Rowe Lucas W, Akotoye Christian, Harris Alon, Ciulla Thomas A
Department of Ophthalmology, Glick Eye Institute, Indiana University School of Medicine, Indianapolis, IN, USA.
Department of Ophthalmology, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
Expert Opin Pharmacother. 2025 Jun;26(8):939-952. doi: 10.1080/14656566.2025.2496424. Epub 2025 May 11.
Intravitreal injections remain the standard for treating common retinal diseases including age-related macular degeneration (AMD), diabetic macular edema (DME) and diabetic retinopathy. However, frequent administration creates significant treatment burden due to limited drug half-life and the chronic nature of these conditions.
This review summarizes emerging drug delivery techniques and therapies for retinal disease that have achieved FDA approval within the past five years or have advanced to Phase 3 development, including intravitreal sustained-release platforms and alternative delivery routes (suprachoroidal, subretinal, topical, and subcutaneous). Specific innovations discussed include the ranibizumab port delivery system, EYP-1901 (Duravyu, vorolanib implant), KSI-301 (tarcocimab tedromer), KSI-501, OTX-TKI (Axpaxli, axitinib implant), 4D-150, revakinagene taroretcel-lwey (Encelto, NT-501, encapsulated cell therapy), Xipere (triamcinolone acetonide injectable suspension), AU-011 (belzupacap sarotalocan targeted delivery), ABBV-RGX-314, elamipretide, and OCS-01 (high concentration dexamethasone).
Promising innovations include sustained-release intravitreal implants, topical and subcutaneous delivery systems, and targeted methods like suprachoroidal and subretinal injections, each with unique advantages and limitations. Challenges include overcoming the blood-retinal barrier, surgical complications with implantable devices, and ensuring patient adherence. Advances in smart delivery systems, drug formulations, and predictive models, alongside interdisciplinary collaboration, will be crucial in achieving personalized, effective, and sustainable retinal therapies.
玻璃体内注射仍然是治疗包括年龄相关性黄斑变性（AMD）、糖尿病性黄斑水肿（DME）和糖尿病视网膜病变在内的常见视网膜疾病的标准方法。然而，由于药物半衰期有限以及这些疾病的慢性性质，频繁给药会带来巨大的治疗负担。
本综述总结了过去五年内已获得美国食品药品监督管理局（FDA）批准或已进入3期开发阶段的用于视网膜疾病的新兴药物递送技术和疗法，包括玻璃体内缓释平台和替代递送途径（脉络膜上腔、视网膜下、局部和皮下）。讨论的具体创新包括雷珠单抗端口递送系统、EYP - 1901（Duravyu，伏罗尼布植入剂）、KSI - 301（tarcocimab tedromer）、KSI - 501、OTX - TKI（Axpaxli，阿昔替尼植入剂）、4D - 150、瑞伐基因他洛瑞赛尔 - lwey（Encelto，NT - 501，封装细胞疗法）、Xipere（曲安奈德注射用混悬液）、AU - 011（贝祖帕卡普沙罗洛坎靶向递送）、ABBV - RGX - 314、艾拉米肽和OCS - 01（高浓度地塞米松）。
有前景的创新包括玻璃体内缓释植入物、局部和皮下递送系统以及脉络膜上腔和视网膜下注射等靶向方法，每种方法都有独特的优点和局限性。挑战包括克服血视网膜屏障、可植入设备的手术并发症以及确保患者依从性。智能递送系统、药物制剂和预测模型的进展，以及跨学科合作，对于实现个性化、有效和可持续的视网膜治疗至关重要。
