Macular thickness varies with age-related macular degeneration genetic risk variants in the UK Biobank cohort

AbstractTo evaluate the influence AMD risk genomic variants have on macular thickness in the normal population. UK Biobank participants with no significant ocular history were included using the UK Biobank Resource (project 2112). Spectral-domain optical coherence tomography (SD-OCT) images were taken and segmented to define retinal layers. The influence of AMD risk single-nucleotide polymorphisms (SNP) on retinal layer thickness was analysed. AMD risk associated SNPs were strongly associated with outer-retinal layer thickness. The inner-segment outer segment (ISOS)-retinal pigment epithelium (RPE) thickness measurement, representing photoreceptor outer segments was most significantly associated with the cumulative polygenic risk score, composed of 33 AMD-associated variants, resulting in a decreased thickness (p = 1.37 × 10–67). Gene–gene interactions involving the NPLOC4-TSPAN10 SNP rs6565597 were associated with significant changes in outer retinal thickness. Thickness of outer retinal layers is highly associated with the presence of risk AMD SNPs. Specifically, the ISOS-RPE measurement. Changes to ISOS-RPE thickness are seen in clinically normal individuals with AMD risk SNPs suggesting structural changes occur at the macula prior to the onset of disease symptoms or overt clinical signs.

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Outer Retinal Layer Thickness Changes in White Matter Hyperintensity and Parkinson's Disease

Frontiers in Neuroscience ◽

10.3389/fnins.2021.741651 ◽

2021 ◽

Vol 15 ◽

Author(s):

Yitian Zhao ◽

Jinyu Zhao ◽

Yuanyuan Gu ◽

Bang Chen ◽

Jiaqi Guo ◽

...

Keyword(s):

Parkinson’S Disease ◽

Parkinson's Disease ◽

White Matter ◽

Layer Thickness ◽

Pigment Epithelium ◽

Retinal Pigment ◽

Plexiform Layer ◽

White Matter Hyperintensity ◽

Retinal Layer ◽

Retinal Layers

Purpose: To investigate the thickness changes of outer retinal layers in subjects with white matter hyperintensities (WMH) and Parkinson's Disease (PD).Methods: 56 eyes from 31 patients with WMH, 11 eyes from 6 PD patients, and 58 eyes from 32 healthy controls (HC) were enrolled in this study. A macular-centered scan was conducted on each participant using a spectral-domain optical coherence tomography (SD-OCT) device. After speckle noise reduction, a state-of-the-art deep learning method (i.e., a context encoder network) was employed to segment the outer retinal layers from OCT B-scans. Thickness quantification of the outer retinal layers was conducted on the basis of the segmentation results.Results: WMH patients had significantly thinner Henle fiber layers, outer nuclear layers (HFL+ONL) and photoreceptor outer segments (OS) than HC (p = 0.031, and p = 0.005), while PD patients showed a significant increase of mean thickness in the interdigitation zone and the retinal pigment epithelium/Bruch complex (IZ+RPE) (19.619 ± 4.626) compared to HC (17.434 ± 1.664). There were no significant differences in the thickness of the outer plexiform layer (OPL), the myoid and ellipsoid zone (MEZ), and the IZ+RPE layer between WMH and HC subjects. Similarly, there were also no obvious differences in the thickness of the OPL, HFL+ONL, MEZ and the OS layer between PD and HC subjects.Conclusion: Thickness changes in HFL+ONL, OS, and IZ+RPE layers may correlate with brain-related diseases such as WMH and PD. Further longitudinal study is needed to confirm HFL+ONL/OS/IZ+RPE layer thickness as potential biomarkers for detecting certain brain-related diseases.

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Photoreceptor layer thinning is an early biomarker for age-related macular degeneration development: Epidemiological and genetic evidence from UK Biobank optical coherence tomography data

10.1101/2021.08.18.21262226 ◽

2021 ◽

Author(s):

Seyedeh Maryam Zekavat ◽

Sayuri Sekimitsu ◽

Yixuan Ye ◽

Hongyu Zhao ◽

Tobias Elze ◽

...

