Pharmaceutics

The purpose of this study is to evaluate the visual acuity (VA) gain profiles between patients with drug-naive diabetic macular edema (DME) treated by dexamethasone implant (DEX-implant) and assess the baseline anatomical and functional factors that could influence the response to the treatment in real-life conditions. A retrospective, multi-center observational study included 129 eyes with drug-naive DME treated by DEX-implant. The Median follow-up was 13 months. Two groups of VA gain trajectories were identified-Group A, with 71% (n = 96) of patients whose average VA gain was less than five letters and Group B, with 29% (n = 33) of patients with an average gain of 20 letters. The probability of belonging to Group B was significantly higher in patients with baseline VA \textbackslashtextless 37 letters (p = 0.001). Ellipsoid zone alterations (EZAs) or disorganization of retinal inner layers (DRILs) were associated with a lower final VA (53.0 letters versus 66.4, p = 0.002) but without a significant difference in VA gain (4.9 letters versus 6.8, p = 0.582). Despite a low baseline VA, this subgroup of patients tends to have greater visual gain, encouraging treatment with DEX-implant in such advanced-stage disease. However, some baseline anatomic parameters, such as the presence of EZAs or DRILs, negatively influenced final vision

Reduced Vessel Density in the Mid-Periphery and Peripapillary Area of the Superficial Capillary Plexus in Non-Proliferative Diabetic Retinopathy

Our aim in this study was to assess the vessel density (VD) and vessel skeleton density (VSD) in the nasal area of the superficial capillary plexus (SCP) of diabetic subjects without diabetic retinopathy (DR), or in those with a non-proliferative diabetic retinopathy (NPDR), and to evaluate the relationship between the VD and VSD and the severity of DR. In this prospective study, the VD and VSD in the SCP were measured and analyzed on 6 × 6-mm macular and nasal optical coherence tomography angiography scans. The three concentric circles of the Early Treatment of Diabetic Retinopathy Study (ETDRS) grid were used and divided into zones numbered from 1 to 9 in the macular area and from 1 to 8 in the nasal area. The VD was significantly lower in the nasal peripapillary area (p = 0.0028), and both the VD and VSD were significantly lower in the macular area (p = 0.0131 and p = 0.0132, respectively) in patients with more severe DR. The SD was significantly lower in zones 5 (p = 0.0315) and 6 (p = 0.0324) in the nasal grid in patients with more severe DR. We showed a lower superficial capillary flow in the nasal periphery and peripapillary area in patients with more severe DR

Comparison of the Effect of Ranibizumab and Aflibercept on Changes in Macular Choroidal Thickness in Patients Treated for Diabetic Macular Edema

Purpose. The aim of this study was to assess the effect of intravitreal injections (IVI) of ranibizumab and aflibercept on the choroidal thickness (CT) in patients with treatment-naive diabetic macular edema (DME) before and after monthly IVI. Patients and Methods. Prospective monocenter study. Inclusion criteria were treatment-naive DME eyes without concomitant panretinal photocoagulation, associated with a decrease in best-corrected visual acuity ≤75 letters on the Early Treatment Diabetic Retinopathy Study (ETDRS) scale. DME was defined by a central retinal thickness ≥300 μm on swept-source OCT (Triton DRI OCT, Topcon Corporation, Itabashi, Japan). Patients received 5 IVI of ranibizumab or aflibercept. The primary endpoint was the change in the central subfield CT (CSCT) between inclusion (M0) and 1 month after the fifth IVI (M5). The secondary endpoint was the CT changes between M0 and M5 in other locations of the macular ETDRS grid. Results. Twenty-four eyes of 24 patients with a mean age of 61.1 years were included. Eleven and 13 patients were, respectively, treated with ranibizumab and aflibercept, and 86.4% had type 2 diabetes. The overall CSCT decreased significantly by −12 μm between M0 and M5 (231.7 μm at M0 and 219.7 μm at M5) (p=0.03). It decreased by −15.2 μm (p=0.02) in the aflibercept group (206.9 μm at M0 and 191.7 μm at M5) and by −7.3 μm (p=0.4) in the ranibizumab group (267.5 μm at M0 and 260.2 μm at M5). The CSCT decreased by −4.9 μm in noninjected contralateral eyes (242.3 μm at M0 and 237.4 μm at M5). CT changes between M0 and M5 in the superior, temporal, inferior, and nasal macular inner ring were significant in the aflibercept group but not in the ranibizumab and control groups. Conclusion. In DME patients, the CSCT decreases after 5 IVI of anti-VEGF, especially after aflibercept treatment

Ultra-Wide-Field Fluorescein Angiography Assessment of Non-Perfusion in Patients with Diabetic Retinopathy Treated with Anti-Vascular Endothelial Growth Factor Therapy

