Therapy of Retinal Angiomas of VHL

Retinal angioma in the eye may be one of the earliest manifestations of VHL disease.  As many as 60% of patients in some studies of large kindreds may have eye involvement. The clinical appearance of these angiomas is very typical and diagnostic of VHL.  The initial appearance of a retinal angioma is a subtle red or grayish dot no larger than a few hundred microns.  As the proliferation of the vascular tumors (mostly of capillaries) progresses, secondary alterations occur to produce a distinctive clinical appearance.  The blood vessels leading to and away from the tumor become characteristically dilated with marked enlargement.  This tumor can lead to leakage of fluid and fatty deposits both around the tumor and in the central important area of the retina, the macula, which is responsible for the fine vision needed for reading, driving, etc. If the angiomas enlarge to an extent that the retina can be detached, hemorrhaging and scarring can occur.  These can all lead to decrease in visual acuity of the affected individual.  Rarely can these tumors regress spontaneously.

Often patients do not have symptoms as these lesions tend to progress slowly.  The tumors can be detected in children to adults in the eighth decade of life on a routine exam.   Symptoms such as decreased vision or a turned-in eye (crossed-eye) may result in the detection of VHL in children.  Decreased visual acuity can also cause adults to seek medical help and subsequent detection of the disease.

The treatment of the retinal angiomas will depend on the location and size of the lesions.  Small lesions are easy to treat successfully while large lesions are notoriously difficult to treat.  Laser photocoagulation can eradicate small retinal angiomas in most locations. However, for those tumors too large or located in the very periphery of the retina, cryotherapy (freezing treatment) may be indicated. 

If the tumor is located on the optic nerve, the nerve that connects the eye to the brain, treatment is fraught with difficulties.  Marked adverse side-effects are associated with treatment of such tumors with laser photocoagulation.  Fortunately, these tumors may remain asymptomatic for long periods of time.  For patients with the more severe changes such as retinal detachment, hemorrhage and scarring, the procedure called vitrectomy can be performed. This involves the introduction of microinstruments under the guidance of a microscope to remove the areas of scarring and to flatten out the retina.  Other treatments that have had some limited success include radiotherapy.  However, experience with this modality is somewhat limited.  Other therapies have also included photodynamic therapy which has been reported to have beneficial results in few cases. 

More recently, 10 cases of severe optic nerve tumors or multiple tumors of the retina were treated with 2 different types of anti-Vascular Endothelial Growth Factor (VEGF) drugs (Macugen and Lucentis) with very limited success at the National Eye Institute/NIH.  We are now testing the use of oral Sutent  (sunitinib malate) in cases of severe optic nerve tumors or multiple tumors of the retina that are causing vision loss.  This drug is FDA approved for the treatment of metastatic renal cell carcinoma. Because of its ability to attack the tumor through different mechanisms of action, it might be important in the therapy of these retinal angiomas that are not amenable to other treatment.   This is an open label study in which all patients will receive the therapy for at least 9 months.  The study is now open for recruitment. 

The importance of maintaining good visual function in patients affected with VHL depends on regular dilated (the opening of the pupil of the eye with drops) eye examination.  For patients who are at risk of developing VHL, an annual dilated eye exam will provide important information and help maintain good vision.  It is very important that all patients affected or who are at risk be examined annually through DILATED pupils.  Good vision can be achieved and maintained in many affected individuals, especially if the lesions are detected and treated early in the course of the disease.

For those individuals who are interested in the NEI/NIH trial of Sutent for optic nerve tumors associated with VHL, please contact Katherine Shimel, RN at Katherine.Shimel@nih.gov or by telephone:  (301 402 2863).