Risk of Moderate to Severe Ocular Surface Disease Associated with Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor Therapy: A Multicenter Cohort Study

Introduction: Moderate to severe ocular surface disease (OSD) can substantially impair quality of life in patients with lung cancer receiving epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) therapy. Although multiple studies have reported cases of OSD associated with EGFR-TKI therapy, few have investigated major risk factors. In this study, we investigated the key risk factors for moderate to severe OSD in patients with lung cancer receiving EGFR-TKI therapy. Methods: This multicenter retrospective (November 2004–December 2019) cohort study included 31,491 patients with lung cancer. Moderate to severe OSD was defined as severe conjunctivitis, dry eye disease necessitating at least step 2 treatment, keratitis, corneal ulcer, corneal perforation, or OSD necessitating surgery. Risk factors for moderate to severe OSD were investigated using univariate and multivariate Cox proportional hazards models. Results: Among 6677 eligible patients who received EGFR-TKI therapy, 220 (3.3%) developed moderate to severe OSD. Multivariate analysis revealed the following independent risk factors: female sex (hazard ratio [HR]: 1.43; 95% CI: 1.08–1.90), prior ocular surgery (HR: 4.15; 95% CI: 1.54–11.21), older age (HR: 1.16; 95% CI: 1.03–1.31), autoimmune disease (HR: 3.38; 95% CI: 1.38–8.25), peptic ulcer (HR: 1.90; 95% CI: 1.35–2.68), thyroid disease (HR: 2.34; 95% CI: 1.03–5.28), and systemic steroid use (HR: 1.50; 95% CI: 1.13–1.97). The following were specific risk factors for severe OSD: distant metastasis (HR: 3.29; 95% CI: 1.16–9.28), prior radiotherapy (HR: 2.29; 95% CI: 1.13–4.65), thyroid disease (HR: 3.78; 95% CI: 1.15–12.40), and high Charlson Comorbidity Index scores (HR: 1.11; 95% CI: 1.01–1.23). Conclusion: Patients with the identified risk factors are at an elevated risk of moderate to severe OSD during EGFR-TKI therapy. Early recognition and timely intervention by ophthalmologists and oncologists in high-risk individuals may mitigate disease progression and improve quality of life.