Management Of Diabetic Macular Edema Research Articles

Aqueous Humor Cytokine Levels and Anatomic Response to Intravitreal Ranibizumab in Diabetic Macular Edema

Variability in response to anti-vascular endothelial growth factor (VEGF) treatment in diabetic macular edema (DME) remains a significant clinical challenge. Biomarkers could help anticipate responses to anti-VEGF therapy. To investigate aqueous humor cytokine level changes in response to intravitreal ranibizumab therapy for the management of DME, and to determine the association between baseline aqueous levels and anatomic response. In this prospective multicenter cohort study, 49 participants with diabetes mellitus complicated by center-involving DME, with a central subfield thickness of 310 μm or greater on spectral-domain optical coherence tomography (SD-OCT), were recruited from December 22, 2011, to June 13, 2013 and statistical analysis were performed from March 1, 2017, to June 1, 2017. A total of 48 participants proceeded to follow-up. Participants received monthly injections of ranibizumab, 0.5 mg, for 3 months. Aqueous fluid for cytokine analysis was obtained at baseline and repeated at the 2-month visit. Multiplex immunoassay was carried out in duplicate for VEGF, placental growth factor, transforming growth factor beta 2, intercellular adhesion molecule 1 (ICAM-1), interleukin 6 (IL-6), IL-8, IL-10, vascular intercellular adhesion molecule, and monocyte chemoattractant protein 1. Baseline and 2-month change in aqueous cytokine levels, 3-month change in SD-OCT central subfield thickness and macular volume (MV), and the statistical association between baseline aqueous cytokine levels and these measures of anatomic response to ranibizumab in center-involving DME. Among the 48 participants, the mean (SD) age was 61.9 (7.1) years and 36 participants (75.0%) were men. The following cytokines were lower at month 2 vs baseline: ICAM-1 (median change, -190.88; interquartile range [IQR], -634.20 to -26.54; P < .001), VEGF (median change, -639.45; IQR, -1040.61 to -502.61; P < .001), placental growth factor (median change, -1.31; IQR, -5.99 to -0.01; P < .001), IL-6 (median change, -38.61; IQR, -166.72 to -2.80; P < .001), and monocyte chemoattractant protein 1 (median change, -90.13; IQR, -382.74 to 109.47; P = .01). When controlling for age, foveal avascular zone size, and severity of retinopathy, multiple linear regression determined that increasing baseline aqueous ICAM-1 was associated with a favorable anatomic response, in terms of reduced SD-OCT MV at 3 months (every additional 100 pg/mL of baseline ICAM-1 was associated with a reduction of 0.0379 mm3; P = .01). Conversely, increasing baseline aqueous VEGF was associated with a less favorable SD-OCT MV response at 3 months (every additional 100 pg/mL of baseline VEGF was associated with an increase of 0.0731 mm3; P = .02) and was associated with lower odds of being a central subfield thickness responder (odds ratio, 0.868; 95% CI, 0.755-0.998). Elevated aqueous ICAM-1 and reduced VEGF levels at baseline are associated with a favorable anatomic response to ranibizumab in DME, although there is not always direct correlation between anatomic and visual acuity response.

Efficiency of fenofibrate in facilitating the reduction of central macular thickness in diabetic macular edema.

Purpose:The purpose of this study is to study the benefit of addition of oral fenofibrate to the current regimen of diabetic macular edema (DME) management and quantify its effect on macular thickness and visual function in DME.Methods:Fifty-three eyes of 50 patients were randomized into treatment (Group A) (oral fenofibrate 160 mg/day) and control groups (Group B). Both groups underwent treatment of DME as per the standard treatment protocol of our hospital including intravitreal injections (anti-vascular endothelial growth factor/steroid) and grid laser. Patients were followed up every 2 months to note the visual acuity and central macular thickness (CMT) for 6 months.Results:Our groups were matched with respect to age (P = 0.802), mean diabetic age (P = 0.878), serum HbA1C levels (P = 0.523), and serum triglyceride levels (P = 0.793). The mean reduction in CMT was 136 μ in Group A and 83 μ in Group B at the end of 6 months. This difference was statistically significant (P = 0.031). Visual acuity improvement was 0.15 in Group A and 0.11 in Group B at the end of 6 months (P = 0.186). On subgroup analysis in Group A, we found that there was no difference in reduction of CMT between hypertensives and normotensives (P = 0.916), in patients with normal triglyceride levels and increased triglyceride levels (P = 0.975).Conclusion:Addition of fenofibrate to the standard protocol of DME management seems to facilitate reduction of CMT and probably have an added benefit on the visual functions.

