Chapter 155 – Hemangiomas of Retina
JAMES J. AUGSBURGER
ZÉLIA MARIA S. CORRÊA
• Benign primary blood vessel tumors of retina in two distinct types: retinal capillary hemangiomas (von Hippel tumors) and retinal cavernous hemangiomas.
• Capillary hemangioma of retina: spherical bright red intraretinal tumor associated with dilated afferent artery and efferent vein.
• Cavernous hemangioma of retina: sessile intraretinal lesion composed of cluster of dark red vascular saccules.
• Distinct ophthalmic and systemic features that correspond to specific type of retinal hemangioma.
CAPILLARY HEMANGIOMA OF RETINA
The retinal capillary hemangioma (von Hippel tumor) is a benign vascular tumor that arises from the blood vessels of the retina or optic disc. It develops unifocally or multifocally and unilaterally or bilaterally, tends to enlarge progressively, and frequently leads to exudative or tractional retinal complications that impair vision in the affected eye or eyes. This lesion occurs in both syndromic and isolated clinical settings. In the syndromic form, retinal capillary hemangiomas occur as manifestations of the von Hippel–Lindau syndrome (VHLS). In the isolated nonsyndromic form of the disease, a single retinal capillary hemangioma is usually detected in only one eye of an otherwise healthy individual. If a patient has only the characteristic retinal lesion and its associated ocular complications, that patient is said to have von Hippel’s disease (angiomatosis retinae) and not VHLS.
EPIDEMIOLOGY AND PATHOGENESIS
The retinal capillary hemangioma is uncommon, but its precise frequency in the general population is unknown. Men and women are affected equally, without any racial predilection. The age at the time of initial detection of the retinal lesion can range from younger than 10 years to older than 80 years; however, the average age at initial detection is usually between 15 and 35 years. The lesions can occur unilaterally or bilaterally and unifocally or multifocally in affected persons. The precise relative incidences of unilateral, unifocal lesions versus bilateral, multifocal retinal capillary hemangiomas are unknown.
The principal recognized risk factor for development of one or more retinal capillary hemangiomas is presence of the gene for VHLS. Most individuals who have multifocal bilateral retinal capillary hemangiomas have this syndrome, whereas most persons who have a single tumor in one eye do not.
Blurred vision in the affected eye or loss of visual field is the usual presenting symptom. In families known to contain members who have VHLS, ophthalmic screening examinations frequently identify asymptomatic small tumors in one or both eyes.
The typical retinal capillary hemangioma appears as a reddish spherical lesion fed and drained by dilated tortuous retinal blood vessels ( Fig. 155-1 ). Prominent afferent and efferent vessels of this type are commonly associated with tumors as small as 1?mm in diameter. In many cases, the feeding arteries and draining veins also become irregularly segmented with fusiform dilations along their course. Intraretinal and subretinal exudation overlying and surrounding a retinal capillary hemangioma is common, particularly when the tumor is more than 2–3?mm in diameter. In many eyes, the accumulation of intraretinal and subretinal exudates is accentuated in the macular region even if the hemangioma is remote from the macula. An exudative retinal detachment may occur and become chronic, frequently leading to iris neovascularization and neovascular glaucoma. Some eyes that have one or more retinal capillary hemangiomas develop proliferative vitreoretinopathy as a prominent feature. The vitreous membranes are strongly adherent to the hemangioma; consequently, contraction of the membranes often leads to a tractional retinal detachment.
Capillary hemangiomas can also arise from the optic disc. Lesions of this type usually retain the reddish color of extrapapillary retinal capillary hemangiomas but frequently appear less well defined than their extrapapillary counterparts.  The development of exudative intraretinal and subretinal fluid around the lesion and disc can obscure the margins of the lesion.
DIAGNOSIS AND ANCILLARY TESTING
Fluorescein angiography of a typical retinal capillary hemangioma shows rapid filling of the afferent artery, brisk filling of the retinal vascular tumor, intense hyperfluorescence of the entire vascular lesion shortly thereafter, and subsequent rapid filling
Figure 155-1 Typical retinal capillary hemangioma. Note associated intraretinal exudates and shallow exudative retinal detachment. The patient was a 62-year-old man who did not have the von Hippel–Lindau syndrome.
Figure 155-2 Fluorescein angiography of retinal capillary hemangioma. A, Retinal arterial phase frame shows early hyperfluorescence of entire mass. B, Late phase frame that shows intense generalized hyperfluorescence of hemangioma plus leakage of fluorescein into adjacent vitreous.
Differential Diagnosis of Retinal Capillary Hemangioma
Astrocytoma of retina
Idiopathic retinal telangiectasis (Coats’ disease and Leber’s retinal aneurysms)
Acquired fibrovascular retinal hemangiomatous lesion
of the efferent vein ( Fig. 155-2 ). An active retinal capillary hemangioma characteristically leaks fluorescein exuberantly into the overlying vitreous, often causing the late phase frames to be extremely hazy because of diffuse vitreous fluorescence. Fluorescein also leaks into the subretinal fluid of an associated exudative retinal detachment.
