[Show abstract][Hide abstract] ABSTRACT: Purpose:
While exposure to ultraviolet radiation (UVR) is a recognized risk factor for cataract, its association is more controversial with age-related macular degeneration (AMD). We report the associations of lifetime exposure to ambient UVR with cataract extraction and AMD.
The Alienor Study is a population-based study of 963 residents of Bordeaux (France), aged 73 years or more. Lifetime exposure to ambient UVR was estimated from residential history and Eurosun satellite-based estimations of ground UVR. It was divided in three groups (lower quartile, intermediate quartiles, upper quartile), using the intermediate quartiles as the reference. Early and late AMD was classified from retinal color photographs. Cataract extraction was defined as absence of the natural lens at slit-lamp.
After multivariate adjustment, subjects in the upper quartile of lifetime ambient UVR exposure were at increased risk for cataract extraction (odds ratio [OR] = 1.53; 95% confidence interval [CI], 1.04-2.26; P = 0.03) and for early AMD (OR = 1.59; 95% CI, 1.04-2.44; P = 0.03), by comparison with subjects in the intermediate quartiles. Subjects in the lower quartile of UVR exposure also were at increased risk for early AMD (OR = 1.69; 95% CI, 1.06-2.69; P = 0.03), by comparison with those with medium exposure. Associations of late AMD with UVR exposure was not statistically significant.
This study further confirms the increased risk for cataract extraction in subjects exposed to high ambient UVR. Moreover, it suggests that risk for early AMD is increased in subjects exposed to high UVR, but also to low UVR, by comparison with medium exposures.
[Show abstract][Hide abstract] ABSTRACT: Lipid metabolism and particularly high-density lipoprotein (HDL) may be involved in the pathogenic mechanism of age-related macular degeneration (AMD). However, conflicting results have been reported in the associations of AMD with plasma HDL and other lipids, which may be confounded by the recently reported associations of AMD with HDL-related genes. We explored the association of AMD with plasma lipid levels and lipid-lowering medication use, taking into account most of HDL-related genes associated with AMD.
The Alienor study is a population-based study on age-related eye diseases performed in 963 elderly residents of Bordeaux (France). AMD was graded from non mydriatic color retinal photographs in three exclusive stages: no AMD (n = 430 subjects, 938 eyes); large soft distinct drusen and/or large soft indistinct drusen and/or reticular drusen and/or pigmentary abnormalities (early AMD, n = 176, 247); late AMD (n = 40, 61). Associations of AMD with plasma lipids (HDL, total cholesterol (TC), Low-density lipoprotein (LDL), and triglycerides (TG)) were estimated using Generalized Estimating Equation logistic regressions. Statistical analyses included 646 subjects with complete data.
After multivariate adjustment for age, sex, educational level, smoking, BMI, lipid-lowering medication use, cardiovascular disease and diabetes, and for all relevant genetic polymorphisms (ApoE2, ApoE4, CFH Y402H, ARMS2 A69S, LIPC rs10468017, LIPC rs493258, LPL rs12678919, ABCA1 rs1883025 and CETP rs3764261), higher HDL was significantly associated with an increased risk of early (OR = 2.45, 95%CI: 1.54-3.90; P = 0.0002) and any AMD (OR = 2.29, 95%CI: 1.46-3.59; P = 0.0003). Association with late AMD was far from statistical significance (OR = 1.58, 95%CI: 0.48-5.17; p = 0.45). No associations were found for any stage of AMD with TC, LDL and TG levels, statin or fibrate drug use.
This study suggests that elderly patients with high HDL concentration may be at increased risk for AMD and, further, that HDL dysfunction might be implicated in AMD pathogenesis.
PLoS ONE 03/2014; 9(3):e90973. DOI:10.1371/journal.pone.0090973 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Several genes implicated in high-density lipoprotein (HDL) metabolism have been reported to be associated with age-related macular degeneration (AMD). Furthermore, HDL transport the two carotenoids, lutein and zeaxanthin, which are highly suspected to play a key-role in the protection against AMD. The objective is to confirm the associations of HDL-related loci with AMD and to assess their associations with plasma lutein and zeaxanthin concentrations.
Alienor study is a prospective population-based study on nutrition and age-related eye diseases performed in 963 elderly residents of Bordeaux, France. AMD was graded according to the international classification, from non-mydriatic colour retinal photographs. Plasma lutein and zeaxanthin were determined by normal-phase high-performance liquid chromatography. The following polymorphisms were studied: rs493258 and rs10468017 (LIPC), rs3764261 (CETP), rs12678919 (LPL) and rs1883025 (ABCA1).
