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ABSTRACT: 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 (Philadelphia, Pa.) 03/2013; · 2.93 Impact Factor
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ABSTRACT: : 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.
: All consecutive patients with geographic atrophy underwent FAF (excitation λ = 488 nm; emission λ > 500 nm), NIR-FAF (excitation λ = 787 nm; emission λ > 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.
: 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 μm vs. 1,228 ± 912 μm, P < 0.001 and 1,201 ± 922 μm, P < 0.001, respectively). Retinal fixation was predominantly central and stable in 97.3% of eyes with foveal sparing.
: Spectral domain OCT is an appropriate imaging modality for evaluating the presence and extent of foveal sparing, followed by NIR-FAF and FAF.
Retina (Philadelphia, Pa.) 03/2013; 33(3):482-9. · 2.93 Impact Factor
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ABSTRACT: PURPOSE:: Large colloid drusen (LCD) are a subgroup of early onset drusen recently reported. The aim of this study was to describe morphologic features in patients affected with LCD using high-resolution spectral-domain optical coherence tomography (SD-OCT). METHODS:: A complete ophthalmologic examination including SD-OCT was performed in 22 eyes of 11 consecutive patients. RESULTS:: Mean age was 35 years old at diagnosis, and mean visual acuity was 20/25. In all eyes, SD-OCT showed multiple dome-shaped retinal pigment epithelium detachments corresponding to the drusen. Mean height of drusen was 199 μm (range, 108-316 μm) and mean width was 419 μm (range, 190-681 μm). Indocyanine green angiography hypofluorescent LCD were larger and more reflective on SD-OCT than indocyanine green angiography hyperfluorescent LCD. All drusen appeared convex with medium and homogeneous internal reflectivity. Retina overlying LCD appeared wavy and overall thinned. Prominent diffuse hyperreflective haze in the Henle fiber layer over drusen was noted in 73% of the eyes. No geographic atrophy or choroidal neovascularization was observed. CONCLUSION:: The peculiar SD-OCT features reported in the current series give insight on the ultrastructure of LCD. Further studies with follow-up evaluation and possibly histologic evaluation are needed to clarify the clinical significance of LCD.
Retina (Philadelphia, Pa.) 01/2013; · 2.93 Impact Factor
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ABSTRACT: PURPOSE: To analyze the contribution of fluorescein angiography (FA) and spectral-domain optical coherence tomography (SD OCT) to the diagnosis of recent choroidal neovascularization (CNV) associated with high myopia. DESIGN: Retrospective, observational case series. METHODS: Ninety eyes of 73 highly myopic patients (refractive error ≥-6 diopters) with CNV in 1 or both eyes were included. Epidemiologic features, refractive error, fundus examination, fluorescein angiography, and SD OCT findings at onset of CNV were analyzed. RESULTS: Mean age at onset of CNV was 54.4 ± 14 years. CNV was bilateral in 17 of 73 cases. Mean refractive error was -13.9 ± 5.2 diopters. Myopic CNV was associated more frequently with patchy or geographic atrophy (P = .019). CNV was associated with exudative features on fluorescein angiography in 82% of cases (64/78), and on SD OCT in 48.6% of cases (36/74). There was no agreement about signs of active CNV between these 2 imaging methods (κ = 25.7 ± 10%; P = .0044). CNV area was significantly smaller in younger patients (<55 years) than in older patients (0.57 mm(2) vs 1.21 mm(2), respectively; P = .023). CONCLUSIONS: Exudative features of myopic CNV are more obvious on FA than on SD OCT, suggesting that fluorescein angiography should be performed when new-onset myopic CNV is suspected. Myopic CNV occurring in older patients (≥55 years) is larger than those seen in younger patients and resembles CNV associated with age-related macular degeneration. This suggests an overlap between myopic CNV in older patients and age-related macular degeneration.
American journal of ophthalmology 01/2013; · 3.83 Impact Factor
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Julien Tilleul,
Florence Richard,
Nathalie Puche,
Jennyfer Zerbib, Nicolas Leveziel,
Jose Alain Sahel,
Salomon Yves Cohen,
Jean-Francois Korobelnik,
Josue Feingold,
Arnold Munnich,
Josseline Kaplan,
Jean-Michel Rozet,
Eric H Souied
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ABSTRACT: 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.
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.
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).
