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Alteration of the outer retina leads to various diseases such as age-related macular degeneration or retinitis pigmentosa characterized by decreased visual acuity and ultimately blindness. Despite intensive research in the field of retinal disorders, there is currently no curative treatment. Several therapeutic approaches such as cell-based replacement and gene therapies are currently in development. In the context of cell-based therapies, different cell sources such as embryonic stem cells, induced pluripotent stem cells, or multipotent stem cells can be used for transplantation. In the vast majority of human clinical trials, retinal pigment epithelial cells and photoreceptors are the cell types considered for replacement cell therapies. In this review, we summarize the progress made in stem cell therapies ranging from the pre-clinical studies to clinical trials for retinal disease.

In 2021, WHO Member States endorsed a global target of a 40-percentage-point increase in effective refractive error coverage (eREC; with a 6/12 visual acuity threshold) by 2030. This study models global and regional estimates of eREC as a baseline for the WHO initiative.The Vision Loss Expert Group analysed data from 565 448 participants of 169 population-based eye surveys conducted since 2000 to calculate eREC (met need/[met need + undermet need + unmet need]). A binary logistic regression model was used to estimate eREC by Global Burden of Disease (GBD) Study super region among adults aged 50 years and older.In 2021, distance eREC was 79·1% (95% CI 72·4-85·0) in the high-income super region; 62·1% (54·7-68·8) in north Africa and Middle East; 49·5% (45·0-54·0) in central Europe, eastern Europe, and central Asia; 40·0% (31·7-48·2) in southeast Asia, east Asia, and Oceania; 34·5% (29·4-40·0) in Latin America and the Caribbean; 9·0% (6·5-12·0) in south Asia; and 5·7% (3·1-9·0) in sub-Saharan Africa. eREC was higher in men and reduced with increasing age. Global distance eREC increased from 2000 to 2021 by 19·0%. Global near vision eREC for 2021 was 20·5% (95% CI 17·8-24·4).Over the past 20 years, distance eREC has increased in each super region yet the WHO target will require substantial improvements in quantity and quality of refractive services in particular for near vision impairment.WHO, Sightsavers, The Fred Hollows Foundation, Fondation Thea, Brien Holden Vision Institute, Lions Clubs International Foundation.

Myopia typically starts and progresses during childhood, but onset and progression can occur during adulthood. The goals of this review are to summarize published data on myopia onset and progression in young adults, aged 18 to 40 years, to characterize myopia in this age group, to assess what is currently known, and to highlight the gaps in the current understanding. Specifically, the peer-reviewed literature was reviewed to: characterize the timeline and age of stabilization of juvenile-onset myopia; estimate the frequency of adult-onset myopia; evaluate the rate of myopia progression in adults, regardless of age of onset, both during the college years and later; describe the rate of axial elongation in myopic adults; identify risk factors for adult onset and progression; report myopia progression and axial elongation in adults who have undergone refractive surgery; and discuss myopia management and research study design. Adult-onset myopia is common, representing a third or more of all myopia in western populations, but less in East Asia, where onset during childhood is high. Clinically meaningful myopia progression continues in early adulthood and may average 1.00 diopters (D) between 20 and 30 years. Higher levels of myopia are associated with greater absolute risk of myopia-related ocular disease and visual impairment, and thus myopia in this age group requires ongoing management. Modalities established for myopia control in children would be options for adults, but it is difficult to predict their efficacy. The feasibility of studies of myopia control in adults is limited by the long duration required.

BackgroundData on population-based self-reported dual vision and hearing impairment are sparse in Europe. We aimed to investigate self-reported dual sensory impairment (DSI) in European population.MethodsA standardised questionnaire was used to collect medical and socio-economic data among individuals aged 15 years or more in 29 European countries. Individuals living in collective households or in institutions were excluded from the survey.ResultsAmong 296 677 individuals, the survey included 153 866 respondents aged 50 years old or more. The crude prevalence of DSI was of 7.54% (7.36–7.72). Among individuals aged 60 or more, 9.23% of men and 10.94% of women had DSI. Eastern and southern countries had a higher prevalence of DSI. Multivariable analyses showed that social isolation and poor self-rated health status were associated with DSI with ORs of 2.01 (1.77–2.29) and 2.33 (2.15–2.52), while higher income was associated with lower risk of DSI (OR of 0.83 (0.78–0.89). Considering country-level socioeconomic factors, Human Development Index explained almost 38% of the variance of age-adjusted prevalence of DSI.ConclusionThere are important differences in terms of prevalence of DSI in Europe, depending on socioeconomic and medical factors. Prevention of DSI does represent an important challenge for maintaining quality of life in elderly population.

Undetected refractive errors (REs) in children can lead to irreversible vision loss. This study aimed to show the proportions of REs in French children using cycloplegic refraction. Multicentre cross-sectional retrospective study including children with cycloplegic refraction and without associated ocular conditions from 2015 to 2018 in French eye clinics. The following data were collected: age, symptoms of eye strain, best-corrected visual acuity (BCVA), cycloplegic refraction. The analysis included 48,163 children (mean age: 7.75 years, range: 2 to 12 years). The proportion of each RE was as follows: emmetropia (− 0.50 $$ < SE $$\le$$ ≤ +5; 17.2%), myopia (− 6 $$\le$$ ≤ SE $$\le$$ ≤ − 0.50; 15.5%), high myopia (SE + 5; 3.6%), mixed astigmatism (4.9%). Anisometropia (SE difference ≥ 1.5) was found in 5.0%. Functional amblyopia in children attending primary school (aged over 6 years) was encountered in 2.7%. Symptoms of eye strain were frequent (70%) but not specific to any RE. REs are frequently found in French children and may remain undetected in the absence of symptoms of eye strain. Few studies have investigated REs in children using cycloplegic refraction, which has been shown to be the gold standard for RE assessment.

