scholarly journals Updates on the Current Treatments for Diabetic Retinopathy and Possibility of Future Oral Therapy

2021 ◽  
Vol 10 (20) ◽  
pp. 4666
Author(s):  
Yohei Tomita ◽  
Deokho Lee ◽  
Kazuo Tsubota ◽  
Kazuno Negishi ◽  
Toshihide Kurihara

Diabetic retinopathy (DR) is a complication of diabetes and one of the leading causes of vision loss worldwide. Despite extensive efforts to reduce visual impairment, the prevalence of DR is still increasing. The initial pathophysiology of DR includes damage to vascular endothelial cells and loss of pericytes. Ensuing hypoxic responses trigger the expression of vascular endothelial growth factor (VEGF) and other pro-angiogenic factors. At present, the most effective treatment for DR and diabetic macular edema (DME) is the control of blood glucose levels. More advanced cases require laser, anti-VEGF therapy, steroid, and vitrectomy. Pan-retinal photocoagulation for non-proliferative diabetic retinopathy (NPDR) is well established and has demonstrated promising outcomes for preventing the progressive stage of DR. Furthermore, the efficacy of laser therapies such as grid and subthreshold diode laser micropulse photocoagulation (SDM) for DME has been reported. Vitrectomy has been performed for vitreous hemorrhage and tractional retinal detachment for patients with PDR. In addition, anti-VEGF treatment has been widely used for DME, and recently its potential to prevent the progression of PDR has been remarked. Even with these treatments, many patients with DR lose their vision and suffer from potential side effects. Thus, we need alternative treatments to address these limitations. In recent years, the relationship between DR, lipid metabolism, and inflammation has been featured. Research in diabetic animal models points to peroxisome proliferator-activated receptor alpha (PPARα) activation in cellular metabolism and inflammation by oral fenofibrate and/or pemafibrate as a promising target for DR. In this paper, we review the status of existing therapies, summarize PPARα activation therapies for DR, and discuss their potentials as promising DR treatments.

2020 ◽  
Vol 21 (17) ◽  
pp. 6243 ◽  
Author(s):  
Yohei Tomita ◽  
Deokho Lee ◽  
Yukihiro Miwa ◽  
Xiaoyan Jiang ◽  
Masayuki Ohta ◽  
...  

Diabetic retinopathy (DR) is one of the leading causes of blindness globally. Retinal neuronal abnormalities occur in the early stage in DR. Therefore, maintaining retinal neuronal activity in DR may prevent vision loss. Previously, pemafibrate, a novel selective peroxisome proliferator-activated receptor alpha modulator, was suggested as a promising drug in hypertriglyceridemia. However, the role of pemafibrate remains obscure in DR. Therefore, we aimed to unravel systemic and retinal changes by pemafibrate in diabetes. Adult mice were intraperitoneally injected with streptozotocin (STZ) to induce diabetes. After STZ injection, diet supplemented with pemafibrate was given to STZ-induced diabetic mice for 12 weeks. During the experiment period, body weight and blood glucose levels were examined. Electroretinography was performed to check the retinal neural function. After sacrifice, the retina, liver, and blood samples were subjected to molecular analyses. We found pemafibrate mildly improved blood glucose level as well as lipid metabolism, boosted liver function, increased serum fibroblast growth factor21 level, restored retinal functional deficits, and increased retinal synaptophysin protein expression in STZ-induced diabetic mice. Our present data suggest a promising pemafibrate therapy for the prevention of early DR by improving systemic metabolism and protecting retinal function.


2020 ◽  
Author(s):  
Lijie Dong ◽  
Zhe Zhang ◽  
Xun Liu ◽  
Qiong Wang ◽  
Yaru Hong ◽  
...  

Abstract Backgroud: Diabetic retinopathy, currently considered a neurovascular disease, has become the major cause of blindness. Continuously high glucose levels are regarded as a risk factor for DR. Intravitreal injection of anti-VEGF drugs is a classic treatment for DR; however, anti-VEGF drugs can exacerbate fibrosis and eventually lead to retinal detachment.Methods: We explored changes in gene expression in high-glucose-induced vascular endothelial cells using RNA sequencing technology, utilized transcriptome signatures to explore the pathogenesis of DR and identified new treatments that can provide dual-target intervention for angiogenesis and fibrosis. We identified BMP4 and SMAD9 among 449 differentially expressed genes from RNA-seq data and investigated the expression of these two genes in the blood of diabetes patients and in STZ-induced rat retinas. Moreover, considering that DR is a multifactorial and multicellular disease, we used H2O2, AGEs, CoCl2, 4HNE and hypoxia to induce three human retinal cell types (Müller, RPE and HRCECs) to simulate the pathogenesis of DR and then verified the overexpression of these two genes in the cell models. We further tested the effects of BMP4 on retinal cells. Results: The results demonstrated that BMP4 and SMAD9 were highly expressed in both in vivo and in vitro models, while BMP4 could significantly upregulate the expression of SMAD9 and promote the expression of VEGF and fibrosis factors.Conclusions: This study is the first to analyze the mechanism by which high glucose levels affect retinal vascular endothelial cells through RNA transcriptome sequencing and indicates that BMP4 may be a potential target for the dual-target treatment (anti-VEGF and antifibrosis) of DR.


