascular disorder characterized by telangiectasia, intraretinal exudation, and exudative retinal detachment. Although Coats’ disease can present at any age, it usually is diagnosed in young males between 4 and 10 years of age.4 It is most commonly a unilateral disease process. In the early stages of Coats’ disease, localized, shallow retinal detachments may occur. In more advanced cases, total exudative detachments secondary to leakage from aneurysmal blood vessels are observed. This exudative process results in yellow cholesterol crystal deposition in the subretinal space that can be observed clinically as refractile bodies. These particles are much less reflective than the calcium particles in retinoblastoma. Ultrasonography is helpful in differentiating the two entities, in that in retinoblastoma a distinct tumor can be detected beneath the retinal detachment, whereas no distinct mass is seen in Coats’ disease (Figure 11.5).
Toxocariasis is caused by ocular infestation by Toxocara canis. It typically occurs in older children with a history of soil ingestion or exposure to dogs. Clinically, ocular toxocariasis may present as a large retinal inflammatory mass with diffuse vitreitis. The appearance can simulate endophytic retinoblastoma, or if ocular toxocariasis presents with a solitary subretinal granuloma with little vitreous inflammation, the lesion can resemble exophytic retinoblastoma. In toxocariasis, the chorioretinal mass is most commonly located in the peripheral fundus and produce vitreoretinal bands that can extend to the optic disc. Contraction of these vitreoretinal membranes result in tractional retinal detachment. In contrast, tractional retinal detachments are extremely rare in retinoblastoma. Ultrasonography is useful in differentiating the two diseases, because vitreous traction bands and tractional retinal folds or detachments are characteristic of ocular toxocariasis. Additionally, the calcification which would be expected to be seen in retinoblastoma is absent in ocular toxocariasis.
Medulloepithelioma is a congenital neuroepithelial tumor that typically manifests during the first decade of life. It most commonly arises from the ciliary body, however involvement of the iris and optic nerve has also been reported.5–10 On ophthalmic examination, the tumor appears as a lightly pigmented or amelanotic cystic mass. Large cysts may break off from the main tumor and float freely in the anterior chamber or vitreous cavity. Because of their appearance and because medulloepithelioma may present with leukocoria, these tumors are an important consideration in the differential diagnosis of retinoblastoma. A-scan of medulloepithelioma shows mainly high internal reflectivity with a medium spike corresponding to cystic regions of the tumor. On B-scan, medulloepitheliomas typically appear as a dome-shaped, highly reflective mass with irregular internal structures. Cystic spaces can be demonstrated in some lesions (Figure 11.6).
In the following section, several of the more commonly encountered benign tumors of the uveal tract are discussed. Some of these tumors occur in isolation while others occur in association with various systemic disease manifestations. Ultrasound biomicroscopy (UBM), A-scan, and B-scan are helpful in characterizing these lesions and in making the correct diagnosis.
Circumscribed and diffuse choroidal hemangiomas are benign hamartomas. Although commonly asymptomatic, these tumors are prone to developing exudative retinal detachment which can result in significant reduction in visual function, metamorphopsia, and photopsia. Additionally, diffuse choroidal hemangiomas are associated with the development of glaucoma secondary to developmental anomalies of the anterior chamber angle and increased episcleral venous pressure.
On ophthalmoscopic examination, circumscribed choroidal hemangiomas appear as an orange choroidal mass with indistinct margins that blend with the surrounding choroid. They are frequently located in the macular region of the posterior pole, and are not usually thicker than 6 mm.11 Although these tumors are highly vascular, dilated and tortuous feeder vessels are not typically observed. Surrounding subretinal fluid leading to exudative retinal detachment with macular involvement is common in symptomatic cases. Retinal hard exudates are minimal or absent. Diffuse choroidal hemangiomas appear as orange, diffuse choroidal thickening that has been likened to a “tomato-catsup fundus.” Focal regions of excessively thickened choroid within the diffuse hemangioma may simulate circumscribed choroidal hemangioma. As with circumscribed hemangiomas, there may be associated exudative retinal detachment that often does not become manifest until adolescence.
On A-scan, circumscribed choroidal hemangiomas demonstrate high internal reflectivity with negligible attenuation. This differs from other tumors in the differential diagnosis including malignant melanoma which classically demonstrates low to medium reflectivity on A-scan. On B-scan, circumscribed choroidal hemangioma appears as a dome-shaped choroidal mass with smooth contours. They are hyperechoic with regular internal structure and little internal blood flow. Serous retinal detachment at the tumor margins and calcification on the tumor surface may be present.11 Angiographic studies such as fluorescein and indocyanine green (ICG) can also be diagnostic. Fluorescein angiography demonstrates a hyperfluorescent mass with a fine lacy vascular network of intrinsic vessels in the early phases followed by increasing hyperfluorescence throughout the angiogram with variable leakage in late views.12 With ICG angiography, a rapid increase in hyperfluorescence is seen early on followed by a “washout” effect in the late phase.13 OCT can also be helpful in evaluating secondary changes in the overlying retina such as shallow subretinal fluid or cystoid macular edema (Figure 11.7).
Figure 11.7 Circumscribed choroidal hemangioma. Clinical photograph with elevated choroidal mass with indistinct borders (A), Axial B-scan showing dome-shaped mass (B), A-scan with high internal reflectivity (C). Spectral domain OCT shows anterior bowing of the retina due to underlying choroidal hemangioma but the retinal architecture is normal (D).