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Purpose: Cataract and glaucoma are among the leading causes of blindness worldwide in older people, and they are often concomitant. To assess topical intraocular (IOP)-lowering agents delivery changes after cataract extraction. Material and methods: Longitudinal matched exposed–unexposed study from the French national healthcare database from January 1, 2005 to January 1, 2017. We compared individuals using topical IOP-lowering agents who underwent bilateral cataract extraction with individuals matched on IOP-lowering agents load, age, and sex who did not undergo cataract extraction. IOP-lowering agents number of drops was assessed 12 months before the first cataract extraction and compared with number of drops 12 months after the second cataract extraction. Results: About 1194 individuals treated with IOP-lowering agents were included, 597 exposed to bilateral cataract extraction and 597 unexposed to any surgery (total mean age 74.8 ± 8.3 years; 69.0% women). Mean IOP-lowering agents delivery at baseline was 1.4 daily drops in both groups. The mean number of drops decreased greater in the exposed than unexposed group (−25.5% vs −3.5%; p < 0.0001). Overall, 159 (26.6%) and 48 (8.0%) individuals in the exposed and unexposed groups interrupted medication ( p < 0.0001). Conclusions: A decrease of around one quarter of IOP-lowering agents delivery was observed after cataract extraction in the present real-life study with a longstanding interruption observed in one quarter of patients. Phacoemulsification as a standalone procedure reduces IOP-lowering agents delivery in ocular hypertension and glaucoma.

Background The 96 weeks’ assessment from the VIEW studies provided insights into the long-term efficacy of intravitreal aflibercept (IVT-AFL) in neovascular age-related macular degeneration (nAMD) and demonstrated that it was possible to maintain long-term outcomes while moving from a fixed bimonthly regimen in Year 1 to a variable dosing regimen in Year 2. The aim of this analysis was to perform a literature review and meta-analysis assessing the use of IVT-AFL and real-world outcomes in treatment-naïve patients with nAMD treated with IVT-AFL for 2 years, as per label. Methods A literature review and meta-analysis were performed to provide an overview of the baseline characteristics of the population, the 2-year outcomes, the associated treatment burden, and safety. Results Eleven publications providing data from patients with nAMD who had treatment initiated with IVT-AFL between 2012 and 2016 were identified. The mean baseline age of patients was 78.62 years, with a baseline best-corrected visual acuity (BCVA) of 57.73 Early Treatment Diabetic Retinopathy Study (ETDRS) letters. Patients reported a mean BCVA at 2 years of 62.55 ETDRS letters, with 47.39% of patients having a BCVA ≥ 70 ETDRS letters. Mean gain in BCVA versus baseline was + 4.49 ETDRS letters for the combined population (+ 5.91 letters for patients treated with a treat-and-extend regimen). Over the 2 years of the study, patients received an average of 12.34 injections, with a reduction in injections in Year 2 versus Year 1. The qualitative assessment of the safety data suggested that no new safety signals were identified. Conclusion Patients treated with IVT-AFL reported significant gains in visual acuity versus baseline after 2 years. The evidence identified indicates that the visual gains achieved during the first year of treatment are maintained through the second year and that these were achieved with a reduction in the mean number of IVT-AFL injections administered in Year 2 of treatment. Supplementary Information The online version contains supplementary material available at 10.1007/s40123-021-00350-5.

Background Evaluate risk factors for paediatric myopia in a contemporary French cohort taking into account consumption of refined carbohydrates (starches and sugars). Methods An epidemiological cross-sectional study was conducted between May 2017 and May 2018. Two hundred sixty-four children aged 4 to 18 years attending the Centre Hospitalier Universitaire Gui de Chauliac in Montpellier were recruited. Ophthalmologic or optometric cycloplegic refraction were measured. Evaluated risk factors for myopia were collected, including family history of myopia, outdoor time, reading time, screen time, physical activity, and consumption of refined carbohydrates. Association between the probability of at least one eye showing myopia (defined as Results Overall, 86/264 (32.6%) children investigated showed myopia in at least one eye. We included 180 children exhibiting refraction P = 0.009) but decreased it for boys (OR = 0.94; 95% CI, 0.89–0.98; P = 0.011). The probability of myopia was marginally increased with increased screen time (OR = 2.32; 95% CI, 0.94–6.47; P = 0.083). Outdoor time seemed marginally protective (OR = 0.74; 95% CI, 0.54–1.01; P = 0.057). Conclusion Refined carbohydrates consumption could be associated with child myopia, with increased probability for girls and unexpected reduced probability for boys, possibly due to the fact that frequency of carbohydrates consumption do not really capture boy’s chronic hyperglycemia, boys being more physically active than girls at all ages. Some known risk/protective factors of myopia were marginally significant: screen time (risk) and outdoor time (protective). This study reinforces the belief that modifiable risk factors for myopia could be targets for future public health actions.

International audience; PURPOSE: The aim of this study was to investigate the prevalence of vitreomacular interface abnormalities (VMIAs) and to identify associated factors in an elderly population in Europe. METHODS: The MONTRACHET (Maculopathy Optic Nerve nuTRition neurovAsCular and HEarT diseases) Study is a population-based study, conducted in subjects older than 75 years. Vitreomacular adhesions, vitreomacular tractions, macular holes, epiretinal membranes, and macular cysts were assessed on spectral-domain optical coherence tomography examinations. The prevalence of VMIAs was estimated. We studied the association of demographic and clinical factors with VMIAs. RESULTS: The mean age of the participants was 82.3 (SD, 3.8) years, and 37.3% were men. The prevalence rates of VMIAs were vitreomacular adhesions (17.7%), vitreomacular tractions (1.4%), lamellar macular holes (1.0%), full-thickness macular holes (0.2%), macular pseudoholes (0.4%), epiretinal membranes (38.9%), and macular cysts (5.8%). In multivariate analysis, vitreomacular adhesions were positively associated with male sex (P < 0.001) and negatively associated with older age (P < 0.001) and cataract extraction (P < 0.001). Epiretinal membranes were positively associated with older age (P < 0.001) and cataract extraction (P < 0.001). CONCLUSION: The prevalence of VMIAs based on spectral-domain optical coherence tomography analysis was high in subjects older than 75 years.

Purpose: To describe the use of eye care services among adults treated for diabetes from 2008 to 2017 in the French population. Methods: We used a random representative sampling of the French national health insurance database. Participants were adults treated for diabetes. Data regarding visits to ophthalmologists, eye examination procedures, and medical treatments were extracted using reimbursement codes. Cross-sectional analyses of eye care claims were performed each year from 2008 to 2017. Results: Less than 50% of people with diabetes underwent an annual eye examination (2008: 44.7%; 2017: 47.9%), and less than two-thirds underwent a biennial eye examination (2008–2009: 62.6%; 2016–2017: 66.4%). From 2008 to 2017, the yearly use of optical coherence tomography examinations increased steadily and markedly from 2.7% to 16.2%, while the use of fluorescein and indocyanine green angiographies decreased from 2.4% to 0.9%. In the same period, the yearly rate of intravitreal injection increased from 0.3% to 1.5%, and the use of laser photocoagulation decreased progressively from 2008 to 2014 (1.3% vs. 0.7%) but slightly increased from 2015 to 2017 (0.8% vs. 1.0%). Conclusions: Strategies to increase compliance with eye care recommendations are needed to improve early detection and management of diabetic eye complications.

