Intrafamilial similarity of wide-field fundus autofluorescence in inherited retinal dystrophy

Abstract

Purpose: A number of genotype-phenotype correlation studies in inherited retinal dystrophy described intra-familial variety; some of them reported the similarity and the others reported the wide variety. In the present study, we examined the similarity of the wide-field fundus autofluorescence (FAF) of siblings and patient-child in inherited retinal dystrophy.

Methods: We examined 17 siblings and 10 pairs of patient-child, which comprised of 12 families with typical retinitis pigmentosa (RP) and 5 families with cone-rod dystrophy (CRD), 8 families with RP and 2 families with CRD, respectively. We evaluated the similarity of wide-field FAF by 2 ways. One is (1) multiple choice questions and the other is (2) quantification of similarity. (1) About 17 siblings, we showed 32 raters (21 retinal specialists and 11 non-experts) the wide-field FAF of the elder brother or sister and let them pick out the younger brother’s or sister’s one among three images. Two of the three images were obtained from age-matched unrelated patients with RP or CRD. (2) We cropped an elliptically shaped area of 3000×2100 pixels centered on fovea from the original image and converted it to the binary images by thresholding the value of optic disc area. Then two images from the pairs were superimposed and created into a new image by subtraction tool, which shows agreement or disagreement of each pixel between the pair. We defined the number of agreed pixels as similarity of two wide-field FAF images in this study. The estimated similarity of the siblings was compared with the one of the pairs of parent-child and with the one of the age-matched unrelated patients.

Results: (1) The mean number of the correct answers was 11.2 (95%CI 10.6-11.8) and it was significantly higher than the expected value (17/3 = 5.7). (2) The similarity of the siblings was significantly higher than the one of the parent-child and the one of age-matched unrelated patients (P=0.004, and P=0.049, respectively).

Conclusions: Wide-field FAF images were similar within a sibling with inherited retinal dystrophy but different within a parent-child. This suggests that aging is a confounding factor in genotype-phenotype correlation studies.

Keywords: 702 retinitis • 550 imaging/image analysis: clinical • 494 degenerations/dystrophies