BackgroundThe prevalence of myopia is increasing worldwide. The purpose of this study was to evaluate the progression of myopia in teenagers and adults in France.MethodsThis nationwide prospective study followed 630 487 myopic adults and teenagers (mean age 43.4 years±18.2, 59.8% of women) between January 2013 and January 2019. Myopia and high myopia were defined as a spherical equivalent less than or equal to –0.50 and –6.00 diopters (D), respectively. Demographic data were collected at first visit and refractive characteristics were collected at each visit. Analysis of short-term progression (first 12 to 26 months postbaseline) was modelled using analysis of variance (ANOVA). Progression of myopia was stratified according to age, gender and spherical equivalent at first visit.ResultsHigher proportions of progressors were observed in the youngest age groups: 14–15 (18.2 %) and 16–17 years old (13.9 %). In multivariate analysis, after adjustment for over age, spherical equivalent and gender, the mean short-term progression decreased from –0.36 D in the 14–15 years age group to –0.13 D in the 28–29 years age group. Young age and higher myopia at baseline together were strongly associated with the risk of developing high myopia, the 5-year cumulative risk being 76% for youngest teenager with higher myopia status at baseline.ConclusionIn this large cohort of myopic teenagers and adults, myopia progression was reported in 18.2% and 13.9% of the 14–15 and 16–17 age groups, respectively. The risk to develop high myopia was higher for younger individuals with higher myopia at baseline examination.

Age-related macular degeneration (AMD) is characterized by retinal pigment epithelial (RPE) cell dysfunction beginning at early stages of the disease. The lack of an appropriate in vitro model is a major limitation in understanding the mechanisms leading to the occurrence of AMD. This study compared human-induced pluripotent stem cell- (hiPSC-) RPE cells derived from atrophic AMD patients (77 y/o ± 7) to hiPSC-RPE cells derived from healthy elderly individuals with no drusen or pigmentary alteration (62.5 y/o ± 17.5). Control and AMD hiPSC-RPE cell lines were characterized by immunofluorescence, flow cytometry, and electronic microscopy. The toxicity level of iron after Fe-NTA treatment was evaluated by an MTT test and by the detection of dichloro-dihydro-fluorescein diacetate. Twelve hiPSC-RPE cell lines (6 AMD and 6 controls) were used for the experiment. Under basal conditions, all hiPSC-RPE cells expressed a phenotypic profile of senescent cells with rounded mitochondria at passage 2. However, the treatment with Fe-NTA induced higher reactive oxygen species production and cell death in hiPSC-RPE AMD cells than in hiPSC-RPE Control cells. Interestingly, functional analysis showed differences in lysosomal activity between the two populations. Indeed, Cathepsin B activity was higher in hiPSC-RPE AMD cells compared to hiPSC-RPE Control cells in basal condition and link to a pH more acidic in this cell population. Moreover, oxidative stress exposure leads to an increase of Cathepsin D immature form levels in both populations, but in a higher proportion in hiPSC-RPE AMD cells. These findings could demonstrate that hiPSC-RPE AMD cells have a typical disease phenotype compared to hiPSC-RPE Control cells.

BackgroundData on myopia prevalence and progression in European children are sparse. The aim of this work was to evaluate the progression of myopia in children and teenagers in a large prospective study.MethodsA prospective study involving a nationwide cohort. Myopia was defined as a spherical equivalent (SE) of ≤ –0.50 diopters (D). Data on refractive error, gender and age were collected in 696 optical centres in France between 2013 and 2019, including 136 333 children (4–17 years old) in the analysis.Progression of myopia was assessed between the first visit and the last visit over up to 6.5 years.ResultsMean age was 11.3±3.8 years (55.0% of female). The proportion of children progressing more than –0.50 D per year was higher in age groups 7–9 years and 10–12 years and in children with SE ≤ –4.00 D at first visit, representing 33.1%, 29.4% and 30.0% of these groups, respectively. In multivariate analysis, progression during the first 11–24 months was higher in the 7–9 and 10–12 age groups (–0.43 D and –0.42 D, respectively), for higher SE at baseline (at least –0.33 D for SE ≤ –1 D) and for girls (–0.35 D).ConclusionThis is the first French epidemiological study to investigate myopia progression in a large-scale cohort of children. Sex, age groups and myopia severity are associated with differing rates of progression.

Retina is the part of the eye suffering most damage from pharmaceutical molecules. Drug-induced retinopathies have been described but data are scarce and sometimes conflicting especially concerning its potential seriousness. The aim of this study was to investigate potential associations between drugs and retinal disorders using the French Pharmacovigilance data. We used the case/non-case method in the French PharmacoVigilance Database (FPVD) to identify drugs able to induce retinopathies. Cases were reports of retinal disorders in the FPVD between January 2008 and December 2012. Non-cases were all other reports during the same period. To assess the association between retinopathy and drug intake, we calculated the odds-ratio (OR) [with their 95% confidence intervals] for all drugs associated with at least 3 cases of retinopathy. Among the 123 687 adverse drug reactions recorded during the studied period, we identified 164 cases of retinal disorders. Significant associations were found for 11 drugs. The main therapeutic classes were antirhumatismals (hydroxychloroquine, chloroquine and etanercept: 18 cases), anti-infective (ribavirine, PEG-interferon-alfa-2a and cefuroxime: 16 cases) and antineoplastic drugs (imatinib and letrozole: 8 cases. Three other drugs were also found: raloxifene (5 cases), erythropoietin beta (4 cases) and ranibizumab (3 cases). Taking into account the limits of the methodology, our study confirmed the association between retinopathy and some expected drugs such as aminoquinolines, interferons, imatinib or ranibizumab. Other drugs like erythropoietin beta, cefuroxime, letrozole and etanercept were significantly associated with retinal disorders although this was not or poorly described in the literature. Thus, further prospective studies are necessary to confirm such associations.

