Age-related macular degeneration discordance in monozygotic twin pairs.

PURPOSE: To examine age-related macular degeneration (AMD) and retinal pigment epithelium (RPE)-Bruch's membrane (BrM) complex volume associations in monozygotic twin pairs. METHODS: In this study, 106 elderly twins (53 twin pairs) from the Finnish Twin Cohort study were recruited. Each participant underwent dilated 35-degree digital colour fundus photography (CFP), and spectral domain optical coherence tomography (OCT) and replied to a structured study questionnaire. The CFPs were graded according to the Age-Related Eye Disease Study (AREDS) classification. The OCT images were segmented and volumetric data of the RPE-BrM complex volume was calculated with the Orion™ software. The worse eye according to AREDS classification was used for the analysis. RESULTS: Twenty-nine (55%) of the twin pairs were discordant with regard to AREDS classification. Fourteen (26%) pairs were discordant with one twin participant having AMD (AREDS 2-4) and the other being unaffected (AREDS 1). Four (8%) pairs had one twin participant with intermediate or late AMD (AREDS 3-4) versus the other being unaffected (AREDS 1). The within-pair polychoric correlation for AREDS was 0.605 (95% confidence interval 0.418-0.792). In multivariate analysis intermediate and late AMD as well as age associated with RPE-BrM complex volume. RPE-BrM complex volume showed a within twin pair correlation, r = 0.430 (95% confidence interval 0.172-0.688, p < 0.01). CONCLUSION: A substantial proportion of monozygotic twin pairs are discordant with regard to age-related macular degeneration phenotype. RPE-BrM complex volume associated with age and intermediate and late AMD.

Retinal pigment epithelium-Bruch's membrane volume in grading of age-related macular degeneration.

AIM: To assess the agreement of optical coherence tomography (OCT) algorithm-based retinal pigment epithelium -Bruch's membrane complex volume (RBV) with fundus photograph-based age-related macular degeneration (AMD) grading. METHODS: Digital color fundus photographs (CFPs) and spectral domain OCT images were acquired from 96 elderly subjects. CFPs were graded according to Age-Related Eye Disease Study (AREDS) classification. OCT image segmentation and RBV data calculation were done with Orion™ software. Univariate and multivariate analyses were performed to find out whether AMD lesion features associated with higher RBVs. RESULTS: RBV correlated with AMD grading (rs=0.338, P=0.001), the correlation was slightly stronger in early AMD (n=52; rs=0.432, P=0.001). RBV was higher in subjects with early AMD compared with those with no AMD lesions evident in fundus photographs (1.05±0.20 vs 0.96±0.13 mm3, P=0.023). In multivariate analysis higher RBVs were associated significantly with higher total drusen (ß=0.388, P=0.027) and pigmentation areas (ß=0.319, P=0.020) in fundus photographs, whereas depigmentation area (ß=-0.295, P=0.015) associated with lower RBV. CONCLUSION: RBV correlate with AMD grading status, with a stronger association in patients with moderate, non-late AMD grades. This effect is driven mostly by lesions with drusen or pigmentation. Lesions with depigmentation tend to have lower values. RBV is more comprehensive measurement of the key area of AMD pathogenesis, compared to sole drusen volume analysis. RBV measurements are independent on grader variations and offer a possibility to quantify early and middle grade AMD lesions in a research setting, but may not substitute fundus photograph-based grading in the whole range of AMD spectrum.

Early middle age cholesterol levels and the association with age-related macular degeneration.

PURPOSE: To examine whether serum cholesterol in early middle age is associated with age-related macular degeneration (AMD) later in life. METHODS: A group of Helsinki Businessmen Study (HBS) participants (n = 209) were recruited for the study. Total cholesterol (TC), triglyceride and body mass index (BMI) were measured at the HBS baseline visit in 1964-1973. Lipid subfractions, BMI, smoking status and statin use were recorded in 2011 and fundus photographs graded for AMD in 2005-2012. The subjects were genotyped for the main AMD risk single nucleotide polymorphisms (SNPs). RESULTS: TC measured at baseline 1964-1973 was significantly higher in subjects later developing intermediate or late AMD (6.67 mmol/l versus 6.20 mmol/l, p = 0.024) or with drusen size of ≥125 µm (6.68 mmol/l versus 6.21 mmol/l, p = 0.030) compared with the rest of the study population. TC, LDL and TG values at follow-up 2011 were lower in subjects with AMD compared to those without, whereas HDL levels showed no difference. In multivariate analysis, baseline TC associated with intermediate or late AMD (OR 1.59, p = 0.004) and drusen size ≥ 125 µm (OR 1.57, p = 0.006) when corrected for age, BMI, AMD risk SNPs and smoking. Lipid values measured 2011 had no associations after correction. CONCLUSIONS: High systemic total cholesterol in early middle age may have a role in the initial development of AMD, especially in patients later developing large drusen.