Publications by authors named "Ruth E Hogg"

57 Publications

Determinants of Test Variability in Scotopic Microperimetry: Effects of Dark Adaptation and Test Indices.

Transl Vis Sci Technol 2021 Jan 15;10(1):26. Epub 2021 Jan 15.

Optometry and Visual Sciences, City, University of London, London, UK.

Purpose: To test the effect of different dark adaptation conditions and reliability indices on the variability of two color scotopic microperimetry.

Methods: We analyzed data from 22 consecutive visually healthy adults. Scotopic microperimetry was performed (Macular Integrity Assessment microperimeter, CenterVue, Padua, Italy) with two wavelength stimuli, cyan (505 nm) and red (627 nm), after a dark adaptation time of 10, 20, or 30 minutes. All tests were repeated twice to measure test-retest variability with Bland-Altman plots. We also provide a method to more accurately quantify the false-positive (FP) responses based on response data (button pressing) from the device, similar to FP responses used in standard static perimetry. Data on fixation stability (95% bivariate contour ellipse area) and blind spot responses were also extracted. Their relationship with measured sensitivity (in decibels) and test-retest variability was quantified through linear mixed effect models.

Results: Dark adaptation had a significant effect on the sensitivity (dB) measured with the cyan stimulus ( < 0.001), but no effect on the red stimulus. Of the three metrics, the novel FP responses showed the best association with test-retest variability and was the only predictor consistently significant for all tests ( < 0.01).

Conclusions: Dark adaptation protocols should be carefully standardized for scotopic testing, especially if a cyan stimulus is used. The proposed FP responses should be used to assess reliability of microperimetry examinations instead of other metrics.

Translational Relevance: We developed a method to calculate a more accurate estimate of the FP responses using data available to all researchers, generalizable to all Macular Integrity Assessment microperimeter tests.
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http://dx.doi.org/10.1167/tvst.10.1.26DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7814359PMC
January 2021

Structure-Function Analysis in Macular Drusen With Mesopic and Scotopic Microperimetry.

Transl Vis Sci Technol 2020 12 28;9(13):43. Epub 2020 Dec 28.

City, University of London-Optometry and Visual Sciences, London, UK.

Purpose: To investigate the structure-function relationship in eyes with drusen with mesopic and scotopic microperimetry.

Methods: We analyzed structural and functional data from 43 eyes with drusen. Functional data were acquired with mesopic and scotopic two-color (red and cyan) microperimetry. Normative values were calculated using data from 56 healthy eyes. Structural measurements were green autofluorescence and dense macular optical coherence tomography scans. The latter were used to calculate the retinal pigment epithelium elevation (RPE-E) and the photoreceptor reflectivity ratio (PRR). The pointwise structure-function relationship was measured with linear mixed models having the log-transformed structural parameters as predictors and the sensitivity loss (SL, deviation from normal) as the response variable.

Results: In the univariable analysis, the structural predictors were all significantly correlated ( < 0.05) with the SL in the mesopic and scotopic tests. In a multivariable model, mesopic microperimetry yielded the best structure-function relationship. All predictors were significant ( < 0.05), but the predictive power was weak (best = 0.09). The relationship was improved when analyzing locations with abnormal RPE-E (best = 0.18).

Conclusions: Mesopic microperimetry shows better structure-function relationship compared to scotopic microperimetry; the relationship is weak, likely due to the early functional damage and the small number of tested locations affected by drusen. The relationship is stronger when locations with drusen are isolated for the mesopic and scotopic cyan test.

Translational Relevance: These results could be useful to devise integrated structure-function methods to detect disease progression in intermediate age-related macular degeneration.
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http://dx.doi.org/10.1167/tvst.9.13.43DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7774115PMC
December 2020

Authors' Reply.

Ophthalmic Physiol Opt 2021 Jan 29;41(1):206. Epub 2020 Nov 29.

Centre of Public Health, Queens University Belfast, Belfast, UK.

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http://dx.doi.org/10.1111/opo.12765DOI Listing
January 2021

Revisiting the Drasdo Model: Implications for Structure-Function Analysis of the Macular Region.

Transl Vis Sci Technol 2020 09 14;9(10):15. Epub 2020 Sep 14.

City, University of London-Optometry and Visual Sciences, London, UK.

Purpose: To provide a consistent implementation of a retinal ganglion cell (RGC) displacement model proposed by Drasdo et al. for macular structure-function analysis, customizable by axial length (AL).

Methods: The effect of axial length on the shape of the inner retina was measured on 235 optical coherence tomography (OCT) scans from healthy eyes, to provide evidence for geometric scaling of structures with eye size. Following this assumption, we applied the Drasdo model to map perimetric stimuli on the radially displaced RGCs using two different methods: Method 1 only displaced the center of the stimuli; Method 2 applied the displacement to every point on the edge of the stimuli. We compared the accuracy of the two methods by calculating, for each stimulus, the number of expected RGC receptive fields and the number RGCs calculated from the histology map, expected to be equivalent. The same calculation was repeated on RGC density maps derived from 28 OCT scans from 28 young healthy subjects (age < 40 years) to confirm our results on clinically available measurements.

Results: The size of the retinal structures significantly increased with AL ( < 0.001) and was well predicted by geometric scaling. Method 1 systematically underestimated the RGC counts by as much as 60%. No bias was observed with Method 2.

Conclusions: The Drasdo model can effectively account for AL assuming geometric scaling. Method 2 should be used for structure-function analyses.

Translational Relevance: We developed a free web App in Shiny R to make our results available for researchers.
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http://dx.doi.org/10.1167/tvst.9.10.15DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7490226PMC
September 2020

Genome-wide association meta-analysis for early age-related macular degeneration highlights novel loci and insights for advanced disease.

BMC Med Genomics 2020 08 26;13(1):120. Epub 2020 Aug 26.

Institute of Human Genetics, University of Regensburg, Regensburg, Germany.

Background: Advanced age-related macular degeneration (AMD) is a leading cause of blindness. While around half of the genetic contribution to advanced AMD has been uncovered, little is known about the genetic architecture of early AMD.

Methods: To identify genetic factors for early AMD, we conducted a genome-wide association study (GWAS) meta-analysis (14,034 cases, 91,214 controls, 11 sources of data including the International AMD Genomics Consortium, IAMDGC, and UK Biobank, UKBB). We ascertained early AMD via color fundus photographs by manual grading for 10 sources and via an automated machine learning approach for > 170,000 photographs from UKBB. We searched for early AMD loci via GWAS and via a candidate approach based on 14 previously suggested early AMD variants.

