No abstract

Primary open angle glaucoma (POAG), a major cause of blindness worldwide, is a complex disease with a significant genetic contribution. We performed Exome Array (Illumina) analysis on 3504 POAG cases and 9746 controls with replication of the most significant findings in 9173 POAG cases and 26 780 controls across 18 collections of Asian, African and European descent. Apart from confirming strong evidence of association at CDKN2B-AS1 (rs2157719 [G], odds ratio [OR] = 0.71, P = 2.81 × 10−33), we observed one SNP showing significant association to POAG (CDC7–TGFBR3 rs1192415, ORG-allele = 1.13, Pmeta = 1.60 × 10−8). This particular SNP has previously been shown to be strongly associated with optic disc area and vertical cup-to-disc ratio, which are regarded as glaucoma-related quantitative traits. Our study now extends this by directly implicating it in POAG disease pathogenesis.

PurposeTo determine peripapillary vessel density in eyes with perimetric glaucoma (PG) or preperimetric glaucoma (PPG) compared to normal controls using optical coherence tomography-angiography (OCT-A).MethodsWe recruited 13 patients with unilateral perimetric normal-tension glaucoma (NTG) and fellow preperimetric NTG showing only inferotemporal retinal nerve fiber layer (RNFL) defect in red-free RNFL photography in both eyes. We also enrolled 9 healthy controls. Using OCT-A, radial peripapillary capillary densities at inferotemporal and superotemporal regions were evaluated. Paired comparison of peripapillary vessel density was performed for PG eye, PPG eye, and normal eye.ResultsA total of 26 eyes of the 13 patients with unilateral PG and fellow PPG eyes and 18 eyes of 9 normal controls were analyzed. Vessel densities at the whole peripapillary region and inferotemporal region in PG eyes were significantly lower than those in PPG eyes (P = 0.001, P<0.001, respectively). Comparison between PPG and normal eyes showed no significant difference in the whole peripapillary region or the inferotemporal region (P = 0.654, P = 0.174, respectively). There was no significant (P = 0.288) difference in vessel density at superotemporal region among the three types of eyes (PG eye, PPG eye, and normal eye).ConclusionPPG eyes and normal eyes were found to have the similar densities of peripapillary microvasculature at the area with nerve fiber layer defect, whereas in PG eye, there was a significant decrease in vessel density at the area of RNFL thinning. This provides evidence that microvascular compromise in the retina might be a secondary change to nerve fiber layer degeneration in the pathogenesis of NTG.

Temporalized angular locations of deep ONH parameters were associated with the presence of NTG in myopia. In myopic NTGs, the locations of deep ONH parameters were consistent with the locations of RNFL defect.