Keyword(s):

Optical Coherence Tomography ◽

Macular Degeneration ◽

Early Stage ◽

Age Related Macular Degeneration ◽

Retinal Layer ◽

Polygenic Risk Score ◽

Uk Biobank ◽

Polygenic Risk ◽

Age Related ◽

Clinical Biomarker

AbstractIntroductionAge-related macular degeneration (AMD) is a blinding condition for which there is currently no early-stage clinical biomarker. AMD is characterized by thinning of the outer retina and drusen formation leading to thickening of the Bruch’s membrane and RPE complex, but the timing between these two events, as well as the role of genetic variants in these processes, are unclear. Here, we jointly analyzed genomic, electronic health record, and optical coherence tomography (OCT) data across 44,823 individuals from the UK Biobank to characterize the epidemiological and genetic associations between retinal layer thicknesses and AMD.MethodsThe Topcon Advanced Boundary Segmentation algorithm was used for automated retinal layer segmentation. We associated 9 retinal layer thicknesses with prevalent AMD (present at enrollment) in a logistic regression model, and with incident AMD (diagnosed after enrollment) in a Cox proportional hazards model. Next, we tested the association of AMD-associated genetic alleles, individually and as a polygenic risk score (PRS), with retinal layer thicknesses. All analyses were adjusted for age, age2, sex, smoking status, and principal components of ancestry.ResultsPhotoreceptor segment (PS) thinning was observed throughout the lifespan of individuals analyzed and accelerated at age 45, while retinal pigment epithelium and Bruch’s membrane complex (RPE+BM) thickening started after age 57. Each standard deviation (SD) of PS thinning and RPE+BM thickening were associated with prevalent AMD (PS: OR 1.37, 95% CI 1.25-1.49, P=2.5×10−12; RPE+BM: OR=1.34, 95% CI 1.27-1.41, P=8.4×10−28) and incident AMD (PS: HR 1.35, 95% CI 1.23-1.47, P=3.7×10−11; RPE+BM: HR 1.14, 95% CI 1.06-1.22, P=0.00024). An AMD polygenic risk score (PRS) was associated with PS thinning (Beta -0.21 SD per 2-fold genetically increased risk of AMD, 95% CI -0.23 to -0.19, P=2.8×10−74), and its association with RPE+BM was U-shaped (thinning with AMD PRS<92nd percentile and thickening with AMD PRS>92nd percentile suggestive of drusen formation). The loci with strongest support were AMD risk-raising variants CFH:rs570618-T, CFH:10922109-C, and ARMS2/HTRA1:rs3750846-C on PS thinning, and SYN3/TIMP3:rs5754227-T on RPE+BM thickening.ConclusionsEpidemiologically, PS thinning precedes RPE+BM thickening by decades, and is the retinal layer most strongly predictive of future AMD risk. Genetically, AMD risk variants are associated with decreased PS thickness. Overall, these findings support PS thinning as an early-stage clinical biomarker for future AMD development.

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Correlation between Visual Functions and Retinal Morphology in Eyes with Early and Intermediate Age-Related Macular Degeneration

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph17176379 ◽

2020 ◽

Vol 17 (17) ◽

pp. 6379

Author(s):

Rituparna Ghoshal ◽

Sharanjeet Sharanjeet-Kaur ◽

Norliza Mohamad Fadzil ◽

Haliza Abdul Mutalib ◽

Somnath Ghosh ◽

...

Keyword(s):

Visual Acuity ◽

Macular Degeneration ◽

Layer Thickness ◽

Reading Speed ◽

Retinal Pigment ◽

Age Related Macular Degeneration ◽

Morphological Alteration ◽

Retinal Layer ◽

Visual Functions ◽

Age Related

In early and intermediate age related macular degeneration (ARMD), visual acuity alone has failed to explain the complete variation of vision. The aim of the present study was to determine correlation between different visual functions and retinal morphology in eyes with early and intermediate ARMD. In this single center cross sectional study, patients diagnosed as early or intermediate ARMD in at least one eye were recruited. Visual functions measured were best- corrected distance visual acuity (DVA), near vision acuity (NVA), reading speed (RS), and contrast sensitivity (CS). Parameters such as thickness (RT) and volume (RV) of the retina, outer retinal layer thickness (ORLT) and volume (ORLV), outer nuclear layer thickness (ONLT) and volume (ONLV), retinal pigment epithelium layer-Bruch’s membrane complex thickness (RPET) and volume (RPEV) were assessed employing semi-auto segmentation method of Spectralis optical coherence tomography (OCT). Twenty-six eyes were evaluated. DVA, CS, and RS showed significantly good correlation with RPET, ONLT, and ONLV, whereas NVA showed good correlation with ONLV and RPET. The present study concluded that RS, CS, NVA, and DVA represent the morphological alteration in early stages and should be tested in clinical settings. ONLT, ONLV, and RPET morphological parameters can be employed as important biomarkers in diagnosis of early to intermediate ARMD.