Results: Altogether, we identified 10 independent loci with statistical significance for early AMD: (i) 8 from our GWAS with genome-wide significance (P < 5 × 10), (ii) one previously suggested locus with experiment-wise significance (P < 0.05/14) in our non-overlapping data and with genome-wide significance when combining the reported and our non-overlapping data (together 17,539 cases, 105,395 controls), and (iii) one further previously suggested locus with experiment-wise significance in our non-overlapping data. Of these 10 identified loci, 8 were novel and 2 known for early AMD. Most of the 10 loci overlapped with known advanced AMD loci (near ARMS2/HTRA1, CFH, C2, C3, CETP, TNFRSF10A, VEGFA, APOE), except two that have not yet been identified with statistical significance for any AMD. Among the 17 genes within these two loci, in-silico functional annotation suggested CD46 and TYR as the most likely responsible genes. Presence or absence of an early AMD effect distinguished the known pathways of advanced AMD genetics (complement/lipid pathways versus extracellular matrix metabolism).

Conclusions: Our GWAS on early AMD identified novel loci, highlighted shared and distinct genetics between early and advanced AMD and provides insights into AMD etiology. Our data provide a resource comparable in size to the existing IAMDGC data on advanced AMD genetics enabling a joint view. The biological relevance of this joint view is underscored by the ability of early AMD effects to differentiate the major pathways for advanced AMD.
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http://dx.doi.org/10.1186/s12920-020-00760-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7449002PMC
August 2020

Monitoring for neovascular age-related macular degeneration (AMD) reactivation at home: the MONARCH study.

Eye (Lond) 2021 Feb 4;35(2):592-600. Epub 2020 May 4.

Bristol Trials Centre (CTEU), University of Bristol, Bristol Royal Infirmary, Bristol, BS2 8HW, UK.

Aims: This study aims to quantify the diagnostic test-accuracy of three visual function self-monitoring tests for detection of active disease in patients with neovascular age-related macular degeneration (nAMD) when compared with usual care. An integrated qualitative study will investigate the acceptability of these home-based testing strategies.

Methods: All consenting participants are provided with an equipment pack containing an iPod touch with two vision test applications installed and a paper journal of reading tests. Participants self-monitor their vision at home each week with all three tests for 12-18 months. Usual care continues over this period. Key eligibility criteria are: age ≥50 years; at least one eye with AMD with ≥6-≤42 months since first AMD treatment; and vision not worse than Snellen 6/60, LogMAR 1.04 or 33 letters. The primary outcome, and reference standard, is diagnosis of active disease during usual care monitoring in the Hospital Eye Service. Secondary outcomes include duration of study participation, ability of participants to do the tests, adherence to weekly testing and acceptability of the tests to participants.

Conclusions: Recruitment is in progress at five NHS centres. Challenges in procuring equipment, setting up the devices and transporting devices containing lithium batteries to participating sites delayed the start of recruitment. The study will describe the performance of the tests self-administered at home in detecting active disease compared to usual care monitoring. It will also describe the feasibility of the NHS implementing patient-administered electronic tests or similar applications at home for monitoring health.
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http://dx.doi.org/10.1038/s41433-020-0910-4DOI Listing
February 2021

Assessment of the Vitreomacular Interface Using High-Resolution OCT in a Population-Based Cohort Study of Older Adults.

Ophthalmol Retina 2020 08 29;4(8):801-813. Epub 2020 Feb 29.

Centre for Public Health, Queen's University Belfast, Belfast, United Kingdom. Electronic address:

Purpose: To describe the prevalence of vitreomacular interface (VMI) features and their associated risk factors in the Northern Ireland Cohort for the Longitudinal Study of Ageing (NICOLA) Study.

Design: Cross-sectional population-based study.

Participants: Noninstitutionalized Northern Irish adults 40 years of age or older.

Methods: Using geographic stratification, a representative sample of people in Northern Ireland was invited to participate in the NICOLA Study. SD OCT images of participants were graded for vitreomacular traction (VMT), macular hole (MH), and epiretinal membrane (ERM) according to the International Vitreomacular Traction Study Group. A subsample was graded in more detail to estimate the prevalence of VMA and VMA area detailing size and location of VMA. Descriptive analysis and risk factors for each VMI feature were determined using generalized estimating equations. Results were standardized to the Northern Ireland population census (2011).

Main Outcome Measures: Cohort profile, standardized prevalence, and risk factor associations of each VMI feature.

Results: Three thousand three hundred fifty-one NICOLA participants had gradable SD OCT images available for at least 1 eye. The prevalence of VMT was 0.5% (CI, 0.31%-0.70%), that for MH was 0.3% (CI, 0.23%-0.52%), and that for ERM was 7.6% (CI, 7.0%-8.3%). A detailed VMA analysis was performed on a subsample consisting of the first 1481 participants. The prevalence of VMA was 22.6% (CI, 21.1-24.2), and VMA area ranged from 0.25 to 42.7 mm (mean, 12.53 mm; standard deviation, 6.90 mm). In multivariate analyses, increased age was associated with an increased odds ratio (OR) of VMT, MH, and ERM. VMA area was positively associated with younger age and normal blood pressure. ERM and MH were present more often in more myopic eyes, associated with an increase in levels of high-density lipoprotein (HDL) cholesterol and triglycerides.

Conclusions: The epidemiologic characteristics of VMI features indicated that VMI interactions throughout life are age dependent. Vitreous separation reduced to a greater extent in the horizontal meridians compared with the vertical, differing from previous studies. Future longitudinal studies of the evolution of these VMI changes over time would be of great interest.
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http://dx.doi.org/10.1016/j.oret.2020.02.013DOI Listing
August 2020

Delayed attendance at routine eye examinations is associated with increased probability of general practitioner referral: a record linkage study in Northern Ireland.

Ophthalmic Physiol Opt 2020 05 16;40(3):365-375. Epub 2020 Apr 16.

Centre for Public Health, Queen's University Belfast, Belfast, UK.

Purpose: To investigate relationships between health and socio-economic status with delayed attendance at routine eye examinations and risk of subsequent general practitioner (GP) referral in Northern Ireland.

Methods: We constructed a cohort of 132 046 community dwelling individuals aged ≥60 years, drawing contextual information from the 2011 Northern Ireland Census. Using linked administrative records of routine eye examinations between 2009 and 2014, we calculated 311 999 examination intervals. Multinomial models were used to estimate associations between contextual factors and examination interval (classified into three groups: early recall, on-time, delayed attendance). Associations between examination interval and referral risk were estimated using logistic regression.

Results: Delayed attendance was recorded for 129 857 (41.6%) examination intervals, 53 759 (17.2%) delayed by ≥6 months. Female sex, poor general or mental health were each associated with delay, as were longer distances to optometry services among those aged ≥70 years (longest vs shortest: Relative Risk Ratio = 1.21 [1.14, 1.28]). Low income and residence in social housing were associated with reduced delay risk. There were 3347 (3.5%) and 11 401 (5.3%) GP referrals in the 60-69 and ≥70 years age groups respectively. Delayed attendance was associated with increased referral risk in both groups (Odds Ratios: 60-69 years = 1.30 [1.04, 1.61]; ≥70 years = 1.07 [1.01, 1.13]).

