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Optical Coherence Tomography (Angiography) Biomarkers in the Assessment and Monitoring of Diabetic Macular Edema.
Suciu, CI, Suciu, VI, Nicoara, SD
Journal of diabetes research. 2020;:6655021
Abstract
Retinopathy is one of the most severe diabetes-related complications, and macular edema is the major cause of central vision loss in patients with diabetes mellitus. Significant progress has been made in recent years in optical coherence tomography and angiography technology. At the same time, various parameters have been attributed the role of biomarkers creating the frame for new monitoring and treatment strategies and offering new insights into the pathogenesis of diabetic retinopathy and diabetic macular edema. In this review, we gathered the results of studies that investigated various specific OCT (angiography) parameters in diabetic macular edema, such as central subfoveal thickness (CST), cube average thickness (CAT), cube volume (CV), choroidal thickness (CT), retinal nerve fiber layer (RNFL), retinal thickness at the fovea (RTF), subfoveal choroidal thickness (SFCT), central macular thickness (CMT), choroidal vascularity index (CVI), total macular volume (TMV), central choroid thickness (CCT), photoreceptor outer segment (PROS), perfused capillary density (PCD), foveal avascular zone (FAZ), subfoveal neuroretinal detachment (SND), hyperreflective foci (HF), disorganization of the inner retinal layers (DRIL), ellipsoid zone (EZ), inner segment/outer segment (IS/OS) junctions, vascular density (VD), deep capillary plexus (DCP), and superficial capillary plexus (SCP), in order to provide a synthesis of biomarkers that are currently used for the early diagnosis, assessment, monitoring, and outlining of prognosis.
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NOD-like Receptors in the Eye: Uncovering Its Role in Diabetic Retinopathy.
Lim, RR, Wieser, ME, Ganga, RR, Barathi, VA, Lakshminarayanan, R, Mohan, RR, Hainsworth, DP, Chaurasia, SS
International journal of molecular sciences. 2020;(3)
Abstract
Diabetic retinopathy (DR) is an ocular complication of diabetes mellitus (DM). International Diabetic Federations (IDF) estimates up to 629 million people with DM by the year 2045 worldwide. Nearly 50% of DM patients will show evidence of diabetic-related eye problems. Therapeutic interventions for DR are limited and mostly involve surgical intervention at the late-stages of the disease. The lack of early-stage diagnostic tools and therapies, especially in DR, demands a better understanding of the biological processes involved in the etiology of disease progression. The recent surge in literature associated with NOD-like receptors (NLRs) has gained massive attraction due to their involvement in mediating the innate immune response and perpetuating inflammatory pathways, a central phenomenon found in the pathogenesis of ocular diseases including DR. The NLR family of receptors are expressed in different eye tissues during pathological conditions suggesting their potential roles in dry eye, ocular infection, retinal ischemia, cataract, glaucoma, age-related macular degeneration (AMD), diabetic macular edema (DME) and DR. Our group is interested in studying the critical early components involved in the immune cell infiltration and inflammatory pathways involved in the progression of DR. Recently, we reported that NLRP3 inflammasome might play a pivotal role in the pathogenesis of DR. This comprehensive review summarizes the findings of NLRs expression in the ocular tissues with special emphasis on its presence in the retinal microglia and DR pathogenesis.
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The Burden of Macular Diseases in Central and Eastern Europe-Implications for Healthcare Systems.
