Arsaell Arnarsson

Common sequence variants in the LOXL1 gene confer susceptibility to exfoliation glaucoma.

Glaucoma is a leading cause of irreversible blindness. A genome-wide search yielded multiple single-nucleotide polymorphisms (SNPs) in the 15q24.1 region associated with glaucoma. Further investigation revealed that the association is confined to exfoliation glaucoma (XFG). Two nonsynonymous SNPs in exon 1 of the gene LOXL1 explain the association, and the data suggest that they confer risk of XFG mainly through exfoliation syndrome (XFS). About 25% of the general population is homozygous for the highest-risk haplotype, and their risk of suffering from XFG is more than 100 times that of individuals carrying only low-risk haplotypes. The population-attributable risk is more than 99%. The product of LOXL1 catalyzes the formation of elastin fibers found to be a major component of the lesions in XFG.

Prevalence of age-related macular degeneration in old persons: Age, Gene/environment Susceptibility Reykjavik Study.

PURPOSE To describe the prevalence and signs of early and late age-related macular degeneration (AMD) in an old cohort. DESIGN Population-based cohort study. PARTICIPANTS We included 5272 persons aged ≥66 years, randomly sampled from the Reykjavik area. METHODS Fundus images were taken through dilated pupils using a 45-degree digital camera and graded for drusen size, type, area, increased retinal pigment, retinal pigment epithelial depigmentation, neovascular lesions, and geographic atrophy (GA) using the modified Wisconsin Age-Related Maculopathy Grading System. MAIN OUTCOME MEASURES Age-related macular degeneration in an elderly cohort. RESULTS The mean age of participants was 76 years. The prevalence of early AMD was 12.4% (95% confidence interval [CI], 11.0-13.9) for those aged 66 to 74 years and 36% (95% CI, 30.9-41.1) for those aged ≥85 years. The prevalence of exudative AMD was 3.3% (95% CI, 2.8-3.8). The prevalence of pure GA was 2.4% (95% CI, 2.0-2.8). The highest prevalence of late AMD was among those aged ≥85 years: 11.4% (95% CI, 8.2-14.5) for exudative AMD and 7.6% (95% CI, 4.8-10.4) for pure GA. CONCLUSIONS Persons aged ≥85 years have a 10-fold higher prevalence of late AMD than those aged 70 to 74 years. The high prevalence of late AMD in the oldest age group and expected increase of elderly people in the western world in coming years call for improved preventive measures and novel treatments.

Prevalence and causes of visual impairment and blindness in Icelanders aged 50 years and older: the Reykjavik Eye Study.

Purpose:  This study aimed to study the prevalences and causes of visual impairment and blindness in an Icelandic adult population.

Five-year incidence of visual impairment and blindness in older Icelanders: the Reykjavik Eye Study.

Purpose:  This study examined age, sex and cause‐specific 5‐year incidence of visual impairment and blindness in a middle‐aged and elderly Icelandic population.

Increased disk size in glaucomatous eyes vs normal eyes in the Reykjavik eye study

PURPOSE To evaluate the use of disk diameter as an indicator in the identification of glaucomatous optic neuropathy. METHODS We evaluated all available stereofundus photographs for 1,040 right eyes obtained in the Reykjavik Eye Study. Horizontal and vertical disk diameters were determined in a masked manner by a glaucoma specialist (K.F.D.). All disk diameters were corrected for refractive error. RESULTS There were significant differences (P <.05) between the corrected vertical disk diameters of normal subjects (0.189 +/- 0.018 inches) and those suspected of having glaucoma (0.202 +/- 0.020 inches) as well as between the normal and the glaucoma groups (0.206 +/- 0.029 inches). The corrected horizontal measurement showed the same pattern. CONCLUSIONS In the Reykjavik Eye Study, optic disks meeting structural criteria for glaucoma are significantly larger than normal nerves.

The role of GABA in modulating the Xenopus electroretinogram

We have recorded the electroretinogram (ERG) from the superfused eyecup of the Xenopus retina in order to assess the effects of the inhibitory neurotransmitter gamma-aminobutyric acid (GABA), and its agonists and antagonists, on individual ERG components. We found that GABA (0.5-10 mM) reduced the amplitudes of both the b- and d-waves of the Xenopus ERG. The GABA uptake blocker nipecotic acid (1 mM) had similar effects on b- and d-waves. GABA at 5 mM and 10 mM also caused an increase in the a-wave. The GABA antagonist picrotoxin (0.1-2 mM) and the GABA/a antagonist bicuculline (0.2 mM) both increased the amplitude of the b- and d-waves of the ERG. The GABA/b agonist baclofen (0.3 mM) reduced the amplitude of the ERG b-wave, enhanced the amplitude of the a-wave, and slightly reduced the amplitude and increased the peak time of the d-wave. The GABA/b antagonists phaclofen and saclofen had no reliable effects on the Xenopus ERG. Glutamate analogs known to affect specific types of retinal neurons were applied to modify the retinal circuitry and then the effects of GABA and its antagonists were examined under these modified conditions. 2-amino-4-phosphonobutyric acid (APB) increased the d-wave, and blocked the b-wave and the effect of GABA on the ERG, but not the antagonist-induced increase in the d-wave. KYN blocked the antagonist-induced increase in the b-wave, while GABA increases the amplitude of the b-wave if the d-wave has been removed by prior superfusion with kynurenic acid (KYN). N-methyl-DL-aspartate (NMDLA), which acts only in the proximal retina, reduced the amplitude of the ERG and blocked the effect of GABA and the antagonist-induced increase in ERG b- and d-waves amplitude. These results suggest that GABAergic mechanisms related to both A and B receptor types can influence the amplitude and light sensitivity of all the components of the Xenopus ERG. Since GABA is found in greatest abundance in the proximal retina, and B type of receptors are present almost exclusively there, the data suggests that most of the effects of GABA agonists and antagonists observed are dependent on proximal retinal mechanisms, and that there are separate mechanisms in the proximal retina related to the b- and the d-waves.

