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Purpose: We observed hyperreflective dome-shaped or pyramidal structures (HPS) on spectral domain optical coherence tomography (SD-OCT) in patients affected with geographic atrophy (GA). Our purpose was to describe the multimodal imaging features of HPS identified in areas of GA in patients with age-related macular degeneration. Methods: This is a retrospective case series of patients with GA harboring HPS in atrophic areas. Multimodal imaging examination including infrared reflectance, fundus autofluorescence, and SD-OCT, was performed for each patient. Infrared and fundus autofluorescence appearance and mean SD-OCT height of HPS in GA were analyzed. Results: A total of 36 eyes of 25 patients (20 women; mean age, 82.3 +/- 5.9 years, range, 73-92 years) with GA were included. A total of 96 HPS in GA were analyzed by SD-OCT. In all HPS (96/96, 100%), the peripheral part was hyperreflective. In 66 of 96 HPS (69%), the center was heterogeneously hyperreflective, whereas in 30 of 96 HPS (31%), the center was hyporeflective. On infrared reflectance images, HPS in GA appeared as hyporeflective lesions surrounded by hyperreflective halos, within an area of background hyperreflectivity because of GA in all eyes. On fundus autofluorescence, 39 of 96 HPS (41%) were heterogeneously hyperautofluorescent, whereas 57 of 96 HPS (59%) were hypoautofluorescent. Mean height of HPS was 91 +/- 50.9 mu m in the foveal scan (range, 42-291 mu m). Conclusion: We describe a multimodal imaging of distinctive lesions that presented as hyperreflective pyramidal structures on SD-OCT. We suggest the name "ghost drusen" because these HPS appear in GA areas, and because of their pyramidal or dome-shaped aspect on SD-OCT.

PURPOSE: To analyze the outer retinal and retinal pigment epithelium (RPE) features of reticular pattern dystrophy of the retina using spectral-domain optical coherence tomography (SDOCT). DESIGN: Retrospective observational case series. METHODS: Consecutive patients with reticular pattern dystrophy of the retina underwent a complete ophthalmologic examination, including assessment of best-corrected visual acuity (BCVA), fundus biomicroscopy, fluorescein angiography (FA), and SDOCT. RESULTS: Twenty-two eyes of 13 patients (6 men, 7 women, mean age 68.6 +/- 14.5 years) were included. In the foveal area, the RPE layer appeared normal in 45.5% of eyes, while small RPE elevations and RPE bumps were detected in 31.8% and 22.7% of eyes, respectively. The SDOCT scans showed disruption of inner segment/outer segment (IS/OS) junction in 54.6% of eyes, a slight elevation in 59.1% of eyes, and an absence in 45.5% of eyes. The outer limiting membrane (OLM) appeared disrupted in 50.0% of eyes: absent in 22.7% of eyes, and elevated in 63.6% of eyes. Hyper-reflective subretinal material accumulation or hyporeflective subretinal lesions in the retrofoveolar region were detected in 70% and in 20% of eyes, respectively. SDOCT showed hyporeflective retinal pseudocysts in 13.6% of eyes. CONCLUSION: In this study on reticular pattern dystrophy of the retina, SDOCT provided a description of the material deposits and the alterations of the RPE and the different retinal layers. We observe that the lesions present specific features distinct from other macular dystrophies, but closer to those reported in fundus flavimaculatus than those reported in adult-onset foveomacular vitelliform dystrophy. Further analyses are needed, particularly to analyze the progression of the lesions. ((C) 2013 by Elsevier Inc. All rights reserved.)

PURPOSE To describe the case of a patient presenting with persistent placoid maculopathy imaged with optical coherence tomography angiography. METHODS Case report of a 72-year-old man who presented with blurred vision in his right eye. fundus photography, fluorescein angiography, infracyanine green angiography, fundus autofluorescence imaging, spectral domain optical coherence tomography, optical coherence tomography angiography, and split spectrum amplitude decorrelation angiography were performed. The diagnosis was made based on ophthalmological manifestations and multimodal imaging. RESULTS The spectral domain optical coherence tomography image of the right eye revealed disruption of the ellipsoid layers, and an underlying sliver of hyporeflectance. In the left eye, there were no obvious changes on spectral domain optical coherence tomography. In both eyes, infracyanine green angiography showed hypocyanescence of the lesions, persisting throughout late phases. In optical coherence tomography angiography, imaging of the choroidal capillary layers revealed hyposignal lesions, topographically corresponding exactly to hypocyanescent lesions on infracyanine green angiography. CONCLUSION In this patient, a distinct hyposignal on optical coherence tomography angiography, combined with hypocyanescence on infracyanine green angiography, was interpreted as indicating focal hypoperfusion of the choriocapillaris.