Pharmaceutics ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1137
Author(s):  
Irini Chatziralli ◽  
Anat Loewenstein

Background: Diabetic retinopathy (DR) is the leading cause of blindness in the working-age population. The purpose of this review is to gather the existing literature regarding the use of the approved anti-vascular endothelial growth (anti-VEGF) agents in the treatment of DR. Methods: A comprehensive literature review in PubMed engine search was performed for articles written in English language up to 1 July 2021, using the keywords “diabetic retinopathy”, “ranibizumab”, “aflibercept”, and “anti-VEGF”. Emphasis was given on pivotal trials and recent robust studies. Results: Intravitreal anti-VEGF agents have been found to significantly improve visual acuity and reduce retinal thickness in patients with diabetic macular edema (DME) in a long-term follow-up ranging from 1 to 5 years and are considered the standard-of-care in such patients. Regarding DR, intravitreal anti-VEGF agents provided ≥2-step improvement in DR severity on color fundus photography in about 30–35% of patients with NPDR at baseline, in the majority of clinical trials originally designed to evaluate the efficacy of intravitreal anti-VEGF agents in patients with DME. Protocol S and CLARITY study have firstly reported that intravitreal anti-VEGF agents are non-inferior to panretinal photocoagulation (PRP) in patients with proliferative DR (PDR). However, the use of new imaging modalities, such as optical coherence tomography-angiography and wide-field fluorescein angiography, reveals conflicting results about the impact of anti-VEGF agents on the regression of retinal non-perfusion in patients with DR. Furthermore, one should consider the high “loss to follow-up” rate and its devastating consequences especially in patients with PDR, when deciding to treat the latter with intravitreal anti-VEGF agents alone compared to PRP. In patients with PDR, combination of treatment of intravitreal anti-VEGF agents and PRP has been also supported. Moreover, in the specific case of vitreous hemorrhage or tractional retinal detachment as complications of PDR, intravitreal anti-VEGF agents have been found to be beneficial as an adjunct to pars plana vitrectomy (PPV), most commonly given 3–7 days before PPV, offering reduction in the recurrence of vitreous hemorrhage. Conclusions: There is no general consensus regarding the use of intravitreal anti-VEGF agents in patients with DR. Although anti-VEGF agents are the gold standard in the treatment of DME and seem to improve DR severity, challenges in their use exist and should be taken into account in the decision of treatment, based on an individualized approach.


2019 ◽  
Vol 8 (11) ◽  
pp. 1960
Author(s):  
Andrea Russo ◽  
Antonio Longo ◽  
Teresio Avitabile ◽  
Vincenza Bonfiglio ◽  
Matteo Fallico ◽  
...  

The study’s purpose was to determine the incidence, risk factors, and outcomes of tractional macular detachment after anti-vascular endothelial growth factor (VEGF) pretreatment before vitrectomy for complicated proliferative diabetic retinopathy. Patients who underwent primary vitrectomy for complicated proliferative diabetic retinopathy, from January 2012 to 31 December 2018, were enrolled. Ophthalmic and pre-operative data were extracted from electronic record systems. All eyes with a valuable Optical Coherence Tomography (OCT)performed within 5 days before injection of anti-VEGF and on the day of vitrectomy were included. Multivariable logistic regression showed that significant risk factors for developing tractional macular detachment included days between anti-VEGF and vitrectomy (OR, 0.71 [95% CI 0.65–0.76]; p < 0.001), vitreous hemorrhage (OR, 0.23 [95% CI 0.11–0.49]; p < 0.001), and age (OR, 1.05 [95% CI 1.02–1.08]; p < 0.001). Decision-tree analysis showed that the stronger predictors of tractional macular detachment were the time between anti-VEGF injection and vitrectomy (p < 0.001). Secondary predictors were the presence of vitreous hemorrhage (p = 0.012) in eyes that underwent vitrectomy between 6 and 10 days after anti-VEGF injection and younger age (p = 0.031) in eyes that underwent vitrectomy 10 days after anti-VEGF injection. Tractional macular detachment occurs in 10% of eyes after anti-VEGF injection, the main risk factors being days between anti-VEGF injection and vitrectomy, vitreous hemorrhage, and age.


Circulation ◽  
2004 ◽  
Vol 110 (9) ◽  
pp. 1128-1133 ◽  
Author(s):  
Yi Liu ◽  
Yi Zhu ◽  
Francois Rannou ◽  
Tzong-Shyuan Lee ◽  
Kitty Formentin ◽  
...  

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