Purpose To investigate the incidence, characteristics, and baseline predictors of poor visual outcomes in eyes with neovascular age-related macular degeneration (nAMD) receiving intravitreal anti–vascular endothelial growth factor (anti-VEGF) agents in daily clinical practice. Design Observational study. Participants Treatment-naive eyes starting anti-VEGF therapy for nAMD between 2007 and 2012 tracked in the Fight Retinal Blindness! registry. Eyes had sustained ≥15 letters of loss from baseline without recovery of visual acuity (VA) at final end point. A subgroup analysis included eyes that sustained ≥30 letters of loss. Controls had not sustained ≥15 letters of loss. Methods Kaplan–Meier curves estimated time to first development of loss of ≥15 letters. Cox proportional hazards models evaluated predictors of loss of ≥15 letters. Main Outcome Measures The proportion of eyes with sustained VA loss within 5 years, the time to development of sustained VA loss, and baseline predictors of sustained VA loss. Results There were 1760 eyes in total and 856 eyes that completed 5 years follow-up. The proportion of eyes with sustained VA loss of ≥15 letters at 5 years was 22.9% (95% confidence interval [CI], 20.7%–25.1%) and VA loss of ≥30 letters was 10.8% (95% CI, 9.1%–12.5%). Factors independently associated with higher incidence of sustained ≥15-letter loss included age >80 years (odds ratio [OR], 1.33 for patients >80 years vs. ≤80 years; 95% CI, 1.05–1.69; P = 0.02), fewer injections (OR, 0.97 per injection; 95% CI, 0.96–0.98; P = 0.0005), and more visits at which the choroidal neovascularization was graded as active (OR, 1.97 for eyes in upper quartile of active visits vs. eyes in lowest quartile of active visits; 95% CI, 1.39–2.79; P = 0.0001). Baseline VA ≥70 letters was associated with reduced risk of sustained ≥30-letter loss (OR, 0.61; 95% CI, 0.38–0.98; P = 0.04). Baseline angiographic lesion criteria were not significantly associated with sustained VA loss. Conclusions Twenty-three percent of eyes with nAMD developed sustained VA loss of ≥15 letters over 5 years of anti-VEGF therapy. Baseline predictors of poor outcomes provide more accurate assessment of the potential benefit from anti-VEGF therapy.

PURPOSE: Genetic and epidemiologic studies have shown that lipid genes and High Density Lipoproteins (HDL) are implicated in age-related macular degeneration (AMD). We studied circulating lipid levels in relation to AMD in a large European dataset, and investigated whether this relationship is driven by certain sub fractions. DESIGN: (Pooled) analysis of cross-sectional data. PARTICIPANTS: 30,953 individuals aged 50+ participating in the E3 consortium; and 1530 individuals from the Rotterdam Study with lipid sub fraction data. METHODS: In E3, AMD features were graded per eye on fundus photographs using the Rotterdam Classification. Routine blood lipid measurements were available from each participant. Data on genetics, medication and confounders such as body mass index, were obtained from a common database. In a subgroup of the Rotterdam Study, lipid sub fractions were identified by the Nightingale biomarker platform. Random-intercepts mixed-effects models incorporating confounders and study site as a random-effect were used to estimate the associations. MAIN OUTCOME MEASURES: early, late or any AMD, phenotypic features of early AMD, lipid measurements. RESULTS: HDL was associated with an increased risk of AMD, corrected for potential confounders (Odds Ratio (OR) 1.21 per 1mmol/L increase (95% confidence interval[CI] 1.14-1.29); while triglycerides were associated with a decreased risk (OR 0.94 per 1mmol/L increase [95%CI 0.91-0.97]). Both were associated with drusen size, higher HDL raises the odds of larger drusen while higher triglycerides decreases the odds. LDL-cholesterol only reached statistical significance in the association with early AMD (p=0.045). Regarding lipid sub fractions: the concentration of extra-large HDL particles showed the most prominent association with AMD (OR 1.24 [95%CI 1.10-1.40]). The CETP risk variant (rs17231506) for AMD was in line with increased-HDL levels (p=7.7x10-7); but LIPC risk variants (rs2043085, rs2070895) were associated in an opposite way (p=1.0x10-6 and 1.6x10-4). CONCLUSIONS: Our study suggests that HDL-cholesterol is associated with increased risk of AMD and triglycerides negatively associated. Both show the strongest association with early AMD and drusen. Extra-large HDL sub fractions seem to be drivers in the relation with AMD, variants in lipid genes play a more ambiguous role in this association. Whether systemic lipids directly influence AMD or represent lipid metabolism in the retina remains a question to be answered.

International audience; PURPOSE: To describe the glaucoma surgery offer in France in 2016. METHODS: We used the French National Health Care System database to identify all medical procedures carried out in 2016. The study investigated the entire population aged 30 years and older that had undergone glaucoma surgery, alone or combined with another surgery. We calculated the incidence of surgeries per 100 000 inhabitants 30 years of age and older performed by ophthalmologists carrying out at least 50 procedures annually, the number of surgeons doing these surgeries, the mean age of these practitioners, and the number of surgeons older than 55 years. RESULTS: In 2016, 16 854 glaucoma surgeries were performed in patients aged 30 years and older, for an incidence of 40.8 per 100 000 inhabitants aged 30 years and older. The most frequent procedure performed was trabeculectomy followed by non-penetrating deep sclerectomy (16.7 and 11.7, respectively, per 100 000 inhabitants 30 years of age and older). Private practice glaucoma surgery accounted for 47% of the activity of surgeons performing at least 50 surgeries per year and 60% of the total surgical activity. Of the private practice ophthalmologists performing at least 50 glaucoma surgery procedures per year, 58.5% were over 55 years of age, and 23.5% of public hospital ophthalmologists were over 55 years of age. CONCLUSIONS: This study demonstrates that surgeons performing glaucoma surgeries are often older. It is necessary to take note of the country's educational capacity to ensure that the number of ophthalmological surgeons remains adapted to demand.

PRECIS Micropulse transscleral cyclophotocoagulation (MP-TSCPC) with a 120-second setting reduces intraocular pressure (IOP) with a 6-month success of 45.5%. Only late (>6 mo) failure seem to present a benefit for retreatment. PURPOSE The purpose of this study was to assess MP-TSCPC efficacy, safety, factors of success, and retreatment benefit in open-angle glaucoma. PATIENTS AND METHODS A retrospective consecutive case series study. We included patients with open-angle glaucoma who were naive of a cycloablative procedure and underwent MP-TSCPC at 2000 mW for 120 seconds between May 1, 2017, and October 31, 2019. Success was defined as IOP >5 and ≤21 mm Hg with IOP reduction ≥20% from baseline, without any retreatment and visual acuity better than negative light perception. MP-TSCPC retreatment was early and late, before and after 6 months postoperatively, respectively. RESULTS We included 94 eyes in 94 patients [mean (SD) age: 67.2 (13.4) y; 47.9% women]. The mean preoperative IOP was 24.9 (7.1) mm Hg and was reduced to 18.9 (6.3) at month 6 (P

International audience; Despite the growing importance of real-world evidence (RWE) for guiding clinical decisions in retinal disease, there is currently no widely used guidance available for assessing the quality and relevance of RWE studies in ophthalmology. This paper summarizes the development of a user-friendly tool that facilitates assessment of the quality of available RWE for neovascular age-related macular degeneration (nAMD), diabetic macular oedema (DME) and retinal vein occlusion (RVO). A literature search was conducted to identify tools developed to assess the quality of RWE, in order to identify the most appropriate framework on which to base this tool. The Good Research for Comparative Effectiveness (GRACE) guidelines was chosen for this purpose as it is designed to assess the quality of observational studies and has been extensively validated, including demonstration of strong sensitivity and specificity. The GRACE guidelines were adapted to develop a straightforward tabular tool that allows simple assessment and comparison of the quality of published evidence in retinal disease for researchers and physicians alike, and includes guidance on treatment details, outcome measures, study population, and controlling for bias. The newly developed tool provides a simple method to support assessment of the strength of evidence and certainty of conclusions drawn from RWE in retinal disease, to ensure clinical decision-making is influenced by the highest quality evidence.

