Corneal staining: Beyond the grade

Grading of corneal fluorescein (NaFl) staining is routinely used in the diagnosis and treatment of dry eye disease (DED), Sjögren's Disease, and ocular Graft Versus Host Disease. It is also a critical outcome measure in clinical trials assessing treatments for these conditions. The current understanding of NaFl staining and grading in DED is reviewed, and a case is presented for re-examining and enhancing our methodologies. It is suggested that the current reliance on punctate staining and counting dots may not adequately reflect the extent and severity of corneal damage in DED. The appearance of corneal staining can change markedly over time, raising questions as to when the true "grade" should be assessed. NaFl corneal staining is compared to lissamine green to highlight differential staining. Attributes of NaFl corneal staining in DED, such as NaFl dye diffusion, patterns and sizes of punctate and coalescent staining, and corneal location and area are discussed. A mathematical model and method for measuring NaFl dye diffusion as a metric of corneal barrier dysfunction is presented, emphasizing the importance of NaFl dye diffusion in DED corneal heath assessment. A hypothetical mechanism for the progression of punctate to coalesced staining is presented and additional quantitative metrics that may enhance our understanding and aid in categorizing various types of DED and staining presentations are suggested. Further research is recommended to ensure that DED grading scales are based on the natural history and progression of NaFl staining in DED.