http://repub.eur.nl/res/aut/4247/ List of Publications en http://repub.eur.nl/static-eur/img/logo.png http://repub.eur.nl http://repub.eur.nl/res/pub/35024/ 2012-01-04T00:00:00Z Background: Open-angle glaucoma (OAG) is a progressive neurodegenerative disease that may lead to blindness. An elevated intraocular pressure (IOP) is its major risk factor. OAG treatment is currently exclusively directed towards the lowering of the IOP. IOP lowering does not prevent disease progression in all patients and thus other treatment modalities are needed. Earlier studies reported cholesterol-lowering drugs to have neuroprotective properties. The aim of this study was to determine the associations between the use of cholesterol-lowering drugs and incident OAG. Methodology/Principal Findings: Participants in a prospective population-based cohort study underwent ophthalmic examinations, including IOP measurements and perimetry, at baseline and follow-up. The use of statins and non-statin cholesterol-lowering drugs was monitored continuously during the study. Associations between the use of cholesterol-lowering drugs and incident OAG were analyzed with Cox regression; associations between cholesterol-lowering drugs and IOP at follow-up were analyzed with multiple linear regression. During a mean follow-up of 9.8 years, 108 of 3939 eligible participants (2.7%) developed OAG. The hazard ratio for statin use was 0.54 (95% confidence interval 0.31-0.96; P = 0.034) and for non-statin cholesterol-lowering drugs 2.07 (0.81-5.33; P = 0.13). The effect of statins was more pronounced with prolonged use (hazard ratio 0.89 [0.41-1.94; P = 0.77] for use two years or less; 0.46 [0.23-0.94; P = 0.033] for use more than two years; P-value for trend 0.10). The analyzes were adjusted for age and gender, baseline IOP and IOP-lowering treatment, the family history of glaucoma, and myopia. There was no effect of statins on the IOP. Conclusions/Significance: Long-term use of statins appears to be associated with a reduced risk of OAG. The observed effect was independent of the IOP. These findings are in line with the idea that statins have neuroprotective properties and may open a way to a new OAG treatment modality. http://repub.eur.nl/res/pub/33589/ 2011-12-01T00:00:00Z Objective: Genome-wide association studies have revealed new insights into the genetic determinants of open-angle glaucoma (OAG). This study was performed to determine to what extent variants within established genes (MYOC, OPTN, and WDR36) and newly identified common genetic variants (ATOH7, CDKN2B, and SIX1) contribute to the risk of OAG. Design: Population-based setting, family-based setting, and a case-control study. Participants: The Rotterdam Study I cohort (N = 5312; mean age±standard deviation [SD], 68.0±8.4 years). Findings were replicated in the Genetic Research in Isolated Populations combined with the Erasmus Rucphen Family study (N = 1750; mean age±SD, 48.3±15.2 years), and a cohort from Southampton (N = 702; mean age±SD, 72.5±10.7 years). Methods: After identifying common variants associated with OAG within the established genes, the risk of OAG was analyzed using logistic regression. Discriminative accuracy was assessed by comparing the area under the receiver operator characteristic curve (AUC) for models, including the number of risk alleles, intraocular pressure, age, and gender, with the AUC for the same model but without the risk alleles. Main Outcome Measures: Odds ratios and AUCs of individual and combined risk alleles. Results: No consistent significant associations for the established genes (MYOC, OPTN, and WDR36) with OAG were found. However, when comparing the load of risk variants between cases and controls, 2 of 3 studies showed a significant increased risk of OAG for participants carrying more risk alleles of the 3 established genes. When combining all 6 genes, participants carrying a high number of risk alleles (highest tertile) had a 2.29-fold to 3.19-fold increase in risk of OAG compared with those carrying only a few risk alleles. The addition of the newly identified genes to IOP, age, and gender resulted in a higher AUC compared with the AUC without the newly identified genes (P = 0.027). Conclusions: A significant contribution to the risk of OAG was found for the new common variants identified by recent genome-wide association studies, but not for variants within the established genes. Participants carrying a high number of risk alleles had an approximately 3-fold increase in the risk of OAG compared with those with a low number of risk alleles. http://repub.eur.nl/res/pub/31372/ 2011-08-01T00:00:00Z Aim: To determine the