International audience; Purpose Preservatives contained in glaucoma eye drops have been shown to have a deleterious impact on the ocular surface. We aimed to assess the association between preservative exposure and the occurrence of further glaucoma surgery among patients with glaucoma or ocular hypertension in France. Methods The study concerned all patients who first received glaucoma eye drop treatments in a French medical-administrative database (EGB) between 2008 and 2015. Three groups were created according to the level of preservative exposure during the whole follow-up: '0% preservatives', 'mixed' and '100% preservatives'. The occurrence of glaucoma surgery was estimated according to preservative exposure indicators in Cox multivariate models adjusted on age, sex, number of glaucoma eye drops simultaneously used, systemic antihypertensive treatment and duration of treatment. Results The sample consisted of 12 454 patients. The median (interquartile range) follow-up was 4.1 (1.7-6.1) years. A total of 231 (1.9%) patients underwent glaucoma surgery during follow-up. On multivariable analysis, the risk of glaucoma surgery was increased for the 'mixed' group (hazard ratio [HR] = 3.94 [95% CI, 1.54-10.05]) and for the '100% preservative' group (HR = 7.97 [95% CI, 3.07-20.67]) when compared with the 0% preservative group. Conclusion We found an association between exposure to glaucoma eye drop preservatives and the prevalence of further glaucoma surgery. While these data might be used to support the consideration of routine use of preservative-free drops, in the absence of a randomized clinical trial, they cannot prove a direct cause-and-effect relationship between preservative-free glaucoma eye drops and further glaucoma surgery.

International audience; Background and purpose: The purpose was to evaluate, in a consecutive series of patients with isolated acute retinal ischaemia, the proportion of patients with acute silent brain infarcts (SBIs) on diffusion-weighted imaging (DWI) and to assess risk of recurrence within 3 months.Methods: In all, 103 consecutive patients with isolated acute retinal ischaemia (central retinal artery occlusion, branch retinal artery occlusion or transient monocular vision loss) were included between January 2015 and December 2016. They all had cerebral magnetic resonance imaging including DWI as well as a standardized aetiological workup and 3 months of follow-up. The presence of DWI-positive cerebral lesions was recorded. Main clinical and radiological characteristics between DWI-positive and DWI-negative patients were compared.Results: Of the 103 patients (including 42 transient monocular vision loss), 20 (19.5%) had SBIs on DWI, which were ipsilateral to the acute retinal ischaemia in 30% and involved different and/or multiple vascular territories in 70% of cases. Ipsilateral carotid stenosis and occlusion were respectively identified in 17 and eight patients whereas cardioaortic embolism was found in 19 patients. Overall, patients with and without acute SBIs were comparable. The topography of SBIs was related to the aetiology of the acute retinal ischaemia. At 3 months of follow-up, one patient suffered from ischaemic stroke and five had recurrent retinal ischaemia.Conclusions: Irrespective of the baseline characteristics of the patients, SBIs are present in about 20% of patients with isolated acute retinal ischaemia and may be of interest in the aetiological workup. Overall risk of recurrence is low, favoured by rapid aetiological workup and appropriate treatment.

The aim of this work was to evaluate the contribution of real-world evidence (RWE) in changing anti-vascular endothelial growth factor (VEGF) therapy treatment practices and improving real-world treatment strategies for neovascular age-related macular degeneration (nAMD).A PubMed literature search was performed to review the large number of English-language studies conducted to investigate the real-world effectiveness of anti-VEGF (aflibercept and ranibizumab) treatment paradigms available for nAMD.The evidence for pro re nata (PRN), treat-and-extend (T&E) and fixed bimonthly dosing regimens for anti-VEGF treatment of nAMD were reviewed and findings are summarised. RWE demonstrated that T&E regimens optimise visual outcomes while reducing burden on patients, clinics and physicians, compared with both fixed-dose and PRN regimens.RWE has helped to develop and improve real-world treatment strategies in nAMD, with the aim of optimising visual outcomes and reducing treatment burden in clinical practice. Of the various regimens, a T&E regimen is most likely to adequately balance clinical outcomes and treatment burden for patients with nAMD.

Indexation en cours.; International audience; PURPOSE: Contact lens (CL)-related microbial keratitis (MK) has major public health implications, with about 300 million wearers worldwide, and certain potentially modifiable risk factors. This study aimed to identify the risk factors of CL-related MK. METHODS: A multicenter case-control study was conducted between 2014 and 2017. Cases presenting with CL-related MK were submitted to an anonymous 52-item questionnaire, which was also completed by healthy controls. Univariate followed by multivariate logistic regression analysis was performed. Risk factors for CL-related MK were given as odds ratio (OR) with 95% confidence interval and P-value. RESULTS: The study included a total of 2267 patients (1198 cases and 1069 controls). The MK risk factors for the daily disposable lenses group were exceeding the lens renewal period (OR = 9.16, P = 0.008) and occasionally wearing CL when sleeping (OR = 15.83, P = 0.035). The most important risk factors in the nondaily disposable lenses group were lens cleaning solution distributed by eye care brands (OR = 3.50, P < 0.001) and failure to renew lens cases (OR = 3.39, P = 0.001). Statistically and clinically significant variables were used to establish the MK risk equation for CL wearers, allowing an individual calculation of the risk of MK under lenses. CONCLUSIONS: The MK risk equation is a valuable tool for educating patients about the risks associated with wearing CL. It allows the patient to be informed about their overall risk of infection while detailing the precipitating elements of the infectious risk with the aim of modifying risk behavior.

International audience; PURPOSE:To report the incidence of acute postoperative endophthalmitis (POE) after macular surgery in France between 2006 and 2016 and to identify associated factors.METHODS:This retrospective database study included all hospital discharge records involving a surgical procedure for an epiretinal membrane or a macular hole in France from January 2006 to October 2016. Acute POE was identified by two codes in the tenth edition of the International Classification of Diseases within 42 days of a macular surgical procedure in the French national administrative database.RESULTS:In France, 152 034 macular surgical procedures for epiretinal membranes or macular holes were recorded from 1 January 2006 to 31 October 2016. Suspected acute POE was reported in 381 cases. The incidence of POE was 0.25% overall, 0.30% for epiretinal membrane surgery and 0.14% for macular hole surgery. In multivariable Poisson regression analysis, epiretinal membrane surgery was associated with POE [incidence rate ratio (IRR), 2.24; 95% CI, 1.62-3.11; p < 0.001]. For epiretinal membrane surgery, the 2010-2011 period was significantly associated with a higher risk of POE (IRR, 1.66; 95% CI, 1.13-2.42; p = 0.03).CONCLUSION:The incidence of POE after macular surgery was 0.25% overall in France between 2006 and 2016 and twice higher for epiretinal membrane surgery than for macular hole surgery. For epiretinal surgery only, the incidence of POE was higher in 2010-2011 (period of the switch to transconjunctival vitrectomy) than in the rest of the study period.

Introduction: The rate of unknown glaucoma is around 50% in industrialized countries. The purpose of our study was to estimate the prevalence of unknown cases of ocular hypertension, glaucoma suspects, and glaucoma in patients consulting for refractive disorders in France. Methods: A retrospective study in the Point Vision ophthalmology center was led in Toulouse, France. All participants consulting for refractive disorders between June 2015 and June 2017 in the ophthalmology center were included. The cases were identified by the assessment of intraocular pressure, optic nerve head structure, and visual field. Ocular hypertension was defined as an intraocular pressure >21 mm Hg. Glaucoma was defined as the association of a glaucomatous papilla and two successive pathological visual fields. Glaucoma suspect was defined as the association of a glaucomatous papilla without visual field defect. The primary endpoint was the prevalence of unknown ocular hypertension, glaucoma suspects, and glaucoma in patients seen in an ophthalmology center. Results: A total of 66,068 patients (mean age = 37 years) consulted for a refraction visual assessment during the study period. Among them, 234 had a visual field and a retinal nerve fiber layer assessment for ocular hypertension and/or suspicious papilla. The prevalence of unknown cases of ocular hypertension, glaucoma suspect, and glaucoma was 2.6, 0.8, and 0.5 per 1,000 consultants, respectively. Median age at diagnosis of ocular hypertension, glaucoma suspect, and glaucoma was 52, 53, and 65 years, respectively. Conclusion: The present study highlights the importance of glaucoma screening in people over 40 years old with the measurement of intraocular pressure and an optic nerve head assessment.