After multivariate adjustment, the TT genotype of the LIPC rs493258 variant was significantly associated with a reduced risk for early and late AMD (OR=0.64, 95%CI: 0.41-0.99; p=0.049 and OR=0.26, 95%CI: 0.08-0.85; p=0.03, respectively), and with higher plasma zeaxanthin concentrations (p=0.03), while plasma lipids were not significantly different according to this SNP. Besides, the LPL variant was associated with early AMD (OR=0.67, 95%CI: 0.45-1.00; p=0.05) and both with plasma lipids and plasma lutein (p=0.047). Associations of LIPC rs10468017, CETP and ABCA1 polymorphisms with AMD did not reach statistical significance.
These findings suggest that LIPC and LPL genes could both modify the risk for AMD and the metabolism of lutein and zeaxanthin.
PLoS ONE 11/2013; 8(11):e79848. DOI:10.1371/journal.pone.0079848 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Objective
Previous research has suggested an association between dementia and glaucoma through common risk factors or mechanisms. Our aim was to evaluate the longitudinal relationship between open-angle glaucoma (OAG) and incident dementia. Methods
The Three-City-Bordeaux-Alienor study is a population-based cohort of 812 participants with a 3-year follow-up period. All participants were aged 72 years or older. An eye examination was performed on all subjects. An OAG was determined based on optic nerve damage and visual field loss. Incident dementia was actively screened for and confirmed by a neurologist. ResultsA total of 41 participants developed dementia over the 3-year follow-up period. Future incident dementia cases had an increased prevalence of OAG (17.5% vs 4.5% for nondemented participants, p = 0.003). After adjustment for age, gender, education, family history of glaucoma, vascular comorbidities, and apolipoprotein epsilon 4, our results showed that participants with an OAG were four times more likely to develop dementia during the 3-year follow-up period (odds ratio = 3.9, 95% confidence interval = 1.5-10.4, p = 0.0054). An increased risk of dementia was also associated with 2 markers of optic nerve degeneration (vertical cup:disk ratio and minimal rim:disk ratio). However, no association was found between a high intraocular pressure and/or the use of intraocular pressure-lowering medications and incident dementia. InterpretationIf the association between OAG and dementia is confirmed, direct and noninvasive quantification of the amount of retinal ganglion cell axonal loss may be a useful biomarker of cerebral axonal loss in the future. It may also offer new breakthroughs in understanding the underlying pathophysiological mechanisms of both diseases.
Annals of Neurology 09/2013; 74(2). DOI:10.1002/ana.23926 · 9.98 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Retinal detachment (RD) describes a separation of the neurosensory retina from the retinal pigmented epithelium (RPE). The RPE is essential for normal function of the light sensitive neurons, the photoreceptors. Detachment of the retina from the RPE creates a physical gap that is filled with extracellular fluid. RD initiates cellular and molecular adverse events that affect both the neurosensory retina and the RPE since the physiological exchange of ions and metabolites is severely perturbed. The consequence for vision is related to the duration of the detachment since a rapid reapposition of the two tissues results in the restoration of vision (1). The treatment of RD is exclusively surgical. Removal of vitreous gel (vitrectomy) is followed by the removal non essential part of the retina around the detached area to favor retinal detachment. The removed retinal specimens are res nullius (nothing) and consequently normally discarded. To recover RNA from these surgical specimens, we developed the procedure jouRNAl that allows RNA conservation during the transfer from the surgical block to the laboratory. We also standardized a protocol to purify RNA by cesium chloride ultracentrifugation to assure that the purified RNAs are suitable for global gene expression analysis. The quality of the RNA was validated both by RT-PCR and microarray analysis. Analysis of the data shows a simultaneous involvement of inflammation and photoreceptor degeneration during RD.
Journal of Visualized Experiments 08/2013; DOI:10.3791/50375 · 1.33 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Purpose:
To describe dry eye disease in French elderly subjects.
The Alienor Study is a population-based study on age-related eye disease in 963 residents of Bordeaux (France), aged 73 years or more. Self-reported dry eye disease and use of artificial tears were documented through face-to-face interview. Dry eye symptoms were assessed using the Ocular Surface Disease Index (OSDI) questionnaire and tear film stability by tear break-up time measurements (TBUT). Definite dry eye disease was defined as self-reported dry eye, confirmed by use of artificial tears and/or OSDI greater or equal to 22.
