Vitreomacular interface abnormalities in the Ghanaian African.

BACKGROUND/OBJECTIVE: Describe vitreomacular interface abnormalities (VMIA) using spectral-domain optical coherence tomography (SD-OCT), and correlations with age-related macular degeneration (AMD) grade in Ghanaian Africans. SUBJECTS/METHODS: Prospective, cross-sectional study of adults aged ≥50 years recruited in Ghana AMD Study. Participant demographics, medical histories, ophthalmic examination, digital colour fundus photography (CFP) were obtained. High-resolution five-line raster OCT, Macular Cube 512 × 128 scans, and additional line scans in areas of clinical abnormality, were acquired. SD-OCT VMI features classified by International Vitreomacular Traction Study Group system and relationships to AMD grade were evaluated. OUTCOMES: VMIA prevalence, posterior vitreous detachment (PVD), vitreomacular adhesions (VMA), vitreomacular traction (VMT), epiretinal membranes (ERM), correlations with AMD grade. RESULTS: The full Ghana AMD cohort included 718 participants; 624 participants (1248 eyes) aged ≥50 years (range = 50-101, mean = 68.8), 68.9% female were included in this analysis. CFP with OCT scans were available for 776 eyes (397 participants); 707 (91.1%) had gradable CFP and OCT scans for both AMD and VMI grading forming the dataset for this report. PVD was absent in 504 (71.3%); partial and complete PVD occurred in 16.7% and 12.0% respectively. PVD did not increase with age (p = 0.720). VMIA without traction and macular holes were observed in 12.2% of eyes; 87.8% had no abnormalities. VMIA was not significantly correlated with AMD grade (p = 0.819). CONCLUSIONS: This provides the first assessment of VMIA in Ghanaian Africans. VMIA are common in Africans; PVD may be less common than in Caucasians. There was no significant association of AMD grade with VMIA.

Retinal and Choroidal Thickness in an Indigenous Population from Ghana: Comparison with Individuals with European or African Ancestry.

Purpose: To evaluate the thickness of the macular retina and central choroid in an indigenous population from Ghana, Africa and to compare them with those measured among individuals with European or African ancestry. Design: Cross-sectional study, systematic review, and meta-analyses. Participants: Forty-two healthy Ghanaians, 37 healthy individuals with European ancestry, and an additional 1427 healthy subjects with African ancestry from previously published studies. Methods: Macular retinal thickness in the fovea, parafovea, and perifovea and central choroidal thickness were extracted from OCT volume scans. Associations with ethnicity, age, and sex were assessed using mixed-effect regression models. Monte Carlo simulations were performed to determine the sensitivity of significant associations to additional potential confounders. Pooled estimates of retinal thickness among other groups with African ancestry were generated through systematic review and meta-analyses. Main Outcome Measures: Macular retinal thickness and central choroidal thickness and their association with ethnicity, age, and sex. Results: When adjusted for age and sex, the macular retina and central choroid of Ghanaians are significantly thinner as compared with subjects with European ancestry (P < 0.001). A reduction in retinal and choroidal thickness is observed with age, although this effect is independent of ethnicity. Meta-analyses indicate that retinal thickness among Ghanaians differs markedly from that of African Americans and other previously reported indigenous African populations. Conclusions: The thickness of the retina among Ghanaians differs not only from those measured among individuals with European ancestry, but also from those obtained from African Americans. Normative retinal and choroidal parameters determined among individuals with African or European ancestry may not be sufficient to describe indigenous African populations. Financial Disclosures: Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Usher Syndrome on the Island of Ireland: A Genotype-Phenotype Review.