BackgroundTo estimate the 10-year incidence of referable diabetic retinopathy (DR) in a French population with type 1 and 2 diabetes mellitus (DM). A secondary objective was the assessment of safe screening intervals in patients with diabetes without retinopathy.MethodsObservational, prospective and multicentric study between June 2004 and September 2017 based on a regional screening programme for DR in the Paris region. The incidence of referable DR in patients without retinopathy at baseline was calculated by the Turnbull survival estimator. A safe screening interval was defined as a 95% probability of remaining without referable DR.ResultsAmong the 25 745 participants with type 1 (n=6086) or type 2 (n=19 659) DM, the 10-year cumulative incidence of referable DR was 19.10% (95% CI 17.21% to 21.14%) and 17.03% (15.78% to 18.35%), median (IQR) follow-up=3.33 (4.24) years. The safe screening interval for patients without DR at the first examination for type 1 and 2 DM was 2.2 (95% CI 2.0 to 2.4) and 3.0 (2.9 to 3.1) years, respectively. In a subgroup of low-risk patients with type 2 DM, the safe screening interval was 4.2 (3.8 to 4.6) years.ConclusionsThese data suggest that in Paris area, a 2-year, 3-year and 4-year screening interval was considered safe for type 1 DM, type 2 DM and for low-risk patients with type 2 DM, respectively, without DR at the first examination. While these data might be used to support the consideration of extending screening intervals, a randomised clinical trial would be suitable to confirm the safety for patients with DM.

International audience; PURPOSE: Ocular and brain microcirculation share embryological and histological similarities. The retinal vascular fractal dimension (FD) is a marker of retinal vascular complexity of the vascular tree. The purpose of this study was to explore the relationship between cerebral blood flow (CBF), retinal vascular FD and other retinal vascular markers. METHODS: Cross-sectional analysis comprising 26 individuals >/=65 years old from the Cognitive REServe and Clinical ENDOphenotype (CRESCENDO) cohort of relative healthy older adults. Retinal vascular FD was measured from fundus photographs by using the semi-automated Singapore Eye Vessel Assessment (SIVA) software. CBF was estimated using a 2D pulsed ASL MRI sequence. Associations between blood flow and retinal parameters were analysed using linear regression models adjusted for age and sex. RESULTS: Cerebral blood flow was positively associated with venular FD (R(2) = 0.32, p = 0.03). This association was stronger in the anterior versus posterior brain territories (R(2) = 0.35 [p = 0.001] versus R(2) = 0.16 [p = 0.07], respectively). Global CBF was correlated with arteriolar branching angle (R(2) = 0.23, p = 0.01) and tortuosity (R(2) = 0.20, p = 0.02). Global CBF was not correlated with other SIVA parameters. CONCLUSIONS: Retinal venular complexity summarized by the FD was associated with cerebral blood flow as well as retinal arteriolar tortuosity and branching angle. Larger prospective clinical studies are needed to confirm these results.

Background Systematically review the evidence describing the impact of anti–vascular endothelial growth factor (anti-VEGF) therapy on neovascular age-related macular degeneration (nAMD) patient outcomes and healthcare resource utilization. Methods A systematic literature review was completed using Medline and EMBASE for publications prior to July 2018, and proceedings from major ophthalmology conferences (January 2016 to July 2018). The search strategy combined terms for nAMD with terms for anti-VEGF and study design. The review focused on publications describing the impact of anti-VEGF on blindness, visual impairment, vision-related quality of life (VRQoL), mortality, and costs. The search targeted data collected in epidemiological or observational studies to reflect real-world outcomes but also considered modeling-based approaches. Results The use of anti-VEGF in clinical practice was associated with significant reduction in the incidence of blindness by nAMD. Population-based analyses reported reduction in incidence among the general population of 47% (9.1 cases/100,000 in 2006 to 4.8 cases/100,000 in 2011). Among patients aged ≥50 years, a reduction of 50% was observed (52.2 cases/100,000 in 2000 to 25.7 cases/100,000 in 2010). In some cases, the odds of decreased vision (defined as decline from normal to moderate, moderate to severe, or severe to blindness) fell by 41% following introduction of anti-VEGF. Patients’ VRQoL improved with treatment, with patients reporting a positive impact shortly after treatment was initiated. Change on National Eye Institute 25-Item Visual Function Questionnaire score from baseline to month 12 ranged from 0.7 to 4.4. Although nAMD patients report signs of depression and anxiety, the evidence suggests that there is no association between the use of anti-VEGF and the prevalence or diagnosis of depression. The introduction of anti-VEGF led to increased overall treatment costs due to replacement of existing less frequently administered treatments (e.g. photodynamic therapy) and increased number of patients treated (prior to anti-VEGF, only ~ 20% of patients were eligible for treatment). Conclusions The introduction of anti-VEGF agents has been associated with a positive impact on patient-relevant outcomes, including a significant reduction in incidence of blindness and visual impairment by nAMD. Anti-VEGF agents replaced less-effective treatments, improving patient outcomes and broadening the patient population eligible for treatment.

ObjectiveTo report the outcomes of cataract surgery performed by non-physician cataract surgeons due to lack of ophthalmologists in remote areas of North Cameroon.DesignProspective cohort study.SettingThe main centre of the non-governmental organisation Ophtalmo Sans Frontières in Lagdo.Participants and interventionsAge-related cataract surgery performed between 28 November 2016 and 17 May 2017.Main outcomes measuresThe main outcome measure was presenting visual acuity (PVA) 1–4 weeks after surgery, classified according to the WHO as good (PVA ≥6/18), borderline (PVA 6/60–6/18) and poor (PVA ResultsWe included 474 eyes of 474 patients; the mean (SD) age was 63.9 (15) years (42.2% female). At 1–4 weeks after surgery, the surgical outcome was good for 170 patients (41.1%), borderline for 213 (51.5%) and poor for 31 (7.5%). In all, 224 patients (47.2%) had blindness or severe visual impairment before cataract surgery and 22 (5.3%) at 1–4 weeks after surgery. Poor visual outcome was associated with older age (p=0.018), preoperative blindness or severe impairment (p=0.012) and surgical complications (p=0.019).ConclusionBlindness and severe visual impairment were significantly decreased in the early postoperative period. Poor outcomes were associated with older age, low preoperative binocular visual acuity and intraoperative complications. Non-physician cataract surgeons may compensate for the lack of ophthalmologists in remote areas of low-income and middle-income countries.

Objectives:To examine the longitudinal risk of vision loss (VL) or hearing loss (HL) for experiencing suicidal ideation in older adults.Design:The Three-City study, examining data from three waves of follow-up (2006–2008, 2008–2010, and 2010–2012).Setting:Community-dwelling older French adults.Participants:N = 5,438 adults aged 73 years and over.Measurements:Suicidality was assessed by the Mini-International Neuropsychiatric Interview, Major Depressive Disorder module. Mild VL was defined as Parinaud of 3 or 4 and severe VL as Parinaud >4. Mild HL was self-reported as difficulty understanding a conversation and severe HL as inability to understand a conversation.Results:Severe VL was associated with an increased risk of suicidal ideation at baseline (OR = 1.59, 95% CIs = 1.06–2.38) and over five years (OR = 1.65, 95% CIs = 1.05–2.59). Mild and severe HL were associated with an increased risk of suicidal ideation, both at baseline (OR = 1.29, 95% CIs = 1.03–1.63; OR = 1.78, 95% CIs = 1.32–2.40) and over five years (OR = 1.47, 95% CIs = 1.17–1.85; OR = 1.97, 95% CIs = 1.44–2.70).Conclusion:Sensory losses in late life pose a risk for suicidal ideation. Suicidality requires better assessment and intervention in this population.