A low concentration of macular carotenoid pigment (lutein and zeaxanthin) is a significant risk factor for macular degeneration. The goal of this paper is to investigate the relationship between macular pigment optical density (MPOD) and lacquer cracks (LC) in high myopia.This is a prospective comparative observational study (NCT02205632) including high myopic patients with or without LC. High myopia was defined as a refractive error greater than 6 diopters of myopia or axial length greater than 26mm. All patients underwent best-corrected visual acuity in logMAR, MPOD measurement, multicolor imaging, SD-OCT, autofluorescence and axial length measurement. MPOD was calculated using heterochromatic flicker photometry. Group 1 was defined as eyes without LC and group 2 as eyes with LC.Forty-five eyes of 32 patients with a mean age of 51.3 years were included in group 1, and 15 eyes of 13 patients aged 54.1 in group 2 (P=0.56). Mean spherical equivalent was -10.11 diopters in group 1 and -15.11 in group 2 (P=0.0004). Mean visual acuity was +0.08 logMAR (0.8 in decimal notation) in group 1 and +0.11 logMAR (0.8 in decimal notation) in group 2 (P=0.061). Axial length was 27.8mm in group 1 and 29.2 in group 2 (P=0.0052). Central macular thickness was lower in group 1 (295μm) than in group 2 (305μm) (P0.0001), and macular choroidal thickness did not differ between the two groups (P=0.094). Mean MPOD in group 2 was 0.52 and 0.63 in group 1 (P=0.042). Differences in axial length were not related to MPOD measurements (P=0.74).A lower rate of MPOD was observed in cases of LC in high myopia. Further studies are needed to investigate if dietary carotenoids could have a protective effect in reducing the risk of LC.

Purpose:\ud \ud Uncorrected refractive errors are the first cause of vision impairment worldwide. High myopia is a frequent cause of sight‐threatening chorioretinal complications. The aim of this study was to evaluate the prevalence of macular complications, visual impairment and blindness in patients with myopia.\ud \ud Methods:\ud \ud A cross‐sectional multicenter study carried out in French eye clinics mainly dedicated to refractive errors. Myopia severity was defined as mild (−0.5 to −3 D), moderate (−3 to −6 D), high (−6 to −10 D) and very high (more than −10 D). Macular complications related to myopia included lacquer cracks, myopic choroidal neovascularization, chorioretinal atrophy and retinoschisis. The prevalences of macular complications, blindness and vision impairment were estimated with respect to degree of myopia and age. Eligibility criteria were myopia on the left eye of −0.5 D or more. Exclusion criteria included any missing data related to subjective refractive error, age, gender and any history of cataract or refractive surgery.\ud \ud Results:\ud \ud Data files from 198 641 myopic individuals with a mean age of 34 years (SD: 15 years) were analysed. The prevalence of mild, moderate, high and very high myopia was, respectively, 65.95%, 26.14%, 6.72% and 1.19%. The prevalence of macular complications in the high and very high myopia groups was 0.5% [0.39–0.64] and 4.27% [3.49–5.17]. The prevalence of blindness or vision impairment was observed in 10.10% [8.91–11.39%] of the very high myopic group. At 60 years old or over, the prevalences of blindness or vision impairment were, respectively, 9.75% [7.91–11.85%] and 25.71% [21.00–30.87%] in the high and very high myopia groups.\ud \ud Conclusions:\ud \ud This multicenter cross‐sectional study provides new insights in terms of prevalence of macular complications related to myopia. To our knowledge, this is one of the largest European studies focusing on individuals with myopia, particularly on the macular complications and the functional consequences in relation to myopia.

The ARPE-19 cell line is currently used as an in vitro model for retinal diseases such as age-related degeneration (AMD). However, several studies have pointed out morphological and genetic differences between ARPE-19 cells and human fetal or adult retinal pigment epithelial (hRPE) cells. This study aims to compare ARPE-19 cells to hRPE cells derived from human induced pluripotent stem cells (hiPSCs) in both normal and oxidative stress conditions induced by Fe-NTA treatment. Indeed, oxidative stress is an essential contributing factor in AMD. hiPSC obtained from peripheral venous blood samples or fibroblasts of individuals aged over 60 years were first reprogrammed to hiPSC and then differentiated into RPE cells. In contrast to ARPE-19 cells, hiPSC-RPE cells expressed β-galactosidase activity, suggesting that only the latter display signs of senescence. Treatment with 10 mM of FeNTA induced a higher reactive oxygen species (ROS) production and increased cell death in hiPSC-RPE cells compared to ARPE-19 cells. Moreover, morphological analysis and Annexin V and Propidium iodide (PI) test suggested a necrotic cell death pattern induced by treatment in hiPSC-RPE cells that is not observed in ARPE-19 cells. Taken as a whole, our findings suggest that hiPSC-RPE cells are more sensitive to oxidative stress than ARPE-19 cells.

