Background <p>Severe vernal keratoconjunctivitis (VKC) can lead to total limbal stem cell deficiency (LSCD), a condition characterized by conjunctivalization of the cornea and neovascularization that often results in severe vision loss and typically requires surgical intervention. This report presents a novel case where a condition clinically simulating total LSCD, induced by chronic inflammation from VKC, was reversed using only anti-inflammatory therapy.</p> Case presentation <p>A 15-year-old male with a 7-year history of inadequately managed VKC presented with typical signs of clinically apparent total LSCD in both eyes. Clinical examination revealed diffuse corneal conjunctivalization, superficial neovascularization, and visual acuity reduced to counting fingers. The patient was treated with a topical regimen consisting of 0.5% loteprednol, 0.1% tacrolimus, and preservative-free artificial tears. Over 7 months of continuous treatment, the corneas regained significant transparency. Notably, the patient experienced a recurrence of corneal conjunctivalization at month 24 after self-discontinuing medication at month 23, which was again successfully reversed by resuming the anti-inflammatory therapy.</p> Conclusions <p>This case demonstrates that severe functional LSCD secondary to VKC can be successfully reversed through intensive, non-surgical anti-inflammatory therapy. Our findings highlight the critical importance of controlling chronic inflammation and suggest that in selected cases of inflammatory or functional LSCD, exhaustive medical management should be prioritized before considering surgical intervention.</p>