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.

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.

Choroidal neovascularization (CNV) secondary to traumatic rupture of Bruch's membrane is a rare condition, without standardized treatment. Here we describe one case of CNV related to traumatic rupture of Bruch's membrane which was successfully treated with intravitreal injection of ranibizumab.A 14-year-old patient was referred for ocular contusion, complicating interpapillomacular rupture of Bruch's membrane in left eye. Indeed, a correct initial visual acuity, juxtafoveolar CNV appeared 4 months later on the border of Bruch's membrane rupture. The patient was treated with an off-label intravitreal ranibizumab because of worsening of visual acuity.One month after intravitreal injection, visual acuity improved, from 20/40 to 20/25. At 12-month follow-up, visual acuity remained at 20/25, fundus examination. Fluorescein angiography, indocyanine green angiography and optic coherence tomography showed fibrotic evolution of CNV. The Bruch's membrane rupture remained stable. No side-effect of intravitreal injection of ranibizumab was observed.For this patient affected with CNV secondary to traumatic Bruch's membrane, one single intravitreal ranibizumab injection was efficient, with 1-year follow-up.

Purpose:To analyze retrospectively the efficacy of intravitreal ranibizumab injections for the management of choroidal neovascularization in patients with angioid streaks over a long term.Methods:In this nonrandomized, double-center, retrospective, interventional case series, a consecutive series of patients affected with choroidal neovascularization associated with angioid streaks were treated with intravitreal ranibizumab injections (0.5 mg/0.05 mL). Best-corrected visual acuity, fundus photography, optical coherence tomography, and fluorescein angiography were examined before and after treatment. The primary endpoint was the percentage of eyes with stable or improved visual acuity at the end of follow-up (loss of less than 3 Early Treatment Diabetic Retinopathy Study lines). Secondary endpoints were the percentage of eyes with stable or decreased macular thickness on optical coherence tomography (less than a 10% increase in macular thickness) and the percentage of eyes with persistent leakage on fluorescein angiography at the last observation carried forward.Results:Thirty-five eyes of 27 patients were treated with repeated intravitreal ranibizumab injections (mean of 9.9 7.2 injections, range 2-26) for a mean of 48.6 +/- 17.1 months (range 8-66). At the end of follow-up, best-corrected visual acuity was stabilized or improved in 22 of 35 eyes (62.9%). Macular thickness had stabilized or decreased in 16 of 35 eyes (45.7%). At the last follow-up examination, on fluorescein angiography, no further leakage was observed in 27 of 35 eyes (77.1%).Conclusion:In this large series of patients with choroidal neovascularization associated with angioid streaks followed for 4 years, ranibizumab injections allowed stabilization of best-corrected visual acuity in most eyes. Ranibizumab appear as an effective therapeutic option in CNV associated with angioid streaks over long time.

PURPOSE We assessed the associations of serum, red blood cell membranes (RBCM) and dietary long-chain n-3 polyunsaturated fatty acids (LC-PUFAs) with neovascular age-related macular degeneration (AMD). METHODS We included 290 patients of the Nutritional AMD Treatment 2 Study (NAT2) with neovascular AMD in one eye and early AMD lesions in the other eye, and 144 normal vision controls without AMD. Dietary intake of seafood was estimated by food frequency questionnaire. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) composition in serum and RBCM were determined by gas chromatography from 12-hour fasting blood samples and was expressed as percentages of total fatty acids profile. Logistic regressions estimated associations of neovascular AMD with dietary intake of seafood and circulating n-3 LC-PUFAs. RESULTS Dietary oily fish and seafood intake were significantly lower in AMD patients than in controls. After adjustment for all potential confounders (age, sex, CFH Y402H, ARMS2 A69S, and ApoE4 polymorphisms, plasma triglycerides, hypertension, hypercholesterolemia, and family history of AMD), serum EPA was associated significantly with a lower risk for neovascular AMD (odds ratio [OR] = 0.41; 95% confidence interval [CI], 0.22-0.77; P = 0.005). Analysis of RBCM revealed that EPA and EPA+DHA were associated significantly with a lower risk for neovascular AMD (OR = 0.25; 95% CI, 0.13-0.47; P < 0.0001 and OR = 0.52; 95% CI, 0.29-0.94; P = 0.03, respectively). CONCLUSIONS The RBCM EPA and EPA+DHA, as long-term biomarkers of n-3 dietary PUFA status, were associated strongly with neovascular AMD and may represent an objective marker identifying subjects at high risk for neovascular AMD, who may most benefit from nutritional interventions. (http://www.controlled-trials.com/isrctn number, ISRCTN98246501).

