Dataset Information

Association of Glaucoma Risk Genes with Retinal Nerve Fiber Layer in a Multi-ethnic Asian Population: The Singapore Epidemiology of Eye Diseases Study.

ABSTRACT: Purpose: Genome-wide association studies have identified several genes associated with glaucoma. However, their roles in the pathogenesis of glaucoma remain unclear, particularly their effects on retinal nerve fiber layer (RNFL) thickness. The aim of this study was to investigate the associations between the identified glaucoma risk genes and RNFL thickness.

Methods: A total of 3843 participants (7,020 healthy eyes) were enrolled from the Singapore Epidemiology of Eye Diseases (SEED) study, a population-based study composing of three major ethnic groups-Malay, Indian, and Chinese-in Singapore. Ocular examinations were performed, and spectral-domain optical coherence tomography (SD-OCT) was used to measure circumpapillary RNFL thickness. We selected 35 independent glaucoma-associated genetic loci for analysis. An linear regression model was conducted to determine the association of these variants with circumpapillary RNFL, assuming an additive genetic model. We conducted association analysis in each of the three ethnic groups, followed by a meta-analysis of them.

Results: The mean age of the included participants was 59.4 ± 8.9 years, and the mean RFNL thickesss is 92.3 ± 11.2 µm. In the meta-analyses, of the 35 glacuoma loci, we found that only SIX6 was significantly associated with reduction in global RNFL thickness (rs33912345; ? = -1.116 um per risk allele, P = 1.64E-05), and the effect size was larger in the inferior RNFL quadrant (? = -2.015 µm, P = 2.9E-6), and superior RNFL quadrant (? = -1.646 µm, P = 6.54E-5). The SIX6 association were consistently observed across all three ethnic groups. Other than RNFL, we also found several genetic varaints associated with vertical cuo-to-disc ratio (ATOH7, CDKN2B-AS1, and TGFBR3-CDC7), rim area (SIX6 and CDKN2B-AS1), and disc area (SIX6, ATOH7, and TGFBR3-CDC7). The association of SIX6 rs33912345 with NRFL thickness remained similar after further adjusting for disc area and 3 other disc parameter associated SNPs (ATOH7, CDKN2B-AS1, and TGFBR3-CDC7).

Conclusions: Of the 35 glaucoma identified risk loci, only SIX6 is significantly and independently associated with thinner RNFL. Our study further supports the involvement of SIX6 with RNFL thickness and pathogensis of glaucoma.

SUBMITTER: Chai X

PROVIDER: S-EPMC7445359 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature

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Association of Glaucoma Risk Genes with Retinal Nerve Fiber Layer in a Multi-ethnic Asian Population: The Singapore Epidemiology of Eye Diseases Study.

Chai Xiaoran X Low Kok Yao KY Tham Yih Chung YC Chee Miao Li ML Thakur Sahil S Zhang Liang L Tan Nicholas Y NY Khor Chiea Chuen CC Aung Tin T Wong Tien Yin TY Cheng Ching-Yu CY

Investigative ophthalmology & visual science 20200801 10

<h4>Purpose</h4>Genome-wide association studies have identified several genes associated with glaucoma. However, their roles in the pathogenesis of glaucoma remain unclear, particularly their effects on retinal nerve fiber layer (RNFL) thickness. The aim of this study was to investigate the associations between the identified glaucoma risk genes and RNFL thickness.<h4>Methods</h4>A total of 3843 participants (7,020 healthy eyes) were enrolled from the Singapore Epidemiology of Eye Diseases (SEED ...[more]