Jaki Mekjavić, P, Jūratė Balčiūnienė, V, Ćeklić, L, Ernest, J, Jamrichova, Z, Zsolt Nagy, Z, Petkova, I, Teper, S, Gardašević Topčić, I, Veith, M
Value in health regional issues. 2019;:1-6
Abstract
BACKGROUND Despite the significant impact of retinal diseases such as wet age-related macular degeneration (wAMD) and diabetic macular edema (DME), there is a limited understanding of how these conditions are managed in Central and Eastern Europe (CEE). OBJECTIVES To provide a comprehensive overview of the clinical and economic burden of wAMD and DME in CEE and the status quo associated with their management. METHODS A narrative literature review was undertaken to identify existing data on wAMD and DME, including epidemiology, economic burden, clinical guidelines, and available and reimbursed treatments. Data were collected from relevant sources such as PubMed, ophthalmology associations, national statistical offices, and government agency websites; practical viewpoints were provided by local ophthalmologists and healthcare economics experts in CEE. RESULTS Epidemiological data on wAMD and DME are limited in CEE, and intercountry comparison is difficult because of differences in data collection methodologies. There are effective treatment options for wAMD and DME, and international guidelines advocate the use of intravitreal anti-vascular endothelial growth factor injections as first-line therapy. Local expert organizations broadly support these recommendations; nevertheless, no clinical practice guidelines exist on the treatment of wAMD and DME in CEE. Access to and reimbursement of anti-vascular endothelial growth factor agents vary significantly in the region and, as a result, many patients remain untreated or inadequately treated. CONCLUSIONS There is an urgent need for the creation of a wAMD/DME treatment program in CEE to ensure that patients have timely access to the most appropriate treatments.
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Emerging therapies in the management of macular edema: a review.
Sacconi, R, Giuffrè, C, Corbelli, E, Borrelli, E, Querques, G, Bandello, F
F1000Research. 2019
Abstract
Macular edema (ME) is a major complication of several vascular and inflammatory retinal diseases. Multiple mechanisms are implicated in its development and lead to visual impairment that could be reversible (the acute stages) or not reversible (long-standing ME). For this reason, an effective approach to the treatment of ME is of paramount importance in order to prevent irreversible damage of visual function. In this review, we discuss the management of ME and, in particular, current data of studies and clinical trials about drugs that have already been evaluated or are under investigation in the management of ME. Although several diseases could lead to the development of ME, we focus on the three main causes: diabetic retinopathy (DR), retinal vein occlusion (RVO), and uveitis. The introduction into clinical practice of anti-vascular endothelial growth factor injections (ranibizumab and aflibercept) and dexamethasone implants has revolutionized the treatment of ME secondary to DR and RVO. However, new drugs are needed in the treatment of resistant forms of ME secondary to DR and RVO. A fluocinolone acetonide implant has been approved by the US Food and Drug Administration for the treatment of diabetic ME but not for RVO. Furthermore, brolucizumab and abicipar pegol have been shown to be effective in preliminary studies and have the chance to be approved soon for diabetic ME treatment. In ME secondary to uveitis, a crucial role is played by corticosteroids and non-biologic immunomodulatory drugs. However, several new biologic agents are under investigation in different clinical trials and could be important new therapeutic options in cases with a low response to first-line therapy. However, only a few of these drugs will enter the market after proving their safety and efficacy. Only after that will we be able to offer a new therapeutic option to patients affected by uveitic ME.
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The efficacy and safety of aflibercept and conbercept in diabetic macular edema.
Cai, S, Yang, Q, Li, X, Zhang, Y
Drug design, development and therapy. 2018;:3471-3483
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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6.
Multimodal Imaging in Diabetic Macular Edema.
Acón, D, Wu, L
Asia-Pacific journal of ophthalmology (Philadelphia, Pa.). 2018;(1):22-27
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Abstract
Throughout ophthalmic history it has been shown that progress has gone hand in hand with technological breakthroughs. In the past, fluorescein angiography and fundus photographs were the most commonly used imaging modalities in the management of diabetic macular edema (DME). Today, despite the moderate correlation between macular thickness and functional outcomes, spectral domain optical coherence tomography (SD-OCT) has become the DME workhorse in clinical practice. Several SD-OCT biomarkers have been looked at including presence of epiretinal membrane, vitreomacular adhesion, disorganization of the inner retinal layers, central macular thickness, integrity of the ellipsoid layer, and subretinal fluid, among others. Emerging imaging modalities include fundus autofluorescence, macular pigment optical density, fluorescence lifetime imaging ophthalmoscopy, OCT angiography, and adaptive optics. Technological advances in imaging of the posterior segment of the eye have enabled ophthalmologists to develop hypotheses about pathological mechanisms of disease, monitor disease progression, and assess response to treatment. Spectral domain OCT is the most commonly performed imaging modality in the management of DME. However, reliable biomarkers have yet to be identified. Machine learning may provide treatment algorithms based on multimodal imaging.