The purpose of the CAP (Creteil AMD PHRC-funded) Study was to analyze risk factors of exudative age-related macular degeneration (AMD) in a large French case–control population. One thousand and twenty-four patients with exudative AMD and 275 controls were recruited. Information about lifestyle, medical history, and dietary intake were collected. Associations of risk factors were estimated using logistic regression. After multivariate adjustment, CFH Y402H and ARMS2 A69S polymorphisms were associated with very high risk for exudative AMD (OR = 6.21 and OR = 11.7, respectively, p

PURPOSE: To investigate the effects of ranibizumab 0.5 mg on gray hyper-reflective subretinal lesions diagnosed by spectral-domain optical coherence tomography (SD OCT) in patients with exudative age-related macular degeneration (AMD). DESIGN: Retrospective interventional study. METHODS: Data from 28 consecutive patients affected with neovascular AMD that presented subretinal hyper-reflective lesions as visualized by SD OCT were collected. Gray hyper-reflective subretinal lesion characteristics were analyzed before and after intravitreal ranibizumab 0.5 mg injection. RESULTS: Thirty eyes of 28 patients (5 male, 23 female, aged 57-91 years) were included. At study entry, gray lesion was associated with exudative features in 24 of 30 eyes (80%), including subretinal fluid (SRF) in 20 of 30 eyes (67%) and retinal cystoid spaces in 11 of 30 eyes (37%). Twenty-four eyes with exudative features at study entry received prompt treatment; 6 eyes without exudative features at study entry received deferred treatment (after 1 month observation), when exudative signs emerged (SRF in 3/6 eyes and retinal cystoid spaces in 5/6 eyes). Ninety-three percent of the gray lesions responded to ranibizumab treatment at 2 months and 77% at 6 months. Gray hyper-reflective subretinal lesion thickness was significantly reduced after treatment at both 2 months (from 482 +/- 116 mu m to 367 +/- 102 mu m, P < .0001) and 6 months (from 482 +/- 116 mu m to 369 +/- 71 mu m, P < .0001). CONCLUSION: Our findings suggest that gray hyper-reflective subretinal lesions might be considered as a qualitative criterion for retreatment of exudative AM:D. They may represent an early sign of active choroidal neovascularization, and should prompt to early treatment. ((C) 2014 by Elsevier Inc. All rights reserved.)

PURPOSE. To compare macular choroidal thickness (MCT) in eyes with adult onset foveomacular vitelliform dystrophy (AOFVD) and eyes with AMD. METHODS. Five groups of 38 eyes each were included in a prospective, observational, comparative study: AOFVD eyes with fluid accumulation; AOFVD fellow eyes without fluid (early stage); advanced exudative (wet) AMD; advanced dry AMD; and healthy normal eyes. All study eyes underwent a comprehensive ophthalmologic examination. Macular choroidal thickness was measured using enhanced depth imaging optical coherence tomography (EDI-OCT). RESULTS. Subfoveal choroidal thickness (SFCT) in AOFVD with subretinal fluid (325.66 +/- 85.98 mu m) was significantly (P < 0.001) thicker compared with that in exudative AMD (158.55 +/- 57.87 mu m) and in dry AMD (157.53 +/- 67.08 mu m). Also, in AOFVD, the choroid was significantly (P = 0.001) thicker than that in the normal group (255.87 +/- 87.46 mu m). However, in AOFVD, there was no significant difference (P = 0.69) between the SFCT in the study eye and in the fellow eye (317.66 +/- 90.04 mu m). The choroidal thickness at each of the other 12 measured points showed similar results. CONCLUSIONS. This study demonstrates choroidal thickening in AOFVD in contrast with the choroidal thinning observed in advanced AMD. These findings suggest that the pathogenic mechanisms in AOFVD are different from those in exudative AMD. Choroidal thickness measurement could help differentiate the challenging diagnosis between exudative AMD and the advanced stage of AOFVD (with fluid accumulation but without choroidal neovascularization).

