Purpose: To evaluate the corneal phenotype of patients with corneal dystrophy and the R124H mutation in the BIGH3 gene.
Methods: We examined the corneas of 24 unrelated Japanese individuals who had an R124H mutation in the BIGH3 gene. Large, discrete, granular deposits were present in the anterior stroma of all patients. They were subdivided into two types according to the appearance of the cornea. Histologic examination of the cornea after Masson trichrome and Congo red staining also was performed in specimens from patients who underwent keratoplasty.
Results: The first and the most common type of corneal findings on slit-lamp examination (20 of 24 patients) were discrete granular deposits in the anterior stromal layer and star-shaped opacities in the mid-to-deep stroma. The central subepithelial diffuse opacity increased with age. Amyloid deposits were seen mainly in the mid-to-deep stroma in five of the seven such patients evaluated. The second type of corneal appearance (four of 24 patients) was the presence of diffuse subepithelial opacities in the anterior stroma predominantly, rather than granular or linear opacities. Amyloid deposits were present in the anterior cornea of three of these four patients.
Conclusion: The corneal lesions documented in patients with the R124H mutation were not unique to that disease but could be divided into two types, which likely represent a disease continuum. The lesion location, amount of amyloid deposition, or an interaction between the granular materials and amyloid may influence the varied appearance of the corneal lesion in patients with this disease.