amount of myopic shift in children after cataract surgery with intraocular lens (IOL) implantation and to evaluate success in achieving the target refraction. Methods: The children were assigned into three groups depending on age at time of surgery: Group A, 0-1 years old; Group B, 1-7 years old; Group C, 7-18 years old. Multiple regression analysis was used to create a formula for expected myopic shift and to find out which variables were associated with a higher absolute prediction error. Results: Children less than 12 months of age experienced higher myopic shifts and a larger mean rate of refractive change per year compared with older children. We found higher myopic shifts in younger children at time of surgery and children with unilateral cataract. Absolute prediction error was significantly higher in Group A compared with Groups B and C (p=0.022 and p=0.037, respectively). Multiple regression analysis showed that corneal radius was the only variable significantly associated with absolute prediction error. Conclusion: Our data demonstrate the complexity in predicting the postoperative refraction in children under 1 year old and show that age at surgery and laterality are factors to consider when deciding which IOL power to implant in children. http://repub.eur.nl/res/pub/33413/ 2011-06-01T00:00:00Z Objective: To determine whether lifestyle-related risk factors, such as socioeconomic status, smoking, alcohol consumption, and obesity, are associated with open-angle glaucoma (OAG). Methods: Participants from the Rotterdam Study, a prospective population-based cohort study, were considered eligible if they participated at both baseline and follow-up and if they had no OAG at baseline. All participants underwent an identical ophthalmologic examination at all visits, including intraocular pressure measurements, optic nerve head assessment, and perimetry. Lifestyle-related factors were assessed by questionnaires by trained research assistants or measured during the examinations (body mass index and waist to hip ratio). Cox proportional hazard regression analysis was applied to calculate hazard ratios. Results: Of 3939 eligible participants, 108 (2.7%) developed OAG during 9.7 years' mean follow-up. No statistically significant effect of socioeconomic status, smoking, or alcohol intake was found. In women, each unit increase in body mass index resulted in a 7% decrease in the risk of developing OAG (P = .04). There was a significant increasing effect of body mass index on intraocular pressure (P < .001) in women. Conclusions: Obesity appears to be associated with a higher intraocular pressure and a lower risk of developing OAG. These associations were only present in women. Other lifestyle-related factors, such as socioeconomic status, smoking, and alcohol consumption, were not associated with OAG. http://repub.eur.nl/res/pub/34059/ 2011-06-01T00:00:00Z Open-angle glaucoma (glaucoma) is a major eye disorder characterized by optic disc pathology. Recent genome-wide association studies identified new loci associated with clinically relevant optic disc parameters, such as the optic disc area and vertical cup-disc ratio (VCDR). We examined to what extent these loci are involved in glaucoma. The loci studied include ATOH7, CDC7/TGFBR3 and SALL1 for optic disc area, and CDKN2B, SIX1, SCYL1/LTBP3, CHEK2, ATOH7 and DCLK1 for VCDR. We performed a metaanalysis using data from six independent studies including: the Rotterdam Study (n = 5736), Genetic Research in Isolated Populations combined with Erasmus Rucphen Family study (n = 1750), Amsterdam Glaucoma Study (n = 296) and cohorts from Erlangen and Tü bingen (n = 1363), Southampton (n = 702) and deCODE (n = 36 151) resulting in a total of 3161 glaucoma cases and 42 837 controls. Of the eight loci, we found significant evidence (P = 1.41 3 10-8) for the association of CDKN2B with glaucoma [odds ratio (OR) for those homozygous for the risk allele: 0.76; 95% confidence interval (CI): 0.70-0.84], for the role of ATOH7 (OR: 1.28; 95% CI: 1.12-1.47) and for SIX1 (OR: 1.20; 95% CI: 1.10-1.31) when adjusting for the number of tested loci. Furthermore, there was a borderline significant association of CDC7/TGFBR3. http://repub.eur.nl/res/pub/23054/ 2011-01-01T00:00:00Z Background: Although the vertical cup-disc ratio (VCDR) and intraocular pressure (IOP) are important determinants of open angle glaucoma (OAG), it is unclear to what extent the genetic origin of these traits overlap with those of OAG. We evaluated whether the same genes that determine VCDR and IOP also predict OAG. Methods: Genetic risk scores were constructed from single nucleotide