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Reduced vessel density in deep capillary plexus correlates with retinal layer thickness in choroideremia

British Journal of Ophthalmology ◽

10.1136/bjophthalmol-2020-316528 ◽

2020 ◽

pp. bjophthalmol-2020-316528

Author(s):

Alessandro Arrigo ◽

Francesco Romano ◽

Maurizio Battaglia Parodi ◽

Peter Charbel Issa ◽

Johannes Birtel ◽

...

Keyword(s):

Layer Thickness ◽

Pigment Epithelium ◽

Outer Nuclear Layer ◽

Retinal Pigment ◽

Plexiform Layer ◽

Vessel Density ◽

Retinal Layer ◽

Inner Plexiform Layer ◽

Retinal Layers ◽

Clinical Series

BackgroundTo assess retinal layer thickness in choroideremia (CHM) and to reveal its correlation with optical coherence tomography (OCT) angiography (OCTA) findings.MethodsThe study was designed as an observational, cross-sectional clinical series of patients with CHM, which included 14 CHM eyes and 14 age-matched controls. Multimodal imaging included OCT and OCTA. The vessel density (VD) of superficial capillary (SCP), deep capillary (DCP) and choriocapillaris (CC) plexuses was analysed by OCTA. The apparently preserved retinal islet and atrophic regions were investigated separately. Main outcome measures were as follows: best-corrected visual acuity (BCVA), total retinal layers, ganglion cell layer (GCL), inner plexiform layer (IPL), inner nuclear layer (INL), outer plexiform layer (OPL), outer nuclear layer (ONL), ellipsoid zone–retinal pigment epithelium (EZ-RPE) layer, choroidal thickness and VDs of SCP, DCP and of CC.ResultsMean BCVA was 0.0±0.0 LogMAR in both groups. GCL, ONL, EZ-RPE and choroid were significantly thinned in CHM, particularly in the atrophic region. OPL was unaffected in the apparently preserved islet, whereas INL and IPL were similarly thinned in the atrophic and apparently preserved retina. DCP appeared severely affected in both regions, while CC was only altered in the atrophic retina. Significant correlations were found between OCT and OCTA parameters.ConclusionsOur study showed severe alterations in both outer and inner retinal layers of patients with CHM. The extended retinal involvement might be the consequence of neuronal and vascular trophic factor reduction produced by the primarily altered RPE and/or secondary Müller glial cell reaction.

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Relationships between retinal layer thickness and brain volumes in the UK Biobank cohort

European Journal of Neurology ◽

10.1111/ene.14706 ◽

2020 ◽

Author(s):

Sharon YL Chua ◽

Gerassimos Lascaratos ◽

Denize Atan ◽

Bing Zhang ◽

Charles Reisman ◽

...

Keyword(s):

Layer Thickness ◽

Retinal Layer ◽

Uk Biobank ◽

Brain Volumes ◽

The Uk

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Statin use in relation to intraocular pressure, glaucoma, and ocular coherence tomography parameters in the UK Biobank

10.1101/2021.12.12.21267685 ◽

2021 ◽

Author(s):

Jihye Kim ◽

Marianne T. Kennedy Neary ◽

Hugues Aschard ◽

Mathew M. Palakkamanil ◽

Ron Do ◽

...

Keyword(s):

