Current and Novel Therapeutic Approaches for Treatment of Neovascular Age-Related Macular Degeneration

Abstract

Age-related macular degeneration AMD is one of the leading causes of blindness in the elderly population. An advanced form of AMD known as neovascular AMD (nAMD) is implicated as the main attributor of visual loss among these patients. The hallmark feature of nAMD is the presence of neovascular structures known as choroidal neovascular membranes (CNVs), along with fluid exudation, hemorrhages, and subretinal fibrosis. These pathological changes eventually result in anatomical and visual loss. A type of proangiogenic factor known as vascular endothelial growth factor (VEGF) has been known to mediate the pathological process behind nAMD. Therefore, therapy has transitioned over the years from laser therapy that ablates the lesions to using Anti-VEGF to target the pathology directly. In this work, we provide an overview of current and emerging therapies for the treatment of nAMD. Currently approved Anti-VEGF agents include ranibizumab, aflibercept, and brolucizumab. Bevacizumab, also an Anti-VEGF agent, is used to manage nAMD even though this is an off-label use. While Anti-VEGF agents have provided a favorable prognosis for nAMD, they are associated with a substantial financial burden for patients and the healthcare system, due to their high cost as well as the need for frequent repeat treatments and visits. Emerging therapies and studies aim to extend the intervals between required treatments and introduce new treatment modalities that would improve patients’ compliance and provide superior results.

Comparative efficacy and safety of Faricimab and other anti-VEGF therapy for age-related macular degeneration and diabetic macular edema: A systematic review and meta-analysis of randomized clinical trials

“…[1] This has led to the development of several drugs designed to block VEGF, thereby limiting the damage caused by vascular leakage, edema, and neovascularisation in the eye. [14–17]…”

“…[1] This has led to the development of several drugs designed to block VEGF, thereby limiting the damage caused by vascular leakage, edema, and neovascularisation in the eye. [14][15][16][17] [18,19] Although anti-VEGF is widely recommended clinically for the treatment of patients with AMD and DME, its main reported drawbacks are mainly the short half-life of anti-VEGF therapy and the subsequent need for repeat injections. [20] Longterm follow-up studies have established that the gains achieved in the first 2 years are not maintained over time.…”

Severe Subconjunctival Hemorrhage After Intravitreal Injection in a Patient With Hemophilia A

“…Longer lasting disease control through newer agents, such as the VEGF-angiopoietin 2 bispecific antibody faricimab, aims to extend the intervals between required treatments. 16 Last, the use of home or remote optical coherence tomography has the potential to allow as-needed regimens for intravitreal injections in patients with lower treatment needs. 17 In conclusion, this case report highlights the potential complications of intravitreal injections in patients with preexisting hemophilia.…”

Enhanced Biosafety of the Sleeping Beauty Transposon System by Using mRNA as Source of Transposase to Efficiently and Stably Transfect Retinal Pigment Epithelial Cells

“…The choroidal neovascularization (CNV) is a result of an imbalance between pro-angiogenic factors, such as the vascular endothelial growth factor (VEGF), and anti-angiogenic factors, such as the pigment epithelium-derived factor (PEDF), leading to visual impairment and potentially rapid loss of vision [ 1 , 2 , 3 , 4 , 5 , 6 ]. The current treatment is the intraocular injection of costly biopharmaceuticals, i.e., ranibizumab, aflibercept, brolucizumab, and bevacizumab (off-label use), which counteracts the promotion of blood vessel growth by VEGF; these biopharmaceuticals halt or retard the progression of neovascularization in 90% of patients, with 30–40% regaining some lost vision [ 7 , 8 , 9 , 10 , 11 , 12 , 13 ]. In addition to being costly, the treatment, which requires frequent, often monthly intraocular injections due to a short half-life time of a few days [ 14 , 15 ], is challenging for the elderly and visually impaired patients and their accompanying care-givers, and it is associated with various risks for side effects, such as endophthalmitis, cataract formation, and ocular hemorrhage, which accumulate with the repeated injections [ 16 , 17 , 18 , 19 , 20 ].…”