Purpose: Usher syndrome (USH) is a genetically heterogeneous group of autosomal recessive (AR) syndromic inherited retinal degenerations (IRDs) representing 50% of deaf-blindness. All subtypes include retinitis pigmentosa, sensorineural hearing loss, and vestibular abnormalities. Thorough phenotyping may facilitate genetic diagnosis and intervention. Here we report the clinical/genetic features of an Irish USH cohort. Methods: USH patients were selected from the Irish IRD registry (Target 5000). Patients were examined clinically (deep-phenotyping) and genetically using a 254 IRD-associated gene target capture sequencing panel, USH2A exon, and whole genome sequencing. Results: The study identified 145 patients (24.1% USH1 [n = 35], 73.8% USH2 [n = 107], 1.4% USH3 [n = 2], and 0.7% USH4 [n = 1]). A genetic diagnosis was reached in 82.1%, the majority (80.7%) being MYO7A or USH2A genotypes. Mean visual acuity and visual field (VF) were 0.47 ± 0.58 LogMAR and 31.3° ± 32.8°, respectively, at a mean age of 43 years. Legal blindness criteria were met in 40.7%. Cataract was present in 77.4%. ADGRV1 genotypes had the most VF loss, whereas USH2A patients had greater myopia and CDH23 had the most astigmatism. Variants absent from gnomAD non-Finnish Europeans and ClinVar represented more than 20% of the variants identified and were detected in ADGRV1, ARSG, CDH23, MYO7A, and USH2A. Conclusions: USH is a genetically diverse group of AR IRDs that have a profound impact on affected individuals and their families. The prevalence and phenotype/genotype characteristics of USH in Ireland have, as yet, gone unreported. Understanding the genotype of Irish USH patients may guide clinical and genetic characterization facilitating access to existing/novel therapeutics.

Detailed analysis of an enriched deep intronic ABCA4 variant in Irish Stargardt disease patients.

Over 15% of probands in a large cohort of more than 1500 inherited retinal degeneration patients present with a clinical diagnosis of Stargardt disease (STGD1), a recessive form of macular dystrophy caused by biallelic variants in the ABCA4 gene. Participants were clinically examined and underwent either target capture sequencing of the exons and some pathogenic intronic regions of ABCA4, sequencing of the entire ABCA4 gene or whole genome sequencing. ABCA4 c.4539 + 2028C > T, p.[= ,Arg1514Leufs*36] is a pathogenic deep intronic variant that results in a retina-specific 345-nucleotide pseudoexon inclusion. Through analysis of the Irish STGD1 cohort, 25 individuals across 18 pedigrees harbour ABCA4 c.4539 + 2028C > T and another pathogenic variant. This includes, to the best of our knowledge, the only two homozygous patients identified to date. This provides important evidence of variant pathogenicity for this deep intronic variant, highlighting the value of homozygotes for variant interpretation. 15 other heterozygous incidents of this variant in patients have been reported globally, indicating significant enrichment in the Irish population. We provide detailed genetic and clinical characterization of these patients, illustrating that ABCA4 c.4539 + 2028C > T is a variant of mild to intermediate severity. These results have important implications for unresolved STGD1 patients globally with approximately 10% of the population in some western countries claiming Irish heritage. This study exemplifies that detection and characterization of founder variants is a diagnostic imperative.

Characterization of West African Crystalline Macular Dystrophy in the Ghanaian Population.