Vitrectomy in the management of diabetic macular edema in treatment-naïve patients

ObjectiveTo determine the efficacy of vitrectomy in eyes with treatment-naïve diabetic macular edema (DME). MethodsConsecutive patients with treatment-naïve DME who underwent pars plana vitrectomy with internal limiting membrane peeling at a single institution were identified from the electronic medical records. Morphologic and visual acuity changes from baseline were analyzed at both the primary temporal endpoint (6 months) and the final examination with the investigators. The primary outcome measures included changes in best-corrected visual acuity (BCVA) and central retinal thickness (CRT). ResultsForty-four eyes of 44 patients were included in this retrospective study. The mean BCVA improved significantly from baseline until the 6-month primary endpoint (1.35 logMAR vs 0.83 logMAR, p < 0.001) and stabilized through the final examination (0.77 logMAR). The BCVA improved by at least 0.1, 0.3, and 0.6 logMAR in 26 (60%), 24 (55%), and 14 (32%) of eyes, respectively, whereas it worsened by 0.3 logMAR in only 1 (2%) eye. Final BCVA correlated inversely with duration of diabetes (p = 0.01), presence of an epiretinal membrane (p = 0.02), and initial visual acuity (p = 0.03). Mean CRT decreased significantly from baseline through 6 months (595 µm vs 266 µm; p < 0.001), and edema recurred in only 3 eyes (6%), one of which was subsequently treated with intravitreal bevacizumab. ConclusionsPars plana vitrectomy significantly improves macular edema and visual acuity in eyes with treatment-naïve DME. Prospective randomized trials are needed to better determine the efficacy of early vitrectomy.

Management of diabetic macular edema in Japan: a review and expert opinion.

Diabetic retinopathy is a frequent cause of visual impairment in working-age adults (≥30years) and in Japan is most commonly observed in those aged 50-69years. Diabetic macular edema (DME) is one of the main causes of vision disturbance in diabetic retinopathy, which is a clinically significant microvascular complication of diabetes. Anti-vascular endothelial growth factor (VEGF) therapy is becoming the mainstay of treatment for DME. However, to achieve sustained long-term improvement in visual acuity, conventional laser photocoagulation, vitrectomy and steroid therapy are also expected to play a role in the treatment of DME. This review summarizes the epidemiology and pathology of diabetic retinopathy and DME, evaluates the findings regarding the diagnosis and treatment of DME, and underscores the importance of systemic management of the disease in the context of the current health care situation in Japan. Finally, the unmet needs of patients with DME and prospects for research are discussed. The weight of evidence suggests that it is important to establish a multipronged treatment strategy centered on anti-VEGF therapy.

Evolving Role of Regional Depot Corticosteroids in Management of Diabetic Macular Edema.

Evolving Role of Regional Depot Corticosteroids in Management of Diabetic Macular Edema.

Surgical management of diabetic macular edema – For

SummaryDiabetic retinopathy may require surgical management in case of vitreomacular interface disorders. Indications and prognostic factors will be discussed.Furthermore, after many anti‐VEGF without any reduction of diffuse macular edema, surgical approach may be proposed. In histopathological analysis, myofibroblasts have been detected and cause the contraction of vitreoretinal interface disorders affecting visual acuity. Removal of epiretinal membrane associated with ILM peeling is essential in these cases in order to eliminate the contractile elements.

