Corneal Staining Improvement via NEI Scale Linked to DED Symptom Improvement

The analyses included patients with different dry eye subtypes and severity, studies tested different treatments and conducted in different geographical regions; yet all showed a consistent pattern of better symptom improvements in corneal fluorescein staining responders. This suggests that the observed association between an improvement in corneal staining score ≥ three grades and symptom improvement can be generalizable. Photo: Scott G. Hauswirth, OD. Click image to enlarge.  Corneal staining using fluorescein dye is the most frequently performed clinical test in eye care to diagnose and manage dry eye disease (DED). Researchers and clinicians like it because it’s reliable and objective. In fact, the corneal staining score has been proposed as the primary objective outcome measure to assess the efficacy of dry eye treatments. Can staining be used as a proxy for patient symptomology as a way of removing some ambiguity from that subjective assessment? A recent study published in Ophthalmology assessed the correlations between corneal punctate erosions and patient-reported symptoms and aimed to define “corneal staining responder” as a physician-measured and clinically meaningful DED outcome to be used in clinical studies and patient care. Its analysis demonstrated that an improvement in corneal staining score ≥ three grades using the National Eye Institute (NEI) scale was associated with significant corresponding DED symptom improvement. The study researchers noted that this finding may represent a meaningful physician-measured endpoint for clinical studies and patient care independent of the nature of the disease or treatment used.Overall, 1,704 adult patients with evaporative or aqueous-deficient DED participated in four large-scale randomized controlled studies that evaluated two different dry eye medications (a water-free cyclosporine 0.1% solution and perfluorohexyloctane ophthalmic solution). They evaluated the corneal punctate epithelial erosions using fluorescein and graded the staining score according to the NEI scale (zero to 15). “Corneal staining responder” was defined as ≥ three-grade improvement from baseline, based on published literature and expert opinion. Patient symptoms were assessed using the visual analog scale (zero to 100).In all four studies, corneal staining responders showed a numerically greater improvement in all assessed dry eye symptoms compared to non-responders. Overall, 36 comparisons were performed involving 14 different symptoms. In 75% of the comparisons, the magnitude of the symptom improvement in responders was statistically significantly greater compared to non-responders. This finding was consistent across all four studies, irrespective of the treatment applied, patient demographics and the severity or type of dry eye.“The magnitude of difference (about five units) between responder and non-responder for measures of dryness/ocular discomfort is in the same range as seen for previously FDA-approved products compared to their vehicles, suggesting that the level of difference is meaningful,” the researchers noted in their paper.On the other hand, a smaller improvement in corneal fluorescein staining ( ≥ two grades) was not associated with such a consistent effect on symptomatology, supporting the study’s tentative threshold definition of ≥ three severity grades as a clinically relevant response.Click here for the journal source. Akpek EK, Sheppard JD, Krösser S. Corneal staining responder analysis: a clinically meaningful dry eye outcome. Ophthalmology. July 24, 2025. [Epub ahead of print].This article was developed by the editorial staff in conjunction with experts in the field. In the process, AI may have been among the editorial tools used to meet the goals of human editors, who approved all content.