OBJECTIVE: West African crystalline maculopathy (WACM) is characterized by the presence of macular hyperrefractile crystal-like deposits. Although the underlying pathophysiology has not been elucidated, a few biologic drivers have been proposed. We analyzed a large WACM case series to gain a more robust understanding of its features and etiology. DESIGN: Prospective, cross-sectional cohort study. SUBJECTS: Participants with WACM were selected from the large cohort recruited in the Ghana Age-Related Macular Degeneration Study. METHODS: Demographic and detailed medical histories, full ophthalmic examinations, digital color fundus photographs, and OCT images were obtained. All cases with WACM were evaluated by 3 retina experts. Crystal numbers, location, and distribution were determined. Associations between WACM and White age-related macular degeneration (AMD) risk variants were assessed using Firth's bias-reduced logistic regression, including age and sex as covariates. MAIN OUTCOME MEASURES: Phenotypic features of, and genetic associations with, WACM. RESULTS: West African crystalline maculopathy was identified in 106 eyes of 53 participants: 22 were bilateral and 24 were unilateral. Grading for AMD was not possible in 1 eye in 7 participants with WACM; therefore, laterality was not assessed in these subjects. Thirty-eight participants were women and were 14 men; sex was unrecorded for 1 participant. The mean age was 68.4 years (range, 45-101 years). Typical WACM crystals were demonstrated on OCT, which were more easily identified at high contrast and predominantly located at the inner limiting membrane. In eyes with copathology, crystals localized deeper in the inner retina, with wider retinal distribution over copathology lesions. There was no association with age or sex. A significant association was observed between the complement factor H (CFH) 402H risk variant and WACM. CONCLUSIONS: This study confirms the localization of crystals adjacent to the inner limiting membrane and distribution over lesions in eyes with copathology. The evaluation of OCT images under high contrast allows improved identification. West African crystalline maculopathy may be associated with the CFH-CFHR5 AMD risk locus identified among Whites; however, it is also possible that the combination of crystals and the CFH 402H allele increases the risk for developing late AMD. Further analyses using larger sample sizes are warranted to identify causalities between genotype and WACM phenotype.

Surgical planning during a pandemic: Identifying patients at high risk of severe disease or death due to COVID-19 in a cohort of patients on a cataract surgery waiting list.

BACKGROUND: The delivery of cataract surgery during the COVID-19 pandemic is challenging because of the risk of nosocomial SARS-CoV-2 infection when patients attend hospital for elective care. In order to ascertain the risk to patients awaiting cataract surgery, this study aimed to identify the presence of systemic comorbidities that are associated with a high risk of severe disease or death due to COVID-19. METHODS: A prospective study of 315 patients (630 eyes) was conducted from 3rd June to 31st July 2020. An electronic health record was used to identify any systemic comorbidities that would render a patient 'clinically extremely vulnerable' to COVID-19, as outlined by the Department of Health for Northern Ireland. Patient demographics, best-corrected visual acuity (VA) and risk of postoperative anisometropia were also recorded. RESULTS: The median age of patients awaiting cataract surgery was 76 years (range 22-97). Of the 315 patients, 72% were aged over 70 and 16% were aged over 85. A systemic comorbidity that would confer high risk status was identified in 21% of patients. This high risk status was attributable to severe respiratory disease, cancer, and immunosuppression therapies in the majority of cases. The high risk group were younger than those deemed non-high risk, but there were no significant differences with respect to gender, anticipated degree of surgical difficulty, VA, or whether the patient was undergoing first or second eye surgery. Of those patients awaiting first eye cataract surgery, the mean VA in the listed eye was 0.84 logMAR and 39% (70/179) had a VA <0.3 logMAR (6/12 Snellen acuity) in their fellow eye. 57% of patients were awaiting first eye surgery, and 32% of those patients would be at risk of symptomatic anisometropia postoperatively. CONCLUSION: One-fifth of patients awaiting cataract surgery were found to be at high risk of severe disease or death from COVID-19 and these patients may experience delays in their surgical care. Additional planning is required in order to minimise the morbidity associated with delayed cataract surgery.

Ocular sarcoidosis prevalence and clinical features in the Northern Ireland population.