Importance: Poor adherence or persistence to treatment can be a barrier to optimizing clinical practice (real-world) outcomes to intravitreal injection therapy in patients with neovascular age-related macular degeneration (nAMD). Currently, there is a lack of consensus on the definition and classification of adherence specific to this context.Objective: To describe the development and validation of terminology on patient nonadherence and nonpersistence to anti-vascular endothelial growth factor therapy.Design, Setting, and Participants: Following a systematic review of currently used terminology in the literature, a subcommittee panel of retinal experts developed a set of definitions and classification for validation. Definitions were restricted to use in patients with nAMD requiring intravitreal anti-vascular endothelial growth factor therapy. Validation by the full nAMD Barometer Leadership Coalition was established using a modified Delphi approach, with predetermined mean scores of 7.5 or more signifying consensus. Subsequent endorsement of the definitions was provided from a second set of retinal experts, with more than 50% members agreeing or strongly agreeing with all definitions.Main Outcomes and Measures: Development of consensus definitions for the terms adherence and persistence and a classification system for the factors associated with treatment nonadherence or nonpersistence in patients with nAMD.Results: Nonadherence was defined as missing 2 or more treatment or monitoring visits over a period of 12 months, with a visit considered missed if it exceeded more than 2 weeks from the recommended date. Nonpersistence was defined by nonattendance or an appointment not scheduled within the last 6 months. The additional terms planned discontinuation and transfer of care were also established. Reasons for treatment nonadherence and nonpersistence were classified into 6 dimensions: (1) patient associated, (2) condition associated, (3) therapy associated, (4) health system and health care team associated, (5) social/economic, and (6) other, with subcategories specific to treatment for nAMD.Conclusions and Relevance: This classification system provides a framework for assessing treatment nonadherence and nonpersistence over time and across different health settings in the treatment of nAMD with current intravitreal anti-vascular endothelial growth factor treatments. This may have additional importance, given the potential association of the coronavirus pandemic on adherence to treatment in patients with nAMD.

Background Real-world data (RWD) has been a valuable addition to the scientific literature regarding treatment pathways, clinical outcomes and characteristics of patients with retinal diseases in recent years. Registries, observational studies and patient databases are often used for real-world research. However, there is limited information for each data source on the design, consistency, data captured, limitations and usability for assessing research questions. Using a systematic approach, we identified RWD sources for patients with retinal diseases and assessed them for completeness of data relating to different outcomes. Methods A systematic literature review was carried out to identify RWD sources for patients with retinal disease. Potentially relevant articles published between 2006 and 2016 were screened following electronic searches in Embase and MEDLINE. Congress and supplementary searches were undertaken to identify RWD sources that may not be referenced in full publications. For each data source, availability and quantity of data on baseline status, clinical outcomes, treatment and management, safety, and patient-reported and economic burden were assessed using a bespoke completeness assessment tool based on International Consortium for Health Outcomes Measurement guidelines for macular degeneration. Completeness of data for each area of interest in each data source was assessed and rated using a ‘good–moderate–poor’ rating system based on availability and quantity of available data. Each data source was then given an overall score based on its score for each of the 7 areas of interest. Results A total of 128 RWD sources from 32 countries were identified. Of the identified sources, 64 sources from 16 countries of interest were analyzed. Most of these sources provided information on baseline status and clinical outcomes and treatment, but few collected data on economic and patient-reported burden. Of the RWD sources analyzed, 10 scored highly in the overall completeness assessment, collecting data on most or all of the areas of interest; these sources are considered to be robust data sources for performing ophthalmology real-world studies. Conclusions The study provides a comprehensive list of RWD sources for patients with retinal disease, many of which will be useful for conducting real-world studies in the field of ophthalmology.

Purpose To report the effectiveness of intravitreal aflibercept (IVT-AFL) treatment for diabetic macular edema (DME) in French clinical practice. Methods APOLLON (NCT02924311) was a prospective, observational cohort study of patients with DME. Effectiveness was evaluated by change from baseline in best-corrected visual acuity (BCVA) at 12 months in treatment-naïve patients (i.e., had not received any anti-vascular endothelial growth factor [anti-VEGF] agent, laser, or steroid at IVT-AFL treatment start) and previously treated patients (i.e., previously treated with anti-VEGF agents other than IVT-AFL, laser, or steroids at IVT-AFL treatment start). Secondary endpoints included change in central retinal thickness (CRT) over 12 months, frequency of injections, and proportion of patients with safety events. Results Of the 147 patients followed for at least 12 months and included in the effectiveness analysis, 52.4% (n = 77) were treatment-naïve and 47.6% (n = 70) were previously treated. Mean (standard deviation [SD]) BCVA score at baseline was 62.7 (14.3) Early Treatment Diabetic Retinopathy Study (ETDRS) letters in treatment-naïve patients and 60.0 (13.7) ETDRS letters in previously treated patients. At month 12, mean (SD) change in BCVA was + 7.8 (12.3) letters in treatment-naïve patients and + 5.0 (11.3) letters in previously treated patients. Mean CRT decreased in both patient cohorts. The mean (SD) number of IVT-AFL injections at month 12 was 7.6 (2.5) for treatment-naïve patients and 7.6 (2.3) for previously treated patients. Of 388 patients included in the safety analysis, ocular treatment-emergent adverse events occurred in 54.1% (n = 210) of patients. Conclusion IVT-AFL treatment was associated with improvements in functional and anatomic outcomes in both treatment-naïve and previously treated patients with DME in France.

Importance Long-term data of intravitreal injections of vascular endothelial growth factor (VEGF) inhibitors are lacking. Background This study aims to assess visual and anatomic outcomes of eyes with neovascular age-related macular degeneration (nAMD) after 10 years of anti-VEGF therapy. Design Retrospective analysis of data from a prospectively designed database. Participants One hundred and sixteen eyes with nAMD (94 participants) that started anti-VEGF therapy at least 10 years earlier. Methods Eyes were tracked by the Fight Retinal Blindness! registry. Main outcome measures Mean change in visual acuity at 10 years vs baseline. Visual acuity was assessed by the number of letters read on a logarithm of the minimum angle of resolution chart. Results Eyes received a median of 27.5 injections over 10 years. Mean visual acuity was 57.5 letters (SD 17.5) at baseline. It increased slightly at 1 year, then dropped steadily by 18 letters (95% CI: 13.7; 22.3) at 10 years. Overall, 10% of eyes gained ≥10 letters, 64% lost ≥10 letters and 23% remained stable (±5 letters from baseline). Geographic atrophy and subretinal fibrosis were found in 93% and 71%, respectively, after 10 years, both mostly affecting the centre of the fovea. Pre-treated eyes (47.5%) had significantly worse visual acuity than treatment-naive eyes at baseline and during follow-up and were significantly more likely to have atrophy and fibrosis. Conclusions and relevance Despite short-term stabilization, long-term visual outcomes of nAMD eyes under anti-VEGF therapy may be poor. Development of atrophy and fibrosis, resulting from the natural progression of the disease, may partly explain this evolution.

BackgroundTo assess the prevalence and characteristics associated with macular atrophy (MA) in eyes with neovascular age-related macular degeneration (nAMD) treated with vascular endothelial growth factor (VEGF) inhibitors.MethodsThis was a retrospective, cross-sectional study of nAMD eyes that commenced anti-VEGF between January 2006 and August 2016. MA (absent/extrafoveal/subfoveal) was graded by treating practitioners based on multimodal imaging from April 2016. The prevalence of MA over time and risk factors of MA were assessed.ResultsThe prevalence of MA in a cohort of 1689 eyes was 9.9% (22/222) in eyes within 1 year of starting treatment, 41.5% (71/171) after 5 years and 48.4% (30/62) after 9 years of treatment. Risk factors for subfoveal MA included the proportion of visits at which the lesion was graded as inactive ((adjusted OR (AOR) 3.72 for the highest vs lowest the quartile of frequency of inactive gradings (95% CI 2.33 to 6.07)), age (AOR 1.05 per year (95% CI 1.02 to 1.07)), baseline visual acuity (AOR 3.9 for ≤35 letters vs ≥70 letters (95% CI 2.4 to 6.4)) and the number of injections received (AOR 1.20 every 10 injections (95% CI 1.08 to 1.33)). Similar associations were observed with extrafoveal MA.ConclusionsThe risk of MA appeared to drop in eyes that had not developed it within 5 years. Low choroidal neovascularisation activity was by far the strongest predictor. We could not determine whether the increased prevalence of MA with time was due to anti-VEGF treatment or the natural history of the condition.

