Genetic and environmental risk factors for age-related macular degeneration in persons 90 years and older.

PURPOSE: We studied associations of genetic polymorphisms in age-related maculopathy susceptibility 2 (ARMS2) and complement factor H (CFH) in nonagenarians with age-related macular degeneration (AMD). METHODS: This case-control study comprised 2737 persons (1204 controls, 1433 AMD cases), including 166 nonagenarians (52 controls, 114 AMD cases). Single nucleotide polymorphisms (SNPs) in the genes ARMS2 and CFH were determined. Risk scores were computed by multiple logistic regression analysis, including genetic and environmental risk factors (smoking, hypertension, body mass index, diabetes) for different age groups (<70, 70-79, 80-89, ≥ 90 years [nonagenarians]). RESULTS: In nonagenarians, ARMS2 showed the weakest associations with AMD (odds ratio [OR] = 1.52, P = 0.127) compared to the other groups (OR, 70 years = 2.23, P = 1.03 × 10(-13); OR, 70-79 years = 2.70, P = 1.00 × 10(-13); OR, 80-89 years = 3.11, P = 6.56 × 10(-8)). For CFH, ORs for AMD increased with age (<70 years OR = 1.96, P = 1.80 × 10(-11); 70-79 years OR = 1.89, P = 4.48 × 10(-13); 80-89 years OR = 2.71, P = 1.28 × 10(-7)), but decreased again in the nonagenarians (OR = 2.21, P = 0.005). Compared to the group <70 years, reduced minor allele frequencies (MAFs) for AMD patients were observed in the nonagenarians (CFH 0.54 vs. 0.43, P = 0.009; ARMS2 0.44 vs. 0.29, P = 2.97 × 10(-5)), while the MAFs in controls were not significantly different. The genetic risk score revealed the lowest discriminative power in the nonagenarians with an area-under-curve (AUC) of 0.658 for receiver-operating characteristics (AUC 80-89 years = 0.768, 70-79 years = 0.704, <70 years = 0.682), while no significant difference was seen for the environmental risk score (AUC < 70 years = 0.579, 70-79 years = 0.567, 80-89 years = 0.600, >90 years = 0.608). CONCLUSIONS: Risk alleles in CFH and ARMS2 have a significantly smaller effect on AMD development in nonagenarians, while environmental factors retain a similar effect.

Long-term stability of vascular endothelial growth factor suppression time under ranibizumab treatment in age-related macular degeneration.

PURPOSE: To determine intra-individual long-term stability of vascular endothelial growth factor (VEGF) suppression time in eyes with neovascular age-related macular degeneration (AMD) treated with ranibizumab. DESIGN: Nonrandomized, prospective clinical study. METHODS: Eighty-three eyes of 83 patients with neovascular AMD undergoing intravitreal ranibizumab injections were included in the study. A total of 859 aqueous humor specimens were taken before each intravitreal ranibizumab injection. Vascular endothelial growth factor A was measured by multiplex bead analysis. RESULTS: Ranibizumab resulted in complete VEGF suppression within a mean period of 36.4 days (standard deviation ±6.7 days; range, 26-69 days). Intra-individual suppression time was stable within a period of up to 3 years. Among 859 VEGF measurements, only 5 (0.58%) deviated from this pattern. Nonsuppressed VEGF levels did not differ significantly between baseline and recurrence (68.0 pg/mL vs 69.3 pg/mL) and did not correlate with choroidal neovascularization size and lesion type. CONCLUSIONS: Both the long-term stability and the broad range of individual suppression times after ranibizumab injections would allow and justify adjustment of continuous injections individually in order to achieve permanent VEGF suppression in patients.

Spectral-domain optical coherence tomography in subjects over 60 years of age, and its implications for designing clinical trials.

AIMS: To study the variability of central retinal thickness (CRT), its concordance to the fellow eye, and the implications for designing future clinical trials using spectral-domain optical coherence tomography (SD-OCT). METHODS: Cross-sectional retrospective analysis of European Genetic Database. 632 eyes of 316 subjects over 60 years of age without macular pathology were examined using SD-OCT. RESULTS: Mean CRT was 280.22 µm and 281.02 µm for the right and left eyes, respectively. There was a strong concordance for all measured values between right and left eyes. Men had significantly thicker CRT than women. Variation up to 23 µm difference between both eyes was seen. To detect a change of at least 30 µm in CRT, a sample size of 90 or 176 per group is needed for a single-arm or double-arm study, respectively (α=0.05, power=0.80, no loss to follow up, assuming SD in future studies=100 µm). CONCLUSIONS: Clinical trials using CRT as an endpoint are feasible in terms of sample size needed.