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Remote Ischemic Preconditioning and Diabetic Macular Edema

Remote Ischemic Preconditioning and Diabetic Macular Edema

This was a pilot single-blinded randomized controlled trial (RCT) to determine the effect of IPC on diabetic macular edema in patients referring to Yazd Diabetes Research Center. Inclusion criteria: age between 30-60 years old, at least five years of diabetes history, candidate for anti-VEGF therapy. Exclusion criteria: blood pressure≥160/90 mmHg, triglyceride≥400 mg/dl, total cholesterol≥500 mg/d, previous coronary bypass surgery, severe heart failure requiring percutaneous cardiopulmonary support. This study was a pilot study and therefore we didn't determine sample size for it. Forty patients were selected and put into two groups randomly. Simple randomization was done. The written and oral consent was received from all of the participants. This research was presented to the ethics committee of Shahid Sadoughi University of Medical Sciences and approved by the internal medicine department. The ethics committee approved the study with the number 17/138561 on October 1, 2014. The
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Association of statin use and hypertriglyceridemia with diabetic macular edema in patients with type 2 diabetes and diabetic retinopathy

Association of statin use and hypertriglyceridemia with diabetic macular edema in patients with type 2 diabetes and diabetic retinopathy

The severity of DR was graded using the early treat- ment DR study (ETDRS) scale, with seven-field stereo photographs and fluorescein angiography performed simultaneously [21]. Diabetic macular edema was defined as retinal thickening in the macular area of either eye, according to the ETDRS scale, and identified by optical coherence tomography (OCT) [22]. Patients with diabetic macular edema were defined as those who developed macular edema during the follow-up period. Central reti- nal thickness in cases with diabetic macular edema was measured as the distance from the hyperreflective line of the internal limiting membrane to the hyperreflective line of the retinal pigment epithelium/Bruch’s membrane complex using OCT [23]. Patients were excluded if they had follow-ups for less than 1 year, fewer than 2 fundus photographs, other retinal diseases, no DR, vitrectomy, use of lipid-lowering agents other than statins (such as fenofibrate, niacin, and/or fish oil), and no records on use of systemic medications.
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Critical appraisal of ranibizumab in the treatment of diabetic macular edema

Critical appraisal of ranibizumab in the treatment of diabetic macular edema

Abstract: Diabetic retinopathy is the leading cause of blindness among individuals of working age in industrialized nations, with most of the vision loss resulting from diabetic macular edema (DME). The formation of DME depends on the action of several growth factors and inflammatory mediators, but vascular endothelial growth factor (VEGF) appears to be critical for breaking down the blood-retinal barrier and promoting the accumulation of macular edema. Laser photocoagulation has been the standard-of-care for three decades, and although it stabilizes vision, significant gains in visual acuity after treatment are unusual. Several VEGF inhibitors (pegaptanib, aflibercept, and ranibizumab) have been initially developed and tested for the treatment of age-related macular degeneration and subsequently for DME. In Phase I, II, and III trials for DME, ranibizumab has been shown to be superior to macular laser photocoagulation and intraocular triamcinolone acetonide injections for improving visual acuity and drying the macula. As a result, ranibizumab is the only anti-VEGF drug that has been approved by the United States Food and Drug Administration for the treatment of DME. Most experts now consider intravitreal anti-VEGF therapy to be standard-of-care for DME involving the fovea.
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<p>Retinal angiographic alteration in diabetic macular edema after dexamethasone implantation: a case report</p>

<p>Retinal angiographic alteration in diabetic macular edema after dexamethasone implantation: a case report</p>

Abstract: Here we reported a rare case of the implantation of a dexamethasone intravitreal implant (DEX) in which decreased retinal vessel density (VD) was found by optical coherence tomography angiography (OCTA). A 74-year-old male with diabetes mellitus presented with bilateral macular edema. The best-corrected visual acuity (BCVA) was 0.6 in the right eye. Diabetic macular edema (DME) was diagnosed. A DEX for the right eye was planned, and the preoperative evaluation showed a super fi cial VD of 48.74 percent, a deep VD of 53.12 percent, and a foveal avascular zone (FAZ) 0.165 mm 2 in size by OCTA. The BCVA in the right eye recovered to 0.8, and a notably lower super fi cial VD of 45.97 percent and a deep VD of 45.40 percent were observed with an enlarged FAZ of 0.294 mm 2 one month postoperatively. Moreover, BCVA in the right eye was maintained at 0.8, while further reductions in both super fi cial (40.07 percent) and deep (40.91 percent) VD were noted with a FAZ measured at 0.305 mm 2 two months postoperatively. In conclusion, retinal super fi cial and deep VD decreased, while the FAZ increased, after the implantation of the DEX in a patient with DME.
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Subthreshold diode-laser micropulse photocoagulation as a primary and secondary line of treatment in management of diabetic macular edema

