Genotype-Specific Clinical Course And Surgical Recurrence In Tgfbi-Related Bowman’S Layer Corneal Dystrophies After Transepithelial Photokeratectomy (T-Ptk)

Bowman’s layer corneal dystrophies (BCD) associated with mutations in the transforming growth factor beta-induced (TGFBI) gene show overlapping phenotypes but heterogeneous clinical courses. This study aimed to evaluate whether TGFBI genotype predicts age at surgical intervention, recurrence dynamics, and visual outcomes after transepithelial phototherapeutic keratectomy (t-PTK) and keratoplasty, in order to refine prognostic assessment and surgical planning.

Single tertiary academic referral center for corneal diseases in Paris, France, with integrated clinical, imaging, and molecular genetics facilities.

A retrospective genotype–phenotype analysis was conducted in 2 unrelated French families with genetically confirmed TGFBI-associated BCD. Twenty-four patients (48 eyes) carrying either the p.(Arg124Leu) variant, associated with Reis–Bücklers corneal dystrophy, or the p.(Arg555Gln) variant, associated with Thiel–Behnke corneal dystrophy, were included. Clinical records from 2016 to 2024 were reviewed for age at first PTK, surgical procedures, delay for recurrence requiring re-intervention, and best-corrected visual acuity. Phenotypic assessment was based on slit-lamp biomicroscopy and anterior segment optical coherence tomography. Recurrence was defined as clinically significant redeposition leading to visual impairment and further surgery.

Patients with the p.(Arg124Leu) variant required first PTK significantly earlier than those with p.(Arg555Gln) (mean 18.4 ± 4.5 vs 28.8 ± 4.2 years; p < 0.001). The mean interval to clinically significant recurrence after PTK was substantially shorter in the p.(Arg124Leu) group (48.3 ± 10.4 months) compared with the p.(Arg555Gln) group (121.2 ± 20.4 months; p < 0.001). Visual acuity improvement following PTK was comparable between genotypes. After keratoplasty, recurrence occurred earlier in p.(Arg124Leu) eyes than in p.(Arg555Gln) eyes, confirming a genotype-dependent recurrence pattern across surgical modalities.

TGFBI genotype is a strong determinant of disease severity and surgical recurrence in Bowman’s layer corneal dystrophies. The p.(Arg124Leu) variant is associated with earlier surgical need and faster recurrence, whereas p.(Arg555Gln) follows a slower, less aggressive course. Incorporating genetic testing into routine clinical practice provides actionable prognostic information that can guide surgical timing, choice of procedure, and long-term patient counseling in corneal dystrophy management.