Progression of Fuchs corneal dystrophy in a family linked to the FCD1 locus.
OBJECTIVE
Fuchs corneal dystrophy (FCD) is a progressive corneal disease marked by the development of guttae, focal excrescences of Descemet's membrane. Retroillumination photography is a useful technique for illuminating the presence of guttae and has been used to document progression of disease. This study was undertaken to quantitatively assess disease progression in a cohort of individuals with late-onset FCD linked to chromosome 13.


METHODS
Retroillumination photography was performed on 13 related individuals (26 eyes) with the FCD1 disease haplotype at a 30- to 34-month interval. Individual guttae were counted in each image and the distribution recorded. A polar coordinate system was used to delineate regional differences in development of guttae.


RESULTS
An increase of 29.1% was found in the total number of guttae over approximately 30 months (mean increase of 669 guttae/eye, P < 0.001) among 26 eyes. A rapid rate of progression begins at approximately age 50, representing an exponential increase (r(2) = 0.60) among individuals mildly affected for decades. Individuals with the disease haplotype but with two affected parents demonstrated an earlier disease onset. A significantly greater proportion of guttae were present in the inferotemporal quadrant of the cornea (P < 0.001), an effect that grew in significance over time.


CONCLUSIONS
The study demonstrated quantitative progression of FCD with the use of retroillumination photography in an FCD1-linked pedigree. Comparison of severity versus age suggests a rapid increase in the number of guttae at approximately age 50. Individuals with the FCD1 disease haplotype and a second likely genetic lesion exhibit a markedly increased disease severity suggestive of genetic interaction between FCD loci.
Meadows
Danielle N
DN
Center for Corneal Genetics, Cornea and External Disease Service, The Wilmer Eye Institute, Baltimore, MD 21287, USA.
Eghrari
Allen O
AO
Riazuddin
S Amer
SA
Emmert
David G
DG
Katsanis
Nicholas
N
Gottsch
John D
JD
D000293:Adolescent; D000328:Adult; D000368:Aged; D002882:Chromosomes, Human, Pair 13 / Q000235:genetics*; D018450:Disease Progression; D005260:Female; D005642:Fuchs' Endothelial Dystrophy / Q000235:genetics* / Q000503:physiopathology*; D008040:Genetic Linkage; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D010781:Photography