An association between AMD and the T2 haplogroup, previously described in North American and Australian populations, was not confirmed in a large French population.
Molecular vision 01/2013; 19:1132-40. · 2.20 Impact Factor
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ABSTRACT: 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 msonth, 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.
Albrecht von Graæes Archiv für Ophthalmologie 12/2012; · 2.17 Impact Factor
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ABSTRACT: Background: To assess the ability of the Spectralis optical coherence tomography (OCT) segmentation software to identify the inner limiting membrane and Bruch's membrane in exudative age-related macular degeneration (AMD) patients. Methods: Thirty-eight eyes of 38 naive exudative AMD patients were retrospectively included. They all had a complete ophthalmologic examination including Spectralis OCT at baseline, at month 1 and 2. Reliability of the segmentation software was assessed by 2 ophthalmologists. Reliability of the segmentation software was defined as good if both inner limiting membrane and Bruch's membrane were correctly drawn. Results: A total of 38 patients charts were reviewed (114 scans). The inner limiting membrane was correctly drawn by the segmentation software in 114/114 spectral domain OCT scans (100%). Conversely, Bruch's membrane was correctly drawn in 59/114 scans (51.8%). The software was less reliable in locating Bruch's membrane in case of pigment epithelium detachment (PED) than without PED (42.5 vs. 73.5%, respectively; p = 0.049), but its reliability was not associated with SRF or CME (p = 0.55 and p = 0.10, respectively). Conclusion: Segmentation of the inner limiting membrane was constantly trustworthy but Bruch's membrane segmentation was poorly reliable using the automatic Spectralis segmentation software. Based on this software, evaluation of retinal thickness may be incorrect, particularly in case of PED. PED is effectively an important parameter which is not included when measuring retinal thickness.
Ophthalmologica 11/2012; · 1.42 Impact Factor
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Cynthia Fourgeux,
Brice Dugas,
Florence Richard,
Ingemar Björkhem,
Niyazi Acar,
Alain M Bron,
Jean-François Korobelnik, Nicolas Leveziel,
Jennyfer Zerbib,
Nathalie Puche,
Catherine P Creuzot-Garcher,
Eric Souied,
Lionel Bretillon
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ABSTRACT: 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.
Investigative ophthalmology & visual science 09/2012; 53(11):7026-33. · 3.43 Impact Factor
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American journal of ophthalmology 09/2012; 154(3):427-8. · 3.83 Impact Factor
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ABSTRACT: BACKGROUND: To analyze the morphological and functional characteristics of malattia leventinese. METHODS: This was a chart review of patients with Malattia Leventinese. All patients underwent a complete ophthalmologic examination, including best-corrected visual acuity (BCVA), fundus autofluorescence (FAF), fluorescein angiography (FA), indocyanine green angiography (ICGA), and optical coherence tomography (OCT). Microperimetry and Preferential Hyperacuity Perimeter (PHP) were performed in a subset of patients. RESULTS: Twelve eyes of six patients were included. BCVA ranged from 20/25 to 20/200. The largest drusen were round, not radially distributed, localized in the perimacular area and around the optic disc. The smallest drusen were not round, radially distributed, mostly localized temporally to the macula. FAF revealed an intense autofluorescence of large drusen. On both FA and ICGA, large round drusen turned to hyperfluorescent in the late phase, while small radial drusen progressively decreased their fluorescence. OCT showed the large round drusen as focal or diffuse deposition of hyperreflective material between the RPE and Bruch membrane within the macula, determining focal dome-shaped or diffuse RPE elevation respectively, and the small radial drusen, which ranged from irregular slight thickening of the RPE/Bruch membrane complex to sawtooth RPE elevation. In three patients (six eyes) that underwent microperimetry and PHP, there was a good correspondence between macular sensitivity and PHP score. Functional impairment correlated topographically to sub-RPE deposition of drusenoid material. CONCLUSIONS: In this series, large round drusen of Malattia Leventinese appeared similar to drusen in age-related macular degeneration, while small radial drusen of Malattia Leventinese shared similarities with early-onset cuticular drusen.