BACKGROUND/OBJECTIVES: To record the prevalence of ocular sarcoidosis (OS) cases present in Northern Ireland as diagnosed using the International Workshop on Ocular Sarcoidosis (IWOS) classification, 2019. There are currently no data regarding OS in this population. SUBJECTS/METHODS: Retrospective case review of OS cases as identified by IWOS criteria 2019. Mid-year population estimates were used to calculate disease prevalence. Additional data collected included uveitis features, ocular complications and the presence of ocular only or multi-system disease. RESULTS: A total of 86 patients were identified meeting the criteria for a diagnosis of OS, and the prevalence of OS in Northern Ireland was estimated to be 4.5 cases per 100,000. The most common type of uveitis was panuveitis in 36% of cases, and the most common ocular complication was ocular hypertension in 36% of cases and detectable glaucomatous changes in 10%. Overall, 80% of cases presenting with ocular only sarcoidosis subsequently developed second organ involvement at a rate of 14%/person-years. The most common extra-ocular site of sarcoidosis was pulmonary. CONCLUSIONS: The Northern Ireland population has a relatively high prevalence of OS compared with other European countries. OS presenting with only ocular involvement progressed to second organ involvement in 80% of patients at a rate of 14%/person-years. Raised intra-ocular pressure with or without glaucomatous damage was a frequent finding. Thoracic CT imaging should be requested if clinical suspicion of OS exists and the presence of lymphopenia has utility in diagnosis with concurrent use of systemic ACE inhibitors.

Target 5000: a standardized all-Ireland pathway for the diagnosis and management of inherited retinal degenerations.

INTRODUCTION: Inherited retinal degenerations (IRD) are rare genetic disorders with > 300 known genetic loci, manifesting variably progressive visual dysfunction. IRDs were historically underserved due to lack of effective interventions. Many novel therapies will require accurate diagnosis (phenotype and genotype), thus an efficient and effective pathway for assessment and management is required. METHODS: Using surveys of existing practice patterns and advice from international experts, an all-Ireland IRD service (Target 5000) was designed. Detailed phenotyping was followed by next generation genetic sequencing in both a research and accredited laboratory. Unresolved pedigrees underwent further studies (whole gene/whole exome/whole genome sequencing). Novel variants were interrogated for pathogenicity (cascade screening, in silico analysis, functional studies). A multidisciplinary team (MDT; ophthalmologists, physicians, geneticists, genetic counsellors) reconciled phenotype with genotype. A bespoke care plan was created for each patient comprising supports, existing interventions, and novel therapies/clinical trials. RESULTS AND DISCUSSION: Prior to Target 5000, a significant cohort of patients were not engaged with healthcare/support services due to lack of effective interventions. Pathogenic or likely pathogenic variants in IRD-associated genes were detected in 62.3%, with 11.6% having variants of unknown significance. The genotyping arm of Target 5000 allowed a 42.73% cost saving over independent testing, plus the value of MDT expertise/processing. Partial funding has transferred from charitable sources to government resources. CONCLUSION: Target 5000 demonstrates efficacious and efficient clinical/genetic diagnosis, while discovering novel IRD-implicated genes/variants and investigating mechanisms of disease and avenues of intervention. This model could be used to develop similar IRD programmes in small/medium-sized nations.

Pathogenic alleles in microtubule, secretory granule and extracellular matrix-related genes in familial keratoconus.

Keratoconus is a common corneal defect with a complex genetic basis. By whole exome sequencing of affected members from 11 multiplex families of European ancestry, we identified 23 rare, heterozygous, potentially pathogenic variants in 8 genes. These include nonsynonymous single amino acid substitutions in HSPG2, EML6 and CENPF in two families each, and in NBEAL2, LRP1B, PIK3CG and MRGPRD in three families each; ITGAX had nonsynonymous single amino acid substitutions in two families and an indel with a base substitution producing a nonsense allele in the third family. Only HSPG2, EML6 and CENPF have been associated with ocular phenotypes previously. With the exception of MRGPRD and ITGAX, we detected the transcript and encoded protein of the remaining genes in the cornea and corneal cell cultures. Cultured stromal cells showed cytoplasmic punctate staining of NBEAL2, staining of the fibrillar cytoskeletal network by EML6, while CENPF localized to the basal body of primary cilia. We inhibited the expression of HSPG2, EML6, NBEAL2 and CENPF in stromal cell cultures and assayed for the expression of COL1A1 as a readout of corneal matrix production. An upregulation in COL1A1 after siRNA inhibition indicated their functional link to stromal cell biology. For ITGAX, encoding a leukocyte integrin, we assayed its level in the sera of 3 affected families compared with 10 unrelated controls to detect an increase in all affecteds. Our study identified genes that regulate the cytoskeleton, protein trafficking and secretion, barrier tissue function and response to injury and inflammation, as being relevant to keratoconus.

