Progression of Late-Onset Stargardt Disease

PURPOSE. Identification of sensitive biomarkers is essential to determine potential effects of emerging therapeutic trials for Stargardt disease. This study aimed to describe the natural history of late-onset Stargardt, and demonstrates the accuracy of retinal pigment epithelium (RPE) atrophy progression as an outcome measure. METHODS. We performed a retrospective cohort study collecting multicenter data from 47 patients (91 eyes) with late-onset Stargardt, defined by clinical phenotype, at least one ABCA4 mutation, and age at disease onset >= 45 years. We analyzed RPE atrophy progression on fundus autofluorescence and near-infrared reflectance imaging using semiautomated software and a linear mixed model. We performed sample size calculations to assess the power in a simulated 2-year interventional study and assessed visual endpoints using time-to-event analysis. RESULTS. Over time, progression of RPE atrophy was observed (mean: 0.22 mm/year, 95% confidence interval [CI]: 0.19-0.27). By including only patients with bilateral RPE atrophy in a future trial, 32 patients are needed to reach a power of 83.9% (95% CI: 83.1-84.6), assuming a fixed therapeutic effect size of 30%. We found a median interval between disease onset and visual acuity decline to 20/32, 20/80, and 20/200 of 2.74 (95% CI: 0.54-4.41), 10.15 (95% CI: 6.13-11.38), and 11.38 (95% CI: 6.13-13.34) years, respectively. CONCLUSIONS. We show that RPE atrophy represents a robust biomarker to monitor disease progression in future therapeutic trials. In contrast, the variability in terms of the course of visual acuity was high

Prevalence of Age-Related Macular Degeneration in Europe: The Past and the Future

Purpose Age-related macular degeneration (AMD) is a frequent, complex disorder in elderly of European ancestry. Risk profiles and treatment options have changed considerably over the years, which may have affected disease prevalence and outcome. We determined the prevalence of early and late AMD in Europe from 1990 to 2013 using the European Eye Epidemiology (E3) consortium, and made projections for the future. Design Meta-analysis of prevalence data. Participants A total of 42 080 individuals 40 years of age and older participating in 14 population-based cohorts from 10 countries in Europe. Methods AMD was diagnosed based on fundus photographs using the Rotterdam Classification. Prevalence of early and late AMD was calculated using random-effects meta-analysis stratified for age, birth cohort, gender, geographic region, and time period of the study. Best-corrected visual acuity (BCVA) was compared between late AMD subtypes; geographic atrophy (GA) and choroidal neovascularization (CNV). Main Outcome Measures Prevalence of early and late AMD, BCVA, and number of AMD cases. Results Prevalence of early AMD increased from 3.5% (95% confidence interval [CI] 2.1%–5.0%) in those aged 55–59 years to 17.6% (95%

Implementing strabismus-specific psychosocial questionnaires in everyday clinical practice: mental health and quality of life in the context of strabismus surgery

Background Strabismus can have a great negative impact on the quality of life and the well-being of affected patients. In the past, these aspects were often neglected and, compared with somatic functioning, placed in the background. The aim of our study is to elicit factors influencing satisfaction with strabismus surgery, quality of life and expectations of surgery in order to better predict who will benefit the most and who may need further support.Methods We made a selection of suitable questionnaires to assess psychosocial aspects of strabismus and decided for Adult Strabismus 20 Questionnaire, Amblyopia and Strabismus Questionnaire, Diplopia Questionnaire, Expectations of Strabismus Surgery Questionnaire and Hospital Anxiety and Depression Scale. We then translated these measures (if not available in German). The patients filled out these forms as part of their preoperative orthoptic and ophthalmological assessment as well as approximately 3 months after strabismus surgery.Results We enrolled 59 patients in this study. Postoperative strabismus-related quality of life was higher after surgery and anxiety and depression levels were lower. Satisfaction with surgery was lower with higher postoperative angle and diplopia; the latter was also a determinant of lower postoperative quality of life. Higher expectations of strabismus surgery were present with higher depression levels and higher preoperative strabismus angle.Conclusion Our data indicate that strabismus surgery may cause a significant improvement in several psychosocial domains. There is evidence that psychosocial factors can have significant impact on expectations with surgery. Hence, it is important to consider mental health aspects of this disease in order to treat patients in the best possible way

Impact of visual impairment on physical activity in early and late age-related macular degeneration.