Conclusions: Poor health and longer distances to optometry services were associated with delayed attendance at routine eye examinations but low income was not. Delayed attendance was associated with increased GP referral risk, indicative of missed opportunities to detect potentially serious eye conditions.
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http://dx.doi.org/10.1111/opo.12685DOI Listing
May 2020

Association of reduced inner retinal thicknesses with chronic kidney disease.

BMC Nephrol 2020 01 31;21(1):37. Epub 2020 Jan 31.

Centre for Public Health, Queen's University Belfast, Block B, Royal Hospital, Grosvenor Road, Belfast, Northern Ireland, BT12 6BA.

Background: Tissue derived biomarkers may offer utility as indicators of accumulated damage. Reduced thickness of retinal neuronal tissue and the vascular choroid have previously been associated with vascular damage and diabetes. We evaluated associations between retinal thickness, retinal microvascular and choroidal measures, and renal function in a population with a high burden of comorbidity.

Methods: Participants were recruited from nuclear cardiology or renal medicine clinics. Retinal and choroidal thickness were measured from spectral-domain optical coherence tomograms. Retinal microvascular parameters were assessed from digital fundus photographs using a semi-automated software package.

Main Outcome Measure: Chronic kidney disease (CKD) categorised as: CKD stages 1-2, eGFR ≥60 ml/min/1.73m; CKD stage 3, eGFR 30-59 ml/min/1.73m, and CKD stages 4-5, eGFR ≤29 ml/min/1.73m.

Results: Participants (n = 241) had a mean age of 65 years and a mean eGFR of 66.9 ml/min/1.73m. Thirty-nine % of the cohort had diabetes and 27% were using diuretics. Thinning of the inner retina and changes to its microvascular blood supply were associated with lower eGFR and CKD stages 4 and 5, while no associations were found between the outer retinal layers or their choroidal blood supply and CKD of any stage. These associations remained following adjustment for age, mean arterial blood pressure, diabetes status, low-density lipoprotein, body mass index, and sex.

Conclusions: Inner retinal thinning and retinal microvascular variation is associated with advanced CKD (stages 4 & 5) independent of important confounding factors, but not with earlier stage CKD (stage 3) and, therefore, its utility as a biomarker for early CKD is not supported in this study.
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http://dx.doi.org/10.1186/s12882-019-1679-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6995224PMC
January 2020

Comparison of Goldmann applanation and Ocular Response Analyser tonometry: intraocular pressure agreement and patient preference.

Eye (Lond) 2020 03 27;34(3):584-590. Epub 2019 Aug 27.

Centre for Public Health, Queen's University Belfast, Belfast, UK.

Objectives: To evaluate the agreement between Goldmann applanation tonometry (GAT) and Ocular Response Analyser (ORA) intraocular pressure (IOP) measurements, and patients' preferences.

Methods: Both eyes of participants in the 'Glaucoma within the Northern Ireland Cohort for the Longitudinal Study of Ageing' (GwNICOLA) were included. Participants underwent GAT by a glaucoma expert and ORA tonometry in a random order. Investigators were masked to measurements between devices. Participants were asked which tonometer, if any, they would prefer. We estimated the 95% limits of agreement (95% LoA) and the variables that influence agreement between tonometers.

Results: There were 228 eyes of 120 participants included in this study. Mean age of participants was 68.0 years (SD 8.79) and 52.5% were female. For GAT-ORA IOPcc the mean difference with GAT (95% CI) was -0.23 mmHg (-0.57 mmHg, 0.11 mmHg) and the 95% LoA (95% CIs) were from 4.82 mmHg (5.15 mmHg, 4.48 mmHg) to -5.28 mmHg (-5.61 mmHg, -4.94 mmHg). 40.8% of eyes had an IOP difference of 2 mmHg or more between GAT and ORA IOPcc. Corneal resistance factor (CRF) as estimated by ORA influenced the agreement between GAT and ORA IOPcc. There were no differences in preference for method of tonometry.

Conclusions: Although ORA IOPcc measurements with ORA did not show significant bias compared with GAT, the relatively large proportion of measurement differences between ORA IOPcc and GAT that were >2 mmHg indicates that GAT and ORA IOP measurements may not be interchangeable. There were no differences in preference for method of tonometry.
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http://dx.doi.org/10.1038/s41433-019-0556-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7042243PMC
March 2020

Changes in Retinal Layer Thickness in the Contralateral Eye of Patients with Unilateral Neovascular Age-Related Macular Degeneration.

Ophthalmol Retina 2019 02 27;3(2):112-121. Epub 2018 Sep 27.

Doheny Eye Institute, Los Angeles, California; Department of Ophthalmology, David Geffen School of Medicine at University of California-Los Angeles, Los Angeles, California. Electronic address:

Purpose: To evaluate the thickness of the outer retinal layers and its relationship with visual function in fellow eyes of participants with unilateral neovascular age-related macular degeneration (AMD).

Design: Longitudinal study.

Participants: We enrolled 105 subjects with unilateral neovascular AMD from 3 clinical centers in Europe.

Methods: The fellow eye, without advanced AMD, was selected for the study. Subjects were followed up with visits occurring every 6 months for 2 years. Spectral domain optical coherence tomography volume scans were collected at 3 clinical sites, in Belfast, Northern Ireland; Coimbra, Portugal; and Milan, Italy. Detailed manual segmentation of outer retinal layers was performed using the custom-designed and validated grading software 3D OCTOR. Thickness measurements for neurosensory retina, photoreceptor layer (PRL) outer segments, retinal pigment epithelium plus drusen (RPE+drusen) complex, and choroidal layers from each sector of the standard macular grid were obtained. Measures of vison were distance visual acuity, near visual acuity, Smith-Kettlewell Institute low-luminance acuity score, and reading speed. Subjects were grouped based on the presence or absence of subretinal drusenoid deposits (SDDs) for further analysis.

Main Outcome Measures: Change in thickness of retinal layers and change in measures of vision.

Results: In all, 85 eyes were included in the analysis. The average duration of follow-up was 20.5 ± 5.8 months. By the final visit, the RPE+drusen complex was significantly thinner when compared with baseline (29.7 μm vs. 34.09 μm; P = 0.03). Low-luminance deficit was significantly worse at the final visit (P < 0.001) and correlated with PRL outer segment thickness (r = 0.33; P =0.02). The RPE+drusen complex was significantly thicker in eyes with SDDs compared with that in those without SDDs (30.67 μm vs. 28.64 μm; P = 0.02). PRL outer segments became significantly thinner over time in eyes with SDDs compared with those in eyes without SDDs.

Conclusions: The RPE+drusen complex layer becomes thinner over time in fellow eyes of subjects with unilateral neovascular AMD. The rate of PRL outer segment thinning was higher in eyes with SDDs than in eyes without SDDs. These findings are preliminary steps in the identification of early biomarkers for detecting and monitoring the progression of AMD.
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http://dx.doi.org/10.1016/j.oret.2018.09.017DOI Listing
February 2019

Serum amyloid A levels are associated with polymorphic variants in the serum amyloid A 1 and 2 genes.