COVID-19: The regional impact of COVID-19 on the certification of vision impairment in Northern Ireland.

PURPOSE: In this paper we highlight the impact which the disruption of secondary care ophthalmic services, resulting from COVID-19, has had on Sight Impairment (SI) and Severe Sight Impairment (SSI) certification in Northern Ireland. METHODS: Regional data on SI and SSI certification in the period after the onset of the lockdown (19 March 2020-18 June 2020) were compared to the period immediately before lockdown (1 January 2020-18 March 2020) and to the same periods in 2019. Change documented was compared to post-lockdown reductions in primary and secondary ophthalmic care activity. RESULTS: In 2019, during the 3-month period (19 March 2019-18 June 2019), 115 individuals were certified as sight impaired (SI 36, SSI 75, unspecified 4). Of those certified, 65 were female, 49 male. Principal causes of certification were: Age-related macular degeneration (AMD) (N = 45), glaucoma (N = 20) and diabetic eye disease (DED) (N = 10). Mean VA, recorded from the better eye of those certified, was 0.96 LogMAR. In the 3 months following the onset of lockdown (19 March 2020-18 June 2020), only 37 individuals were certified (SI 6, SSI 31), 12 female and 25 male. AMD was the most frequent cause of sight impairment (N = 20). There were only two DED certifications and one due to glaucoma. Mean VA in the better eye of those certified was 1.15LogMAR. The numbers of CVI certifications completed following the introduction of COVID-19 lockdown fell by 68%, compared to the 2019 data. There was a significant reduction in the proportion of female certifications (p = 0.01), and in certifications due to glaucoma (p = 0.02). The proportion of those certified as SSI as opposed to SI in the period after the onset of lockdown rose from 68% in 2019 to 84% in 2020. The mean VA of those certified in the period after the onset of lockdown, when compared to those certified in the other three periods, was worse by between 0.21 and 0.19 LogMAR (p = 0.06). Reductions reflected change in overall primary and secondary ophthalmic care activity. CONCLUSIONS: It is inconceivable that COVID-19 has reduced the incidence of sight-threatening eye disease. We must therefore assume that a flood of newly presenting sight loss will present once the pandemic has passed. New presentations will include those who would normally have attended during the lockdown period, and patients who, had they accessed ophthalmic care at the appropriate time, would have been saved from severe levels of blindness. The implications of the predicted increase in demand for medical, social and low vision related services are huge.

Plasma level of lipocalin 2 is increased in neovascular age-related macular degeneration patients, particularly those with macular fibrosis.

BACKGROUND: Previously, we and others have reported higher populations of circulating neutrophils in patients with neovascular age-related macular degeneration (nAMD). Neutrophil gelatinase-associated lipocalin (NGAL, also known as lipocalin-2, LCN2), an important innate immune mediator, is known to be critically involved in sterile inflammation-mediated organ failure, fibrosis, cancer progression and retinal degeneration. This study investigated the plasma levels of LCN2, matrix metalloproteinase 9 (MMP9) and LCN2/MMP9 complex in different types of nAMD and examined whether the levels were related to patients' responsiveness to anti-VEGF therapy. RESULTS: One hundred and seventy-four nAMD patients, including 108 with choroidal neovascularisation (CNV), 32 with retinal angiomatous proliferation (RAP), 23 with polypoidal choroidal vasculopathy (PCV) and 11 unclassified patients, and 43 healthy controls were recruited to this case-control study. Fifty-eight nAMD patients had macular fibrosis and 110 patients did not. Out of the 174 nAMD patients, 80 patients responded completely, 90 responded partially, and 4 did not respond to the anti-VEGF therapy. The plasma levels of LCN2 in nAMD patients (181.46 ± 73.62 ng/ml) was significantly higher than that in healthy controls (152.24 ± 49.55 ng/ml, P = 0.047). However, the difference disappeared after adjusting for age. A positive correlation between plasma level of LCN2 and age was observed in nAMD patients (r = 0.29, P = 0.0002) but not in healthy controls. The plasma level of LCN2 was also positively correlated with circulating neutrophils in nAMD patients (r = 0.34, p = 0.0007) but not in healthy controls (r = 0.057, p = 0.77). No correlation was observed between age and circulating neutrophils. Further analysis of nAMD subtypes uncovered a significantly higher level of LCN2 in patients with macular fibrosis even after adjusting for age. No relationship was observed between plasma levels of LCN2 and patients' responsiveness to anti-VEGF therapy. The plasma levels of MMP9 and LCN2/MMP9 complex were comparable between nAMD and controls. CONCLUSIONS: Our results suggest that higher plasma levels of LCN2 in nAMD are related to ageing and increased population of circulating neutrophils. Our results also suggest that higher levels of LCN2 may increase the risk of macular fibrosis in nAMD.

