A Mutation Within Exon 12 of the TGFBI (BIGH3) Gene in a Patient With Reis-Bücklers Dystrophy Treated With Phototherapeutic Keratectomy and a Biopsy Assisted by Epikeratome

Abstract

Purpose:: To describe the clinical features, management, histopathological and genetic diagnosis, and outcome in a patient with Reis-Bücklers dystrophy.

Methods:: A 23 year-old male complained of blurred vision and entoptic phenomena since childhood. He had no previous history of another diseases. He referred a sister with a similar condition. On ophthalmic examination his visual acuity was 20/60(.)20/60 OD, and 20/60(.)20/50 OS with an intraocular pressure of 11 mmHg UO. The refraction was -2.00=-2.50x170° and -1.50=-3.50x10° respectively. We found in both eyes fine reticular superficial corneal opacities in Bowman's layer, affecting the central and mid peripheral cornea sparing the peripheral cornea. The rest of the examination of both eyes was within normal limits. We performed an excimer laser phototherapeutic keratectomy (Nidek EC-5000) assisted with an epikeratome (Centurion CES) with a 6.0mm optic zone and an ablation depth of 60µm. We also performed histopathological studies of the epithelium dissected by the epikeratome, and genetic analysis.

Results:: After phototherapeutic keratectomy the visual acuity did not show significant improvement, but the patient referred improvement in his vision quality and symptoms. The refraction after the procedure was -0.50=-4.00x10° and +0.50=-3.00x175° respectively. The wavefront analysis did not show high-order aberrations. The histopathological study showed subepithelial deposits of amorphic material and there was no staining with Periodic Acid Schiff (PAS) and Congo Red stains. Molecular analysis of the TGFBI (BIGH3) gene demonstrated a point mutation within exon 12 which predicted the change of arginine to tryptophan in residue 555 of the protein (R555W).

Conclusions:: Dispite the lack of visual acuity improvement in our patient, he referred improvement in his symptoms. Phototherapeutic keratectomy is a treatment option in patients with Reis-Bücklers distrophy. Epikeratomes can help obtain enough tissue to perform histopathological studies. The R555W TGFBI mutation has been classically linked to granular type I dystrophy and to the best of our knowledge this the first patient with histopathologically demonstrated Reis-Bücklers dystrophy carrying such mutation. These results emphasize the importance of genetic studies in patients with corneal dystrophies.

Keywords: degenerations/dystrophies • genetics