Management Of Diabetic Macular Edema Research Articles

Effectiveness of the Dexamethasone Intravitreal Implant for Treatment of Patients with Diabetic Macular Oedema.

Diabetic macular oedema (DMO) is a leading cause of vision loss in the working-age population worldwide. Corticosteroid drugs have been demonstrated to inhibit the expression of both the vascular endothelial growth factor (VEGF) gene and other anti-inflammatory mediators, such as prostaglandins. Triamcinolone, fluocinolone and dexamethasone are the main steroids that have been studied for the treatment of macular oedema. Over the last few years, several studies have suggested an important role for dexamethasone in the management of DMO. The dexamethasone intravitreal implant (DEX implant) (Ozurdex®; Allergan, Inc., Irvine, CA) is a novel approach approved by the US Food and Drug Administration (FDA) and by the EU for the intravitreal treatment of macular oedema after branch or central retinal vein occlusion, and for the treatment of non-infectious uveitis affecting the posterior segment of the eye. We reviewed manuscripts that had investigated the pharmacokinetics, efficacy and safety of the DEX implant regarding DMO treatment.

Effectiveness of the Dexamethasone Intravitreal Implant for Treatment of Patients with Diabetic Macular Oedema

Diabetic macular oedema (DMO) is a leading cause of vision loss in the working-age population worldwide. Corticosteroid drugs have been demonstrated to inhibit the expression of both the vascular endothelial growth factor (VEGF) gene and other anti-inflammatory mediators, such as prostaglandins. Triamcinolone, fluocinolone and dexamethasone are the main steroids that have been studied for the treatment of macular oedema. Over the last few years, several studies have suggested an important role for dexamethasone in the management of DMO. The dexamethasone intravitreal implant (DEX implant) (Ozurdex®; Allergan, Inc., Irvine, CA) is a novel approach approved by the US Food and Drug Administration (FDA) and by the EU for the intravitreal treatment of macular oedema after branch or central retinal vein occlusion, and for the treatment of non-infectious uveitis affecting the posterior segment of the eye. We reviewed manuscripts that had investigated the pharmacokinetics, efficacy and safety of the DEX implant regarding DMO treatment.

Anti-VEGF for the management of diabetic macular edema.

Diabetic retinopathy (DR) is an important cause of vision loss around the world, being the leading cause in the population between 20 and 60 years old. Among patients with DR, diabetic macular edema (DME) is the most frequent cause of vision impairment and represents a significant public health issue. Macular photocoagulation has been the standard treatment for this condition reducing the risk of moderate visual loss by approximately 50%. The role of vascular endothelial growth factor (VEGF) in DR and DME pathogenesis has been demonstrated in recent studies. This review addresses and summarizes data from the clinical trials that investigated anti-VEGF for the management of DME and evaluates their impact on clinical practice. The literature searches were conducted between August and October 2013 in PubMed and Cochrane Library with no date restrictions and went through the most relevant studies on pegaptanib, ranibizumab, bevacizumab, and aflibercept for the management of DME. The efficacy and safety of intravitreal anti-VEGF as therapy for DME have recently been proved by various clinical trials providing significantly positive visual and anatomical results. Regarding clinical practice, those outcomes have placed intravitreal injection of anti-VEGF as an option that must be considered for the treatment of DME.

Laser-based strategies to treat diabetic macular edema: history and new promising therapies.

Diabetic macular edema (DME) is the main cause of visual impairment in diabetic patients. The management of DME is complex and often various treatment approaches are needed. At the present time, despite the enthusiasm for evaluating several new treatments for DME, including the intravitreal pharmacologic therapies (e.g., corticosteroids and anti-VEGF drugs), laser photocoagulation still remains the current standard in DME. The purpose of this review is to update our knowledge on laser photocoagulation for DME and describe the developments in laser systems. And we will also discuss the new laser techniques and review the latest results including benefits of combined therapy. In this paper, we briefly summarize the major laser therapeutics for the treatment of diabetic macular edema and allude to some future promising laser therapies.