ObjectiveTo compare the outcomes of trainee-led and specialist-led management of neovascular age-related macular degeneration.DesignProspective multicentre registry-based observational study.SettingOphthalmology training centres in Australia and Europe where both trainee-led and specialist-led models of care coexist.ParticipantsTreatment-naïve eyes with neovascular age-related macular degeneration and at least 12 months follow-up. 726 eyes were included in the study from two centres, 534 receiving trainee-led treatment and 192 specialist-led treatment.InterventionsThe management and outcomes of patients receiving trainee-led care were compared with those receiving specialist-led care.Main outcomes measuresThe primary outcome was the mean change in visual acuity at 12 months from first injection. Outcomes were also presented at 36 months where available.ResultsThe mean age of participants was 79 years and 65% were female. The adjusted change in acuity at 12 months in trainee-led vs specialist-led eyes was +3.2 letters vs +4.1 letters (difference −0.9 letters, 95% CI −3.4 to 1.5, p=0.473). The mean adjusted change in acuity at 36 months was −0.9 letters in trainees vs +0.2 letters for specialists (difference −1.1 letters, 95% CI −5.1 to 2.9, p=0.596). Eyes treated by trainees received fewer injections on average to 36 months (15.0 vs 19.0, p=0.004), although this trend was observed at one centre only.ConclusionsNo significant differences in outcome between eyes managed by trainees and eyes managed by specialists were observed. Appropriately structured trainee-led management of neovascular age-related macular degeneration is a reasonable approach where regulatory and practical considerations allow it.

PurposeTo assess the incidence of acute postoperative endophthalmitis (POE) after cataract surgery combined with corneal, glaucoma or vitreoretinal surgical procedures from 2005 to 2014 in France.MethodsIn this cohort study, acute POE occurring within 6 weeks after surgery was identified by means of billing codes recorded in a national database in patients operated for cataract extraction with phacoemulsification, or corneal, glaucoma or vitreoretinal surgical procedures, either combined or stand-alone.ResultsFrom January 2005 to December 2014, up to 6 260 477 eyes underwent phacoemulsification cataract surgery as a single procedure and 115 468 eyes underwent phacoemulsification combined with corneal, glaucoma or vitreoretinal surgical procedures. The crude incidence of acute POE after stand-alone or combined cataract surgery was 0.102% and 0.149%, respectively. In multivariate Poisson analysis, combined surgery taken as a whole was at higher risk than cataract stand-alone surgery, with an adjusted incidence rate ratio (IRR) (95% CI) of 1.38 (1.11 to 1.70; p=0.0054). Glaucoma surgeries were associated with a lower acute POE incidence compared with phacoemulsification, conversely to vitreoretinal surgical procedures: IRR 0.63 (0.47 to 0.85; pConclusionA higher incidence of acute POE after combined cataract surgery than after cataract surgery done as a stand-alone procedure was observed based on the French nationwide medical-administrative database. The incidence of acute POE after combined surgery was related to the type of surgery performed simultaneously with cataract extraction.

International audience; Pourfour du Petit syndrome is an uncommon cause of eyelid retraction, associated with unilateral mydriasis and hemifacial hyperhidrosis. This syndrome is caused by hyperactivity of the ipsilateral oculosympathetic pathway and needs to be recognized because it has an opposite clinical presentation but the same topographic and diagnostic value as Horner syndrome. The authors report a rare case of Pourfour du Petit syndrome associated with cluster headache and discuss pathophysiological hypotheses, clinical presentation, complementary exams, pharmacologic testing, treatment options, and prognosis. Early detection of these symptoms may lead to swift diagnosis and treatment.

International audience; INTRODUCTION:To present long-term follow-up data on evisceration performed with autogenous scleral grafting and ceramic implantation in a modified scleral shell.METHODS:This was a retrospective analysis of all consecutive eviscerations performed in the Department of Ophthalmology, Montpellier University Hospital, France, between February 1998 and October 2015. For all patients, the technique used was a conventional anterior evisceration after total keratectomy, disinsertion of the medial rectus muscle, sectioning of the optic nerve and excision of sclera centered on the papilla. The scleral graft was then sutured just behind the sutured keratectomy, and the bioceramic implant was inserted by posterior way in the scleral shell. Demographic characteristics, implant size and type, cosmetic results from pictures of all patients and complications were recorded. This study was performed with Ethics Review Committee Approval, and in compliance with the Declaration of Helsinki.RESULTS:In total, 133 patients (36.6% women) were identified during the study period. The mean (SD) implant size was 17.32 (1.84) mm. The median follow-up after evisceration was 57.43 (24.7, 68.3) months. Two cases of implant exposure (1.5%) were recorded. For 24 patients (17.9%), additional surgeries were performed for ptosis (2.2%), conjunctival cyst (1.5%), or post-evisceration socket syndrome (6.7%). Cosmetics results were excellent for 50.1% of cases, good for 33.3% and fair for 16.6%; using a grading scale based on the superior sulcus deformity.CONCLUSION:Evisceration with autogenous scleral grafting and ceramic implantation can result in a high volume of restoration, good cosmetic results, and low risk of exposure of the implant.

International audience; PURPOSE:To explore various methods for assessing the early response to vascular endothelial growth factor (VEGF) inhibitors for neovascular age-related macular degeneration and investigate their association with 3-year visual acuity (VA) outcomes.DESIGN:Database study, prospectively designed.PARTICIPANTS:Treatment-naïve eyes in the Fight Retinal Blindness! registry that commenced anti-VEGF therapy between January 1, 2007, and March 1, 2014, that received 3 anti-VEGF injections within the first 3 months.METHODS:The early response was defined as occurring up until the fourth injection. Various early response metrics were explored: (1) achieving good VA (≥70 letters; Snellen equivalent, 20/40), (2) absolute change in VA from baseline, (3) time to first grading of the choroidal neovascular lesion as inactive, and (4) maximum rate of VA change between successive injections.MAIN OUTCOME MEASURES:Proportion of eyes achieving ≥70 letters 3 years.RESULTS:This study included 2051 treatment-naïve eyes from 1828 patients. Achieving good vision at 3 years was associated significantly with (1) having good vision by the fourth injection (VA ≥70 vs. VA 5 letters) early VA gains (vs. early VA loss: OR, 1.8; 95% CI, 1.2-2.6; P = 0.002; and OR, 1.8; 95% CI, 1.3-2.5; P < 0.001), (3) fewer injections until first grading of lesion inactivity (≤3 vs. >3 injections: OR, 1.6; 95% CI, 1.2-2.1; P < 0.001), (4) gradual change (between -4 and 4 letters) or rapid gains (≥5 letters) between successive injections (vs. rapid loss: OR, 1.7; 95% CI, 1.1-2.6; P = 0.015; and OR, 1.6; 95% CI, 1.1-2.3; P = 0.018). Eyes that achieved small or large early gains had similar vision at 3 years (65.0 and 64.7 letters, respectively) and had better vision than eyes with early VA loss (57.2 letters).CONCLUSIONS:Attainment of good vision by the fourth injection was associated strongly with 3-year visual outcomes, whereas other early response parameters showed a moderate association. The early response during the initial 3 monthly injections can be a useful guide for subsequent treatment decisions.

International audience; Purpose: To measure subfoveal choroidal thickness (SFCT) in the elderly and to determine the associations among SFCT, cardiovascular history, and the 10-year risk of fatal cardiovascular disease (CVD). Methods: We conducted a population-based study, the Montrachet (Maculopathy Optic Nerve, nuTRition neurovAsCular, and HEarT disease) study, in subjects older than 75 years. SFCT was measured with spectral-domain optical coherence tomography (SD-OCT) with enhanced-depth mode imaging. Participants underwent a comprehensive eye examination. The history of CVD, CVD risk factors, and a score-based estimation of their 10-year risk of cardiovascular mortality (Heart Score) were collected. Results: Overall, 764 participants were retained for analysis. The mean SFCT was 206.4 +/- 83.0 mum. The mean age was 81.9 +/- 3.6 years. After a multivariable analysis, older age (beta = -32.56 mum, P < 0.001) and longer axial length (beta = -20.71 mum, P < 0.001) were independently associated with thinner SFCT. SFCT was not significantly associated with sex, cardiovascular history, classical CVD risk factors, or prognostic risk score. Conclusions: This study confirms that longer axial length and older age are associated with thinner SFCT. However, SFCT does not appear to be a biomarker for cardiovascular history in this study.

