G. Mimoun

Ranibizumab versus Bevacizumab for Neovascular Age-related Macular Degeneration: Results from the GEFAL Noninferiority Randomized Trial.

OBJECTIVE To evaluate the relative efficacy and safety profile of bevacizumab versus ranibizumab intravitreal injections for the treatment of neovascular age-related macular degeneration (AMD). DESIGN Multicenter, prospective, noninferiority, double-masked, randomized clinical trial performed in 38 French ophthalmology centers. The noninferiority limit was 5 letters. PARTICIPANTS Patients aged ≥50 years were eligible if they presented with subfoveal neovascular AMD, with best-corrected visual acuity (BVCA) in the study eye of between 20/32 and 20/320 measured on the Early Treatment of Diabetic Retinopathy Study chart and a lesion area of less than 12 optic disc areas (DA). METHODS Patients were randomly assigned to intravitreal administration of bevacizumab (1.25 mg) or ranibizumab (0.50 mg). Hospital pharmacies were responsible for preparing, blinding, and dispensing treatments. Patients were followed for 1 year, with a loading dose of 3 monthly intravitreal injections, followed by an as-needed regimen (1 injection in case of active disease) for the remaining 9 months with monthly follow-up. MAIN OUTCOME MEASURES Mean change in visual acuity at 1 year. RESULTS Between June 2009 and November 2011, 501 patients were randomized. In the per protocol analysis, bevacizumab was noninferior to ranibizumab (bevacizumab minus ranibizumab +1.89 letters; 95% confidence interval [CI], -1.16 to +4.93, P < 0.0001). The intention-to-treat analysis was concordant. The mean number of injections was 6.8 in the bevacizumab group and 6.5 in the ranibizumab group (P = 0.39). Both drugs reduced the central subfield macular thickness, with a mean decrease of 95 μm for bevacizumab and 107 μm for ranibizumab (P = 0.27). There were no significant differences in the presence of subretinal or intraretinal fluid at final evaluation, dye leakage on angiogram, or change in choroidal neovascular area. The proportion of patients with serious adverse events was 12.6% in the bevacizumab group and 12.1% in the ranibizumab group (P = 0.88). The proportion of patients with serious systemic or ocular adverse events was similar in both groups. CONCLUSIONS Bevacizumab was noninferior to ranibizumab for visual acuity at 1 year with similar safety profiles. Ranibizumab tended to have a better anatomic outcome. The results are similar to those of previous head-to-head studies.

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.

A new approach of geodesic reconstruction for drusen segmentation in eye fundus images

Segmentation of bright blobs in an image is an important problem in computer vision and particularly in biomedical imaging. In retinal angiography, segmentation of drusen, a yellowish deposit located on the retina, is a serious challenge in proper diagnosis and prevention of further complications. Drusen extraction using classic segmentation methods does not lead to good results. We present a new segmentation method based on new transformations we introduced in mathematical morphology. It is based on the search for a new class of regional maxima components of the image. These maxima correspond to the regions inside the drusen. We present experimental results for drusen extraction using images containing examples having different types and shapes of drusen. We also apply our segmentation technique to two important cases of dynamic sequences of drusen images. The first case is for tracking the average gray level of a particular drusen in a sequence of angiographic images during a fluorescein exam. The second case is for registration and matching of two angiographic images from widely spaced exams in order to characterize the evolution of drusen.

Analysis of progression of reticular pseudodrusen by spectral domain-optical coherence tomography.

PURPOSE To analyze reticular pseudodrusen progression using spectral domain-optical coherence tomography (SD-OCT). METHODS Thirty-three consecutive patients (48 eyes) underwent SD-OCT using the eye-tracked follow-up protocol 24 ± 2 months after baseline examination. Each pair of B-scans (only one per eye was evaluated among those showing pseudodrusen progression) was compared with respect to pseudodrusen appearance and retinal layer structure. Stage 1 pseudodrusen was defined as granular material between the RPE and the inner segment/outer segment (IS/OS), stage 2 as mounds of material sufficient to alter the contour of the IS/OS, stage 3 as thicker material adopting a conical appearance and breaking through the IS/OS, and stage 4 as fading of the material because of reabsorption and migration within the inner retinal layers. RESULTS A total of 78 pseudodrusen (detected on the 48 analyzed B-scans, and counting for a mean of 2.3 pseudodrusen per scan) showed progression over a mean of 23.9 ± 1.2 months. All 58 pseudodrusen (100%) graded as stage 1 at baseline examination progressed to stage 2. Thirteen of 16 pseudodrusen (81.3%) graded as stage 2 at baseline examination progressed to stage 3, and three (18.7%) progressed to stage 4. All four pseudodrusen (100%) graded as stage 3 at baseline examination progressed to stage 4. Among pseudodrusen that were stage 3 or 4 at follow-up (n = 20), 100% had IS/OS disruption whereas 12.1% (n = 7) had IS/OS disruption at stage 1 or 2 (n = 58) (OR, 1.736; 95% CI, 1.02-2.43). CONCLUSIONS The frequency of stage changes over time suggest that reticular pseudodrusen are dynamic pathologic structures.

