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  • Corneal Defects Common in Wolfram Syndrome

    By Lynda Seminara
    Selected By: Richard K. Parrish II, MD
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    Journal Highlights

    American Journal of Ophthalmology, September 2020

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    Knowledge of the corneal topography of patients with Wolfram syndrome (WFS) is lacking. In a comprehensive study of the corneal features of WFS, Waszczykowska et al. found that cor­neal anomalies were common in both human and mouse corneas. The clinical and topographic features were similar to keratoconus. Results of immuno­histochemistry confirmed wolframin expression in corneal tissue.

    This study was a comparative longitudinal case series of 12 Polish patients with biallelic mutations in the WFS1 gene and clinical symptoms of WFS. The control group consisted of 30 people with type 1 diabetes. All 42 participants underwent complete oph­thalmic exams, computer videokera­tography, and assessment of corneal thickness and endothelial features. Nine of the patients with WFS also had longitudinal videokeratography and Pentacam evaluation. Corneal features were documented and compared. In addition, human and murine corneas underwent immunohistochemistry and microscopic evaluation.

    Clinical and topographic abnor­malities, similar to those in keratoco­nus, were observed in 14 eyes of eight patients with WFS. The WFS and control groups differed substantially in flat keratometry, inferior-superior dioptric asymmetry, and skewed radial axis. They also differed with regard to indexes of keratoconus percentage, central keratoconus, surface variance, vertical asymmetry, height asymmetry, and height decentration. Immunohis­tochemistry showed wolframin expres­sion in the human and mouse corneas. Moreover, differences in corneal thick­ness and epithelial features were found between WFS1 gene knockout mice and wild-type mice.

    The results indicate that many pa­tients with WFS have a host of corneal defects that seem compatible with subclinical or early keratoconus. To the authors’ knowledge, this is the first published report of these anomalies in WFS. The mechanism by which wol­framin deficiency causes corneal defects is not known. Possibilities include the autophagic lysosomal pathway and high endoplasmic reticulum stress. The authors recommend routine corneal surveillance in patients with WFS, and they encourage long-term prospec­tive studies to better understand the findings.

    The original article can be found here.