polymorphisms (SNPs) using genome wide association data of 9326 participants from the Rotterdam Study cohorts (mean±SD age: 64.6±9.1 years). These risk scores were used to calculate the explained variance of VCDR and IOP in an independent cohort (Erasmus Rucphen Family study) consisting of 1646 participants (mean±SD age: 46.8614.1 years) and the OAG risk in a subset of the Rotterdam Study cohorts. To evaluate false positive findings, we generated two new variables containing randomly sampled values to serve as a negative control. Results: The explained variance of VCDR increased when increasing the number of SNPs included in the risk score, suggesting a polygenic model. We found no clear evidence for a similar model for IOP, suggesting that a small number of SNPs determine the susceptibility to IOP. The SNPs related to IOP in terms of p values contributed little to VCDR. The risk scores associated with VCDR were also associated significantly with OAG. This suggests a common polygenic background for VCDR and OAG Conclusions: We found evidence for a polygenic model underlying one of the major traits of OAG, VCDR, and OAG itself. The IOP did not show any evidence for such a model. http://repub.eur.nl/res/pub/21442/ 2010-11-07T00:00:00Z Background: Although the vertical cup-disc ratio (VCDR) and intraocular pressure (IOP) are important determinants of open angle glaucoma (OAG), it is unclear to what extent the genetic origin of these traits overlap with those of OAG. We evaluated whether the same genes that determine VCDR and IOP also predict OAG. Methods: Genetic risk scores were constructed from single nucleotide polymorphisms (SNPs) using genome wide association data of 9326 participants from the Rotterdam Study cohorts (mean±SD age: 64.6±9.1 years). These risk scores were used to calculate the explained variance of VCDR and IOP in an independent cohort (Erasmus Rucphen Family study) consisting of 1646 participants (mean±SD age: 46.8±14.1 years) and the OAG risk in a subset of the Rotterdam Study cohorts. To evaluate false positive findings, we generated two new variables containing randomly sampled values to serve as a negative control. Results: The explained variance of VCDR increased when increasing the number of SNPs included in the risk score, suggesting a polygenic model. We found no clear evidence for a similar model for IOP, suggesting that a small number of SNPs determine the susceptibility to IOP. The SNPs related to IOP in terms of p values contributed little to VCDR. The risk scores associated with VCDR were also associated significantly with OAG. This suggests a common polygenic background for VCDR and OAG Conclusions: We found evidence for a polygenic model underlying one of the major traits of OAG, VCDR, and OAG itself. The IOP did not show any evidence for such a model. http://repub.eur.nl/res/pub/20277/ 2010-09-01T00:00:00Z Purpose: To determine the 10-year incidence of glaucomatous visual field loss (GVFL) and to investigate the influence of risk factors for open-angle glaucoma on this incidence. Design: Population-based cohort study. Participants: Participants aged ≥55 years from the Rotterdam Study. Methods: Of the 7983 participants in the Rotterdam Study, 6806 underwent ophthalmic examinations at baseline (1990-1993). In 6723 of these 6806 participants (99%), both visual field screening and an assessment of the optic disc were performed. After exclusion of 93 participants with GVFL at baseline, 6630 participants at risk of developing GVFL remained. These participants underwent similar ophthalmic examinations during 2 follow-up visits (1997-1999 and 2002-2006). The incidence of GVFL was determined as an incidence rate and recalculated to a 10-year risk. Risk factors for open-angle glaucoma (age, gender, positive family history of glaucoma, baseline intraocular pressure (IOP), myopia, and baseline vertical cup-to-disc ratio [VCDR]) were assessed using Cox regression. The dependent variable was the development of GVFL. Main Outcome Measures: Ten-year risk and incidence rates of GVFL. Hazard ratios of the above-mentioned risk factors. Results: Of 6630 participants, 3939 (59%) completed at least 1 follow-up examination and 2571 (39%) completed both; 108 participants developed GVFL. The overall incidence rate and 10-year risk of GVFL were 2.9 per 1000 person-years (95% confidence interval [CI], 2.4-3.5) and 2.8% (2.3-3.4), respectively. The 10-year risk increased from 1.9% at age 55 to 59 years to 6.4% at age ≥80 years (P<0.001). The incidence increased by 11% per millimeter of mercury increase in IOP (hazard ratio 1.11; 95% CI, 1.06-1.15). Male gender (1.62; 1.10-2.38), high