Nathalie Puche

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 ≥3 lines in 15 of 32 eyes (46.8%). The median central thickness was 336 &mgr;m (range, 179-663 &mgr;m) at baseline and 233 &mgr;m (range, 125-465 &mgr;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.

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).

Comparison of macular choroidal thickness in adult onset foveomacular vitelliform dystrophy and age-related macular degeneration.

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 μm) was significantly (P < 0.001) thicker compared with that in exudative AMD (158.55 ± 57.87 μm) and in dry AMD (157.53 ± 67.08 μm). Also, in AOFVD, the choroid was significantly (P = 0.001) thicker than that in the normal group (255.87 ± 87.46 μm). 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 μm). 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).

Genotypic Influences on Severity of Exudative Age-Related Macular Degeneration

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.

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.

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.

Analysis of Retinal Flecks in Fundus Flavimaculatus Using High-Definition Spectral-Domain Optical Coherence Tomography

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.

Ranibizumab for exudative age-related macular degeneration: A five year study of adherence to follow-up in a real-life setting.

PURPOSE To analyze adherence to follow-up over 5 years in patients treated with intravitreal ranibizumab for exudative age-related macular degeneration (AMD) in a tertiary health care center. To investigate factors associated with failure to continue follow-up. METHODS Retrospective chart review of all consecutive patients with exudative AMD, who received their first intravitreal ranibizumab injection at the Créteil Intercommunal University Hospital Eye Clinic between October 1, 2006 and March 31, 2007. Patient clinical characteristics at baseline and at the last follow-up visit were recorded. Distance from home to hospital was measured for each patient. A multiple-choice telephone survey was conducted for patients lost to follow-up to determine the main reasons for failure to continue follow-up. RESULTS Two hundred and one patients were included. The rate of loss to follow-up over the 5-year period was 57% (115/201). Fifty-eight patients lost to follow-up completed the questionnaire. The main reasons reported by patients for follow-up discontinuation were long distance from home to hospital (51.7%, 30/58), subjective dissatisfaction with the benefits of intravitreal injections (34.5%, 20/58), and the excessive burden of periodic follow-up visits (24.1%, 14/58). Three factors were significantly associated with follow-up discontinuation: high age at baseline (82.2 vs. 76.5 years, P<0.001), poor best-corrected visual acuity (BCVA) at baseline (42.5 vs. 51.0 letters, P=0.020), and long distance from home to hospital (132 vs. 17.1km, P<0.001). CONCLUSION In this study, adherence to follow-up over 5 years was poor. Age and BCVA at baseline and distance from home to hospital were independently associated with long-term adherence.

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 &mgr;m in the foveal scan (range, 42–291 &mgr;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.

Gray Hyper-Reflective Subretinal Exudative Lesions in Exudative Age-Related Macular Degeneration

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 μm to 367±102 μm, P<.0001) and 6 months (from 482±116 μm to 369±71 μm, P<.0001). CONCLUSION Our findings suggest that gray hyper-reflective subretinal lesions might be considered as a qualitative criterion for retreatment of exudative AMD. They may represent an early sign of active choroidal neovascularization, and should prompt to early treatment.