Intraocular Vascular Tumors
Retinal Capillary Hemangioma
Retinal Capillary Hemangioma is a benign vascular tumor that arises from the retina or optic disc. The average age at initial detection is usually between 15 and 35 years1 with mean age at diagnosis in von Hippel Lindau syndrome (VHL)being approximately 25 years.2 This lesion occurs in both syndromic (von Hippel Lindau syndrome) and isolated clinical settings, and can be further classified on the basis of their location within the retina (peripheral and juxtapapillary), morphology (endophytic, exophytic and sessile); and its effects on the retina (exudative and tractional form). If a patient has only characteristic retinal lesion and its associated ocular complications, that patient is said to have von Hippel disease rather than VHL syndrome. Most individuals who have multifocal bilateral retinal capillary hemangiomas have the syndrome, whereas most persons who have a single tumor is one eye do not.
Blurred vision in the affected eye or loss of visual field is the usually presenting symptom. The lesion typically appears as a reddish spherical lesion fed and drained by dilated tortuous retinal blood vessels. Prominent afferent and efferent vessels of this type are commonly associated with tumors as small as 1 mm in diameter. In many cases veins also become irregular and segmented with fusiform dilations along their course. Intraretinal and subretinal exudation is often seen around the tumor or in the macula. The majority of the retinal capillary hemangiomas are located in the superotemporal and inferotemporal peripheral retina. Exudation overlying and surrounding a retinal capillary hemangioma is common particularly when the tumor is more than 2-3 mm in diameter.3 Exudative retinal detachment may occur and become chronic, frequently leading to iris neovascularization and neovascular glaucoma. Vitreous membranes are strongly adhering to the hemangioma; consequently contraction of the membranes leads to a complex tractional retinal detachment.3
Fluorescein angiography: 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 of the efferent vein. An active lesion characteristically leaks fluorescein exuberantly into the vitreous.4 Optical coherence tomography can be extremely helpful in monitoring the course and extend of submacular exudation.4 Computed tomography and magnetic resonance imaging are effective for the detection of concurrent central nervous system vascular lesions and abdominal visceral lesions of von Hippel Lindau Syndrome.
- Astrocytoma of retina
- Coat´s disease
- Leber´s multiple retinal arterial aneurysms
- Acquired fibrovascular retinal hemangiomatous lesion
Management decisions should be based on the desire to preserve or restore vision in affected eyes. The most commonly employed method of management is photocoagulation of the vascular tumor which is particularly effective against tumor that are less than or equal to 2 mm in attached retina. In successfully treated patients, the hemangioma becomes atrophic and involutes, the feeding and draining retinal vessels lose their dilation and tortuosity, and associated exudates disappear gradually. For peripheral and some larger postequatorial lesions, transconjunctival or trans-scleral cryotherapy can be employed. Treatment must be repeated at intervals of 4-6 weeks until the lesion is totally obliterated and the retinal feeder and drainer vessels are back to normal caliber.8-10 Some authors use intravitreal steroids to modulate the initial exuberant exudative response that can occur following laser or cryotherapy. Eyes with secondary exudative or tractional retinal detachment associated with large retinal capillary hemangioma or multiple retinal capillary hemangiomas usually require pars plana vitrectomy with membrane peeling and frequently endophotocoagulation of the retinal tumor or tumors. Plaque radiotherapy appears to work well for medium-sized to large retinal capillary hemangiomas located 3 mm or more from the optic disc.11,12
The natural history is highly varied. Visual prognosis depend on the size, location and number of lesions, the extend of intraretinal and subretinal exudation and the amount of vitreoretinal fibroplasia that develops in response to the lesion. Most retinal capillary hemangiomas can now be controlled, if not eradicated by local obliterative therapy.12
Retinal Cavernous Hemangioma
Retinal Cavernous Hemangioma is a benign vascular hamartoma, usually sporadic and restricted to the retina or optic nerve head; but can also occur in a familial (autosomal dominant) pattern and may be associated with intracranial and skin hemangiomas. The lesions are characterized by the formation of grape-like clusters of thin-walled saccular angiomatous lesions in the inner retina or on the optic nerve head. The blood flow is derived from the retinal circulation and is relatively stagnant, producing a characteristic fluorescein picture (see below). The lesion has no recognized malignant potential. Some patients also will have small hemangiomas and telangiectasias of the skin or central nerve system. 13
Generally asymptomatic, unless it involves the macula or bleeds into the vitreous. Most patients tumor is detected on routine ophthalmic examination. Typical appears as a cluster of vascular saccules within the sensory retina in association with retinal vein of anomalous appearance that is neither dilated or tortuous.13,14
Fluorescein angiography: The dilated saccular lesions fill slowly during angiography and plasma-erythrocyte layering occurs as a result of the sluggish blood flow; leakage is characteristically absent, correlating with the absence of subretinal fluid and exudate, serving to differentiate it from retinal telangiectasia, von Hippel retina angiomatosis and racemose aneurysm of the retina.15
The only lesions that resemble cavernous hemangioma of retina clinically are the microaneurysmal lesions of idiopathic retinal telangiectasia (Coat´s disease) and Leber multiple retinal arterial aneurysms.