myopia (spherical equivalent ≤-4 D myopic; 2.31; 1.19-4.49), and a baseline VCDR above the 97.5th percentile (4.64; 2.72-7.91) were associated with the development of GVFL. A positive family history was only significantly associated with the development of GVFL if IOP was removed from the model (2.0; 1.2-3.3; P = 0.012). Conclusions: These data provide an estimate of the incidence of GVFL in a white population. The development of GVFL was related to higher IOP, older age, high myopia, male gender, a positive family history of glaucoma, and a larger baseline VCDR. Financial Disclosure(s): The author(s) have no proprietary or commercial interest in any materials discussed in this article http://repub.eur.nl/res/pub/20162/ 2010-06-01T00:00:00Z The optic nerve head is involved in many ophthalmic disorders, including common diseases such as myopia and open-angle glaucoma. Two of the most important parameters are the size of the optic disc area and the vertical cup-disc ratio (VCDR). Both are highly heritable but genetically largely undetermined. We performed a meta-analysis of genome-wide association (GWA) data to identify genetic variants associated with optic disc area and VCDR. The gene discovery included 7,360 unrelated individuals from the population-based Rotterdam Study I and Rotterdam Study II cohorts. These cohorts revealed two genome-wide significant loci for optic disc area, rs1192415 on chromosome 1p22 (p =6.72*10-19) within 117 kb of the CDC7 gene and rs1900004 on chromosome 10q21.3-q22.1 (p=2.67*10-33) within 10 kb of the ATOH7 gene. They revealed two genome-wide significant loci for VCDR, rs1063192 on chromosome 9p21 (p =6.15*10-11) in the CDKN2B gene and rs10483727 on chromosome 14q22.3-q23 (p=2.93*10-10) within 40 kbp of the SIX1 gene. Findings were replicated in two independent Dutch cohorts (Rotterdam Study III and Erasmus Rucphen Family study; N=3,612), and the TwinsUK cohort (N=843). Meta-analysis with the replication cohorts confirmed the four loci and revealed a third locus at 16q12.1 associated with optic disc area, and four other loci at 11q13, 13q13, 17q23 (borderline significant), and 22q12.1 for VCDR. ATOH7 was also associated with VCDR independent of optic disc area. Three of the loci were marginally associated with open-angle glaucoma. The protein pathways in which the loci of optic disc area are involved overlap with those identified for VCDR, suggesting a common genetic origin. © 2010 Ramdas et al. http://repub.eur.nl/res/pub/16952/ 2009-12-01T00:00:00Z http://repub.eur.nl/res/pub/16865/ 2009-05-19T00:00:00Z Background: Falls are a serious problem in the elderly, and have recently been described as cardiovascular-mediated side effects of beta-blocker eye drops. Therefore, we investigated the possible association between the long-term use of beta-blockers, prostaglandins and their combinations in eye drops, and falls, dizziness and orthostatic hypotension in older patients. Methods: All participants were long-term users of eye drops containing beta-blockers, prostaglandins or their combinations. They underwent a structured falls interview and blood pressure measurement for testing of orthostatic hypotension. The odds ratio for presence of orthostatic hypotension or a positive falls history according to use of beta-blocker eye drops was calculated with a binary logistic regression analysis. The main outcome measures were a positive falls history and the presence of orthostatic hypotension. Results: In total, 148 of 286 subjects participated. After adjustment for age, gender, and use of fall-risk-increasing drugs other than beta-blocker eye drops, we found no significant difference in fall risk [odds ratio (OR): 0.60; 95% confidence interval (CI): 0.268-1.327] between patients using ophthalmic beta-blockers or a combination of ophthalmic beta-blockers and prostaglandins, and patients using ophthalmic prostaglandins only. Although prevalence of orthostatic hypotension was higher in the beta-blocker group (OR: 1.67; 95% CI: 0.731-3.793) compared to the prostaglandin group, this was a non-significant difference. Conclusions: In our study, we did not find a significant association between long-term use of beta-blockers eye drops and falls, dizziness or orthostatic hypotension in older ophthalmic outpatients, compared to long-term use of prostaglandin eye drops. http://repub.eur.nl/res/pub/29408/ 2008-11-01T00:00:00Z Purpose: To study the associations between long-term and short-term use of topical β-blockers and mortality. Design: Prospective population-based cohort study. Participants: To examine long-term effects, 3842 participants aged 55 years and older were