Albrecht von Graæes Archiv für Ophthalmologie 07/2012; · 2.17 Impact Factor
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Lucia Sobrin,
Stephan Ripke,
Yi Yu,
Jesen Fagerness,
Tushar R Bhangale,
Perciliz L Tan,
Eric H Souied,
Gabriëlle H S Buitendijk,
Joanna E Merriam,
Andrea J Richardson, [......],
Johannes R Vingerling,
Milam A Brantley,
Paul N Baird,
Caroline C W Klaver,
Rando Allikmets,
Nicholas Katsanis,
Robert R Graham,
John P A Ioannidis,
Mark J Daly,
Johanna M Seddon
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ABSTRACT: 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.
Sibling correlation study and genome-wide association study (GWAS).
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.
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.
Concordance of advanced AMD subtypes in sibling pairs and associations between SNPs with GA and CNV advanced AMD subtypes.
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).
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.
Ophthalmology 06/2012; 119(9):1874-85. · 5.45 Impact Factor
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Nicolas Leveziel,
Yi Yu,
Robyn Reynolds,
Albert Tai,
Weihua Meng,
Violaine Caillaux,
Patrick Calvas,
Bernard Rosner,
François Malecaze,
Eric H Souied,
Johanna M Seddon
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ABSTRACT: Nonsyndromic high myopia, defined by a refractive error greater than -6 diopters (D), is associated with an increased risk of macular choroidal neovascularization (CNV), a vision-threatening complication. The aim of this study was to investigate whether genetic factors associated with age-related macular degeneration (AMD) are related to myopic CNV.
We conducted a case-control study, including 71 cases with myopic CNV and 196 myopic controls without CNV, from Creteil and Toulouse, France, and Boston, MA. Single nucleotide polymorphisms (SNPs) from 15 genes reported to be related to AMD were selected for association testing in this study.
In univariate analysis, the rs10033900 SNP located in CFI was associated with myopic CNV (P = 0.0011), and a SNP in APOE was also related (P = 0.041). After adjustment for age, sex, and degree of myopia, SNPs in three genes were significantly associated, including CFI (odds ratio [OR] 2.1, 95% confidence interval [CI] 1.3-3.37, P = 0.0023), COL8A1 (OR 1.88, 95% CI 1.18-2.98, P = 0.0076), and CFH (OR 1.65, 95% CI 1.02-2.66, P = 0.04). After correction for multiple testing, only CFI remained significantly related to high myopic CNV (P = 0.045).
We report the first genetic associations with choroidal neovascularization (CNV) in a high myopic Caucasian population. One SNP (rs10033900) in the CFI gene, which encodes a protein involved in the inflammatory pathway, was significantly associated with myopic CNV in multivariate analysis after correction for multiple testing. This SNP is a plausible biological marker associated with CNV outgrowth among high myopic patients. Results generate hypotheses about potential loci related to CNV in high myopia, and larger studies are needed to expand on these findings.
Investigative ophthalmology & visual science 06/2012; 53(8):5004-9. · 3.43 Impact Factor
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Nicolas Leveziel,
Sylvie Bastuji-Garin,
Franck Lalloum,
Giuseppe Querques,
Pascale Benlian,
Michel Binaghi,
Gabriel Coscas,
Gisèle Soubrane,
Dora Bachir,
Frédéric Galactéros,
Eric H Souied
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ABSTRACT: 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 11/2011; 90(6):372-8. · 4.35 Impact Factor
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ABSTRACT: 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.
Ophthalmologica 07/2011; 226(3):87-102. · 1.42 Impact Factor
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Yi Yu,
Tushar R Bhangale,
Jesen Fagerness,
Stephan Ripke,
Gudmar Thorleifsson,
Perciliz L Tan,
Eric H Souied,
Andrea J Richardson,
Joanna E Merriam,
Gabriëlle H S Buitendijk, [......],
Caroline C W Klaver,
Rando Allikmets,
Milam A Brantley,
Paul N Baird,
Nicholas Katsanis,
Unnur Thorsteinsdottir,
John P A Ioannidis,
Mark J Daly,
Robert R Graham,
Johanna M Seddon
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ABSTRACT: 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 × 10(-8)] and rs4711751 on 6p12 near VEGFA (OR 1.15; P = 8.7 × 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.
Human Molecular Genetics 06/2011; 20(18):3699-709. · 7.64 Impact Factor
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Jennyfer Zerbib,
Nathalie Puche,
Florence Richard, Nicolas Leveziel,
Salomon Y Cohen,
Jean-François Korobelnik,
José Sahel,
Arnold Munnich,
Josseline Kaplan,
Jean-Michel Rozet,
Eric H Souied
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ABSTRACT: 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.