Ultrasonography is not particularly helpful for the identification and delineation of the extent of individual retinal capillary hemangiomas. Computed tomography and magnetic resonance imaging are effective for the detection of concurrent central nervous system (CNS) vascular lesions of VHLS.
The important lesions in the differential diagnosis of retinal capillary hemangioma are listed in Box 155-1 .
As already indicated, there is a strong association between retinal capillary hemangiomas and VHLS. However, the precise proportions of isolated and syndromic cases are unknown. In general, patients who have VHLS are likely to develop retinal capillary hemangioma at an earlier age and are more likely to have multiple, bilateral retinal tumors than patients who have sporadic retinal capillary hemangioma.  
Baseline Systemic Evaluation
Individuals who have multifocal or bilateral retinal capillary hemangiomas, a family history of capillary hemangiomas of the
Treatment Options for Retinal Capillary Hemangiomas
• Plaque radiotherapy
• Proton beam irradiation
Enucleation (blind painful eyes due to tumor-related complications)
retina, vascular CNS tumors, or renal cell carcinoma should be considered to have VHLS until proved otherwise.  These individuals should undergo comprehensive evaluation for features of VHLS. If possible, family members should also be examined ophthalmoscopically to see if any other affected individuals can be identified.
The von Hippel tumor consists of small capillary-like blood vessels lined by endothelial cells and a delicate stroma of vacuolated fibrous astrocytes. Although vascular components of von Hippel tumors are much more prominent clinically than the stromal elements, cytogenetic studies have shown the stromal cells to be the ones with chromosome 3p25-26 abnormalities.
Management decisions for capillary hemangiomas of the retina should be based on the desire to preserve or restore vision in affected eyes ( Box 155-2 ). The most commonly employed method of management is photocoagulation of the vascular tumor. This treatment is particularly effective against tumors that are up to about 3?mm in diameter. Treatment usually entails creation of a confluent white burn that encompasses the entire hemangioma. Large spot sizes and relatively long-duration exposures are generally recommended. Multiple treatment sessions are usually required to eradicate the hemangioma. Laser treatment of the retinal arteriole that supplies the hemangioma is sometimes performed in an attempt to occlude that vessel and thereby enhance the direct treatment effect. Also, scatter laser treatment is frequently given to the retina surrounding the capillary hemangioma in an effort to prevent post-treatment extension of any exudative retinal detachment. In successfully treated patients, the hemangioma becomes atrophic and involuted, the feeding and draining retinal vessels lose their dilation and tortuosity, and associated exudates disappear gradually. Depending on the extent of macular retinal degeneration and scarring, the vision may or may not recover.
For peripheral retinal capillary hemangiomas and some larger postequatorial lesions of this type, transconjunctival or transscleral cryotherapy can be employed as an alternative to photocoagulation. Double or even triple freeze-thaw therapy is applied to the tumor; during treatment, the ice ball is allowed to come completely through the lesion into the overlying vitreous. This form of treatment must be repeated at intervals of about 4–6 weeks until the lesion is totally obliterated and the retinal feeder and drainer vessels are back to normal caliber.
In some eyes that contain an extremely large retinal capillary hemangioma, a few experienced ophthalmic surgeons have employed aggressive surgical techniques such as penetrating diathermy and microsurgical tumor resection in an attempt to salvage the eye. A relatively new method for the treatment of selected retinal capillary hemangiomas associated with massive exudative retinal detachment is focal tumor irradiation using either a radioactive plaque or charged particle beam. Plaque radiotherapy
appears to work well for medium-sized to large retinal capillary hemangiomas located 3?mm or more from the optic disc, and charged particle beam irradiation is particularly appropriate for juxtapapillary and epipapillary tumors. Some eyes that contain a large retinal capillary hemangioma or multiple capillary hemangiomas of the retina can also be managed by pars plana vitrectomy coupled with endophotocoagulation or endodiathermy of the tumors. Finally, some eyes that become blind and painful or phthisical eventually come to enucleation.
Patients who have a small retinal capillary hemangioma that causes no exudative phenomena and those who have one or more previously treated regressed retinal capillary hemangiomas must continue to be monitored periodically for local tumor reactivation or new tumor formation.
COURSE AND OUTCOMES
The natural history of retinal capillary hemangiomas is highly varied. Although some retinal capillary hemangiomas have been observed to remain stable for months to even years and others to regress spontaneously without resultant exudative phenomena, many if not most capillary hemangiomas of the retina enlarge to at least a limited degree during follow-up. Some cases progress to a blind painful eye. Visual prognosis in eyes that have retinal capillary hemangioma depends on the size, location, and number of lesions, the extent of intraretinal and subretinal exudation that occurs, and the amount of vitreoretinal fibroplasia that develops in response to the lesion. Fortunately, most retinal capillary hemangiomas can now be controlled, if not eradicated, by local obliterative therapy. Unfortunately, many affected eyes still suffer mild to profound uncorrectable visual impairment.
