Chapter 152 – Choroidal Hemangiomas
JAMES J. AUGSBURGER
GEORGE E. SANBORN
• Benign congenital vascular hamartoma of choroid.
• Red-orange, ill-defined, disc-shaped choroidal tumor located 3?mm or less from optic disc, foveola, or both.
• Diffuse or circumscribed growth patterns.
• Congenital, infantile, or juvenile glaucoma.
• Serous nonrhegmatogenous retinal detachment.
• Metaplasia of retinal pigment epithelium overlying tumor.
• Cystic degeneration of sensory retina overlying tumor.
• Other features of Sturge-Weber syndrome in patients who have diffuse choroidal hemangioma.
The choroidal hemangioma is a benign vascular tumor of the choroid. It occurs in two distinct clinical forms: a circumscribed form that is almost always isolated and nonsyndromic and a diffuse form that is usually part of the Sturge-Weber syndrome of encephalofacial hemangiomatosis.
EPIDEMIOLOGY AND PATHOGENESIS
Choroidal hemangiomas appear to be vascular birthmarks. They are relatively uncommon, but their precise incidence in the general population is unknown. They affect both sexes and all ethnic groups. Although probably congenital in most if not all patients, they are frequently not detected until the second through fourth decades of life. No cause has ever been identified. Neither form of the disease appears to be hereditary.
Most circumscribed choroidal hemangiomas are noted first when they produce visual symptoms caused by accumulation of serous subretinal fluid, degenerative changes in the macular retina, or both. Diffuse choroidal hemangiomas are usually detected at baseline ophthalmic evaluation of patients who have a facial nevus flammeus before the onset of symptoms. Visual impairment in eyes that have either diffuse or circumscribed choroidal hemangioma ranges from none to total blindness.
The diffuse choroidal hemangioma, usually part of the Sturge-Weber syndrome, is generally identified ipsilaterally to a facial nevus flammeus. The fundus on the affected side typically has a much more saturated red appearance than does the fundus on the uninvolved side ( Fig. 152-1 ). The choroid tends to be thickened diffusely by the hemangiomatous vascular lesion, but accentuated
Figure 152-1 Asymmetric fundus appearance in patient with diffuse choroidal hemangioma. A, Right fundus has saturated red color caused by diffuse choroidal hemangioma. Note large deep cup of optic disc. B, Uninvolved left fundus has more orange choroid than right. Note normal appearance of optic disc.
and sometimes nodular thickening occurs frequently in the macular and circumpapillary regions. The choroidal hemangioma becomes progressively thinner peripherally and gradually blends into the normal peripheral choroid. The choroidal thickening around the optic disc commonly results in prominent disc cupping that resembles glaucomatous optic neuropathy. Because elevated intraocular pressure, which is usually caused by elevated episcleral and orbital venous pressure, angle malformation, or both, is a feature of many eyes that have diffuse choroidal hemangioma, the optic disc can also exhibit true glaucomatous cupping. Although the retinal vasculature is sometimes normal in eyes that have a diffuse choroidal hemangioma, marked retinal vascular tortuosity is observed frequently in such eyes. The retinal pigment epithelium that overlies thicker portions of a diffuse choroidal hemangioma often undergoes fibrous metaplasia. The fibrous tissue on the surface of the hemangioma gives a whitish appearance to that part of the lesion. The neurosensory retina that overlies thicker portions of a diffuse choroidal hemangioma typically becomes thickened and cystic. Serous nonrhegmatogenous retinal detachment, either partial or total, is an eventual complication in many eyes that have diffuse choroidal hemangioma.
The circumscribed choroidal hemangioma is a reddish-orange, round to oval choroidal tumor located largely if not completely in the posterior half of the fundus ( Fig. 152-2 ). The typical lesion ranges from approximately 3–7?mm in diameter and 1–3?mm in thickness at the time of detection and diagnosis, but larger lesions
Figure 152-2 Clinical appearance of circumscribed choroidal hemangioma. Juxtapapillary reddish choroidal tumor is associated with shallow serous subretinal fluid that involves the central macula.
Figure 152-3 Indocyanine green angiography of circumscribed choroidal hemangioma (same lesion shown in Fig. 152-2 ). A, Early phase frame shows filling of prominent large-caliber intralesional blood vessels. B, Intermediate phase frame shows intense diffuse hyperfluorescence of hemangioma. C, Late phase frame shows central washout of fluorescence from tumor but persistent hyperfluorescence at margins of tumor.
occur occasionally. Almost all circumscribed choroidal hemangiomas are located within two disc diameters from the optic disc, foveola, or both at their posterior margins.  Such tumors almost never extend anterior to the equator unless they are extremely large. The retinal pigment epithelium that overlies a circumscribed choroidal hemangioma commonly undergoes degenerative changes, including fibrous metaplasia and occasionally bone formation, and the neurosensory retina overlying such lesions frequently becomes thickened and cystic. Partial or total nonrhegmatogenous retinal detachment occurs frequently as a complication
Figure 152-4 B-scan ultrasonography of circumscribed choroidal hemangioma. Lesion appears fusiform in cross-sectional shape and is almost as sonoreflective as orbital fat. Note localized retinal detachment overlying tumor.
of circumscribed choroidal hemangiomas, but massive accumulation of subretinal or intraretinal exudates, as occurs with retinal capillary hemangiomas and Coats’ disease, is rare.
