Abstract:
Purpose: Inflammation plays a key role in the development and propagation of dry eye disease (DED). Clinically confirming the presence of inflammation to justify anti-inflammatory therapy remains challenging. This study sought to explore levels of agreement between clinical tests of inflammation and the diagnostic utility of clinical markers of inflammation relative to laboratory markers.
Methods: Participants (n=53), with or without DED, underwent clinical evaluation of inflammation via subjective and automated objective bulbar conjunctival hyperaemia assessment with clinical grading scales and the Oculus Keratograph 5M respectively; the InflammaDry® test; and the Tearcheck® Ocular Surface Inflammation Evaluation (OSIE®). Conjunctival impression cytology samples underwent droplet digital PCR to quantify gene copies of MMP-9, IL-8 and IL-1β. Inter and intra observer agreement in clinical grading was also evaluated, and the diagnostic utility of clinical inflammation tests and DED markers assessed relative to laboratory markers.
Results: Data suitable for laboratory analysis was obtained from 47 participants (79% female, median age 58 (22-82); 37 with DED). MMP-9 levels were positively associated with DED severity. Subjective and objective conjunctival hyperemia grading, and positive InflammaDry® outcomes were predictive of elevated MMP-9 levels (all p<0.05). Of the DED diagnostic markers and subclassification tests, tear film stability (with diagnostic cut off of <5.7 s), symptom scores (with cut offs of >9 for DEQ-5 and >33.3 for OSDI), and a thin lipid layer (grade ≤ 2) best predicted elevated MMP-9 (p<0.05). Elevated IL-8 and IL-1 levels could not be predicted from clinical tests. Clinical grading scales were confirmed not to be interchangeable based on the levels of agreement. The VBR-5 grading scale aligned most closely with objective hyperaemia grades.
Conclusion: Clinical ocular surface tests were poorly predictive of IL-8 and IL-1β levels, however clinical tests of inflammation were found to usefully predict elevated MMP-9 levels as an index of ocular surface inflammation. Results suggest some prediction was possible from clinical testing, but there was limited agreement between test scores which indicates that current clinical tests of inflammation cannot be used interchangeably. More research is required to define diagnostic cut offs for use in guiding treatment in different subtypes of DED.