Surgical management of diabetic macular edema – Against

SummaryDiabetic macular edema (DME) is the leading cause of visual impairment in patients with diabetes mellitus. Disruption of the blood‐retinal‐barrier has been implicated to the pathogenesis of DME. In addition, vascular endothelial growth factor (VEGF) and other inflammatory mediators have been found to be major contributors to angiogenesis and to increased vascular permeability, leading to DME.Although surgical management of DME has been proposed as a treatment option, since it releases vitreous traction at the macula and improves oxygenation of the posterior segment, complications and persistence of macular edema postoperatively put this treatment modality in suspicion. In fact, eyes with refractory edema and no observable traction seem less likely to improve after surgical treatment. Moreover, in the majority of cases, there is no functional improvement, despite the encouraging anatomical results.Nowadays, anti‐VEGF agents still remain the standard of care in the management of DME, while intravitreal steroids gain interest as well. In cases, in which DME coexists with vitreoretinal interface pathology, pars plana vitrectomy in selected cases may be useful.

Bevacizumab‐treated diabetic macular edema: a pilot yearlong analysis of anatomic and functional outcomes from a referral center in Portugal

PurposeThere is high quality evidence that antiangiogenic drugs are a valuable option on diabetic macular edema (DME) treatment. However, evidence under real‐world conditions is lacking. This paradigmatic pilot study aims to characterize and discuss the 1‐year functional and anatomic response of intravitreal bevacizumab in DME.MethodsObservational retrospective study. Clinical charts from consecutive patients referred from the Lisbon and Tagus valley region (Portugal) between Jan‐2014 and Dec‐2015 were reviewed. All patients who underwent intravitreal injection of bevacizumab for DME were analyzed. Efficacy outcomes were i) visual acuity (VA) improvement (i.e. halving the visual angle or doubling the decimal value), and ii) a 10% or higher decrease in central macular thickness (CMT), both after a 12‐months follow‐up period. Statistical analysis were performed using STATA.ResultsA total of 107 eyes of 84 patients, with a mean age of 66.0 ± 8.8 years were studied. Mean time elapsed since diabetes diagnosis was 19.1 ± 7.9 years, and mean HbA1c levels were 8.1 ± 1.2%. Baseline VA improved from 0.35 ± 0.22 at baseline to 0.39 ± 0.25 after 12 months (P &lt; 0.05). Also CMT significantly decreased from 464 ± 144 to 379 ± 144 μm one year after injection. The rate of VA and CMT improvement was 31% and 48%, respectively. A non‐statistically significant trend was observed for better outcomes in patients who were concomitantly treated with either focal laser or intravitreal triancinolone. No differences were noted considering the loading dose. No major complications were observed.ConclusionsThis pilot study suggests intravitreal bevacizumab was effective in the DME treatment of our cohort, with a good safety profile. A longer follow‐up and larger sample will help building better evidence to DME management.

Diabetic macular oedema: evidence-based treatment recommendations for Asian countries.

Diabetic macular oedema is the most common cause of diabetic retinopathy-induced vision loss. Efficacy of anti-vascular endothelial growth factor therapy in diabetic macular oedema has been demonstrated in randomized controlled trials. An Asian-specific guideline for diabetic macular oedema treatment is needed as patients in Asia tend to present with far more advanced disease than seen elsewhere in the world. Previous reviews of diabetic macular oedema management lacked a broader assessment of anti-vascular endothelial growth factor treatment choices and newer trials. Recent clinical trial data allow head-to-head comparisons between the different anti-vascular endothelial growth factor agents and treatment regimens. This review aims to summarize the clinical evidence related to various treatment regimens for clinicians, with a focus on anti-vascular endothelial growth factor therapies, and to provide guidance on the treatment of diabetic macular oedema in Asian patients.

Corticosteroid Treatment in Diabetic Macular Edema.

