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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 partially characterized by retinal pigment epithelial (RPE) cell dysfunction. This study focused on phagocytosis activity and its involvement in AMD. Phagocytic activity was analyzed by flow cytometry using porcine photoreceptor outer segment (POS) and fluorescent beads in basal and under oxidative stress condition induced by Fe-NTA in fifteen hiPSC-RPE cell lines (six controls, six atrophic AMD and three exudative AMD). Oxidative stress exposure inhibited phagocytosis in the same manner for control, atrophic AMD (AMDa) and exudative AMD (AMDe) cell lines. However, altered phagocytosis in basal condition in hiPSC-RPE AMDa/e was observed compared to control cell lines. Gene expression after 3 or 24 h of POS incubation was analyzed by RNA-Seq based transcriptomic profiling. Differential gene expression was observed by RNA seq after 3 and 24 h POS exposure. We have focused on the genes involved in mTOR/PI3K-AKT/MEK-ERK pathway. We investigated differences in gene expression by analyzing the expression levels and activity of the corresponding proteins by Western blot. We showed the involvement of three proteins essential for phagocytosis activity: fak, tuberin and rictor. These findings demonstrate that hiPSC-RPE AMDa/e cells have a typical disease phenotype characterized by alteration of the main function of RPE cells, phagocytosis activity.

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.

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.

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.

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.

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.

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.

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.

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.

International audience; PURPOSE: We investigated the association of single nucleotide polymorphism (SNP) in the cholesterol-24S-hydroxylase (CYP46A1) gene, according to CFH and LOC387715 SNPs, with age-related macular degeneration (AMD). METHODS: We enrolled 1388 AMD patients with neovascular AMD or geographic atrophy and 487 unrelated control subjects. SNPs were genotyped in the CYP46A1 (rs754203), LOC387715 (rs10490924), and CFH (rs1061170) genes. Plasma 24S-hydroxycholesterol, the metabolic product of CYP46A1, was quantified by gas chromatography-mass spectrometry using an authentic deuterated internal standard in subgroups of patients and controls. The χ(2) test was used to compare categoric allelic and genotype distributions between cases and controls. The odds ratio (OR) with a 95% confidence interval (95% CI) was calculated for AMD risk, and adjusted for age and gender. Significance levels were set at P < 0.05. RESULTS: The rs754203 SNP in the CYP46A1 gene was not associated with AMD (crude OR = 1.2, 95% CI = 0.9-1.4, P = 0.2). The crude OR for risk of AMD was 2.9 (95% CI = 2.4-3.4, P < 0.0001) according to the number of rs10490924 T alleles in the LOC387715 gene, and 2.0 (95% CI = 1.7-2.3, P < 0.0001) according to the number of rs1061170 C alleles in the CFH gene. After adjustment for age and gender, an OR of 2.2 (95% CI = 1.1-4.1, P = 0.04) was obtained for AMD cases with the C allele in the CYP46A1 gene, and carrying no risk alleles in the CFH and LOC387715 genes. CONCLUSIONS: The rs754203 C allele in the CYP46A1 gene may confer a higher risk for exudative AMD in patients who carry no risk alleles in the CFH and LOC387715 genes. Additional studies with larger sample sizes are needed in AMD subjects at no risk in CFH and LOC387715.

Purpose To analyze the contribution of fluorescein angiography (FA) and spectral-domain optical coherence tomography (SD OCT) to the diagnosis of recent choroidal neovascularization (CNV) associated with high myopia. Design Retrospective, observational case series. Methods Ninety eyes of 73 highly myopic patients (refractive error ≥−6 diopters) with CNV in 1 or both eyes were included. Epidemiologic features, refractive error, fundus examination, fluorescein angiography, and SD OCT findings at onset of CNV were analyzed. Results Mean age at onset of CNV was 54.4 ± 14 years. CNV was bilateral in 17 of 73 cases. Mean refractive error was −13.9 ± 5.2 diopters. Myopic CNV was associated more frequently with patchy or geographic atrophy ( P = .019). CNV was associated with exudative features on fluorescein angiography in 82% of cases (64/78), and on SD OCT in 48.6% of cases (36/74). There was no agreement about signs of active CNV between these 2 imaging methods (κ = 25.7 ± 10%; P = .0044). CNV area was significantly smaller in younger patients ( 2 vs 1.21 mm 2 , respectively; P = .023). Conclusions Exudative features of myopic CNV are more obvious on FA than on SD OCT, suggesting that fluorescein angiography should be performed when new-onset myopic CNV is suspected. Myopic CNV occurring in older patients (≥55 years) is larger than those seen in younger patients and resembles CNV associated with age-related macular degeneration. This suggests an overlap between myopic CNV in older patients and age-related macular degeneration.

b c a p h t d A GE-RELATED MACULAR DEGENERATION (AMD) IS A complex multifactorial disease. Since the first association between a genetic polymorphism and AMD was discovered, the role of genetic factors in the occurrence of AMD is commonly admitted. Smoking and ody mass index are important environmental factors ssociated with an increased risk of AMD, whereas the urden of genetic factors leads to attributable risk estimates p to 60%. Prediction models based on known genetic nd environmental factors associated with AMD recently ere established. Seddon and associates described a model howing that the risk of developing exudative AMD in the econd eye may vary between 20% and 80% at 3 years, epending on environmental and genetic factors. The next steps to elucidate the role of genetics in AMD attempt to establish genotype–phenotype correlations, to investigate the genes involved in the natural course and severity of AMD, and to analyze the genes potentially involved in therapeutic responses. It is predictable that genes involved in these diverse steps would differ and that genes involved in the occurrence of AMD would not be the same as genes involved in therapeutic responses.

