Martha Dietzel

Determinants of Macular Pigment Optical Density and Its Relation to Age-Related Maculopathy: Results from the Muenster Aging and Retina Study (MARS)

PURPOSE The controversial protective effect of macular pigment (MP), consisting of lutein (L) and zeaxantin (Z), in age-related maculopathy (ARM) and its late-stage, age-related macular degeneration (AMD) is discussed. Determinants of MP optical density (MPOD) and its relation to ARM were investigated. METHODS MPOD was accessed at eccentricities of 0.5° and 2.0° from the fovea in 369 participants in the 2.6-year follow-up examination of the prospective Muenster Aging and Retina Study using dual-wavelength analysis of autofluorescence images. ARM was graded from standardized fundus photographs according to the International Classification System. RESULTS MPOD at 0.5° and 2.0° between pairs and within single eyes was strongly correlated (P < 0.001). Smoking and body mass index showed moderately inverse associations with MPOD at 2.0°, and age was positively related to MPOD at both eccentricities. Serum L, measured at the baseline examination, was significantly associated with MPOD measured at follow-up. Likewise, use of L/Z-containing supplements raised MPOD. Crude mean MPOD increased with ascending stage of ARM. However, adjustment for influential factors and exclusion of L supplement users removed differences of mean MPOD between ARM stages. Considering further the accompanying eye, study eyes with ARM had significantly higher MPOD when the contralateral eye had AMD. CONCLUSIONS MPOD levels showed a high degree of intraindividual concordance and interindividual variability. Long-standing serum L levels, and in particular L supplementation, were the strongest determinants of MPOD. The hypothetical inverse association between MPOD and ARM stage was not confirmed.

Smoking history and the incidence of age-related macular degeneration - results from the Muenster Aging and Retina Study (MARS) cohort and systematic review and meta-analysis of observational longitudinal studies.

To compare the association of smoking with age-related macular degeneration (AMD) in the Muenster Aging and Retina Study (MARS) cohort with current evidence. Adjusted risk ratios for incident AMD in MARS were compared with findings of a systematic review and meta-analysis of observational prospective studies. 9.6% of MARS participants progressed to AMD over a median of 30.9 months. In MARS the adjusted risk ratio in current versus never smokers was 3.25 (95% confidence interval [1.50-7.06]), and 1.28 [0.70-2.33] in former smokers versus never smokers. The meta-analysis of previous studies showed a pooled adjusted risk ratio of 2.51 [1.09-5.76] in current versus never smokers. Inclusion of the MARS findings removed between-study heterogeneity and accentuated the pooled adjusted risk ratio for current smokers to 2.75 [1.52-4.98]. Specific analyses in MARS revealed a protective effect for time since smoking cessation in former smokers with an adjusted risk ratio=0.50 [0.29-0.89] per log(year). Current smoking nearly triples AMD incidence, while smoking cessation lowers AMD incidence in a non-linear fashion even in the elderly.

LOC387715, smoking and their prognostic impact on visual functional status in age-related macular degeneration-The Muenster Aging and Retina Study (MARS) cohort.

Purpose: To prospectively evaluate the impact of homozygosity in the A69S-SNP of the LOC387715-gene, smoking history, and their interaction on visual functional status (v-FS) in age-related macular degeneration (AMD). Methods: The Muenster Aging and Retina Study (MARS) cohort (n = 656; 58.8% women, mean age 70.2 years) was followed over a mean of 2.5 years. AMD-status, genotype and smoking history were assessed at baseline. V-FS [from 0 (low) to 100 (unimpaired) points in general-, near- and far-vision], were AMD-status assessed at baseline and at follow-up. Linear models with stepwise adjustments for covariates were used to analyze decline of v-FS over time. Results: In initial models, homozygosity for the A69S-variant was negatively associated with all three dimensions of the v-FS. After including smoking history, ever smoking was negatively associated with declines in near and far vision (-4.82 and -5.12 points, respectively; each p < 0.05). In smokers homozygous for the A69S-variant the number of cigarettes smoked per day (smoking intensity) was negatively associated with all three dimensions of the v-FS (interaction term each p < 0.05). Time since smoking cessation in former smokers protected against declines in near and far vision. These effects were independent of the AMD-status at baseline. Conclusions: The interaction of homozygosity for the A69S-variant and smoking intensity had a negative impact on general-, near-, and far visual functional status independent of AMD-status. Quitting smoking seemed to have a time-dependent protective effect on near and far vision.

