Glaucoma, the world’s leading cause of irreversible blindness, is a complex disease, with differential presentation as well as ethnic and geographic disparities. The multifactorial nature of glaucoma complicates the study of genetics and genetic involvement in the disease process. This review synthesizes the current literature on glaucoma and genetics, as stratified by glaucoma subtype and ethnicity. Primary open-angle glaucoma (POAG) is the most common cause of glaucoma worldwide, with the only treatable risk factor (RF) being the reduction of intraocular pressure (IOP). Genes associated with elevated IOP or POAG risk include: ABCA1, AFAP1, ARHGEF12, ATXN2, CAV1, CDKN2B-AS1, FOXC1, GAS7, GMDS, SIX1/SIX6, TMCO1, and TXNRD2. However, there are variations in RF and genetic factors based on ethnic and geographic differences; it is clear that unified molecular pathways accounting for POAG pathogenesis remain uncertain, although inflammation and senescence likely play an important role. There are similar ethnic and geographic complexities in primary angle closure glaucoma (PACG), but several genes have been associated with this disorder, including MMP9, HGF, HSP70, MFRP, and eNOS. In exfoliation glaucoma (XFG), genes implicated include LOXL1, CACNA1A, POMP, TMEM136, AGPAT1, RBMS3, and SEMA6A. Despite tremendous progress, major gaps remain in resolving the genetic architecture for the various glaucoma subtypes across ancestries. Large scale carefully designed studies are required to advance understanding of genetic loci as RF in glaucoma pathophysiology and to improve diagnosis and treatment options.

Purpose To investigate the relationship of changes in ocular blood flow with optic nerve head and retinal morphology in open-angle glaucoma patients of African versus European descent over four years. Materials and Methods In this study, 112 patients with open-angle glaucoma were examined at baseline, 79 (59 European descent, 20 African descent) of which were followed for four years. Retinal capillary blood flow was assessed with Heidelberg retinal flowmetry. Retrobulbar blood flow was measured by color Doppler imaging. Retinal structural changes were examined with optical coherence tomography and Heidelberg retinal tomography-III. Mixed-model analysis of covariance was used to test for the significance of change from baseline to four-year follow-up, and Pearson correlation coefficients were calculated to evaluate linear associations. Results In open-angle glaucoma patients of African descent, structural changes of the optic nerve head demonstrated a strong association with the end diastolic velocities and resistive indices of the short posterior ciliary arteries over four years. In addition, there was a significantly larger increase in the avascular area of the inferior retina in patients of African descent, and this reduction in retinal capillaries strongly correlated with a reduction in macular thickness. Conclusion Reductions in retinal capillary and retrobulbar blood flow strongly correlated with changes in the optic nerve head and macular thickness over four years in open-angle glaucoma patients of African descent compared to European descent. This data suggests that ocular vascular health may be a more influential contributing factor in the pathophysiology of open-angle glaucoma in patients of African descent compared to European descent.