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.
Purpose
There is an urgent need to address how to best provide ophthalmic care for patients with retinal disease receiving intravitreal injections with anti-vascular endothelial growth factor agents ...during the ongoing global COVID-19 pandemic. This article provides guidance for ophthalmologists on how to deliver the best possible care for patients while minimizing the risk of infection.
Methods
The Vision Academy’s Steering Committee of international retinal disease experts convened to discuss key considerations for managing patients with retinal disease during the COVID-19 pandemic. After reviewing the existing literature on the issue, members put forward recommendations that were systematically refined and voted on to develop this guidance.
Results
The considerations focus on the implementation of steps to minimize the exposure of patients and healthcare staff to COVID-19. These include the use of personal protective equipment, adherence to scrupulous hygiene and disinfection protocols, pre-screening to identify symptomatic patients, and reducing the number of people in waiting rooms. Other important measures include triaging of patients to identify those at the greatest risk of irreversible vision loss and prioritization of treatment visits over monitoring visits where possible. In order to limit patient exposure, ophthalmologists should refrain from using treatment regimens that require frequent monitoring.
Conclusion
Management of patients with retinal disease receiving intravitreal injections during the COVID-19 pandemic will require adjustment to regular clinical practice to minimize the risk of exposure of patients and healthcare staff, and to prioritize those with the greatest medical need. The safety of patients and healthcare staff should be of paramount importance in all decision-making.
Given the anatomical and functional similarities between the retina and the brain, the retina could be a “window” for viewing brain structures. We investigated the association between retinal nerve ...fiber layers (peripapillary retinal nerve fiber layer, ppRNFL; macular ganglion cell‐inner plexiform layer, GC‐IPL; and macular ganglion cell complex, GCC), and brain magnetic resonance imaging (MRI) parameters in young health adults. We included 857 students (mean age: 23.3 years, 71.3% women) from the i‐Share study. We used multivariate linear models to study the cross‐sectional association of each retinal nerve layer thickness assessed by spectral‐domain optical coherence tomography (SD‐OCT) with structural (volumes and cortical thickness), and microstructural brain markers, assessed on MRI globally and regionally. Microstructural MRI parameters included diffusion tensor imaging (DTI) and Neurite Orientation Dispersion and Density Imaging (NODDI). On global brain analysis, thicker ppRNFL, GC‐IPL and GCC were all significantly associated with patterns of diffusion metrics consistent with higher WM microstructural integrity. In regional analyses, after multiple testing corrections, our results suggested significant associations of some retinal nerve layers with brain regional gray matter occipital volumes and with diffusion MRI parameters in a region involved in the visual pathway and in regions containing associative tracts. No associations were found with global volumes or with global or regional cortical thicknesses. Results of this study suggest that some retinal nerve layers may reflect brain structures. Further studies are needed to confirm these results in young subjects.
In a sample composed exclusively of young healthy subjects, we found significant associations between retinal nerve layers with occipital brain volumes, and with brain diffusion MRI parameters, globally and in regions containing associative, commissural tracts, and in a projection area involved in the visual pathway. Our results suggest common maturational processes in the retina and the brain. Further studies are needed to confirm these results and to study common factors that might explain the parallel maturation of the retina and the brain.
.
Purpose: To describe dry eye disease in French elderly subjects.
Methods: 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.
Results: 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).
Conclusions: 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).
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.
To document reticular pseudodrusen (RPD) using multimodal imaging in French elderly subjects.
A total of 494 subjects (970 eyes) aged 77 years or more, from the Alienor study, were examined in 2011 ...and 2012. Reticular pseudodrusen were defined as definite if they were present with at least two imaging methods among color retinal photographs, macular cube (20° × 15°) of spectral-domain optical coherence tomography (SD-OCT), fundus autofluorescence (FAF), and infrared reflectance (IR). The Youden index was calculated as specificity + sensitivity - 1.