Pseudoexfoliation in the Reykjavik Eye Study: Five-Year Incidence and Changes in Related Ophthalmologic Variables

PURPOSE To examine the 5-year incidence of pseudoexfoliation (PEX) and monitor changes in related ophthalmologic variables. DESIGN Population-based, prospective cohort study. METHODS A random sample from the Reykjavik Population Census for persons 50 years and older was used. At baseline 1,045 participants were examined for signs of PEX including peripheral band and/or central shield of exfoliative material on the anterior lens capsule. Five years later, 846 (88.2%) of survivors returned for a follow-up visit. RESULTS The 5-year incidence of PEX was 3.5% in right eyes only, and 5.2% in either eye. Age increased the risk of 5-year incidence by 5% when looking at 10-year age groups (P = .02); the incidence was higher in female subjects (P = .05) than in male. A total of 27% of clinically asymmetric cases converted to clinically bilateral disease over 5 years. Intraocular pressure increased in the group that developed PEX during the 5 years, but the size of the optic cup increased most in eyes that already had PEX at baseline. CONCLUSION This incidence study from Iceland confirms findings from previous prevalence studies that PEX is increasingly common with older age in this population. Earliest changes related to PEX may be subtle and difficult to detect, which may lead to some misclassification. Further study is needed to identify clinical features that can reliably detect patients at risk for developing PEX.

Twelve-year Incidence of Exfoliation Syndrome in the Reykjavik Eye Study

Purpose:  To examine the 12‐year incidence of exfoliation syndrome (XFS) in persons aged 50–79 years at baseline and also to monitor changes in related ophthalmologic variables, to identify possible risk factors for incidence and to estimate the reliability of our diagnostic criteria.

Exfoliation syndrome in the Reykjavik Eye Study: risk factors for baseline prevalence and 5-year incidence.

Aim To examine the age- and gender-specific prevalent and 5-year incident risk of developing exfoliation syndrome (XFS). Methods and participants In a population-based random sample of citizens 50 years and older, 1045 persons had baseline examination in 1996; 846 of the 958 survivors (88.2%) had a follow-up examination in 2001. Following maximum dilatation of pupils, a diagnosis of exfoliation was established on slit-lamp examination. An extensive questionnaire was administered at baseline and follow-up. Prevalent and incident risk was then calculated using a multivariate analysis. Results The following variables were found to correlate significantly with prevalence risk of XFS at baseline: age, female gender, increased iris pigmentation, moderate use of alcohol and self-reported asthma. We also found that, compared with those who consumed dietary fibre-rich vegetables, green or yellow vegetables, and fruit less than once a month in their 20s and 40s, those consuming the same food items once or twice every 2 weeks were found to be less likely to have XFS. The same applied to those consuming dietary fibre rich once or twice every 2 weeks in their 40s and 60s. Conclusion Food items that are possibly surrogates for antioxidative effect may correlate with decreased risk of XFS and increased iris pigmentation may correlate with increased risk. Given the large number of comparisons, these findings require validation through additional clinical studies. Increased age and female gender increase the likelihood of XFS.

Epidemiology of the optic nerve grey crescent in the Reykjavik Eye Study

Aim: To establish the epidemiology of the grey crescent in a white population within the age range most susceptible to glaucoma. Methods: Bruce Shields was first to use this term to describe a localised, physiological pigmentation of the optic nerve neuroretinal rim tissue that is distinct from peripapillary pigmentation. An experienced glaucomatologist (KFD) evaluated stereofundus photographs of the participants of the Reykjavik Eye Study (RES)—a random sample from the national population census including people 50 years and older. 1012 right eyes could be evaluated for grey crescent. Results: The prevalence of grey crescent in the right eyes was 22.0% (95% CI 10 to 25). It was more commonly found in women (27.0%: 95% CI 23 to 30) than in men (17.0%: 95% CI 14 to 21), and was most often located temporally (36.9%), 360° (15.9%), or nasally (15.4%). The spherical equivalent was +1.30 dioptres (D) for those with and +0.80 D for those without grey crescent (p = 0.002), respectively. Vertical optic disc diameters were 0.203 v 0.195 units (p<0.001). There was no difference in the prevalence of grey crescent in glaucomatous or non-glaucomatous eyes (OR = 1.05, 95% CI 0.49 to 2.26). The prevalence of a grey crescent was inversely related to the prevalence of peripapillary atrophy (p = 0.001). Conclusions: The grey crescent needs to be recognised as a physiological variant in order to avoid falsely labelling eyes as having glaucomatous optic nerve damage.