recruited. To examine short-term effects, 484 incident β-blocker users and 4700 age-matched controls were recruited. All participants were recruited as part of the Rotterdam Study. Methods: To examine long-term effects, associations between topical β-blocker use before and at baseline, between 1990 and 1997, and mortality between 1997 and 2005 were studied. Data were analyzed using Cox regression, and hazard ratios were adjusted for age, gender, smoking, systemic hypertension, diabetes mellitus, and angina pectoris. Short-term effects were defined as death within 3 months after the first prescription of a topical β-blocker. Mortality was compared between incident β-blocker users, that is, participants who started using a topical β-blocker between the onset of the Rotterdam Study in 1990 and October 1, 2004, and age-matched controls. Short-term effects were examined using a chi-square test. Confounding by smoking was analyzed by stratification. Main Outcome Measures: For long-term effects, hazard ratios of topical β-blocker use for all-cause mortality and cardiovascular mortality; for short-term effects, chi-square statistics between mortality of incident topical β-blocker users and age-matched controls. Results: With regard to long-term effects, mean age at baseline was 72 years (standard deviation, 7 years). Topical β-blockers were used by 228 participants. Seven hundred nine participants died during the follow-up (18%); 135 (3.5%) died of a cardiovascular cause. The hazard ratio of topical β-blocker use was 0.94 (95% confidence interval [CI], 0.71-1.25; P = 0.69) for all-cause mortality and 1.02 (95% CI, 0.56-1.86; P = 0.95) for cardiovascular mortality. With regard to short-term effects, 4 (0.8%) of the 484 incident topical β-blocker users died within 3 months after their first prescription; 65 (1.4%; P = 0.31) of the 4700 aged-matched controls died within a similar period. Conclusions: Use of topical β-blockers seems not to be associated with excess mortality. Financial Disclosure(s): The authors have no proprietary or commercial interest in any materials discussed in this article. http://repub.eur.nl/res/pub/28824/ 2008-09-01T00:00:00Z Aim: To study the additional yield of a periodic screening programme for open-angle glaucoma (OAG) by comparing, in a population-based setting, incident OAG (iOAG) cases detected in regular ophthalmic care with those detected during screening. Methods: Participants aged 55 and over from the population-based Rotterdam Study underwent the same ophthalmic examination at baseline (1991-3) and follow-up (1997-9), including visual field testing and simultaneous stereo optic disc photography. Of 3842 participants, 87 (2.3%) developed iOAG during a mean follow-up time of 6.5 years. Of these 87 iOAG cases, 78 (90%) were included in this study. Results: Of the 78 iOAG cases detected at follow-up, 23 (29%) had already been detected before during regular ophthalmic care. The remaining 55 (71%) undetected iOAG cases more often showed glaucomatous optic neuropathy without glaucomatous visual field loss (29 of 55 (53%)) as compared with the detected cases (four of 23 (17%); p = 0.009). Of the undetected iOAG cases, only four had developed significant visual field loss in their better eye. Conclusion: The additional yield of a periodic OAG screening programme is lower than expected from published prevalence data. In the discussion, the authors estimate that-in a white population with a low prevalence of pseudoexfoliation-about one in 1000 screened persons could be saved from bilateral end-stage OAG. http://repub.eur.nl/res/pub/30436/ 2008-02-15T00:00:00Z We describe another patient with the combination of apple peel intestinal atresia, microcephaly, microphthalmia, and anterior eye chamber anomalies. Development so far seems to be normal, although there is major visual impairment due to the corneal clouding. Mutation analysis of the PAX6, FOX1, PITX2, and MYNC genes was normal as was MLPA for these genes. Autosomal recessive inheritance is possible as recurrence in sibs was described, although germ line mosaicism or a microdeletion due to a very small parental translocation cannot be ruled out. http://repub.eur.nl/res/pub/32391/ 2008-01-01T00:00:00Z Objective: To investigate whether polymorphisms in the estrogen receptor alpha (ESR1) and beta (ESR2) genes were a risk factor for open-angle glaucoma (OAG). Methods: Participants 55 years and older from the population-based Rotterdam Study underwent, at baseline and at follow-up, the same ophthalmic examination, including visual field screening and stereo optic disc photography. A diagnosis of OAG was based on an