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

Abstract

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.

Smart molecules in ophthalmology: Hydrogels as responsive systems for ophthalmic applications

“…[55] The most prevalent therapy for suppressing angiogenesis includes intraocular injection of anti-VEGF (vascular endothelial growth factors) molecules every 4-6 weeks [56] However, numerous challenges have been raised throughout the years with its use. [57] Anti-VEGF therapies were shown to induce a persistent increase in IOPs, [58] contribute to the incidence of retinal tears [59] and geographic atrophy progression, [60] induce corneal endothelial and limbal mesenchymal stem cell injuries due to multiple drug administrations, [61] and reduce the choroid vessel thickness. [62,63] Furthermore, a recent retrospective study showed that anti-VEGF intravitreal administration for wet AMD over a 10-year period still leads to a decline in visual acuity, with persistent retinal fluid in 72% of affected eyes.…”

“…Age‐related macular degeneration (AMD) is a vision‐threatening condition that involves the abnormal growth of new blood vessels [55] . The most prevalent therapy for suppressing angiogenesis includes intraocular injection of anti‐VEGF (vascular endothelial growth factors) molecules every 4–6 weeks [56] However, numerous challenges have been raised throughout the years with its use [57] . Anti‐VEGF therapies were shown to induce a persistent increase in IOPs, [58] contribute to the incidence of retinal tears [59] and geographic atrophy progression, [60] induce corneal endothelial and limbal mesenchymal stem cell injuries due to multiple drug administrations, [61] and reduce the choroid vessel thickness [62,63] .…”

Update on the Management of Diabetic Retinopathy: Anti-VEGF Agents for the Prevention of Complications and Progression of Nonproliferative and Proliferative Retinopathy

“…Adherence to follow-up for anti-VEGF injections is critical for the effective management of DR and maintaining visual outcomes over the long term. From a pharmacokinetics standpoint, it takes a monthly injection to maintain adequate drug levels if the goal is continuous action of anti-VEGF therapy [ 36 ]. Cessation of monthly injections may promptly result in disease worsening, even in patients who quickly showed improvement and then remained stable over the long term.…”

Characterisation of RNA editing and gene therapy with a compact CRISPR-Cas13 in the retina

“…Regular (monthly/bimonthly) administration of anti-VEGF drugs is the approved front-line treatment modality for these patients (17). Delivered through intravitreal injections, frequent administration of anti-VEGF drugs poses a significant clinical burden on healthcare institutions and patients due to the risk of infection, patient anxiety, clinic capacity and availability of trained healthcare personnel among others (18).…”