Universität zu Köln

Gliem, Martin, Mueller, Philipp L., Mangold, Elisabeth, Holz, Frank G., Bolz, Hanno J., Stoehr, Heidi, Weber, Bernhard H. F. and Issa, Peter Charbel ORCID: 0000-0002-0351-6673 (2015). Sorsby Fundus Dystrophy: Novel Mutations, Novel Phenotypic Characteristics, and Treatment Outcome. Invest. Ophthalmol. Vis. Sci., 56 (4). S. 2664 - 2677. ROCKVILLE: ASSOC RESEARCH VISION OPHTHALMOLOGY INC. ISSN 1552-5783

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Abstract

PURPOSE. To report novel TIMP3 mutations, and to characterize the ocular phenotype of Sorsby fundus dystrophy (SFD), including a novel early sign for the disease and to report the effect of anti-VEGF therapy. METHODS. Twenty-one probands of three unrelated families with SFD were investigated using wide-field imaging, confocal laser scanning ophthalmoscopy with autofluorescence imaging, optical coherence tomography (OCT), indocyanine green-angiography (ICG-A), and molecular diagnostic for causative mutations. RESULTS. Molecular genetic analysis revealed two novel (p.Tyr174Cys, p.Tyr177Cys) and one previously described (p.Tyr182Cys) missense mutations in TIMP3. In families with p.Tyr177Cys and p.Tyr182Cys, metamorphopsia and/or decrease in visual acuity were the initial symptoms occurring at approximately the sixth decade of life. The p.Tyr174Cys mutation carriers had first symptoms at approximately the third decade with dark adaptation problems and visual field defects. The ocular phenotype included drusen-like deposits, rapidly progressive geographic atrophy, choroidal neovascularization (CNV), and polypoidal choroidal neovascularization (PCV). Late disease manifestations were uniform with widespread chorioretinal atrophy, fibrosis, and choroidal thinning. Three asymptomatic young carriers of a TIMP3 mutation with otherwise normal findings on funduscopy and retinal imaging showed a characteristically reduced fluorescence on late-phase ICG-A images. This phenotypic sign was more pronounced and widespread in later disease stages. Patients with CNV or PCV showed a favorable response to therapy with intravitreally injected bevacizumab. CONCLUSIONS. This study expands the spectrum of mutations in the TIMP3 gene and associated phenotypic findings. Imaging using late-phase ICG-A may be useful for early identification of individuals at risk for developing SFD. Intravitreal anti-VEGF therapy if initiated timely is effective in SFD patients with CNV.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Gliem, Martin UNSPECIFIED UNSPECIFIED UNSPECIFIED Mueller, Philipp L. UNSPECIFIED UNSPECIFIED UNSPECIFIED Mangold, Elisabeth UNSPECIFIED UNSPECIFIED UNSPECIFIED Holz, Frank G. UNSPECIFIED UNSPECIFIED UNSPECIFIED Bolz, Hanno J. UNSPECIFIED UNSPECIFIED UNSPECIFIED Stoehr, Heidi UNSPECIFIED UNSPECIFIED UNSPECIFIED Weber, Bernhard H. F. UNSPECIFIED UNSPECIFIED UNSPECIFIED Issa, Peter Charbel UNSPECIFIED orcid.org/0000-0002-0351-6673 UNSPECIFIED
URN:	urn:nbn:de:hbz:38-404179
DOI:	10.1167/iovs.14-15733
Journal or Publication Title:	Invest. Ophthalmol. Vis. Sci.
Volume:	56
Number:	4
Page Range:	S. 2664 - 2677
Date:	2015
Publisher:	ASSOC RESEARCH VISION OPHTHALMOLOGY INC
Place of Publication:	ROCKVILLE
ISSN:	1552-5783
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language TISSUE INHIBITOR; METALLOPROTEINASES-3 TIMP3; CHOROIDAL NEOVASCULARIZATION; GEOGRAPHIC ATROPHY; INDOCYANINE GREEN; GENE; PROGRESSION; FAMILY; LOCALIZATION; MEMBRANE Multiple languages Ophthalmology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/40417