Current trends in the treatment of diabetic macular edema

Since the introduction of focal/grid macular laser over 25 years ago and until recently, laser photocoagulation has been the standard of care in the treatment of diabetic macular edema (DME). Whilst laser photocoagulation was shown to halve the risk of moderate visual loss over 3 years, from 24% to 12%, only < 5% of patients achieves better visual acuity. Within the last 5 years, the use of intravitreal corticosteroids and intravitreal anti-vascular endothelial growth factor (VEGF) agents have come into clinical practice for the management of DME and several recent randomized clinical trials have shown superior effectiveness of anti-VEGF treatments compared to conventional macular laser. The introduction of depot steroid injections as flucinolone acetoinde has also lead to a current increase in interest in the use of intravitreal corticosteroids for DME treatment. In this review, we discuss the ocular treatment options currently available for the treatment of DME, mainly focusing on macular laser as well as intravitreal anti-VEGF and corticosteroid treatments.

Anti-vascular endothelial growth factor therapy for diabetic macular edema.

Diabetes mellitus is a serious health problem that affects over 350 million individuals worldwide. Diabetic retinopathy (DR), which is the most common microvascular complication of diabetes, is the leading cause of new cases of blindness in working-aged adults. Diabetic macular edema (DME) is an advanced, vision-limiting complication of DR that affects nearly 30% of patients who have had diabetes for at least 20 years and is responsible for much of the vision loss due to DR. The historic standard of care for DME has been macular laser photocoagulation, which has been shown to stabilize vision and reduce the rate of further vision loss by 50%; however, macular laser leads to significant vision recovery in only 15% of treated patients. Mechanisms contributing to the microvascular damage in DR and DME include the direct toxic effects of hyperglycemia, sustained alterations in cell signaling pathways, and chronic microvascular inflammation with leukocyte-mediated injury. Chronic retinal microvascular damage results in elevation of intraocular levels of vascular endothelial growth factor A (VEGF), a potent, diffusible, endothelial-specific mitogen that mediates many important physiologic processes, including but not limited to the development and permeability of the vasculature. The identification of VEGF as an important pathophysiologic mediator of DME suggested that anti-VEGF therapy delivered to the eye might lead to improved visual outcomes in this disease. To date, four different inhibitors of VEGF, each administered by intraocular injection, have been tested in prospective, randomized phase II or phase III clinical trials in patients with DME. The results from these trials demonstrate that treatment with anti-VEGF agents results in substantially improved visual and anatomic outcomes compared with laser photocoagulation, and avoid the ocular side effects associated with laser treatment. Thus, anti-VEGF therapy has become the preferred treatment option for the management of DME in many patients.

The impact of metabolic parameters on clinical response to VEGF inhibitors for diabetic macular edema

AimsEvaluate the role of systemic factors on the functional and anatomic outcomes of anti-VEGF therapy for diabetic macular edema (DME). MethodsA retrospective consecutive case series of 124 patients with DME treated with anti-VEGF therapy was collected. The main outcome measures were change in best corrected visual acuity (BCVA) and change central subfield macular thickness (CST) measured with spectral-domain ocular tomography coherence (SD-OCT); and their correlation with clinical findings. ResultsPatients with serum hemoglobin A1c values (HbA1c)≤7.0% had a statistically significant improvement in BCVA (20/66 to 20/43, p<0.001), and those patients with HBA1c>7.0% also had a significant but less robust improvement in BCVA (20/78 to 20/62, p=0.024). CST improved significantly in both groups, but showed a larger magnitude of improvement in the group with better DM control [−140.7 microns (p<0.001) and −83.3 microns (p<0.001)]. Mean HBA1c levels remained relatively stable during the follow-up in both groups, but patients with improved glucose control during the study duration had a significantly lower retinal thickness than patients that had a stable or worsening HbA1c (mean final CST of 324.3 versus 390.0μm, respectively, p=0.042). Other systemic parameters were not correlated with changes in OCT thickness or BCVA. There was not a significant difference related to number of intravitreal injection in the HbA1c≤7.0% group compared to HbA1c>7.0% group, mean of 5.48 and 6.0 intravitreal injections respectively (p=0.362). ConclusionThis study suggests that glucose regulation can impact the response to anti-VEGF therapy in the management of DME.