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A meta-analysis of the effect of a dexamethasone intravitreal implant versus intravitreal anti-vascular endothelial growth factor treatment for diabetic macular edema.
He, Y, Ren, XJ, Hu, BJ, Lam, WC, Li, XR
BMC ophthalmology. 2018;(1):121
Abstract
BACKGROUND This meta-analysis evaluated the effectiveness and safety of dexamethasone (DEX) implant and intravitreal anti-vascular endothelial growth factor (VEGF) treatment for diabetic macular edema (DME). METHODS The PubMed, Embase, clinicaltrials.gov website and Cochrane Library databases were comprehensively searched for studies comparing DEX implant with anti-VEGF in patients with DME. Best-corrected visual acuity (BCVA), central subfield thickness (CST) and adverse events were extracted from the final eligible studies. Review Manager (RevMan) 5.3 for Mac was used to analyze the data and GRADE profiler were used to access the quality of outcomes. RESULTS Based on four randomized clinical trials assessing a total of 521 eyes, the DEX implant can achieve visual acuity improvement for DME at rates similar to those achieved via anti-VEGF treatment (mean difference [MD] = - 0.43, P = 0.35), with superior anatomic outcomes at 6 months (MD = - 86.71 μm, P = 0.02), while requiring fewer injections, in comparison to anti-VEGF treatment. Although the mean reduction in CST did not showed significant difference at 12 months (MD = - 33.77 μm, P = 0.21), the significant in BCVA from baseline to 12 months supported the anti-VEGF treatment (MD = - 3.26, P < 0.00001). No statistically significant differences in terms of the serious adverse events. However, use of the DEX implant has higher risk of intraocular pressure elevation and cataract than anti-VEGF treatment. CONCLUSIONS Compared with anti-VEGF, DEX implant improved anatomical outcomes significantly. However, this did not translate to improved visual acuity, which may be due to the progression of cataract. Therefore, the DEX implant may be recommended as a first chioce for select cases, such as for pseudophakic eyes, anti-VEGF-resistant eyes, or patients reluctant to receive intravitreal injections frequently.
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Intravitreal Bevacizumab in Diabetic Retinopathy. Recommendations from the Pan-American Collaborative Retina Study Group (PACORES): The 2016 Knobloch Lecture.
Arevalo, JF, Liu, TYA, ,
Asia-Pacific journal of ophthalmology (Philadelphia, Pa.). 2018;(1):36-39
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Abstract
The advent of intravitreal anti-vascular endothelial growth factor (anti-VEGF) medications has revolutionized the treatment of diabetic eye diseases. Herein, we report the outcomes of clinical studies carried out by the Pan-American Collaborative Retina Study Group (PACORES), with a specific focus on the efficacy of intravitreal bevacizumab in the management of diabetic macular edema and proliferative diabetic retinopathy. We will also discuss the use of intravitreal bevacizumab as a preoperative, adjuvant therapy before vitrectomy for proliferative diabetic retinopathy.
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Widening use of dexamethasone implant for the treatment of macular edema.