Purpose The pathophysiologic pathways that govern the development of choroidal neovascularization (CNV) are complex. Patchy atrophy and lacquer cracks are known to be major anatomic risk factors for the development of myopic CNV, but they are not alone and much remains to be understood about other factors that influence development. In addition, a greater understanding of the modifiable and nonmodifiable factors that influence outcome, resolution, and recurrence after intravitreal injection of anti-vascular endothelial growth factor (VEGF) could lead to more personalized treatment algorithms that integrate parameters other than the presence of CNV itself and could help improve clinical outcomes and reduce recurrence. Methods We reviewed recently published data on risk factors for CNV and predictors of response to anti-VEGF treatments. In particular, data pertaining to age, sex, genetic predisposition, baseline visual acuity, axial length, staphyloma, lacquer cracks, atrophic lesions, choroidal thickness or choroidal thinning, characteristics of CNV such as duration, localization, and size of CNV, and treatment considerations such as choice of treatment, loading doses, and combination treatments were reviewed. Results Our analysis showed that the body of evidence is incomplete. Conclusions Additional studies are required to identify high-risk patients and to develop personalized therapeutic approaches.

International audience

Purpose: Age-related macular degeneration (AMD) is the main cause of visual loss in the elderly population. With the use of anti-vascular endothelial growth factor, the visual outcomes of exudative AMD patients have been improved. This study was aimed at assessing the quality of life (QoL) of exudative AMD patients treated with ranibizumab and at determining its drivers in a real-life setting. Methods: We performed a national, cross-sectional, observational survey based on questionnaires sent to members of French associations relative to AMD between December 2012 and March 2013. Patients suffering from exudative AMD with at least one intravitreal injection of ranibizumab within the last 6 months were included. Demographics, AMD characteristics, visual acuity (VA) and past and ongoing treatments were collected. The 25-item National Eye Institute Visual Function Questionnaire (NEI-VFQ-25) was self-administered. A multivariate model was used to identify QoL drivers. Results: 416 questionnaires fulfilled the complete criteria for both QoL and cost analyses. The mean age of exudative AMD patients was 78.0 years and bilateral involvement was reported in 60.4%. The overall mean QoL score was 53.4. Mental health, driving and role difficulties were the most widely affected domains. After bivariate analyses, long-term illness status, worse VA and higher number of unpaid aids were associated with worse QoL, with odds ratios of 2.4, 5.2 and 11.6, respectively. The mean cost per year and per patient was 1,741 EUR. The main components of costs were aids and services and the purchase of visual equipment. Conclusions: The main predictors of QoL in exudative AMD patients treated with ranibizumab are VA outcomes, home healthcare and social services provided to the patients.

Choroidal neovascularisation (CNV) is a common vision-threatening complication of myopia and pathological myopia. Despite significant advances in understanding the epidemiology, pathogenesis and natural history of myopic CNV, there is no standard definition of myopic CNV and its relationship to axial length and other myopic degenerative changes. Several treatments are available to ophthalmologists, but with the advent of new therapies there is a need for further consensus and clinical management recommendations. Verteporfin photodynamic therapy has been an established treatment for subfoveal myopic CNV for many years, but this treatment does not restore visual acuity and is associated with long-term chorioretinal atrophy. More recently, clinical trials investigating the efficacy and safety of anti-vascular endothelial growth factor agents in patients with myopic CNV have demonstrated substantial visual acuity gains and quality of life increases compared with photodynamic therapy. These enhanced outcomes provide updated evidence-based clinical management guidelines of myopic CNV, and increase the need for a generally accepted definition for myopic CNV. This review critically summarises the latest myopic CNV literature in the context of clinical experience and recommends a myopic CNV treatment algorithm.

Purpose: The aim of this study was to detect immune responses induced by intravitreal injection (IVT) of ranibizumab in patients with exudative age-related macular degeneration (AMD) in real life conditions. Methods: An ELISA protocol from blood samples, following 2 different steps, was used to detect antibodies directed against the variable regions of ranibizumab. Results: Among 91 patients included, 46 received more than 10 IVTs, 36 had received 10 IVTs or fewer, and 9 were treatment naïve. Specific antiranibizumab immunoglobulins G were detected in 14/82 treated patients (17.1%). No immunization was detected among naïve patients. For patients with 10 or fewer previous IVTs, immunization against ranibizumab was detected in 4/36 patients (11.1%) whereas immunization was observed in 10/46 patients (21.7%) with more IVTs (p = 0.20). Conclusions: Immunization against ranibizumab can be detected in 17% of treated patients. Further clinical studies are needed to investigate the relationship between specific immunization to anti-vascular endothelial growth factor antibodies and response or resistance to ranibizumab treatments.

International audience; Fluorescein angiography has been so far the gold-standard test to assess diabetic macular ischemia (DMI), a cause of irreversible visual impairment in diabetic patients. The aim of this study was to investigate foveal avascular zone (FAZ) and perifoveal microcirculation changes in eyes with nonproliferative diabetic retinopathy (NPDR) using optical coherence tomography angiography (OCTA), a new and noninvasive vascular imaging technique.Cross-sectional study including eyes of diabetic patients with NPDR.All patients underwent medical history, best-corrected visual acuity (BCVA) measurement, slit-lamp and fundus examination, multicolor imaging, SD-OCT, and swept-source OCT. OCTA was performed in order to assess macular superficial and deep capillary plexus, and swept-source OCT was performed to evaluate the central choroidal thickness.Fifty-eight eyes of 35 patients with a mean age of 61.8 years (±12.1) with mean HbA1C level of 7.6% (±1.5) were included in this study. Among them, 19 eyes had mild NPDR, 24 eyes had moderate NPDR, and 15 eyes had severe NPDR. There was a significant progression between NPDR stages for FAZ grade (P

