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1.
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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2.
Posterior segment drug delivery for the treatment of exudative age-related macular degeneration and diabetic macular oedema.
Wong, CW, Wong, TT
The British journal of ophthalmology. 2019;(10):1356-1360
Abstract
Inhibitors of vascular endothelial growth factors are used to treat a myriad of retinal conditions, including exudative age-related macular degeneration (AMD), diabetic macular oedema (DME) and diabetic retinopathy. Although effective, long-term efficacy is limited by the need for frequent and invasive intravitreal injections. The quest for sustained action therapeutics that can be delivered to target tissue in the least invasive manner is an arduous endeavour that has ended in premature failure for several technologies in Phase II or III trials. Nevertheless, there have been promising preclinical studies, and more are on the horizon: port delivery systems for the treatment of exudative AMD have entered Phase III trials and a wide array of preclinical studies have demonstrated the potential for nanoparticles, such as liposomes, dendrimers and cell penetrating peptides to deliver therapeutics into the posterior segment via minimally invasive routes. In this review, we discuss the challenges posed by ocular barriers for drug penetration and present the recent advancements of the most pertinent drug delivery platforms with a focus on the treatment of exudative AMD and DME.
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3.
Evaluation of ranibizumab and aflibercept for the treatment of diabetic macular edema in daily clinical practice.
Plaza-Ramos, P, Borque, E, García-Layana, A
PloS one. 2019;(10):e0223793
Abstract
PURPOSE To evaluate the efficacy and safety of ranibizumab and aflibercept in the treatment of diabetic macular edema in a real world study, and to compare the two treatments with each other. METHODS Retrospective observational study of 213 eyes from 141 patients with diabetic macular edema was completed between June 2014 and June 2016. 122 were treated with ranibizumab intravitreal injection and 91 with aflibercept intravitreal injection, with a loading phase of 3 injections and a Pro Re Nata protocol. The drug was selected by the physician and fluorescein angiography was performed by physician`s criteria. Re-treatment was performed when a decline in BCVA, an increase of central macular thickness or an increase or persistence of intraretinal fluid in OCT was observed. The primary outcome was the mean change in best corrected visual acuity at 1 year, while central macular thickness, central macular volume, the number of injections and visits were evaluated as secondary outcomes. The correlation between BCVA at 4th month visit and BCVA at 12th month visit was also evaluated. RESULTS The mean baseline best corrected visual acuity for the eyes treated with ranibizumab was 0.55 (+/- 0.35) logMAR, and with aflibercept it was 0.48 (+/- 0.29) (P = 0.109). Best corrected visual acuity improved in both groups, and at the end of the follow-up was 0.40 (+/- 0.35) in the ranibizumab group and 0.40 (+/- 0.29) in the aflibercept group (P = 0.864). Best corrected visual acuity at 4th month visit is correlated at a high value (R = 0.789) with the one at the end of the study. No differences were found in central macular thickness, central macular volume and glycosylated hemoglobin when adjusting with baseline values. The overall number of injections was 5.77 (+/- 2.01), being 5.56 (+/- 2.0) in the ranibizumab group and 6.07 (+/- 1.99) in the aflibercept group (P = 0.069). The main outcome determining final best corrected visual acuity was the baseline best corrected visual acuity (P<0.001). CONCLUSION There are no differences in efficacy between ranibizumab and aflibercept in diabetic macular edema treatment in this real world study.
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4.
Difference in Treatment Effect Between Intravitreal Aflibercept Injection and Laser by Baseline Factors in Diabetic Macular Edema.
Singh, RP, Silva, FQ, Gibson, A, Thompson, D, Vitti, R, Berliner, AJ, Saroj, N
Ophthalmic surgery, lasers & imaging retina. 2019;(3):167-173
Abstract
BACKGROUND AND OBJECTIVE To evaluate the effect of baseline factors on differences in vision gains with intravitreal aflibercept injection (IAI) versus laser control in patients with diabetic macular edema (DME). PATIENTS AND METHODS This was an integrated post-hoc subanalysis of two phase 3 trials (VISTA, VIVID) in patients with DME. Least square (LS) mean differences of patients treated with IAI compared to laser control in best-corrected visual acuity (BCVA) change from baseline at week 100 were evaluated for association with baseline demographics and baseline systemic disease characteristics. RESULTS At week 100, LS mean differences in BCVA change from baseline with IAI compared to laser control were not significant for association with baseline age, gender, and race or status of glycosylated hemoglobin, body mass index, renal impairment, hypertension, cerebrovascular disease, and ischemic heart disease. CONCLUSION Vision gains with IAI were significantly greater than laser control and were not influenced by demographics and systemic disease control at baseline. [Ophthalmic Surg Lasers Imaging Retina. 2019;50:167-173.].
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5.
Surgical Therapy for Macular Edema: What We Have Learned through the Decades.
Bae, JH, Al-Khersan, H, Yannuzzi, NA, Hasanreisoglu, M, Androudi, S, Albini, TA, Nguyen, QD
Ocular immunology and inflammation. 2019;(8):1242-1250
Abstract
Macular edema is a leading cause of functional visual loss in retinal vascular or ocular inflammatory diseases. Because persistent macular edema can lead to irreversible retinal damage, multi-approached treatment should be considered to achieve complete resolution of macular edema. With an enhanced understanding of its pathophysiology, numerous therapeutic options have been developed for the management of macular edema over the decades. Although medical therapies account for the mainstay of treatment, surgical approaches with vitrectomy can play an important role in the management of macular edema, depending on its mechanism of fluid accumulation. The index review focuses on the efficacy of surgical therapy for macular edema secondary to various ocular diseases including diabetic retinopathy, uveitis, and retinal vein occlusion, and consequently provides the evidences that may expand the knowledge and support the employment of surgical options.