Diabetic macular edema is the most common cause of visual impairment in patients with diabetes mellitus. The pathogenesis of macular edema is complex and multifactorial. For many years, laser photocoagulation has been considered the standard therapy for the treatment of diabetic macular edema; however, few patients achieve significant improvements in visual acuity. Today the intravitreal administration of anti-inflammatory or anti-angiogenic agents together with the use of laser photocoagulation represents the standard of care for the treatment of this complication. The intravitreal route of administration minimizes the systemic side effects of corticosteroids. Steroid-related ocular side effects are elevated intraocular pressure and cataract, while injection-related complications include endophthalmitis, vitreous hemorrhage, and retinal detachment. In order to reduce the risks and complications, intravitreal implants have been developed recently to provide sustained release of corticosteroids and reduce repeated injections for the management of diabetic macular edema. In this review, the efficacy, safety, and therapeutic potential of intravitreal corticosteroids in diabetic macular edema are discussed with a review of recent literature.

Comparison of efficacy and safety of the combined laser treatment technology versus conventional laser photocoagulation in diabetic macular edema management

Aim. To evaluate the efficacy and safety of the novel combined laser treatment technology compared with those of the conventional laser photocoagulation in diabetic macular oedema management.&#x0D; Material and methods. Fifty eyes of 44 patients with clinically significant diabetic macular oedema were enrolled. Patients of the main group (25 eyes) underwent combined laser treatment, whereas patients in the control group (25 eyes) underwent modified ETDRS (mETDRS) focal/grid photocoagulation.&#x0D; Results. Mean central point thickness (CPT) in the main group decreased from 411.24 126 m to 359.86 120.4 m (p 0.05), with a subsequent increase in the mean best-corrected visual acuity (BCVA) from 0.52 0.2 at baseline to 0.71 0.2 (p 0.05) at the 12-month follow-up. The mean central retinal sensitivity (RS) improved from 11.27 3.8 dB to 13.24 3.2 dB (p 0.05). In the control group, our results showed similar improvement in BCVA and CPT values at the 12-month follow-up (from 0.59 0.12 to 0.72 0.23 and from 424.17 68.12 m to 387.51 93.45 m, respectively, p 0.05). The RS value, on the contrary, decreased from 12.32 0.90 dB to 10.14 0.71 dB (p 0.05).&#x0D; Conclusions. The combined laser technology is a safe treatment technique that allows to minimise the extent of laser-induced chorioretinal complex damage due to the contribution of subthreshold micropulse laser photocoagulation. The efficacy of this novel technology is comparable with that of the mETDRS technique in the resolution of macular oedema and BCVA increase. This technology also provides an advantage of RS improvement and the possibility of safe and repetitive treatment sessions.

The Early Treatment Diabetic Retinopathy Study historical review and relevance to today's management of diabetic macular edema.

To provide an historical review of the Early Treatment Diabetic Retinopathy Study (ETDRS) in the management of diabetic macular edema (DME), and to discuss its relevance to the management of DME. The ETDRS reported that argon laser treatment is beneficial in the management of 'clinically significant' DME. The study provided guidelines for the treatment with focal and/or grid laser based on fluorescein angiographic patterns. In today's world, with the advent of optical coherence tomography, 'clinically significant' DME is now classified into center-involved DME (CI DME) and noncenter-involved DME (non-CI DME). Modified ETDRS focal/grid laser photocoagulation has been utilized in more recent clinical trials [diabetic retinopathy clinical research (DRCR) Protocols I and T] in combination with intravitreal injections. The ETDRS provided outcomes data for DME, both untreated and following laser therapy. In the management of patients with DME today, the modified ETDRS focal/grid laser photocoagulation treatments remain relevant in combination with anti-vascular endothelial growth factor (anti-VEGF) therapy as ophthalmologists and their patients choose how best to treat DME. Ongoing studies in eyes with DME, nonproliferative diabetic retinopathy, and good visual acuity will help further define the place of modified ETDRS focal/grid laser in the treatment of DME.

Impact of intravitreal pharmacotherapies including antivascular endothelial growth factor and corticosteroid agents on diabetic retinopathy.

