Credit: Genome Decoration Page/NCBI
A diagram of chromosome 22 showing the location of the TIMP3 gene, which is associated with Sorsby's fundus dystrophy.
Learn about the diagnosis and treatment of a rare form of inherited retinal degeneration, called Sorsby’s fundus dystrophy, which can appear similar to age-related macular degeneration (AMD), especially in its early stages.
What is Sorsby’s Fundus Dystrophy?
Sorsby’s fundus dystrophy is a rare, inherited retinal disease that can look similar to AMD, especially in its early stages. People with AMD have drusen, which are yellowish-white spots under the retina detected by an ophthalmologist during a dilated eye exam. People with Sorsby’s can also have drusen-like deposits, leading them to be diagnosed initially with AMD.
How is Sorsby’s Different from Age-Related Macular Degeneration?
It’s important to make the distinction between Sorsby’s and AMD, because Sorsby’s often progresses more rapidly and requires more frequent monitoring and treatment. One clue suggesting the possibility of Sorsby’s is a strong family history of macular degeneration, since Sorsby’s is inherited in a dominant manner. A dominant genetic trait is expressed in a person even if they have only one copy of that gene. AMD also has a hereditary component, so family history alone is not enough to make the Sorsby’s diagnosis.
Earlier onset can also suggest Sorsby’s. Patients with Sorsby’s can begin to have drusen-like retinal deposits in their 40s, while AMD usually begins between the ages of 50 and 70. Difficulty with dark adaptation (seeing in a dark room immediately after coming in from a bright area) or night-blindness can be prominent symptoms in Sorsby’s (but slow dark adaptation can also occur in AMD). Other symptoms in Sorsby’s and AMD can include distorted/reduced central vision.
Diagnosis of Sorsby’s Fundus Dystrophy
A retinal imaging test called an ICG angiogram, which can be done in a retina specialist’s office, can help to diagnose Sorsby’s, since it appears unusually dark, even in young, asymptomatic people who carry the Sorsby’s gene. The definitive diagnosis can be made using genetic testing.
Patients with Sorsby’s have dominant mutations in the TIMP3 gene, which is located on chromosome 22. This gene is expressed in the retina, and normally helps maintain a thin membrane that separates the retina from its underlying blood vessels. When the gene is mutated, the retinal pigment epithelial cells sitting in the membrane can die, or the membrane can be penetrated by abnormal blood vessels that leak and bleed.
Treatment of Sorsby’s Fundus Dystrophy
Abnormal new blood vessels in patients with Sorsby’s can be treated in the same way as those in wet AMD: by injections into the eye of anti-VEGF antibodies such as Avastin. These injections can stop harmful leakage from the abnormal blood vessels.
Sorsby’s patients who lose vision can be aided by a low vision specialist. These optometrists are specially trained to provide optimal glasses, lights, magnifiers and electronic devices, along with patient training to make the best use of their existing vision.
Hope for the Future
Currently, there are no other effective treatments for Sorsby’s, but recent advances in gene therapy for the retina, including FDA approval for Leber congenital amaurosis (LCA), a different form of inherited blindness, provide hope for a genetic therapy in the future. Since Sorsby’s is a dominant disease, gene therapy is more difficult, but recent advances in genetic therapies, like CRISPR/Cas, suggest that even dominant retinal diseases may be treatable after further cutting-edge research.