Ir J Med Sci 2019 Nov 9;188(4):1175-1183. Epub 2019 Mar 9.

Centre for Public Health, Queen's University Belfast, Belfast, Northern Ireland.

Background: Serum amyloid A (SAA) is secreted by liver hepatocytes in response to increased inflammation whereupon it associates with high-density lipoprotein (HDL) and alters the protein and lipid composition of HDL negating some of its anti-atherogenic properties.

Aims: To identify variants within the SAA gene that may be associated with SAA levels and/or cardiovascular disease (CVD).

Methods: We identified exonic variants within the SAA genes by deoxyribonucleic acid (DNA) Sanger sequencing. We tested the association between SAA variants and serum SAA levels in 246 individuals with and without CVD.

Results: Increased SAA was associated with rs2468844 (beta [β] = 1.73; confidence intervals [CI], 1.14-1.75; p = 0.01), rs1136747 (β = 1.53 (CI, 1.11-1.73); p = 0.01) and rs149926073 (β = 3.37 (CI, 1.70-4.00); p = 0.02), while rs1136745 was significantly associated with decreased SAA levels (β = 0.70 (CI, 0.53-0.94); p = 0.02). Homozygous individuals with the SAA1.3 haplotype had significantly lower levels of SAA compared with those with SAA1.1 or SAA1.5 (β = 0.43 (CI, 0.22-0.85); p = 0.02) while SAA1.3/1.5 heterozygotes had significantly higher SAA levels compared with those homozygous for SAA1.1 (β = 2.58 (CI, 1.19-5.57); p = 0.02).

Conclusions: We have identified novel genetic variants in the SAA genes associated with SAA levels, a biomarker of inflammation and chronic disease. The utility of SAA as a biomarker for inflammation and chronic disease may be influenced by underlying genetic variation in baseline levels.
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http://dx.doi.org/10.1007/s11845-019-01996-8DOI Listing
November 2019

Diagnostic Accuracy of Spectral-Domain OCT Circumpapillary, Optic Nerve Head, and Macular Parameters in the Detection of Perimetric Glaucoma.

Ophthalmol Glaucoma 2019 Sep - Oct;2(5):336-345. Epub 2019 Jun 27.

Centre for Public Health, Queen's University Belfast, Belfast, United Kingdom. Electronic address:

Purpose: To evaluate the diagnostic accuracy of circumpapillary retinal nerve fiber layer (cRNFL), optic nerve head, and macular parameters for the detection of glaucoma using Heidelberg Spectralis OCT (Heidelberg Engineering, Inc., Heidelberg, Germany).

Design: Cross-sectional study.

Participants: Participants of the Northern Ireland Cohort for the Longitudinal Study of Ageing with a vertical cup-to-disc ratio of 0.7 or more, vertical cup-to-disc ratio asymmetry of 0.2 or more, vertical neuroretinal rim ratio of 0.1 or less, intraocular pressure of 25 mmHg or more, or a combination thereof were invited to the study.

Methods: Participants underwent clinical examination by a masked glaucoma expert and full-threshold visual field testing to define glaucoma. Five index tests were performed: (1) standard cRNFL thickness, (2) macular Early Treatment Diabetic Retinopathy Study (ETDRS) scans, (3) macular posterior pole asymmetry analysis (PPAA) scans, (4) Bruch's membrane opening minimum rim width (BMO MRW), and (5) Glaucoma Module Premium Edition (GMPE) cRNFL Anatomic Positioning System (APS) scans. We analyzed the eye with more advanced disease per participant.

Main Outcome Measures: Analysis of receiver operating characteristic (ROC) curve; area under the ROC curve (AUC); and partial AUC (pAUC) at specificity of 0.80 to 1, 0.90 to 1, and 0.95 to 1. Sensitivity at 0.95 specificity and specificity at 0.95 sensitivity were reported. Primary analysis included all available scans.

Results: One hundred twenty-eight eyes from 128 participants were enrolled (52 eyes with perimetric glaucoma and 76 eyes without glaucoma). One hundred thirteen standard cRNFL thickness scans; 107 GMPE cRNFL APS 3.5-mm, 4.1-mm, and 4.7-mm scans; 107 BMO-MRW scans; 98 ETDRS scans; and 97 PPAA scans were available. Standard cRNFL mean global thickness showed highest AUC (0.869; 95% confidence interval [CI], 0.800-0.938) and the highest pAUC at specificity of 0.80 to 1 (0.815; 95% CI, 0.742-0.887), at specificity of 0.90 to 1 (0.794; 95% CI, 0.713-0.875), and at specificity of 0.95 to 1 (0.765; 95% CI, 0.696-0.861). Standard cRNFL mean global thickness scans provided the highest sensitivity at 0.95 specificity (0.630), whereas ETDRS mGCL outer inferior sector provided the highest specificity at 0.95 sensitivity (0.522).

Conclusions: Macular and optic nerve head OCT parameters were not better than cRNFL measurements to diagnose glaucoma in this population.
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http://dx.doi.org/10.1016/j.ogla.2019.06.003DOI Listing
June 2019

Confocal infrared imaging with optical coherence tomography provides superior detection of a number of common macular lesions compared to colour fundus photography.

Ophthalmic Physiol Opt 2018 11;38(6):574-583

Centre for Public Health, Queen's University Belfast, Belfast, UK.

Purpose: To compare diagnostic accuracy of confocal infrared reflectance (IR), with and without optical coherence tomography (OCT), to colour fundus photography (CFP) in the Northern Ireland Cohort for the Longitudinal Study of Ageing (NICOLA) Study.

Methods: Cross-sectional observational study of participants in NICOLA. CFP, IR and IR/OCT of 640 eyes were graded for hard, soft and reticular pseudodrusen; geographic atrophy; choroidal neovascularisation; naevus; epiretinal membrane; and haemorrhages. Test characteristics (sensitivity and specificity) for each imaging modality with respect to each retinal feature were calculated.

Results: With CFP as the reference standard, sensitivity of IR by itself ranged from 75% for RPD to 93.5% for hard drusen and specificity was above 90% for all features except hard drusen (71.7%). For IR combined with OCT, sensitivity ranged from 80% for choroidal neovascularisation to 96.5% for hard drusen. When IR alone was the reference standard, CFP sensitivity was high for naevi (97.5%) but reduced markedly for epiretinal membrane (48.5%). When the combination of IR and OCT was the reference standard, sensitivity for CFP was least for epiretinal membrane (31.5%), low for geographic atrophy and reticular pseudodrusen (77.8% and 76.2% respectively) and high for all other lesion types.

Conclusion: Our findings support the use of confocal IR with OCT as a screening tool for a variety of features of macular disease in community optometric practice.
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http://dx.doi.org/10.1111/opo.12592DOI Listing
November 2018

Dietary patterns were not associated with age-related macular degeneration: a cross-sectional analysis in the Irish Nun Eye Study.