Purpose. - To describe the results obtained with intravitreal ranibizumab injections in a patient with adult onset foveomacular vitelliform dystrophy (AOFVD) complicated by Type 3 choroidal neovascularization (CNV). Methods. - A 78-year old man diagnosed with AOFVD presented at our department for decreased vision in his left eye (LE) (20/80). Upon a complete ophthalmologic examination, including fluorescein angiography, indocyanine green angiography, and spectral-domain optical coherence tomography, the patient was diagnosed with Type 3 CNV. Three monthly injections of ranibizumab 0.05 ml/0.5 mg were administered intravitreally without complications. Results. - After the first injection, visual acuity of the LE improved (20/64) and regression of the Type 3 CNV was observed by fluorescein angiography, indocyanine green angiography and OCT. Six months after the final ranibizumab injection, a more-or-less complete resolution of the exudative retinal changes was observed. Conclusions. - Type 3 CNV may be associated with AOFVD. Intravitreal ranibizumab may represent a possible therapeutic option in this unusual context. (C) 2012 Elsevier Masson SAS. All rights reserved. Purpose. - To describe the results obtained with intravitreal ranibizumab injections in a patient with adult onset foveomacular vitelliform dystrophy (AOFVD) complicated by Type 3 choroidal neovascularization (CNV). Methods. - A 78-year old man diagnosed with AOFVD presented at our department for decreased vision in his left eye (LE) (20/80). Upon a complete ophthalmologic examination, including fluorescein angiography, indocyanine green angiography, and spectral-domain optical coherence tomography, the patient was diagnosed with Type 3 CNV. Three monthly injections of ranibizumab 0.05 ml/0.5 mg were administered intravitreally without complications. Results. - After the first injection, visual acuity of the LE improved (20/64) and regression of the Type 3 CNV was observed by fluorescein angiography, indocyanine green angiography and OCT. Six months after the final ranibizumab injection, a more-or-less complete resolution of the exudative retinal changes was observed. Conclusions. - Type 3 CNV may be associated with AOFVD. Intravitreal ranibizumab may represent a possible therapeutic option in this unusual context. (C) 2012 Elsevier Masson SAS. All rights reserved.

Resume Introduction La neovascularisation myopique est la premiere cause de neovaisseaux choroidiens chez le sujet jeune. Le seul traitement a avoir l’autorisation de mise sur le marche est la phototherapie dynamique a la visudyne (PDT). Le but de cette etude etait de comparer l’efficacite du traitement par ranibizumab au traitement par PDT. Patients et methodes Etude retrospective comparant le traitement par ranibizumab au traitement par PDT chez des patients avec neovaisseaux choroidiens myopiques. Chaque patient a beneficie d’un examen ophtalmologique complet. Resultats Vingt-sept yeux de 25 patients naifs traites par PDT (groupe 1) et 18 yeux de 17 patients naifs traites par IVT de ranibizumab (groupe 2) ont ete etudies. Les donnees demographiques et le degres de myopie etaient similaires entre les deux groupes. L’AV mediane initiale etait de 20/80 pour le groupe 1 et de 20/160 pour le groupe 2 ( p = 0,37). A un an l’AV mediane etait de 20/80 pour le groupe 1 ( p = 0,32) et de 20/63 dans le groupe 2 ( p = 0,04). Une amelioration de trois lignes ou plus etait presente a un an dans 23,1 % et dans 27,3 % des cas respectivement dans les groupe 1 et 2 ( p = 0,53). Une perte de trois lignes ou plus etait presente a un an dans 34,6 % des cas dans le groupe 1 et dans 9,1 % des cas dans le groupe 2 ( p = 0,21). Conclusion Cette etude confirme la superiorite du traitement par anti-VEGF par rapport a la PDT dans cette indication. S’il est licite de se poser la question d’une etude prospective comparative, il semble peu ethique de mener actuellement une telle etude.

Major genetic factors for age-related macular degeneration (AMD) have recently been identified as susceptibility risk factors. The CX3CR1 gene has been shown to be associated with AMD in some studies. Our purpose was to analyze the role of the T280M polymorphism of the CX3CR1 gene in a large French population, in a case-control study. 1093 patients with exudative AMD and 396 controls have been recruited and genotyped for the Y402H of CFH, rs10490924 of ARMS2 and T280M of the CX3CR1 gene. The distribution of the Y402H of CFH and of the rs10490924 of ARMS2 was significantly different between cases and controls (p 0.0001). The distribution of the T280M genotypes was not significantly different in the AMD patients compared to controls (p = 0.99). The Odds Ratio compared to TT individuals was 1.0 (95% CI 0.8-1.3) for TM individuals and 1.0 (95% CI 0.5-2.1) for MM individuals. The M allele frequency was 0.157 in cases and 0.154 in controls (p = 0.87). Our study exclude an association between the T280M of the CX3CR1 gene and exudative AMD in a French population.