Purpose: To assess intraobserver and interobserver agreement among physicians with different degrees of clinical experience, using a novel fundus autofluorescence semiautomated software for quantification of geographic atrophy in clinical setting. Methods: Fundus autofluorescence frames (excitation: 488 nm; emission: 500-700 nm) of 29 eyes (20 patients; mean age, 79.6 +/- 6.2 years) with geographic atrophy secondary to age-related macular degeneration, and no signs of choroidal neovascularization, were analyzed using Region Finder, a semiautomated software embedded in Spectralis (Heidelberg Engineering, Heidelberg, Germany). For each study eye, semiautomated atrophy identification and quantification were independently performed, twice (in a 2-week time frame), by 3 readers with different degrees of clinical experience (2 fellows, and 1 resident). Intraobserver and interobserver agreements were assessed. Results: Mean difference in intraobserver agreement (Bland-Altman statistics) ranged from -0.17 mm(2) to 0.13 mm(2). Intraobserver agreement was excellent until the geographic atrophy threshold value of 15.72 mm(2). Variability correlated with the size of atrophy. Mean difference in interobserver agreement (Bland-Altman statistics) ranged from -0.25 mm(2) to 0.27 mm(2), with no significant difference between senior and junior readers. Multifocal lesion or foveal involvement in atrophy was not the cause of disagreement. Conclusion: Region Finder is a reliable tool for the identification and quantification of geographic atrophy in patients with age-related macular degeneration, in a clinical setting even when performed by junior reader.

To compare choroidal thickness (CT) between eyes with adult onset foveo macular vitelliform dystrophy (AOFVD) eyes with age-related macular degeneration (AMD). 5 group (38 eyes each) with AOFVD, fellow eyes with AOFVD wet AMD, dry AMD, age-matched normal subjects.Choroidal thickness was measured using enhanced-depth imaging optical coherence tomography (EDI-OCT) with Spectralis. Subfoveal choroidal thickness (SFCT) in each eye was analyzed with measurement of the vertical distance from the Bruch’s membrane to the innermost choroid/sclera junction, at 500µm intervals up to 1500µm, from temporal to nasal and from superior to inferior to the center of the fovea.The difference between SFCT AOFVD (325.66 +/- 86 µm) versus CT in wet AMD (168.21 +/- 57.7 µm) and CT in dry AMD (158.77 +/- 68 µm) and versus elderly normal (238,33 +/- 83µm) are statistically significant, (p <

Background Our purpose was to describe the different morphological features in adult onset foveomacular vitelliform dystrophy (AOFVD), using en face enhanced depth imaging (EDI) spectral-domain optical coherence tomography (SD-OCT). Methods Thirty eyes of 22 consecutive patients presenting with diagnosis of AOFVD were enrolled. Diagnosis of AOFVD was concluded based on fundus examination, autofluorescence imaging, fluorescein angiography and SD-OCT. En face OCT imaging was obtained with the Spectralis EDI SD-OCT; 97 inverted sections (nine averaged B-scans per image) were acquired. Results On en face OCT, vitelliform lesions appeared as regular concentric rings of different reflectivity. From the periphery to center of the ring, we observed: (1) the hypereflective ring representing the inner segment/outer segment (IS/OS) junction, which was continuous in 23 out of 30 eyes, and (2) a well-detectable hyporeflective ring between the IS/OS junction and vitelliform material in 20 out of 30 eyes; the innermost composant of the lesion was hypereflective, and it corresponded to vitelliform material. In eight out of 30 eyes, a hyporeflective "croissant"-shaped lesion with inferior concavity in the upper part of the hyperreflective material was present. Hypereflective retinal pigment epithelium (RPE) elevations or bumps were detected in 25 out of 30 eyes. These areas of focal RPE thickening or bumps appeared to be intensely hypereflective on infrared reflectance imaging. Conclusion En face imaging of the retina helps visualizing the distribution of vitelliform material in AOFVD. The sedimentation of vitelliform lesions is characterized by a upper "croissant"-shaped hypoflectivity. The bumps/thickening of RPE appeared as hypereflective lesions on IR imaging.

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

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.

