Intravitreal Bevacizumab for Diabetic Macular Edema Associated With Severe Capillary Loss: One-Year Results of a Pilot Study

PURPOSE: To evaluate the effects of intravitreal bevacizumab in patients with diabetic macular edema (DME) associated with severe capillary loss. DESIGN: Multicenter, open-label, nonrandomized study. METHODS: SETTING: Two tertiary ophthalmic referral centers in Brazil. STUDY POPULATION: Ten consecutive patients with DME and ""severe"" capillary loss. OBSERVATION PROCEDURES: Intravitreal injection(s) of bevacizumab (1.5 mg). Standardized ophthalmic evaluation was performed at baseline and at weeks 8, 16, 24, and 54. MAIN OUTCOME MEASURES: Changes in best-corrected visual acuity (BCVA) and in optical coherence tomography variables (central macular thickness [CMT] and total macular volume [TMV]). RESULTS: Significant changes in BCVA and in CMT/TMV were noted throughout the study (P<.001, P=.009, and P<.001, respectively). The mean logarithm of the minimal angle of resolution Early Treatment Diabetic Retinopathy Study BCVA was 0.786 (similar to 20/125(+1)) at baseline, 0.646 (similar to 20/80(-2)) at week 8, 0.580 (20/80(+1)) at week 16, 0.574 (similar to 20/80(+1)) at week 24, and 0.558 (similar to 20/80(+2)) at week 54. Compared with baseline, a significant change in BCVA was noted at all follow-up visits (P <=.008). The mean CMT/TMV values were, respectively, 472.6/10.9 at baseline, 371.4/9.9 at week 8, 359.5/9.8 at week 16, 323.9/9-4 at week 24, and 274.6/8.7 at week 54. Compared with baseline, a significant change in both CMT and TMV was noted only at 24 and 54 weeks (P <=.007). At 54 weeks, fluorescein angiography demonstrated no change in the extent of macular capillary loss and reduced dye leakage as compared with baseline in all patients. CONCLUSIONS: Favorable changes in BCVA and in CMT/TMV observed throughout 1 year suggest that intra-vitreal bevacizumab may be a viable alternative treatment for the management of patients with DME and severe capillary loss. (Am J Ophthalmol 2009;147:1022-1030. (C) 2009 by Elsevier Inc. All rights reserved.)

Nonsurgical options for treatment of diabetic macular edema

In the new book series 'ESASO Course Series', the essentials of the courses of the European School for Advanced Studies in Ophthalmology (ESASO) are made available to interested ophthalmologists, optometrists, technicians and residents all over the world. In this volume, the seminars on surgical retina presented by renowned experts during ESASO's activities are collected. Many specialists have contributed their knowledge to make this volume a device to give practical support. The topics range from prevention to state-of-the-art diagnostic techniques and the latest surgical treatment options for many eye conditions such as diabetic retinopathy and rhegmatogenous retinal detachment. This publication provides the ophthalmologist with the main aspects of surgical retina in a simple and practical update.

Diabetic macular edema : cases and diagnostics

In the new book series 'ESASO Course Series', the essentials of the courses of the European School for Advanced Studies in Ophthalmology (ESASO) are made available to interested ophthalmologists, optometrists, technicians and residents all over the world. In this volume, the seminars on surgical retina presented by renowned experts during ESASO's activities are collected. Many specialists have contributed their knowledge to make this volume a device to give practical support. The topics range from prevention to state-of-the-art diagnostic techniques and the latest surgical treatment options for many eye conditions such as diabetic retinopathy and rhegmatogenous retinal detachment. This publication provides the ophthalmologist with the main aspects of surgical retina in a simple and practical update.

Sustained-release steroids for the treatment of diabetic macular edema.

Glucocorticoids have been used for decades in the treatment of ocular disorders via topical, periocular, and more recently intravitreal routes. However, their exact mechanisms of action on ocular tissues remain imperfectly understood. Fortunately, two recently approved intravitreal sustained-release drug delivery systems have opened new perspectives for these very potent drugs. To date, among other retinal conditions, their label includes diabetic macular edema, for which a long-lasting therapeutic effect has been demonstrated both morphologically and functionally in several randomized clinical trials. The rate of ocular complications of intravitreal sustained-release steroids, mainly cataract formation and intraocular pressure elevation, is higher than with anti-vascular endothelial growth factor agents. Yet, a better understanding of the mechanisms underlying these adverse effects and the search for the minimal efficient dose should help optimize their therapeutic window.

