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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.

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: 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.

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.

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.

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.

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.

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 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.

Proliferative sickle cell retinopathy (PSCR) is the most frequent vision-threatening complication of sickle cell disease (SCD). We investigated the relationship between the severity of sickle cell retinopathy in heterozygous (SC) or homozygous (SS) adult SCD patients and the clinical and laboratory data obtained during visits to a national SCD referral center. This retrospective longitudinal analysis included 942 SCD patients (313 patients with SC and 629 with SS disease) with ophthalmologic evaluations who were followed over a 19-year period by a multidisciplinary team in a referral center. PSCR was graded using the Goldberg classification. We identified patient and SCD characteristics associated with sickle cell retinopathy severity using multinomial logistic-regression models. Multivariate analysis associated severe PSCR forms (stages III-V) with older age (p = 0.032), pulmonary involvement (documented pulmonary hypertension with pulmonary arterial pressure >= 40 mm Hg, restrictive syndrome >20%, or previous history of pulmonary embolism diagnosed by vascular imaging) (p = 0.029), deafness or tinnitus (p = 0.026), and no history of osteomyelitis (p = 0.013) for SC patients; and with older age (p < 0.001), male sex (p = 0.003), and acute pyelonephritis (p = 0.04) for SS patients. The model of severe PSCR versus no PSCR showed good calibration and discrimination for SC and SS patients. Awareness of the clinical and laboratory factors significantly associated with severe PSCR in patients with SC or SS SCD may contribute to improved preventive strategies. (Medicine 2011;90: 372-378)

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.

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.

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 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.

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.

Acomprehensive list of patient features that influence the management of patients with diabetic macular oedema (DMO) is discussed. These features are grouped into three overarching themes: ocular, systemic and psychosocial. Consensus statements about the relative importance of these features, supported by the literature, were formed by a panel of retinal experts. The major drivers influencing the management of DMO with anti-vascular endothelial growth factor (anti-VEGF) therapy are undoubtedly ocular specific, in particular visual acuity and optical coherence tomography (OCT) central retinal thickness. Systemic factors, such as control of glycated haemoglobin (HbA1c), blood pressure and serum lipid estimations, have limited direct influence on DMO management although they remain important considerations to communicate to the primary diabetic physician. A greater understanding is required on how many other factors, in particular psychosocial factors, influence the care of the DMO patient.