The association of retinal structure and macular pigment distribution.

PURPOSE Macular pigment optical density (MPOD) and age-related macular degeneration (AMD) are thought to be associated; however, the details are not yet understood clearly. This study aimed at investigating how retinal anatomic structures relate with the spatial MPOD distribution in single eyes. METHODS In a subgroup of the third follow-up examination of the Münster Aging and Retina Study (MARS) cohort (mean age, 78.4 years), 124 single eyes of 79 participants with early AMD were examined. The MPOD was assessed using 2-wavelength autofluorescence (AF). Retinal thickness (RT) and fovea pit profile slopes were measured using optical coherence tomography (OCT). The results were analyzed for interocular correlation in 58 pairs of eyes, and for the association of MPOD distribution patterns with RT using uni- and multivariate statistical methods. RESULTS The interocular correlations for several measures of RT and RT layers were high (P < 0.001). The RT was inversely and significantly related to MPOD at 1.0° and at 2.0° from the foveal center, but not to central MPOD. After controlling for sex, age, smoking, and spherical equivalent, RT was significantly thinner (-39.7 μm, P < 0.001) in eyes with ring-like compared to normal MPOD distribution. In particular, a thinner layer between internal and external limiting membrane showed strong associations with ring-like structures. CONCLUSIONS Higher values of MPOD at 1° and 2°, as well as a ring-like distribution of MPOD were associated significantly with thinner maculae, due to thinner inner retinal layers. The MPOD distribution was unrelated to the slope of the foveal pit or the choroidal thickness. Our results suggest that the retinal section between the internal and external limiting membrane is involved in the spatial distribution of MPOD.

Correlation Between Disease Severity and Presence of Ocular Autoantibodies in Juvenile Idiopathic Arthritis- Associated Uveitis

PURPOSE The pathogenesis of juvenile idiopathic arthritis-associated uveitis (JIAU) is undefined. This study intended to analyze the presence of antiocular autoantibodies in serum and their correlation with disease course. METHODS Serum samples from children with JIAU (n = 47); JIA without uveitis (n = 67); idiopathic anterior uveitis (IAU; n = 12); and healthy controls (n = 52) were collected. The binding patterns of serum antibodies to ocular cryosections from swine eyes were analyzed by indirect immunohistochemistry, and were correlated to epidemiological, clinical, and laboratory test results. RESULTS The patient groups differed with respect to their presence of antibody binding to the sections: JIAU (94%), JIA (75%), IAU (75%), and healthy controls (29%) to uveal and/or retinal structures. Serum antibodies of JIAU patients predominantly bound at iris (74%), and ciliary body (79%). Iris/ciliary body positive staining correlated with the presence of uveitis complications (P < 0.005) in JIAU patients, but not with positivity of serum antinuclear antibodies (ANA), rheumatoid factor (RF), or HLA-B27, and was independent from uveitis activity or type of anti-inflammatory therapy. CONCLUSIONS In JIAU patients, antiocular serum antibodies can be detected more frequently than in control groups. Binding patterns to ocular tissue correlate with complicated uveitis course but not with uveitis activity and anti-inflammatory treatment. Antibody binding is not specific for this uveitis entity, and does not correlate with ANA positivity.

Genetic Polymorphisms and the Phenotypic Characterization of Individuals with Early Age-Related Macular Degeneration

Purpose: While the importance of risk polymorphisms for the pathogenesis of age-related macular degeneration (AMD) is well established, their impact on morphological and functional phenotypes is largely unclear. We aimed to characterize individual phenotypes in patients who were either homozygous for a risk allele in the CFH gene, ARMS2 gene, or both as compared to non-carriers. Methods: Patients with early AMD (n = 85) were assessed during a follow-up examination of a prospective study (MARS) with multimodal diagnostics including SD-OCT and microperimetry. Results: Compared to non-carriers, OCT scans revealed lower retinal thickness in patients homozygous for CFH or ARMS2, which was caused by a significantly reduced photoreceptor layer. The number and ultrastructure of drusen were also significantly different. Conclusions: These findings indicate that patients with risk alleles demonstrate distinct phenotypic differences of morphology and function as compared to non-carriers. In particular in the CFH group, a loss of photoreceptors occurred concomitantly with reduced retinal sensitivity. Further studies might help to better understand the pathophysiology.