Redmer van Leeuwen

Epidemiology of Age-Related Maculopathy: A Review

Age-related maculopathy (ARM) is a degenerative disease of the retina and the leading cause of incurable blindness and visual impairment in industrialized countries. By definition, ARM is confined to the age-category above 50 years. The aetiology of ARM is still unknown, despite intensive research on many fronts. In this paper, we provide a review of the epidemiology of ARM. The most prominent findings were an exponential increase in frequency with age, a significant familial and genetic component, and a strong association with smoking. Other risk factors that were found less consistently were atherosclerosis, low intake of antioxidant nutrients, and cataract extraction. Future studies, both observational and experimental, will hopefully identify more risk factors that are amenable to prevention.

Is there a direct association between age-related eye diseases and mortality?: The Rotterdam Study

PURPOSE To study mortality in subjects with age-related maculopathy (ARM), cataract, or open-angle glaucoma (OAG) in comparison with those without these disorders. DESIGN Population-based prospective cohort study. PARTICIPANTS Subjects (n = 6339) aged 55 years and older from the population-based Rotterdam Study for whom complete information on eye disease status was present. MAIN OUTCOME MEASURES Vital status continuously monitored from 1990 until January 1, 2000. METHODS The diagnosis of ARM was made according to the International Classification System. Cataract, determined on biomicroscopy, was defined as any sign of nuclear or (sub)cortical cataract, or both, in at least one eye with a visual acuity of 20/40 or less. Aphakia and pseudophakia in at least one eye were classified as operated cataract. Definite OAG was defined as a glaucomatous optic neuropathy combined with a glaucomatous visual field defect. Diagnoses were assessed at baseline. Mortality hazard ratios were computed using Cox proportional hazard regression analysis, adjusted for appropriate confounders (age, gender, smoking status, body mass index, cholesterol level, atherosclerosis, hypertension, history of cardiovascular disease, and diabetes mellitus). RESULTS The adjusted mortality hazard ratio for subjects with AMD (n = 104) was 0.94 (95% confidence interval [CI], 0.52-1.68), with biomicroscopic cataract (n = 951) was 0.94 (95% CI, 0.74-1.21), with surgical cataract (n = 298) was 1.20 (95% CI, 0.86-1.68), and with definite OAG (n = 44) was 0.39 (95% CI, 0.10-1.55). CONCLUSIONS Both ARM and cataract are predictors of shorter survival because they have risk factors that also affect mortality. When adjusted for these factors, ARM, cataract, and OAG were themselves not significantly associated with mortality.

Risk of bilateral visual impairment in individuals with amblyopia: the Rotterdam study

Background: The excess risk of bilateral visual impairment (BVI; bilateral visual acuity <0.5) among individuals with amblyopia is an argument for screening for amblyopia, but data are scarce. Methods: The risk was estimated by determining the incidence of BVI in the Rotterdam Study, a population-based cohort of subjects aged 55 years or over (n  =  5220), including 192 individuals with amblyopia (3.7%). Using a multistate lifetable, the lifetime risk and excess period spent with BVI were determined. Results: The relative risk of BVI for amblyopes was 2.6 (95% confidence interval 1.4–4.5). For individuals with amblyopia, the lifetime risk of BVI was 18%, whereas they lived on average 7.2 years with BVI. For non-amblyopic individuals, these figures were 10% and 6.7 years, respectively. Conclusion: Amblyopia nearly doubles the lifetime risk of BVI and affected individuals spent an extra six months with BVI. This study provides data for future cost-effectiveness analyses.

Grading of age-related maculopathy for epidemiological studies: Is digital imaging as good as 35-mm film?☆

PURPOSE To compare stereo digital images with stereo 35-mm color transparencies as to the quality and reliability of grading age-related maculopathy (ARM) in the context of a multicenter European epidemiologic study (the EUREYE Study). DESIGN Instrument validation study. PARTICIPANTS Ninety-one subjects (137 eyes) with varying degrees of ARM, including no ARM. METHODS From both eyes of the participants, 35-mm film and digital stereoscopic fundus images were obtained with two identical Topcon fundus cameras. Two experienced graders classified all signs of ARM according to the International Classification System. Agreement between imaging techniques and between graders was calculated using the weighted kappa statistic. MAIN OUTCOME MEASURES Signs of ARM (number, size, and morphologic characteristics of drusen; pigmentary changes; geographic atrophy; and neovascular macular degeneration) as well as an overall staging system of increasing ARM severity. RESULTS The weighted kappa value for between-technique agreement ranged from 0.41 for number of drusen <63 microm to 0.79 for drusen type and total area occupied by drusen. The kappa values for atrophic and neovascular end-stage ARM were 0.87 and 0.94, respectively. The between-technique agreement on stages of ARM was approximately 0.76. The agreement between graders was largely the same for both techniques of imaging. CONCLUSIONS In the described setting, digital images were as good as 35-mm film for the grading of ARM. Considering the practical advantages of digital imaging, this technique may serve well in epidemiologic studies of ARM.

7-Nitro indazole, an inhibitor of neuronal nitric oxide synthase, attenuates pilocarpine-induced seizures

7-Nitro indazole (25-100 mg/kg i.p.), an inhibitor of neuronal nitric oxide (NO) synthase, attenuated the severity of pilocarpine (300 mg/kg i.p.)-induced seizures in mice. This indicates that the decreased neuroexcitability of the central nervous system (CNS) following administration of 7-nitro indazole may be due to inhibition of neuronal NO synthase, implying that NO acts as an excitatory and proconvulsant factor in the CNS.

VIGILANCE AND EEG POWER IN RATS: EFFECTS OF POTENT INHIBITORS OF THE NEURONAL NITRIC OXIDE SYNTHASE

Abstract We examined the effects of potent neuronal nitric oxide synthase inhibitors, 3-bromo-7-nitro indazole (3-Br-7-NI) and S-methyl-L-thiocitrulline (S-Me-TC) on general behaviour, vigilance stages and electro-encephalographic (EEG) power spectra in rats. In addition, we studied the effect of 7-nitro indazole (7-NI) on EEG power spectra in rats during dark and light periods. 3-Br-7-NI induced ptosis and decrease of slow wave sleep and rapid eye movement sleep in the rat. 7-NI and 3-Br-7-NI reduced the EEG power density in all frequency bands in the rat, suggesting a depression of central neuronal activity. This effect of 7-NI was more prominent during the day than during the night, indicating a circadian variation in the nitric oxide synthase (NOS) response to NOS inhibitor. EEG power was the most reduced in the 7-9Hz range of the rhythmic slow activity (theta rhythm), which is in accordance with decreased locomotion observed following administration of NOS inhibitors. Although S-Me-TC is the most potent NOS inhibitor in vitro experiments, it had less effect on vigilance and EEG power in the rat than other NOS inhibitors used in this study, probably due to its short lasting and blood pressure raising effect. The present results indicate that nitric oxide exerts an excitatory and circadian dependent effect in the central neuronal structures involved in the regulation of vigilance.

Epidemiologie der AMD

Dieses Kapitel ist eine Aktualisierung zum Thema »Epidemiologie der altersabhangigen Makuladegeneration« (AMD) und erlautert die seit der letzten Auflage von 2003 neugewonnenen Erkenntnisse. Ziel des Kapitels ist es, eine Ubersicht der aktuellen epidemiologischen Literatur bei AMD zu geben sowie uber Diagnose, Haufigkeit, genetische und umweltbedingte Einflussfaktoren und deren mogliche Interaktionen bei AMD zu informieren.