DIAGNOSIS AND ANCILLARY TESTING
Fluorescein angiography of circumscribed choroidal hemangiomas typically reveals very early fluorescence of large-caliber choroidal blood vessels either before or simultaneously with the initial filling of the retinal arterioles. The entire lesion usually becomes diffusely fluorescent within several seconds after initial vascular filling. By the late frames, fluorescein commonly stains the entire lesion and any associated subretinal fluid.
Indocyanine green angiography of a circumscribed choroidal hemangioma  typically shows early filling of the intralesional vascular channels, intense hyperfluorescence of the lesion by the intermediate frames, and late washout of the central portion of the lesion ( Fig. 152-3 ). The full extent of a circumscribed choroidal hemangioma is usually revealed much more clearly by indocyanine green angiography than by fluorescein angiography.
B-scan ultrasonography of a circumscribed choroidal hemangioma typically shows a fusiform, biconvex cross-sectional shape of the lesion and internal brightness similar to that of orbital fat ( Fig. 152-4 ). B-scan ultrasonography of a diffuse choroidal hemangioma characteristically reveals generalized choroidal thickening by sonoreflective soft tissue and prominent optic disc cupping. On standardized A scan, both types of choroidal hemangioma tend to exhibit high-amplitude, broad-based echo spikes.
The principal lesions and disorders in the differential diagnoses of circumscribed and diffuse choroidal hemangiomas are listed in Box 152-1 .
For patients who have a diffuse choroidal hemangioma and ipsilateral facial nevus flammeus, the Sturge-Weber syndrome or a related multisystem syndrome must be suspected. Circumscribed choroidal hemangiomas are rarely associated with other features of the Sturge-Weber syndrome.
Baseline Systemic Evaluation
Because of the benign nature of choroidal hemangiomas, baseline systemic evaluation to look for evidence of metastatic disease is not appropriate.
Differential Diagnosis of Circumscribed and Diffuse Choroidal Hemangiomas
DIFFERENTIAL DIAGNOSIS OF CIRCUMSCRIBED CHOROIDAL HEMANGIOMA
Amelanotic choroidal nevus or melanoma
Metastatic carcinoma to choroid
Inflammatory choroidal granuloma
Nodular posterior scleritis
DIFFERENTIAL DIAGNOSIS OF DIFFUSE CHOROIDAL HEMANGIOMA
Benign reactive lymphoid hyperplasia of choroid
Leukemic or lymphomatous choroidal infiltration
Diffuse posterior scleritis
Uveal effusion syndrome
Figure 152-5 Histopathology of circumscribed choroidal hemangioma. A, Low-power photomicrograph (H&E, original magnification 100×) shows large choroidal vascular channels constituting choroidal hemangioma, overlying serous retinal detachment, and partially degenerated cystic overlying retina. B, Higher power photomicrograph (H&E, original magnification 200×) shows metaplastic thickening with partial calcification of retinal pigment epithelium overlying circumscribed choroidal hemangioma.
Choroidal hemangiomas usually consist in large part of cavernous vascular channels lined by mature endothelial cells and supported by thin intervascular fibrous septa ( Fig. 152-5 , A–B). Some choroidal hemangiomas, especially those of the diffuse type, also contain a prominent component of small, capillary-type vessels. Circumscribed choroidal hemangiomas appear to end rather abruptly at their margins and to cause some compression of the adjacent normal choroid. In contrast, diffuse choroidal hemangiomas terminate indistinctly in the periphery and do not have abrupt margins. Fibrous transformation of the retinal pigment epithelium occurs frequently over circumscribed choroidal hemangiomas ( Fig. 152-5 , B) and thick posterior regions of diffuse choroidal hemangiomas, and ossification of the transformed pigment epithelium develops in some eyes. The sensory retina that overlies a choroidal hemangioma frequently appears thickened and cystic. Eyes that have a diffuse choroidal hemangioma often have numerous other abnormalities, including dilated episcleral and intrascleral blood vessels, malformation or synechial closure of the anterior chamber angle, and massive cupping of the optic disc.