Layer Thickness ◽

Regression Models ◽

Genome Wide Association Study ◽

Polygenic Risk Score ◽

Inner Plexiform Layer ◽

Uk Biobank ◽

Linear Regression Models ◽

Fiber Layer ◽

The Uk ◽

Statin Use

Objective: To evaluate the relationship between statin use and various glaucoma-related traits. Design: Cross-sectional analysis of UK Biobank data. Participants: We included 118,153 participants (mean age (SD)=56.8 (8.0) years) with data on statin use (5 statin types - 2006-2010) and corneal-compensated IOP measured in 2009-2013. Also, we included 192,283 participants (with 8,982 self-reported glaucoma cases as of 2006-2010) for the glaucoma analyses. After excluding participants with neurodegenerative diseases, 41,638 participants with global macular retinal nerve fiber layer thickness (mRNFL) and 41,547 participants with ganglion cell inner plexiform layer thickness (mGCIPL) measurements in 2009-2010 were available for analysis. Method: We examined associations with statin use utilizing multivariable-adjusted linear regression models for IOP, mRNFL, and mGCIPL and logistic regression models for glaucoma. We assessed whether a 2,673-member polygenic risk score (PRS) identified from a glaucoma multi-trait analysis of genome wide association study (MTAG) modified associations. We performed Mendelian randomization (MR) experiments using 5 gene variants as proxies for the cholesterol-altering effect of statins to investigate associations with various glaucoma-related outcomes. Main Outcome and Measures: IOP; glaucoma; mRNFL; mGCIPL. Results: Statin users had higher unadjusted mean IOP ± SD (16.3 ± 3.9 mm Hg; n = 20,593 participants) than non-users (15.9 ± 3.8 mm Hg; n = 97,560 participants), but in a multivariable-adjusted model, IOP did not differ by statin use (difference = 0.05 mm Hg; 95% CI: −0.02, 0.13; p=0.17). Similarly, statin use was not associated with prevalent glaucoma (OR = 1.05; 95% CI: 0.98, 1.13). Statin use was weakly associated with thinner mRNFL (difference = −0.15 microns; 95% CI: −0.28, -0.01; p=0.03) but not with mGCIPL thickness (difference = −0.12 microns; 95% CI: −0.29, 0.05; p=0.17). Among statins, simvastatin and atorvastatin, the two most commonly used statins, were not associated with any glaucoma outcome measures. No association was modified by the glaucoma MTAG PRS (Pinteraction≥0.16). MR experiments showed no evidence for a causal association between the cholesterol-altering effect of statins and various glaucoma outcomes (inverse weighted variance p≥0.14). Conclusions: Statin use was not associated with lower IOP, lower glaucoma prevalence, thicker mRNFL or thicker mGCIPL in the UK Biobank.

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Long-term retinal changes in progressive geographic atrophy

European Journal of Ophthalmology ◽

10.1177/11206721211035636 ◽

2021 ◽

pp. 112067212110356

Author(s):

Denise Gallagher ◽

Gagan Kalra ◽

Mohammed Abdul Rasheed ◽

Kiran Kumar Vupparaboina ◽

Sumit Randhir Singh ◽

...

Keyword(s):

Regression Analysis ◽

Retinal Pigment ◽

Geographic Atrophy ◽

Age Related Macular Degeneration ◽

Final Visit ◽

Retinal Layer ◽

Retinal Layers ◽

Age Related

Background: Age-related macular degeneration (AMD) is one of the leading causes of blindness with loss of retinal layers over long term. We aim to evaluate these changes in eyes with progressive non-exudative AMD with geographic atrophy (GA). Methods: This retrospective study included patients with GA with a minimum of 4 years follow up. Retinal layers on spectral domain optical coherence tomography (SD-OCT) were segmented based on their reflectivity patterns using validated semi-automated segmentation algorithm. The thickness of the segmented retinal layers was measured. Horizontal length of GA at baseline and last follow-up were also measured. Regression analysis was performed to correlate changes in RPE layer thickness with other retinal layers and the length of GA on OCT. Results: A total of 351-line scans including 17 foveal scans showing presence of GA at final visit that is, a total of 2457 retinal layer bands were analyzed. Outer nuclear layer (ONL) ( p = 0.02), outer segment layers (OSL) ( p = 0.01), and retinal pigment epithelium (RPE) ( p = 0.01) showed a statistically significant variation between baseline and final visit. Regression analysis showed the change in ONL ( r = 0.72; p = 0.01) and OSL ( r = 0.93, p < 0.01) correlated significantly with change in RPE thickness whereas rest of the layers failed to show significant correlation. Conclusion: Outer retinal layers (ONL and OSL) show more significant and widespread changes in retinal thickness and correlated most significantly with RPE thickness changes in eyes with GA due to AMD. Assessment of various retinal layer bands can be used as surrogate quantitative parameters to study eyes with GA.