BACKGROUND:Modifiable risk factors for age-related macular degeneration (AMD) include smoking, nutrition and likely physical activity (PA). Levels of PA, however, are impacted by any visual impairment which makes the assessment of any association with AMD difficult. PURPOSE:To assess the impact of visual impairment under both high and low luminance conditions on levels of PA in early and late AMD. METHODS:Ninety participants with early to late AMD underwent a clinical assessment including conventional best-corrected visual acuity, low luminance visual acuity, contrast sensitivity and the Moorfields acuity test. PA was recorded using a wrist-worn accelerometer (GENEActiv, Activeinsights) on seven consecutive days. Patient characteristics were compared with the Wilcoxon rank-sum test and determinants of moderate-to-vigorous-PA (MVPA) were assessed using linear regression models. RESULTS:Mean age was 73.9 ± 8.5 years (range 50-89) and 47 subjects (52.2%) were women. Average MVPA time was longer in the early (355.1 ± 252.0 minutes/week) compared to the late AMD group (162.2 ± 134.6 minutes/week; p<0.001). Using linear regression, age [β = -0.25; 95% confidence interval (CI): -12.9; -0.8, p = 0.028] and AMD stage (β = -0.28; 95% CI: -230.9, -25.0; p = 0.015) but not visual impairment on any of the employed tests were associated with MVPA (minutes/week). CONCLUSIONS:We found late AMD to be associated with reduced PA. As performance on any of the visual tests was not associated with PA, this association cannot entirely be explained by functional impairment. More research is needed to further explore the association of PA and AMD as PA may be a potentially modifiable risk factor

Yokoyama procedure for esotropia associated with high myopia: real‐world data from a large‐scale multicentre analysis

Purpose High myopic patients may develop strabismus due to globe dislocation out of the normal extraocular muscle cone. Surgical correction of this strabismus type is possible by joining the superior and lateral rectus muscles without the need for a scleral suture called the Yokoyama procedure. Data from large patient samples and the evaluation of a potential effect of an additional medial rectus recession (MRR) have been lacking so far. Methods We pooled retrospective patient data of 14 departments of ophthalmology in Germany and Switzerland and analysed determinants of postoperative results using multivariable regression models. Results We included 133 patients (mean age: 59.7 ± 13.4 years, surgery between 2008 and 2017) with a mean preoperative esotropia (both Yokoyama with and without MRR) of 23.8°±4.6°. The angle of preoperative esotropia increased with age. The postoperative esotropia was 8.7° ± 9.9°, and six patients were overcorrected. While preoperative esotropia was highly associated with postoperative results, we found no association of additional MRR with any of our postoperative outcome measures. The Yokoyama procedure had a higher absolute effect in patients with higher preoperative esotropia. Conclusion Our study confirms the positive effect of the Yokoyama procedure on strabismus due to high myopia in large‐scale real‐world data. In some cases, MRR may be needed because of muscle contracture, although additional MRR statistically did not affect the postoperative outcome. In patients with bilateral high myopic strabismus, correction of both eyes seems beneficial. The effect size of the Yokoyama procedure appears to be mainly driven by preoperative esotropia

Association of lipid-lowering drugs, anti-diabetic drugs, non-steroidal anti-inflammatory drugs, and levodopa with age-related macular degeneration in Europeans: A meta-analysis of the European Eye Epidemiology (E3) - consortium