Experimental Eye Research 05/2011; 93(4):382-6. · 3.26 Impact Factor
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ABSTRACT: 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.
Albrecht von Graæes Archiv für Ophthalmologie 05/2011; 249(11):1617-25. · 2.17 Impact Factor
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ABSTRACT: Drusen are rarely observed in patients < 50 years of age. Two types of early onset drusen (EOD) are commonly described: basal laminar drusen (BLD) and drusen associated with Malattia Leventinese (ML). Our purpose was to classify the phenotype of EOD on the basis of fundus examination, and fluorescein angiography (FA) and indocyanine green angiography (ICGA) features.
We performed a prospective study including 48 consecutive EOD patients. All of them had a complete ophthalmologic examination including FA and ICGA.
BLD (67%) were extremely hyperfluorescent on FA and ICGA. ML (10%) was characterised by a combination of small radial and large round drusen with differences in staining in both FA and ICGA. We evidenced a third type of EOD (23%) harbouring an aspect of large colloid drusen (LCD), mildly hyperfluorescent in the early phases of FA, with a progressive staining in late phases. In intermediate and late phases of ICGA, LCD presented as hypofluorescent dot surrounded by a hyperfluorescent halo bordered by a thin hypofluorescent ring.
Three types of EOD are distinguished by their FA and ICGA features. We report a new kind of juvenile drusen, distinct from BLD and ML, named LCD, associated with a good vision and absence of complications.
The British journal of ophthalmology 02/2011; 95(2):238-44. · 2.92 Impact Factor
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ABSTRACT: 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.
Genetic association study.
Multicenter study.
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.
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).
Differences in allele frequencies between participants with geographic atrophy and CNV.
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.
Genetic variation at the ARMS2/HTRA1 locus confers a differential risk for CNV vs geographic atrophy in a well-powered sample.
American journal of ophthalmology 02/2011; 151(2):345-52.e3. · 3.83 Impact Factor
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ABSTRACT: To determine the visual field patterns obtained by the preferential hyperacuity perimetry (PHP) in patients with Best vitelliform macular dystrophy with mutations in the BEST1 gene.
Consecutive patients with Best vitelliform macular dystrophy underwent a complete ophthalmologic examination, including functional assessment by best-corrected visual acuity and Foresee PHP and morphologic assessment by fundus biomicroscopy, fundus autofluorescence, and spectral-domain optical coherence tomography. The functional "PHP visual field defect index" (which is the max peak value of the metamorphopsia [maximal distortion value at the visual field] + the max peak value of the scotoma [maximal scotoma value at the visual field]) and best-corrected visual acuity were analyzed about the disease stage.
Thirty eyes of 15 consecutive patients (8 men and 7 women; mean age 39 ± 24 years) were included for analysis. Based on fundus biomicroscopy, fundus autofluorescence, and spectral-domain optical coherence tomography, the macular lesions could be counted as follows: previtelliform lesions in 5 eyes of 3 patients (Stage 1), vitelliform lesions in 2 eyes of 2 patients (Stage 2), pseudohypopyon lesions in 6 eyes of 5 patients (Stage 3), vitelliruptive lesions in 4 eyes of 3 patients (Stage 4), atrophic lesions in 7 eyes of 5 patients (Stage 5), and fibrotic lesions in 6 eyes of 4 patients (Stage 6). Best-corrected visual acuity and PHP visual field defect index were averaged for each stage. Best-corrected visual acuity showed a good correlation (P = 0.01) with the morphologic severity (stage) of the disease (Pearson correlation = -0.88). Similarly, the PHP visual field defect index showed a good correlation (P = 0.03) with the morphologic severity (stage) of the disease (Pearson correlation = 0.78). Finally, best-corrected visual acuity showed a good correlation (P = 0.02) with the functional PHP visual field defect index (Pearson correlation = -0.83) about the morphologic stage of the disease.
Preferential hyperacuity perimetry could be considered an adjunctive useful tool in the evaluation of functional impairment and disease progression in patients with Best vitelliform macular dystrophy.
Retina (Philadelphia, Pa.) 01/2011; 31(5):959-66. · 2.93 Impact Factor