Comparison of the Morphology of the Foveal Pit Between African and Caucasian Populations.

Purpose: The purpose of this study was to characterize foveal pit morphology in an African (Ghanaian) population, to compare it to that of a Caucasian group and to determine if it varied with age in the two populations. Methods: The depth, diameter, slope, and volume of the foveal pit were interpolated from optical coherence tomography volume scans recorded in 84 Ghanaian and 37 Caucasian individuals. Their association with age, sex, and ethnicity was investigated using multilevel regression models. Results: The foveal pit differed significantly in width, slope, and volume between Ghanaian men and women (P < 0.001), but only in width and volume between Caucasian men and women (P < 0.01). In Ghanaians, age was associated with a narrowing of the foveal depression and a reduction of its volume. Overall, these changes were more pronounced in women as compared to men and were largely absent from the Caucasian group. When controlled for age, the foveal pit of Ghanaians was significantly wider and larger in volume as compared to the Caucasian group (P < 0.001). Conclusions: The morphology of the foveal pit differs between African and Caucasian individuals. These anatomic differences should be considered when examining differences in prevalence and clinical features of vitreoretinal disorders involving the fovea between the two populations. Translational Relevance: Differences in retinal anatomy may partly explain variations in the prevalence and clinical features of retinal diseases between Africans and Caucasians. Such differences should be adequately considered in diagnoses and monitoring of ocular diseases in patients with African ancestry.

Findings from a Genotyping Study of Over 1000 People with Inherited Retinal Disorders in Ireland.

The Irish national registry for inherited retinal degenerations (Target 5000) is a clinical and scientific program to identify individuals in Ireland with inherited retinal disorders and to attempt to ascertain the genetic cause underlying the disease pathology. Potential participants first undergo a clinical assessment, which includes clinical history and analysis with multimodal retinal imaging, electrophysiology, and visual field testing. If suitable for recruitment, a sample is taken and used for genetic analysis. Genetic analysis is conducted by use of a retinal gene panel target capture sequencing approach. With over 1000 participants from 710 pedigrees now screened, there is a positive candidate variant detection rate of approximately 70% (495/710). Where an autosomal recessive inheritance pattern is observed, an additional 9% (64/710) of probands have tested positive for a single candidate variant. Many novel variants have also been detected as part of this endeavor. The target capture approach is an economic and effective means of screening patients with inherited retinal disorders. Despite the advances in sequencing technology and the ever-decreasing associated processing costs, target capture remains an attractive option as the data produced is easily processed, analyzed, and stored compared to more comprehensive methods. However, with decreasing costs of whole genome and whole exome sequencing, the focus will likely move towards these methods for more comprehensive data generation.

Evaluation of long-term intravitreal anti-vascular endothelial growth factor injections on renal function in patients with and without diabetic kidney disease.

