Hassiba Oubraham

Changes in visual acuity in patients with wet age-related macular degeneration treated with intravitreal ranibizumab in daily clinical practice: the LUMIERE study.

Purpose: The real-life LUMIERE study on patients with wet age-related macular degeneration treated with intravitreal ranibizumab in 2006 to 2009 showed that failure to follow recommendations was associated with lower efficacy than had been observed in the development phase. The TWIN Study reviewed the situation in 2010 to 2011. Methods: Retrospective, descriptive purely observational study of data acquired after 12 months of treatment with intravitreal ranibizumab. Results: In 881 patients (68% women, mean age, 79 years) treated by 21 ophthalmologists, the mean gain in visual acuity was +4.3 ± 15.4 letters (up from 3.2 ± 14.8 in 2006–2009; NS). Significant improvements were documented in the mean interval between diagnosis and treatment initiation (down from 12.6 ± 26.4–7.7 ± 10.9 days; P < 0.001), and in the percentage of patients who received a full course of induction treatment (56.6 vs. 39.6%; P < 0.001). After induction, hardly any patients were monitored every month as recommended, although retreatment was more assiduous (5.6 ± 2.3 vs. 5.1 ± 2.1 injections; P < 0.001). Conclusion: Despite improvements in key parameters, the effectiveness of intravitreal ranibizumab is still compromised by poor compliance with the guidelines, especially the frequency of postinduction monitoring that is now the most important determinant of successful treatment.

Type 2 Neovascularization Secondary To Age-related Macular Degeneration Imaged By Optical Coherence Tomography Angiography

Purpose: Optical coherence tomography angiography is a novel and noninvasive technique for imaging retinal microvasculature by detecting changes in reflectivity that is related to blood flow. The purpose of this study was to describe Type 2 neovascularization characteristics in age-related macular degeneration using optical coherence tomography angiography. Methods: Fourteen eyes of 14 consecutive patients with Type 2 neovascularization were prospectively included. All patients underwent a complete ophthalmological examination, including color and infrared fundus photography, fluorescein and indocyanine green angiography, spectral domain optical coherence tomography angiography, and optical coherence tomography angiography. Results: In all cases, Type 2 lesions could be detected by optical coherence tomography angiography, presenting as a hyperflow lesion in the outer retina, with a glomerulus (4/14) or medusa shape (10/14), surrounded by a dark halo. The superficial layer and the deep retina showed no abnormal flow. Surprisingly, the Type 2 lesions could also be observed in the presumed choriocapillaris layer. These glomerulus- or medusa-shaped lesions were connected, in 10/14 eyes, to a thicker main branch, which seemed to continue deep into the choroidal layers. Conclusion: Optical coherence tomography angiography may be a new imaging method for the diagnosis of Type 2 neovascularization in clinical routine. However, the specificity of the features needs to be investigated in further studies.

Optical Coherence Tomography Angiography in Central Serous Chorioretinopathy

Purpose. To analyze optical coherence tomography angiography (OCTA) findings in eyes with central serous chorioretinopathy (CSC) and to compare them with those obtained with multimodal imaging. Methods. A series of consecutive patients diagnosed with CSC, underwent OCTA and multimodal imaging, including spectral domain OCT, fluorescein, and indocyanine green angiography. OCTA images were performed at three main depth intervals: automatically segmented outer retina, manually adjusted outer retina, and automatically segmented choriocapillaris. Results. Thirty-three eyes of 32 consecutive patients were analyzed. OCTA showed 3 main anomalies at the choriocapillaris: the presence of dark areas (19/33 eyes) which were frequently associated with serous retinal detachment, presence of dark spots (7/33 eyes) which were frequently associated with retinal pigment epithelium detachment, and presence of abnormal vessels (12/33 eyes) which were frequently, but not systematically, associated with choroidal neovascularization, as confirmed by multimodal imaging. Conclusions. OCTA revealed dark areas and dark spots, which were commonly observed. An abnormal choroidal pattern was also observed in one-third of cases, even when multimodal imaging did not evidence any choroidal neovascularization. Abnormal choroidal vessels should be interpreted with caution, and we could assume that this pathological choroidal vascular pattern observed in many CSC cases could be distinct from CNV.

OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY FEATURES OF SUBRETINAL FIBROSIS IN AGE-RELATED MACULAR DEGENERATION.

Purpose: To report the imaging features of subretinal fibrosis secondary to exudative age-related macular degeneration (AMD) on optical coherence tomography angiography. Methods: All consecutive patients diagnosed with subretinal fibrosis complicating exudative AMD were imaged by color retinal photographs or multicolor imaging, fluorescein angiography, spectral domain optical coherence tomography, and optical coherence tomography angiography. Eyes with active exudative features observed during the last 6 months were compared with those without any sign of exudation >6 months. Results: Forty-nine eyes of 47 consecutive patients were included. A blood flow inside the fibrotic scar could be detected in 46 of 49 cases (93.8%). Three patterns of vascular networks could be distinguished, that were described as pruned vascular tree (26 of 49 eyes; 53.1%), tangled network (14 of 49; 28.6%), and/or vascular loop (25 of 49; 51.0%). Furthermore, 2 types of hyporeflective structures, large flow void, and/or dark halo were observed in 63% and in 65% of eyes, respectively. The observed patterns did not differ between eyes with active or inactive lesions. Conclusion: Optical coherence tomography angiography of subretinal fibrosis showed almost constantly a perfused, abnormal vascular network and collateral architectural changes in the outer retina and the choriocapillaris layer. These features were associated with both active and inactive fibrotic choroidal neovessels.

