An update on long-acting therapies in chronic sight-threatening eye diseases of the posterior segment: AMD, DMO, RVO, uveitis and glaucoma

Abstract

In the real-world setting, there is suboptimal compliance with treatments that require frequent administration and assessment visits. This undertreatment frequently has negative consequences in eye disease and carries a real risk to vision. For example, patients with glaucoma risk progression of visual loss even with a small number of missed doses, and patients with neovascular age-related degeneration (nAMD) who fail to attend a bi-monthly clinic appointment to receive an intravitreal anti-vascular endothelial growth factor (VEGF) drug injections may lose the initial vision gains in vision. Protracted regular treatment schedules represent a high burden not only for patients and families, but also healthcare professionals, systems, and ultimately society too. There has been a clear need for longer-acting therapies that reduce the frequency, and therefore the burden, of treatment interventions. Several longer-acting interventions for nAMD, diabetic macular oedema, retinal vein occlusion, uveitis and glaucoma have either been developed or are in late-phase development, some of which employ novel mechanisms of actions, and all of which of promise longer (≥3 month) treatment intervals. This review delivers an overview of anti-VEGF agents with longer durations of action, DARPins, bispecific anti-VEGF/Ang2 therapies, anti-PDGF and anti-integrin therapy, Rho-kinase inhibitors, the Port Delivery System, steroids, gene therapy for retina and uveitis, and for glaucoma, ROCK inhibitors, implants and plugs, and SLT laser and MIGS. The review also refers to the potential of artificial intelligence to tailor treatment efficacy with a resulting reduction in treatment burden.

Efficacy and safety of brolucizumab versus aflibercept in patients with neovascular age-related macular degeneration: a randomized trial in Indian patients

“…However, although found effective, these drugs have limitations, such as poor compliance, frequent dosing injections, and economic burden. Therefore, long-acting anti-VEGF agents that may prolong the dosing interval may help improve the efficacy and adherence [ 9 , 11 ].…”

Recent achievements in nano-based technologies for ocular disease diagnosis and treatment, review and update

“…Several clinical trials are ongoing, such as a study for evaluation of the efficacy and safety study of ENV 515 for the treatment of ocular hypertension (NCT02371746) and glaucoma. AR-13503 (NCT03835884) and AR-1105 (NCT03739593) were designed as intravitreal implants for treating AMD and diabetic macular edema [ 3 , 240 ]. Several other under clinical trial ophthalmic nanomedicines, include Taxol (Paclitaxel albumin-stabilized nanoparticle formulation), which has done phase II clinical trial for treating intraocular melanoma [ 241 ]; GB-102 (Sunitinib malate), in phase I clinical trial for AMD therapy [ 242 ]; KPI-121 (1% and 0.25% loteprednol etabonate), is currently in phase III clinical trial for the treatment of ocular infection, irritation and inflammation [ 243 ] and OCS-01 (dexamethasone cylcodextrin) has done phase II clinical trial for treating eye inflammation and pain [ 244 ] (Table 2 ).…”

Beginn und Fortschritt der nAMD-Behandlung mit VEGF-Inhibitoren

“…Dies kann eine Krankheitsaktivität nach sich ziehen, die durch Neuauftreten oder eine relevante Zunahme der retinalen Flüssigkeiten und Visusverluste gekennzeichnet ist. Auch wenn sich erste Anti-VEGF-Therapien in der nAMD-Behandlung bereits als wirksam erwiesen haben, hat ihre zeitlich begrenzte Wirkdauer bislang häufige Behandlungen und Kontrollen erfordert, was zu einer hohen Behandlungslast der Patient*innen führen kann [15,16]. Dies zeigte sich in einer retrospektiven Studie a aus Frankreich, in der innerhalb des Beobachtungszeitraums von 5 Jahren etwa die Hälfte der Patient*innen ihre Behandlung unter anderem aufgrund von subjektiver Unzufriedenheit mit dem Nutzen der Therapie und der Belastung durch häufige Visiten abbrachen [17].…”

“…Dies zeigte sich in einer retrospektiven Studie a aus Frankreich, in der innerhalb des Beobachtungszeitraums von 5 Jahren etwa die Hälfte der Patient*innen ihre Behandlung unter anderem aufgrund von subjektiver Unzufriedenheit mit dem Nutzen der Therapie und der Belastung durch häufige Visiten abbrachen [17]. Die Ergebnisse verdeutlichen den Bedarf an wirksamen Therapien, die retinale Flüssigkeiten stark und vor allem langanhaltend reduzieren und dadurch potenziell längere Injek tionsintervalle ermöglichen [15,16].…”