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Published on: April 4, 2018
Rare TGFBI Mutation c.1553T>G p.(L518R) in Lattice Corneal Dystrophy: Comprehensive Clinical and Genetic Analysis in
Xinhan Cui1, Lian Shu1, Binghui Liu1
1From the Department of Ophthalmology (X.C., L.S., B.L., Y.L., Y.C., Y.W.), Eye, Ear, Nose, and Throat Hospital of Fudan University, Shanghai, China.
Purpose:
To provide a comprehensive clinical and genetic characterization of a rare variant lattice corneal dystrophy (LCD) from TGFBI mutation c.1553T>G p.(L518R) in a Chinese family.
Design:
Retrospective observational case study.
Methods:
Six patients of a Chinese family with LCD-L518R underwent comprehensive ophthalmic evaluation, including slit-lamp biomicroscopy, anterior segment optical coherence tomography (AS-OCT), and in vivo confocal microscopy (IVCM). Three eyes that had undergone anterior lamellar keratoplasty (ALK) were examined to assess long-term outcomes. Genetic analysis was performed using whole-exome sequencing and confirmed by Sanger sequencing. Histopathological examination of corneal specimens included Congo red, Masson's trichrome, and periodic acid-Schiff staining.
Results:
LCD-L518R was identified in all affected family members, with disease onset earliest in the second decade of life. Slit-lamp examination revealed geographic patterns of thickened, gray, hazy epithelial areas, subepithelial nodular opacities, and fine lattice lines. AS-OCT demonstrated hyperreflective subepithelial deposits with saw-tooth pattern replacement of the Bowman layer. IVCM showed amorphous hyperreflective deposits in the subepithelial region and thin, straight lattice lines in the stroma. Histopathological analysis confirmed amyloid deposits with characteristic red-green dichroism under polarized light. IVCM revealed persistence of lattice structures in the host stroma and varying degrees of recurrence in the graft tissue in post-ALK eyes.
Conclusion:
LCD-L518R exhibits a distinctive phenotype characterized by early Bowman's layer disruption, subepithelial amyloid deposition, and progressive stromal involvement. Our results categorize LCD-L518R with other early or intermediate-onset LCD variants with superficial geographic opacification from Bowman layer deposits. Long-term follow-up of post-ALK cases demonstrates the value of multimodal imaging techniques, particularly IVCM and AS-OCT, in detecting structural changes in both graft and host tissue that may not be apparent on routine slit-lamp examination.
