BackgroundAge-related macular degeneration (AMD) is the most common cause of irreversible visual impairment in the developed world. The two forms of advanced AMD, geographic atrophy and neovascular AMD, represent different pathological processes in the macula that lead to loss of central vision. Soft drusen, characterized by deposits in the macula without visual loss, are considered to be a precursor of advanced AMD. Recently, it has been proposed that a common missense variant, Y402H, in the Complement Factor H (CFH) gene increases the risk for advanced AMD. However, its impact on soft drusen, GA, or neovascular AMD—or the relationship between them—is unclear.Methods and FindingsWe genotyped 581 Icelandic patients with advanced AMD (278 neovascular AMD, 203 GA, and 100 with mixed neovascular AMD/GA), and 435 with early AMD (of whom 220 had soft drusen). A second cohort of 431 US patients from Utah, 322 with advanced AMD (244 neovascular AMD and 78 GA) and 109 early-AMD cases with soft drusen, were analyzed. We confirmed that the CFH Y402H variant shows significant association to advanced AMD, with odds ratio of 2.39 in Icelandic patients (p = 5.9 × 10−12) and odds ratio of 2.14 in US patients from Utah (p = 2.0 × 10−9) with advanced AMD. Furthermore, we show that the Y402H variant confers similar risk of soft drusen and both forms of advanced AMD (GA or neovascular AMD).ConclusionSoft drusen occur prior to progression to advanced AMD and represent a histological feature shared by neovascular AMD and GA. Our results suggest that CFH is a major risk factor of soft drusen, and additional genetic factors and/or environmental factors may be required for progression to advanced AMD.

Through whole-genome sequencing of 2,230 Icelanders, we detected a rare nonsynonymous SNP (minor allele frequency = 0.55%) in the C3 gene encoding a p.Lys155Gln substitution in complement factor 3, which, following imputation into a set of Icelandic cases with age-related macular degeneration (AMD) and controls, associated with disease (odds ratio (OR) = 3.45; P = 1.1 × 10(-7)). This signal is independent of the previously reported common SNPs in C3 encoding p.Pro314Leu and p.Arg102Gly that associate with AMD. The association of p.Lys155Gln was replicated in AMD case-control samples of European ancestry with OR = 4.22 and P = 1.6 × 10(-10), resulting in OR = 3.65 and P = 8.8 × 10(-16) for all studies combined. In vitro studies have suggested that the p.Lys155Gln substitution reduces C3b binding to complement factor H, potentially creating resistance to inhibition by this factor. This resistance to inhibition in turn is predicted to result in enhanced complement activation.

The results indicate a linear association between the severity of HOA and atherosclerosis in older women. The pathological process of HOA seems to have some components in common with atherosclerosis. Prospective studies may help elucidate the possible mechanisms of this relationship.

BackgroundThe objective of the study was to standardize a method using digital photographs to diagnose and grade hand osteoarthritis (HOA), to compare it with radiographs and clinical examination with regard to prevalence and relation to symptoms, and finally to construct a simple shortened version suitable for use in very large studies, where a global estimate may be preferable.MethodsHigh quality photographs with standard distance and hand positioning were analysed for the presence of HOA and subsequently compared with standard radiographs and clinical examination in 381 random participants in the AGES-Reykjavik Study, a large population study. The mean age of the participants was 76 years.ResultsUsing the photographic method, the most commonly affected joints were the second DIP joints followed by the third DIP joints and second and third PIP joints. Both interobserver (ICC = 0.83) and intraobserver reading agreements (ICC = 0.89) were acceptable. On comparison with radiography and clinical examination, aggregate scores were significantly correlated (Rs 0.35-0.69), more so in females (Rs 0.53-0.72) than males. Hand pain in males showed very little association with HOA findings by the three methods but all methods showed a comparable moderate association with hand pain in females. The performance of photography in predicting pain on most days for at least a month in females was comparable to that of radiography and clinical examination (AUC 0.63 p = 0.004). Analysis of intermittent pain yielded similar results for in the DIP and PIP joints (OR 3.2-3.3, p < 0.01), but for the CMC1 joints, both radiography (OR 9.0, p < 0.0001), and clinical examination (OR 9.8, p < 0.0001), had higher predictive odds ratios for pain than photography (OR 3.6, p < 0.0001)., A shortened, rapidly performed form of reading photographs also showed a high degree of correlation with the other methods (Rs 0.56-0.82).ConclusionHigh quality hand photographs can be used to diagnose and grade hand osteoarthritis. The method has the advantage of being inexpensive and easy to perform. By using a slightly simplified method of reading, it appears to be highly suitable for use in large studies.