Usually not indicated unless recurrent vitreous hemorrhage develops, in which case photocoagulation or cryotherapy may be effective. 17,18
Most lesions have been observed for prolonged periods of time remain stable in size and clinical appearance. Visual prognosis is good unless the hemangioma involves the macula.
Choroidal hemangioma is a benign hamartomatous disorder (3A) that occurs in two distinct clinical forms: a circumscribed form that is almost always isolated and nonsyndromic, and diagnosed between the second and fourth decade of life; and a diffuse form that is usually part of the Sturge-Weber syndrome of encephalo-facial hemangiomatosis. They are relatively uncommon, and their exact incidence in unknown.19
Most circumscribed choroidal hemangiomas are noted first when they produce visual symptoms caused by accumulation of serous subretinal fluid, degenerative changes in the macula or both. Diffuse hemangiomas are usually detected at baseline ophthalmic evaluation of patients who have a facial nevus flammeus before the onset of symptoms.
- Diffuse choroidal hemangioma: usually part of the Sturge-Weber syndrome, is generally identified ipsilaterally to a facial nevus flammeus. The fundus typically has a much more saturated red appearance than that of the uninvolved side. The choroid tends to be thickened diffusely by the hemangiomatous vascular lesion, but accentuated and sometimes nodular thickening occurs frequently in the macular and circumpapillary regions. The choroidal thickening around the optic disc commonly results in prominent disc cupping that resembles glaucomatous optic neuropathy. Elevated intraocular pressure usually is caused by elevated episcleral and orbital venous pressure, angle malformation or both; is a feature of many eyes that have diffuse choroidal hemangioma. The retinal pigment epithelium that overlies thicker portions of a diffuse choroidal hemangioma often undergoes fibrous metaplasia which gives the lesion a whitish coloration. Serous retinal detachment is an eventual complication in many eyes that have diffuse choroidal hemangioma.20
- Circumscribed choroidal hemangioma: reddish-orange, round to oval choroidal tumor located largely if not completely in the posterior half of the fundus. Typical lesion ranges from 3 to 7 mm in diameter and 1 to 3 mm in thickness. Almost all are located within two disc diameters from the optic disc, foveola or both at their posterior margins. The retinal pigment epithelium that overlies the lesion commonly undergoes degenerative changes, including fibrous metaplasia and occasionally degenerative calcification. Serous retinal detachment occurs frequently as a complication, and can be mistaken for central serous retinopathy. 21
Clinical diagnosis is based primarily on recognition of the characteristic lesion, or other typical features mentioned. Fluorescein angiography of circumscribed choroidal hemangiomas typically reveals very early hyperfluorescence of larger-caliber choroidal blood vessels either before or simultaneously with the initial filling of the retinal arterioles. By late frames, fluorescein commonly stains the entire lesion and any associated subretinal fluid. Optical coherence tomography can highlight and document the subretinal fluid accumulation along with cystic retinal degeneration that can occur overlying the lesion. 21 Indocyanine green angiography typically shows filling of the intralesional vascular channels, intense hypercyanescence of the lesion by the intermediate frames (peaks around 3-4 minutes) and late washout of the central portion of the lesion. The full extent of a circumscribed choroidal hemangioma is usually revealed much more clearly. 21 B-scan ultrasonography of a circumscribed choroidal hemangioma typically shows a fusiform, biconvex cross-sectional shape of the lesion with A-scan demonstrating high reflectivity. Diffuse choroidal hemangiomas characteristically reveal moderately bright generalized posterior choroidal thickening and prominent optic disc cupping. 21
- Circumscribed choroidal hemangioma: amelanotic choroidal nevus or melanoma, central serous chorioretinopathy, primary extraophthalmic cancer metastatic to choroid, choroidal osteoma, inflammatory choroidal granuloma, nodular posterior scleritis and Harada´s disease.
