Novel CYP1B1 mutations and a possible prognostic use for surgical management of congenital glaucoma

• Main Authors: Mohamed M. Khafagy, Nadia El-Guendy, Marwa A Tantawy, Mohamed A. Eldaly, Hala M. Elhilali, Abdel Hady A. Abdel Wahab
• Format: Article
• Language: English
• Published: Press of International Journal of Ophthalmology (IJO PRESS) 2019-04-01
• Series: International Journal of Ophthalmology
• Subjects: cyp1b1 mutations; primary congenital glaucoma; intraocular pressure; trabeculotomy/trabeculectomy with mitomycin-c.
• Online Access: http://www.ijo.cn/en_publish/2019/4/20190414.pdf

AIM: To identify CYP1B1 gene mutations and evaluate their possible role as a prognostic factor for success rates in the surgical management of Egyptian congenital glaucoma patients. METHODS: Totally 42 eyes of 29 primary congenital glaucoma patients were operated on with combined trabeculotomy/trabeculectomy with mitomycin-C and followed up at 1d, 1wk, 1, 6 and 12mo postoperatively. Genomic DNA was extracted from peripheral blood leukocytes. Coding regions of CYP1B1 gene were amplified using 13 pairs of primers, screened for mutations using single-strand conformation polymorphism followed by sequencing of both strands. Efficacy of the operation was graded as either a success [maintaining intraocular pressure (IOP) less than 21 mm Hg with or without anti-glaucoma medication], or a failure (IOP more than 21 mm Hg with topical antiglaucoma medications). RESULTS: Seven novel mutations out of a total of 15 different mutations were found in the CYP1B1 genes of 14 patients (48.2%). The presence of CYP1B1 gene mutations did not correlate with the failure of the surgery (P=0.156, odds ratio=3.611, 95%CI, 0.56 to 22.89); while the positive consanguinity strongly correlated with failure of the initial procedure (P=0.016, odds ratio=11.25, 95%CI, 1.57 to 80.30). However, the Kaplan-Meier survival analysis revealed a significantly lower time of IOP control in the subgroup with mutations in CYP1B1 versus the congenital primary glaucoma group without mutations (log rank test, P=0.015). CONCLUSION: Seven new CYP1B1 mutations are identified in Egyptian patients. Patients harboring confirmed mutations suffered from early failure of the initial surgery. CYP1B1 mutations could be considered as a prognostic factor for surgery in primary congenital glaucoma.