Purpose To assess the ability of the Spectralis optical coherence tomography (OCT) segmentation software to identify the inner limiting membrane and the Bruch’s membrane in exudative AMD patients. Methods Thirty-eight eyes of 38 naive exudative AMD patients were retrospectively included. They all had a complete ophthalmologic examination including Spectralis OCT at baseline, at month-1 and at month-2. Reliability of the segmentation software was was defined as good if both inner limiting membrane and Bruch’s membrane were correctly drawn. Results A total of 38 patients charts were reviewed (114 scans). The inner limiting membrane was correctly drawn in 114/114 SD-OCT scans (100 %). Conversely, the Bruch’s membrane was correctly drawn in 59/114 scans (51.8 %). The software was less reliable in locating the Bruch’s membrane in case of pigment epithelium detachment (PED) than without PED (42.5% vs 73.5 % respectively, p =0.049). Conclusion Segmentation of inner limiting membrane was constantly trustworthy but Bruch’s membrane segmentation was poorly reliable using the automatic SD-OCT Spectralis segmentation software. Based on this software, evaluation of retinal thickness may be incorrect, particularly in case of PED. • 2612 High-resolution spectral domain optical coherence tomography findings in reticular pattern dystrohy ZERBIB J 1, MASSAMBA N 1, QUERQUES G 1, 2, BLANCOGARAVITO R 1, SROUR M 1, BONNET C 1, SOUIED EH 1 (1) Ophthalmology, Creteil (2) Ophthalmology, Milano Purpose To analyze specific outer retinal and retinal pigment epithelium (RPE) features in reticular pattern dystrophy using spectral-domain optical coherence tomography (SD-OCT). Methods Consecutive patients with reticular pattern dystrophy underwent a complete ophthalmologic examination, including assessment of best-corrected visual acuity (BCVA), fundus biomicroscopy, and SD-OCT (Spectralis SD-OCT, Heidelberg Engineering). Outer retinal and RPE macular features, as evaluated by SD-OCT (scan passing through the fovea) were analyzed by 3 authors (JZ, NM and GQ). Results 24 eyes of 13 patients (5 males, 8 women, mean age 71.4) were included. Mean visual acuity was measured at 0.30 (logMAR). The RPE layer in the foveal area appeared normal in 41.7% of scans, while small RPE elevations and RPE bumps were detected in 33.3% and 20.8% of scans, respectively. Inner segment/outer segment (IS/OS) junction appeared disrupted in 50% of scans, and absent in 58.3% of scans. SD-OCT showed a slight IS/OS elevation in 54.2% of scans. The external limiting membrane (ELM), appeared disrupted in 50% of scans, absent in 37.5% of scans, and elevated in 66.7% of scans. Hypereflective subretinal material accumulation or hyporeflective subretinal lesions, were detected in 33.3% and in 12.5% of scans, respectively. SD-OCT showed hyporeflective retinal pseudocysts in 16.7% of scans. Conclusion In this series of reticular pattern dystrophy, SD-OCT showed disruption of RPE layer and RPE bumps. Outer retinal changes included absence and disruption of both IS/OS junction and ELM. Hypereflective subretinal material accumulation or hyporeflective subretinal lesions, and hyporeflective retinal pseudocysts were also noticed. • 2614 Natural evolution of idiopathic lamellar macular holes (LMH) and macular pseudoholes (MPH) GARCIA FERNÁNDEZ M, CASTRO NAVARRO J Ophthalmology, HUCA, Oviedo Purpose To analyze the natural evolution of idiopathic Lamellar Macular Holes (LMH) and Macular Pseudoholes (MPH), in the long-term, based on Optical Coherence Tomography (OCT) configuration and in Best Corrected Visual Acuity (BCVA) evolution. Methods We prospectively analyzed 68 eyes (41 right eyes and 27 left eyes) of 61 patients (40 female and 21 male), which were diagnosed as having a MPH or a LMH on OCT examination. The following variables were assessed: BCVA, lens status, and hole size (Diameter -D, Residual foveal Thickness –RT, and Perifoveal Thickness -PT)(software Caliper of Cirrus OCT), at baseline and final examination. Eyes with significant cataract underwent phacoemulsification. Results The mean follow-up period was 34.33 ± 15.02 (12-78) months. Mean BCVA (logMAR notation) in the total group at baseline was 0.40 ± 0.25 and at final was 0.36 ± 0.13 (p=0,082). PAM showed slightly better BCVA than LMH (p