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

Purpose: To evaluate the efficacy and the safety of intravitreal ranibizumab injection (Lucentis) in eyes with macular oedema secondary to central retinal vein occlusion (CRVO) or branch retinal vein occlusion (BRVO). Methods: The files of consecutive patients (34 eyes, 15 CRVO, 19 BRVO) were retrospectively analysed. Intravitreal injections of 0.5 mg ranibizumab were administered; retreatment was based on acuity visual changes and optical coherence tomography findings. Patients received 2–4 injections (mean, 2.1). Mean follow-up was 7 months. Results: After the first injection, mean best-corrected visual acuity (BCVA) improved from 20/160 to 20/80 and mean central retinal thickness (CRT) decreased significantly from 549 to 301 μm (p

Purpose To describe the different morphological features in adult onset foveomacular vittelliform dystrophy (AOFVD) using high-resolution spectral domain optical coherence tomography (OCT). Design Prospective observational case series. Methods Complete ophthalmologic examination, including spectral domain OCT, was performed in 49 consecutive AOFVD patients (60 eyes). Results In 28/60 eyes, spectral domain OCT showed hyper-reflective clumps within the outer plexiform and outer nuclear layers. In 9/60 eyes, the photoreceptor inner segment/outer segment (IS/OS) interface appeared highly reflective like a shell all around the vitelliform material, and appeared irregular and discontinued in 27/60 eyes. The Verhoeff membrane was clearly visible at the border of the lesion, disappeared over the vitelliform lesion in 20/60 eyes, became thickened and less defined on the outer aspect of the lesion in 11/60 eyes, appeared without noticeable alterations in 10/60 eyes and not well defined in 19/60 eyes. The vitelliform material appeared as a highly reflective dome-shaped lesion (homogeneous in 14/60 eyes and heterogeneous in 36/60 eyes) located between the photoreceptor layer and the retinal pigment epithelium (RPE). In 10/60 eyes, the macular lesion appeared as hypo/a-reflective. The RPE appeared irregular in 14/60 eyes, with hyper-reflective mottling on its inner aspect. We observed discrete RPE detachments in 29/60 eyes. Conclusions We hypothesise that early changes involve the layer between RPE and the IS/OS interface, first with vitelliform material accumulation beneath the sensory retina, and then with IS/OS alterations, pigments migration towards inner layers and fluid accumulation. These changes come with RPE alterations such as hypertrophy or sub-RPE deposits.

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

Purpose To study the effect of anti–vascular endothelial growth factor (VEGF) therapy on subretinal hyperreflective exudation detected by spectral-domain optical coherence tomography (SD OCT) in myopic choroidal neovascularization (CNV). Design Retrospective consecutive observational cohort study. Methods Thirty-one eyes of 31 consecutive highly myopic patients with CNV and showing a subretinal hyperreflective exudation on SD OCT were included. Morphologic changes were assessed before and after anti-VEGF therapy, based on the subretinal hyperreflective exudation thickness, retinal thickness at the level of the CNV, and central macular thickness. Results After anti-VEGF treatment (mean follow-up of 1.9 ± 0.8 months, mean number of injections 1.8 ± 0.6), the subretinal hyperreflective exudation regressed completely in 29 of 31 eyes (93.5%) and partially in 2 of 31 eyes (6.5%). Mean subretinal hyperreflective exudation thickness, mean retinal thickness at the level of the CNV, and mean central macular thickness significantly decreased from 102 ± 50 μm to 2.6 ± 10.2 μm ( P P P = .0008), respectively. Conclusion The subretinal hyperreflective exudation was an SD OCT finding that correlated with signs of active myopic CNV (either subretinal fluid/intraretinal cysts on SD OCT or dye leakage on fluorescein angiography) and responded to treatment with anti-VEGF agents. The presence of a subretinal hyperreflective exudation on SD OCT could help in making decisions on the need to perform or not perform fluorescein angiography, and regarding treatment or retreatment.

