Differences in optic nerve structure between individuals of predominantly African and European ancestry: Implications for disease detection and pathogenesis

Glaucoma disproportionately affects individual of African ancestry. Additionally, racial differences in the optic nerve head have been well described that may alter the vulnerability to intraocular pressure related injury and, in addition, alter the clinical ability to detect the presence of early optic nerve injury. This paper will review the literature describing racial differences in the optic nerve head between individuals of African and European ancestry with regards to the potential effects of these differences on the ability to detect glaucoma in different racial groups and to potential differences in the pathogenesis of glaucomatous injury

Glaucomatous Patterns in Frequency Doubling Technology (FDT) Perimetry Data Identified by Unsupervised Machine Learning Classifiers

Purpose: The variational Bayesian independent component analysis-mixture model (VIM), an unsupervised machine-learning classifier, was used to automatically separate Matrix Frequency Doubling Technology (FDT) perimetry data into clusters of healthy and glaucomatous eyes, and to identify axes representing statistically independent patterns of defect in the glaucoma clusters. Methods: FDT measurements were obtained from 1,190 eyes with normal FDT results and 786 eyes with abnormal FDT results from the UCSD-based Diagnostic Innovations in Glaucoma Study (DIGS) and African Descent and Glaucoma Evaluation Study (ADAGES). For all eyes, VIM input was 52 threshold test points from the 24-2 test pattern, plus age. Results: FDT mean deviation was -1.00 dB (S.D. = 2.80 dB) and -5.57 dB (S.D. = 5.09 dB) in FDT-normal eyes and FDT-abnormal eyes, respectively (p<0.001). VIM identified meaningful clusters of FDT data and positioned a set of statistically independent axes through the mean of each cluster. The optimal VIM model separated the FDT fields into 3 clusters. Cluster N contained primarily normal fields (1109/1190, specificity 93.1%) and clusters G(1) and G(2) combined, contained primarily abnormal fields (651/786, sensitivity 82.8%). For clusters G(1) and G(2) the optimal number of axes were 2 and 5, respectively. Patterns automatically generated along axes within the glaucoma clusters were similar to those known to be indicative of glaucoma. Fields located farther from the normal mean on each glaucoma axis showed increasing field defect severity. Conclusions: VIM successfully separated FDT fields from healthy and glaucoma eyes without a priori information about class membership, and identified familiar glaucomatous patterns of loss.open0

Preliminary Evaluation of the InCHARGE Program Among Older African Americans in Rural Alabama

Objective: Blindness rates among older African Americans are two times higher than for older whites. Our purpose was to understand attitudes about eye care and perceived barriers to care among older African Americans living in rural Alabama and to determine whether an educational program reduced perceived barriers to care. InCHARGE, an eye health education program for older African Americans, promotes eye disease prevention by conveying the personal benefits of annual dilated comprehensive eye care and by teaching strategies to minimize barriers to eye care. Design and Participants: InCHARGE was presented in five senior centers to 111 individuals. Using a questionnaire before and three months after InCHARGE, we evaluated what impact InCHARGE had on attitudes and knowledge about prevention and strategies for reducing barriers. Results: Before InCHARGE, 52.3% reported receiving an eye examination in the past year. Almost all indicated that they felt finding, getting to, and communicating with a doctor were not problems yet about one-quarter indicated that the cost of an examination and/or eyeglasses were problems. After InCHARGE the percentage saying that cost was a problem increased to almost half. Conclusions: Older African Americans in rural Alabama have positive attitudes about comprehensive eye care, yet only about half reported receiving an exam by an eye care provider in the past year. The cost of care is a barrier for many, a problem that was not mitigated by InCHARGE. In order to improve eye health in this population, eye health education initiatives are not enough; economic strategies must be implemented to address the cost barrier

Mechanisms of retinal ganglion cell injury following acute increases in intraocular pressure

The maintenance of intraocular pressure (IOP) is critical to preserving the pristine optics required for vision. Disturbances in IOP can directly impact the optic nerve and retina, and inner retinal injury can occur following acute and chronic IOP elevation. There are a variety of animal models that have been developed to study the effects of acute and chronic elevation of IOP on the retina, retinal ganglion cell (RGC) morphology, intracellular signaling, gene expression changes, and survival. Acute IOP models induce injury that allows for the study of RGC response to well characterized injury and potential recovery. This review will focus on the initial impact of acute IOP elevation on RGC injury and recovery as these early responses may be the best targets for potential therapeutic interventions to promote RGC survival in glaucoma

Low prevalence of myocilin mutations in an African American population with primary open-angle glaucoma

Purpose Mutations in the myocilin gene (MYOC) are associated with primary open-angle glaucoma (POAG) in many different populations. This study represents the first large survey of MYOC mutations in an African American population. Methods: We recruited 529 African American subjects with POAG and 270 African American control subjects in this study. A complete eye examination and blood collection was performed in all study subjects. Genomic DNA was extracted. The entire coding sequence of MYOC was amplified and sequenced using the Sanger method. Identified MYOC variants were compared with previously reported MYOC mutations. Results: We identified a total of 29 MYOC variants including six potential MYOC mutations. Two mutations (Thr209Asn and Leu215Gln) are novel and are found only in cases and no controls. We also identified four previously reported MYOC mutations in cases and no controls (Tyr453MetfsX11, Gln368X, Thr377Met, and Ser393Arg). The overall frequency of glaucoma-causing MYOC mutations in our African American population with POAG was 1.4%. Conclusions: We identified two novel probable glaucoma-causing MYOC mutations (Thr209Asn and Leu215Gln). This study indicates that, despite the high prevalence of POAG, MYOC mutations are rare in the African American population

