Neovasküler Yaşa Bağlı Makula Dejenerasyonunda Güncel Tedaviler ve Yeni Tedavi Yaklaşımları
Özet
Yaşa bağlı makula dejenerasyonu (YBMD), 65 yaş üstü bireylerde geri dönüşü olmayan körlüğün en yaygın nedenidir ve vasküler endotel büyüme faktörü (VEGF), neovasküler YBMD (nYBMD) patogenezinde ana rol oynar. Mevcut altın standart olan anti-VEGF ajanlar (Pegaptanib, Bevacizumab, Ranibizumab, Aflibercept, Brolucizumab) görme prognozunu büyük ölçüde iyileştirse de, sık enjeksiyon gereksinimi, yüksek tedavi yükü, hasta uyumsuzluğu, fibrozis, retinal skar ve coğrafik atrofi gelişme riski gibi önemli dezavantajlara sahiptir. Bu sınırlamaları aşmak amacıyla, patogenezdeki farklı yolakları hedefleyen çoklu tedavi yaklaşımları ve etki süresini uzatmayı amaçlayan yeni teknolojiler geliştirilmektedir. Bu kapsamda, çift hedefli bir monoklonal antikor olan Faricimab; VEGF-C/D tuzak molekülü OPT-302; ranibizumabın sürekli vitreusa salınımını sağlayan Port Delivery Sistem (PDS); uzun yarı ömürlü abicipar pegol, conbercept ve KSI-301 gibi biyopolimer konjugatları literatürde öne çıkmaktadır. Ayrıca sunitinib malat içeren biyolojik olarak parçalanabilir mikropartiküller (GB-102) ve uzun süreli transgen ekspresyonu sunan adeno-ilişkili virüs vektörlü gen tedavileri (RGX-314 ve ADVM-022) enjeksiyon sıklığını azaltmayı hedefleyen gelecek vaat eden yaklaşımlardır. Mevcut anti-VEGF ajanlar nYBMD tedavisinde devrim yaratmış olsa da henüz tam bir kür sağlanamamıştır; ancak patogenezdeki tüm yolaklara etki edebilecek daha uzun etkili farmasötiklerin bulunmasıyla gelecekte tamamen kür sağlanması muhtemeldir.
Age-related macular degeneration (AMD) is the most common cause of irreversible blindness in individuals over the age of 65, and vascular endothelial growth factor (VEGF) plays a primary role in the pathogenesis of neovascular AMD (nAMD). Although current gold-standard anti-VEGF agents (Pegaptanib, Bevacizumab, Ranibizumab, Aflibercept, Brolucizumab) substantially improve visual prognosis, they possess significant disadvantages such as the requirement for frequent injections, a high treatment burden, patient non-compliance, and risks of developing fibrosis, retinal scarring, and geographic atrophy. To overcome these limitations, multi-targeted therapeutic approaches that address different pathways in the pathogenesis and new technologies aimed at extending the duration of action are being developed. In this context, Faricimab, a bispecific monoclonal antobody; OPT-302, a VEGF-C/D trap molecule; the Port Delivery System (PDS) providing continuous intravitreal release of ranibizumab; and long half-life molecules like abicipar pegol, conbercept, and the biopolymer conjugate KSI-301 stand out in the literature. Additionally, biodegradable microparticles containing sunitinib malate (GB-102) and adeno-associated virus-vectored gene therapies offering long-term transgene expression (RGX-314 and ADVM-022) are promising approaches targeted at reducing injection frequency. While current anti-VEGF agents have revolutionized nAMD treatment, a complete cure is not yet available; however, achieving a total cure may be possible in the future with the discovery of longer-acting pharmaceuticals capable of affecting all pathways in the pathogenesis.
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