Intravitreal Injections and Diabetic Macular Edema: Actual and New Therapeutic Options

The management of diabetic macular edema (DME) has been revolutionized in recent years. Focal and focal/ grid laser photocoagulation have been the mainstay of treatment for DME for much time. However, nowadays, there is growing evidence that intravitreal VEGF-inhibitors (combined or not with laser photocoagulation) provide better visual outcome in patients with diabetic retinopathy. Hence, anti-VEGF injections are considered the new gold standard to treat diabetic macular edema and eyes with a reduced visual function. Further studies assessing different treatment regimens are underway to define better clinical care pathways.

Screening, Prevention, and Ambitious Management of Diabetic Macular Edema in Patients with Type 1 Diabetes

Diabetic macular edema results from progressive retinopathy related to chronic hyperglycemic and inflammatory vascular damage. Loss of vision secondary to diabetic macular edema is the most common cause of vision loss in patients with diabetes. Blood glucose control remains the main means of preventing progression of retinopathy and macular edema. Recent advancements allowing more efficient mechanisms for screening patients and emerging treatments for macular edema have led to improved visual outcomes in this group of patients.

Evidence underlying the clinical management of diabetic macular oedema

Diabetic retinopathy (DR) is the leading cause of visual loss in the developed world in those of working age, and its prevalence is predicted to double by 2025. The management of diabetic retinopathy has traditionally relied on screening, on laser treatment delivered by ophthalmologists, and on optimising blood glucose and blood pressure. Recent evidence suggests that the role of systemic factors is more complex than originally thought, and that drugs such as ACE inhibitors, fibrates and glitazones may all influence the course of diabetic macular oedema. Antagonism of vascular endothelial growth factor offers a new therapeutic avenue that may transform the management of diabetic macular oedema. Several other therapeutic options are under investigation and development, including aminoguanidine, sorbinol, ruboxistaurin and autologous stem cell transfusion.

Intravitreal Corticosteroids in the Management of Diabetic Macular Edema

Diabetic macular edema (DME) remains an important worldwide cause of visual loss. Corticosteroids have a role in the treatment of some patients with advanced or recurrent DME. The best studied steroids for this indication are triamcinolone acetonide, dexamethasone, and fluocinolone acetonide. All steroids are associated with risks of cataract and intraocular pressure elevation. In addition, intravitreal injection of any medication is associated with risks of infectious endophthalmitis, which has led to the investigation of various extended-release steroid implants. At this time, no steroid is approved by the United States Food and Drug Administration (FDA) for the treatment of DME.

Anti-VEGF Therapy for the Management of Diabetic Macular Edema

To review the medical evidence for the use of intravitreal vascular endothelial growth factor (VEGF) inhibitors for the treatment of diabetic macular edema (DME). Evaluation of randomized clinical trials evaluating VEGF inhibitors for center-involved DME. Ranibizumab, an anti-VEGF antibody fragment, was evaluated in two phase III clinical studies entitled RISE and RIDE. At 24 months, significantly more ranibizumab treated patients gained ≥15 letters in vision as compared to the sham group (44.8 and 39.2 % vs. 18.1 %; P < 0.0001). The ranibizumab group improved a mean of 250.6–270.7 µm in central foveal thickness compared to a mean improvement of 125.8–133.4 µm for the sham group. In addition, ranibizumab treated patients were more likely to have improvement in retinopathy. Additional clinical trials have evaluated bevacizumab, another anti-VEGF antibody fragment, and aflibercept, a fusion protein that blocks VEGF. Both bevacizumab and aflibercept have also resulted in superior visual acuity outcomes compared to focal laser photocoagulation. All three agents appear to be safe though these clinical trials were not powered to evaluate safety as a primary outcome. Recent clinical trials have demonstrated the superior outcomes with anti-VEGF agents compared to laser alone or sham treatment. Bevacizumab, ranibizumab and aflibercept have all shown remarkable improvements in both visual acuity outcomes and retinal thickness reductions.

OCT in the Management of Diabetic Macular Edema

Diabetic macular edema (DME) is the most common cause of mild-to-moderate visual loss in diabetes. With the introduction of anti-vascular endothelial growth factor therapies in addition to the previously available medical and laser therapies, OCT has become the cornerstone in the diagnosis, monitoring, therapeutic selection, and gauging response to therapy in eyes with DME. A review of the recent literature shows numerous advancements in the way OCT scanning is used both to monitor DME and to guide the management of DME.