Ir J Med Sci 2019 Aug 22;188(3):1005-1012. Epub 2018 Nov 22.

Centre for Public Health, Queen's University Belfast, Belfast, UK.

Background: Analysing dietary patterns (DP) evaluates overall dietary intake, taking account of its complexity, quality, variance and the interaction between different foods, providing an alternative approach for the evaluation of nutritional influences on age-related macular degeneration (AMD) risk.

Aims: To evaluate the relationship between DP and AMD in an older female population.

Methods: Data was analysed from the cross-sectional Irish Nun Eye Study involving 1233 older women with a restricted lifestyle (mean age 76.3 years [range, 56-100 years). The Wisconsin Age-related Maculopathy Grading System was used to classify digital colour macular fundus images and dietary intake was assessed using a food frequency questionnaire (n = 1033). A posteriori DP were derived using principal component analysis. Logistic regression models examined associations between DP and AMD risk with adjustment for confounders.

Results: Two DP were identified: a 'healthy' pattern characterised by a high intake of oily fish, wholegrains, vegetables and fruit; and an 'unhealthy' pattern characterised by high-fat dairy products, sugar, sweets and chips. Of the participants included within the analysis, AMD status were categorised as controls (n = 818, 86.9%), early AMD (n = 83, 8.8%) and late AMD (n = 21, 2.2%). Regression analysis failed to identify any significant associations between healthy or unhealthy DP and AMD risk, in unadjusted and adjusted models.

Conclusion: No evidence of an association between the DP identified and AMD risk was detected in this well-characterised population. Further research is required to determine the overall dietary influences on AMD risk in general population cohorts.
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http://dx.doi.org/10.1007/s11845-018-1932-9DOI Listing
August 2019

The cost-effectiveness of alternative vision screening models among preschool children in rural China.

Acta Ophthalmol 2019 May 21;97(3):e419-e425. Epub 2018 Oct 21.

OneSight, Mason, Ohio, USA.

Purpose: To explore the accuracy and cost-effectiveness of three vision screening models among preschool children in rural China.

Methods: Vision screening was carried out among children aged 4-5 years in 65 preschools in two counties in Northwest China, using Crowded Single Lea Symbols to test visual acuity. Children were assigned randomly by school to one of three screening models: screening by teachers (15 schools, 1835 children), local optometrists (30 schools, 1718 children) or volunteers (20 schools, 2183 children). Children identifying ≥2 symbols incorrectly in either eye failed screening. Accuracy of screening was compared with screenings executed by experienced optometrists among 141 children selected randomly from the three screening models. Direct and indirect costs for each model were assessed. Costs to detect a true case failed screening were estimated.

Results: The sensitivity for three models ranged from 76.9% to 87.5%, specificity from 84.9% to 86.7% and standardized positive predictive value from 83.7% to 85.7%. None differed significantly between models. The costs per case detected were $37.53, $59.14 and $52.19 for the teachers, local optometrists and volunteers. In producing the cost estimates for teacher screening and local optometrist screening models, we used a salary payment that was identical for both models (with the salary being equal to that of the optometrist). The teacher screening model was the most cost-effective.

Conclusion: Accuracy of screening by teachers, local optometrists and volunteers was the same in this setting, but the use of teachers was most cost-effective, reducing the cost per case detected by almost 40%.
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http://dx.doi.org/10.1111/aos.13954DOI Listing
May 2019

Impact of car transport availability and drive time on eye examination uptake among adults aged ≥60 years: a record linkage study.

Br J Ophthalmol 2019 06 3;103(6):730-736. Epub 2018 Jul 3.

Centre for Public Health, Queen's University Belfast, Belfast, UK.

Aim: To examine associations between uptake of free primary eye care, service availability (density of optometric practices) and service accessibility (household car access and drive time to nearest provider) after accounting for socioeconomic status and other individual, household and area factors.

Methods: We constructed a cohort of 294 870 community-dwelling adults aged 60 years, drawing contextual information from the 2011 Northern Ireland Census. Minimum drive times to the nearest optometry practice (1-19 min) and number of practices were derived for 890 geographical areas. The primary outcome was attendance at one or more publicly funded eye examinations to which all cohort members were entitled between 2009 and 2014. We used multiple log-binomial regression to estimate associations between eye care uptake, car ownership and drive time.

Results: Eye examination uptake was 60.0%. 23.7% of the cohort had no car access, and these individuals had lower uptake than car owners (unadjusted risk ratio (RR) of uptake=0.86 (0.86, 0.87)). Among non-car owners, uptake decreased with drive time (longest vs shortest: RR=0.92 (0.88, 0.97)) with the largest decrease at 4 min drive time (approximately 1.5 miles). This pattern was weaker among car owners. These associations were independent of service availability, which was not associated with uptake.

Conclusion: Both drive time and household car access were associated with eye care use, adjusting for individual, household and area factors. Policies to improve uptake should target those with no car access, especially those beyond walking distance from the nearest eye care provider.
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http://dx.doi.org/10.1136/bjophthalmol-2018-312201DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6582726PMC
June 2019

The Decreasing Prevalence of Nonrefractive Visual Impairment in Older Europeans: A Meta-analysis of Published and Unpublished Data.

Ophthalmology 2018 08 13;125(8):1149-1159. Epub 2018 Mar 13.

Bordeaux Population Health Research Center, Team LEHA, Unité Mixte de Recherche (UMR) 1219, INSERM, Université de Bordeaux, Bordeaux, France; Service d'Ophtalmologie, Centre Hospitalier Universitaire de Bordeaux, Bordeaux, France.

Topic: To estimate the prevalence of nonrefractive visual impairment and blindness in European persons 55 years of age and older.

Clinical Relevance: Few visual impairment and blindness prevalence estimates are available for the European population. In addition, many of the data collected in European population-based studies currently are unpublished and have not been included in previous estimates.

Methods: Fourteen European population-based studies participating in the European Eye Epidemiology Consortium (n = 70 723) were included. Each study provided nonrefractive visual impairment and blindness prevalence estimates stratified by age (10-year strata) and gender. Nonrefractive visual impairment and blindness were defined as best-corrected visual acuity worse than 20/60 and 20/400 in the better eye, respectively. Using random effects meta-analysis, prevalence rates were estimated according to age, gender, geographical area, and period (1991-2006 and 2007-2012). Because no data were available for Central and Eastern Europe, population projections for numbers of affected people were estimated using Eurostat population estimates for European high-income countries in 2000 and 2010.

Results: The age-standardized prevalence of nonrefractive visual impairment in people 55 years of age or older decreased from 2.22% (95% confidence interval [CI], 1.34-3.10) from 1991 through 2006 to 0.92% (95% CI, 0.42-1.42) from 2007 through 2012. It strongly increased with age in both periods (up to 15.69% and 4.39% in participants 85 years of age or older from 1991 through 2006 and from 2007 through 2012, respectively). Age-standardized prevalence of visual impairment tended to be higher in women than men from 1991 through 2006 (2.67% vs. 1.88%), but not from 2007 through 2012 (0.87% vs. 0.88%). No differences were observed between northern, western, and southern regions of Europe. The projected numbers of affected older inhabitants in European high-income countries decreased from 2.5 million affected individuals in 2000 to 1.2 million in 2010. Of those, 584 000 were blind in 2000, in comparison with 170 000 who were blind in 2010.