Macular Ganglion Cell Inner Plexiform Layer Thickness in Glaucomatous Eyes with Localized Retinal Nerve Fiber Layer Defects

Purpose: To investigate macular ganglion cell–inner plexiform layer (mGCIPL) thickness in glaucomatous eyes with visible localized retinal nerve fiber layer (RNFL) defects on stereophotographs. Methods: 112 healthy and 149 glaucomatous eyes from the Diagnostic Innovations in Glaucoma Study (DIGS) and the African Descent and Glaucoma Evaluation Study (ADAGES) subjects had standard automated perimetry (SAP), optical coherence tomography (OCT) imaging of the macula and optic nerve head, and stereoscopic optic disc photography. Masked observers identified localized RNFL defects by grading of stereophotographs. Result: 47 eyes had visible localized RNFL defects on stereophotographs. Eyes with visible localized RNFL defects had significantly thinner mGCIPL thickness compared to healthy eyes (68.3 ± 11.4 μm versus 79.2 ± 6.6 μm respectively, P<0.001) and similar mGCIPL thickness to glaucomatous eyes without localized RNFL defects (68.6 ± 11.2 μm, P = 1.000). The average mGCIPL thickness in eyes with RNFL defects was 14% less than similarly aged healthy controls. For 29 eyes with a visible RNFL defect in just one hemiretina (superior or inferior) mGCIPL was thinnest in the same hemiretina in 26 eyes (90%). Eyes with inferior-temporal RNFL defects also had significantly thinner inferior-temporal mGCIPL (P<0.001) and inferior mGCIPL (P = 0.030) compared to glaucomatous eyes without a visible RNFL defect. Conclusion: The current study indicates that presence of a localized RNFL defect is likely to indicate significant macular damage, particularly in the region of the macular that topographically corresponds to the location of the RNFL defect

Association of severity of primary open-angle glaucoma with serum vitamin D levels in patients of African descent.

PurposeTo study the relationship between primary open-angle glaucoma (POAG) in a cohort of patients of African descent (AD) and serum vitamin D levels.MethodsA subset of the AD and glaucoma evaluation study III (ADAGES III) cohort, consisting of 357 patients with a diagnosis of POAG and 178 normal controls of self-reported AD, were included in this analysis. Demographic information, family history, and blood samples were collected from all the participants. All the subjects underwent clinical evaluation, including visual field (VF) mean deviation (MD), central cornea thickness (CCT), intraocular pressure (IOP), and height and weight measurements. POAG patients were classified into early and advanced phenotypes based on the severity of their visual field damage, and they were matched for age, gender, and history of hypertension and diabetes. Serum 25-Hydroxy (25-OH) vitamin D levels were measured by enzyme-linked immunosorbent assay (ELISA). The association of serum vitamin D levels with the development and severity of POAG was tested by analysis of variance (ANOVA) and the paired t-test.ResultsThe 178 early POAG subjects had a visual field MD of better than -4.0 dB, and the 179 advanced glaucoma subjects had a visual field MD of worse than -10 dB. The mean (95% confidence interval [CI]) levels of vitamin D of the subjects in the control (8.02 ± 6.19 pg/ml) and early phenotype (7.56 ± 5.74 pg/ml) groups were significantly or marginally significantly different from the levels observed in subjects with the advanced phenotype (6.35 ± 4.76 pg/ml; p = 0.0117 and 0.0543, respectively). In contrast, the mean serum vitamin D level in controls was not significantly different from that of the subjects with the early glaucoma phenotype (p = 0.8508).ConclusionsIn this AD cohort, patients with advanced glaucoma had lower serum levels of vitamin D compared with early glaucoma and normal subjects

Genome-wide association study of primary open-angle glaucoma in continental and admixed African populations.

Primary open angle glaucoma (POAG) is a complex disease with a major genetic contribution. Its prevalence varies greatly among ethnic groups, and is up to five times more frequent in black African populations compared to Europeans. So far, worldwide efforts to elucidate the genetic complexity of POAG in African populations has been limited. We conducted a genome-wide association study in 1113 POAG cases and 1826 controls from Tanzanian, South African and African American study samples. Apart from confirming evidence of association at TXNRD2 (rs16984299; OR[T] 1.20; P = 0.003), we found that a genetic risk score combining the effects of the 15 previously reported POAG loci was significantly associated with POAG in our samples (OR 1.56; 95% CI 1.26-1.93; P = 4.79 × 10-5). By genome-wide association testing we identified a novel candidate locus, rs141186647, harboring EXOC4 (OR[A] 0.48; P = 3.75 × 10-8), a gene transcribing a component of the exocyst complex involved in vesicle transport. The low frequency and high degree of genetic heterogeneity at this region hampered validation of this finding in predominantly West-African replication sets. Our results suggest that established genetic risk factors play a role in African POAG, however, they do not explain the higher disease load. The high heterogeneity within Africans remains a challenge to identify the genetic commonalities for POAG in this ethnicity, and demands studies of extremely large size