Diabetic retinopathy is common and increasing in prevalence. Pharmacologic management of diabetic macular edema (DME) has improved tremendously over the last decade with the use of two families of intravitreally administered medications: antivascular endothelial growth factor-specific agents and corticosteroids. Clinical evaluation of these pharmaceuticals has demonstrated that they can have a substantial impact on diabetic retinopathy severity levels and the underlying retinal vasculature itself. Phase 3 trials employing ranibizumab, aflibercept, and fluocinolone acetonide enrolling eyes with center-involving DME causing visual acuity loss have demonstrated impressive alteration of the natural history of progressive diabetic retinopathy worsening over time through blunted progression to proliferative diabetic retinopathy, improving diabetic retinopathy severity levels, and slowing progressive retinal nonperfusion, the underlying disease process central to diabetic retinopathy itself. Accumulating data indicate that the threshold to initiate ocular-specific pharmacologic treatment for diabetic retinopathy, previously predominately limited to eyes with visual loss because of center-involved DME or proliferative diabetic retinopathy, is being lowered to earlier stages of diabetic retinopathy. Ongoing clinical trials and secondary analyses continue to further explore the impact and durability of vascular endothelial growth factor blockade and corticosteroids on modification of diabetic retinopathy and the underlying retinal vasculature itself.

Therapeutic Options in Refractory Diabetic Macular Oedema.

Diabetic macular oedema (DMO) results from alterations of several biochemical pathways in diabetic eyes. Centre-involving DMO is an important cause of visual loss in diabetes. Anti-vascular endothelial growth factor agents are now the mainstay of centre-involving DMO treatment. Oedema that does not achieve optimal response to these agents occurs in a sizeable proportion of eyes and is called refractory or persistent DMO. Management of refractory DMO is challenging. In this paper, the pathophysiology of DMO, and the definitions used in various studies are summarised. Therapeutic options for refractory DMO management including corticosteroids, laser, combination therapies, and surgery are explored. Novel agents on the horizon for DMO control that are being investigated at present are discussed as well. A literature review was performed and a summary of the research studies for each of the agents is provided in order to guide the reader regarding the existing evidence for their application in DMO. Importance of early recognition of disease and prompt treatment to achieve best visual outcome is discussed. Utility of optical coherence tomography to guide disease diagnosis and monitoring is highlighted. An algorithmic approach for DMO management is described. Finally, the impact that personalized medicine and genetics might have on DMO management is assessed.

An Evidence-based Approach to Using Intravitreal Steroids in the Management of Diabetic Macular Oedema

Diabetic macular oedema (DMO) is the leading cause of acquired visual loss in the working age population. The landscape for DMO treatment has changed significantly over the past decade. Macular laser has been reported to reduce the risk of moderate visual loss in seminal clinical trials from the 1980s, but relatively few patients achieved visual gain. With the advent of intravitreal pharmacotherapy it is now possible to achieve visual gains in the majority of patients. Intravitreal anti-vascular endothelial growth factor (VEGF) agents are now a first-line treatment option in centre-involving DMO. This review assesses clinical trial and more recent real-world evidence to guide clinicians as to when intravitreal steroids should be considered in the management of DMO. In particular, intravitreal steroids can be considered in pseudophakic patients, or those due to undergo cataract surgery, in patients unable to attend for regular intravitreal procedures, and non-responders to intravitreal anti-VEGF therapy. Assessing clinical trial data, the dexamethasone implant appears to have a more predictable intraocular rise profile than triamcinolone or fluocinolone with a lower requirement for incisional glaucoma surgery. There is a need for consensus regarding real-world outcome measures for intravitreal steroids in the management of DMO to allow easier comparison across studies.

Intravitreal Steroids in Diabetic Macular Edema.

