RETINOCHOROIDAL ANASTOMOSIS ASSOCIATED WITH ENHANCED S-CONE SYNDROME.

PURPOSE: To describe the phenotype and genotype of a 10-year-old boy affected with enhanced S-cone syndrome associated with neovascularization. METHODS: Fundus autofluorescence, fluorescein angiography, indocyanine green angiography, spectral domain optical coherence tomography, full-field electroretinogram and NR2E3 molecular testing were performed. RESULTS: Best-corrected visual acuity was measured as 20/32, right eye and 20/20, left eye. Fluorescein and indocyanine green angiographies showed unilateral macular retinochoroidal anastomosis on his right eye, and spectral domain optical coherence tomography showed typical signs of subretinal exudation and foveolar pseudoschisis consistent with the diagnosis of enhanced S-cone syndrome. Genetic analysis revealed biparental transmission of mutations in the enhanced S-cone syndrome-causing gene, NR2E3, namely, c.194_202del (p.Asn65_Cys67del), and c.932 G>A (p.Arg311Gln), supporting an autosomal recessive inheritance. The patient received three intravitreal injections of anti-VEGF agents. CONCLUSION: Evidence of retinochoroidal anastomosis in an individual affected with enhanced S-cone syndrome supports the view that neovascularization can occur early in the course of the disease, and raises the question to know whether it might be responsible for previously described enhanced S-cone syndrome-associated hemorrhage-induced fibrosis.

INTRAVITREAL RANIBIZUMAB FOR CHOROIDAL NEOVASCULARIZATION IN ANGIOID STREAKS: Four-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.

Unusual retinopathy associated with hemochromatosis.

PURPOSE: To describe unusual retinal findings of a patient affected by hemochromatosis. METHODS: Case report of a 49-year-old patient who presented a progressive loss of vision. Fundus photography, fluorescein angiography, full-field electroretinogram, autofluorescence imaging, and spectral domain optical coherence tomography were performed. The patient was known to be homozygous for the C282Y mutation in the HFE gene. RESULTS: Visual acuity was measured at 20/20 on his right eye and 20/25 on his left eye. Retinal imaging showed alterations of the retinal pigment epithelium clearly visible on fundus autofluorescence and fluorescein angiography. The spectral domain optical coherence tomography showed retinal pigmentary epithelial atrophy associated with irregularities and focal interruption of the ellipsoid zone. A thin retina was also observed in the foveolar region associated to a thickened choroid. Full-field electroretinogram showed a decrease of rods and cones responses. CONCLUSION: Here, the authors describe the retinal findings of a patient affected by hemochromatosis, characterized by unusual retinal pigment epithelium changes associated to altered visual function. The authors hypothesize that the retinopathy could be linked to hemochromatosis because of the pathophysiology of iron homeostasis and the toxicity of iron overload for the photoreceptors.

Choroidal findings in Bietti's crystalline dystrophy.

PURPOSE: To describe the choroidal findings in a patient with Bietti's crystalline dystrophy. METHODS: A 43-year-old woman with Bietti's crystalline dystrophy underwent a complete ophthalmologic examination including enhanced depth imaging spectral domain optical coherence tomography and en face optical coherence tomography. RESULTS: We observed a severe thinning of the choroid, 123 µm in the right eye and 110 µm in the left eye. Crystal deposits were found not only in the retina but also in the choroid. En face optical coherence tomography clearly showed the intraretinal crystals as small hyperreflective dots in the different retinal layers and in the choroid. CONCLUSION: Our study gives new information on the aspect and the location of crystal deposits in the choroid and the abnormalities of the outer retina associated with the disease.

Multimodal analysis of the progression of Best vitelliform macular dystrophy.

PURPOSE: To investigate the multimodal morphological features in the different stages of Best vitelliform macular dystrophy (VMD) in subjects harboring mutations in the BEST1 gene, and their changes during the progression of the disease. METHODS: In this retrospective observational study performed between January 2007 and December 2012, 21 patients (42 eyes) with Best VMD from eight families with the BEST1 mutation were included. Best-corrected visual acuity (BCVA), fundus autofluorescence (FAF), and spectral domain optical coherence tomography (SDOCT) were evaluated at study entry and at last visit. RESULTS: The mean age of patients was 26.3±17.4 years. Seven new missense mutations in BEST1 were identified. Mean follow-up was 41.1±18.5 months. Mean BCVA was 0.34±0.34 LogMAR at study entry and 0.32±0.33 LogMAR at last follow-up visit (p = 0.2). The overall lesion area on FAF increased from 6.62±4.9 mm² to 7.34±6.1 mm² (p = 0.05). At study entry, on SD-OCT, photoreceptor inner segment ellipsoid portion (ellipsoid zone, EZ) was normal in 15 eyes, disrupted in 14 eyes, and absent in 13 eyes. In two eyes, EZ changed from normal to disrupted during follow-up. Three eyes of three patients showing pseudohypopyon lesions at study entry progressed to vitelliruptive lesions at the last follow-up visit. Three eyes of three patients showing vitelliruptive lesion at study entry reverted to pseudohypopyon lesion with overall enlargement of the lesion size. CONCLUSIONS: Multimodal analysis allowed documenting a continuous material accumulation and reabsorption in Best VMD progression. Blue FAF and SD-OCT could represent noninvasive imaging techniques to monitor Best VMD.