Surgical treatment of subfoveal neovascularization in myopia: Macular translocation vs surgical removal

PURPOSE To compare the visual outcome of two different surgical approaches for subfoveal neovascularization in degenerative myopia: macular translocation and surgical removal of choroidal neovascularization (CNV). DESIGN Interventional case series. METHODS Retrospectively, 32 eyes with degenerative myopia (axial length over 26 mm or refraction over -6 diopters) and subfoveal CNV of 32 consecutive patients operated on by either surgical removal of CNV or limited macular translocation were reviewed. Surgical removal of CNV was performed in 18 eyes and limited macular translocation with a twofold suture in 14 eyes. The main outcome measurements were best-corrected visual acuity (BCVA) and findings from fluorescein angiography. Postoperatively, mean +/- SD follow up was 14 +/- 15 months (range, 6-48 months) in the removal group and 11 +/- 4 months (range, 6-24 months, P =.37) in the translocation group. RESULTS In both groups, there was no significant difference in preoperative age, sex, refractive error, or BCVA. The average of postoperative BCVA was statistically better after macular translocation (10 ETDRS lines or 20/100) than after surgical removal (6 lines 10/125, P =.019). Visual acuity improved by 3.8 lines after macular translocation and was unchanged after surgical removal (-0.7 line, P =.011). Macular translocation was successful in shifting the CNV to an extrafoveal location in 11 out of 14 eyes. Mean foveal displacement of all 18 translocated eyes was 695 +/- 426 microm (range, 100-1520 microm). Recurrence of CNV occurred in seven eyes (39%) after surgical removal and in two eyes (14%) after translocation. Retinal detachment occurred in two eyes in each group. CONCLUSION In this retrospective study, eyes with degenerative myopia and subfoveal neovascularization treated with limited macular translocation had better visual acuity recovery than eyes treated with surgical removal of the choroidal neovascularization. Further studies are required to confirm these results.

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.

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 &mgr;m vs. 260 ± 57 &mgr;m, 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.

Imaging analysis with optical coherence tomography: relevance for submacular surgery in high myopia and in multifocal choroiditis.

Purpose To classify the preoperative and postoperative optical coherence tomography (OCT) findings for subfoveal choroidal neovascularization (CNV) related to high myopia and multifocal choroiditis (MFC) and to correlate these findings with surgical outcome. Methods Ten consecutive patients presenting with subfoveal CNV related to either MFC or degenerative myopia were evaluated. Each patient underwent a biomicroscopic examination, fluorescein and indocyanine green angiographies, as well as OCT before and after surgical removal of CNV. Four different parameters were considered in the analysis of all OCT scans: tissue reflectivity, location of the CNV band, presence or absence of a separation zone, and reflectivity underneath the retinal pigment epithelium (RPE) band. Results For all six eyes with MFC, OCT showed a hyperreflective band anterior to the RPE with a separation zone and an optically clear zone underneath the RPE. Visual acuity improved in all six eyes. For the degenerative myopia group (4 eyes), OCT revealed findings similar to those observed for MFC for 1 eye, which had a favorable postoperative outcome. The remaining three myopic eyes with different OCT patterns had poor postoperative outcomes. Conclusion Optical coherence tomography can provide preoperative clues for submacular surgery. Eyes with CNV located anterior to and separated from the RPE that have an “optically clear zone” underneath are the best candidates for surgical removal. Such a feature was correlated with a good postoperative outcome.

Intravitreal ranibizumab for macular oedema secondary to retinal vein occlusion: a retrospective study of 34 eyes.

Purpose:  To evaluate the efficacy and the safety of intravitreal ranibizumab injection (Lucentis) in eyes with macular oedema secondary to central retinal vein occlusion (CRVO) or branch retinal vein occlusion (BRVO).

Surgical removal of subfoveal choroidal neovascularization: visual outcome and prognostic value of fluorescein angiography and optical coherence tomography

Purpose To study the functional results of macular surgery and determine pre-operative features associated with better final visual outcome. Methods Forty-two consecutive patients underwent surgical removal of subfoveal choroidal neovascularization (CNV), related to age-related macular degeneration (AMD) in 8 eyes, degenerative myopia in 14 eyes, multifocal choroiditis (MFC) in 10 eyes, idiopathic CNV in 6 eyes and other etiologies in 4 eyes. Mean age was 49 years. Pre-operative visual acuity (VA) was 20/200 or less in 30 eyes (71.4%) and never better than 20/40. Fluorescein angiography was analyzed before and after surgery. Pre-operative optical coherence tomographs (OCT) were studied in a masked fashion. Mean follow-up was 12 months (range 4–48 months). Results Final VA was 20/200 or less in 25 eyes (60%). According to the CNV etiology, the percentage were 87.5%, 80%, 57.1% and 20% respectively in eyes with AMD, MFC, high myopia, and idiopathic or other diseases. Post-operative VA improved in 21 eyes (50%) but subsequently declined in 7% by the final examination. Patients younger than 50 years had better functional results (p=0.006). Lack of retinal pigment epithelium (RPE) changes on pre-operative angiography was correlated with good visual outcome (p<0.001). The OCT study confirmed some features already described and showed some different CNV patterns: above and usually separated from the RPE, below and not separated from the RPE, and ungradable. Eyes with the first OCT pattern had the best visual outcome. Main complications included 4 (10%) retinal detachments and 9 (21%) recurrences. OCT was also useful to confirm CNV recurrences post-operatively. Conclusions CNV surgical excision results vary depending on the underlying disease, the RPE and choriocapillaris function, and the features observed on pre-operative OCT images.