algorithm using optic disc measures and visual field loss. Haplotypes of the ESR1 and ESR2 genes were determined. Results: We diagnosed incident OAG in 87 of 3842 participants (2.3%) at risk after a mean follow-up of 6.5 years. We could not detect any association with ESR1 haplotypes. Haplotype 1 of ESR2 showed a 3.6-fold (95% confidence interval, 1.4-9.2) higher risk of incident OAG in men. In women, no association was found between ESR2 and incident OAG. Conclusion: Polymorphisms in the ESR1 gene are unrelated to OAG, but ESR2 polymorphisms seem to lead to increased risk of OAG in men. http://repub.eur.nl/res/pub/29373/ 2008-01-01T00:00:00Z Purpose: To describe two patients with acute angle closure glaucoma after oculoplastic surgery. Design: Interventional case reports. Methods: Review of clinical findings and treatment. Results: A 61-year-old female developed a painful eye with decreased visual acuity a few days after bilateral blepharoplasty. A 69-year-old male developed a painful red eye with decreased visual acuity a few days after ptosis correction. In both cases the intraocular pressure increased to more than 50 mmHg. Both patients were diagnosed with acute angle closure glaucoma and treated appropriately. Conclusions: Acute angle closure glaucoma is a possible complication of oculoplastic surgery. Copyright http://repub.eur.nl/res/pub/35689/ 2007-12-01T00:00:00Z Purpose: To determine the association between systemic antihypertensive medication and incident open-angle glaucoma. Design: Prospective population-based cohort study. Participants: The study population consisted of a subset of 3842 participants of the Rotterdam Study for whom data from identical ophthalmologic examinations at baseline and follow-up were available. Methods: Use of antihypertensive medication was registered over an average follow-up period of 6.5 years. Associations between incident open-angle glaucoma and antihypertensive medication were assessed using multivariate logistic regression models adjusted for age, gender, duration of follow-up, intraocular pressure, intraocular pressure-lowering medication, and cardiovascular disease. Main Outcome Measures: Odds ratios of associations between incident open-angle glaucoma and use of antihypertensive medication. Results: During follow-up, there were 87 incident cases of open-angle glaucoma. Participants using calcium channel antagonists had a 1.8-fold (95% confidence interval [CI], 1.04-3.2; P = 0.037) higher risk of developing incident open-angle glaucoma. β-Blockers were associated with a nonsignificant risk reduction (odds ratio, 0.6; 95% CI, 0.3-1.02; P = 0.060). None of the other classes of antihypertensives was significantly associated with incident open-angle glaucoma. Conclusions: These data suggest that use of calcium channel antagonists is associated with open-angle glaucoma, but this requires confirmation. These results do not support the use of calcium channel antagonists for the treatment of normal-tension glaucoma. http://repub.eur.nl/res/pub/13735/ 2005-04-01T00:00:00Z PURPOSE: It remains unclear whether reduced retinal blood flow and smaller arterioles, reported to exist in patients with open-angle glaucoma (OAG), are a cause or a consequence of ganglion cell loss. We examined whether baseline retinal vessel diameters were related to incident (i)OAG or incident optic disc changes in a population-based sample. METHODS: In the prospective population-based Rotterdam Study, baseline diameters of retinal arterioles and venules (1990-1993) were measured in digitized images of 3469 persons (aged 55 years and older) at risk for OAG. The follow-up examinations took place from 1997 to 1999. iOAG was based on the presence of incident glaucomatous visual field loss and/or incident glaucomatous optic neuropathy. Changes in neuroretinal rim, cup area, or vertical cup-to-disc ratio were calculated with a semiautomated image analyzer in 2782 persons. RESULTS: After a mean follow-up time of 6.5 years, 74 participants had iOAG. At baseline, the mean arteriolar diameter was 147.5 +/- 14.2 microm (SD) and the venular, 222.9 +/- 20.0 microm. Neither arteriolar diameters (odds ratio [OR] per SD decrease: 0.82; 95% confidence interval [CI]: 0.66-1.03) nor venular ones (OR per SD increase: 1.20; 95% CI: 0.95-1.53) were significantly related to iOAG. Baseline retinal vessel diameters did not predict changes in the optic disc. Additional adjustment for cardiovascular risk factors did not alter these results. CONCLUSIONS: The data show that baseline retinal vessel diameters did not influence the risk of iOAG or incident optic disc changes. These data provide no evidence