Over the past decade, great strides have been made in the management of diabetic macular edema (DME). Therapeutic alternatives now include focal/grid laser photocoagulation, vitreo-retinal surgery, and intraocular injection of anti-angiogenic and steroid molecules. Intravitreal administration of steroids represents a fundamental alternative for recalcitrant and naive eyes with DME, especially in those cases when anti-vascular endothelial growth factor (VEGF) agents are contraindicated or a treatment regimen with fewer intravitreal injections is required. Currently, 3 intravitreal corticosteroid options for DME treatment are available: the dexamethasone delivery system, the fluocinolone acetonide insert, and off-label intravitreal triamcinolone acetonide. All 3 agents are associated with risk of cataract progression and intraocular pressure elevation, but they maintain a good safety profile. In patients who remain unresponsive to anti-VEGF therapy, are pseudophakic, at low risk for glaucoma, or who have significant cardiovascular risk, treatment with long-lasting intraocular steroids is suggested. There still remain many unanswered questions about intravitreal drugs, regarding dose, frequency, the correct regimen of each treatment, and the potential long-term side effects.

Practical Lessons from Protocol I for the Management of Diabetic Macular Edema.

Protocol I, a multicenter randomized clinical trial, compared the visual outcomes of patients treated with 0.5 mg intravitreal ranibizumab with either prompt or deferred (by 24 weeks laser), 4 mg intravitreal triamcinolone with prompt laser, or sham injection with prompt laser for the treatment of center-involving diabetic macular edema (DME). A total of 854 adult patients with type I or II diabetes and any level of non-proliferative diabetic retinopathy or proliferative retinopathy with adequate panretinal photocoagulation, with best-corrected visual acuity (BCVA) of 78 to 24 ETDRS letters (Snellen equivalent of 20/32 to 20/320) and visual loss attributed to macular edema, or retinal thickening with central subfield thickness of at least 250 µm by OCT were enrolled. The main outcomes relevant for practicing clinicians are as follows. (1) Intravitreal ranibizumab treatment provides superior visual outcomes compared to conventional laser treatment. (2) Adjunctive laser treatment does not appear to provide substantial visual benefit compared to ranibizumab treatment alone, but may reduce the number of injections required to resolve DME. Deferral of laser is likely beneficial in patients with worse initial visual acuity. (3) Intravitreal triamcinolone provides similar visual outcomes compared to intravitreal ranibizumab in pseudophakic patients but is associated with a clinically important increased risk of increased intraocular pressure (IOP), need for glaucoma medications, and need for glaucoma surgery. (4) Delayed initiation of intravitreal ranibizumab therapy provides improved visual outcome among patients initially treated with conventional laser photocoagulation or triamcinolone, but the magnitude of the benefit is not as great as is observed when ranibizumab treatment is initiated promptly. (5) The number of ranibizumab injections required to achieve the desired visual outcome decreases substantially after the first year, with the majority of patients not requiring further treatment after 3 years. (6) Patients who do not have a rapid response to ranibizumab still display long-term benefit to continued therapy, although perhaps less than those with immediate improvement. (7) Intravitreal ranibizumab is not only effective in reducing retinal edema and improving BCVA among patients with DME, it is also a disease modifying therapy and induces improvement of the diabetic retinopathy severity score by 2 or more steps in approximately one third of patients. Triamcinolone injection also induces improvement in diabetic retinopathy severity in DME patients, but perhaps to a lesser degree. (8) No increased risk of systemic adverse events was observed among patients treated with intravitreal ranibizumab compared to sham-injected controls or triamcinolone-treated patients, but the low frequency of adverse events, restrictive enrollment criteria, and specific posology employed in this study limit the generalization of this conclusion to patients routinely encountered in clinical practice. (9) There was no clinically important increased risk of major ocular complications among patients treated with intravitreal ranibizumab (including the risk of glaucoma), although endophthalmitis is a potentially devastating outcome should it occur. In addition to the risk of endophthalmitis, intravitreal triamcinolone injection was associated with clinically important increased risk of cataract progression and increased IOP.

Update on the Management of Diabetic Macular Edema

Diabetic macular edema (DME) is a treatable sequela of diabetic retinopathy and a significant cause of visual morbidity among working age individuals worldwide. While anti-vascular endothelial growth factor (anti-VEGF) agents are first-line agents in the management of DME, corticosteroids and laser therapy can play a role as well. Despite a growing understanding of best clinical practices, many patients respond unpredictably to therapy. This article will briefly review current treatment modalities and discuss future treatment options for managing DME.