Despite significant progress in the identification of genetic loci for age-related macular degeneration (AMD), not all of the heritability has been explained. To identify variants which contribute to the remaining genetic susceptibility, we performed the largest meta-analysis of genome-wide association studies to date for advanced AMD. We imputed 6 036 699 single-nucleotide polymorphisms with the 1000 Genomes Project reference genotypes on 2594 cases and 4134 controls with follow-up replication of top signals in 5640 cases and 52 174 controls. We identified two new common susceptibility alleles, rs1999930 on 6q21-q22.3 near FRK/COL10A1 [odds ratio (OR) 0.87; P = 1.1 x 10(-8)] and rs4711751 on 6p12 near VEGFA (OR 1.15; P = 8.7 x 10(-9)). In addition to the two novel loci, 10 previously reported loci in ARMS2/HTRA1 (rs10490924), CFH (rs1061170, and rs1410996), CFB (rs641153), C3 (rs2230199), C2 (rs9332739), CFI (rs10033900), LIPC (rs10468017), TIMP3 (rs9621532) and CETP (rs3764261) were confirmed with genome-wide significant signals in this large study. Loci in the recently reported genes ABCA1 and COL8A1 were also detected with suggestive evidence of association with advanced AMD. The novel variants identified in this study suggest that angiogenesis (VEGFA) and extracellular collagen matrix (FRK/COL10A1) pathways contribute to the development of advanced AMD. Hum Mol Genet

Age related macular degeneration (AMD) is the leading cause of vision loss in the elderly in developed countries. Genetic factors play a major role in this multifactorial and polygenic disease. Genomewide analysis identified two loci on 1q25-31 and 10q26 chromosomes associated with AMD, and association studies highlighted the implication of SNPs located in the complement H factor gene (CFH) on 1q25-31 and in PLEKHA1-HTRA1-LOC387715 on 10q26 in the disease. Homozygous carriers for the at-risk alleles of the CFH, HTRA1, and LOC387715 genes have an increased risk to develop exudative AMD with odds ratio of 6.2, 6.9, et 7.3 respectively. Moreover, other genes involved in the complement cascade, namely the genes of the C2, C3 component, and factor B, are associated to the disease. The SCARB1 gene has also recently been associated to AMD. Genotype-phenotype correlations have been performed in AMD patients and found that occult CNV are more often associated to CFH at-risk allele and classic CNV to HTRA1 at-risk allele. This last allele seems also linked to more severe forms of the disease. These new major genetic factors could lead to a new clinical approach of AMD and to the discovery of new therapeutic targets.

Dans les pays developpes, la degenerescence maculaire liee a l’âge (DMLA) represente la premiere cause de cecite apres 55 ans. Au cours des dernieres annees, un faisceau d’arguments tels que l’agregation familiale et les etudes sur les jumeaux avaient suggere une composante genetique dans la DMLA. Leslimites de la mise en evidence de ces facteurs genetiques tiennent d’une part, au fait qu’il existe peu de grandes familles avec plusieurs generations de vivants analysables et, d’autre part, au fait qu’il s’agit d’une maladie multifactorielle et polygenique. La strategie de type gene candidat a permis d’exclure plusieurs genes (VMD2, RDS, TIMP3) et de demontrer l’implication de deux facteurs de predisposition genetique : le gene de l’apoE (proteine de transport des lipides), et le gene ABCA4 (gene de la maladie de Stargardt). L’analyse de cartographie a partir d’etude de paires de germains a permis d’identifier plusieurs loci lies a la DMLA. Secondairement, l’analyse de SNPs (single nucleotide polymorphism) a conduit a l’association entre le polymorphisme Tyr402His du gene CFH, le polymorphisme Ala69Ser du locus LOC387715 , et la DMLA.

Summary Purpose To describe the prevalence of macular complications in patients with visual acuity decrease related to high myopia (HM). To establish correlations between these complications and demographic or anatomical characteristics. Materials and methods Cross-sectional observational study including HM patients undergoing best-corrected visual acuity (BCVA), fundus examination, macular SD-OCT, and fluorescein angiography in the case of suspicion of choroidal neovascularization (CNV). The presence of anatomical criteria (staphyloma, subfoveal choroidal thickness [CT]) and macular complications (CNV, lacquer cracks, central chorioretinal atrophy, dome-shaped macula with serous retinal detachment [SRD], retinal foveoschisis, macular hole and epiretinal membrane) was investigated. Results A total of 87 eyes of 47 patients were included (39 eyes without macular complication and 48 eyes with macular complications). In the case of macular complications, decrease in BCVA was related to CNV in 33%, macular hole in 25%, chorioretinal atrophy in 19%, foveoschisis in 11%, lacquer crack in 6%, to a dome-shape macula with serous retinal detachment in 4% and epiretinal membrane in 2%. After adjusting for interocular correlation and degree of myopia, staphyloma ( P = 0.0023), choroidal thinning ( P = 0.0036), and extrafoveal chorioretinal atrophy ( P = 0.042) were significantly associated with macular complications. Conclusions High myopic patients with staphyloma or choroidal thinning should undergo regular comprehensive retinal screening for retinal complications.

Retina is the part of the eye suffering most damage from pharmaceutical molecules. Drug-induced retinopathies have been described but data are scarce and sometimes conflicting especially concerning its potential seriousness. The aim of this study was to investigate potential associations between drugs and retinal disorders using the French Pharmacovigilance data. We used the case/non-case method in the French PharmacoVigilance Database (FPVD) to identify drugs able to induce retinopathies. Cases were reports of retinal disorders in the FPVD between January 2008 and December 2012. Non-cases were all other reports during the same period. To assess the association between retinopathy and drug intake, we calculated the odds-ratio (OR) [with their 95% confidence intervals] for all drugs associated with at least 3 cases of retinopathy. Among the 123 687 adverse drug reactions recorded during the studied period, we identified 164 cases of retinal disorders. Significant associations were found for 11 drugs. The main therapeutic classes were antirhumatismals (hydroxychloroquine, chloroquine and etanercept: 18 cases), anti-infective (ribavirine, PEG-interferon-alfa-2a and cefuroxime: 16 cases) and antineoplastic drugs (imatinib and letrozole: 8 cases. Three other drugs were also found: raloxifene (5 cases), erythropoietin beta (4 cases) and ranibizumab (3 cases). Taking into account the limits of the methodology, our study confirmed the association between retinopathy and some expected drugs such as aminoquinolines, interferons, imatinib or ranibizumab. Other drugs like erythropoietin beta, cefuroxime, letrozole and etanercept were significantly associated with retinal disorders although this was not or poorly described in the literature. Thus, further prospective studies are necessary to confirm such associations.

