Genotype-Phenotype Correlations and Long-Term Surgical Outcomes in TGFBI-Linked Bowman's Layer Corneal Dystrophies.

PURPOSE: Reis-Bücklers corneal dystrophy (RBCD; Mendelian Inheritance in Man 602082) and Thiel-Behnke corneal dystrophy (TBCD; Mendelian Inheritance in Man 608470) are clinically similar corneal dystrophies affecting Bowman's layer, caused by the TGFBI variants p.(Arg124Leu) and p.(Arg555Gln), respectively. Yet their distinct clinical courses complicate therapeutic decisions. This study aimed to compare the clinical course and surgical outcomes of genetically confirmed RBCD and TBCD.

METHODS

Medical records from 2016 to 2024 were reviewed for age at first surgical intervention, surgical procedure type, and time to clinically significant recurrence (SR). TGFBI genotyping was performed, and phenotypic features were documented using slit-lamp biomicroscopy and anterior segment optical coherence tomography. We retrospectively analyzed clinical data of 2 large French families with 24 patients, 8 being genotyped with either the p.(Arg124Leu) or the p.(Arg555Gln) variants. Main Outcome Measures were the age at first phototherapeutic keratectomy (PTK), recurrence interval after surgery, and visual acuity recovery after PTK.

RESULTS

Patients with the p.(Arg124Leu) variant underwent their first surgical procedure at a younger age (mean: 18.43 ± 4.47 years) than those with the p.(Arg555Gln) variant (mean: 28.8 ± 4.16 years; P <0.001). Furthermore, the interval to SR after PTK was shorter in the p.(Arg124Leu) group (48.3 ± 10.4 months) than in the p.(Arg555Gln) group (121.2 ± 20.4 months; P <0.001).

CONCLUSIONS

Our findings further support that the p.(Arg124Leu) variant is associated with an earlier onset and a more aggressive clinical course than the p.(Arg555Gln) variant. Genetic testing is key to precise differential diagnosis of these CDs and provides clinical prognostication to guide the therapeutic options.