ABSTRACT.Purpose: To determine the incidence rate as well as causative diagnoses and surgi- done, and the three exenterations performed were not included in the study. The mean annual age-adjusted incidence rate of enucleation in Iceland was 1.48 enucleations per 100 000 population in comparison with 2.66 enucleations per 100 000 for the time period 1964-1991. With advancing age, a significant increasing linear trend existed (p < 0.001). The median age at enucleation was 51 years (SD 22; mean 55 years; 16-91 years). The three most common surgical indications for enucleation were blind painful eye, suspected ocular malignancy and acute trauma. The most common causative diagnosis for enucleation was traumatic lesion (39%). The annual incidence was 2.00 enucleations per 100 000 for men and 0.95 for women. There were significantly more men in the traumatic lesion group (p < 0.001), but no gender predominance was found in the other groups of causative diagnoses (p = 0.8). Conclusion: The overall mean annual incidence of enucleation in Iceland is continually decreasing, although the incidence of severe ocular trauma and ocular malignancy is fairly stable.

Objective This study examines the relationship between total knee replacements (TKR),total hip replacements (THR) or replacements of either joint (TJR) due to osteoarthritis (OA) and atherosclerosis in a large population-based study. Methods The participants were 2195 males and 2975 females, mean age 76±6 years. The OA data were analysed in relation to measures of atherosclerosis, including carotid artery intima media thickness and plaque severity (ultrasound), coronary and aortic calcifications (CT), cerebral white matter lesions (MRI) and history of previous cardiac and cerebral events. Results The prevalence of TKR was 223(4.3%) and THR 316(6.1%). The presence of TJR’s in females was associated with a nonsignificant trend towards increased carotid plaque severity, coronary calcifications and periventricular white matter hyperintensities (PVHs) but not with history of cardiac or cerebral events. No associations were seen in males. When TJR’s were grouped according to the presence or absence of HOA there was a highly significant association in the order –TJR/−HOA < +TJR/−HOA < −TJR/+HOA < +TJR/+HOA, for carotid plaque severity, coronary calcifications and PVHs. Conclusion The presence of TJR’s did not show a significant independent association with atherosclerosis but enhanced the strength of the positive association between HOA and subclinical atherosclerosis in females.

ObjectiveTo investigate the reliability and construct validity of an atlas for grading hand osteoarthritis (OA) on photographs in a separate younger community-dwelling population than the development cohort.MethodsParticipants were community-dwelling adults (ages ≥50 years) in North Staffordshire, UK with hand pain or hand problems in the last year who attended a research clinic. High-quality photographs were taken in a standardized position. A photographic atlas was used to score hand joints (second and third distal interphalangeal [DIP], second and third proximal interphalangeal [PIP], and first carpometacarpal [CMC] joints) and joint groups (DIP, PIP, and CMC joints) for OA on a 0–3 scale. Hand radiographs were graded for OA using the Kellgren/Lawrence (K/L) grading system. Clinical features (nodes, bony enlargement, and deformity) were determined by physical examination. Associations of photographic hand OA grades with radiographic OA and clinical features were determined to assess construct validity.ResultsIn total, 558 participants (mean age 64 years, 62% women) were included in the analyses. Reliability for scoring OA on the photographs was good (mean intrarater intraclass correlation coefficient [ICC] 0.77 and mean interrater ICC 0.71). At the joint level, photographic hand OA grade was positively associated with radiographic OA grade (Spearman's ρ = 0.19–0.57, P < 0.001) and the number of clinical features (Spearman's ρ = 0.36–0.59, P < 0.001). At the person level, individuals with higher global photographic OA scores had higher summed K/L scores and higher percentages meeting the American College of Rheumatology clinical hand OA criteria.ConclusionThis photographic scoring system was reliable and a good indicator of hand OA in a separate younger community-dwelling population than the development cohort. This method of data collection offers researchers a feasible alternative to physical examination and radiography.

These data allow an estimation of the incidence of exudative AMD in a Caucasian population and the treatment load with ranibizumab, which may help plan anti-vascular endothelial growth factor treatment programmes and estimate costs.