International audiencePurpose : Changes in lipid metabolism, chronic inflammation and increased oxidative stress have been discussed as patho-etiogenetic drivers in age-related macular degeneration (AMD). Systemic medication, such as lipid-lowering drugs (LLD) and anti-diabetic drugs, affect these pathways and may therefore also play a role in AMD pathogenesis. We aimed to investigate associations of commonly used systemic drugs with AMD prevalence in the European population.Methods : We included 38,694 adults from 14 population-based studies from the European Eye Epidemiology (E3) consortium. We performed multivariable logistic regression modelling to examine medication use association with prevalence of AMD as well as late AMD. Analyses were carried out separately by study and results pooled using random effects meta-analysis. We conducted these analyses separately for LLD, anti-diabetic drugs, non-steroidal anti-inflammatory drugs (NSAID), and L-Dopa.Results : Between studies, mean age ranged from 61.5 ± 7.1 to 82.6 ± 3.8 years and prevalence ranged from 12.1% to 64.5% and from 0.5% to 35.5% for any and any late AMD, respectively. In the meta-analysis of our multivariable models, LLD and anti-diabetic drugs were associated with lower AMD prevalence (OR 0.85, 95% confidence interval (CI)=0.79 - 0.91 and OR 0.78, 95% CI=0.66 - 0.91). We found no association with late AMD or with any other medication.Conclusions : Our study shows an association of LLD and anti-diabetic drug use with lower AMD prevalence across multiple European cohorts. Our findings support the importance of metabolic processes in the complex etiology of AMD

Physical activity, incidence and progression of age-related macular degeneration: A multi-cohort study.

PURPOSE: To investigate the impact of physical activity (PA) on the incidence or progression of age-related macular degeneration (AMD) in the general population. DESIGN: Meta-analysis of longitudinal cohort studies. METHODS: We included a total of 14,630 adults with no or early AMD at baseline from seven population-based studies and examined associations of PA with AMD incidence and progression using multi-state models (MSM) per study and subsequent random effects meta-analysis. Age effects were assessed using meta-regression. MAIN OUTCOME MEASURE: Hazard ratio (HR) for incident early or progression to late AMD. RESULTS: At baseline, mean age ranged from 60.7± 6.9 to 76.4 ± 4.3 years and prevalence of early AMD was 7.7%, ranging from 3.6 to 16.9% between cohorts. During follow-up, 1461 and 189 events occurred for early and late AMD, respectively. In meta-analyses, no or low to moderate PA (high PA as reference) was associated with an increased risk for incident early AMD (HR 1.19; 95%CI=[1.01, 1.40]; p=0.04), but not for late AMD. In subsequent meta-regression, we found no association of age with the effect of PA on incident AMD. CONCLUSIONS: Our study suggests high levels of PA to be protective for the development of early AMD across several population-based cohort studies. Our results establish PA as a modifiable risk factor for AMD and inform further AMD prevention strategies to reduce its public health impact

Association of lipid-lowering drugs and antidiabetic drugs with age-related macular degeneration: a meta-analysis in Europeans

International audienceBackground/aims To investigate the association of commonly used systemic medications with prevalent age-related macular degeneration (AMD) in the general population. Methods We included 38 694 adults from 14 population-based and hospital-based studies from the European Eye Epidemiology consortium. We examined associations between the use of systemic medications and any prevalent AMD as well as any late AMD using multivariable logistic regression modelling per study and pooled results using random effects meta-analysis. Results Between studies, mean age ranged from 61.5±7.1 to 82.6±3.8 years and prevalence ranged from 12.1% to 64.5% and from 0.5% to 35.5% for any and late AMD, respectively. In the meta-analysis of fully adjusted multivariable models, lipid-lowering drugs (LLD) and antidiabetic drugs were associated with lower prevalent any AMD (OR 0.85, 95% CI=0.79 to 0.91 and OR 0.78, 95% CI=0.66 to 0.91). We found no association with late AMD or with any other medication. Conclusion Our study indicates a potential beneficial effect of LLD and antidiabetic drug use on prevalence of AMD across multiple European cohorts. Our findings support the importance of metabolic processes in the multifactorial aetiology of AMD. HOW THIS STUDY MIGHT AFFECT RESEARCH, PRACTICE OR POLICY ⇒ These findings have implications for public health messages, underline the link of AMD with cardiovascular comorbidities and may provide potential future therapeutic targets