Behavior of intraocular pressure after intravitreal injection of triamcinolone acetonide among egyptians.

PurposeTo evaluate the changes in intraocular pressure (IOP) after intravitreal injection of triamcinolone acetonide for the management of diabetic macular edema (DME).MethodsThe study design is a prospective, interventional, two-arm, dose–response study. Nineteen patients with bilateral DME were included, one eye for every patient underwent intravitreal injection of 4 mg triamcinolone acetonide (group A, 19 eyes), and the other eye of the same patient underwent intravitreal injection of 8 mg triamcinolone acetonide (group B, 19 eyes); the selection as to which eye was to receive either dose was random. The patients were followed up for 6 months after injection; complete ophthalmological examination and optical coherent topography were done.ResultsIntravitreal triamcinolone acetonide was effective in reduction of DME in group A in the first 3 months only, while in group B with high dose (8 mg) the improvement continued for 6 months after injection. Significant IOP rise was observed in both groups with an incidence of 68.1% and 73.7% in groups A and B, respectively. IOP-lowering drugs were used to control IOP; however, one patient in each group needed glaucoma filtration surgery in both eyes after intractable glaucoma with failure of medical treatment.ConclusionAlthough intravitreal injection of triamcinolone acetonide is very effective in managing DME and with lower cost than other modalities, the rise in IOP and the burden of glaucoma are major concerns. High corticosteroid responder is an individualized reaction irrespective of the intravitreal triamcinolone acetonide dose used.

Injection frequency and response to bevacizumab monotherapy for diabetic macular oedema (BOLT Report 5)

AimsTo explore the parameters that influence injection frequency in patients treated with intravitreal bevacizumab (ivB) for diabetic macular oedema. Injection frequency was considered as a surrogate marker of persistent or...

A Prospective Randomized Trial of Intravitreal Bevacizumab Versus Ranibizumab for the Management of Diabetic Macular Edema

To compare visual acuity and spectral-domain optical coherence tomography (SDOCT) outcomes associated with intravitreal (IV) bevacizumab vs IV ranibizumab for the management of diabetic macular edema (DME). Prospective randomized trial. Forty-eight patients (63 eyes) with center-involved DME were randomly assigned to receive 1.5 mg (0.06 cc) IV bevacizumab or 0.5 mg (0.05 cc) IV ranibizumab at baseline and monthly if central subfield thickness was greater than 275 μm. Forty-five patients (60 eyes) completed 48 weeks of follow-up. At baseline, mean ± standard error best-corrected visual acuity (BCVA) (logMAR) was 0.60 (20/80) ± 0.05 in the IV bevacizumab group and 0.63 (20/85) ± 0.05 in the IV ranibizumab group. A significant improvement in mean BCVA was observed in both groups at all study visits (P < .05); this improvement was significantly greater in the IV ranibizumab group compared with the IV bevacizumab group at weeks 8 (P = .032) and 32 (P = .042). A significant reduction in mean central subfield thickness was observed in both groups at all study visits compared with baseline (P < .05), with no significant difference in the magnitude of macular thickness reduction between groups. The mean number of injections was significantly higher (P = .005) in the IV bevacizumab group (9.84) than in the IV ranibizumab group (7.67). IV bevacizumab and IV ranibizumab are associated with similar effects on central subfield thickness in patients with DME through 1 year of follow-up. IV ranibizumab is associated with greater improvement in BCVA at some study visits, and the mean number of injections is higher in the IV bevacizumab group.

Early phacoemulsification in diabetic cataract for early recognition and management of diabetic macular oedema.