Bonfiglio, V, Reibaldi, M, Fallico, M, Russo, A, Pizzo, A, Fichera, S, Rapisarda, C, Macchi, I, Avitabile, T, Longo, A
Drug design, development and therapy. 2017;:2359-2372
Abstract
Sustained-release intravitreal 0.7 mg dexamethasone (DEX) implant is approved in Europe for the treatment of macular edema related to diabetic retinopathy, branch retinal vein occlusion, central retinal vein occlusion, and non-infectious uveitis. The implant is formulated in a biodegradable copolymer to release the active ingredient within the vitreous chamber for up to 6 months after an intravitreal injection, allowing a prolonged interval of efficacy between injections with a good safety profile. Various other ocular pathologies with inflammatory etiopathogeneses associated with macular edema have been treated by DEX implant, including neovascular age-related macular degeneration, Irvine-Gass syndrome, vasoproliferative retinal tumors, retinal telangiectasia, Coats' disease, radiation maculopathy, retinitis pigmentosa, and macular edema secondary to scleral buckling and pars plana vitrectomy. We undertook a review to provide a comprehensive collection of all of the diseases that benefit from the use of the sustained-release DEX implant, alone or in combination with concomitant therapies. A MEDLINE search revealed lack of randomized controlled trials related to these indications. Therefore we included and analyzed all available studies (retrospective and prospective, comparative and non-comparative, randomized and nonrandomized, single center and multicenter, and case report). There are reports in the literature of the use of DEX implant across a range of macular edema-related pathologies, with their clinical experience supporting the use of DEX implant on a case-by-case basis with the aim of improving patient outcomes in many macular pathologies. As many of the reported macular pathologies are difficult to treat, a new treatment option that has a beneficial influence on the clinical course of the disease may be useful in clinical practice.
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Association of Diabetic Macular Edema and Proliferative Diabetic Retinopathy With Cardiovascular Disease: A Systematic Review and Meta-analysis.
Xie, J, Ikram, MK, Cotch, MF, Klein, B, Varma, R, Shaw, JE, Klein, R, Mitchell, P, Lamoureux, EL, Wong, TY
JAMA ophthalmology. 2017;(6):586-593
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Abstract
IMPORTANCE Previous studies on the relationship between diabetic retinopathy (DR) and cardiovascular disease (CVD) focused on the early stages of DR. Understanding whether patients with type 2 diabetes and severe stages of DR (diabetic macular edema [DME] and proliferative diabetic retinopathy [PDR]) have a higher risk of CVD will allow physicians to more effectively counsel patients. OBJECTIVE To examine the association of severe stages of DR (DME and PDR) with incident CVD in patients with type 2 diabetes. DATA SOURCES English-language publications were reviewed for articles evaluating the relationship of DR and CVD in MEDLINE, EMBASE, Current Contents, and the Cochrane Library from inception (January 1, 1950) to December 31, 2014, using the search terms diabetic retinopathy OR macular edema AND stroke OR cerebrovascular disease OR coronary artery disease OR heart failure OR myocardial infarction OR angina pectoris OR acute coronary syndrome OR coronary artery disease OR cardiomyopathy. STUDY SELECTION Among 656 studies screened for eligibility, 7604 individuals were included from 8 prospective population-based studies with data on photographic-based DR grading, follow-up visits, and well-defined incident CVD end point. DATA EXTRACTION AND SYNTHESIS Two independent reviewers conducted a systematic search of the 4 databases, and a single pooled database was developed. Incidence rate ratios (IRRs) were estimated for patients with DME, PDR, and vision-threatening DR, compared with persons without these conditions, by using individual participant data followed by a standard inverse-variance meta-analysis (2-step analysis). The review and analyses were performed from January 1, 2009, to January 1, 2017. MAIN OUTCOME AND MEASURES Incident CVD, including coronary heart disease, stroke, or death from cardiovascular causes. RESULTS Among 7604 patients with type 2 diabetes, the prevalence of DME was 4.6% and PDR, 7.4%. After a mean follow-up of 5.9 years (range, 3.2-10.1 years), 1203 incident CVD events, including 916 coronary heart disease cases, were reported. Persons with DME or PDR were more likely to have incident CVD (IRR, 1.39; 95% CI, 1.16-1.67) and fatal CVD (IRR, 2.33; 95% CI, 1.49-3.67) compared with those without DME or PDR. CONCLUSIONS AND RELEVANCE Patients with type 2 diabetes and DME or PDR have an increased risk of incident CVD, which suggests that these persons should be followed up more closely to prevent CVD.