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Mutations in TIMP3 leads to a lack of functional metallopeptidase inhibitor 3 with enhanced destruction of extracellular matrix
Mutations in TIMP3 leads to a lack of functional metallopeptidase inhibitor 3 with enhanced destruction of extracellular matrix

Sorsby Pseudoinflammatory Fundus Dystrophy

Clinical Characteristics

Ocular Features

Sorsby Pseudoinflammatroy Fundus Dystrophy is characterized by progressive degeneration of the central macula of the retina with edema, hemorrhages and exudates with pigment changes.  The onset is typically in the second to fourth decade with development of a disciform central macular atrophy with white and yellow spots (not drusen).  This is followed by subretinal neovascular membranes in the majority of patients.  Further degeneration occurs over years and can spread from the center to the periphery of the retina with a corresponding visual field defect.  Night blindness or difficulties adapting to changes in light intensity may be noted before the central macular degeneration occurs.  In histopathologic studies, a subretinal deposit can be observed in Bruchs membrane.

Systemic Features

No general systemic manifestations are associated with Sorsby Pseudoinflammatory Fundus Dystrophy.

Genetics

Sorsby Pseudoinflammatory Fundus Dystrophy is an autosomal dominant disorder, caused by mutations in the TIMP3 gene, located at 22q12.1-q13.2.  Evidence for a separate recessive form (264420) is somewhat refuted by the fact that genotyping found heterozygosity of the TIMP3 mutation in some families.

Treatment Options

In patients with early stages of the disease, a daily dose of 50,000 IU Vitamin A given by mouth has been shown to reverse the symptoms of night blindness.  Treatment with anti-angiogenic agents or steroids has shown improvement in visual acuity in some patients. Patients with decreased vision may find benefit with low vision aids.

References

Hamilton WK, Ewing CC, Ives EJ, Carruthers JD. Sorsby's fundus dystrophy. Ophthalmology 1989 Dec;96(12):1755-62.

PubMed ID: 
2695876

Michaelides M, Hunt DM, Moore AT. The genetics of inherited macular dystrophies. J Med Genet. 2003 Sep;40(9):641-50.

PubMed ID: 
12960208

Jacobson SG, Cideciyan AV, Regunath G, Rodriguez FJ, Vandenburgh K, Sheffield VC, Stone EM. Night blindness in Sorsby’s Fundus dystrophy reversed by vitamin A. Nat Genet 1995;11:27–32.

PubMed ID: 
7550309

Weber, B. H. F., Vogt, G., Pruett, R. C., Stohr, H., Felbor, U. Mutations in the tissue inhibitor metalloproteinases-3 (TIMP3) in patients with Sorsby's fundus dystrophy. Nature Genet. 8: 352-356, 1994.

PubMed ID: 
7894485

Felbor U, Suvanto EA, Forsius HR, Eriksson AW, Weber BH. Autosomal recessive Sorsby fundus dystrophy revisited: molecular evidence for dominant inheritance. Am J Hum Genet. 1997 Jan;60(1):57-62.

PubMed ID: 
8981947