Conclusions: Despite the increase in the European older population, our study indicated that the number of visually impaired people has decreased in European high-income countries in the last 20 years. This may be the result of major improvements in eye care and prevention, the decreasing prevalence of eye diseases, or both.
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http://dx.doi.org/10.1016/j.ophtha.2018.02.005DOI Listing
August 2018

Prevalence of diabetic retinopathy and visual impairment in patients with diabetes mellitus in Zambia through the implementation of a mobile diabetic retinopathy screening project in the Copperbelt province: a cross-sectional study.

Eye (Lond) 2018 07 5;32(7):1201-1208. Epub 2018 Mar 5.

Department of Ophthalmology, Frimley Park Hospital, Frimley, UK.

Aims: A paucity of literature exists on prevalence of diabetic retinopathy (DR) in sub-Saharan Africa. We aim to estimate the prevalence of DR and visual impairment in Zambia's Copperbelt province through a cross-sectional study.

Methods: All patients with a diagnosis of diabetes mellitus attending a DR screening programme were eligible to participate. Fundus photographs were graded in accordance with the DR grading system used in the UK National Health service (NHS). Visual impairment data were collected from visual acuity measurements recorded using Snellen chart.

Results: A total of 2689 patients were screened and of these, 2153 patients had a least one eye of gradable quality for analysis. Fifty-five per cent (1190/2153) of patients were male. Mean age was 56 (SD 11). Fifty-two per cent (1113/2153) showed evidence of diabetic retinopathy (DR). Thirty-six per cent of patients graded (779/2153) had sight threatening DR. Proliferative DR was found in 7% (14/208) of type 1 diabetics compared to 5% (42/921) type 2 diabetics (p = <0.001). Duration of diabetes, random blood glucose, systolic and diastolic BP, and use of insulin and oral hypoglycaemics were strongly associated with DR in univariate analysis. The associations of increased systolic BP, random blood glucose, duration of diabetes and insulin use with DR were maintained in multivariate analysis.

Conclusion: We observed a high prevalence of sight threatening DR which is close to the upper range of estimates that currently exist on DR. This study represents further evidence of global health inequality and the scale of the epidemic which sub-Saharan African countries now face.
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http://dx.doi.org/10.1038/s41433-018-0055-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6043502PMC
July 2018

Disorganization of Inner Retina and Outer Retinal Morphology in Diabetic Macular Edema.

JAMA Ophthalmol 2018 02;136(2):202-208

Queens University, Belfast, United Kingdom.

Importance: In diabetic macular edema (DME), identification of baseline markers on spectral-domain optical coherence tomography (SD-OCT) and their association with severity of diabetic retinopathy (DR) might aid in disease management and the design of future trials.

Objective: To examine associations between DR severity, retinal morphology on SD-OCT, and visual acuity in participants with DME.

Design, Setting, And Participants: This cross-sectional observational case series was conducted at a single tertiary care referral center. Demographics, visual acuity, SD-OCT, and color fundus photographs of 80 individuals with DME (102 eyes) seen between December 28, 2013, and April 30, 2014, were analyzed between May 1 and July 31, 2016.

Main Outcomes And Measures: Features captured on SD-OCT and thickness metrics. On SD-OCT we graded type and shape of DME, shape and presence of septae within the intraretinal cystoid abnormalities, presence of hyperreflective dots and foci, integrity of the external limiting membrane and ellipsoid zone, presence and extent of disorganization of the inner retinal layers (DRIL), and the status of the vitreomacular interface and epiretinal membrane. We measured retinal thickness at the fovea and at the site of maximum pathology, choroidal thickness at the fovea, and 1000 μm temporal and nasal to the fovea. Color photographs were graded to derive a DR severity stage.

Results: The mean (SD) age was 63 (11) years, and 30 participants (37.5%) were women. The odds of having DRIL were greater in eyes with disrupted external limiting membrane (odds ratio [OR], 4.4; 95% CI, 1.6-12.0; P = .003), disrupted ellipsoid zone (OR, 2.7; 95% CI, 1.0-7.2; P = .03), presence of epiretinal membrane (OR, 2.8; 95% CI, 1.0-7.4; P = .03), and increase in retinal thickness at the fovea (OR, 1.6; 95% CI, 1.1-2.2; P < .001). Occurrence of DRIL was more likely in eyes with proliferative DR (OR, 7.3; 95% CI, 1.7-31.4; P = .007). Mean visual acuity decreased by approximately 4.7 letters for each 100-μm increase in the average global DRIL (95% CI, -7.9 to 1.4; P = .006).

Conclusions And Relevance: An association was found between DRIL and disruption of the outer retina and increasing DR severity. Further longitudinal studies seem warranted to determine whether DRIL is a clinically relevant noninvasive morphological marker in eyes with DME.
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http://dx.doi.org/10.1001/jamaophthalmol.2017.6256DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5838716PMC
February 2018

Can ultra-wide field retinal imaging replace colour digital stereoscopy for glaucoma detection?

Ophthalmic Epidemiol 2018 02 18;25(1):63-69. Epub 2017 Sep 18.

a Centre for Public Health , Queen's University Belfast , Belfast , UK.

Purpose: Ultra-wide field (UWF) retinal imaging (Optomap, Optos plc, Dunfermline, UK) is a novel technique to image the peripheral fundus. The goal of this study was to explore the potential use of UWF imaging to detect glaucoma, and specifically to evaluate the reproducibility of measures of vertical cup-to-disc ratio (VCDR) using ultra-wide field (UWF), and the agreement between UWF and standard colour digital stereoscopy (CDS).

Methods: An observational study. From a population-based epidemiological study we selected 100 eyes from 100 consecutive participants who were imaged using both standard CDS and UWF retinal imaging. Estimation of the VCDR using both modalities was made by a masked glaucoma specialist and two masked independent observers. Reliability and agreement between colour digital stereoscopy and the UWF imaging was assessed by Bland-Altman scatterplots.

Results: Intra-observer reproducibility of the UWF imaging in estimating VCDRs produced Limits of Agreement (LOA) ranging from -0.13 to 0.1 (mean 0.02) and -0.14 to 0.14 (mean 0.0004) for observer 1 and 2 respectively. Inter-observer reliability between observer 1 and the glaucoma specialist for VCDR measurements using CDS and UWF produced LOA ranging from -0.37 to 0.15 (mean -0.11) and -0.24 to 0.26 (mean 0.0005) respectively. Bland Altman plots produced LOA of -0.16 to 0.20 (mean 0.02) between the two imaging methods for assessing VCDR when carried out by a glaucoma specialist.