PMID: 32821913

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Project description:PurposeTo compare the rates of retinal nerve fiber layer (RNFL) loss in patients suspected of having glaucoma who developed visual field damage (VFD) with those who did not develop VFD and to determine whether the rate of RNFL loss can be used to predict the development of VFD.DesignProspective, observational cohort study.ParticipantsGlaucoma suspects, defined as having glaucomatous optic neuropathy or ocular hypertension (intraocular pressure, >21 mmHg) without repeatable VFD at baseline, from the Diagnostic Innovations in Glaucoma Study and the African Descent and Glaucoma Evaluation Study.MethodsGlobal and quadrant RNFL thickness (RNFLT) were measured with the Spectralis spectral-domain optical coherence tomography (SD-OCT; Spectralis HRA+OCT [Heidelberg Engineering, Heidelberg, Germany]). Visual field damage was defined as having 3 consecutive abnormal visual fields. The rate of RNFL loss in eyes developing VFD was compared to eyes not developing VFD using multivariate linear mixed-effects models. A joint longitudinal survival model used the estimated RNFLT slope to predict the risk of developing VFD, while adjusting for potential confounding variables.Main outcome measuresThe rate of RNFL thinning and the probability of developing VFD.ResultsFour hundred fifty-four eyes of 294 glaucoma suspects were included. The average number of SD-OCT examinations was 4.6 (range, 2-9), with median follow-up of 2.2 years (0.4-4.1 years). Forty eyes (8.8%) developed VFD. The estimated mean rate of global RNFL loss was significantly faster in eyes that developed VFD compared with eyes that did not develop VFD (-2.02 μm/year vs. -0.82 μm/year; P<0.001). The joint longitudinal survival model showed that each 1-μm/year faster rate of global RNFL loss corresponded to a 2.05-times higher risk of developing VFD (hazard ratio, 2.05; 95% confidence interval, 1.14-3.71; P = 0.017).ConclusionsThe rate of global RNFL loss was more than twice as fast in eyes that developed VFD compared with eyes that did not develop VFD. A joint longitudinal survival model showed that a 1-μm/year faster rate of RNFLT loss corresponded to a 2.05-times higher risk of developing VFD. These results suggest that measuring the rate of SD-OCT RNFL loss may be a useful tool to help identify patients who are at a high risk of developing visual field loss.

Project description:ImportanceHigher intraocular pressure variability may be associated with faster structural changes in patients with glaucoma.ObjectivesTo investigate the association of mean intraocular pressure and intraocular pressure variability (defined as the SD of intraocular pressure and the intraocular pressure range) with the rate of retinal nerve fiber layer thinning over time in patients with glaucoma.Design, setting, and participantsIn this retrospective analysis of a longitudinal cohort, patients were enrolled from the Diagnostic Innovations in Glaucoma Study and the African Descent and Glaucoma Evaluation study. A total of 815 eyes (564 with perimetric glaucoma and 251 with preperimetric glaucoma) from 508 patients with imaging follow-up for a mean of 6.3 years from December 2008 to October 2020 were studied. Data were analyzed from November 2021 to March 2022.Main outcomes and measuresIn this longitudinal study, eyes with at least 4 visits and 2 years of follow-up optical coherence tomography and intraocular pressure measurement were included. A linear mixed-effect model was used to investigate the association of intraocular pressure parameters with the rates of retinal nerve fiber layer thinning. Dominance analysis was performed to determine the relative importance of the intraocular pressure parameters.ResultsOf 508 included patients, 280 (55.1%) were female, 195 (38.4%) were African American, 24 (4.7%) were Asian, 281 (55.3%) were White, and 8 (1.6%) were another race or ethnicity; the mean (SD) age was 65.5 (11.0) years. The mean rate of retinal nerve fiber layer change was -0.67 (95% CI, -0.73 to -0.60) μm per year. In multivariable models adjusted for mean intraocular pressure and other confounding factors, faster annual rate of retinal nerve fiber layer thinning was associated with a higher SD of intraocular pressure (-0.20[ 95% CI, -0.26 to -0.15] μm per 1-mm Hg higher; P < .001) or higher intraocular pressure range (-0.05 [95% CI, -0.06 to -0.03] μm per 1-mm Hg higher; P < .001).Conclusions and relevanceIn this study, intraocular pressure variability was independently associated with structural change in patients with glaucoma, even after adjustment for mean intraocular pressure, supporting its potential value in clinical management.

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Dataset Information

Association of Glaucoma Risk Genes with Retinal Nerve Fiber Layer in a Multi-ethnic Asian Population: The Singapore Epidemiology of Eye Diseases Study.

Publications

Association of Glaucoma Risk Genes with Retinal Nerve Fiber Layer in a Multi-ethnic Asian Population: The Singapore Epidemiology of Eye Diseases Study.

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