Lucentis® (Ranibizumab Ophthalmic Injection) for Diabetic Macular Edema (DME)

Objective: To review the efficacy, safety and pharmacologic parameters of ranibizumab (Lucentis®) intravitreal ophthalmic injection versus alternative agents in the management of diabetic macular edema (DME). Data sources: Information was reviewed from: MEDLINE (January 2000-December 2015), both manufacturers of ranibizumab (Genentech and Novartis), and the United States (U.S.) Food and Drug Administration (FDA). The internet was searched using the following key terms: avastin, diabetic macular edema (DME), eye, injection, intravitreal, lucentis, microvascular, ophthalmic, pharmacologic, ranibizumab, and retinopathy. Study selection and data extraction: All English-language articles and abstracts were evaluated for inclusion. Appropriate, randomized controlled trials in DME are included in this review. Data synthesis: The safety and efficacy of ranibizumab intravitreal ophthalmic injection (0.3 mg every 28-days) versus (0.5 mg every 28-days) versus placebo was evaluated in two randomized, double-masked studies in patients with DME over 24-36 months. Patients were between 21-91 years old (mean age 62); all patients were eligible for additional types of treatment, if needed, beginning month three of the studies [i.e., macular laser treatment or pan retinal photocoagulation (PRP)]. At month 24, compared to monthly ranibizumab 0.3 mg, no additional benefit was observed with monthly treatment with the ranibizumab 0.5 mg dose; therefore, outcomes measured in months 24-36 were ranibizumab 0.3 mg vs. placebo and based on changes in visual acuity. They were defined as: a. Gain of greater than or equal (>) to15 letters b. Loss of less than (<) 15 letters visual acuity and c. Mean change in visual acuity. Conclusions: Ranibizumab (Lucentis®) intravitreal ophthalmic injection 0.3 mg given every 28 days was shown to be safe and effective for the management of diabetic macular edema (DME) and is the first and only FDA approved pharmacological choice. Ranibizumab received its fourth FDA indication for treatment of serious eye diseases in February, 2015. It is now approved for the treatment of diabetic retinopathy in those with DME.

Clinical practice pattern in management of diabetic macular edema in Japan: survey results of Japanese retinal specialists.

To elucidate the current clinical practice patterns of diabetic macular edema (DME) management by retinal specialists in Japan in the era of anti-vascular endothelial growth factor (VEGF) therapy. Forty-six retinal specialists were administered a survey regarding the pathology and clinical practice of DME. Nearly, half of the specialists (45.2%) think that the main biochemical factor involved in DME development is the vascular permeability-potentiating action of VEGF-A. Most specialists (70.6%) use three modalities for detecting DME: optical coherence tomography, fluorescein angiography, and fundus examination. For focal macular edema, focal laser is used as first-line therapy by 70.3% of specialists, whereas 21.6% use medical treatment in combination with focal/grid laser. For diffuse macular edema, anti-VEGF therapy is the first choice (72.5%), irrespective of visual acuity, whereas 17.5% select off-label sub-Tenon's steroid injections. Vitrectomy is often performed for vitreomacular traction (86.5%) or when anti-VEGF agent/laser therapy is ineffective (73.2%). For persistent DME after vitrectomy, anti-VEGF agents (46.3%) or steroids (intravitreal injections, 14.6%; sub-Tenon's injections, 36.6%) are selected. When applying anti-VEGF treatment regimen, most specialists continue loading injections until central retinal thickness stabilized (51.4%) or both visual acuity and central retinal thickness stabilized (24.3%). In the maintenance phase, many specialists provide injections with pro re nata (76.3%), whereas 50.0% responded that the treat-and-extend regimen is ideal. Our survey presents the current views about the DME management and practice patterns of anti-VEGF therapy by one part of the retinal specialists in Japan, and highlights the differences or gaps between evidence and actual clinical practice.