To get optimal visualization of fundus by early phacoemulsification in diabetic cataract for early recognition and management of diabetic macular oedema. Interventional study. Ophthalmology Unit III, Sindh Government Lyari General Hospital and Dow University of Health Sciences and Al-Noor Eye Hospital, Karachi, from July 2008 to June 2009. Patients with uncontrolled type-II diabetes mellitus of more than 10 years of duration were selected. Patients with clinical significant macular oedema (CSME), non-proliferative diabetic retinopathy (NPDR) and proliferative diabetic retinopathy (PDR) were excluded. Follow-up was done on day 1, 1 week, 1 month, 3 months and 6 months. The male to female ratio was 1:1.44. Out of 218 patients; 129 (59.2%) were males and 89 (40.8%) were females. CSME was found in 82 patients (37.6%) at first postoperative week which declined to 29 cases (13.3%) at first month follow-up. Three subjects developed mild to moderate NPDR. In majority of the subjects, best corrected visual acuity (BCVA) gradually improved in each subsequent follow-up visit. Early phacoemulsification in diabetic cataract offers optimal posterior pole visualization and clears the ambiguity of decreased vision either caused by cataract or macular oedema. Uncomplicated phacoemulsification does not accelerate diabetic macular oedema or retinopathy provided glycemic control and co-morbids are well addressed.

Current State of Care for Diabetic Retinopathy in India

In this article we review the current state of care of diabetic retinopathy in India. We discuss the magnitude of the problem; diabetes, and diabetic retinopathy in India. We highlight the causes of vision loss in diabetic retinopathy. The current level of awareness among general population and physicians is a concern. Current screening strategies practiced in India and the situational analysis of ophthalmologists in India are also reviewed. We review the current management of diabetic macular edema and proliferative diabetic retinopathy. To know the current practice pattern among retinal surgeons in India, a survey was done and the results of the survey are presented. There are few studies in the Indian population which have found some genetic risk and protective factors and a summary of these studies are also presented in this article.

Glial Cell and Inflammatory Responses to Retinal Laser Treatment: Comparison of a Conventional Photocoagulator and a Novel, 3-Nanosecond Pulse Laser

Retinal laser photocoagulation represents a major treatment strategy for the management of diabetic macular edema (DME). However, the thermal nature of this procedure defines that collateral tissue injury result, meaning that it cannot be used near the fovea centralis. We studied inflammatory and glial responses resulting from treatment of rats with a conventional laser and with a novel short-duration, nonthermal laser (retinal regeneration therapy [2RT]) at clinically relevant energy levels. Pigmented Dark Agouti rats were treated with either a conventional thermal continuous wave (CW; 532-nm, 100-ms pulse duration) or a short-pulse (2RT; 532-nm, Q-switched, 3-ns pulse) laser. Settings were at visible threshold for the CW laser (12.7 J/cm(2)/pulse) and at supra- and subvisible thresholds for the 2RT laser ("high," 2RT-H, 163 mJ/cm(2)/pulse; "low," 2RT-L, 109 mJ/cm(2)/pulse). Rats were killed at various subsequent time points. Samples were processed for histology, immunohistochemistry, RT-PCR, and Western blotting. The CW laser caused outer retinal lesions that were associated with photoreceptor death, astrocyte and Müller cell activation, and infiltration of macrophages and neutrophils. Furthermore, inflammatory cytokines, heat shock proteins, endogenous trophic factors, and matrix metalloproteinases were induced. In comparison, all of these changes were drastically attenuated when the 2RT laser was used, particularly at the subthreshold setting. The conventional laser produced marked retinal damage and cellular responses consistent with an inflammatory response to thermal injury. In contrast, the 2RT laser produced negligible retinal damage and cellular responses at clinically relevant settings. These results may have important implications for the treatment of retinal disease.

Management of Diabetic Macular Oedema – Challenges and Solutions Along the Patient Journey

A symposium hosted by the European Society of Ophthalmology discussed challenges in the management of diabetic macular oedema (DMO). Clinical evidence suggests that the longer the duration of DMO, the worse the response to anti-vascular endothelial growth factor (anti-VEGF) agents and better the response to corticosteroids. This is explained by the fact that inflammation is involved in the perpetuation of retinal changes in diabetes. At early disease stages, VEGF is primarily responsible for retinal changes; however, chronic microglia activation resulting from retinal damage leads to cytokine production by retinal cells and subsequent inflammatory cascades. Steroids are most effective at this stage. Clinical trial data have demonstrated the efficacy of the Iluvien® fluocinolone acetonide (FA) intravitreal implant, which retains its efficacy in disease of long duration. However, it is important to remember two things: that diabetes is a multifactorial disease with potential complications and to monitor for safety effects. In terms of the latter, anti-VEGF agents are associated with potential systemic effects, whereas steroids raise intraocular pressure and are associated with increased incidence of cataract.