- Diffuse choroidal hemangioma: Benign reactive lymphoid hyperplasia of choroid, leukemic choroidal infiltration, diffuse posterior scleritis and uveal effusion syndrome.
The treatment is directed toward limitation or reversal of visual loss related to secondary retinal detachment, glaucoma or other complications. Some asymptomatic cases can be observed. Photodynamic therapy (PDT) using verteporfin has been used with considerable success as treatment of small to medium-size circumscribed choroidal hemangiomas and is currently regarded as the treatment of choice for such lesions in many centers. In some cases PDT has been combined with intravitreal anti-vascular endothelial growth factor drug therapy to treat eyes with a large amount of turbid subretinal fluid, subfoveal tumor location, or both. In patients who have an extremely thick choroidal hemangioma, extensive non-rhegmatogenous retinal detachment, or a diffuse or circumscribed choroidal hemangioma that is refractory to PDT, low-dose ocular irradiation appears to be an effective therapeutic option. Several different radiation therapy methods (external beam photon radiotherapy, plaque radiotherapy, proton beam irradiation, gamma knife radiotherapy and stereotactic radiotherapy) have been employed with good success in selected patients. Radiation therapy induces partial or total tumor regression, stimulates gradual reabsorption of subretinal fluid that is usually sustained for many months to years, and preserves useful vision in at least some affected eyes. 22-27
Visual impairment ranges from none to total blindness if progressive degeneration of the overlying retinal pigment epithelium and sensory retina occurs in the macula. In addition, secondary serous retinal detachment can cause profound visual impairment. Chronic bullous retinal detachment is frequently followed by neovascularization of the iris and neovascular glaucoma. Following PDT prompt clinical regression of the tumor generally occurs, associated subretinal fluid usually disappears promptly within 3 months. Sustained local tumor regression and lack of reaccumulation of subretinal fluid have been reported in most but not all cases. Following radiation therapy, the hemangioma generally undergoes partial regression and the subretinal fluid slowly resolves, but this may take up to 6 months or more. In the great majority of eyes treated by radiation therapy, the subretinal fluid never reaccumulates. The low dose of radiation used to treat such tumors rarely causes side effects.
Retinal arterio-venous malformation (Wyburn-Mason Syndrome)
Retinal arterio-venous malformation (also known as a racemose angioma) is a rare sporadic disorder that primarily affects the retina and brain, and is characterized by congenital arterio-venous malformation in which no intervening capillary bed exists (unlike retinal capillary hemangioma). Lesions are typically unilateral, nonhereditary and located in the retina or optic nerve. The diagnosis is most commonly made later in childhood, often detected as an incidental finding in an asymptomatic patient or as cause of visual impairment in an amblyopic eye.28,29
The malformations have been classified into three groups depending upon the severity
- Group I: Abnormal capillary plexus between the major vessels of the arterio-venous malformations.
- Group II: Arteriovenous malformations lack any intervening capillary between the artery and vein.
- Group III: Arteriovenous malformations are the most extensive with dilated and tortuous vessels and no apparent distinction between the artery and vein.
