Correlation between pathogenic CYP1B1 variants and trabeculodysgenesis under ultrasound biomicroscopy in primary congenital glaucoma

To explore the genetic variants of trabeculodysgenesis under ultrasound biomicroscopy (UBM) and its association with surgical outcomes in patients with primary congenital glaucoma (PCG).

In this prospective case series, consecutive patients with PCG underwent microcatheter-assisted trabeculotomy (MAT) and followed for at least 24-month after surgery. All participants underwent UBM and whole-exome sequencing prior to MAT and were classified into two groups with severe trabeculodysgenesis or mild trabeculodysgenesis under UBM. Surgical success was defined as a postoperative IOP of ≤21 mm Hg with at least a 20% reduction from preoperative IOP without additional medical or surgical therapy.

Severe trabeculodysgenesis was observed in 23 (40%) eyes of 14 patients (median age: 57mo, range: 3–169mo; 11 males) with 8 carrying causative CYP1B1 variants, while mild trabeculodysgenesis occurred in 34 eyes (60%) of 18 patients (median age: 23.5mo, range: 3–110mo; 12 males) without any causative variants. The success rate of MAT was 0 in patients with causative CYP1B1 gene variants and 75.0% in those without (P<0.001). Cox regression survival analysis showed that carrying CYP1B1 gene variants [OR_CYP1B1=0.356 (95%CI: 0.132, 0.962), P=0.042] and having severe trabeculodysgenesis [OR_Type=0.116 (95%CI: 0.034, 0.403), P=0.001] were associated with a higher risk of surgical failure.

PCG patients with severe trabeculodysgenesis under UBM are prone to harbor causative CYP1B1 gene variants, which could serve as a valuable predictor of potential Schlemm’s canal dysgenesis and MAT prognosis. Genetic screening in patients with severe trabeculodysgenesis under UBM is beneficial for genetic counseling and may help reduce the incidence of complex cases.