Purpose To report the incidence and characteristics of endophthalmitis after intravitreal injections of anti–vascular endothelial growth factor agents or corticosteroids and to describe the clinical and bacteriologic characteristics, management, and outcome of these eyes with acute endophthalmitis in France. Design Retrospective, nationwide multicenter case series. Methods From January 2, 2008 to June 30, 2013, a total of 316 576 intravitreal injections from 25 French ophthalmic centers were included. For each center, the number of intravitreal injections was determined using billing codes and the injection protocol was recorded. A registry and hospital records were reviewed to identify patients treated for endophthalmitis after injection during the same time period. The main outcome measures were the incidence of clinical endophthalmitis and visual acuity of endophthalmitis cases. Results During the study period, 65 cases of presumed endophthalmitis were found, giving an overall incidence of 0.021% (2.1 in 10 000 injections) (95% confidence interval [CI], 0.016%–0.026%). The median number of days from injection to presentation was 4 [1–26] days. The most common symptom was vision loss. Bacterial identification was achieved in 43.4%. The most frequent pathogens were gram-positive bacteria (91.3%), including coagulase-negative Staphylococcus in 78.3%. Neither the interval between injection and presentation for endophthalmitis nor the clinical signs differentiated culture-positive from culture-negative cases. In multivariate analysis, the use of a disposable conjunctival mould assist device and the use of prophylaxis with an antibiotic or antiseptic were significantly associated with an increased incidence of endophthalmitis ( P = .001). The majority of patients had worse visual acuity after 3 months of follow-up when compared with acuity before endophthalmitis. Conclusions The incidence of presumed endophthalmitis after intravitreal injections of anti–vascular endothelial growth factors or corticosteroids was low and the prognosis poor. Prevention and management remain challenging. It remains to be determined whether the findings of this study are relevant for other countries using different techniques for intravitreal injections.

Background/aim: Malattia leventinese (ML) is an inherited macular degeneration characterised by the presence of small radial drusen. Despite extensive descriptions of this study of the fundus, angiographic features of ML have been inadequately described. The aim is to describe the indocyanine green angiography (ICG) features observed in ML. Methods: 10 eyes from five consecutive ML patients (aged 27–44 years) were prospectively included. A complete ophthalmological examination including colour fundus photographs, autofluorescence, fluorescein angiography (FA), and ICG was performed. Results: ICG differentiated two types of drusen. Large round aggregated drusen were consistently hypofluorescent in the early phases and presented as hyperfluorescent spots surrounded by halos of hypofluorescence in the late phases. Conversely, small radial drusen were mostly hyperfluorescent in the early phases with decreased fluorescence in the late phases of the ICG sequence. FA also showed differences in staining between the two types of drusen. Conclusions: ICG angiography revealed marked differences between the large round and small radial drusen observed in ML. The large central drusen presented with an unusual pustuliform feature on the late phases of the ICG sequence. This distinct feature may be useful in the diagnosis of late stage disease when drusen consolidation could obscure the radial drusen.

Purpose: To compare the ability of spectral domain optical coherence tomography (SD-OCT), blue light fundus autofluorescence (FAF), and near-infrared fundus autofluorescence (NIR-FAF) to evaluate foveal involvement in geographic atrophy as a result of age-related macular degeneration. Methods: All consecutive patients with geographic atrophy underwent FAF (excitation lambda = 488 nm; emission lambda > 500 nm), NIR-FAF (excitation lambda = 787 nm; emission lambda > 800 nm), and simultaneous SD-OCT scanning (Spectralis HRA + OCT; Heidelberg Engineering). Two readers independently graded foveal involvement on FAF, NIR-FAF, and SD-OCT and measured the width of foveal sparing. In eyes with an intergrader agreement of foveal sparing by at least one among FAF, NIR-FAF, and SD-OCT, microperimetry (Spectral OCT/SLO; OPKO-OTI) was analyzed. Results: A total of 158 eyes (83 patients; 53 women, 30 men, mean age 69.2 +/- 4.8 years) with geographic atrophy were included. Spectral domain OCT showed the highest intergrader agreement of foveal involvement (k = k' = 0.8, P = 0.001 vs. k = k' = 0.7, P = 0.01 for NIR-FAF and k = k' = 0.5, P = 0.01 for FAF). In 74 eyes (46.8%) foveal sparing was present according to interobserver agreement. Width of the foveal sparing was larger on SD-OCT than on NIR-FAF and FAF (1,334 +/- 943 mu m vs. 1,228 +/- 912 mu m, P < 0.001 and 1,201 +/- 922 mu m, P < 0.001, respectively). Retinal fixation was predominantly central and stable in 97.3% of eyes with foveal sparing. Conclusion: Spectral domain OCT is an appropriate imaging modality for evaluating the presence and extent of foveal sparing, followed by NIR-FAF and FAF. RETINA 33:482-489, 2013

International audience; Even if a lot of work has been done on Optical Coherence Tomography (OCT) and color images in order to detect and quantify diseases such as diabetic retinopathy, exudates or neovascularizations, none of them is able to evaluate the diffusion of the neovascularizations in retinas. Our work has been to develop a tool able to quantify a neo-vascularization and the fluorescein leakage during an angiography. The proposed method has been developed following a clinical trial protocol, images are taken by a Spectralis (Heidelberg Engineering). Detections are done using a supervised classification using specific features. Images and their detected neovascularizations are then spatially matched by an image registration.We compute the expansion speed of the liquid that we call diffusion index. This last one specifies the state of the disease and permits to indicate the activity of neovascularizations and allows a follow-up of patients. The method proposed in this paper has been built to be robust, even with laser impacts, to compute a diffusion index.

