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.

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.

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.

Evaluation of semiautomated measurement of geographic atrophy in age-related macular degeneration by fundus autofluorescence in clinical setting.

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 mm² to 0.13 mm². Intraobserver agreement was excellent until the geographic atrophy threshold value of 15.72 mm². Variability correlated with the size of atrophy. Mean difference in interobserver agreement (Bland-Altman statistics) ranged from -0.25 mm² to 0.27 mm², 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.

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.

Ranibizumab for choroidal neovascularization associated with adult-onset foveomacular vitelliform dystrophy: one-year results.

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 µm vs. 260 ± 57 µm, 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.

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.

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.

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.

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.

Intravitreal ranibizumab for choroidal neovascularization complicating pathologic myopia.

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 > or = 3 lines in 15 of 32 eyes (46.8%). The median central thickness was 336 microm (range, 179-663 microm) at baseline and 233 microm (range, 125-465 microm) 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.

[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.

Intravitreal ranibizumab for choroidal neovascularization related to traumatic Bruch's membrane rupture.

PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: For this patient affected with CNV secondary to traumatic Bruch's membrane, one single intravitreal ranibizumab injection was efficient, with 1-year follow-up.

PERSISTENT PLACOID MACULOPATHY IMAGED BY OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY.

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.

Spectral-Domain Optical Coherence Tomography of Subretinal Hyperreflective Exudation in Myopic Choroidal Neovascularization.

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 < .0001), from 419 ± 99 µm to 312 ± 64 µm (P < .0001), and from 361 ± 69 µm to 326 ± 72 µm (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.

CFH Y402H and ARMS2 A69S Polymorphisms and Oral Supplementation with Docosahexaenoic Acid in Neovascular Age-Related Macular Degeneration Patients: The NAT2 Study.

PURPOSE: Genetic susceptibility could be modified by environmental factors and may also influence differential responses to treatments for age-related macular degeneration (AMD). We investigated whether genotype could influence response to docosahexaenoic acid (DHA)-supplementation in the occurrence of choroidal new vessels (CNV). METHODS: The Nutritional AMD Treatment 2 (NAT2) study was a randomized, placebo-controlled, double-blind, parallel, comparative study, including 250 patients aged 55 to 85 years with early lesions of age-related maculopathy, visual acuity better than 0.4 Logarithm of Minimum Angle of Resolution units in the study eye and neovascular AMD in the fellow eye. Patients were randomized at baseline to receive either 3 daily fish-oil capsules, each containing 280 mg DHA, 90 mg EPA and 2 mg Vitamin E, or placebo. RESULTS: Patients carrying the risk allele (C) for CFH Y402H had no statistically significant increased risk for developing CNV in the study eye (Hazard Ratio (HR)=0.97; 95% Confidence Interval (CI): 0.54-1.76 for heterozygous and HR=1.29; 95%CI: 0.69-2.40 for homozygous). Patients carrying the risk allele (T) for ARMS2 A69S had no statistically significant increased risk for developing CNV in the study eye (HR=1.68; 95%CI: 0.91-3.12) for heterozygous and HR=1.78; 95%CI: 0.90-3.52 for homozygous). A significant interaction was observed between CFH Y402H and DHA-supplementation (p=0.01). We showed a protective effect of DHA-supplementation among homozygous non-risk patients. Among these patients, occurrence of CNV was 38.2% in placebo group versus 16.7% in DHA group (p=0.008). CONCLUSIONS: These results suggest that a genetic predisposition to AMD conferred by the CFH Y402H variant limits the benefit provided by DHA supplementation. TRIAL REGISTRATION: ISRCTN registry 98246501.

Circulating omega-3 Fatty acids and neovascular age-related macular degeneration.

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).