Conclusion: Grading of UWF imaging has high reproducibility in evaluating VCDR and agreement with stereoscopic optic disc imaging and may be suitable for glaucoma diagnosis in situations where CDS is not available.
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http://dx.doi.org/10.1080/09286586.2017.1351998DOI Listing
February 2018

IDENTIFYING FEATURES OF EARLY AND LATE AGE-RELATED MACULAR DEGENERATION: A Comparison of Multicolor Versus Traditional Color Fundus Photography.

Retina 2018 09;38(9):1751-1758

Centre for Public Health, Queen's University, Institute of Clinical Science, Belfast, Co. Antrim, Northern Ireland.

Purpose: To compare multicolor (MC) and traditional color fundus photography (CFP) in their ability to detect features of early and late age-related macular degeneration (AMD).

Methods: Study design: Observational case series.

Participants: fundus images captured using standard CFP and MC imaging from 33 patients attending hospital clinics and 26 participants from the pilot phase of the Northern Ireland Cohort for the Longitudinal Study of Ageing (NICOLA). Systematic grading of early and late AMD features; (hard drusen, soft drusen, reticular pseudodrusen, pigment clumping, non-geographic atrophy hypopigmentation, atrophy, hemorrhage, and fibrosis) on CFP and MC.

Results: There were 105 eyes with gradable images for comparison. Using CFP as the gold standard, sensitivity values for MC ranged from 100% for atrophy, non-geographic atrophy hypopigmentation, and fibrosis to 69.7% for pigment clumping. Specificity values were high: >80% for all features. On using MC as the comparator, CFP had lower sensitivity for the detection of early AMD features (27.8% for reticular drusen to 77.8% for non-geographic atrophy hypopigmention). Analysis of OCT in discrepant cases showed better agreement with MC for all AMD lesions, except hemorrhage and non-geographic atrophy hypopigmentation. For pigment clumping, CFP and MC were in equal agreement with OCT.

Conclusion: Multicolor retinal imaging allowed for improved detection and definition of AMD features.
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http://dx.doi.org/10.1097/IAE.0000000000001777DOI Listing
September 2018

Evaluation of coronary artery disease as a risk factor for reticular pseudodrusen.

Br J Ophthalmol 2018 04 19;102(4):483-489. Epub 2017 Aug 19.

Centre for Public Health, Queen's University Belfast, Belfast, UK.

Purpose: Reticular pseudodrusen (RPD) are a risk factor for late age-related macular degeneration (AMD). Associations between RPD and coronary artery disease (CAD) have been reported from small case-control studies. This study investigated the association of RPD within a predominantly CAD cohort.

Methods: A subgroup of subjects from a multicentre randomised controlled trial of CT coronary angiography (CTCA) underwent ultrawide field (UWF) retinal imaging CAD determined by CTCA and was categorised as normal, non-obstructive or obstructive. Specific AMD features in UWF images were graded. Standardised grids were used to record the spatial location of AMD features, including RPD. Multivariate confounder adjusted regression models assessed the association between RPD and CAD.

Results: The 534 participants were aged 27-75 years (mean 58±9 years; 425 (80%) ≥50 years) with a male preponderance (56%). Within the study sample, 178 (33%) had no CAD, 351 (66%) had CAD. RPD was detected in 30 participants (5.6%) and bilaterally in 23. Most participants with bilateral RPD had intermediate AMD 17 (74%). After adjustment for potential confounders (age, sex, drusen >125 µm, smoking status), multivariate analysis found no significant association between CAD and RPD (OR 1.31; 95% CI (0.57 to 3.01); p=0.52). A significant association was identified between RPD and intermediate AMD (OR 3.18; 95% CI (1.61 to 6.27); p=0.001).

Conclusion: We found no evidence to support an association between CAD and RPD. RPD was strongly associated with intermediate AMD features.

Trial Registration Number: NCT01149590, Post results.
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http://dx.doi.org/10.1136/bjophthalmol-2017-310526DOI Listing
April 2018

Association of C-Reactive Protein Genetic Polymorphisms With Late Age-Related Macular Degeneration.

JAMA Ophthalmol 2017 09;135(9):909-916

Faculty of Epidemiology and Population Health, London School of Hygiene and Tropical Medicine, London, England.

Importance: C-reactive protein (CRP) is a circulating inflammatory marker associated with late age-related macular degeneration (AMD). It remains uncertain whether the association between CRP concentrations and AMD is causal.

Objective: To assess whether CRP (OMIM 123260) single-nucleotide polymorphisms that influence circulating CRP concentrations are associated with late AMD.

Design, Setting, And Participants: Participants in 2 UK, hospital-based, case-control studies (Cambridge AMD study and Moorfields Eye Hospital AMD study) and 1 pan-European, cross-sectional, population-based study (the European Eye [EUREYE] Study) were recruited between November 6, 2000, and April 30, 2007. Participants underwent dilated stereo-digital fundus photography graded according to the International Classification of Age-related Maculopathy and Macular Degeneration. There were 1727 cases of late AMD (1151 neovascular, 384 geographic atrophy, and 192 mixed [neovascular AMD and geographic atrophy]) and 1153 controls. Early AMD cases (n = 574) were included only from the EUREYE Study. Data analysis was performed from August 1 to November 30, 2016. Four common single-nucleotide polymorphisms (rs1205, rs1130864, rs1800947, and rs3093077) were selected based on demonstrated influence on circulating CRP concentrations in the literature. In one study, genotyping of rs3093077 failed, and rs1800947 was typed in only 1 study.

Main Outcomes And Measures: A genetic multiplicative model was used for the association of single-nucleotide polymorphisms with late AMD adjusted for age and sex.

Results: Among the 1727 patients with late AMD, the mean (SD) age was 78.7 (7.4) years, and 668 (38.7%) were men. The mean (SD) age of the controls was 74.9 (7.0) years, and 510 (44.2%) were men. In the pooled results of all 3 studies, neither rs1205 (odds ratio [OR], 0.99; 95% CI, 0.86-1.14) nor rs1130864 (OR, 0.96; 95% CI, 0.83-1.11) was associated with late AMD. For geographic atrophy, rs1205 had an OR of 0.91 (95% CI, 0.74-1.13) and rs1130864 had an OR of 0.94 (95% CI, 0.76-1.16). For neovascular AMD, rs1205 had an OR of 1.01 (95% CI, 0.87-1.19) and rs1130864 had an OR of 0.99 (95% CI, 0.84-1.16). There was no association of rs3093077 and rs1800947 with late AMD or any late AMD phenotype. There were no significant findings for early AMD.

Conclusions And Relevance: Our results do not support a causal association between CRP concentrations and AMD.
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http://dx.doi.org/10.1001/jamaophthalmol.2017.2191DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5710541PMC
September 2017

Individual differences in human eye movements: An oculomotor signature?

Vision Res 2017 12 12;141:157-169. Epub 2017 Apr 12.