Hyperreflective pyramidal structures on optical coherence tomography in geographic atrophy areas.

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 µm in the foveal scan (range, 42-291 µm). 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.

En face enhanced depth imaging optical coherence tomography features in adult onset foveomacular vitelliform dystrophy.

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.

Risk factors for exudative age-related macular degeneration in a large French case-control study.

PURPOSE: 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. PATIENTS AND METHODS: 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. RESULTS: 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 < 0.0001). Risk for exudative AMD was increased in current smokers (OR = 3.79, p = 0.0003) and former smokers having quitted since less than 20 years ago (OR = 2.30, p = 0.002), but not in former smokers having quitted since 20 years or more ago (OR = 0.81, p = 0.43). Heavy smokers (at least 25 pack-years) were particularly at risk (OR = 3.61, p < 0.0001). Use of cooking oils rich in omega 3 fatty acids was significantly associated with a reduced risk of exudative AMD (OR = 0.55, 95 % CI: 0.36-0.84, p = 0.006), as well as a high consumption of fruits (OR = 0.60, 95 % CI: 0.37-0.98, p = 0.04), but not the consumption of fish, vegetables or oils rich in omega 6. High waist circumference was associated with increased risk for exudative AMD (OR = 2.53, p < 0.0001), but not hypercholesterolemia, hypertension, or body mass index. CONCLUSIONS: The CAP Study confirms major genetic risk factors for exudative AMD. It further documents the high risk in heavy smokers and the long persistence of risk after smoking cessation, and the associations with waist circumference and fruit consumption. Furthermore, we observed an inverse correlation between AMD and cooking oils harboring a beneficial omega-3 fatty acid profile.

Reticular pattern dystrophy of the retina: a spectral-domain optical coherence tomography analysis.

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.

Rare variants in CFI, C3 and C9 are associated with high risk of advanced age-related macular degeneration.

To define the role of rare variants in advanced age-related macular degeneration (AMD) risk, we sequenced the exons of 681 genes within all reported AMD loci and related pathways in 2,493 cases and controls. We first tested each gene for increased or decreased burden of rare variants in cases compared to controls. We found that 7.8% of AMD cases compared to 2.3% of controls are carriers of rare missense CFI variants (odds ratio (OR) = 3.6; P = 2 × 10(-8)). There was a predominance of dysfunctional variants in cases compared to controls. We then tested individual variants for association with disease. We observed significant association with rare missense alleles in genes other than CFI. Genotyping in 5,115 independent samples confirmed associations with AMD of an allele in C3 encoding p.Lys155Gln (replication P = 3.5 × 10(-5), OR = 2.8; joint P = 5.2 × 10(-9), OR = 3.8) and an allele in C9 encoding p.Pro167Ser (replication P = 2.4 × 10(-5), OR = 2.2; joint P = 6.5 × 10(-7), OR = 2.2). Finally, we show that the allele of C3 encoding Gln155 results in resistance to proteolytic inactivation by CFH and CFI. These results implicate loss of C3 protein regulation and excessive alternative complement activation in AMD pathogenesis, thus informing both the direction of effect and mechanistic underpinnings of this disorder.

Genetic association study of mitochondrial polymorphisms in neovascular age-related macular degeneration.

PURPOSE: Age-related macular degeneration (AMD) is a multifactorial disease involving genetic and environmental factors. Most of the genetic factors identified so far involve the nuclear genome. Recently, two studies in North America and Australia reported an association between advanced AMD and the mitochondrial T2 haplogroup. Our purpose was to assess this association in a large French population. METHODS: This case control study included 1,224 patients with neovascular AMD and 559 controls with normal fundus. Mitochondrial DNA polymorphisms at and around nucleotides 4917, 11,812, and 14,233 were determined using PCR amplification and direct sequencing of mitochondrial DNA. RESULTS: No association was found between the mitochondrial T2 haplogroup and neovascular AMD in the French population: 94/1,152 patients with neovascular AMD had the T2 haplogroup (8.2%) versus 34/482 controls (7.1%; odds ratio=0.9 [0.5-1.5], p=0.66). CONCLUSIONS: An association between AMD and the T2 haplogroup, previously described in North American and Australian populations, was not confirmed in a large French population.

Genetic and environmental factors associated with reticular pseudodrusen in age-related macular degeneration.

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.