If the lesions are larger they may be associated with subretinal fluid and exudate. 29
Fluorescein angiography is the most helpful diagnostic test. It demonstrates abnormal arteriovenous connections and presence34 or absence of intervening capillaries. In the most severe cases (Grade III) arteries and veins cannot be differentiated even on angiography. Abnormal retinal vasculature characteristically demonstrates absence of leakage.30
The retinal vascular malformations are usually not amenable to any therapy. 31
Retinal Vasoproliferative Tumor
Retinal vasoproliferative tumors are uncommon retinal lesions which were initially termed as ¨presumed acquired retinal hemangiomas¨ to differentiate them from capillary hemangioma.32,33 Usually present in the third of fourth decade and both sexes are equally affected. May be primary (74%) or secondary to pre-existing ocular disease (26%) usually inflammatory, vascular, traumatic, dystrophic and degenerative ocular disease such as intermediate uveitis and retinitis pigmentosa. The majority of patients with primary tumors are solitary (87%) in contrast to those with secondary tumors where multiple lesions were found in 42% of cases.34 The exact nature of these remains uncertain, but histologically these lesions are composed of mixture of glial cells and a network of fine capillaries with some larger dilated blood vessels.35
Vasoproliferative tumors appear as a globular yellowish-pink vascular mass in the peripheral retina lacking the feeder vessels typically seen in retinal capillary hemangioma. Sub-retinal exudation, which may be extensive, is common occurring in over 80% of cases. Macular fibrosis may lead to visual loss. 34
Most vasoproliferative retinal tumors can be treated successfully with triple freeze thaw transconjunctival cryotherapy, although repeat treatments may be required. Small peripheral vasoproliferative tumors, lacking significant exudate or maculopathy may be managed by periodic observation. Other treatment options include plaque brachytherapy, laser photocoagulation and photodynamic therapy. 34-36
1. Gass JD, Braunste in R. Sessile and exophytic capillary angiomas of the juxtapapillary retina and optic nerve head. Arch Ophthalmol. 1980;98: 1790-1797.
2. Maher ER, Yates JR, Harries R, et al. Clinical features and natural history of von Hippel Lindau disease. QJ Med 1990;77:1151-1163.
3. Colvard DM, Robertson DM, Traytmann JC. Cavernous hemangioma of the retina. Arch Ophthalmol 1978;96:2042-4.
4. Gaudric A, Krivosic V, Duquid G, et al. Vitreoretinal surgery for severe retinal capillary hemangiomas in von Hippel Lindau disease. Ophthalmol 1980;98:1790
5. Singh AD, Shields CL, Shields JA. von Hippel-Lindaudisease. Surv Ophthalmol 2001;46:117-142.
6. Hardwig P, Robertson OM. von Hippel - Lindau disease: a familial, often lethal, multi-system phakomatosis. Ophthalmology. 1984;91:263- 270.
7. Shields JA, Decker WL, Sanborn GE, Augsburger JJ, Goldberg RE. Presumed acquired retinal hemangiomas. Ophthalmology. 1983;90: 1292- 1300.
8. Schmidt-Erfurth UM, Kusserow C, Barbazetto IA, Laqua H. Benefits and complications of photodynamic therapy of papillary capillary hemangiomas. Ophthalmology 2002;109:1256-1266.
9. Schmidt D, Natt E, Neumann HP. Long-term results of laser treatment for retina angiomatosis in von Hippel. Saudi Journal of Ophthalmology, Volume 21, No. 1, January – March 2007 Lindau disease. Eur J Med Res 2000;5:47-58.
10. Blodi CF, Russell SR, Pulido JS, Folk JC. Direct and feeder vessel photocoagulation of retinal angiomas with dye yellow laser. Ophthalmology 1990;97:791-797.
11. Welch RB. The recognition and treatment of early angiomatosis retinae and use of cryosurgery as an adjunct to therapy. Trans Am Ophthalmol Soc 1970;68:367-424.
12. Atebara NH. Retinal capillary hemangioma treated with verteporfin photodynamic therapy. Am J Ophthalmol 2002;134:788-790.
13. Gass JD. Cavernous hemangioma of the retina. A neurooculo- cutaneous syndrome. Am J Ophthalmol 1971;71:799-814.
14. Messmer E, Laqua H, Wessing A, et al. Nine cases of cavernous hemangioma of the retina. American Journal of Ophthalmology 1983;95:383-390.