Subthreshold diode-laser micropulse photocoagulation as a primary and secondary line of treatment in management of diabetic macular edema

Mean best-corrected visual acuity showed stabilization at 4 months (P,0.017, Table 2) and was maintained throughout the study in 159 eyes (85%). There was an improvement in best-corrected visual acuity in 24 (15%) of the 159 eyes over 14 months of follow-up, with corresponding improvement in foveal thickness and exudates (Figure 4). During follow-up, additional SDM treatment was necessary in 43 eyes (23%). The median number of SDM treatments was two (range one to three). Twenty-eight eyes showed persistent macular edema and worsening of visual acuity on follow-up (14.96%). These eyes were retreated with SDM at the 4-month follow-up. Further management included intravitreal injection of tri- amcinolone acetonide 4 mg/0.1 mL in 22 eyes (11.76%) and pars plana vitrectomy in six eyes (3.2%). For group 2 patients, the mean foveal thickness was 428.89 ± 68.94 µ m. Mild to moderate nonproliferative retinopathy was seen in ten cases and severe nonproliferative retinopathy in 22 cases. These patients were managed by SDM with a median of three sessions (range one to five) 4 months apart. At 4 months, central foveal thickness improved significantly to 356 ± 63.76 µ m (P,0.001, Table 1) and showed gradual stabilization to 262.73 ± 58.5 µ m at the 12-month follow-up in 22 cases (65%). Visual acuity was stable in 20 eyes at 4 months (P = 0.441, Table 2), and one Snellen’s line of acuity improvement was documented in two eyes at the 12-month follow-up. Eleven eyes (33%) showed a poor response to SDM and were injected with triamcinolone. SDM could improve CSDME without inducing further noticeable damage to the macular area after maximum argon laser photocoagula- tion (Figure 5). The results were maintained at 12 months in 65% of cases. Eleven eyes needed intravitreal triamcinolone injection for diabetic macular edema that did not respond to
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Vitrectomy for center-involved diabetic macular edema

Vitrectomy for center-involved diabetic macular edema

spective, randomized clinical trial comparing vitrectomy to serial anti-VEGF injections is needed to determine the rela- tive efficacy and cost-effectiveness of these two treatments for CI-DME. Such an idea has been submitted to the DRCR network, which has the infrastructure enabling execution of such a trial. Relevant evidence for this protocol idea can be obtained from the International Consortium Investigating Early Vitrectomy in Diabetic Macular Edema Patients trial (clinical trials identifier #NCT02639507), a prospective, international, multicenter trial with standardized collection of VA and OCT data that is currently enrolling patients.
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Hospitalized cardiovascular events in patients with diabetic macular edema

Hospitalized cardiovascular events in patients with diabetic macular edema

Diabetic macular edema (DME) may occur at any stage of diabetic retinopathy (DR) and is the leading cause of moderate vision loss in adults of working age [1]. The prevalence of DME is about one-tenth that of back- ground DR and one-third that of proliferative DR [2]. Microvascular complications, like DR and DME, are associated with progressive or uncontrolled diabetes. Cardiovascular events, such as myocardial infarctions (MI) or cerebrovascular accidents (CVA)/stroke, are known macrovascular complications of diabetes mellitus. Microvascular complications of diabetes are commonly diagnosed as eye diseases; however, pathologic changes to cardiac and cerebral circulation also occur [3].
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The clinical utility of aflibercept for diabetic macular edema

