Nanomaterial-Enhanced Corneal Cross-Linking: Engineering Strategies for Transforming Keratoconus Management

Keratoconus, a progressive corneal ectasia, remains a major cause of irreversible visual impairment worldwide. Conventional corneal cross-linking (CXL) with riboflavin/ultraviolet A (UVA) has revolutionized clinical management, yet its efficacy is still constrained by epithelial barriers, oxygen dependence, and safety concerns in thin corneas. Emerging nanotechnology provides a transformative opportunity to overcome these bottlenecks. This review highlights the enhancement of riboflavin delivery efficiency by nanocarriers, the photodynamic optimization of nano-enhanced cross-linking agents, and the synergistic strengthening effect of nanocomposites on corneal mechanical strength. We emphasize not only their potential to enhance drug penetration, improve cross-linking efficiency, and extend clinical indications, but also their role in advancing toward a new generation of personalized, intelligent, and minimally invasive corneal therapy. Finally, we discuss translational challenges, including manufacturing, long-term biosafety, and regulatory frameworks, and present a theoretical roadmap that integrates nanotechnology, real-time imaging, and artificial intelligence (AI)-assisted decision-making to achieve a closed-loop “sense–decide–act” therapeutic system. By situating nanomaterial-enhanced CXL within precision ophthalmology, this review highlights its capacity to redefine the standard of care for keratoconus and related ectatic disorders.