To directly compare visual acuity (VA) outcomes with ranibizumab vs. aflibercept for eyes with neovascular age-related macular degeneration (nAMD) treated in routine clinical practice.Database observational study.Treatment-naïve eyes with nAMD tracked by the Fight Retinal Blindness outcome registry that commenced anti-vascular endothelial growth factor therapy with ranibizumab or aflibercept between December 1, 2013, and January 31, 2015. Eyes were matched at baseline for VA, age, and choroidal neovascular membrane (CNV) size.Locally weighted scatterplot smoothing curves were used to display VA results. Eyes that switched or discontinued treatment were included with their last observation carried forward.Change in mean VA (number of letters read on a logarithm of the minimum angle of resolution chart); number of injections and visits; proportion of eyes with inactive CNV over 12 months.We identified 394 eyes (197 treated with ranibizumab and 197 with aflibercept) from 372 patients who received treatment from 34 practitioners. Baseline parameters were well matched. The mean (standard deviation [SD]) VA of ranibizumab-treated eyes increased from 58.6 (20.3) letters at baseline to 62.3 (23.9) (+3.7 [95% confidence interval {CI} 1.4-6.1]) letters (P = 0.001), compared with 58.9 (19.2) letters at baseline to 63.1 (21.5) (+4.26 [95% CI 2.0-6.5]) letters (P0.001) for eyes receiving aflibercept. The difference in change in crude VA of 0.6 letters between the 2 groups was not statistically significant (P = 0.76), nor was the difference in adjusted mean VA of the 2 groups (P = 0.26). In completers, the mean (SD) numbers of injections (8.1 [2.1] vs. 8.0 [2.3]; P = 0.27) and visits (9.6 [3.0] vs. 9.5 [3.1]; P = 0.15) did not differ between the 2 groups. The adjusted proportion of eyes in which the CNV lesion was graded as inactive during the study was similar between the eyes receiving ranibizumab and aflibercept (74% vs. 77%, respectively; P = 0.63).Visual acuity outcomes at 12 months did not differ between ranibizumab and aflibercept used for nAMD in this large observational study, nor was a difference in treatment frequency found.

Purpose To search for WFS1 mutations in patients with optic atrophy (OA) and assess visual impairment. Design Retrospective molecular genetic and clinical study. Participants Patients with OA followed at a national referral center specialized in genetic sensory diseases. Methods Mutation screening in WFS1 was performed by Sanger sequencing. WFS1 -positive patients were evaluated on visual acuity (VA) and retinal nerve fiber layer (RNFL) thickness using time-domain (TD) or spectral-domain (SD) optical coherence tomography (OCT). Statistical analysis was performed. Main Outcome Measures Mutation identification, VA values, and RNFL thickness in sectors. Results Biallelic WFS1 mutations were found in 3 of 24 unrelated patients (15%) with autosomal recessive nonsyndromic optic atrophy (arNSOA) and in 8 patients with autosomal recessive Wolfram syndrome (arWS) associated with diabetes mellitus and OA. Heterozygous mutations were found in 4 of 20 unrelated patients (20%) with autosomal dominant OA. The 4 WFS1 -mutated patients of this latter group with hearing loss were diagnosed with autosomal dominant Wolfram-like syndrome (adWLS). Most patients had VA decrease, with logarithm of the minimum angle of resolution (logMAR) values lower in arWS than in arNSOA (1.530 vs. 0.440; P = 0.026) or adWLS (0.240; P = 0.006) but not differing between arNSOA and adWLS ( P = 0.879). All patients had decreased RNFL thickness that was worse in arWS than in arNSOA (SD OCT, 35.50 vs. 53.80 μm; P = 0.018) or adWLS (TD-OCT, 45.84 vs. 59.33 μm; P = 0.049). The greatest difference was found in the inferior bundle. Visual acuity was negatively correlated with RNFL thickness ( r = −0.89; P = 0.003 in SD OCT and r = −0.75; P = 0.01 in TD-OCT). Conclusions WFS1 is a gene causing arNSOA. Patients with this condition had significantly less visual impairment than those with arWS. Thus systematic screening of WFS1 must be performed in isolated, sporadic, or familial optic atrophies.

International audience; To assess the efficacy and safety of the second-generation probe of ultrasonic circular cyclocoagulation (UC3) in naive or refractory glaucoma, with a 6-month follow-up.Methods: A retrospective consecutive case-series study included patients having a UC3 procedure with the second-generation probe of the EyeOP1 device, intraocular pressure (IOP) ≥ 21 mmHg and under maximum tolerated medical treatment, with or without previous glaucoma surgery. Surgical success was defined at the 6-month post-operative visit as IOP > 5 and ≤ 21 mmHg with IOP reduction ≥ 20% from baseline, without any reoperation, and visual acuity better than negative light perception.Results: 100 patients were included and 97 (97.0%; 97 eyes) attended the 6-month follow-up. At 6 months, surgical success was obtained in 48 eyes (49.5%). Intraocular pressure was reduced from a mean ± SD preoperative value of 28.0 ± 5.6 mmHg to 19.3 ± 7.1 mmHg at 6 months (p 2 Snellen lines. Postsurgical macular edema was associated with a history of epiretinal membranes, uveitis or retinal detachment. Risk factors for hypotony were a history of diabetes or trabeculectomy.Conclusions: The second-generation UC3 probe significantly reduced IOP in eyes with naive and refractory glaucoma but severe post-operative complications were often observed. Further studies are needed to better identify responders and decrease the high risk for complications associated with the procedure.

OBJECTIVE: The present study aims to examine the longitudinal relationship between hearing loss (HL) with depression in older adults over 12 years of follow-up. METHOD: Eight thousand three hundred forty-four French community-dwelling adults aged 65 and above participated in the Three-City prospective population-based study. Baseline relationships between self-reported mild and severe HL with depression-assessed by both the Mini International Neuropsychiatric Interview and by the Centre for Epidemiology Studies Depression scale-were explored using logistic regression analyses. Logistic mixed models assessed whether baseline HL was associated with incident depression diagnosis or symptom onset over 12 years in those who were depression-free at baseline. RESULTS: At baseline, mild and severe HL were associated with depression symptoms as assessed by the CESD (OR = 1.29, 95% CIs 1.14-1.47; OR = 1.51, 95% CIs 1.22-1.87; respectively), although only mild HL was significantly related to major depression diagnosis (OR = 1.51, 95% CIs 1.07-2.12). Over 12 years, mild and severe HL were associated with incident depression as assessed by the CESD in those without depression at baseline (OR = 1.36, 95% CIs 1.15-1.61; OR = 1.69, 95% CIs 1.15-2.30; respectively), but was not associated with a major depression diagnosis. CONCLUSIONS: Both mild and severe thresholds of HL are associated with depression symptoms over time, but not with incident diagnosis of major depression. Improved and ongoing detection of subthreshold depression amongst older adults with HL may improve quality of life for this population.

