Purpose Severe dry eye is widely prevalent yet difficult to treat. This study aims to evaluate for improvement in epithelial status and the risk factors for lack of improvement in a cohort of patients in Singapore with severe dry eye.

Methods We retrospectively identified 1712 patients with severe dry eye (≥grade 3 Delphi) in at least one eye, referred to a tertiary centre dry eye clinic from 2006 to 2017. We included patients with central corneal staining grade of ≥2 at referral and minimum follow-up duration of 6 months (n=407). An epithelial staining grade of <2 at the last visit was considered a significantly improved outcome.

Results The mean follow-up duration was 4.0±2.4 years, with 88.0% (358/407) of patients achieving significant improvement. Various treatment modalities including topical corticosteroids (32.4%), cyclosporine (52.8%) and punctal plugs (24.1%) were used. Risk factors for non-improvement of staining grade include autoimmune disease (OR 3.2, 95% CI: 1.7 to 6.1), rheumatoid arthritis (RA) (OR 3.4 (1.8 to 6.6)), graft-versus-host disease (GVHD) (OR 3.4 (1.0 to 11.7)), reduced baseline Schirmer’s test (OR 2.1 (1.2 to 3.9)) and reduced tear break up time (OR 2.0 (1.0 to 3.8)). On multivariate analyses, RA and GVHD were still significant risk factors. Gender, age and meibum viscosity were not significantly associated with epithelial staining grade improvement.

Conclusions Overall, a high rate of corneal epithelial improvement was achieved. Nevertheless, there is an unmet need for more effective measures to reduce epitheliopathy in severe dry eye, especially in patients with systemic immune-mediated disease.