for a retinal vascular role in the pathogenesis of OAG. http://repub.eur.nl/res/pub/9726/ 2001-01-01T00:00:00Z PURPOSE: To describe the incidence rate of age-related macular degeneration (AMD) and the progression rates of early stages of age-related maculopathy (ARM), and to study the hierarchy of fundus features that determine progression. METHODS: A group of 4953 subjects aged 55 years and older living in Rotterdam, The Netherlands, was studied at baseline and at 2-year follow-up to determine the incidence of neovascular and atrophic AMD. A subgroup of 1244 subjects was studied for progression of early stages of ARM. Fundus transparencies were graded for features of ARM using the International Classification System. ARM was stratified in four exclusive stages, according to type of drusen and presence of pigmentary irregularities. RESULTS: The overall 2-year cumulative incidence of AMD was 0.2%, increasing to 1.8% in subjects of 85 years and older. Of those in the early stages, one fourth showed progression to a more severe stage. The most important predictors for progression were more than 10% of macular area covered by drusen (odds ratio [OR] 5.7, 95% confidence interval [CI] 2.9-11.3), presence of depigmentation (OR 4.0, 95% CI 2.5-6.4), and hyperpigmentation (OR 3.4, 95% CI 2.1-5.4). CONCLUSIONS: The incidence of AMD appears to be lower in The Netherlands than in the United States. Progression of early ARM stages occurs in a distinct pattern at a stable rate, with a large area of drusen and presence of pigmentary changes as the most important predictors. http://repub.eur.nl/res/pub/19845/ 1999-06-09T00:00:00Z http://repub.eur.nl/res/pub/5918/ 1998-01-01T00:00:00Z OBJECTIVE: To investigate to what extent age-related maculopathy (ARM) is genetically determined. DESIGN AND SETTING: Familial aggregation study based on probands derived from the population-based Rotterdam Study. PARTICIPANTS: First-degree relatives of 87 patients with late ARM, i.e., atrophic or neovascular macular degeneration, were compared with first-degree relatives of 135 control subjects without ARM. MAIN OUTCOME MEASURES: Presence and stage of ARM as diagnosed on fundus transparencies, odds ratio, lifetime risk, risk ratio, and population-attributable risk. RESULTS: Independent of other risk factors, the prevalence of early (odds ratio = 4.8, 95% confidence interval [CI] = 1.8-12.2) and late (odds ratio = 19.8, 95% CI = 3.1-126.0) ARM was significantly higher in relatives of patients with late ARM. The lifetime risk estimate of late ARM was 50% (95% CI = 26%-73%) for relatives of patients vs 12% (95% CI = 2%-16%) for relatives of controls (P < .001), yielding a risk ratio of 4.2 (95% CI = 2.6-6.8). Relatives of patients expressed the various features of ARM at a younger age. The population-attributable risk related to genetic factors was 23%. CONCLUSIONS: First-degree relatives of patients with late ARM developed ARM at an increased rate at a relatively young age. Our findings indicate that approximately one fourth of all late ARM is genetically determined and suggest that genetic susceptibility may play an important role in determining the onset of disease. http://repub.eur.nl/res/pub/5919/ 1998-01-01T00:00:00Z OBJECTIVES: To study familial aggregation of primary open-angle glaucoma in a general population and to determine the absolute and relative risks for first-degree relatives. METHODS: First-degree relatives of patients with glaucoma (n = 48) and control subjects (n = 155) from the population-based Rotterdam Study underwent a standardized examination, including perimetry. MAIN OUTCOME MEASURES: Intraocular pressure, vertical cup-disc ratio; and the presence of glaucoma, defined as a visual field defect with a cup-disc ratio of 0.7 or higher or asymmetry of 0.3 or higher between both eyes. RESULTS: The prevalence of glaucoma was 10.4% in siblings of patients, 1.1% in offspring of patients, 0.7% in siblings of controls, and 0% in offspring of controls. Life-time risk of elevated intraocular pressure in relatives of patients vs relatives of controls was 42.5% vs 6.7%, of enlarged cup-disc ratio was 62.2% vs 16.6%, and of glaucoma was 22.0% vs 2.3%, yielding a risk ratio for glaucoma of 9.2 (95% confidence interval = 1.2-73.9). The population-attributable risk of glaucoma was 16.4%. CONCLUSIONS: In a general population, relatives of patients with glaucoma have a strongly increased risk of glaucoma. Enlarged cup-disc ratio, not intraocular pressure, was the earliest and most prominent feature of familial aggregation. Further studies are needed to disentangle the genetic components of the increased familial risk.