Nine hundred and fifteen subjects, with mean age of 80 ± 4 years, returned the OSDI questionnaire. Of these, 271 (29.6%) subjects reported a dry eye disease and 135 (14.7%) were using artificial tears. An OSDI score > 22 was found in 359 (39.2%) subjects and a TBUT < 5 seconds in 335/746 (44.9%) subjects. Overall, definite dry eye affected 21.9% of subjects and was more frequent in women (27.1%) than in men (13.6%). After multivariate adjustment, dry eye disease was also significantly less frequent in subjects with high educational level (odds ratio (OR) = 0.49, 95% confidence interval (CI): 0.31-0.78 for long secondary school) and more frequent in subjects with ocular hypertension (OR = 1.61, 95% CI: 1.02-2.57) and those using anxiolytics (OR = 1.53, 95% CI: 1.02-2.29).
This large observational study confirmed the high prevalence of dry eye symptoms among elderly subjects and confirmed some of the previously identified risk factors (in particular female gender and use of anxiolytics).
[Show abstract][Hide abstract] ABSTRACT: High dietary intakes of n3 (Ω3) PUFA and fish have been consistently associated with a decreased risk for age-related macular degeneration (AMD). We assessed the associations of late AMD with plasma n3 PUFA, a nutritional biomarker of n3 PUFA status. The Antioxydants Lipides Essentiels Nutrition et Maladies Occulaires (Alienor) Study is a prospective, population-based study on nutrition and age-related eye diseases performed in 963 residents of Bordeaux (France) aged ≥73 y. Participants had a first eye examination in 2006-2008 and were followed for 31 mo on average. Plasma fatty acids were measured by GC from fasting blood samples collected in 1999-2001. AMD was graded from non-mydriatic color retinal photographs at all examinations and spectral domain optical coherence tomography at follow-up. After adjustment for age, gender, smoking, education, physical activity, plasma HDL-cholesterol, plasma TGs, CFH Y402H, apoE4, and ARMS2 A69S polymorphisms, and follow-up time, high plasma total n3 PUFA was associated with a reduced risk for late AMD [OR = 0.62 for 1-SD increase (95% CI: 0.44-0.88); P = 0.008]. Associations were similar for plasma 18:3n3 [OR = 0.62 (95% CI: 0.43-0.88); P = 0.008] and n3 long-chain PUFA [OR = 0.65 (95% CI: 0.46-0.92); P = 0.01]. This study gives further support to the potential role of n3 PUFAs in the prevention of late AMD and highlights the necessity of randomized clinical trials to determine more accurately the value of n3 PUFAs as a means of reducing AMD incidence.
Journal of Nutrition 02/2013; 143(4). DOI:10.3945/jn.112.171033 · 3.88 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Purpose:
To explore the association of AMD with long-term average blood pressure (BP) parameters, including pulse pressure (PP).
The ALIENOR study is a population-based study on age-related eye diseases in 963 residents of Bordeaux, France, aged 73 years or older. AMD was graded from nonmydriatic color retinal photographs, in three exclusive stages: no AMD (1015 eyes), large soft distinct drusen and/or large soft indistinct drusen and/or reticular drusen and/or pigmentary abnormalities (early AMD, 276 eyes), and late AMD (66 eyes). BP parameters were measured at four occasions over a 7-year period. PP was defined as systolic BP minus diastolic BP. Associations of AMD with BP parameters were estimated using generalized estimating equation logistic regressions. Statistical analyses included 702 subjects (1357 eyes) with complete data.
After adjustment for age, sex, educational level, smoking, body mass index, plasma HDL and LDL cholesterol, CFH Y402H, ApoE2, ApoE4, and ARMS2 A69S polymorphisms, elevated PP was significantly associated with an increased risk of late AMD (odds ratio [OR] = 1.37 for a 10-mm Hg increase, 95% confidence interval [CI]: 1.03-1.82). Associations were similar for late atrophic and late neovascular AMD (OR = 1.39, 95% CI: 1.01-1.92, P = 0.04, and OR = 1.43, 95% CI: 0.90-2.23, P = 0.13, respectively). Association with early AMD was in the same direction but did not reach statistical significance (OR = 1.12, 95% CI: 0.98-1.28). Early and late AMD were not significantly associated with systolic or diastolic BP, hypertension, or use of antihypertensive medications.
This study suggests that high PP may be associated with increased risk for AMD.
[Show abstract][Hide abstract] ABSTRACT: To assess the correlation between macular pigment optical density and plasma levels of lutein, zeaxanthin, and fatty acids, especially omega-3 polyunsaturated fatty acids (PUFAs).