Micro-implant d'acétonide de fluocinolone (ILUVIEN(®)) pour l'oedème maculaire diabétique chronique [Fluocinolone acetonide (ILUVIEN®) micro-implant for chronic diabetic macular edema].

Diabetic macular edema (DME) is a frequent complication of diabetic retinopathy and may cause severe visual loss. In this article, we examine the pathophysiology of DME and review various treatment options, such as laser photocoagulation, anti-vascular endothelial growth factor (VEGF) receptor antibodies, and steroids including ILUVIEN(®), which is a new sustained-release, non biodegradable, injectable, intravitreal micro-implant containing fluocinolone acetonide. The results of the FAME (Fluocinolone Acetonide in Diabetic Macular Edema) studies, conducted to evaluate the efficacy and safety of ILUVIEN(®) in DME, are discussed.

Intravitreal injection versus sub-Tenon's infusion of triamcinolone acetonide for refractory diabetic macular edema: A randomized clinical trial

PURPOSE. To compare the effectiveness of posterior sub-Tenon's infusion (STi) and intravitreal injection (IVI) of triamcinolone acetonide (TA) for treatment of refractory diffuse diabetic macular edema.METHODS. Thirty-six phakic diabetic patients with refractory diffuse diabetic macular edema were prospectively enrolled. Patients randomly received either 40 mg STi or 4 mg IVI of TA. Comprehensive ophthalmic evaluation was performed at baseline and 1, 2, 4, 8 +/- 1, 12 +/- 2 and 24 +/- 2 weeks after treatment. Macular morphologic changes detected by optical coherence tomography and visual acuity, intraocular pressure, and lens status were evaluated.RESULTS. Twenty-eight patients (28 eyes) completed the 24-week study. Central macular thickness was significantly reduced in the IVI group when compared with the STi group at 2, 4, 8, 12, and 24 weeks after treatment (P < 0.01). Mean visual acuities (in logarithm of the minimum angle of resolution [logMAR]) at week-4, -8, and -12 follow-up examinations were significantly higher in the IVI group (0.74, 0.75, and 0.82, respectively) when compared with the STi group (0.88, 0.88, and 0.90, respectively; P < 0.01). A significant change from baseline in mean intraocular pressure (mm Hg) was seen at weeks 4 (+/- 3.21) and 8 (+/- 3.35) in STi the group (P < 0.01), and at week 8 (+/- 2.78) in the IVI group (P < 0.05). No patient had cataract progression during the study.CONCLUSIONS. Although the number of patients and length of follow-up in this preliminary study were limited, the changes in central macular thickness and visual acuity observed after treatment suggest that IVI TA may be more effective than STi for the management of refractory diffuse diabetic macular edema. Further studies are needed to confirm these preliminary findings.

INTRAVITREAL INJECTION OF RANIBIZUMAB DURING CATARACT SURGERY IN PATIENTS WITH DIABETIC MACULAR EDEMA

Purpose: To investigate macular thickness and visual acuity changes after 1 intravitreal injection of 0.5-mg ranibizumab during phacoemulsification cataract surgery in eyes with diabetic macular edema refractory to laser treatment. Methods: Eleven eyes of 11 patients with diabetic macular edema refractory to modified Early Treatment Diabetic Retinopathy Study laser therapy received intravitreal during phacoemulsification cataract surgery. Comprehensive ophthalmic evaluation was performed preoperatively and at 1, 4, 8 +/- 1, and 12 +/- 2 weeks postoperatively. Main outcome measures included central subfield thickness and best-corrected Early Treatment Diabetic Retinopathy Study visual acuity. Results: Eleven patients completed the 12-week study visit. Mean central subfield thickness (+/- SEM) was 399.82 +/- 29.50 mu m at baseline and did not change significantly at any postoperative study visit (P > 0.05). Mean (+/- SEM) best-corrected Early Treatment Diabetic Retinopathy Study visual acuity was 0.95 +/- 0.13 logarithm of the minimum angle of resolution (20/200) at baseline and was significantly improved at Weeks 1 (0.38 +/- 0.13), 4 (0.38 +/- 0.11), 8 (0.35 +/- 0.08), and 12 (0.46 +/- 0.12) after treatment (P < 0.05). Conclusion: In this case series of patients with diabetic macular edema refractory to laser therapy, intravitreal ranibizumab administered during cataract surgery was associated with no significant change in central subfield thickness postoperatively. Significant improvement in best-corrected Early Treatment Diabetic Retinopathy Study visual acuity was observed after treatment, likely because of cataract removal. RETINA 32:1799-1803, 2012

Safety and Efficacy of Ranibizumab in Diabetic Macular Edema (RESOLVE Study): A 12-month, randomized, controlled, double-masked, multicenter phase II study

The expression of vascular endothelial growth factor (VEGF) is elevated in diabetic macular edema (DME). Ranibizumab binds to and inhibits multiple VEGF variants. We investigated the safety and efficacy of ranibizumab in DME involving the foveal center.