Causes of unsuccessful ranibizumab treatment in exudative age-related macular degeneration in clinical settings.

Purpose: To identify the causes of loss of vision after ranibizumab therapy in patients with exudative age-related macular degeneration treated in three clinical settings. Methods: A retrospective multicentric analysis of 290 consecutive eyes comprising cohorts from 3 clinical settings showed that 21 eyes lost ≥15 letters on the Early Treatment Diabetic Retinopathy Study chart 1 year after the start of ranibizumab treatment. Fundus images of these eyes were analyzed by two independent readers to investigate the causes of visual loss. The three cohorts were compared. A search was made for factors predisposing to visual loss. A second analysis was performed to compare the baseline characteristics of patients who gained (visual acuity gainers) or lost (visual acuity losers) ≥15 letters. Results: Among the 290 eyes included, the proportions from each center experiencing visual loss were not significantly different (mean, 7.24%, P = 0.2631). Mean visual loss of affected eyes was 27 letters. There was no significant difference between these eyes and others as regards age and gender of patients, laterality, type of choroidal neovascularization, number of visits, or initial visual acuity. Visual loss was secondary to the progression of atrophy in eight eyes, fibrosis in five eyes, a combination of fibrosis and atrophy in three eyes, severe subretinal hemorrhage in three eyes, and retinal pigment epithelial tear in two eyes. A significant difference between visual acuity gainers and losers was observed for 2 parameters: age of patients, 80.9 ± 5.3 years in visual acuity losers versus 77.5 ± 7.3 years in visual acuity gainers (P = 0.0473) and visual acuity at diagnosis, respectively, 56.2 ± 11.2 versus 49.0 ± 12.0 (P = 0.0288). Conclusion: Although uncommon, visual loss may occur during ranibizumab treatment and is because of the natural course of age-related macular degeneration in most cases.

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.

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.

Imaging in retina units: changes observed during the last 12 years.

Purpose: The last decade has seen many improvements in the imaging of the choroids, retina, and vitreous. However, there are no available data about changes in the practice of imaging in retina units. The present study was therefore undertaken to document the 12-year changes in this practice in retina units in France, particularly the relative changes in the distribution of the different imaging methods. Methods: This retrospective study was performed in 4 different retina units considered to be representative of retina units in France. They comprise 2 departments of ophthalmology in university-based hospitals in Paris and Nantes, one in a non-university-based general hospital in Orleans, and one private tertiary care clinical center located in Paris. The annual numbers for the different retinal imaging methods performed in the 4 units between 2000 and 2011 were recorded, analyzed, and compared. Results: The total of images performed increased during the last decade, from 16,084 in 2000 to 76,318 in 2011. The distribution of the imaging techniques performed each year changed significantly during this period (p<0.0001, χ2 test): the share of fluorescein angiography decreased from 78.7% in 2000 to 7.0% in 2011. During this period, the share of indocyanine green angiography also dropped from 11.3% to 1.3%. The share of optical coherence tomography increased from 26.4% in 2003 to 53.4% in 2012. Conclusions: The present study documents the increasing share of noninvasive imaging and the decreasing share of angiography in retina units over the last 12 years.

Dietary, environmental, and genetic risk factors of Extensive Macular Atrophy with Pseudodrusen, a severe bilateral macular atrophy of middle-aged patients

EMAP (Extensive Macular Atrophy with Pseudodrusen) is a maculopathy we recently described that shares pseudodrusen and geographic atrophy with Age-related Macular Disease (AMD). EMAP differs from AMD by an earlier age of onset (50-55 years) and a characteristic natural history comprising a night blindness followed by a severe visual loss. In a prospective case-control study, ten referral centers included 115 EMAP (70 women, 45 men) patients and 345 matched controls to appraise dietary, environmental, and genetic risk factors. The incidence of EMAP (mean 2.95/1.106) was lower in Provence-Côte d’Azur with a Mediterranean diet (1.9/1.106), and higher in regions with intensive farming or industrialized activities (5 to 20/1.106). EMAP patients reported toxic exposure during professional activities (OR 2.29). The frequencies of common AMD complement factor risk alleles were comparable in EMAP. By contrast, only one EMAP patient had a rare AMD variant. This study suggests that EMAP could be a neurodegenerative disorder caused by lifelong toxic exposure and that it is associated with a chronic inflammation and abnormal complement pathway regulation. This leads to diffuse subretinal deposits with rod dysfunction and cone apoptosis around the age of 50 with characteristic extensive macular atrophy and paving stones in the far peripheral retina.