New dawn for keratoconus treatment: potential strategies for corneal stromal regeneration

Keratoconus is a progressive, ectatic and blinding disorder of the cornea, characterized by thinning of corneal stroma. As a highly prevalent among adolescents, keratoconus has been a leading indication for corneal transplantation worldwide. However, the severe shortage of donor corneas is a global issue, and the traditional corneal transplantation surgeries may superinduce multiple complications, necessitating efforts to develop more effective strategies for keratoconus treatment. In this review, we summarized several strategies to promote corneal stromal regeneration or improve corneal stromal thickness, including cell-based therapies, biosynthetic alternatives for inducing corneal regeneration, minimally invasive intrastromal implantation and bioengineered tissues for implantation. These strategies provided more accessible but safer alternatives from various perspectives for keratoconus treatment, paving the way for arresting the keratoconus progression in its earlier stage. For the treatments of corneal ectatic diseases beyond keratoconus, these approaches will provide important references and widen the therapy options in a donor tissue-independent manner.