Purpose To investigate whether the 2 subtypes of advanced age-related macular degeneration (AMD), choroidal neovascularization (CNV), and geographic atrophy (GA) segregate separately in families and to identify which genetic variants are associated with these 2 subtypes. Design Sibling correlation study and genome-wide association study (GWAS). Participants For the sibling correlation study, 209 sibling pairs with advanced AMD were included. For the GWAS, 2594 participants with advanced AMD subtypes and 4134 controls were included. Replication cohorts included 5383 advanced AMD participants and 15 240 controls. Methods Participants had the AMD grade assigned based on fundus photography, examination, or both. To determine heritability of advanced AMD subtypes, a sibling correlation study was performed. For the GWAS, genome-wide genotyping was conducted and 6 036 699 single nucleotide polymorphisms (SNPs) were imputed. Then, the SNPs were analyzed with a generalized linear model controlling for genotyping platform and genetic ancestry. The most significant associations were evaluated in independent cohorts. Main Outcome Measures Concordance of advanced AMD subtypes in sibling pairs and associations between SNPs with GA and CNV advanced AMD subtypes. Results The difference between the observed and expected proportion of siblings concordant for the same subtype of advanced AMD was different to a statistically significant degree ( P = 4.2×10 –5 ), meaning that in siblings of probands with CNV or GA, the same advanced subtype is more likely to develop. In the analysis comparing participants with CNV to those with GA, a statistically significant association was observed at the ARMS2/HTRA1 locus (rs10490924; odds ratio [OR], 1.47; P = 4.3×10 –9 ), which was confirmed in the replication samples (OR, 1.38; P = 7.4×10 –14 for combined discovery and replication analysis). Conclusions Whether CNV versus GA develops in a patient with AMD is determined in part by genetic variation. In this large GWAS meta-analysis and replication analysis, the ARMS2/HTRA1 locus confers increased risk for both advanced AMD subtypes, but imparts greater risk for CNV than for GA. This locus explains a small proportion of the excess sibling correlation for advanced AMD subtype. Other loci were detected with suggestive associations that differ for advanced AMD subtypes and deserve follow-up in additional studies. Financial Disclosure(s) Proprietary or commercial disclosure may be found after the references.

Age-related macular degeneration (AMD) is a complex, multifactorial disease associated with environmental and genetic factors. This review emphasizes the clinical impact of the major genetic factors mainly located in the complement factor H gene and on the 10q26 locus, and their current and future implications for the management of AMD. Copyright (C) 2011 S. Karger AG, Basel

To analyze the integrated confocal scanning laser ophthalmoscopy (cSLO) fundus and angiographic imaging and corresponding spectral domain optical coherence tomography (SD-OCT) features of cuticular drusen. Twenty-one consecutive patients with cuticular drusen were submitted to cSLO fundus and angiographic imaging [infrared reflectance (IR), fundus autofluorescence (FAF), near-infrared autofluorescence (NIA), fluorescein angiography (FA), and indocyanine green angiography (ICGA)) and “eye-tracked” SD-OCT. A total of 42 eyes were included for analysis. BCVA ranged from 20/20 to 20/400. In 5/42 eyes, cSLO imaging and corresponding SD-OCT showed coincident vitelliform macular detachment, and in 9/42 eyes showed coincident geographic atrophy (GA). The “typical” cuticular drusen, intensely staining on early FA phase (“stars-in-the-sky” appearance in the fundus), appeared as “sawtooth” retinal pigment epithelium (RPE) elevation on SD-OCT. Some “atypical” cuticular drusen appeared, on early FA and ICGA frames, as hyper-fluoresecent lesions surrounded by faint hypo-fluoresecent halos. These lesions, which became intensely hyper-fluorescent in the late FA and ICGA phases, appeared, on SD-OCT, as small, confluent “dome-shaped” RPE elevations. Interestingly, some less intensely staining cuticular drusen (FA and ICGA) appeared as irregular slight thickening of RPE/Bruch's membrane complex on SD-OCT scans. Integrated imaging makes it possible to highlight different features within cuticular drusen-containing regions, and gives insights into pathology. We suggest that “typical” cuticular drusen may represent a continuous layer of early basal laminar deposit (BLamD) associated with membranous debris accumulation. As early BLamD thicken, the lesions become richer in solid lipid particles, and “atypical” cuticular drusen may develop.

Summary Purpose To report the angiographic and optical coherence tomography (OCT) features of isolated “perifoveal exudative vascular anomalous complex (PEVAC)”, a peculiar clinical entity. Methods A complete ophthalmologic examination was performed in two patients (a 82-year old woman [case 1]; a 52-year old man [case 2]) that were referred to our department for unilateral blurred vision. Results In both cases, fundus examination of the right eye showed a perifoveal isolated large aneurismal change, accompanied by small hemorrhages, intraretinal exudation, and small hard exudates accumulation. Both FA and ICGA revealed the absence of any other retinal or choroidal vascular abnormality associated. OCT showed a round hyperreflective lesion in correspondence of the perifoveal vascular anomalous complex, surrounded by intraretinal cystic spaces. In case 2, the lesion remained unchanged despite 3 monthly intravitreal injections of ranibizumab. Conclusion PEVAC may develop in absence of capillary ischemia or inflammation, probably due to progressive retinal endothelial cell degeneration. This could explain the unresponsiveness to anti-VEGF treatments.