BACKGROUND: Administering anti-vascular endothelial growth factor (anti-VEGF) by intraocular injection has been shown to have a safe systemic profile. Nevertheless, incidents of acute kidney injury following anti-VEGF injection have been reported. We assessed the long-term effect of multiple intravitreal anti-VEGF injections on measures of renal function in patients with diabetes including rate of change of estimated glomerular filtration rate (eGFR) and urine albumin-to-creatinine ratio (ACR). METHODS: A retrospective review of patients receiving diabetic macular oedema (DMO) treatment was undertaken. Serum creatinine, ACR, number of intravitreal anti-VEGF injections and clinical characteristics were collected from electronic healthcare records (EHR). A co-efficient of eGFR and ACR change with time was calculated over a mean duration of 2.6 years. Regression modelling was used to assess variation in the number of anti-VEGF injections and change in eGFR and ACR. RESULTS: The EHR of 85 patients with DMO (59% male, 78% type 2 diabetes mellitus [T2DM]) were reviewed. On average, 26.8 intravitreal anti-VEGF injections were given per patient over a mean duration of 31 months. No association between increasing number of anti-VEGF injections and rate of eGFR decline (beta = 0.04, 95% confidence intervals [CI]: - 0.02, 0.09; p = 0.22) or ACR change over time (beta = 0.02, CI: - 0.19, 0.23; p = 0.86) was detected, following adjustment for hypertension, cerebrovascular disease, T2DM, and medications taken. CONCLUSION: Our data suggests regular long-term intravitreal VEGF inhibition does not significantly alter the rate of change in eGFR and/or ACR with increasing number of treatment injections.

Serum xanthophyll carotenoids are associated with estimated glomerular filtration rate in an aged cohort.

Progressive renal decline is associated with increasing oxidative stress. However, the majority of studies have investigated endogenous antioxidants in predominantly advanced stages of kidney disease. Many traditional risk factors associated with renal dysfunction have been linked with cognitive decline as the kidneys and brain share comparable anatomic and haemodynamic characteristics that leave them susceptible to common pathogenic mechanisms. The objective of this study was to examine serum dietary antioxidants and their association with renal function characterised by estimated glomerular filtration rate (eGFR) in a cross-sectional analysis of 570 participants. High performance liquid chromatography quantified serum levels of retinol, α-tocopherol, γ-tocopherol and six carotenoids (α-carotene, ß-carotene, ß-cryptoxanthin, lutein, lycopene and zeaxanthin) in participants. Multiple regression analyses were used to evaluate associations while adjusting for potential confounders. A sensitivity analysis was performed in cognitively-intact participants only. Serum levels of the xanthophyll carotenoid lutein were positively associated with eGFR in analyses adjusted for age (years), gender, smoking, APOE4 status and Alzheimer's disease. Retinol was inversely associated with eGFR, although was no longer significant in the smaller sensitivity analysis. Our findings identify significant associations between the xanthophyll carotenoids and eGFR. Further investigations are required to confirm these findings.

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

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.

Dietary patterns and chronic kidney disease: a cross-sectional association in the Irish Nun Eye Study.

Associations between dietary patterns and chronic kidney disease are not well established, especially in European populations. We conducted a cross-sectional study of 1033 older Irish women (age range 56-100 years) with a restricted lifestyle. Dietary intake was assessed using a food frequency questionnaire. Renal function was determined by estimated glomerular filtration rate. Two dietary patterns were identified within the study population using factor analysis. A significant negative association was found between unhealthy dietary pattern adherence and renal function in both unadjusted and adjusted models controlling for potential confounding variables (p for trend <0.001), with a mean difference in estimated glomerular filtration rate of -6 ml/min/1.73 m2 between those in the highest fifth of adherence to the unhealthy dietary pattern compared to the lowest, in the fully adjusted model. Chronic kidney disease risk was significantly greater for the highest fifth, compared to the lowest fifth of unhealthy dietary pattern adherence in adjusted models (adjusted odds ratio = 2.62, p < 0.001). Adherence to the healthy dietary pattern was not associated with renal function or chronic kidney disease in adjusted models. In this cohort, an unhealthy dietary pattern was associated with lower renal function and greater prevalence of chronic kidney disease.

