Diagnostic accuracy of next generation sequencing-based genetic research for primary glaucoma: A systematic review...

Our study aims to assess the utility of various next-generation sequencing (NGS) technologies and explore their role in primary glaucoma genetic research. We conducted a systematic review as of January 19, 2025, using PubMed, Scopus, and Web of Science, with study quality evaluated using the QUADAS-2 checklist. We assessed the diagnostic rates of various NGS technologies across different glaucoma subtypes. The study protocol was registered with the International Prospective Register of Systematic Reviews (PROSPERO: CRD42024614663). We included 19 studies utilizing whole exome sequencing (WES), whole genome sequencing (WGS), and panel sequencing for assessing genetic features in primary angle-closure glaucoma (PACG), primary congenital glaucoma (PCG), primary open-angle glaucoma (POAG), and juvenile open-angle glaucoma (JOAG). The overall diagnostic rate of NGS technologies was 26.2 % (95 % CI: 15.9 %-36.5 %). WES showed superior performance in PCG (46.7 %), POAG (8.9 %), and JOAG (12.4 %), while panel sequencing achieved a higher rate in PACG (56.4 %). Subtype-specific genes included CYP1B1 in PCG, MYOC in JOAG, and WDR36 in POAG/PACG. Notably, all CYP1B1 gene variant loci are concentrated in 2 specific regions on chromosome 2. This study underscores the significance of NGS in primary glaucoma genetic research, advocating for subtype-specific sequencing strategies to facilitate precise diagnosis and treatment.