Aim To investigate the ability of the preferential hyperacuity perimeter test to assess responsiveness to ranibizumab therapy for exudative age-related macular degeneration (AMD). Methods Fourteen consecutive patients with newly diagnosed choroidal neovascularisation underwent a preferential hyperacuity perimeter metamorphopsia test (main outcome measures) 1 h before (baseline) and 1 h, 1 day, 1 week and 1 month after one intravitreal injection of ranibizumab (0.05 ml/0.5 mg). Best corrected visual acuity (BCVA) and several spectral domain optical coherence tomography (OCT) parameters (secondary outcome measures) were compared with the metamorphopsia test. Results Fourteen eyes (14 patients, 78% women, mean age 83 +/- 6.2 years) were included in the analysis. The mean preferential hyperacuity perimeter metamorphopsia test score improved significantly from 20.4 +/- 35 at baseline to 9.2 +/- 23 after the single ranibizumab injection (p < 0.05). The mean reduction in central macular thickness, maximal retinal thickness at the fovea, maximal height of subretinal fluid, maximal diameter of the largest retinal cyst and maximal height of pigment epithelial detachment, as evaluated by spectral domain OCT, closely reflected the functional improvements as evaluated by preferential hyperacuity perimeter, showing a significant correlation with metamorphopsia changes (Spearman correlation 0.9, p < 0.05). Mean BCVA improved significantly from 20/80 to 20/60 (p < 0.05). A significant correlation was also found between the mean BCVA changes and the mean metamorphopsia changes (Spearman correlation 0.97, p < 0.05). The correlation coefficient between OCT measurements and preferential hyperacuity perimeter score within subjects was 0.51 (p < 0.05). Conclusion The improvement in metamorphopsia test score after intravitreal ranibizumab injection, which correlated closely with improvement in several OCT parameters, suggests that the preferential hyperacuity perimeter test may be used to monitor the response to anti-vascular endothelial growth factor (VEGF) treatment in patients with exudative AMD.

Purpose To determine if genetic variants that have been associated with age-related macular degeneration (AMD) have a differential effect on the risk of choroidal neovascularization (CNV) and geographic atrophy. Design Genetic association study. Methods setting: Multicenter study. study population: Seven hundred forty-nine participants with geographic atrophy and 3209 participants with CNV were derived from 4 AMD studies with similar procedures from Tufts Medical Center, the Age-Related Eye Disease Study, University of Utah, and Hopital Intercommunal de Creteil. procedures: AMD grade was assigned based on fundus photography and examination using the clinical age-related maculopathy staging system. All samples were genotyped for single nucleotide polymorphisms (SNPs) previously associated with AMD. Allele frequencies were compared between participants with CNV and geographic atrophy using PLINK within each cohort and Mantel-Haenszel meta-analysis was performed to combine odds ratios (OR). main outcome measures: Differences in allele frequencies between participants with geographic atrophy and CNV. Results The frequency of the T allele of ARMS2/HTRA1 rs10490924 was significantly higher in participants with CNV than in those with geographic atrophy (OR, 1.37; 95% confidence interval, 1.21–1.54; P value=4.2 × 10 −7 ). This result remained statistically significant when excluding individuals who had geographic atrophy in 1 eye and CNV in the contralateral eye ( P = 2.2 × 10 −4 ). None of the other SNPs showed a significant differential effect for CNV vs geographic atrophy, including CFH, C2/CFB, C3, CFI, LIPC , and TIMP3 . Conclusions Genetic variation at the ARMS2/HTRA1 locus confers a differential risk for CNV vs geographic atrophy in a well-powered sample.

Aims Drusen are rarely observed in patients

Purpose Major genetic factors for age-related macular degeneration (AMD) have recently been identified as susceptibility risk factors, underlying the role of the complement pathway in AMD. Our purpose was to analyze the role of the R102G polymorphism of the complement component (C3) gene in a French population, in a case-control study. Methods A total of 1,080 patients with exudative AMD and 406 controls were recruited and genotyped for Y402H of complement factor H (CFH), rs10490924 of age-related maculopathy susceptibility 2 (ARMS2), and R102G of the C3 gene. Results The distribution of the R102G genotypes was significantly different in the AMD patients compared to controls (p=0.02). The Odds Ratio compared to C/C individuals was 1.4 (95% CI 1.1–1.8) for C/G individuals and 1.4 (95% CI 0.8–2.4) for G/G individuals. In a dominant model, the adjusted Odds Ratio for carriers of the G allele is 1.4 (95% CI 1.0–1.9; p=0.03). Conclusions Our study shows C3 to be a moderate susceptibility gene for exudative AMD in the French population.

PURPOSE: To assess morphologic changes associated with retinal flecks in fundus flavimaculatus using spectral-domain optical coherence tomography (SD-OCT). DESIGN: Observational case series. METHODS: Simultaneous recordings of SD-OCT and confocal scanning laser ophthalmoscope (cSLO) fundus autofluorescence images were obtained in fundus flavimaculatus patients. Morphologic aspects of the retinal flecks were analyzed and classified. RESULTS: Thirty-one eyes of 17 consecutive patients (8 male, 9 female; mean age 47.9 +/- 17.1 years) were included for analysis. SD-OCT revealed 5 distinct types of lesions. Group A lesions were limited to the outer segment (OS) of the photoreceptors, the retinal pigment epithelium (RPE) interdigitations, and the RPE/Bruch membrane complex. Group B showed a protrusion of the hyper-reflective material through the interface of inner segment (IS)/OS of the photoreceptors up to the external limiting membrane. A further protrusion of the hyper-reflective material into the outer nuclear layer was seen in group C lesions. Group D lesions were characterized by an accumulation of the hyper-reflective material limited to the outer nuclear layer. Type E lesions can be described as drusen-like retinal pigment detachments. No significant correlation between the different types of flecks and visual acuity was observed (P > .05). CONCLUSIONS: SD-OCT allows one to distinguish at least 5 different types of lesions associated with retinal flecks in fundus flavimaculatus. The ability to characterize the different types of flecks and to analyze the photoreceptor layers surrounding these lesions suggests that SD-OCT might have a potential clinical role in the evaluation and follow-up of the structural changes in fundus flavimaculatus. (Am J Ophthalmol 2010;150: 330-337. (C) 2010 by Elsevier Inc. All rights reserved.)