15. Dobyns WB, Michels VV, Groover RV, et al. Familial cavernous malformations of the central nervous system and retina. Ann Neurol 1987;21:578-583.
16. Siegel AM. Familial cavernous angioma: an unknown, known disease. Acta Neurol Scand 1998;98:369-371.
17. Haller JA, Knox DL. Vitrectomy for persistent vitreous hemorrhage from cavernous hemangioma of the optic disc. Am J Ophthalmol 1993;116:107-7
18. Goldberg RE, Pheasant TR, Shields JA. Cavernous hemangioma of the retina. A four-generation pedigree with neurocutaneous manifestations and an example of bilateral retinal involvement. Arch Ophthalmol 1979;97:2321-2324.
19. Witschel H, Font RL. Hemangioma of the choroid. A clinicopathologic study of 71 cases and a review of the literature. Survey of Ophthalmology 1976;20:415-431.
20. Anand R, Augsburger JJ, Shields JA. Circumscribed choroidal hemangiomas. Arch Ophthalmol 1989;107:1338-1342.
21. Sullivan TJ, Clarke MP, Morin JD. The ocular manifestations of the Sturge-Weber syndrome. Journal of Pediatric Ophthalmology & Strabismus 1992;29:349-356.
22. Singh AD, Kaiser PK, Sears JE, Gupta M, Rundle PA, Rennie IG. Photodynamic therapy of circumscribed choroidal haemangioma. Br J Ophthalmol 2004;88:1414-1418. 8. Singh AD, Kaiser PK, Sears JE. Choroidal hemangioma. Ophthalmol Clin North Am 2005;18:151-161, ix.
23. Schmidt-Erfurth UM, Michels S, Kusserow C, Jurklies B, Augustin AJ. Photodynamic therapy for symptomatic choroidal hemangioma: visual and anatomic results. Ophthalmology 2002;109:2284-2294.
24. Madreperla SA. Choroidal hemangioma treated with photodynamic therapy using verteporfin. Arch Ophthalmol 2001;119:1606-1610.
25. Porrini G, Giovannini A, Amato G, Ioni A, Pantanetti M. Photodynamic therapy of circumscribed choroidal hemangioma. Ophthalmology 2003;110:674-680.
26. Jurklies B, Anastassiou G, Ortmans S, et al. Photodynamic therapy using verteporfin in circumscribed choroidal haemangioma. Br J Ophthalmol 2003;87:84-89.
27. Jurklies B, Bornfeld N. The role of photodynamic therapy in the treatment of symptomatic choroidal hemangioma. Graefes Arch Clin Exp Ophthalmol 2005;243:393-396
28. Wyburn-Mason R. Arteriovenous aneurysm of midbrain and retina, facial nevi and mental changes. Brain Develop 1943;66:163-203.
29. Theron J, Newton TH, Hoyt WF. Unilateral retinocephalic vsacular malformations. Neuroradiology 1974;7:185-196.
30. Archer DB, Deutman A, Ernest JT, Krill AE. Arteriovenous communications of the retina. Am J Ophthalmol 1973;75:224-241.
31. Hopen G, Smith JL, Hoff JT, Quencer R. The Wyburn- Mason syndrome. Concomitant chiasmal and fundus vascular malformations. Journal of Clinical Neuro-Ophthalmology 1983;3:53-62.
32. Shields JA, Decker WL, Sanborn GE, Augsburger JJ, Goldberg RE. Presumed acquired retinal hemangiomas. Ophthalmology 1983;90:1292-1300.
33. . Shields CL, Shields JA, Barrett J, De Potter P.Vasoproliferative tumors of the ocular fundus. Classification and clinical manifestations in 103 patients. Arch Ophthalmol 1995;113:615-623.
34. . Irvine F, O’Donnell N, Kemp E, Lee WR. Retinal vasoproliferative tumors: surgical management and histological findings. Arch Ophthalmol 2000;118:563-569.
35. Heimann H, Bornfeld N, Vij O, et al. Vasoproliferative tumours of the retina. Br J Ophthalmol 2000;84:1162- 1169.
36. Barbezetto IA, Smith RT. Vasoproliferative tumor of the retima treated with PDT. Retina 2003;23:565-567.