title: Sorsby's fundus dystrophy in a family with a Ser-181-CVS mutation in the TIMP-3 gene: poor outcome after laser photocoagulation.
abstract: OBJECTIVE
  Mutations in the TIMP-3 (tissue inhibitor of metalloproteinase-3) gene can cause Sorsby's fundus dystrophy (SFD) and lead to choroidal neovascular membrane (CNV) formation. We studied a large American family of Irish Protestant descent with CNV inherited as an autosomal dominant trait, to determine the phenoptype and to learn whether a mutation was present in TIMP-3.
  
  
  METHODS
  Twelve members of 5 generations were evaluated clinically, with psychophysical and electroretinographic testing, and by fluorescein angiography. Blood samples for DNA extraction were obtained from 21 affected and unaffected family members and from 1 unrelated spouse. DNA sequence was determined, and affected individuals showed a Ser-181-Cys mutation in TIMP-3 exon 5.
  
  
  RESULTS
  Observable pathology involved primarily the macula, and both the full-field ERG and visual fields were normal. Acute CNV occurred during the third through fifth decades, with second eyes typically also affected during the subsequent year. Three affected members complained of nyctalopia prior to developing CNV. A Ser-181-Cys mutation in the TIMP-3 gene cosegregated with CNV in 10 affected subjects but was absent in 3 relatives at risk and sufficiently old to trust the clinical designation of normalcy. Nine eyes of 6 family members were treated by laser photocoagulation by 5 different ophthalmologists for foveal and juxtafoveal CNV. All eyes had recurrent CNV and lost acuity to 20/300 or less within several months.
  
  
  CONCLUSIONS
  Laser photocoagulation of CNV did not stem vision loss in this SFD family. Although possible benefits of laser treatment were not put to formal clinical trial owing to the limited number of Sorsby's cases, it appears that photocoagulation is not of long-term benefit for preserving vision loss from the TIMP-3 Ser-181-Cys mutation. Several younger family members with the mutation are thus far not clinically affected and are being followed up.
authors.affiliation: Department of Ophthalmology, University of Michigan, Ann Arbor, USA.
authors.forename: P A
authors.initials: PA
authors.lastname: Sieving
authors.forename: S
authors.initials: S
authors.lastname: Boskovich
authors.forename: E
authors.initials: E
authors.lastname: Bingham
authors.forename: H
authors.initials: H
authors.lastname: Pawar
mesh_terms: D000328:Adult; D002829:Choroid / Q000098:blood supply; D004596:Electroretinography; D005260:Female; D005451:Fluorescein Angiography; D005654:Fundus Oculi; D006801:Humans; D017075:Laser Coagulation; D008268:Macular Degeneration / Q000235:genetics* / Q000503:physiopathology / Q000601:surgery*; D008297:Male; D008875:Middle Aged; D009389:Neovascularization, Pathologic / Q000209:etiology / Q000235:genetics / Q000503:physiopathology; D010375:Pedigree; D017354:Point Mutation; D011480:Protease Inhibitors; D011506:Proteins / Q000235:genetics*; D012694:Serine; D019717:Tissue Inhibitor of Metalloproteinase-3; D016896:Treatment Outcome; D014786:Vision Disorders / Q000209:etiology / Q000235:genetics / Q000503:physiopathology; D014792:Visual Acuity
chemical_list: D011480:Protease Inhibitors; D011506:Proteins; D019717:Tissue Inhibitor of Metalloproteinase-3; D012694:Serine