PURPOSE Major genetic risk factors have recently been identified for age-related macular degeneration (AMD), including the ARMS2/LOC387715 and CFH at-risk polymorphisms. The study was conducted to establish correlations between the AMD genotype and both the phenotype and severity of AMD. METHODS In a prospective cohort of 1216 AMD patients, four genotypic homozygous groups were identified (n = 264): double homozygous for wild-type alleles (group 1, n = 49), homozygous for the at-risk allele of ARMS2/LOC387715 only (group 2, n = 57), homozygous for the at-risk allele of CFH only (group 3, n = 106), and double homozygous for both at-risk alleles (group 4, n = 52). The phenotypic classification of exudative AMD was based on fluorescein angiography. RESULTS Mean age at presentation was significantly lower in group 4 than in group 1 (P < 0.014). Patients in group 4 presented more often with bilateral CNV and fibrovascular scars than did patients in group 1 (P < 0.001 and < 0.0031 respectively) and with significantly lower visual acuity (VA) in the first affected eye than did patients in group 1 (P < 0.02). Patients in group 2 presented with worse VA than did patients in group 3 (P < 0.003). Classic CNV was more commonly associated with the at-risk allele of the ARMS2/LOC387715 locus than with the at-risk allele of the CFH gene (P < 0.026). CONCLUSIONS This study demonstrates an association between the at-risk allele of the ARMS2/LOC387715 locus and classic CNV, fibrovascular lesions, and poor VA. Individuals double homozygous for both at-risk alleles had a higher risk of being affected with a severe form of AMD at an earlier age.

Purpose: The purpose of this study was to evaluate the efficacy of intravitreal injections of ranibizumab in choroidal neovascularization secondary to pathologic myopia. Methods: A prospective case series of 32 eyes of 32 patients affected with choroidal neovascularization secondary to pathologic myopia treated by intravitreal injections of ranibizumab. Best-corrected visual acuity, fundus examination, fluorescein angiography, indocyanine green angiography, and spectral domain-optical coherence tomography were performed for the diagnosis of myopic choroidal neovascularization. Best-corrected visual acuity and central retinal thickness measurement were performed monthly during the follow-up. Results: The median number of injections was 3 with a median follow-up of 17 months. The median visual acuity at baseline was 20/100 and improved to 20/50 at final examination (P < 0.0001). Best-corrected visual acuity improved by >= 3 lines in 15 of 32 eyes (46.8%). The median central thickness was 336 mu m (range, 179-663 mu m) at baseline and 233 mu m (range, 125-465 mu m) at final examination (P < 0.0001). No severe drug-related side effect was reported. Conclusion: In our series of myopic choroidal neovascularization, intravitreal injections of ranibizumab showed visual acuity improvement and retinal thickness reduction. Further prospective multicentric clinical trials are needed to evaluate the safety and the efficacy of this treatment. RETINA 30: 399-406, 2010

Age-related Macular Degeneration (AMD) is the main cause of vision loss in developed countries. Spectral domain OCT (SD-OCT) is a non invasive technique providing in vivo imaging of the retina, with a higher resolution than time domain OCT. This SIS will describe the clinical features of exudative AMD with SD-OCT, including occult choroidal neovascularization (CNV), classic CNV, idiopathic polypoidal vasculopathy, and chorioretinal anastomosis. The improvement of the resolution of retinal imaging will provide a better classification and explanation of the pathological processes observed during AMD.

Purpose Type 2 Macular Telangiectasia is a progressive disease starting in the fifth to seventh decade and characterized by a progressive damage of the neurosensory retina.. The purpose of this study is to compare the images obtained using two non-invasive techniques, High-Resolution Optical Coherence Tomography (HR-OCT) and Adaptive Optics (AO), in Type 2 Macular Telangiectasia. Methods Nine eyes of 5 patients affected by Type 2 Macular Telangiectasia underwent examination including visual acuity measurement with ETDRS (Early Treatment of Diabetic Retinopathy Study) chart, color photographs, monochromatic photographs, Spectral-Domain Optical Coherence Tomography with Heidelberg Spectralis™ OCT and Adaptive Optics assessment with Imagine Eyes™ System. The neurosensory retina and the photoreceptor layer were analyzed using both HR-OCT and AO imaging. Results The disruptions of the photoreceptor layer on HR-OCT correspond to a cellular loss on Adaptive Optics Imaging. On the other hand, Adaptive optics Imaging allows the measurement of cellular density in areas which have a normal aspect on HR-OCT. Conclusion The diagnosis of Macular Telangiecctasia is based on biomicroscopy and fluorescein angiography. Adaptive Optics Imaging is helpful to analyze the retinal damages, especially the cone abnormalities. This technique will certainly allow a better understanding of this rare disease. Author Disclosure Information: K. Atmani, None; N. Leveziel, None G. Soubrane, None.

