The classical signs of ARK comprise limbal stem cell deficiency associated with impaired epithelial cell adhesion, corneal conjunctivalization, epithelial erosions, and corneal vascular pannus that typically only appear after childhood.
4–7 Incipient corneal vascularization in early-stage ARK can be documented with fluorescein anterior segment angiography.
8 Limbal stem cells of aniridia patients lack one copy of PAX6, and the chronic progressive keratopathy seems to be the result of several different factors, including affected differentiation of limbal stem cells, changed corneal epithelial differentiation pathways that cause fragile epithelial cells, and altered cornea healing due to abnormal extracellular metabolism.
9 Proliferative cells from the limbal region of ARK patients have been previously successfully amplified, but their proliferative capacity or their limbal identity could not be confirmed, as conjunctival contamination could also have occurred.
10 Epithelial cell migration is severely delayed possibly because the cells are in a chronic wound-healing state with compromised barrier function.
11 Defective calcium signaling mechanisms are also responsible for delayed wound-healing, which allows for minor abrasions to persist and compromise the corneal stroma.
12 Other described factors include a reduction in the available cell adhesion molecules.
13,14 slow degradation of the corneal epithelial phenotype, breakdown of the limbal niche function,
15 and invasion of the clear cornea by individual conjunctival islands before encroachment of a conjunctival pannus.
16 Management of ARK depends on the severity of the involvement of the ocular surface and can include preservative-free lubricants, autologous serum, and amniotic membrane transplantation, but in severe ARK, a source of limbal stem cells is needed.
17 Limbo-keratoplasty has been shown to be a better treatment option in ARK than penetrating keratoplasty. The latter has a limited prognosis in aniridia patients because of the stem cell deficiency and altered healing responses.
18,19 Keratolimbal allograft (KLAL) transplantation, an additional surgical alternative available for the management of ARK, includes the transplantation of two to three crescents of corneoscleral rim to the host eye in order to completely surround the limbus of the patient.
20,21 It typically requires triple immunosuppression to be successful.
22,23 Chronic stromal inflammation is associated with limbal stem cell deficiency and can interfere with the capacity of limbal stem cell grafts to originate healthy corneal epithelium and is, therefore, a threat to the success of transplanted limbal epithelial stem cells in different pathologies.
24 It is very difficult to acquire corneal button samples of eyes with ARK, as aniridia is a rare condition and surgical treatments are generally reserved as the last therapeutic option.