The prevalence of definite RPD was 13.4% and was higher among women (15.6%) than men (10.2%). It increased with age and reached almost 50% in subjects over 85 years. Infrared reflectance was the most sensitive technique (100%) and color fundus photography the least sensitive (34.5% at left eyes and 48.1% at right eyes). The best Youden index was obtained with IR (0.96 at both eyes) followed by SD-OCT (0.87 at right eye and 0.78 at left eye). Reticular pseudodrusen were present in 4.6% of eyes without AMD, 13.0% with early AMD1, 62.6% with early AMD2, 34.6% with atrophic AMD, and 8.1% with neovascular AMD. Reticular pseudodrusen were significantly associated with central and pericentral intermediate soft drusen (odds ratio OR: 2.14; 95% confidence interval CI = 1.11-4.14 and OR: 1.49; 95% CI = 1.16-1.90, respectively) and central large soft drusen (OR: 1.67; 95% CI = 1.16-2.42).
Using multimodal imaging, the prevalence of RPD appears higher than previously reported in studies based on retinal photography only. Reticular pseudodrusen frequently accompany other signs of AMD. Infrared reflectance and SD-OCT appear to be particularly relevant methods to diagnose RPD.
A head-to-head comparison was performed between vascular endothelial growth factor blockade and laser for treatment of diabetic macular edema (DME).
Two similarly designed, double-masked, randomized, ...phase 3 trials, VISTA(DME) and VIVID(DME).
We included 872 patients (eyes) with type 1 or 2 diabetes mellitus who presented with DME with central involvement.
Eyes received either intravitreal aflibercept injection (IAI) 2 mg every 4 weeks (2q4), IAI 2 mg every 8 weeks after 5 initial monthly doses (2q8), or macular laser photocoagulation.
The primary efficacy endpoint was the change from baseline in best-corrected visual acuity (BCVA) in Early Treatment Diabetic Retinopathy Study (ETDRS) letters at week 52. Secondary efficacy endpoints at week 52 included the proportion of eyes that gained ≥ 15 letters from baseline and the mean change from baseline in central retinal thickness as determined by optical coherence tomography.
Mean BCVA gains from baseline to week 52 in the IAI 2q4 and 2q8 groups versus the laser group were 12.5 and 10.7 versus 0.2 letters (P < 0.0001) in VISTA, and 10.5 and 10.7 versus 1.2 letters (P < 0.0001) in VIVID. The corresponding proportions of eyes gaining ≥ 15 letters were 41.6% and 31.1% versus 7.8% (P < 0.0001) in VISTA, and 32.4% and 33.3% versus 9.1% (P < 0.0001) in VIVID. Similarly, mean reductions in central retinal thickness were 185.9 and 183.1 versus 73.3 μm (P < 0.0001) in VISTA, and 195.0 and 192.4 versus 66.2 μm (P < 0.0001) in VIVID. Overall incidences of ocular and nonocular adverse events and serious adverse events, including the Anti-Platelet Trialists' Collaboration-defined arterial thromboembolic events and vascular deaths, were similar across treatment groups.
At week 52, IAI demonstrated significant superiority in functional and anatomic endpoints over laser, with similar efficacy in the 2q4 and 2q8 groups despite the extended dosing interval in the 2q8 group. In general, IAI was well-tolerated.
To demonstrate noninferiority of a quarterly treatment regimen to a monthly regimen of ranibizumab in patients with subfoveal choroidal neovascularization (CNV) secondary to age-related macular ...degeneration (AMD).
A 12-month, multicenter, randomized, double-masked, active-controlled, phase IIIb study.
Patients with primary or recurrent subfoveal CNV secondary to AMD (353 patients), with predominantly classic, minimally classic, or occult (no classic component) lesions.
Patients were randomized (1:1:1) to 0.3 mg quarterly, 0.5 mg quarterly, or 0.3 mg monthly doses of ranibizumab. Treatment comprised of a loading phase (3 consecutive monthly injections) followed by a 9-month maintenance phase (either monthly or quarterly injection).
Mean change in best-corrected visual acuity (BCVA) and central retinal thickness (CRT) from baseline to month 12 and the incidence of adverse events (AEs).
