Abstract
Purpose :
Primary angle closure glaucoma (PACG) is a major form of glaucoma especially in Asia. Recently, we conducted a whole-exome sequencing survey on 4,684 PACG cases and 5,508 controls from Singapore, Hong Kong, Japan, and Vietnam. We observed significant enrichment between rare, coding genetic variants at a protein involved in the E2 ubiquitination pathway with >2-fold increased risk of PACG. We sought to evaluate the relationship between these qualifying variants and risk of previous acute-primary angle closure (APAC) compared to chronic angle-closure glaucoma (CACG).
Methods :
Participants with PACG were ascertained using gonioscopy and PACG were verified by a glaucoma specialist after a comprehensive clinical examination. Previous APAC was defined by the presence of at least two of the following symptoms: ocular or periocular pain, nausea or vomiting, and history of intermittent blurring of vision; a presenting IOP of more than 28 mmHg on Goldmann applanation tonometry; and the presence of at least three of the following signs: conjunctival injection, corneal epithelial edema, mid-dilated non-reactive pupil, and shallow anterior chamber. Those who presented with asymptomatic disease were classified as CACG.
Results :
Of the 4,684 PACG cases analysed, 4,235 had available and unambiguous classification data on either APAC or CACG status. Qualifying variants in the E2 ubiquitination pathway gene were observed in 105 participants with available APAC or CACG classification. We did not observe significant differential enrichment of qualifying variant carriers in patients with APAC (N=37 carriers out of 1,442 participants with AACG; 2.57%) compared to CACG (N=68 carriers out of 2,793 participants with CACG; 2.43%). Secondary analysis suggests that qualifying variants who were female had 3.94-fold excess odds of APAC (95% confidence interval; 1.00–15.4; P=0.029) over and above that of baseline non-carriers.
Conclusions :
Although the gene was involved in the pathogenesis of PACG overall, carriers of qualifying variants in the E2 ubiquitination pathway gene was not differentially enriched between patients with either APAC or CACG. The possibility that female carriers of qualifying variants having a nearly 4-fold increase in risk of APAC over and above baseline demographic risk may have potential implications on precision medicine efforts, but more confirmatory studies are needed.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.