Behavior of SD-OCT-detected hyperreflective foci in the retina of anti-VEGF-treated patients with diabetic macular edema

Hyperreflective foci (HFs) are observable within the neurosensory retina in diabetic macular edema (DME) using spectral domain optical coherence tomography (SD-OCT). HFs have also been seen in wet age-related macular degeneration (AMD), although the origin is still unknown; however, they reduced significantly during anti-VEGF (vascular endothelial growth factor) therapy, and their baseline amount seemed to correlate with treatment success. In this study the behavior of HFs was evaluated during anti-VEGF therapy for DME.

Differentiation of Diabetic Macular Edema From Pseudophakic Cystoid Macular Edema by Spectral-Domain Optical Coherence Tomography.

PURPOSE: To differentiate diabetic macular edema (DME) from pseudophakic cystoid macular edema (PCME) based solely on spectral-domain optical coherence tomography (SD-OCT). METHODS: This cross-sectional study included 134 participants: 49 with PCME, 60 with DME, and 25 with diabetic retinopathy (DR) and ME after cataract surgery. First, two unmasked experts classified the 25 DR patients after cataract surgery as either DME, PCME, or mixed-pattern based on SD-OCT and color-fundus photography. Then all 134 patients were divided into two datasets and graded by two masked readers according to a standardized reading-protocol. Accuracy of the masked readers to differentiate the diseases based on SD-OCT parameters was tested. Parallel to the masked readers, a computer-based algorithm was established using support vector machine (SVM) classifiers to automatically differentiate disease entities. RESULTS: The masked readers assigned 92.5% SD-OCT images to the correct clinical diagnose. The classifier-accuracy trained and tested on dataset 1 was 95.8%. The classifier-accuracy trained on dataset 1 and tested on dataset 2 to differentiate PCME from DME was 90.2%. The classifier-accuracy trained and tested on dataset 2 to differentiate all three diseases was 85.5%. In particular, higher central-retinal thickness/retinal-volume ratio, absence of an epiretinal-membrane, and solely inner nuclear layer (INL)-cysts indicated PCME, whereas higher outer nuclear layer (ONL)/INL ratio, the absence of subretinal fluid, presence of hard exudates, microaneurysms, and ganglion cell layer and/or retinal nerve fiber layer cysts strongly favored DME in this model. CONCLUSIONS: Based on the evaluation of SD-OCT, PCME can be differentiated from DME by masked reader evaluation, and by automated analysis, even in DR patients with ME after cataract surgery. The automated classifier may help to independently differentiate these two disease entities and is made publicly available.

RETINAL LAYER RESPONSE TO RANIBIZUMAB DURING TREATMENT OF DIABETIC MACULAR EDEMA: Thinner is Not Always Better.

PURPOSE To identify individual retinal layer thickness changes associated with visual acuity gain in diabetic macular edema treated with ranibizumab using layer segmentation on high-resolution optical coherence tomography scans. METHODS Retrospective observational case series. Thirty-three treatment-naive eyes with diabetic macular edema were imaged by spectral domain optical coherence tomography at monthly visits while receiving intravitreal ranibizumab treatment as needed, guided by visual acuity. Thickness changes of individual layers after 1 year were quantitatively analyzed and correlated with visual acuity gain. RESULTS The mean best-corrected visual acuity improvement at 1 year was 6.2 (SEM ± 1.5) Early Treatment Diabetic Retinopathy Study letters, and central retinal thickness decreased by 66 ± 18 μm. In the central subfield, there was a significant decrease of thickness for all layers (P < 0.05) except the outer nuclear layer. Multiple linear regression analysis revealed that thickness decrease of the inner retina was associated with better visual acuity, whereas for the outer retina the opposite was true. The best estimate of final visual acuity (R = 0.817, P < 0.001) was obtained, by including baseline visual acuity and thickness change of the inner and outer plexiform layers in the model. CONCLUSION Whereas thickness decrease of the inner retina was positively associated with visual acuity gain, the opposite was found for the outer retina. This might be indirect evidence for recovery of the outer retina during ranibizumab treatment.This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0 (CC BY-NC-ND), which permits downloading and sharing the work provided it is properly cited. The work cannot be changed in any way or used commercially.