Spontaneous combined full-thickness retinal and pigment epithelium macular hole in age-related macular degeneration.

The authors describe a case of combined full-thickness retinal and pigment epithelium macular hole that spontaneously developed in the right eye of an 86-year-old woman with age-related macular degeneration (AMD). One year prior, the patient had been diagnosed with drusenoid pigment epithelium detachment (PED) in the right eye and geographic atrophy in the left eye. Full-thickness macular hole associated with PED and spontaneous rip of the retinal pigment epithelium (RPE) associated with macular hole have been previously reported in eyes with exudative AMD. However, the authors are unaware of any report of spontaneous full-thickness retinal and pigment epithelium hole at the macula in AMD. The pathogenic mechanisms of this unusual macular hole, which involves the full retinal thickness and RPE, may include stretching forces at the vitreomacular interface and pushing from within the PED.

Intravitreal dexamethasone implant (Ozurdex) for macular edema secondary to retinitis pigmentosa.

BACKGROUND: To evaluate the anatomical and functional outcomes of intravitreal dexamethasone implant in patients with macular edema (ME) secondary to retinitis pigmentosa (RP). METHODS: Three patients (four eyes), aged 24 to 46 years, presented with refractory ME secondary to RP. Intravitreal dexamethasone implant (Ozurdex) was administered to treat ME. The anatomical (central macular thickness [CMT]) and functional (best-corrected visual acuity [BCVA]) outcomes as well as adverse events were recorded. RESULTS: All patients completed 6 months follow-up. After intravitreal Ozurdex all patients showed regression of ME. At baseline, mean CMT was 443 ± 185 µm (range 213-619 µm); ME improved to 234 ± 68 µm (range 142-307 µm) at 1 month, to 332 ± 177 µm (range 139-513 µm) at 3 months, and to 305 ± 124 µm (range 144-447 µm) at 6 months. Recurrent ME was recorded in 2 patients (both patients at 3 months from intravitreal dexamethasone implant). Retreatment with intravitreal Ozurdex was performed in two patients. Mean BCVA improved form 20/160 (range 20/50-20/200) (baseline) to 20/100 (range 20/40-20/125) at 1 month, to ∼20/125 (range 20/100-20/200) at 3 months, and to ∼ 20/125 (range 20/100-20/160) at 6 months. No serious ocular and systemic adverse events were observed during the study period. CONCLUSIONS: Intravitreal dexamethasone implant provides anatomic and functional improvements and may represent a valuable treatment option for patients with ME secondary to RP.

Single nucleotide polymorphism in the cholesterol-24S-hydroxylase (CYP46A1) gene and its association with CFH and LOC387715 gene polymorphisms in age-related macular degeneration.

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.

Genetic factors associated with age-related macular degeneration.

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.

No association between the T280M polymorphism of the CX3CR1 gene and exudative AMD.

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.

The spectrum of subclinical Best vitelliform macular dystrophy in subjects with mutations in BEST1 gene.

PURPOSE: To describe the morphologic and functional characteristics of subclinical Best vitelliform macular dystrophy (VMD) in subjects with mutation in the BEST1 gene. METHODS: Best-corrected visual acuity (BCVA), funduscopic appearance, fundus autofluorescence (FAF), spectral-domain optical coherence tomography (SD-OCT), and electro-oculography (EOG) were assessed in 23 consecutive subjects from nine unrelated families with known mutations in the BEST1 gene (eight distinct BEST1 mutations). RESULTS: Six subjects were identified with BEST1 mutations (three male, three female; aged 8 to 30 years) without clinically detectable (subclinical) Best VMD (absence of both symptoms and funduscopic lesions). All six subjects showed 20/20 BCVA and normal FAF findings. In these 6 of 26 subjects from five different families, we found five distinct mutations in the BEST1 gene. In three (six eyes) out of these six subjects with BEST1 gene mutations (two families: p.G15D; p.A243V), SD-OCT showed overall normal findings. In the other three subjects (six eyes) with BEST1 gene mutations (three families: p.V9A; p.R92C; p.I230T), we found, on SD-OCT, a thicker and more reflective appearance of the layer between the retinal pigment epithelium and the interface of inner segments and outer segments of the photoreceptor (the Verhoeff's membrane). EOG showed a reduced light-peak:dark-trough ratio in 5 of 12 eyes. Changes on SD-OCT were present in the absence of EOG abnormalities (two of six eyes), and vice versa (one of six eyes). CONCLUSIONS: Subclinical Best VMD (absence of both symptoms and funduscopic lesions) in subjects with BEST1 mutation may vary from the absence of any morphologic and functional abnormalities to the presence of specific SD-OCT and EOG changes.

R102G polymorphism of the C3 gene associated with exudative age-related macular degeneration in a French population.

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.

[Genetic factors associated with age-related macular degeneration]. / Génétique de la dégénérescence maculaire liée à l'âge.

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.