Association of reduced inner retinal thicknesses with chronic kidney disease.

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/1.73m2; CKD stage 3, eGFR 30-59 ml/min/1.73m2, and CKD stages 4-5, eGFR ≤29 ml/min/1.73m2. RESULTS: Participants (n = 241) had a mean age of 65 years and a mean eGFR of 66.9 ml/min/1.73m2. 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.

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

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 [ß] = 1.73; confidence intervals [CI], 1.14-1.75; p = 0.01), rs1136747 (ß = 1.53 (CI, 1.11-1.73); p = 0.01) and rs149926073 (ß = 3.37 (CI, 1.70-4.00); p = 0.02), while rs1136745 was significantly associated with decreased SAA levels (ß = 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 (ß = 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 (ß = 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.

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.

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

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.

Endothelial progenitor cells in diabetic retinopathy.

Diabetic retinopathy (DR) is a leading cause of visual impairment worldwide. Patients with DR may irreversibly lose sight as a result of the development of diabetic macular edema (DME) and/or proliferative diabetic retinopathy (PDR); retinal blood vessel dysfunction and degeneration plays an essential role in their pathogenesis. Although new treatments have been recently introduced for DME, including intravitreal vascular endothelial growth factor inhibitors (anti-VEGFs) and steroids, a high proportion of patients (~40-50%) do not respond to these therapies. Furthermore, for people with PDR, laser photocoagulation remains a mainstay therapy despite this being an inherently destructive procedure. Endothelial progenitor cells (EPCs) are a low-frequency population of circulating cells known to be recruited to sites of vessel damage and tissue ischemia where they promote vascular healing and re-perfusion. A growing body of evidence suggests that the number and function of EPCs are altered in patients with varying degrees of diabetes duration, metabolic control, and in the presence or absence of DR. Although there are no clear-cut outcomes from these clinical studies, there is mounting evidence that some EPC sub-types may be involved in the pathogenesis of DR and may also serve as biomarkers for disease progression and stratification. Moreover, some EPC sub-types have considerable potential as therapeutic modalities for DME and PDR in the context of cell therapy. This study presents basic clinical concepts of DR and combines this with a general insight on EPCs and their relation to future directions in understanding and treating this important diabetic complication.