KSI-301: antibody biopolymer conjugate in retinal disorders

Zhang²,

et al. 2022

Cells

105

Diabetic retinopathy (DR), with increasing incidence, is the major cause of vision loss and blindness worldwide in working-age adults. Diabetic macular edema (DME) remains the main cause of vision impairment in diabetic patients, with its pathogenesis still not completely elucidated. Vascular endothelial growth factor (VEGF) plays a pivotal role in the pathogenesis of DR and DME. Currently, intravitreal injection of anti-VEGF agents remains as the first-line therapy in DME treatment due to the superior anatomic and functional outcomes. However, some patients do not respond satisfactorily to anti-VEGF injections. More than 30% patients still exist with persistent DME even after regular intravitreal injection for at least 4 injections within 24 weeks, suggesting other pathogenic factors, beyond VEGF, might contribute to the pathogenesis of DME. Recent advances showed nearly all the retinal cells are involved in DR and DME, including breakdown of blood-retinal barrier (BRB), drainage dysfunction of Müller glia and retinal pigment epithelium (RPE), involvement of inflammation, oxidative stress, and neurodegeneration, all complicating the pathogenesis of DME. The profound understanding of the changes in proteomics and metabolomics helps improve the elucidation of the pathogenesis of DR and DME and leads to the identification of novel targets, biomarkers and potential therapeutic strategies for DME treatment. The present review aimed to summarize the current understanding of DME, the involved molecular mechanisms, and the changes in proteomics and metabolomics, thus to propose the potential therapeutic recommendations for personalized treatment of DME.

Section: Therapeutic Strategies For Dmementioning

confidence: 99%

Diabetic Macular Edema: Current Understanding, Molecular Mechanisms and Therapeutic Implications

Zhang²,

et al. 2022

Cells

105

“…It contains high molecular weight phosphorylcholine biopolymer by which the intraocular durability and the duration of the pharmacological effects increase. Consequently, it enhances the beneficial effects in the long term [ 167 ]. Phase III trials for retinal vein occlusion as well as nAMD and diabetic macular edema are ongoing ( Table 2 ) [ 168 ].…”

Section: Retinal Vein Occlusionmentioning

confidence: 99%

Risk Factors and Treatment Strategy for Retinal Vascular Occlusive Diseases

Terao

Fujino

Ahmed

2022

JCM

Retinal occlusive diseases are common diseases that can lead to visual impairment. Retinal artery occlusion and retinal vein occlusion are included in the clinical entity, but they have quite different pathophysiologies. Retinal artery occlusion is an emergent eye disorder. Retinal artery occlusion is mainly caused by thromboembolism, which frequently occurs in conjunction with life-threatening stroke and cardiovascular diseases. Therefore, prompt examinations and interventions for systemic vascular diseases are often necessary for these patients. Retinal vein occlusion is characterized by retinal hemorrhage and ischemia, which may impair visual function via several complications such as macular edema, macular ischemia, vitreous hemorrhage, and neovascular glaucoma. Even though anti-vascular endothelial growth factor therapy is the current established first-line of treatment for retinal vein occlusion, several clinical studies have been performed to identify better treatment protocols and new therapeutic options. In this review, we summarize the current findings and advances in knowledge regarding retinal occlusive diseases, particularly focusing on recent studies, in order to provide an update for a better understanding of its pathogenesis.

Section: Features Of Anti-vegf Agentsmentioning

confidence: 99%

“…It has been shown to bind VEGF-A with high affinity (KD 6.75 pM), higher than its cognate receptors VEGFR1 and VEGFR2, and has a high bioavailability in both the retina and choroid/RPE. 65 The ocular tissue half-life has been demonstrated to be > 10.5 days in the retina and > 12.5 days in the choroid in rabbit models. 66 The clinical results (Phase 1a and Phase 1b) of KSI-301 have thus far shown excellent safety and greater efficacy in three retinal diseases: nAMD, DME, and RVO.…”

Section: Ksi-301mentioning

confidence: 99%

Progress and Challenges of Anti-VEGF Agents and Their Sustained-Release Strategies for Retinal Angiogenesis

Xu¹,

Fan²,

Fan³

et al. 2022

DDDT

Currently, the treatment for ocular neovascular diseases, including diabetic macular edema (DME) and age-related macular degeneration (AMD), mainly involves repeated intravitreal injection of anti-vascular endothelial growth factor (VEGF) drugs. Although it can preserve vision, repeated injections are an invasive treatment modality, leading to serious complications and reducing patient adherence to treatment. To reduce the frequency of administration, prolong the time of drug action, and avoid repeated intravitreal injections, the combination of sustained-release materials with anti-VEGF drug therapy has become an emphasis in ophthalmology. In this review, we highlight the current state of anti-VEGF technology, its challenges, and the sustained-release strategies under investigation or being used in clinical practice. Both continuous release and considerable therapeutic effects can be achieved by encapsulating anti-VEGF drugs in sustained-release materials to minimize the number of intravitreal injections. At present, two sustained-release materials are being tested in clinical research, and although basic research shows the strong therapeutic application prospects of extended-release drugs, its challenges mainly involve the discrepancy between the release rates in vitro and the efficiency of the drugs in vivo. Briefly, sustained release of anti-VEGF agents is an advantageous strategy for treating retinal angiogenesis.