Target 5000: Target Capture Sequencing for Inherited Retinal Degenerations.

There are an estimated 5000 people in Ireland who currently have an inherited retinal degeneration (IRD). It is the goal of this study, through genetic diagnosis, to better enable these 5000 individuals to obtain a clearer understanding of their condition and improved access to potentially applicable therapies. Here we show the current findings of a target capture next-generation sequencing study of over 750 patients from over 520 pedigrees currently situated in Ireland. We also demonstrate how processes can be implemented to retrospectively analyse patient datasets for the detection of structural variants in previously obtained sequencing reads. Pathogenic or likely pathogenic mutations were detected in 68% of pedigrees tested. We report nearly 30 novel mutations including three large structural variants. The population statistics related to our findings are presented by condition and credited to their respective candidate gene mutations. Rediagnosis rates of clinical phenotypes after genotyping are discussed. Possible causes of failure to detect a candidate mutation are evaluated. Future elements of this project, with a specific emphasis on structural variants and non-coding pathogenic variants, are expected to increase detection rates further and thereby produce an even more comprehensive representation of the genetic landscape of IRDs in Ireland.

Estimated Glomerular Filtration Rate is not Associated with Alzheimer's Disease in a Northern Ireland Cohort.

BACKGROUND: Alzheimer's disease (AD) prevalence is increasing globally and typically progresses for several years prior to clinical presentation of dementia. Renal dysfunction and vascular disease have been reported in association with dementia in several cross-sectional and longitudinal studies, and may contribute to AD risk. Experimental and observational studies suggest amyloid-ß (Aß) clearance may be impaired in chronic kidney disease (CKD) indicating a mechanism for increased AD risk. OBJECTIVE: The objective of this study was to compare estimated glomerular filtration rate (eGFR) between individuals with AD and cognitively intact controls, controlling for potential confounding factors. METHODS: A cross-sectional, case-control study was carried out in 317 cognitively normal participants and 253 cases with a clinical diagnosis of AD in a UK tertiary care dementia clinic. Associations were considered using logistic regression adjusting for confounding variables (age, APOEɛ4 genotype, systolic blood pressure, education (left school at 14), and smoking status). RESULTS: AD cases were older than cognitively intact controls, had lower MMSE scores, were more likely to have at least one APOEɛ4 allele, had higher rates of smoking, were more likely to be taking aspirin and/or clopidogrel, and had lower blood pressure. We found no significant association between eGFR and AD both before and following adjustment for appropriate confounders. CONCLUSION: This study failed to find an association between eGFR and AD in a cross-sectional sample study of elderly white individuals.

Serum concentrations of vitamin E and carotenoids are altered in Alzheimer's disease: A case-control study.

INTRODUCTION: Oxidative stress has been implicated in the pathogenesis of Alzheimer's disease (AD). We investigated associations between serum levels of lipophilic antioxidants and AD. METHODS: Serum concentrations of retinol, two forms of vitamin E (α- and γ-tocopherol) and six carotenoids were quantified by high-performance liquid chromatography from patients with AD (n = 251) and cognitively intact controls (n = 308) and assessed by regression analyses. RESULTS: Serum levels of α-tocopherol and all six carotenoids were significantly lower in patients with AD compared with cognitively intact controls (P < .001). In contrast, γ-tocopherol was significantly higher in the serum of patients with AD (odds ratio = 1.17 [confidence intervals: 1.05-1.31]). DISCUSSION: Our findings implicate compromised serum antioxidant defenses in AD pathogenesis and differing biological roles for vitamin E isoforms. This highlights the need for improved understanding in the balanced upregulation of exogenous antioxidants related to dietary intake or supplement use in future nutritional intervention studies.