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.
more »
« less
Asian Race and Primary Open-Angle Glaucoma: Where Do We Stand?
Primary open-angle glaucoma (POAG) is an optic neuropathy characterized by irreversible retinal ganglion cell damage and visual field loss. The global POAG prevalence is estimated to be 3.05%, and near term is expected to significantly rise, especially within aging Asian populations. Primary angle-closure glaucoma disproportionately affects Asians, with up to four times greater prevalence of normal-tension glaucoma reported compared with high-tension glaucoma. Estimates for overall POAG prevalence in Asian populations vary, with Chinese and Indian populations representing the majority of future cases. Structural characteristics associated with glaucoma progression including the optic nerve head, retina, and cornea are distinct in Asians, serving as intermediates between African and European descent populations. Patterns in IOP suggest some similarities between races, with a significant inverse relationship between age and IOP only in Asian populations. Genetic differences have been suggested to play a role in these differences, however, a clear genetic pattern is yet to be established. POAG pathogenesis differs between Asians and other ethnicities, and it may differ within the broad classification of the Asian race. Greater awareness and further research are needed to improve treatment plans and outcomes for the increasingly high prevalence of normal tension glaucoma within aging Asian populations.
more »
« less
- PAR ID:
- 10439410
- Date Published:
- Journal Name:
- Journal of Clinical Medicine
- Volume:
- 11
- Issue:
- 9
- ISSN:
- 2077-0383
- Page Range / eLocation ID:
- 2486
- Format(s):
- Medium: X
- Sponsoring Org:
- National Science Foundation
More Like this
-
-
Glaucoma is a multifactorial disease and a leading cause of irreversible blindness worldwide. Current data has demonstrated the approximate distribution of primary openangle glaucoma (POAG) in patients of European, African, Hispanic, and Eastern Asian descent. However, a significant gap in the literature exists regarding the prevalence of POAG in Middle Eastern (ME) populations. Current studies estimate ME POAG prevalence based on a European model. Herein we screened 65 total publications on ME prevalence of POAG and specific risk factors using keywords: “glaucoma”, “prevalence”, “incidence”, “risk factor”, “Middle East”, “Mideast”, “Persian”, “Far East”, as well as searching by individual ME countries through PubMed, Embase, Ovid, Scopus, and Trip searches with additional reference list searches from relevant articles published up to and including March 1, 2021. Fifty qualifying records were included after 15 studies identified with low statistical power, confounding co-morbid ophthalmic diseases, and funding bias were excluded. Studies of ME glaucoma risk factors that identify chromosomes, familial trend, age/gender, socioeconomic status, lifestyle, intraocular pressure, vascular influences, optic disc hemorrhage, cup-to-disc ratio, blood pressure, obstructive sleep apnea, and diabetes mellitus were included in this systematic review. We conclude that the prevalence of POAG in the ME is likely higher than the prevalence rate that European models suggest, with ME specific risk factors likely playing a role. However, these findings are severely limited by the paucity of population-level data in the ME. Well-designed, longitudinal population-based studies with rigorous inclusion and exclusion criteria are ultimately needed to accurately assess the epidemiology and specific mechanistic risk factors of glaucoma in ME populations.more » « less
-
Précis:The relationship between structural and hemodynamic parameters in patients with primary open angle glaucoma is strongest in the temporal region of the optic nerve. Purpose:To investigate the relationship between radial peripapillary capillary (RPC) vessel density (VD) and retinal nerve fiber layer (RNFL) thickness in quadrants and sectors of the optic nerve head (ONH) in patients with and without primary open angle glaucoma (POAG). Methods:In a cross-sectional prospective analysis, 191 subjects (80 early-stage POAG; 111 non-glaucomatous controls) were assessed for RNFL thickness and RPC VD in each quadrant [superior (S), inferior (I), nasal (N) and temporal (T)] and sector [inferior-temporal (IT), temporo-inferior (TI), temporo-superior (TS), superior-temporal (ST), inferior-nasal (IN), naso-inferior (NI), naso-superior (NS), and superior-nasal (SN) sectors] of the ONH through optical coherence tomography angiography (OCTA). Pearson correlations were used to test for associations between measurements, withP<0.05 considered statistically significant. Results:Significantly stronger positive correlations were found between RPC VD and RNFL thickness in the S, I, and T quadrants in POAG patients compared with non-glaucomatous controls (allP<0.05). The temporal quadrant in POAG patients displayed the largest difference in correlation compared with controls. A stronger positive correlation was also found between RPC VD and RNFL thickness in the temporal sectors of the ONH in POAG patients compared with controls, with the largest difference in the TS sector (allP<0.05). Conclusion:Early-stage POAG patients have a stronger relationship between RPC VD and RNFL in the temporal regions of the ONH compared with non-glaucomatous controls, with the TS sector demonstrating the largest difference between groups. Temporal sector VD loss may represent an early-stage biomarker for vascular-linked POAG disease.more » « less
-
Background/Objectives: To investigate macular vascular biomarkers for the detection of primary open-angle glaucoma (POAG). Methods: A total of 56 POAG patients and 94 non-glaucomatous controls underwent optical coherence tomography angiography (OCTA) assessment of macular vessel density (VD) in the superficial (SCP), and deep (DCP) capillary plexus, foveal avascular zone (FAZ) area, perimeter, VD, choriocapillaris and outer retina flow area. POAG patients were classified for severity based on the Glaucoma Staging System 2 of Brusini. ANCOVA comparisons adjusted for age, sex, race, hypertension, diabetes, and areas under the receiver operating characteristic curves (AUCs) for POAG/control differentiation were compared using the DeLong method. Results: Global, hemispheric, and quadrant SCP VD was significantly lower in POAG patients in the whole image, parafovea, and perifovea (p < 0.001). No significant differences were found between POAG and controls for DCP VD, FAZ parameters, and the retinal and choriocapillaris flow area (p > 0.05). SCP VD in the whole image and perifovea were significantly lower in POAG patients in stage 2 than stage 0 (p < 0.001). The AUCs of SCP VD in the whole image (0.86) and perifovea (0.84) were significantly higher than the AUCs of all DCP VD (p < 0.05), FAZ parameters (p < 0.001), and retinal (p < 0.001) and choriocapillaris flow areas (p < 0.05). Whole image SCP VD was similar to the AUC of the global retinal nerve fiber layer (RNFL) (AUC = 0.89, p = 0.53) and ganglion cell complex (GCC) thickness (AUC = 0.83, p = 0.42). Conclusions: SCP VD is lower with increasing functional damage in POAG patients. The AUC for SCP VD was similar to RNFL and GCC using clinical diagnosis as the reference standard.more » « less
-
Growing evidence suggests that intracranial pressure (ICP) plays an important role in the pathophysiology of glaucoma, especially in normal-tension glaucoma (NTG) patients. Controversial results exist about ICP’s relationship to visual field (VF) changes. With the aim to assess the relationship between ICP and VF zones in NTG patients, 80 NTG patients (age 59.5 (11.6) years) with early-stage glaucoma were included in this prospective study. Intraocular pressure (IOP) (Goldmann), visual perimetry (Humphrey) and non-invasive ICP (via a two-depth Transcranial Doppler, Vittamed UAB, Lithuania) were evaluated. Translaminar pressure difference (TPD) was calculated according to the formula TPD = IOP − ICP. The VFs of each patient were divided into five zones: nasal, temporal, peripheral, central, and paracentral. The average pattern deviation (PD) scores were calculated in each zone. The level of significance p < 0.05 was considered significant. NTG patients had a mean ICP of 8.5 (2.4) mmHg. Higher TPD was related with lower mean deviation (MD) (p = 0.01) and higher pattern standard deviation (PSD) (p = 0.01). ICP was significantly associated with the lowest averaged PD scores in the nasal VF zone (p < 0.001). There were no significant correlations between ICP and other VF zones with the most negative mean PD value. (p > 0.05). Further studies are needed to analyze the involvement of ICP in NTG management.more » « less
An official website of the United States government