International audience; INTRODUCTION:To report 12-month pharmacoepidemiologic data on aflibercept and ranibizumab use in treatment-naïve eyes with neovascular age-related macular degeneration (nAMD).METHODS:Participants were treatment-naïve eyes with nAMD tracked by the Fight Retinal Blindness! registry starting therapy with aflibercept or ranibizumab treatment between January 1st, 2013 and 31st December, 2016. Demographic and clinical characteristics were compared between treatment groups.RESULTS:During the study period, 689 eyes initiated treatment with ranibizumab compared to 568 with aflibercept. We found a similar rate of use of both drugs. Ranibizumab-treated patients were older than aflibercept-treated patients (overall mean [SD] 82.0 [8.4] vs. 78.6 [8.1], P

International audience; Clinical trials identified intravitreal vascular endothelial growth factor inhibitors (anti-VEGF agents) have the potential to stabilise or even improve visual acuity outcomes in neovascular age-related macular degeneration (AMD), a sight-threatening disease. Real-world evidence allows us to assess whether results from randomised controlled trials can be applied to the general population. We describe the development of global registries, in particular the Fight Retinal Blindness! registry that originated in Australia, the United Kingdom AMD Electronic Medical Records User Group and the IRIS registry in the USA. Real-world observations relating to efficacy, safety and resource utilisation of intravitreal anti-VEGF therapy for neovascular AMD are then summarised. Novel observations that would have been challenging to identify in a clinical trial setting are then highlighted, including the risk of late disease reactivation, outcomes in second versus first treated eyes, and the increased risk of posterior capsular rupture during cataract surgery in patients who have received intravitreal anti-VEGF therapy. We conclude by exploring future directions in the field. This includes the development of a global consensus on real-world outcome measures to allow greater comparison of results. Real-world neovascular AMD outcome registries can be linked with other databases to determine systemic safety or genetic predictors of treatment efficacy. Machine learning offers opportunities to extract useful insights from "Big Data" often collected in these registries. Real-world registries could be used by drug regulatory authorities and industry as an alternative to more costly and time-consuming phase 4 clinical trials, potentially allowing medication costs to be based on outcomes achieved.

International audience; PURPOSE:To determine the characteristics and outcomes of eyes with neovascular age-related macular degeneration (nAMD) in which choroidal neovascular (CNV) lesion activity was graded as uncertain.DESIGN:Prospective, database, observational study.PARTICIPANTS:Treatment-naïve patients with nAMD tracked by the Fight Retinal Blindness! (FRB!) registry initiating treatment between January 1, 2008, and January 1, 2014, with 2 years of follow up.METHODS:Lesion activity was determined by the clinical judgment of the providing physician on the basis of clinical examination with ancillary testing. Eye-based analysis investigated clinical characteristics and outcomes by proportion of visits with uncertain CNV lesion activity. Encounter-based analysis investigated CNV lesion grading over time with corresponding treatment and follow up.MAIN OUTCOME MEASURES:Change in mean visual acuity (number of letters read on a logarithm of the minimum angle of resolution chart) at 2 years. Secondary outcomes included the number of visits and injections.RESULTS:We identified 1631 eyes of 1419 patients with 27 974 visits to 46 retinal specialists. The CNV lesion activity was uncertain at 4601 encounters (16.4%) and experienced by the majority of eyes (52%) and providers (72%). Uncertainty of CNV lesion activity did not significantly decline with increasing number of visits in individual patients (P = 0.97) but did decline from 32% in 2010 to 4% in 2015 (P < 0.001). Eyes having no visits with uncertain CNV lesion grading gained more letters (mean, 7.0) than eyes with moderate or high levels of uncertainty (mean, 3.98 and 3.37; P = 0.03 and 0.02, respectively). The mean probability of receiving an injection was higher in visits with active (0.89) compared with inactive (0.68, P < 0.001) and uncertain (0.69, P < 0.001) CNV lesion activity. Subsequent follow-up length was also decreased in visits with active (mean ± standard deviation [SD], -0.9±39 days) compared with inactive and uncertain CNV lesion activity (mean ± SD, 1.9±39 days, P < 0.001, and 2.4±39 days, P < 0.001, respectively).CONCLUSIONS:Rates of uncertainty regarding CNV lesion activity were high, and eyes with higher rates of uncertain CNV activity had worse outcomes. Further studies are warranted to establish whether eyes should be treated more aggressively when the activity status of the CNV lesion is uncertain.

International audience; Importance: Amyloid-β is a major component of retinal drusen, the primary lesions of age-related macular degeneration (AMD), and autopsy and animal models suggested that anticholinergic drug (ACD) use increased brain amyloid-β deposition. Objective: To investigate the association between exposure to ACDs and late AMD (features of neovascular AMD or geographic atrophy of the retinal pigment epithelium in at least 1 eye). Design, Setting and Participants: A multicenter case-control study in 4 French ophthalmologic centers comprising 200 cases with late AMD and 200 controls enrolled from July 2016 to June 2017. Exposures: Exposure to at least 3 months of ACDs started before AMD diagnosis was recorded during a specific interview. A dose-effect association with cumulative exposure duration and Anticholinergic Burden Score was explored. The association between ACD exposure and AMD was assessed by multivariate logistic regression analysis adjusted for age, sex, smoking status, family history of AMD, alcohol consumption, and use of anticoagulant and anti-inflammatory drugs. Odds ratios (ORs) and 95% confidence intervals were estimated. Main Outcomes and Measures: Association between exposure to ACDs and late AMD. Results: Among case participants, the mean (SD) age was 74.8 (9.2) years, 129 (64.5%) were women, 192 (96%) were white, 65 (32.5%) had geographic atrophy, 135 (67.5%) had neovascular AMD, 116 (58%) had unilateral AMD, and 84 (42%) had bilateral AMD. Among control participants, the mean (SD) age was 75.5 (7.2) years, with 116 (58%) women and 187 (93.5%) white participants. Twenty-six cases (13%) and 10 controls (5%) were exposed to ACDs throughout life for at least 3 months before AMD onset. Risk of AMD was increased with ever exposure to ACDs (adjusted OR [aOR], 2.84; 95% CI, 1.33-6.06; P = .007), high Anticholinergic Burden Score (>=3) (aOR, 6.42; 95% CI, 1.38-29.92; P = .02), and longest cumulative exposure to ACD (>=15 years) (aOR, 5.88; 95% CI, 1.22-28.31; P = .03). Conclusions and Relevance: Risk of late AMD may be increased with at least 3 months' use of ACDs. A dose-effect association was suggested by a greater association with prolonged use and high Anticholinergic Burden Score. Further studies, in particular those with longitudinal design, are needed to confirm this association.

Original Investigation; International audience; Importance: The number of patients affected by retinal diseases treated with intravitreal injections (IVTs) has resulted in a rapidly growing number of procedures. One of the worst complications after these injections is endophthalmitis. Objective: To evaluate the incidence of acute endophthalmitis after IVTs of corticosteroids or anti-vascular endothelial growth factor (anti-VEGF) agents. Design, Setting, and Participants: This population-based cohort study included patients undergoing IVTs from January 1, 2012, through December 31, 2015, in France. Data were acquired from the French medical-administrative database (Système National d'Information Inter-Régime de l'Assurance Maladie), which collects hospitalization discharge abstracts and out-of-hospital care information for the whole country. Data were analyzed from March through July 2017. Exposures: Intravitreal injections of corticosteroid or anti-VEGF agents. Main Outcomes and Measures: Incidence of acute endophthalmitis within 6 weeks after IVT by means of billing codes from a national database. Results: During the study period, 1 811 977 IVTs of corticosteroids or anti-VEGF agents performed on 254 927 patients (60.4% female; median age, 79 years [interquartile range, 70-85 years]) were analyzed. A total of 444 acute endophthalmitis cases (crude incidence, 0.0245%) were recorded. In multivariable analysis, which did not include adjustment for when the endophthalmitis occurred during the study period, the risk of endophthalmitis was lower in male patients (incidence rate ratio [IRR], 0.78; 95% CI, 0.63-0.96; P = .02), higher for corticosteroids than for anti-VEGF agents (IRR, 3.21; 95% CI, 2.33-4.44; P \textless .001), and higher for nonprefilled syringes of anti-VEGF medications than prefilled syringes for ranibizumab (IRR, 1.63; 95% CI, 1.15-2.30) and aflibercept (IRR, 1.82; 95% CI, 1.25-2.66; P \textless .001). Conclusions and Relevance: The findings from this study of a nationwide database appear to have confirmed the low incidence rate of acute endophthalmitis after IVTs of corticosteroids or anti-VEGF agents. Although an association may not necessarily indicate a cause and effect, the risk for acute endophthalmitis after IVTs appeared to be higher for corticosteroids compared with anti-VEGF agents, while a lower risk of endophthalmitis appeared to be found with prefilled syringes of anti-VEGF medications.