CAVERNOUS HEMANGIOMA OF RETINA
Cavernous hemangioma of the retina is a benign retinal vascular hamartoma. It is generally asymptomatic and visually insignificant unless it involves the macula or causes intravitreal bleeding. Although occasionally associated with cutaneous vascular lesions and minimal nonprogressive intracranial vascular lesions, the retinal cavernous hemangioma usually appears to be nonsyndromic in nature. It is most frequently identified in a unifocal nonfamilial situation, but occasional bilateral familial cases have been reported. The lesion has no recognized malignant potential.
EPIDEMIOLOGY AND PATHOGENESIS
Cavernous hemangioma of the retina is uncommon, but its precise frequency in the general population is unknown. It affects both sexes and occurs in all ethnic groups. The lesion is congenital but may not be detected until relatively late in life. Most affected patients have a single lesion in one eye and no evidence of a multisystem syndrome; however, occasional patients have multiple retinal lesions and some have a familial disorder characterized by benign cavernous hemangiomas or telangiectatic vascular lesions of the skin and CNS.
Most patients are asymptomatic, and their tumor is detected on routine ophthalmic examination. In some cases, vision is blurred because of the macular location of the lesion. In other cases, the patient reports floaters attributable to intravitreal bleeding from the hemangioma.
The typical retinal cavernous hemangioma appears as a cluster of vascular saccules within the sensory retina in association
Figure 155-3 Typical cavernous hemangioma of the retina.
Figure 155-4 Fluorescein angiography of cavernous hemangioma of retina. A, Laminar venous phase frame shows most vascular saccules that comprise the lesion to be nonfluorescent. B, Late phase frame shows hyperfluorescence of most vascular saccules. Note the plasma-erythrocyte separation in some larger vascular saccules.
with a retinal vein of anomalous appearance that is neither dilated nor tortuous ( Fig. 155-3 ).  The individual intraretinal lesion typically measures approximately 1–4 disc areas in size, and the component vascular saccules generally range from microaneurysmal size to about 0.1?mm in diameter. In some of the larger vascular saccules, gravitational plasma-erythrocyte separation can sometimes be observed. Larger lesions commonly have associated whitish glial proliferation on their surface, which can be mistaken for intraretinal exudates. True subretinal and intraretinal exudates are extremely uncommon in association with such lesions. Occasional cavernous hemangiomas of the retina give rise to spontaneous vitreous hemorrhage, which may be recurrent and massive.
Cavernous hemangiomas of the retina can arise from all regions of the retina and also from the optic disc.
DIAGNOSIS AND ANCILLARY TESTING
Fluorescein angiography ( Fig. 155-4 ) typically shows hypofluorescence of the entire lesion in the early phase frames and slow filling of the lesion as the study progresses. The component vascular saccules accumulate fluorescein gradually and then remain brightly fluorescent long after normal intravascular fluorescence has faded. Fluorescein leakage into the retina or vitreous is usually not evident, even in late phase frames.
Ultrasonography is generally not helpful in the diagnostic assessment of retinal cavernous hemangiomas.
Differential Diagnosis of Retinal Cavernous Hemangioma
Idiopathic retinal telangiectasis
Retinal arterial macroaneurysm
The only lesions that resemble cavernous hemangioma of retina clinically are the microaneurysmal lesions of idiopathic retinal telangiectasia and retinal arterial macroaneurysms ( Box 155-3 ).
Most patients who have a cavernous hemangioma of the retina have no associated systemic disorder. However, occasional patients have small hemangiomas and telangiectases of the skin and similar lesions in the CNS.    In some families, this multisystem disorder appears to be inherited as an autosomal dominant syndrome. Individuals who have this syndrome are more likely to have multifocal retinal cavernous hemangiomas, bilateral retinal cavernous hemangiomas, or both than persons who have sporadic nonfamilial disease.
Baseline Systemic Evaluation
If the family history or examination of family members suggests an autosomal dominant inheritance pattern and examination of affected individuals reveals multifocal or bilateral retinal cavernous hemangiomas or cutaneous hemangiomas and telangiectases, baseline CNS imaging and even periodic follow-up imaging are probably advisable. 
The cavernous hemangioma of the retina consists of a cluster of large-caliber thin-walled intraretinal vascular saccules lined by normal vascular endothelial cells. The tumor thickens and replaces the sensory retina at the affected site. Because it is a congenital tumor composed of benign tissue elements that occur normally in the retina, the retinal cavernous hemangioma is generally considered to be a hamartoma.
Most eyes that contain a cavernous hemangioma of the retina or optic disc have no visual problems and require no treatment ( Box 155-4 ). If recurrent massive vitreous hemorrhage from a cavernous hemangioma of the retina occurs, transscleral cryotherapy or pars plana vitrectomy with endophotocoagulation may be required.
Treatment Options for Retinal Cavernous Hemangiomas
Excision of hemangioma via vitrectomy
COURSE AND OUTCOMES
Most retinal cavernous hemangiomas that have been observed for prolonged periods of time remain stable in size and clinical appearance. Occasional hemangiomas of this type bleed repeatedly into the vitreous over the course of many years. The visual prognosis of the affected eyes is good unless the hemangioma involves the macular retina.
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