Refractive error (RE), particularly myopia, is the first cause of visual impairment throughout the world. This study aimed to depict the prevalence of myopia in a multicentric series of French individuals.This cross-sectional analysis was carried out between January 2012 and November 2013 in eye clinics dedicated to REs. Data collection included age, gender, best-corrected visual acuity, RE, and any relevant medical history involving laser refractive surgery and cataract surgery. Exclusion criteria consisted of monophthalm patients or those with incomplete demographic data.Prevalences in the overall population, by gender and by age groups were reported for mild myopia (-0.50 to -2.75 diopter [D]), moderate myopia (-3 to -5.75 D), high myopia (less than -6 D), and very high myopia (less than -10 D).The analysis included 100,429 individuals, mean age 38.5 years (± 16.9). Overall prevalence of myopia was 39.1% (95% CI 38.8-39.4). Prevalences of mild, moderate, high and very high myopia were respectively 25.1% (95% CI 25.4-24.9), 10.6% (95% CI 10.4-10.8), 3.4% (95% CI 3.3-3.5) and 0.5% (95% CI 0.48-0.57).Even if possible bias occurred in recruitment, our results are similar to RE data collected in nationally representative samples of Caucasians in other studies. This is to our knowledge, one of the largest European series of individuals dedicated to myopia prevalences in different age groups. These results confirm the importance of myopia as a major health issue in Western countries.

Two focal scleral ectasias in areas of geographic chorioretinal atrophy secondary to pathologic myopia. A, Multicolor imaging of the left eye showing 2 scleral ectasias into geographic atrophy related to highmyopia. B, Mosaic multicolor imaging centered on the optic nerve. The geographic lesion is located on the temporal and nasal part of the optic nerve. C, Infrared imaging of the same eye showing the location of the optical coherence tomographic scan (green line). D, Spectral-domain optical coherence tomographic scan showing the scleral ectasias. JAMA Ophthalmol. 2015;133(3):e141980. doi:10.1001/jamaophthalmol.2014.1980

Background/aim: Retinal flecks are commonly observed in both Stargardt disease and fundus flavimaculatus (FFM). The aim was to determine the precise localisation of these flecks within the retinal layers using Stratus optical coherence tomography (OCT). Methods: A prospective observational case series. A complete ophthalmological examination, including autofluorescence, fluorescein angiography (FA), and Stratus OCT (Carl Zeiss) was performed in 49 eyes of 26 consecutive patients with FFM. Six to 12 Stratus OCT linear scans focused on the retinal flecks were performed in each eye. Results: The age at presentation ranged from 23 years to 71 years and visual acuity ranged from 20/20 to 20/400. Hyper-reflective deposits classified into two types were observed on Stratus OCT: type 1 lesions (94% of eyes) presented as dome-shaped deposits located in the inner part of the retinal pigment epithelium (RPE) layer and type 2 lesions (86% of eyes) presented as small linear deposits located at the level of the outer nuclear layer and clearly separated from the RPE layer. Conclusions: Stratus OCT is a non-invasive instrument that provides new information on the location of flecks in FFM. The location of type 2 lesions is quite unusual among macular dystrophies; OCT may therefore be useful in the diagnosis of retinal flecks in some cases of FFM.

Nonsyndromic high myopia, defined by a refractive error greater than -6 diopters (D), is associated with an increased risk of macular choroidal neovascularization (CNV), a vision-threatening complication. The aim of this study was to investigate whether genetic factors associated with age-related macular degeneration (AMD) are related to myopic CNV.We conducted a case-control study, including 71 cases with myopic CNV and 196 myopic controls without CNV, from Creteil and Toulouse, France, and Boston, MA. Single nucleotide polymorphisms (SNPs) from 15 genes reported to be related to AMD were selected for association testing in this study.In univariate analysis, the rs10033900 SNP located in CFI was associated with myopic CNV (P = 0.0011), and a SNP in APOE was also related (P = 0.041). After adjustment for age, sex, and degree of myopia, SNPs in three genes were significantly associated, including CFI (odds ratio [OR] 2.1, 95% confidence interval [CI] 1.3-3.37, P = 0.0023), COL8A1 (OR 1.88, 95% CI 1.18-2.98, P = 0.0076), and CFH (OR 1.65, 95% CI 1.02-2.66, P = 0.04). After correction for multiple testing, only CFI remained significantly related to high myopic CNV (P = 0.045).We report the first genetic associations with choroidal neovascularization (CNV) in a high myopic Caucasian population. One SNP (rs10033900) in the CFI gene, which encodes a protein involved in the inflammatory pathway, was significantly associated with myopic CNV in multivariate analysis after correction for multiple testing. This SNP is a plausible biological marker associated with CNV outgrowth among high myopic patients. Results generate hypotheses about potential loci related to CNV in high myopia, and larger studies are needed to expand on these findings.

International audience; Major genetic factors for age-related macular degeneration (AMD) have recently been identified as susceptibility risk factors, including variants in the CFH gene and the ARMS2 LOC387715/HTRA1locus. Our purpose was to perform a case-control study in two populations among individuals who did not carry risk variants for CFHY402H and LOC387715 A69S (ARMS2), called ‘‘study’’ individuals, in order to identify new genetic risk factors. Based on a candidate gene approach, we analyzed SNP rs5888 of the SCARB1 gene, coding for SRBI, which is involved in the lipid and lutein pathways. This study was conducted in a French series of 1241 AMD patients and 297 controls, and in a North American series of 1257 patients with advanced AMD and 1732 controls. Among these individuals, we identified 61 French patients, 77 French controls, 85 North American patients and 338 North American controls who did not carry the CFH nor ARMS2 polymorphisms. An association between AMD and the SCARB1 gene was seen among the study subjects. The genotypic distribution of the rs5888 polymorphism was significantly different between cases and controls in the French population (p,0.006). Heterozygosity at the rs5888 SNP increased risk of AMD compared to the CC genotypes in the French study population (odds ratio (OR) = 3.5, CI95%: 1.4–8.9, p,0.01) and after pooling the 2 populations (OR = 2.9, 95% CI: 1.6–5.3, p,0.002). Subgroup analysis in exudative forms of AMD revealed a pooled OR of 3.6 for individuals heterozygous for rs5888 (95% CI: 1.7–7.6, p,0.0015). These results suggest the possible contribution of SCARB1, a new genetic factor in AMD, and implicate a role for cholesterol and antioxidant micronutrient (lutein and vitamin E) metabolism in AMD