Nathalie Puche1, Olivier Offret1, Jean-Antoine Bernard1, Francine Behar-Cohen1,21Department of Ophthalmology, Hotel Dieu de Paris, AP-HP, Université Paris Descartes; 2Inserm UMRS872, Physiopathology of Ocular Diseases: Therapeutic Innovations, Centre de Recherche des Cordeliers, Université Paris Descartes, Paris, FrancePurpose: To report the time course of retinal morphologic changes in a patient with acute retinal pigment epithelitis (ARPE) using spectral domain optical coherence tomography (SD-OCT).Methods: A 30-year old man was referred for blurred vision of his right eye after five days that appeared suddenly 15 days after recovery from a flu-like syndrome. SD-OCT was performed immediately, followed by fluorescein and infracyanine angiography at eight days and then at three weeks.Results: At presentation, a bubble of sub-macular deposit was observed on the right macula with central golden micronodules in a honeycomb pattern. SD-OCT showed an “anterior dislocation” of all the retinal layers up to the inner/outer segment (IS/OS) line and irregular deposits at the OS level together with thickening of the retinal pigment epithelial (RPE) layer. As visual acuity increased, eight days later, the OCT showed reduction of the sub-retinal deposits and an abnormal hyperflectivity of the sub-retinal and RPE layers was observed. The patient showed a positive serology for picornavirus.Discussion: The acute SD-OCT sections of this patient with ARPE were compared with histological sections of a 35 day old Royal College of Surgeons rat. Similar findings could be observed, with preservation of the IS/OS line and accumulation of debris at the OS level, suggesting that ARPE symptoms could result from a transient phagocytic dysfunction of the RPE at the fovea, inducing reversible accumulation of undigested OS. Picornaviruses comprising enterovirus and coxsachievirus described as being associated with acute chorioretinitis. In this case, it was responsible for ARPE.Conclusion: We hypothesize that ARPE syndrome results from a transient dysfunction of RPE, which can occur as a post viral reaction.Keywords: acute retinal pigment epithelitis, picornavirus, SD-OCT

Introduction Le but de cette etude est de comparer l’aspect des taches flavimaculees en auto-fluorescence et simultanement en imagerie avec tomographie en coherence optique a haute resolution et determiner la localisation du materiel vitelliforme dans les differentes couches de la retine Materiels et methodes Cette etude prospective, non-comparative a inclus 13 patients (26 yeux). Chaque patient a eu un examen ophtalmologique complet avec examen du fond d’œil, imagerie par auto-fluorescence et avec simultanement une tomographie en coherence optique a haute resolution. Resultats Des taches flavimaculees peuvent etre observees autour de la fovea ou plus a distance, autour de l’aire maculaire, au pole posterieur ou en peripherie retinienne. Elles sont tres polymorphes. Quatre types ont pu etre identifies en OCT. Le premier type de lesion est le moins visible en auto-fluorescence et peut etre decrit comme une accumulation de materiel hyper-reflective dans la couche externe des segments externes des photorecepteurs et des cellules de l’epithelium pigmentaire (ligne 4 et ligne 3). Le second type de lesion est caracterise par une accumulation plus importante de materielhyper-reflective, mais encore limite aux memes couches de la retine en forme de dome soulevant les couches internes des photorecepteurs et de la membrane limitante externe (ligne 2 et ligne 1). Le troisieme type montre une accumulation plus importante de materiel hyper-reflective dans toutes les couches de la retine externe incluant la ligne 2 et la ligne 1. Le quatrieme type correspond au type 3 avec une progression de materiel hyper-reflective dans les couches nucleaires externes. Les lesions de type 3 ou 4 sont souvent associees a une perte des photorecepteurs adjacents et par ailleurs par une diminution de l’epaisseur de la couche des cellules de l’epithelium pigmentaire et de celle de la membrane de Bruch. Discussion Les deux techniques d’imagerie sont contributives pour l’evaluation de l’atteinte retinienne dans le syndrome des taches flavimaculees. Conclusion Cette etude est la premiere analyse en mode simultane des differents types de taches flavimaculees en auto-fluorescence et leur localisation dans les differentes couches retiniennes en tomographie en coherence optique a haute resolution.

Objectif Evaluer l’efficacite et la securite des injections intravitreennes de ranibuzimab dans les yeux avec œdeme maculaire secondaire a une occlusion de la veine centrale de la retine ou une occlusion de la branche de la veine centrale de la retine. Materiels et Methodes Etude retrospective interventionnelle d’une serie de patients traites Une serie de 34 patients consecutifs (34 yeux 15 OVCR, 19 OBR) ont ete analyses dans cette etude. Une injection intravitreenne de 0,5 mg Ranibuzimab a ete realisee. La decision de retraiter etait basee sur l’OCT et l’AV. Resultats Une a quatre injections ont ete realisees pour chaque patient. L’epaisseur moyenne initiale de l’epaisseur maculaire etait 548 μm et l’acuite visuelle moyenne etait 20/160. Apres la premiere injection, l’epaisseur maculaire diminuait significativement a 301 μm (p Discussion Depuis que les anti VEGF ont ete approuves dans le traitement de la degenerescence liee a l’âge, ce traitement represente une nouvelle approche dans l’œdeme maculaire des occlusions veineuses retiniennes. Notre etude demontre une efficacite fonctionnelle et anatomique comparable au Bevacizumab avec 5 mois de recul. Cette etude retrospective apporte de bonnes conclusions sur la securite, cette securite ayant deja ete demontree dans des etudes cliniques dans la DMLA. Conclusion Les injections intravitreennes de ranibuzimab paraissent etre une option sure et efficace dans le traitement de l’œdeme maculaire secondaire a une occlusion veineuse retinienne.

