Environmental and genetic risk factors for aging macula disorder

What’s in a name? Since the first description of age-related macular degeneration in 1874 as “Symmetrical central choroido-retinal disease occurring in senile persons”, 1 over 20 different names have been given to this disorder, often reflecting the pathophysiological thinking at a certain time. Because there was need for an internationally accepted classification, the International ARM Epidemiological Study Group named all signs of age-related macular changes age-related maculopathy (ARM), and its end stages, age-related macular degeneration (AMD) following the convention at that time.2 Both the laymen and the medical public found these two names confusing, so gradually all ARM was called AMD, to be divided in early and late AMD. Recently it was proposed to use AMD as an acronym for “Aging Macula Disorder”, essentially the same disease as age-related macular degeneration, for the following reasons.3 Age-related does not differentiate between juvenile macular disease and that associated with old age. Aging better describes the process of becoming older. Although AMD is a complex disorder with a large genetic component, the lifelong changes in the retinal pigment epithelium (RPE) and surrounding tissues in the macula seem a key component in its pathogenesis. Patients do not like to hear associations with senility anymore, nor with degeneration. Finally, it is not clear if and when early or late AMD becomes a disease, therefore we prefer calling it a disorder. Thus we opted for using aging macula disorder as the basis for AMD in this thesis

Alcohol consumption and risk of aging macula disorder in a general population: the Rotterdam Study

To investigate the possible relationship between overall or specific alcohol consumption and risk of aging macula disorder (AMD), a synonym for age-related macular degeneration, in a general population. Alcohol consumption and risk of early or late incident AMD (iAMD) were examined among all participants in the prospective population-based Rotterdam Study, with complete data on alcohol consumption among 4229 subjects at risk of AMD. Aging macula disorder was graded according to the International Classification and Grading System for AMD by 2 trained professionals who were masked for all other determinants. We used Cox proportional hazards regression models to estimate hazard ratios and corresponding 95% confidence intervals. During a mean follow-up period of 8.0 years, 600 cases of iAMD were identified, of which 519 were early iAMD and 81 were late iAMD. After correction for age, sex, smoking, complement factor H genotype status, and other potential confounders, we did not find an association between overall or specific alcohol consumption and development of early iAMD or dry or wet late iAMD. Our findings suggest that overall or specific alcohol consumption is not a risk factor for AM

C-reactive protein level and risk of aging macula disorder: The Rotterdam Study

To examine whether C-reactive protein (CRP) level is a risk factor for aging macula disorder (AMD) in a general population. We examined serum high-sensitivity CRP (HsCRP) levels in 4914 participants of the population-based Rotterdam Study at risk for AMD. After a mean follow-up of 7.7 years, 561 cases of early and 97 cases of late incident AMD (iAMD) were identified. We used Cox proportional hazards regression models to estimate hazard ratios and corresponding 95% confidence intervals (CIs). After adjustment for age and sex, hazard ratios were 1.11 (95% CI, 1.02-1.21) per standard deviation increase in HsCRP level for early iAMD and 1.28 (95% CI, 1.02-1.60) for late iAMD. Hazard ratios for early iAMD increased per quartile increase in HsCRP level as follows: second quartile, 1.19 (95% CI, 0.94-1.52); third quartile, 1.29 (95% CI, 1.01-1.64); and fourth quartile, 1.33 (95% CI, 1.05-1.70). The risk of late iAMD was higher in all upper quartiles of HsCRP. Elevated baseline levels of HsCRP were associated with the development of early and late AMD in this large population-based cohor

