Glaucoma is an inherited complex and heterogeneous disease, and one of the most prevalent causes of definitive blindness in the world. Recent reports have indicated that heterozygous mutations of the CYTOCHOROME P4501B1 (CYP1B1) gene are present in 4-10% of patients with primary open-angle glaucoma (POAG). To further evaluate the role of CYP1B1 mutations in POAG we extended our previous association study and carried out a functional analysis of the mutations identified by polymerase chain reaction (PCR) DNA sequencing of the three exons of the gene in a total of 245 unrelated Spanish patients and 326 control subjects. Eight of nine different mutations identified in these patients were cloned and functionally assessed by measuring ethoxyresorufin O-deethylation activity and CYP1B1 stability in transiently transfected HEK-293T cells. All these mutants showed reduced catalytic activity, ranging from 20% to 60% of wild-type and/or decreased protein stability and, therefore, they were classified as hypomorphic alleles. No null alleles were identified in these patients. We found heterozygous hypomorphic CYP1B1 mutations in 17 (6.7%) patients and in seven controls (2.1%) showing that these mutations are associated with an increased risk of POAG (p = 0.005; odds ratio = 3.2; 95% confidence interval = 1.30-9.19). Our data suggest that hypomorphic CYP1B1 mutations are, to date, the main known genetic risk factor in POAG.
Rare WDR36 variants and the P53 p.R72P polymorphism behaved as moderate glaucoma risk factors in Spanish patients. The authors provide evidence for a genetic interaction between WDR36 and P53 variants in POAG susceptibility, although this finding must be confirmed in other populations.
RESUMENObjetivos: Evaluar los hallazgos postquirúrgicos y el éxito tras cirugía combinada mediante facoemulsificación e implante Ex-PRESS comparado con cirugía combinada con trabeculectomía estándar. Métodos: En esta serie prospectiva de 40 ojos consecutivos comparamos 20 ojos de 17 pacientes tratados mediante facoemulsificación combinada con cirugía filtrante de glaucoma con implante de vál-vula Ex-PRESS bajo un colgajo escleral con 20 ojos controles en 20 enfermos que fueron sometidos a facoemulsificación combinada con trabeculectomía estándar. Resultados: El tiempo de seguimiento medio fue de 9,7 meses (rango: 4,5-15) en el grupo Ex-PRESS y 10,3 meses (rango 3,5-14,5) en el grupo trabeculectomía. La PIO media fue significativamente superior en el postoperatorio precoz en el grupo Ex-PRESS comparada con el de trabeculectomía. La tasa de complicaciones en dicho período resultó superior en el grupo sometido a trabeculectomía. No se objetivaron diferencias significativas en la tasa de éxito entre ambos grupos más allá de la primera semana.
ABSTRACTPurpose: To evaluate postoperative outcomes and success after combined phacoemulsification and glaucoma surgery with Ex-PRESS miniature implant compared with combined surgery with standard trabeculectomy. Methods: In this prospective series of 40 consecutive eyes we compared 20 eyes in 17 patients treated with combined phacoemulsification and glaucoma filtering surgery with the Ex-PRESS miniature glaucoma implant under a scleral flap with 20 matched control eyes in 20 patients who underwent combined cataract and glaucoma surgery with trabeculectomy. Results: The average follow-up was 9.7 months (range 4.5 to 15) for the Ex-PRESS group and 10.3 months (range 3.5 to 14.5) for the trabeculectomy group. The mean IOP was significantly higher in the early postoperative period in the Ex-PRESS group compared with the trabeculectomy group. Complications rate in the early postoperative period was significantily higher in the trabeculectomy group. No significant differences were objectified in success between both groups after the first week.
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