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Young woman referred for bilateral retinal masses
The patient had von Hippel-Lindau syndrome, and a pheochromocytoma was previously removed from her right adrenal gland.
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A 25-year-old woman was referred for evaluation and management of bilateral retinal masses, which were initially identified by a local retinal specialist. The patient otherwise had no ocular history, and she had no visual complaints at that time. She denied changes in vision, eye pain, flashes or floaters.
Her medical history was remarkable for von Hippel-Lindau (VHL) syndrome, and she previously had a pheochromocytoma removed from her right adrenal gland. A recent MRI study was negative for central nervous system lesions. She took no medications. Her family history was significant for VHL in her father and sister, and her social history was not pertinent.
Examination
On examination, the patient’s best corrected visual acuity was 20/20 in the right eye and 20/25 in the left. No afferent pupillary defect was present. Confrontational visual fields were full bilaterally. IOP was within normal limits, and anterior segment exam was unremarkable. Dilated fundus exam of the right eye revealed an elevated, hyperemic, vascularized lesion that measured approximately 1.5 mm located at the inferotemporal margin of the optic disc. Subretinal fluid without exudate was visible adjacent to the lesion but did not extend to the fovea. There were no visible afferent or efferent retinal blood vessels associated with the lesion. The left eye was remarkable for a shallow lesion immediately inferior to the disc, which was located deep to the inferior arcade vessels with no subretinal fluid or exudate present. No additional lesions were identified on thorough peripheral exam.
What is your diagnosis?
Vascularized lesion
The differential diagnosis for a vascular lesion of the retina includes retinal capillary hemangioma, retinal cavernous hemangioma, retinal vasoproliferative tumor and racemose hemangiomatosis of the retina.
Retinal capillary hemangiomas appear as red- or orange-colored circumscribed masses located within the retina, classically with prominent afferent and efferent blood vessels. However, juxtapapillary lesions may not have large visible feeding and draining vessels.
Retinal cavernous hemangiomas appear as clusters of red vascular tissue. They are generally unilateral, and they can occur in all regions of the retina, including near the optic disc. Although retinal cavernous hemangiomas tend to be characteristically identifiable, in uncertain cases fluorescein angiography can be helpful in differentiating a retinal capillary hemangioma from a retinal cavernous hemangioma, in that the former hyperfluoresces rapidly while the latter tends to demonstrate hyperfluorescence slowly.
Retinal vasoproliferative tumor was originally termed “presumed acquired nonfamilial retinal hemangioma” and is characterized as yellow-red vascularized lesions located at the level of the retina with associated retinal feeder vessels and lipid exudation. It is subdivided into primary and secondary forms, the latter of which denotes the presence of pre-existing retinal or choroidal disease. Retinal vasoproliferative tumors are not associated with VHL.
Racemose hemangiomatosis of the retina is associated with Wyburn-Mason syndrome and is characterized by arteriovenous malformations, which can cause the appearance of prominent congested vascular tissue at the optic nerve head.
A broader differential may include combined hamartoma and amelanotic melanoma, both of which can arise in a juxtapapillary location and demonstrate prominent intralesional blood vessels. Additionally, choroidal hemangiomas are another type of vascular tumor, classified as either circumscribed or diffuse, with the latter being part of Sturge-Weber syndrome, or encephalofacial hemangiomatosis.
Diagnosis
Given the patient’s medical and family history of VHL and her classic bilateral exam findings, a diagnosis of retinal capillary hemangiomas at the optic nerve head was straightforward. Management of such lesions, however, oftentimes proves to be challenging.
Color fundus photos showing an elevated, vascularized lesion at the inferotemporal disc margin with associated retinal fluid in the right eye and a shallow light-colored lesion at the inferior disc margin in the left eye.
Source: Lewen M, Duker JS
Fluorescein angiography of the right and left eyes at early, middle and late phases. Note the early hyperfluorescence in the lesions with leakage in late phases, more pronounced in the lesion in the right eye.
OCT images of the right and left eyes. Note in the right eye the hyperreflective inner surface of the lesion with intense shadowing, as well as cystoid macular edema but no subretinal fluid.
Follow-up and management
After discussion with the patient and her family, it was decided that observation was prudent, given her 20/20 vision despite the subretinal fluid in the right eye. Additionally, the juxtapapillary location of the lesion limited potential treatment options. She continued to be stable on follow-up visits at 3- to 4-month intervals.
She planned on becoming pregnant with close follow-up to monitor for ocular complications, and shortly after delivery of her child, her visual acuity decreased to 20/80 in the right eye and fovea-involving subretinal and intraretinal fluid was present. Treatment options included focal laser, photodynamic therapy, intravitreal medication and external beam radiation therapy. She was treated with intravitreal triamcinolone with a good response that lasted only 2 months. After a second injection with a similar length of response, she was treated with light focal argon green laser directly to the surface of the retinal capillary hemangioma. Immediately after laser treatment, she developed worsened macular edema and decreased visual acuity, but her vision ultimately recovered to 20/40. She required three additional injections of intravitreal triamcinolone and two more focal laser treatments to the right eye during the ensuing 16 months.
Discussion
VHL is characterized by the development of both benign and malignant tumors in multiple organ systems. Extraocular manifestations include hemangioblastomas of the cerebellum, pons, medulla or spinal cord, meningioma, renal cell carcinoma, pheochromocytoma, and cysts of visceral and reproductive organs. The VHL tumor suppressor gene is located on chromosome 3, and transmission is autosomal dominant.
Between 49% and 85% of VHL patients have retinal capillary hemangiomas, which are frequently bilateral, and additional lesions can develop over time. Exudation of these lesions can lead to serous retinal detachment, and fibrovascular proliferation associated with peripherally located hemangiomas can result in tractional retinal detachment. Juxtapapillary retinal capillary hemangiomas are less frequent, occurring in 11% to 15% of VHL patients, but have worse visual acuity outcomes than peripheral lesions.
Recent studies on the effect of pregnancy on both the size and number of central nervous system hemangioblastomas in VHL have not demonstrated a statistically significant association, although some smaller case studies reported an association.
Observation can be considered for small lesions without exudation or subretinal fluid. Treatment typically involves laser or cryotherapy for peripheral lesions. To date, anti-VEGF injections have not demonstrated a significant effect on lesions or leakage of fluid. Photodynamic therapy has demonstrated efficacy, but fibrosis of the lesion after successful treatment can cause retinal traction. Additional treatment modalities include external beam or plaque radiotherapy and vitreoretinal surgery. Juxtapapillary lesions limit treatment choices to prevent collateral damage to the optic nerve during treatment.
Conclusion
This patient’s vision continues to fluctuate between 20/40 and 20/200 in the right eye, and vision in the left eye has remained stable at 20/20 with no leakage from the hemangioma. Discussions for future management have included considering photodynamic therapy.
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For more information:
Michael Lewen, MD, and Jay S. Duker, MD, can be reached at New England Eye Center, Tufts University School of Medicine, 750 Washington St., Box 450, Boston, MA 02111; 617-636-4219; website: www.neec.com.Edited by Gregory D. Lee, MD, and Nora W. Muakkassa, MD. They can be reached at New England Eye Center, Tufts University School of Medicine, 750 Washington St., Box 450, Boston, MA 02111; 617-636-4219; website: www.neec.com.