The PIMAVOSA study is an observational study of 107 healthy volunteers, aged 20 to 60 years and born in southwest France, without histories of ocular disease. Macular pigment optical density (MPOD) was measured using the two-wavelength autofluorescence method with a modified scanning laser ophthalmoscope. Plasma measurements (lutein, zeaxanthin, and fatty acids) were performed from fasting blood samples collected on the day of the eye examination.
MPOD within 6° correlated with plasma levels of lutein and zeaxanthin (r = 0.35, P < 0.001, and r = 0.30, P < 0.005, respectively). MPOD also significantly correlated with total plasma omega-3 PUFAs (r = 0.22, P < 0.05). Among the different omega-3 PUFAs, docosapentaenoic acid (DPA) had the highest correlation with MPOD (r = 0.31, P < 0.001), whereas correlation with eicosapentaenoic acid (EPA) was moderate (r = 0.21, P < 0.05) and did not reach statistical significance for docosahexaenoic acid (r = 0.14, P = 0.14).
In the present study, macular pigment density was associated not only with plasma lutein and zeaxanthin but also with omega-3 long-chain PUFAs, particularly with EPA and DPA. Further studies will be needed to confirm these findings and to identify the underlying mechanisms.
[Show abstract][Hide abstract] ABSTRACT: Retinal detachment often leads to a severe and permanent loss of vision and its therapeutic management remains to this day exclusively surgical. We have used surgical specimens to perform a differential analysis of the transcriptome of human retinal tissues following detachment in order to identify new potential pharmacological targets that could be used in combination with surgery to further improve final outcome.
Statistical analysis reveals major involvement of the immune response in the disease. Interestingly, using a novel approach relying on coordinated expression, the interindividual variation was monitored to unravel a second crucial aspect of the pathological process: the death of photoreceptor cells. Within the genes identified, the expression of the major histocompatibility complex I gene HLA-C enables diagnosis of the disease, while PKD2L1 and SLCO4A1 -which are both down-regulated- act synergistically to provide an estimate of the duration of the retinal detachment process. Our analysis thus reveals the two complementary cellular and molecular aspects linked to retinal detachment: an immune response and the degeneration of photoreceptor cells. We also reveal that the human specimens have a higher clinical value as compared to artificial models that point to IL6 and oxidative stress, not implicated in the surgical specimens studied here.
This systematic analysis confirmed the occurrence of both neurodegeneration and inflammation during retinal detachment, and further identifies precisely the modification of expression of the different genes implicated in these two phenomena. Our data henceforth give a new insight into the disease process and provide a rationale for therapeutic strategies aimed at limiting inflammation and photoreceptor damage associated with retinal detachment and, in turn, improving visual prognosis after retinal surgery.
PLoS ONE 12/2011; 6(12):e28791. DOI:10.1371/journal.pone.0028791 · 3.23 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: Previous studies have suggested a lower risk for age-related maculopathy (ARM) in subjects with high dietary intake of long-chain omega-3 polyunsaturated fatty acids (PUFA). The authors report the associations of ARM with past dietary intakes in French elderly subjects.
The Alienor Study is a population-based epidemiologic study on nutrition and age-related eye diseases performed in residents of Bordeaux 73 years of age and older. Six hundred sixty-six subjects (1289 eyes) with complete data were included in the analyses. ARM was classified from retinal photographs taken in 2006 to 2008 in five exclusive stages: late neovascular ARM (n = 21 subjects, 29 eyes); late atrophic ARM (n = 19 subjects, 33 eyes); large soft indistinct drusen and/or reticular drusen and/or large distinct drusen with pigment abnormalities (early ARM2, n = 67 subjects, 100 eyes); large soft distinct drusen alone or pigment abnormalities alone (early ARM1, n = 119 subjects, 163 eyes); and no ARM (n = 440 subjects, 964 eyes). Dietary intakes were estimated from a 24-hour dietary recall performed by dieticians (2001-2002). Associations were estimated using logistic Generalized Estimating Equation.
After multivariate adjustment, subjects with high intake of long-chain omega-3 PUFA showed a decreased risk for early ARM1 (odds ratio [OR], 0.83; 95% confidence interval [95% CI], 0.71-0.98; P = 0.03) and late neovascular ARM (OR, 0.26; 95% CI, 0.08-0.83; P = 0.02). Associations with late atrophic ARM were in the same direction but did not reach statistical significance (OR, 0.74; 95% CI, 0.52-1.06; P = 0.10). Overall, high intakes of long-chain omega-3 PUFA were associated with reduced risk for late ARM (OR, 0.59; 95% CI, 0.39-0.88; P = 0.01).