Purpose: To follow the evolution of peripheral ischemia by fluorescein angiography (FA) on ultra-wide-field (UWF) images in diabetic patients treated with anti-vascular endothelial growth factor (anti-VEGF) for macular edema. Methods: Prospective, non-interventional cohort study analyzing UWF-FA images of 48 patients with diabetic retinopathy (48 eyes) treated for diabetic macular edema. UWF-FA was performed at baseline and after one year of anti-VEGF therapy (M12). The primary endpoint was the change in the non-perfusion index. Results: Of the 48 patients included in this study, 25 completed the one-year follow-up, and 20 had FA images of sufficient quality to be interpreted. The non-perfusion index did not significantly change from baseline after one year of anti-VEGF treatment (0.7% of the non-perfused area at baseline versus 0.5% at M12; p = 0.29). In contrast, the diabetic retinopathy severity score improved significantly between baseline and M12. Conclusions: Anti-VEGF treatment with aflibercept for diabetic macular edema had no impact on the retinal perfusion assessed by FA, but it allowed for artificially improving diabetic retinopathy severity scores

Ultra-Wide-Field Fluorescein Angiography Assessment of Non-Perfusion in Patients with Diabetic Retinopathy Treated with Anti-Vascular Endothelial Growth Factor Therapy

Purpose: To follow the evolution of peripheral ischemia by fluorescein angiography (FA) on ultra-wide-field (UWF) images in diabetic patients treated with anti-vascular endothelial growth factor (anti-VEGF) for macular edema. Methods: Prospective, non-interventional cohort study analyzing UWF-FA images of 48 patients with diabetic retinopathy (48 eyes) treated for diabetic macular edema. UWF-FA was performed at baseline and after one year of anti-VEGF therapy (M12). The primary endpoint was the change in the non-perfusion index. Results: Of the 48 patients included in this study, 25 completed the one-year follow-up, and 20 had FA images of sufficient quality to be interpreted. The non-perfusion index did not significantly change from baseline after one year of anti-VEGF treatment (0.7% of the non-perfused area at baseline versus 0.5% at M12; p = 0.29). In contrast, the diabetic retinopathy severity score improved significantly between baseline and M12. Conclusions: Anti-VEGF treatment with aflibercept for diabetic macular edema had no impact on the retinal perfusion assessed by FA, but it allowed for artificially improving diabetic retinopathy severity scores

Switching to Aflibercept in Diabetic Macular Edema Not Responding to Ranibizumab and/or Intravitreal Dexamethasone Implant

International audiencePurpose: To assess short-term functional and anatomical outcomes of refractory diabetic macular edema (DME) following a switch from ranibizumab or dexamethasone to aflibercept. Methods. We included retrospectively eyes with persistent DME after at least 3 ranibizumab and/or one dexamethasone implant intravitreal injections (IVI). The primary endpoint was the mean change in visual acuity (VA) at month 6 (M6) after switching.Results. Twenty-five eyes were included. Before switching to aflibercept, 23 eyes received a median of 9.5 ranibizumab, and among them, 6 eyes received one dexamethasone implant after ranibizumab and 2 eyes received only one dexamethasone implant. Baseline VA, before any IVI, was 52.9 ± 16.5 letters, and preswitch VA was 57.1 ± 19.6 letters. The mean VA gain was +8 letters () between preswitch and M6. The mean central retinal thickness was 470.8 ± 129.9 μm before the switch and 303.3 ± 59.1 μm at M6 ().Conclusion. Switching to aflibercept in refractory DME results in significant functional and anatomical improvement. The study was approved by the France Macula Federation ethical committee (FMF 2017-138)

Using Patient-Level Data to Develop Meaningful Cross-Trial Comparisons of Visual Impairment in Individuals with Diabetic Macular Edema

INTRODUCTION: The aim of this study was to assess the impact of baseline characteristics on visual outcome of patients with diabetic macular edema and compare the results of clinical trials with different patient populations. METHODS: A model was created with patient-level data from the RESPOND/RESTORE trials to estimate the impact of baseline characteristics on increases in best-corrected visual acuity (BCVA) with anti-vascular endothelial growth factor therapies, measured by letters gained on the Early Treatment Diabetic Retinopathy Study scale from baseline to month 12. Mean BCVA gains with ranibizumab 0.5 mg pro re nata or laser photocoagulation monotherapy were predicted, assuming baseline characteristics equivalent to those in the VIVID-DME/VISTA-DME trials. These results were compared with the gain with aflibercept 2.0 mg every 8 weeks in VIVID-DME/VISTA-DME. Sensitivity analyses assessed outcome robustness. RESULTS: Baseline BCVA and central retinal thickness differed significantly between trials. In unadjusted data, patients in RESPOND/RESTORE receiving ranibizumab gained an additional 6.6 letters [95% confidence interval (CI): 4.5–8.7] compared with patients receiving laser monotherapy. After adjusting data to assume baseline characteristics equivalent to VIVID-DME/VISTA-DME, patients receiving ranibizumab were predicted to gain an additional 9.9 letters (95% CI: 7.3–12.4) compared with those receiving laser monotherapy. These results were similar (0.1-letter difference in favor of aflibercept; 95% CI: −2.9 to 3.2; P = 0.94) to the gain in BCVA in patients receiving aflibercept in VIVID-DME/VISTA-DME compared with those receiving laser monotherapy (10.0 letters, 95% CI: 8.3–11.7). CONCLUSION: After adjusting for baseline characteristics, the difference in letters gained between patients receiving ranibizumab versus aflibercept was non-significant across trials, highlighting the importance of adjusting for baseline characteristics in future comparisons. FUNDING: Novartis Pharma AG. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s12325-016-0310-0) contains supplementary material, which is available to authorized users