PURPOSE. Major genetic factors for age-related macular degeneration (AMD) have recently been identified as susceptibility risk factors, including polymorphisms of HTRA1 and CFH genes. The purpose was to analyze the angiographic features of patients harboring homozygous genotypes for HTRA1 and CFH genes in a French exudative AMD population. METHODS. Two hundred patients affected with exudative AMD were genotyped for the polymorphisms rs11200638 of the HTRA1 gene and rs10611710 of the CFH gene. Four homozygous groups were extracted from the entire cohort: double homozygous for wild-type alleles of both genes (group 1), homozygous for the polymorphism of the HTRA1 gene only (group 2), homozygous for the polymorphism of the CFH gene only (group 3), and double homozygous carriers for both polymorphisms (group 4). Choroidal neovascularization (CNV) was graded as classic and predominantly classic (PC), occult, minimally classic (MC), or retinal angiomatosis proliferation (RAP). RESULTS. Group 1 (n = 9) presented 44.4% classic and PC, 33.3% occult, 11.1% MC, and 11.1% RAP. Group 2 (n = 12) presented 50.0% classic and PC, 33.3% occult, no MC CNV and 16.7% RAP. Group 3 (n = 28) presented 10.7% classic and PC, 67.9% occult, 14.3% MC, and 7.1% RAP. Group 4 (n = 17) presented 29.4% classic and PC, 52.9% occult, 11.8% MC, and 5.9% RAP. Occult CNV or MC CNV was more frequently observed in group 3 than in group 2 (82.1% vs 33.3%; P < 0.02). Classic and PC CNV were more frequently observed in group 2 than in group 3 (50% vs. 10.7%; P < 0.03). CONCLUSIONS. This attempt at a genotypic- angiographic correlation in an exudative AMD sample suggests an association between occult or MC CNV and the CFH polymorphism and between classic and PC CNV and the HTRA1 polymorphism.

Purpose. To report on a patient with retinal astrocytic hamartoma, who developed a choroidal neovascularization (CNV), effectively treated by intravitreal ranibizumab injections. Methods. A 74-year-old woman who, 12 years before, had been diagnosed with a yellow-gray lesion in the left eye (OS) presented in our department for OS decreased vision of recent onset. Results. Upon a complete ophthalmologic examination including ultrasonography, fluorescein angiography (FA), and spectral domain optical coherence tomography (SD-OCT), the patient was diagnosed with retinal astrocytic hamartoma and coincident CNV on its foveal border. Six months after 3 monthly intravitreal ranibizumab injections, FA and OCT revealed the CNV closure and absence of intraretinal and subretinal fluid on the foveal border of the retinal astrocytic hamartoma. Conclusions. Associations between retinal astrocytic hamartoma and CNV have not been previously reported. Intravitreal ranibizumab injection appears an attractive therapeutic option for patients showing such an unusual association.

Purpose Large colloid drusen (LCD) are a subgroup of early onset drusen recently reported. The aim of this study was to describe morphologic features in patients affected with LCD using high-resolution spectral-domain optical coherence tomography (SD-OCT). Methods A complete ophthalmologic examination including SD-OCT was performed in 22 eyes of 11 consecutive patients. Results Mean age was 35 years old at diagnosis, and mean visual acuity was 20/25. In all eyes, SD-OCT showed multiple dome-shaped retinal pigment epithelium detachments corresponding to the drusen. Mean height of drusen was 199 μm (range, 108-316 μm) and mean width was 419 μm (range, 190-681 μm). Indocyanine green angiography hypofluorescent LCD were larger and more reflective on SD-OCT than indocyanine green angiography hyperfluorescent LCD. All drusen appeared convex with medium and homogeneous internal reflectivity. Retina overlying LCD appeared wavy and overall thinned. Prominent diffuse hyperreflective haze in the Henle fiber layer over drusen was noted in 73% of the eyes. No geographic atrophy or choroidal neovascularization was observed. Conclusion The peculiar SD-OCT features reported in the current series give insight on the ultrastructure of LCD. Further studies with follow-up evaluation and possibly histologic evaluation are needed to clarify the clinical significance of LCD.

Background: To assess the ability of the Spectralis optical coherence tomography (OCT) segmentation software to identify the inner limiting membrane and Bruch’s membrane in exudative age-related macular degeneration (AMD) patients. Methods: Thirty-eight eyes of 38 naive exudative AMD patients were retrospectively included. They all had a complete ophthalmologic examination including Spectralis OCT at baseline, at month 1 and 2. Reliability of the segmentation software was assessed by 2 ophthalmologists. Reliability of the segmentation software was defined as good if both inner limiting membrane and Bruch’s membrane were correctly drawn. Results: A total of 38 patients charts were reviewed (114 scans). The inner limiting membrane was correctly drawn by the segmentation software in 114/114 spectral domain OCT scans (100%). Conversely, Bruch’s membrane was correctly drawn in 59/114 scans (51.8%). The software was less reliable in locating Bruch’s membrane in case of pigment epithelium detachment (PED) than without PED (42.5 vs. 73.5%, respectively; p = 0.049), but its reliability was not associated with SRF or CME (p = 0.55 and p = 0.10, respectively). Conclusion: Segmentation of the inner limiting membrane was constantly trustworthy but Bruch’s membrane segmentation was poorly reliable using the automatic Spectralis segmentation software. Based on this software, evaluation of retinal thickness may be incorrect, particularly in case of PED. PED is effectively an important parameter which is not included when measuring retinal thickness.

