Simple limbal epithelial transplantation (SLET) has emerged as an effective treatment option for limbal stem cell deficiency (LSCD). However, the precise molecular mechanisms underlying its success remain incompletely understood. This review delves into the proposed mechanisms involving the donor limbus, host microenvironment, and the amniotic membrane as a scaffold in SLET. The donor limbus contributes to SLET efficacy through various factors secreted by limbal epithelial stem cells, including hepatocyte growth factor (HGF), soluble Fms-like tyrosine kinase-1 (sFLT-1), and pigment epithelium-derived factor (PEDF), which support corneal healing and transparency. Additionally, the presence of melanocytes, immune cells, limbal fibroblasts, and adhesion molecules within the donor tissue helps preserve the integrity of the limbal niche. The host environment plays a critical role in supporting the transplanted stem cells, with mesenchymal stem cell-secreted factors promoting proliferation and differentiation. Although the amniotic membrane has traditionally been used as a scaffold, emerging evidence suggests that it may not always be necessary. Further studies are needed to validate this scaffold-free approach and to evaluate the vitality and functional contributions of individual components used in SLET. Understanding these complex interactions and molecular mechanisms sheds light on the importance of the donor tissue, host microenvironment, and scaffold in SLET, paving the way for the optimization of this technique for the effective treatment of LSCD.

Vernal keratoconjunctivitis (VKC) is a chronic pediatric ocular allergy that can progress from seasonal to persistent inflammation with vision-threatening complications. Although Th2-associated mechanisms have been implicated, the immune correlates of disease severity are not well defined. Tear samples from VKC patients (moderate intermittent and moderate persistent) and healthy controls were collected using Schirmer’s strips. Cytokine profiling was performed using the OLINK^® Target 48 Cytokine Panel. Differential expression, correlation with clinical features, and pathway enrichment analyses were performed. Compared to control, IL-15, CXCL11, CXCL9, MMP12, and CCL13 were significantly elevated in VKC, with higher levels in the persistent phenotype. These cytokines correlated with symptom duration, limbal involvement, and papillary hypertrophy. Pathway analysis revealed enrichment of IL-17, JAK–STAT, and chemokine signaling pathways. VKC severity is associated with distinct tear cytokine signatures, with the persistent phenotype showing enhanced chronic inflammatory signaling. These findings identify candidate tear-based markers of disease severity that require validation in larger, independent, and longitudinal cohorts.