The clinical utility of aflibercept for diabetic macular edema

Abstract: The treatment of center-involving diabetic macular edema (DME) has improved because of the proven efficacy of drugs that inhibit the effects of vascular endothelial growth factor (VEGF). The newest anti-VEGF drug, aflibercept, has recently been approved by the United States Food and Drug Administration for the treatment of center-involving DME and for diabetic retinopathy in eyes with DME. In the pivotal Phase III VISTA and VIVID trials, intravitreal aflibercept 2 mg injections every 4 or 8 weeks (after 5 monthly loading doses) pro- duced superior gains in BCVA compared to laser/sham injections. In the Diabetic Retinopathy Clinical Research Network Protocol T trial, which featured monthly anti-VEGF monotherapy for 6 months, followed by monthly pro re nata anti-VEGF injections with laser rescue therapy from months 6 through 12, aflibercept 2 mg monthly was superior to bevacizumab 1.25 mg and ranibizumab 0.5 mg in eyes with BCVA of 20/50 or worse (aflibercept versus bevacizumab: P,0.001; aflibercept versus ranibizumab: P=0.003), but the three regimens were comparable for eyes with VA of 20/40 or better. Only in the 20/50 or worse subgroup did aflibercept achieve clinical superiority (.5 letter difference) to bevacizumab. Each treatment regimen led to sig- nificant macular thinning, with aflibercept being superior to bevacizumab in both visual acuity subgroups (P,0.001 for each), but it was not statistically superior to ranibizumab in either group. In diabetic patients, aflibercept has an excellent safety profile that does not appear to differ from laser/sham or other VEGF inhibitory drugs.
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Effect of intravitreal aflibercept on recalcitrant diabetic macular edema

Effect of intravitreal aflibercept on recalcitrant diabetic macular edema

5. Nguyen QD, Brown DM, Marcus DM, et al. Ranibizumab for diabetic macular edema: results from 2 phase iii randomized trials: RISE and RIDE. Ophthalmology. 2012;119(4):789–801. doi:10.1016/j.ophtha.2011.12.039. 6. Wu L, Martinez-Castellanos MA, Quiroz-Mercado H, et al. Twelve-month safety of intravitreal injections of bevacizumab (Avastin): results of the pan-american collaborative retina study group (PACORES). Graefe’s Arch Clin Exp Ophthalmol. 2008;246(1):81–7. doi:10.1007/s00417-007-0660-z. 7. Michaelides M, Kaines A, Hamilton RD, et al. A prospective randomized
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The role of aflibercept in the management of diabetic macular edema

The role of aflibercept in the management of diabetic macular edema

Abstract: Diabetic macular edema (DME) represents one of the leading causes of visual impairment in working-age adults. Although there are several proven treatments available for this condition, pharmacotherapy through the use of intravitreal antivascular endothelial growth factor agents has revolutionized the management of DME over the past decade with superior outcomes compared to laser therapy. This review summarizes the pathophysiology and available treatment options for the management of DME, with an emphasis on the efficacy and safety profile of a single particular intravitreal antivascular endothelial growth factor agent, aflibercept.
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Comparison of different settings for yellow subthreshold laser treatment in diabetic macular edema

Comparison of different settings for yellow subthreshold laser treatment in diabetic macular edema

for these patients. In a study from Wallick et al., patients with diabetic macular edema were found to have, on aver- age, 25.5 annual days with a health care related visit [6]. In a Canadian study published in 2014 by Gonder et al., the mean 6-month DME-related cost was $2092 per patient [7]. The present day cost is likely higher since the study considered that 70% of patients were injected with bevavi- zumab and the rest with ranibizumab. Thus, there is a constant need for a therapy with long term efficacy for this visually debilitating disease.

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The efficacy and safety of aflibercept and conbercept in diabetic macular edema

The efficacy and safety of aflibercept and conbercept in diabetic macular edema

Abstract: Diabetic macular edema (DME) has shown an increasing prevalence during the past years and is the leading cause of diabetic retinopathy blindness. Traditional treatment modalities include laser and corticosteroid therapy, which, however, either act through unclear mechanisms or cause cataracts and elevated intraocular pressure. In recent years, as the pathogenic role of VEGF in DME has been well-recognized, the intravitreal injection of anti-VEGF drugs has become the first-line treatment of DME due to their great efficacy in improving visual acuity and mitigating macular edema. Advantages have been shown for aflibercept and conbercept, the two recombinant decoy receptors that can bind VEGF with high specificity and affinity, in DME treatment in clinical trials conducted both worldwide and in People’s Republic of China. This review introduces the structural characteristics and molecular mechanisms of action of these two anti-VEGF drugs, and summarizes the clinical trials evaluating their efficacy and safety, with the hope to provide clues for designing optimal and personalized therapeutic regimens for DME patients.
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Intravitreal gas injection for the treatment of diabetic macular edema

Intravitreal gas injection for the treatment of diabetic macular edema

It is likely that the pathogenesis of diabetic macular edema is due to a complex interaction of a number of factors, and these include vitreoretinal relationships at the macula. Specifically, it seems that an attached vitreous may tend to sustain or exacer- bate edema, while conversely a posterior vitreous detachment (PVD) may ameliorate