Treatment Options for Circumscribed and Diffuse Choroidal Hemangiomas
Noncoagulative laser therapy (transpupillary thermotherapy)
Radiation therapy (especially for hemangiomas associated with extensive nonrhegmatogenous retinal detachment)
• External beam radiation therapy
• Plaque radiotherapy
• Proton beam irradiation
Enucleation (blind painful eyes)
The currently employed treatment options for circumscribed choroidal hemangiomas are listed in Box 152-2 . Because choroidal hemangiomas are benign tumors without malignant potential, treatment is directed toward limitation or reversal of visual loss related to secondary retinal detachment, glaucoma, or other complications. Until recently, photocoagulation by means of a xenon arc photocoagulator or argon, krypton, or dye laser was the mainstay of treatment for most circumscribed choroidal hemangiomas and occasional diffuse choroidal hemangiomas associated with nonrhegmatogenous retinal detachment.  An intense, confluent photocoagulation of the entire lesion in an attempt to obliterate it was used for some tumors of this type, but a less intense treatment with spaced burns to the surface of the lesion in an attempt to reduce or block accumulation of subretinal fluid and promote its reabsorption was employed more extensively. Both methods led to partial or complete reabsorption of the subretinal fluid, but the former technique usually caused profound visual loss and the latter was frequently associated with subsequent fluid reaccumulation and progressive visual impairment. As an alternative to photocoagulation, a noncoagulative infrared laser therapy employing relatively large spot sizes and long-duration exposures (transpupillary thermotherapy) has been used to treat such tumors in several centers.  The long-term effectiveness of this therapy is unknown. Photodynamic therapy using verteporfin has been used with considerable success as treatment of small to medium-size circumscribed choroidal hemangiomas in recent years  and is currently regarded as the treatment of choice for such lesions.
In patients who have an extremely thick choroidal hemangioma, extensive nonrhegmatogenous retinal detachment, or a diffuse or circumscribed choroidal hemangioma that failed to respond to photocoagulation, noncoagulative laser therapy, or photodynamic therapy, low-dose ocular irradiation appears to be an effective therapeutic option ( Fig. 152-6 ). Several different radiation therapy methods (external beam photon radiotherapy,  plaque radiotherapy, and proton beam irradiation ) have been employed with good success in selected patients. When external beam radiotherapy or proton beam irradiation is used, the eye is usually treated to a target dose of approximately 12–20?Gy.   When plaque radiotherapy is employed, the tumor is usually treated to an apex dose of approximately 20–30?Gy. These forms of radiation therapy induce partial or total tumor regression, stimulate gradual reabsorption of subretinal fluid that is usually sustained for many months to years, and provide better visual results than obliterative or repeated scatter photocoagulation.
COURSE AND OUTCOMES
If a circumscribed choroidal hemangioma involves the central macula or if a diffuse hemangioma is particularly thick in the macula, progressive degeneration of the overlying retinal pigment epithelium and sensory retina often occurs. These degenerative
Figure 152-6 Radiation therapy of larger circumscribed choroidal hemangioma. A, Pretreatment appearance of choroidal hemangioma. Note secondary serous retinal detachment involving macula and fibrous metaplasia of overlying retinal pigment epithelium. B, Post-treatment appearance of same eye 1 year following I-125 plaque radiotherapy. Note pronounced tumor regression and retinal reattachment. Unfortunately, vision in the eye was only hand motion perception because of extensive retinal degeneration and optic atrophy.
changes can, and commonly do, result in progressive visual loss. In addition, secondary serous retinal detachment can cause profound visual impairment, especially if the subretinal fluid becomes bullous and persists chronically. Chronic, bullous retinal detachment is frequently followed by neovascularization of the iris and neovascular glaucoma. Many patients who have diffuse choroidal hemangioma and facial nevus flammeus also develop primary congenital, infantile, or juvenile glaucoma in the affected eye, and this condition can also impair vision in the eye.
Following obliterative laser therapy, most circumscribed choroidal hemangiomas shrink considerably and develop fibrous scarring on their surface. The associated retinal detachment is usually reabsorbed within a few weeks. Unfortunately, such treatment is often associated with persistent macular retinal traction, chronic cystoid macular edema, or both. After scatter laser therapy to the surface of the tumor, the subretinal fluid usually resolves within a few weeks. The lesion proper typically shows minimal if any change in size. Unfortunately, the subretinal fluid frequently reaccumulates after a few months to a few years. Additional scatter laser therapy can be provided, but each supplemental laser treatment of this type appears less likely to produce a favorable effect on the fluid. The long-term course after laser thermotherapy is currently unknown.
Following photodynamic therapy, prompt clinical regression of the tumor generally occurs.  Associated subretinal fluid usually disappears promptly. Sustained local tumor regression and lack of reaccumulation of subretinal fluid have been reported.
Following external beam radiation therapy or proton beam irradiation, the hemangioma undergoes partial regression and the subretinal fluid slowly goes away.   Even a total bullous retinal detachment usually resolves, but it may take up to 6 months or more for this to happen. The greater the amount of subretinal fluid and the longer it has been present at the time of irradiation, the longer it usually takes for it to go away after that treatment. After plaque radiotherapy, the hemangioma usually undergoes more rapid and more extensive clinical regression than after external beam radiation therapy. Any associated subretinal fluid is reabsorbed slowly, just as occurs after external beam treatment. In the great majority of eyes treated by radiation therapy, the subretinal fluid never reaccumulates. Although concern always exists about radiation retinopathy and papillopathy after irradiation of a choroidal hemangioma, the low dose of radiation used to treat such tumors rarely causes such side effects.
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