Department of Experimental Psychology, University of Cambridge, Downing Street, Cambridge CB2 3EB, United Kingdom. Electronic address:

Human eye movements are stereotyped and repeatable, but how specific to a normal individual are the quantitative properties of his or her eye movements? We recorded saccades, anti-saccades and smooth-pursuit eye movements in a sample of over 1000 healthy young adults. A randomly selected subsample (10%) of participants were re-tested on a second occasion after a median interval of 18.8days, allowing us to estimate reliabilities. Each of several derived measures, including latencies, accuracies, velocities, and left-right asymmetries, proved to be very reliable. We give normative means and distributions for each measure and describe the pattern of correlations amongst them. We identify several measures that exhibit significant sex differences. The profile of our oculomotor measures for an individual constitutes a personal oculomotor signature that distinguishes that individual from most other members of the sample of 1000.
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http://dx.doi.org/10.1016/j.visres.2017.03.001DOI Listing
December 2017

Peripheral blood mononuclear cells from neovascular age-related macular degeneration patients produce higher levels of chemokines CCL2 (MCP-1) and CXCL8 (IL-8).

J Neuroinflammation 2017 02 23;14(1):42. Epub 2017 Feb 23.

Centre for Experimental Medicine, Queen's University Belfast, Belfast, UK.

Background: Infiltrating immune cells including monocytes/macrophages have been implicated in the pathogenesis of neovascular age-related macular degeneration (nAMD). The aim of this study was to investigate the cytokine and chemokine expression and secretion profile of peripheral blood mononuclear cells (PBMCs) from nAMD patients and the relationship between the cytokine/chemokine expression profile and clinical phenotype of nAMD, including macular fibrosis, macular atrophy or the responsiveness to anti-VEGF therapy.

Methods: One hundred sixty-one nAMD patients and 43 controls were enrolled in this study. nAMD patients were divided into subgroups based on the presence/absence of (1) macular atrophy, (2) macular fibrosis and (3) responsiveness to anti-VEGF therapy; 25-30 ml of peripheral blood were obtained from all participants and 5 ml were used for serum collection, and the remaining were used for PBMC isolation using density gradient centrifugation. Intracellular cytokine expressions by PBMCs following phorbol 12-myristate 13-acetate (PMA) and ionomycin stimulation were examined using flow cytometry. Cytokine productions in lipopolysaccharides (LPS)-or 1% oxygen -treated PBMC were measured using cytometric bead array (CBA) assay. In addition, cytokine and chemokine levels in the serum were also measured by CBA assay.

Results: PBMCs from nAMD patients secreted higher levels of IL-8, CCL2 and VEGF, especially following LPS and 1% oxygen stimulation, than those from controls. 60~80% of IL-8 producing cells were CD11bCD3 monocytes. The percentage of CD11bCD3 IL-8 was significantly increased in nAMD patients compared to controls. PBMCs from nAMD patients without macular fibrosis produced the highest levels of IL-8 and CCL2, whilst PBMCs from nAMD patients with macular atrophy produced highest levels of VEGF. In addition, PBMCs from patients who partially responded to anti-VEGF produced higher levels of IL-8 compared to the cells from complete responders. Interestingly, serum level of CCL2 was not increased in nAMD patients although there was a trend of increased IL-8 in nAMD patients.

Conclusions: PBMCs, in particular monocytes, may contribute to CNV development in nAMD through secreting elevated levels of IL-8, CCL2 and VEGF after they are recruited to the macula. Apart from VEGF, IL-8 and CCL2 may be additional targets for nAMD management.
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http://dx.doi.org/10.1186/s12974-017-0820-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5324243PMC
February 2017

Author Response: Statin Use and Open-Angle Glaucoma: Evidence From Observational Studies.

Invest Ophthalmol Vis Sci 2017 01;58(1):158-161

Centre for Public Health, Queens University Belfast, Belfast, United Kingdom.

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http://dx.doi.org/10.1167/iovs.16-21133DOI Listing
January 2017

Author Response: A Meta-Analysis of Glaucoma Risk in Hyperlipidemic Individuals: A Critical Problem in Design.

Invest Ophthalmol Vis Sci 2016 11;57(14):6341

Queen's University Belfast, Centre for Public Health, Institute of Clinical Sciences, Belfast, United Kingdom.

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http://dx.doi.org/10.1167/iovs.16-20233DOI Listing
November 2016

Mediterranean Diet Score and Its Association with Age-Related Macular Degeneration: The European Eye Study.

Ophthalmology 2017 01 5;124(1):82-89. Epub 2016 Nov 5.

Faculty of Epidemiology and Population Health, London School of Hygiene & Tropical Medicine, London, United Kingdom.

Purpose: To examine associations between adherence to a Mediterranean diet and prevalence of age-related macular degeneration (AMD) in countries ranging from Southern to Northern Europe.

Design: Cross-sectional, population-based epidemiologic study.

Participants: Of 5060 randomly sampled people aged 65 years or older from 7 study centers across Europe (Norway, Estonia, United Kingdom, France, Italy, Greece, and Spain), full dietary data were available in 4753. The mean age of participants was 73.2 years (standard deviation, 5.6), and 55% were women.

Methods: Participants underwent an eye examination and digital retinal color photography. The images were graded at a single center. Dietary intake during the previous 12 months was assessed by using a semiquantitative food-frequency questionnaire (FFQ). A previously published Mediterranean Diet Score (MDS) was used to classify participants according to their responses on the FFQ. Multivariable logistic regression was used to investigate the association of the MDS score and AMD, taking account of potential confounders and the multicenter study design.

Main Outcome Measures: Images were graded according to the International Classification System for age-related maculopathy and stratified using the Rotterdam staging system into 5 exclusive stages (AMD 0-4) and a separate category of large drusen (≥125 μm). Age-related macular degeneration 4 included neovascular AMD (nvAMD) and geographic atrophy (GA).

Results: Increasing MDS was associated with reduced odds of nvAMD in unadjusted and confounder-adjusted analysis. Compared with the lowest MDS adherence (≤4 score), those in the highest category MDS adherence (>6 score) showed lower odds of nvAMD (odds ratio, 0.53; 0.27-1.04; P trend = 0.01). The association with MDS did not differ by Y204H risk allele (P = 0.89). For all early AMD (grade 1-3), there was no relationship with MDS (P trend = 0.9). There was a weak trend (P = 0.1) between MDS and large drusen; those in the highest category of MDS had 20% reduced odds compared with those in the lowest (P = 0.05).

Conclusions: This study adds to the limited evidence of the protective effect of adherence to a Mediterranean dietary pattern in those with late AMD, although it does not support previous reports of a relationship with genetic susceptibility. Interventions to encourage the adoption of the Mediterranean diet should be developed, and methods by which such behavior change can be achieved and maintained investigated.
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http://dx.doi.org/10.1016/j.ophtha.2016.09.019DOI Listing
January 2017