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Dexamethasone intravitreal implant in the treatment of diabetic macular edema

Dexamethasone intravitreal implant in the treatment of diabetic macular edema

Abstract: Diabetic macular edema (DME) resembles a chronic, low-grade inflammatory reac- tion, and is characterized by blood–retinal barrier (BRB) breakdown and retinal capillary leakage. Corticosteroids are of therapeutic benefit because of their anti-inflammatory, antiangiogenic, and BRB-stabilizing properties. Delivery modes include periocular and intravitreal (via pars plana) injection. To offset the short intravitreal half-life of corticosteroid solutions (~3 hours) and the need for frequent intravitreal injections, sustained-release intravitreal corticosteroid implants have been developed. Dexamethasone intravitreal implant provides retinal drug delivery for 6 months and recently has been approved for use in the treatment of DME. Pooled findings (n=1,048) from two large-scale, randomized Phase III trials indicated that dexamethasone intra- vitreal implant (0.35 mg and 0.7 mg) administered at 6-month intervals produced sustained improvements in best-corrected visual acuity (BCVA) and macular edema. Significantly more patients showed a 15-letter gain in BCVA at 3 years with dexamethasone intravitreal implant 0.35 mg and 0.7 mg than with sham injection (18.4% and 22.2% vs 12.0%). Anatomical assess- ments showed rapid and sustained reductions in macular edema and slowing of retinopathy progression. Phase II study findings suggest that dexamethasone intravitreal implant is effec- tive in focal, cystoid, and diffuse DME, in vitrectomized eyes, and in combination with laser therapy. Ocular complications of dexamethasone intravitreal implant in Phase III trials included cataract-related events (66.0% in phakic patients), intraocular pressure elevation 25 mmHg (29.7%), conjunctival hemorrhage (23.5%), vitreous hemorrhage (10.0%), macular fibrosis (8.3%), conjunctival hyperemia (7.2%), eye pain (6.1%), vitreous detachment (5.8%), and dry eye (5.8%); injection-related complications (eg, retinal tear/detachment, vitreous loss, endophthalmitis) were infrequent (2%). Dexamethasone intravitreal implant offers a viable treatment option for DME, especially in cases that are persistent or treatment (anti-vascular endothelial growth factor/laser) refractory.
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Primary treatment of diabetic macular edema

Primary treatment of diabetic macular edema

Diabetic retinopathy occurs because the retinal vessels are abnormal, either because they proliferate (proliferative retinopathy) or because the vessels are func- tionally incompetent and leak fl uid and lipid into the retina. Visual impairment occurs when edema affects the central retina or macula (diabetic macular edema, or DME). Macular edema is reversible in the early stages but chronic edema may lead to irreversible changes in the retina. In a large cohort study, diabetics with macular edema had a 50% prevalence of visual impairment and a 20% prevalence of blind- ness, compared to 16% and 4% respectively in diabetic patients without macular edema. 5 Figures 1 and 2 contrast the ophthalmic features of macular edema with a
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Update on corticosteroids for diabetic macular edema

Update on corticosteroids for diabetic macular edema

Abstract: Diabetic macular edema (DME) remains an important cause of visual loss. Although anti-vascular endothelial growth factor (VEGF) agents are generally used as first-line treat- ments for patients with center-involving DME, there is an important role for corticosteroids as well. Corticosteroids may be especially useful in pseudophakic patients poorly responsive to anti-VEGF therapies, in patients wishing to reduce the number of required injections, and in pregnant patients. Intravitreal triamcinolone acetonide has been used for many years but is not approved for this indication. An extended-release bioerodable dexamethasone delivery system and an extended-release nonbioerodable fluocinolone acetonide insert have both achieved regulatory approval for the treatment of DME. All intravitreal corticosteroids are associated with risks of cataract progression, elevation of intraocular pressure, and endophthalmitis. There is no current consensus regarding the use of corticosteroids, but they are valuable for selected patients with center-involving DME.
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COMPARISON OF INTRAVITREAL BEVACIZUMAB (AVASTIN) WITH TRIAMCINOLONE FOR TREATMENT OF DIFFUSED DIABETIC MACULAR EDEMA: A PROSPECTIVE RANDOMIZED STUDYAli Kasiri, Fereydoun Farrahi, Mostafa Feghhi, Behnam Sadeghi, Hesam Hedayati, Seyed Ahmad Rasoulinejad DOW

