Age-related macular degeneration in very old individuals with family history.

PURPOSE: To study age-related macular degeneration (AMD) in old and very old individuals with family history of AMD to find the proportion of those with early and advanced AMD. DESIGN: Retrospective cross-sectional cohort study of individuals with family history of AMD. METHODS: Database of 897 AMD patients ages 75 to 102 years with family history of AMD was compiled. Color fundus photographs were graded in a masked fashion according to the International Classification of AMD. RESULTS: With increasing age, a gradually larger proportion of participants had advanced AMD; 54% (469 of 863) of all those 75 years and older had advanced AMD, 64% (258 of 406) of all those 85 years and older, 74% (37 of 50) of all those 95 years and older, and all (eight of eight) 100 years and older had advanced AMD. CONCLUSIONS: All the centenarians in the present study had advanced AMD.

CFH Y402H confers similar risk of soft drusen and both forms of advanced AMD.

BACKGROUND: Age-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 FINDINGS: We 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 x 10(-12)) and odds ratio of 2.14 in US patients from Utah (p = 2.0 x 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). CONCLUSION: Soft 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.

Enucleation in Iceland 1992-2004: study in a defined population.

PURPOSE: To determine the incidence rate as well as causative diagnoses and surgical indications of enucleation in Iceland during the years 1992-2004. METHODS: A retrospective population-based incidence study involving the entire population of Iceland. Medical records of all patients who underwent enucleation in Iceland from January 1992 through December 2004 were reviewed. The annually updated Icelandic census was used as a denominator data. RESULTS: Fifty-six eyes were enucleated during 1992-2004. No eviscerations were 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.

A rare nonsynonymous sequence variant in C3 is associated with high risk of age-related macular degeneration.

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.

Population-based incidence of exudative age-related macular degeneration and ranibizumab treatment load.

BACKGROUND/AIMS: The use of intravitreal vascular endothelial growth factor antibodies for exudative age-related macular degeneration (AMD) has stressed ophthalmology services and drug budgets throughout the world. The authors study the population-based incidence of exudative AMD in Iceland and the use of intravitreal ranibizumab in a defined population. METHODS: This is a prospective study of 439 consecutive patients aged 60 years and older with exudative AMD starting intravitreal ranibizumab for exudative AMD in Iceland from March 2007 to December 2009. All patients initially received three consecutive ranibizumab injections, with regular follow-up visits and re-treatment as needed. RESULTS: In total, 517 eyes from 439 patients received treatment for exudative AMD (mean age 79 years). The annual incidence of exudative AMD in the population 60 years and older is 0.29%. The incidence increased with advancing age, double for patients 85 years and older compared with those 75-79 years. Approximately 2400 ranibizumab injections per 100,000 persons aged 60 years and older were given each year for exudative AMD. CONCLUSIONS: 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.

[New drug treatment for age-related macular degeneration]. / Ný lyf fyrir hrörnun í augnbotnum og skylda sjúkdóma.

New drugs for age-related macular degeneration present a major advance in the treatment of the most common cause of blindness in Iceland. Vascular endothelial growth factor antibodies reduce the risk of blindness and improve vision in patients with age-related macular degeneration.

[Age related macular degeneration]. / Aldursbundin hrörnun í augnbotnum -yfirlitsgrein.

Age-related macular degeneration (AMD) is the main reason for blindness today in the western hemisphere. According to Björn Olafsson, who was the first ophthalmologist in Iceland a century ago, this disease was not found in Iceland. In the blindness-registry of 1950 6% blindness was due to this disease. Today, AMD is responsible for 54% of legal blindness in Iceland. The incidence of the disease increases with age. Heredity and environmental factors are thought to influence its etiology. Indirect methods, including twin studies and increased frequency of this disease in some families, have demonstrated that hereditary factors may be important. This has been confirmed recently by demonstrating that genes on chromosome 1 and chromosome10 play a role. This disease is classified as early stage, with drusen and pigmentary changes and insignificant visual loss. Treatment options for this stage are limited. The use of vitamin E and C and Zinc has, however, been shown to delay its progress. The second and end stage involves visual loss, either as a dry form with pigment epithelial atrophy or wet form, with new vessel formation. Treatment options for the dry form are limited. The second form is more common in Iceland than in other countries. Treatment options for the wet form have increased. Localised laser and drug treatment to neovascular membranes, either alone or as a combination treatment with drugs that have anti-proliferate effect on new vessels (anti-VEGF) are increasingly used. New treatment methods are also used in assisting those that are already visually handicapped. The use of computers is increasing as are the patients' computer skills. As the number of the elderly increases, AMD will be an increasing health problem in Iceland as in other Western countries. It is therefore important to improve the treatment options and the service and counselling of patients.