Cataract surgery and the risk of aging macula disorder: the rotterdam study

To investigate still-controversial associations between prior cataract surgery and aging macula disorder (AMD) in a general population. Baseline lens status and risk of incident AMD (iAMD) were examined in participants of the prospective population-based Rotterdam Study at risk for AMD (n = 6032). Slit lamp examination was used to determine lens status and stereoscopic color fundus photography to determine the presence of AMD. Odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were estimated with generalized estimating equation (GEE) models. Stratified analyses were also performed for CFH Y402H genotype. After adjusting for age, sex, follow-up time, and the correlation between eyes, a history of cataract surgery was associated with incident dry late AMD (OR, 3.43; 95% CI, 1.82-6.49). This association remained significant after additional adjustment for smoking status and AMD stage at baseline (OR, 3.44; 95% CI, 1.68-7.08). No statistically significant association was found between prior cataract surgery and the incidence of wet late AMD or early AMD. Homozygous CFH Y402H carriers had higher risks for all types of AMD compared to heterozygotes and noncarriers after cataract surgery, particularly for dry AMD. The findings imply that cataract surgery increases the risk of dry AMD, particularly in homozygous CFH Y402H carriers. The risk of AMD progression should be considered before recommending cataract surgery to patients with cataract and early AM

Cataract surgery and the risk of aging macula disorder: The Rotterdam study

PURPOSE. To investigate still-controversial associations between prior cataract surgery and aging macula disorder (AMD) in a general population. METHODS. Baseline lens status and risk of incident AMD (iAMD) were examined in participants of the prospective population-based Rotterdam Study at risk for AMD (n = 6032). Slit lamp examination was used to determine lens status and stereoscopic color fundus photography to determine the presence of AMD. Odds ratios (ORs) and corresponding 95% confidence intervals (CIs) were estimated with generalized estimating equation (GEE) models. Stratified analyses were also performed for CFH Y402H genotype. RESULTS. After adjusting for age, sex, follow-up time, and the correlation between eyes, a history of cataract surgery was associated with incident dry late AMD (OR, 3.43; 95% CI, 1.82- 6.49). This association remained significant after additional adjustment for smoking status and AMD stage at baseline (OR, 3.44; 95% CI, 1.68-7.08). No statistically significant association was found between prior cataract surgery and the incidence of wet late AMD or early AMD. Homozygous CFH Y402H carriers had higher risks for all types of AMD compared to heterozygotes and noncarriers after cataract surgery, particularly for dry AMD. CONCLUSIONS. The findings imply that cataract surgery increases the risk of dry AMD, particularly in homozygous CFH Y402H carriers. The risk of AMD progression should be considered before recommending cataract surgery to patients with cataract and early AMD. Copyrigh

Estrogen receptor alpha gene polymorphisms associated with incident aging macula disorder

It has been suggested that early menopause increases the risk of aging-macula disorder (AMD), the major cause of incurable blindness with a dry and wet late subtype, and that exposure to endogenous or postmenopausal exogenous estrogens reduces this risk. This study was undertaken to investigate whether genetic variations in the estrogen receptor alpha (ESR1) gene are associated with incident AMD. In the Rotterdam Study, a prospective population-based cohort study of participants aged 55 years and older, associations between ESR1 PvuII-XbaI haplotypes and incident early or late AMD were studied in 4571 participants after a mean follow-up time of 7.7 years. Cox proportional hazards regression was used to estimate hazard ratios (HRs) and corresponding 95% confidence intervals (CIs), with adjustment for the most common confounders. ESR1 PvuII-XbaI haplotype 1 was a risk factor for late AMD. Persons with two copies of haplotype 1 were at 3.20 (95% CI, 1.47-6.99) times higher risk for late AMD than noncarriers of haplotype 1, after adjustment for age and sex. This increase was more pronounced for wet AMD (hazard ratio [HR] 4.29; 95% CI, 1.47-12.49) after adjustment for age, sex, smoking, and complement factor H genotype. Correction for additional confounders, including age at menopause, use of hormone replacement therapy, blood pressure, and body mass index did not essentially alter the findings. Persons with one or two copies of ESR1 PvuII-XbaI haplotype 1 have an increased risk of late AMD, especially of the wet for