Corneal Staining Responder Analysis: A Clinically Meaningful Dry Eye Outcome.

Abstract

Thus far, clinical studies related to dry eye disease (DED) have focused on demonstrating a statistically significant difference in various ocular surface and tear film parameters and patient symptoms between the test arm versus comparator. However, it is largely unclear what arm differences or magnitude of improvement for a given parameter are clinically meaningful. This study aims to assess the correlations between corneal punctate erosions and patient-reported symptoms and aims to define "corneal staining responder" as a physician-measured and clinically meaningful DED outcome to be used in clinical studies and patient care. Retrospective analysis of previously published studies. A total of 1704 adult patients with evaporative or aqueous deficient DED who participated in 4 large-scale randomized, controlled studies evaluating 2 different DED medications (a water-free cyclosporine 0.1% solution and perfluorohexyloctane ophthalmic solution) or their respective comparators (vehicle and saline solution). Corneal punctate epithelial erosions were evaluated using fluorescein dye, and the staining score was graded according to the National Eye Institute scale (0-15). "Corneal staining responder" was defined as a ≥3 grade improvement from baseline, based on published literature and expert opinion. A variety of patient symptoms were assessed using a visual analogue scale (0-100). Corneal staining responders were compared with nonresponders regarding improvement in symptoms via analysis of covariance irrespective of the treatment received. In all 4 studies, corneal staining responders showed numerically greater improvement in all assessed DED symptoms compared with nonresponders. Overall, 36 comparisons were performed involving 14 different DED symptoms. In 75% of the comparisons, the magnitude of the symptom improvement in responders was statistically significantly greater compared with nonresponders. This finding was consistent across all 4 studies, irrespective of the treatment applied, the patient demographics, and the severity or type of DED. This analysis demonstrates that a ≥3 severity grade improvement in corneal staining score is consistently associated with significant corresponding symptom improvement and may represent a clinically meaningful DED outcome measure for clinical studies and patient care. Proprietary or commercial disclosure may be found after the references.