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Association of Thiol–disulfide Homeostasis with Retinal Layer Thickness in Patients with Diabetes Mellitus

10.21203/rs.3.rs-791653/v1 ◽

2021 ◽

Author(s):

Muhammet Cuneyt Bilginer ◽

Abbas Ali Tam ◽

Berna Evranos Ogmen ◽

Bagdagul Yuksel Guler ◽

Nagihan Ugurlu ◽

...

Keyword(s):

Diabetes Mellitus ◽

Diabetic Retinopathy ◽

Layer Thickness ◽

Disease Duration ◽

Pigment Epithelium ◽

Retinal Pigment ◽

Control Group ◽

Retinal Layer ◽

Healthy Controls ◽

Total Thiol

Abstract Background: This study aimed to investigate the relationship between early changes in retinal layer thickness and thiol–disulfide homeostasis in patients with type II diabetes mellitus (T2DM).Materials-Methods: There were 69 patients with T2DM (61 patients without retinopathy, 8 patients with retinopathy) and 21 healthy controls. In patients without retinopathy, 31 of the patients had a disease duration under 10 years, 30 of the patients had a disease duration over 10 years. Retinal layer thickness of the right eye was measured using Spectral Domain Optical Coherence Tomography. Results: Patients with T2DM and healthy controls had mean ages of 48.40 ± 8.25 years and 45.94 ± 7.32 years, respectively. The ganglion cell layer and retinal pigment epithelium thicknesses were significantly lesser in patients without diabetic retinopathy than those in the control group. In patients without diabetic retinopathy and with a disease duration of under 10 years, there was a negative correlation between the retinal nerve fiber layer thickness (µm) and disulphide/total thiol ratio, between the inner nuclear layer thickness (µm) and disulphide/native thiol ratio as well as disulphide/total thiol ratio (r= −0.376, p= 0.037; r= −0.356, p= 0.050; r= −0.380, p= 0.035, respectively) and positive correlation between the INL thickness (µm) and native thiol/total thiol ratio (r= 0.359, p= 0.047).Conclusion: Early changes in retinal layers in patients with DM were associated with thiol–disulfide homeostasis. Administration of therapeutic supplements may aid in the management of low thiol concentrations; this increases the importance of the study findings.

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Associations of ophthalmic and systemic conditions with incident dementia in the UK Biobank

British Journal of Ophthalmology ◽

10.1136/bjophthalmol-2021-319508 ◽

2021 ◽

pp. bjophthalmol-2021-319508

Author(s):

Xianwen Shang ◽

Zhuoting Zhu ◽

Yu Huang ◽

Xueli Zhang ◽

Wei Wang ◽

...

Keyword(s):

Heart Disease ◽

Age Related Macular Degeneration ◽

Hospital Inpatient ◽

Uk Biobank ◽

Age Related ◽

Incident Dementia ◽

Increased Risk ◽

The Uk ◽

Systemic Condition

AimsTo examine independent and interactive associations of ophthalmic and systemic conditions with incident dementia.MethodsOur analysis included 12 364 adults aged 55–73 years from the UK Biobank cohort. Participants were assessed between 2006 and 2010 at baseline and were followed up until the early of 2021. Incident dementia was ascertained using hospital inpatient, death records and self-reported data.ResultsOver 1 263 513 person-years of follow-up, 2304 cases of incident dementia were documented. The multivariable-adjusted HRs (95% CI) for dementia associated with age-related macular degeneration (AMD), cataract, diabetes-related eye disease (DRED) and glaucoma at baseline were 1.26 (1.05 to 1.52), 1.11 (1.00 to 1.24), 1.61 (1.30 to 2.00) and (1.07 (0.92 to 1.25), respectively. Diabetes, heart disease, stroke and depression at baseline were all associated with an increased risk of dementia. Of the combination of AMD and a systemic condition, AMD-diabetes was associated with the highest risk for incident dementia (HR (95% CI): 2.73 (1.79 to 4.17)). Individuals with cataract and a systemic condition were 1.19–2.29 times more likely to develop dementia compared with those without cataract and systemic conditions. The corresponding number for DRED and a systemic condition was 1.50–3.24. Diabetes, hypertension, heart disease, depression and stroke newly identified during follow-up mediated the association between cataract and incident dementia as well as the association between DRED and incident dementia.ConclusionsAMD, cataract and DRED but not glaucoma are associated with an increased risk of dementia. Individuals with both ophthalmic and systemic conditions are at higher risk of dementia compared with those with an ophthalmic or systemic condition only.

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