Objectif La Degenerescence Maculaire Liee a l’Âge (DMLA) est une maladie frequente et multifactorielle ou la composante genetique est forte. Nous avons entrepris un travail d’identification de nouveaux facteurs genetiques de predisposition et d’analyse de facteurs genetiques deja connus dans une cohorte de patients ne portant aucun des variants a risque pour les genes CFH et LOC387715 (ARMS2). Materiels et Methodes 1 255 patients atteints de DMLA et 301 controles indemnes de plus de 55 ans ont ete recrutes a partir de 3 centres d’ophtalmologie francais. Un examen ophtalmologique complet a ete realise afin de permettre une classification precise de la DMLA. Les renseignements cliniques generaux ont ete colliges. Dans la cohorte totale patients et controles, un premier criblage des polymorphismes Y402H du CFH et rs10490924 du LOC387715 a ete realise afin d’identifier les patients double homozygotes sauvages pour ces deux genes. Nous avons etudie par une approche gene candidat les genes de l’apolipoproteine J, OSBP2, de la vitronectine, ainsi que les polymorphismes des genes C3, et CX3CR1. Resultats 64 patients et 77 controles etaient double homozygotes sauvages pour les variants a risque des genes CFH et LOC387715 sur l’ensemble de la cohorte. L’etude des genes deja incrimines ainsi que les nouveaux genes candidats, n’a pas mis en evidence d’association avec la DMLA. Discussion Differentes voies sont impliquees dans la physiopathologie de la DMLA telle l’inflammation, la regulation de l’homeostasie lipidique… Dans un groupe de patients doubles homozygotes sauvages, ou il nous apparaissait que les facteurs de predisposition genetique plus modestes pouvaient etre demasques, nous n’avons pas retrouve d’association entre des genes de ces voies et la DMLA. Conclusion La poursuite de cette etude est en cours, afin d’identifier de nouveaux facteurs genetiques dans la DMLA qui, nous l’esperons, pourraient aider a une meilleure connaissance de la physiopathologie de la maladie.

Purpose: To evaluate the efficacy of intravitreal injections of ranibizumab for choroidal neovascularization associated with adult-onset foveomacular vitelliform dystrophy. Methods: Retrospective case series of 24 eyes affected with choroidal neovascularization associated with adult-onset foveomacular vitelliform dystrophy treated by intravitreal injections of ranibizumab (0.5 mg/0.05 mL). Best-corrected visual acuity, fundus examination, spectral domain optical coherence tomography, fundus autofluorescence, and fluorescein and indocyanine green angiography were performed for the diagnosis of adult-onset foveomacular vitelliform dystrophy and choroidal neovascularization. After initial 3 monthly injections of ranibizumab, patients were followed up monthly and retreated if neovascular activity persisted. Outcome measure was the proportion of patients losing fewer than 3 lines of visual acuity from baseline to 12 months (final visit). Results: At final visit, the mean number of ranibizumab injections was 4.5 +/- 1.29. From baseline to final visit, 21 of 24 eyes (87.5%) lost fewer than 3 lines of visual acuity. Mean best-corrected visual acuity did not change significantly from baseline to final visit (0.37 +/- 0.2 logarithm of the minimum angle of resolution vs. 0.30 +/- 0.25 logarithm of the minimum angle of resolution, respectively; P = 0.115). Mean central macular thickness significantly decreased from baseline to final visit (327 +/- 83 mu m vs. 260 +/- 57 mu m, respectively; P = 0.001). Conclusion: In this series, ranibizumab succeeded in stabilizing best-corrected visual acuity in patients with choroidal neovascularization associated with adult-onset foveomacular vitelliform dystrophy. Ranibizumab seems to be a reasonable therapeutic option in this condition. RETINA 33:513-521, 2013