In the per-protocol population (293 patients), BCVA, measured by Early Treatment Diabetic Retinopathy Study-like charts, increased from baseline to month 12 by 4.9, 3.8, and 8.3 letters in the 0.3 mg quarterly (104 patients), 0.5 mg quarterly (88 patients), and 0.3 mg monthly (101 patients) dosing groups, respectively. Similar results were observed in the intent-to-treat (ITT) population (353 patients). The mean decrease in CRT from baseline to month 12 in the ITT population was -96.0 μm in 0.3 mg quarterly, -105.6 μm in 0.5 mg quarterly, and -105.3 μm in 0.3 mg monthly group. The most frequent ocular AEs were conjunctival hemorrhage (17.6%, pooled quarterly groups; 10.4%, monthly group) and eye pain (15.1%, pooled quarterly groups; 20.9%, monthly group). There were 9 ocular serious AEs and 3 deaths; 1 death was suspected to be study related (cerebral hemorrhage; 0.5 mg quarterly group). The incidences of key arteriothromboembolic events were low.
After 3 initial monthly ranibizumab injections, both monthly (0.3 mg) and quarterly (0.3 mg/0.5 mg) ranibizumab treatments maintained BCVA in patients with CNV secondary to AMD. At month 12, BCVA gain in the monthly regimen was higher than that of the quarterly regimens. The noninferiority of a quarterly regimen was not achieved with reference to 5.0 letters. The safety profile was similar to that reported in prior ranibizumab studies.
While the prevalence of age-related macular degeneration (AMD) differs according to continents and races/ethnicities, its incidence in the European continent has been scarcely documented.
To describe ...the incidence and associated risk factors of AMD in elderly French individuals.
This population-based cohort study of 963 residents of Bordeaux, France, who were 73 years or older at baseline and participated in the Antioxydants, Lipides Essentiels, Nutrition et Maladies Oculaires (ALIENOR) Study between October 2, 2006, and December 21, 2012. Of 829 participants at risk for incident AMD, 659 (79.5%) were observed for a mean (SD) duration of 3.8 (1.1) years. Data were analyzed from August 2016 to March 2017.
Age-related macular degeneration was graded from retinal photographs and spectral-domain optical coherence tomography into 5 exclusive stages: no AMD, early AMD1, early AMD2, late atrophic AMD, and late neovascular AMD.
Of the 659 eligible participants, 413 (62.7%) were women, and the mean (SD; range) age was 79.7 (4.4; 73-94) years. A total of 120 incident cases of early AMD and 45 incident cases of advanced AMD were recorded. Incidence rates of early and advanced AMD were 79.9 (95% CI, 66.8-95.5) per 1000 person-years and 18.6 (95% CI, 13.9-24.9) per 1000 person-years, respectively, corresponding to 5-year risks of 32.9% and 8.9%. Incidence of advanced AMD per 1000 eye-years was 1.5 in eyes without any AMD at baseline, 42.4 in those with early AMD1, and 85.1 in those with early AMD2. In multivariate analysis without correction for multiple testing, progression from early to advanced AMD was associated with AMD grade in the fellow eye (hazard ratio HR according to grade, 13.0 95% CI, 2.8-61.2 to 22.5 95% CI, 2.6-195.9), having smoked at least 20 pack-years (calculated as number of smoking years × mean number of cigarettes per day / 20; HR, 3.0; 95% CI, 1.4-6.5), and complement factor H (CFH) Y402H genotype (CC genotype: HR, 2.3; 95% CI, 1.0-5.3; TC genotype: HR, 1.5; 95% CI, 0.6-3.7). Incidence of early AMD was associated with early AMD in the fellow eye (early AMD1: HR, 2.6; 95% CI, 1.6-4.2; early AMD2: HR, 5.6; 95% CI, 3.3-9.4) and high plasma high-density lipoprotein cholesterol levels (HR, 1.2; 95% CI, 1.0-1.4).
In this cohort, AMD incidence rates were similar to those observed in other European populations. This study suggests a high risk for incident early AMD in individuals with high plasma high-density lipoprotein cholesterol levels while confirming the high risk for progression from early to advanced AMD in heavy smokers and carriers of CFH Y402H at-risk genotypes.
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.
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.
A 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 ε4, 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.
If 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.
PDF