Purpose: To determine the visual field patterns obtained by the preferential hyperacuity perimetry (PHP) in patients with Best vitelliform macular dystrophy with mutations in the BEST1 gene. Methods: Consecutive patients with Best vitelliform macular dystrophy underwent a complete ophthalmologic examination, including functional assessment by best-corrected visual acuity and Foresee PHP and morphologic assessment by fundus biomicroscopy, fundus autofluorescence, and spectral-domain optical coherence tomography. The functional "PHP visual field defect index" (which is the max peak value of the metamorphopsia [maximal distortion value at the visual field] + the max peak value of the scotoma [maximal scotoma value at the visual field]) and best-corrected visual acuity were analyzed about the disease stage. Results: Thirty eyes of 15 consecutive patients (8 men and 7 women; mean age 39 6 24 years) were included for analysis. Based on fundus biomicroscopy, fundus autofluorescence, and spectral-domain optical coherence tomography, the macular lesions could be counted as follows: previtelliform lesions in 5 eyes of 3 patients (Stage 1), vitelliform lesions in 2 eyes of 2 patients (Stage 2), pseudohypopyon lesions in 6 eyes of 5 patients (Stage 3), vitelliruptive lesions in 4 eyes of 3 patients (Stage 4), atrophic lesions in 7 eyes of 5 patients (Stage 5), and fibrotic lesions in 6 eyes of 4 patients (Stage 6). Best-corrected visual acuity and PHP visual field defect index were averaged for each stage. Best-corrected visual acuity showed a good correlation (P = 0.01) with the morphologic severity (stage) of the disease (Pearson correlation = -0.88). Similarly, the PHP visual field defect index showed a good correlation (P = 0.03) with the morphologic severity (stage) of the disease (Pearson correlation = 0.78). Finally, best-corrected visual acuity showed a good correlation (P = 0.02) with the functional PHP visual field defect index (Pearson correlation = -0.83) about the morphologic stage of the disease. Conclusion: Preferential hyperacuity perimetry could be considered an adjunctive useful tool in the evaluation of functional impairment and disease progression in patients with Best vitelliform macular dystrophy. RETINA 31:959-966, 2011

First cause of irreversible visual dysfunction in industrialized countries, age-related macular degeneration (AMD) is a retinal disease affecting people after 55 years old. AMD is characterized by the macular degeneration of retina and by formation of drusen. There exist two forms of the disease: the exudative and the atrophic forms. In our study, we focused only on the atrophic one, corresponding to approximately 50% of the clinical cases in Europe, that still today without curative therapy. Despite many researches, AMD's etiology remains unclear even if environmental and genetics factors would be involved. According to the etiopatogenic hypothesis, RPE cells dysfunction has a central role in the physiopathological events leading to AMD. From healthy subjects and patients affected by atrophic AMD, we obtained RPE cells derived from induced pluripotent stem cells and developed a useful human cellular model for the understanding of AMD mechanisms. Indeed, the morphological and functional study of the two types of cells populations underlined a particular phenotype for the RPE cells derived from AMD patients. This cellular model will allow us to have a better understanding of mechanisms leading to AMD and will also be used to screen therapeutic molecules before clinical studies., Première cause de baisse d'acuité visuelle dans les pays industrialisés, la dégénérescence maculaire liée l'âge (DMLA) est une pathologie de la rétine touchant principalement les personnes après 55 ans. Elle est caractérisée par une dégénérescence de la zone maculaire de la rétine et par la formation de drusens. Il existe deux formes de la maladie : la forme exsudative et la forme atrophique. Dans notre étude, nous nous sommes focalisés sur la DMLA atrophique, actuellement sans traitement curatif et qui correspond à environ 50% des cas cliniques en Europe. Malgré de nombreuses recherches, les causes de la DMLA restent encore mal comprises même si des facteurs environnementaux (sénescence, accumulation de lipofuscine, stress oxydatif) et génétiques sont probablement combinés. Selon l'hypothèse étiopathogénique, le dysfonctionnement des cellules de l'épithélium pigmenté de la rétine (EPR) est au centre des événements physiopathologiques de la DMLA. A partir de sujets sains et de patients atteints de la DMLA atrophique, nous avons obtenu des cellules de l'EPR dérivées de cellules souches pluripotentes induites et développé un modèle cellulaire humain utile pour la compréhension des mécanismes physiopathologiques de la DMLA. Ainsi, l'étude morphologique et fonctionnelle de ces deux populations de cellules a souligné un phénotype particulier des cellules de l'EPR provenant de patients atteints pas la DMLA en condition basale et en milieu pro-oxydant. Ce modèle cellulaire pourra nous permettre d'approfondir nos connaissances sur les mécanismes amenant au développement de la DMLA et pourra aussi être utilisé pour le screening des molécules au cours des étapes précliniques.