Universität zu Köln

Kersten, Eveline, Geerlings, Maartje J., den Hollander, Anneke I., de Jong, Eiko K., Fauser, Sascha, Peto, Tunde ORCID: 0000-0001-6265-0381 and Hoyng, Carel B. (2017). Phenotype Characteristics of Patients With Age-Related Macular Degeneration Carrying a Rare Variant in the Complement Factor H Gene. JAMA Ophthalmol., 135 (10). S. 1037 - 1045. CHICAGO: AMER MEDICAL ASSOC. ISSN 2168-6173

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Abstract

IMPORTANCE Rare variants in the complement factor H (CFH) gene and their association with age-related macular degeneration (AMD) have been described. However, there is limited literature on the phenotypes accompanying these rare variants. Phenotypical characteristics could help ophthalmologists select patients for additional genetic testing. OBJECTIVE To describe the phenotypical characteristics of patients with AMD carrying a rare variant in the CFH gene. DESIGN, SETTING, AND PARTICIPANTS In this cross-sectional study, we searched the genetic database of the department of ophthalmology at the Radboudumc (tertiary ophthalmologic referral center) and the European Genetic Database for patients with AMD with a rare genetic variant in the CFH gene. Patient recruitment took place from March 30, 2006, to February 18, 2013, and data were analyzed from November 30, 2015, to May 8, 2017. Phenotypical features on fundus photographs of both eyes of patients were graded by 2 independent reading center graders masked for carrier status. MAIN OUTCOMES AND MEASURES Differences in phenotypical characteristics between rare variant carriers and noncarriers were analyzed using univariable generalized estimated equations logistic regression models accounting for intereye correlation. RESULTS Analyses included 100 eyes of 51 patients with AMD carrying a CFH variant (mean [SD] age, 66.7 [12.1] years; 64.7% female) and 204 eyes of 102 age-matched noncarriers (mean [SD] age, 67.1 [11.8] years; 54.9% female). Carrying a rare pathogenic CFH variant was associated with larger drusen area (odds ratio range, 6.98 [95% CI, 2.04-23.89] to 18.50 [95% CI, 2.19-155.99]; P = .002), presence of drusen with crystalline appearance (odds ratio, 3.24; 95% CI, 1.24-8.50; P = .02), and drusen nasal to the optic disc (odds ratio range, 4.03 [95% CI, 1.70-9.56] to 7.42 [95% CI, 0.65-84.84]; P = .003). CONCLUSIONS AND RELEVANCE Identification of rare CFH variant carriers may be important for upcoming complement-inhibiting therapies. Patients with an extensive drusen area, drusen with crystalline appearance, and drusen nasal to the optic disc are more likely to have a rare variant in the CFH gene. However, it is not likely that carriers can be discriminated from noncarriers based solely on phenotypical characteristics from color fundus images. Therefore, ophthalmologists should consider genetic testing in patients with these phenotypic characteristics in combination with other patient characteristics, such as early onset, cuticular drusen on fluorescein angiography, and family history of AMD.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Kersten, Eveline UNSPECIFIED UNSPECIFIED UNSPECIFIED Geerlings, Maartje J. UNSPECIFIED UNSPECIFIED UNSPECIFIED den Hollander, Anneke I. UNSPECIFIED UNSPECIFIED UNSPECIFIED de Jong, Eiko K. UNSPECIFIED UNSPECIFIED UNSPECIFIED Fauser, Sascha UNSPECIFIED UNSPECIFIED UNSPECIFIED Peto, Tunde UNSPECIFIED orcid.org/0000-0001-6265-0381 UNSPECIFIED Hoyng, Carel B. UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-216697
DOI:	10.1001/jamaophthalmol.2017.3195
Journal or Publication Title:	JAMA Ophthalmol.
Volume:	135
Number:	10
Page Range:	S. 1037 - 1045
Date:	2017
Publisher:	AMER MEDICAL ASSOC
Place of Publication:	CHICAGO
ISSN:	2168-6173
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language GEOGRAPHIC ATROPHY; REFRACTILE DRUSEN; EARLY-ONSET; CFH GENE; MUTATIONS; ASSOCIATION; PREVALENCE; ACTIVATION; FAMILIES; BURDEN Multiple languages Ophthalmology Multiple languages
Refereed:	Yes
URI:	http://kups.ub.uni-koeln.de/id/eprint/21669