Limbal stem cell diseases

Abstract

The function of limbal stem/progenitor cells (LSCs) is critical to maintain corneal epithelial homeostasis. Many external insults and intrinsic defects can be deleterious to LSCs and their niche microenvironment, resulting in limbal stem cell dysfunction or deficiency (LSCD). Ocular comorbidities, frequent in eyes with LSCD, can exacerbate the dysfunction of residual LSCs, and limit the survival of transplanted LSCs. Clinical presentation and disease evolution vary among different etiologies of LSCD. New ocular imaging modalities and molecular markers are now available to standardize the diagnosis criteria and stage the severity of the disease. Medical therapies may be sufficient to reverse the disease if residual LSCs are present. A stepwise approach should be followed to optimize the ocular surface, eliminate the causative factors and treat comorbid conditions, before considering surgical interventions. Furthermore, surgical options are selected depending on the severity and laterality of the disease. The standardized diagnostic criteria to stage the disease is necessary to objectively evaluate and compare the efficacy of the emerging customized therapies.

Keywords: Anterior segment optical coherence tomography; In vivo confocal microscopy; Limbal stem cell; Limbal stem cell deficiency; Limbus; Treatment.

Figure 1

Slit lamp examination in eyes presenting with LSCD Figure 1A: Normal eye under bright light (left panel) and blue cobalt filter (right panel). Figure 1B : Mild stage of LSCD: unremarkable examination under bright light (left panel). Superior linear granular fluorescein staining (right panel). Figure 1C: Moderate stage of LSCD: sectoral irregular epithelial reflex with opacification under bright light (left panel). Fluorescein staining showing a demarcation line between the clear and affected areas, involving the visual axis (right panel). Figure 1D: Severe stage of LSCD: diffuse epithelial opacification and corneal haze under bright light (left panel). Diffuse vortex pattern fluorescein staining (right panel). LSCD = limbal stem cell deficiency

Figure 2

Clinical grading system The grading system includes the evaluation of the limbal involvement in clock hours (top panel), of the corneal surface involvment in areas (central panel) and of the visual axis (bottom panel). Mild score corresponds to 1–4 points, moderate to 5–7 points, and severe to 8–10 points. The eye represented exhibits a total score of 6 points (moderate stage). Reprint from Aravena &al., Cornea 2019.

Figure 3

Management of LSCD Autologous LSCs transplantation includes KLAU, CLAL, autologous SLET, ex vivo-cultivated LSC autograft. Allograft include KLAL, CLAL, ex vivo cultivated LSC allograft. AMT = amniotic membrane; CLAL = conjunctival limbal allograft; COMET = cultivated oral mucosal epithelial transplantation; KLAL = keratolimbal allograft; KLAU = keratolimbal allograft; SLET = simple limbal epithelial transplantation; SSCE = sequential sectorial conjunctival epitheliectomy. Reprint form Deng &al., Cornea 2020.