These results confirm a decreased risk for ARM in subjects with high intake of long-chain omega-3 PUFA.
[Show abstract][Hide abstract] ABSTRACT: To assess the associations of complement factor H (CFH) Y402H polymorphism and smoking with specific features of early AMD (type, location, and area).
The ALIENOR study is a population-based study of age-related eye diseases in 963 residents of Bordeaux (France), aged 73 years or more. AMD features were graded from nonmydriatic color retinal photographs. CFH Y402H was genotyped by using DNA extracted from blood. Statistical analyses included 796 subjects with complete data.
CFH CC genotype was strongly associated with late neovascular AMD (OR, 6.0; 95% confidence interval [CI], 1.5-23.5) but not with late atrophic AMD (OR, 0.9; 95% CI, 0.2-4.3). Among early characteristics, it was associated with central soft drusen (within 500 μm of the fovea), whether of intermediate (63-125 μm; OR, 2.7; 95% CI, 1.5-4.8), or large (>125 μm; OR, 5.9; 95% CI, 2.2-15.7) size, but not with pericentral soft drusen (500-3000 μm from the fovea). It was also strongly associated with a large central area of soft drusen (OR, 5.7; 95% CI, 1.7-19.2). Similarly, heavy smoking (>20 pack-years) was strongly associated with central large drusen (OR, 3.9; 95% CI, 1.6-9.6) and a large central area of drusen (OR, 3.5; 95% CI, 1.2-10.0), but not with pericentral soft drusen. By contrast, both CFH CC and smoking tended to be more strongly associated with pericentral pigmentary abnormalities.
Location of abnormalities, together with type and area, may prove useful for the identification of subjects at high risk for late AMD.
[Show abstract][Hide abstract] ABSTRACT: To report cases of intraocular inflammation after intracameral injection of a very high dose of cefuroxime at the end of uneventful cataract surgery.
Department of Ophthalmology, Bordeaux University Hospital, Bordeaux, France.
Patients were followed on an outpatient basis and were examined postoperatively at 1 and 5 days and 6 weeks. Central macular thickness, angiography, central corneal thickness (CCT), endothelial cell density (ECD), and electroretinography (ERG) were analyzed to evaluate ocular toxicity.
One day postoperatively, the mean corrected distance visual acuity (CDVA) was 0.95 logMAR ± 0.40 (SD). All the cases had moderate anterior inflammation. Retinal optical coherence tomography scans systematically showed extensive macular edema (mean 843.2 ± 212.7 μm) associated with a large serous retinal detachment. Fluorescein angiograms showed diffuse leakage without abnormal retinal perfusion. At 5 days, the mean CDVA improved significantly to 0.52 ± 0.29 logMAR (P < .005), as did the macular edema and serous retinal detachment (mean 339.4 ± 138.3 μm) (P = .005). At 6 weeks, the mean CDVA reached 0.09 ± 0.06 logMAR. Modifications in CCT and ECD were similar to those observed after uneventful phacoemulsification. The macular thickness (mean 288.4 ± 22.6 μm) and profile returned to normal in all patients, although ERG recordings showed reduced rod photoreceptor cell function (P < .05).
Intracameral injection of high doses of cefuroxime induced anterior and posterior inflammation. Without surgical intervention, the final visual outcome was satisfactory in all cases. Long-term retinal function, however, must be assessed through repeated ERG recordings.
Journal of Cataract and Refractive Surgery 02/2011; 37(2):271-8. DOI:10.1016/j.jcrs.2010.08.047 · 2.72 Impact Factor
[Show abstract][Hide abstract] ABSTRACT: A 57-year-old man was referred for a painful acute inferior visual field defect in his right eye. Fundus examination of the right eye revealed diffuse optic disc oedema compatible with a papillitis. Cerebrospinal fluid (CSF) findings were consistent with lymphocytic meningitis, and serologic tests for Lyme disease were positive in both serum and CSF. After treatment with ceftriaxone and bolus of methylprednisolone, right eye inferior altitudinal visual field defect persisted despite resolution of papillitis, and fundus examination disclosed a superior optic atrophy in the right eye. To our knowledge, it is the first reported case of a unilateral Lyme optic neuritis occurring simultaneously to neuroborreliosis and further complicated by non-arteritic anterior ischaemic optic neuropathy.