COMPARISON OF INTRAVITREAL BEVACIZUMAB (AVASTIN) WITH TRIAMCINOLONE FOR TREATMENT OF DIFFUSED DIABETIC MACULAR EDEMA: A PROSPECTIVE RANDOMIZED STUDYAli Kasiri, Fereydoun Farrahi, Mostafa Feghhi, Behnam Sadeghi, Hesam Hedayati, Seyed Ahmad Rasoulinejad DOWNLOAD/VIEW

Diabetic macular edema (DME), is one of the most common causes of visual impairment in the diabetic patients [1]. The worldwide prevalence of diabetes is estimated to rise to 366 million by 2030 [2]. The 10-year incidence of macular edema in patients with type 2 diabetes was up to 14%, and 29% of type 1 progressed into DME over a 25-year period [3,4]. Hence, finding a safe and effective treatment of DME becomes urgent. Despite the high prevalence of DME, there is no definite treatment because of its complicated pathophysiologic mechanism, which is still not fully understood. However, there is no single modality that has been shown to be superior. The Early Treatment Diabetic Retinopathy Study (EDTRS) showed that macular laser photocoagulation (MPC) is effective in reducing the risk of visual loss by approximately 50% in eyes with clinically significant macular edema [5]. However, unsatisfactory outcomes are frequent, and 12% treated eyes developed moderate visual loss. Moreover, about 15% patients fall into the category of refractory DME and do not respond to repeated laser treatments. This shows that in spite of laser being the gold standard treatment of DME, some patients do not respond to laser [6]. Various modalities of treatment are currently being tried in the management of persistent; laser refractory DME such as supplemental laser, intravitreal steroid injection, and anti-vascular endothelial growth factor (anti-VEGF) injection [7].
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The prevalence and systemic risk factors of diabetic macular edema: a cross-sectional study from Turkey

The prevalence and systemic risk factors of diabetic macular edema: a cross-sectional study from Turkey

BCVA: Best corrected visual acuity; CMT: Central macular thickness; CSME: Clinically significant macular edema; DCCT: Diabetes Control and Complications Trial; DIRECT: Diabetic Retinopathy Candesartan Trials; DME: Diabetic macular edema; DR: Diabetic retinopathy; DRCR.net: Diabetic Retinopathy Clinical Research network; EDIC: Epidemiology of Diabetes Interventions and Complications; HbA1c: Hemoglobin A1c; HDL-C: High density lipoprotein cholesterol; IOP: Intraocular pressure; LDL-C: Low density lipoprotein cholesterol; NPDR: Non-proliferative diabetic retinopathy; OCT: Optical coherence tomography; PDR: Proliferative diabetic retinopathy; RAAS: Renin-angiotensin-aldosterone system; RASS: Renin-Angiotensin System Study; VEGF: Vascular endothelial growth factor
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Management of Refractory Diabetic Macular Edema: A Review Article

Management of Refractory Diabetic Macular Edema: A Review Article

Diabetic retinopathy (DR) is a major cause of visual impairment worldwide. Visual reduction in patients with DR is usually related to diabetic macular edema (DME). Today, the intravitreal injection of anti-vascular endothelial growth factors (VEGF) is replacing macular laser photocoagulation as the standard treatment for DME; however, in some patients, incomplete responses to the anti-VEGF injection, defined as refractory DME, may occur. Currently, the sequence of using one treatment option and the timing to switch from one agent to another is not fully understood, and the data from clinical trials on the appropriate approach to manage refractory DME is insufficient. In the current study, a review was conducted to evaluate therapeutic options for the management of refractory DME.
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Epidemiology of diabetic retinopathy, diabetic macular edema and related vision loss

Epidemiology of diabetic retinopathy, diabetic macular edema and related vision loss

Diabetic retinopathy (DR) is a leading cause of vision-loss globally. Of an estimated 285 million people with diabetes mellitus worldwide, approximately one third have signs of DR and of these, a further one third of DR is vision-threatening DR, including diabetic macular edema (DME). The identification of established modifiable risk factors for DR such as hyperglycemia and hypertension has provided the basis for risk factor control in preventing onset and progression of DR. Additional research investigating novel risk factors has improved our understanding of multiple biological pathways involved in the pathogenesis of DR and DME, especially those involved in inflammation and oxidative stress. Variations in DR prevalence between populations have also sparked interest in genetic studies to identify loci associated with disease susceptibility. In this review, major trends in the prevalence, incidence, progression and regression of DR and DME are explored, and gaps in literature identified. Established and novel risk factors are also extensively reviewed with a focus on landmark studies and updates from the recent literature.
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