Purpose: To describe the anatomical and functional outcomes in patients with exudative age-related macular degeneration (AMD) undergoing ranibizumab therapy in real-life practice. Methods: This is a retrospective analysis of patients with exudative AMD treated with ranibizumab. Visual acuity (VA) and optic coherence tomography characteristics at baseline and at the end of the follow-up, clinical forms of the disease, delay between diagnosis and treatment as well as the number of follow-up visits and of intravitreal injections were collected. Results: One hundred and seventy-nine patients (220 eyes) were followed up during a mean of 24 months. The mean delay between diagnosis and treatment was 20.3 days (SD ±16.8). VA stabilization was observed in 46.4% of eyes, 21.7% of eyes gained ≥15 ETDRS (Early Treatment Diabetic Retinopathy Study) letters and 31.9% lost ≥15 ETDRS letters. The mean central retinal thickness decreased from 380.6 μm at baseline to 295.6 µm at the final examination. A lower baseline VA score was associated with a greater gain of letters (OR 1.04, 95% CI 1.02-1.06; p < 0.001). Conclusion: Shortening the delays in diagnosis appears to be a key point in real-life situations.

International audience

International audience

Age-related macular degeneration (AMD) is the main cause of vision loss in the elderly in developed countries. The exudative AMD is the most frequent and severe form of the disease, leading to a rapid loss of vision. The results of MARINA and ANCHOR studies, two multicentric clinical trials analyzing the efficacy of anti-VEGF in exudative AMD, have showed that this modality of treatment results in a stabilisation of the visual acuity in most cases (70%), and in visual improvement in 30 % of the cases. Up till now, the anti-VEGF approach represents a major step in the therapeutic strategy of this disease.

Purpose: To analyze the genetic and environmental factors associated with reticular pseudodrusen (RPD) in age-related macular degeneration (AMD). Methods: In a large population, AMD patients (n = 519) with and without RPD were assessed with a standardized examination including infrared images and spectral domain optical coherence tomography scans. Three groups were defined: Group 1: AMD patients with RPD (n = 105); Group 2: AMD patients without RPD (n = 414); and Group 3: controls with no AMD and no RPD (n = 430). Four genes associated with AMD (CFH, ARMS2/HTRA1, C3, apolipoprotein E) and environmental factors were assessed between the 3 groups. Results: None of the environmental factors studied were more significantly associated to either Group 1 or Group 2. The odds ratios and 95% confidence intervals for individuals homozygous for the CFH risk allele were 4.0 (2.1-7.7) ([95% confidence interval: 2.1-7.7]; P < 0.0004) in Group 1 and 4.3 ([2.6-7.1]; P < 0.0004) in Group 2, compared with Group 3. The odds ratios for individuals homozygous for the ARMS2 risk allele for Groups 1 and 2 compared with Group 3 were 16.3 ([7.6-35.4]; P < 0.0004) and 11.9 ([6.3-22.3]; P < 0.0004), respectively. None of the genotypes studied were more significantly associated to Group 1 than Group 2. Conclusion: Genotypes known to be associated with AMD were similarly observed in patients with and without RPD. RETINA 33: 998-1004, 2013

PURPOSE. To describe focal scleral ectasia in areas of macular/perimacular patchy chorioretinal atrophy secondary to pathologic myopia. METHODS. Thirty-nine consecutive patients with pathologic myopia and chorioretinal atrophy in at least one eye, with and without focal scleral ectasia, were analyzed by infrared reflectance (IR) and/or multicolor imaging, enhanced depth imaging optical coherence tomography (EDI-OCT) (39 patients, 78 eyes), and swept source (SS)-OCT (13 out of 39 patients, 26 eyes) cross-sectional scan. RESULTS. Focal scleral ectasia was found in 12 out of 68 eyes (11 out of 39 consecutive patients, 27 females/12 males; mean age 65.7 +/- 11.9 years) with macular/perimacular patchy chorioretinal atrophy, and was always observed inferior or temporal to the macula (mean 1.25 +/- 0.38/eye). Focal scleral ectasia, appearing on fundus examination as a deep dark round/oval lesion with well-defined borders, was characterized on EDI-OCT and SS-OCT by an abrupt posterior bow of the sclera with different degrees of scleral schisis on its borders. The retinal pigment epithelium and the choroid were absent in all lesions. IR reflectance and multicolor imaging showed large vessels that seem to emerge from the focal scleral ectasia, and crossing the area of patchy atrophy. EDI-OCT and SS-OCT revealed retrobulbar vessels perforating the sclera at the borders/bottom of the abrupt posterior bow of the sclera (i.e., focal scleral ectasia) and running through the superficial scleral thickness for the whole extension of the atrophic area. CONCLUSIONS. We showed that perforating vessels are localized at the border/bottom of focal scleral ectasia in pathologic myopia.

Joint Bone Spine - In Press.Proof corrected by the author Available online since mercredi 9 decembre 2015