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6.
Cytokine and Chemokine Profile Changes in Patients After Intravitreal Conbercept Injection for Diabetic Macular Edema.
Wei, Q, Wan, Z, Hu, Y, Peng, Q
Drug design, development and therapy. 2019;:4367-4374
Abstract
PURPOSE This study aimed to investigate the concentrations of cytokines and chemokines in diabetic macular edema (DME) eyes before and during therapy with the intravitreal injection of conbercept (IVC) and to identify associations with disease activity. METHODS The Bio-Plex® 200 System and the Bio-PlexTM Human Cytokine Standard 27-Plex, Group I (Bio-Rad, Hercules, California, USA) were used to detect cytokine levels in aqueous humour. Experimental aqueous humour samples were collected from 18 patients with DME at the same time that IVC was performed at baseline and at 1 month. Control aqueous humour samples were collected from 16 patients undergoing cataract surgery. RESULTS Significantly higher concentrations of vascular endothelial growth factor (VEGF), interleukin 6 (IL-6), IL-8, eotaxin, granulocyte colony stimulating factor (G-CSF), interferon gamma-induced protein 10 (IP-10), and monocyte chemoattractant protein-1 (MCP-1) were found in the aqueous humour of DME patients than cataract patients. One month after IVC, the intraocular concentrations of VEGF were significantly lower in the eyes of DME patients than at baseline. No other cytokines were significantly altered by conbercept therapy. Best-corrected visual acuity (BCVA) slightly improved following IVC compared with that at baseline, although this difference was not significant, and central macular thickness (CMT) significantly decreased 1 month after IVC treatment. CONCLUSION Angiogenic, inflammatory and growth factors are involved in the development of DME. With the exception of VEGF, IVC did not cause significant differences in any inflammatory cytokines or growth factors in DME patients. CMT is related to VEGF levels in aqueous humour.
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7.
Development of New Proliferative Diabetic Retinopathy in the BEVORDEX Trial.
Mehta, H, Lim, LL, Nguyen, V, Qatarneh, D, Wickremasinghe, SS, Hodgson, LAB, Quin, GJ, McAllister, IL, Gillies, MC, Fraser-Bell, S
Ophthalmology. Retina. 2019;(3):286-287
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8.
Intravitreal corticosteroid implant vs intravitreal ranibizumab for the treatment of macular edema: a meta-analysis of randomized controlled trials.
Wei, Q, Chen, R, Lou, Q, Yu, J
Drug design, development and therapy. 2019;:301-307
Abstract
PURPOSE The purpose of this meta-analysis was to compare the efficacy and safety of corticosteroid implant and intravitreal ranibizumab for the treatment of macular edema (ME). MATERIALS AND METHODS PubMed, Embase, Web of Science, and the Cochrane Central Register of Controlled Trials were comprehensively searched for studies comparing dexamethasone implant with ranibizumab in patients with ME. Best-corrected visual acuity (BCVA), central subfield thickness (CST), and adverse events were extracted from the final eligible studies. RevMan 5.3 software was used to analyze the data, and the modified Jadad assessment tool was used to access the quality of outcomes. RESULTS Three randomized controlled trials (RCTs) were included in our analysis. The types of causes of ME include central retinal vein occlusion (CRVO), branch retinal vein occlusion (BRVO), and diabetic retinopathy (DR). The ranibizumab treatment group had significantly better BCVA compared with the corticosteroid treatment group (standard mean difference [SMD] -0.80; 95% CI -1.08, -0.53; P<0.00001). The ranibizumab treatment group also had higher CST reduction compared with the corticosteroid treatment group, and there was a significant difference (weighted mean difference [WMD] 167.58; 95% CI 125.21-209.95; P<0.00001). There was no significant difference in serious adverse effects between the two groups (SMD 1.67; 95% CI 0.69, 4.05; P=0.26). However, the use of corticosteroid implant had a higher risk of intraocular pressure (IOP) (OR 6.88; 95% CI 4.53-10.44; P<0.00001) elevation and cataract (OR 3.98; 95% CI 1.89-8.37; P=0.0003) than ranibizumab treatment and fewer injections. CONCLUSIONS Compared with ranibizumab, corticosteroid implant did not have greater improved BCVA, but corticosteroid implant had less CST reduction. The advantages of corticosteroids are fewer injections, while the advantages of ranibizumab include fewer side effects.
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9.
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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10.
Experiences and perceptions of patients undergoing treatment and quality of life impact of diabetic macular edema: a systematic review.
Rose, MA, Vukicevic, M, Koklanis, K, Rees, G, Sandhu, S, Itsiopoulos, C
Psychology, health & medicine. 2019;(4):383-401
Abstract
Diabetic macular edema (DME) is a common cause of visual impairment. Current treatments for DME include laser photocoagulation, corticosteroids and Vascular Endothelial Growth Factor (VEGF) antagonists, which are administered via intravitreal injection. The purpose of this systematic review is to explore the experiences and perceptions of patients undergoing laser, corticosteroid implants and intravitreal injection treatment for DME and the impact on Quality of Life (QoL). A systematic search of the Embase, Medline, PsycINFO and Cinahl electronic databases was conducted to identify all studies with an unlimited date range, published in the English language, full text and incorporating human participants. Hand searching identified two articles. Following the application of the Critical Appraisal Skills Programme (CASP) Quantitative and Qualitative Research Checklist 21 articles were selected for inclusion, as they were deemed pertinent for the purpose of this review. Limited studies have examined DME patients' experiences and perceptions of treatment and QoL. The outcomes of these studies lack agreement on the effectiveness of treatment, treatment preferences and impact of QoL in patients with DME. Future research which enhances current knowledge will therefore serve to improve treatment outcomes and QoL in these patients.