Использование микропузырьков при pLIFU улучшает доставку рибофлавина и кросс-линкинг роговицы на модели кератоконуса in vivo у кроликов

Keratoconus is a progressive corneal ectasia characterised by focal stromal thinning, corneal protrusion, irregular astigmatism, and progressive visual loss ¹, ². In cases of advanced disease, corneal transplantation may ultimately be necessary; however, this procedure is constrained by factors including donor availability, the risk of rejection and infection, and the necessity for long-term postoperative management ³. The clinical rationale for early-to-moderate keratoconus treatment is therefore to increase corneal resistance to ectatic deformation before irreversible thinning and scarring occur and to reduce the future need for transplantation ⁴, ⁵. Corneal collagen cross-linking (CXL) represents the only established intervention with the capability to slow or halt keratoconus progression ⁶, ⁷, ⁸, ⁹. Standard CXL involves the removal of the central epithelium to allow for riboflavin penetration prior to UVA (wavelengths 320–400 nm) photoactivation. However, it has been observed that epithelial debridement can lead to disruption of the corneal surface barrier, resulting in an increased risk of pain, infection, inflammation, haze, and delayed epithelial healing [¹⁰, ¹¹]. The epithelium-on CXL procedure was introduced to reduce these epithelial complications; however, the intact epithelium and tight junctions strongly restrict hydrophilic riboflavin transport, leading to weaker cross-linking depth and less consistent stiffening than the epithelium-off procedure ¹², ¹⁰, ¹¹, ¹³. A plethora of research has been conducted on the utilisation of chemical enhancers, iontophoresis, electroosmosis, and carrier-based systems with the objective of enhancing ocular drug delivery. However, the implementation of these methodologies is constrained by factors such as epithelial toxicity, incomplete delivery, and procedural complexity [¹⁰, ¹¹, ¹³, ¹⁴, ¹⁵]. A physical method that improves stromal riboflavin delivery while preserving the epithelial barrier is a critical need for safe and effective epithelium-on CXL.