Patients Enrichment for Increased Dendritiform Cells using in Vivo Confocal Microscopy Results in Improved Response to Topical Steroids in Dry Eye Disease: Results of the Therapeutic Response to Anti-inflammatory agents in the Corneal Epithelium (TRACE) study

Abstract

Purpose : Current dry eye disease (DED) management comprises short-term (2 week) topical steroid pulse induction therapy. However, this regimen, along with other therapies, does not always result in clinical improvement. In vivo confocal microscopy (IVCM) is a clinical tool that can assess and quantify immune/inflammatory cells associated with DED. The purpose of this study is to assess if enrichment of patients by IVCM for increased dendritiform cells (DCs) results in improved efficacy of topical anti-inflammatory therapy.

Methods : A prospective, double-masked, randomized controlled trial (n=67 eyes) was conducted at two clinical sites in 38 patients with DED. Eyes with central corneal DC density of >75cells/mm² ([calculated as density >2 SD above that of healthy cornea (32.0±24.4 cells/mm²)] were included. Patients were randomized into two arms: treatment arm (18 patients, n=31 eyes) received loteprednol etabonate (LE) 0.5% suspension, while controls (20 patients, n=36 eyes) received Soothe Tired Eyes Lubricant Eye Drops artificial tears (AT) for 6 weeks at 4x/day for 2 weeks, 2x/day for 2 weeks, and once daily for 2 weeks. Clinical response of signs and symptoms to treatment was assessed at baseline, 2 and 6 weeks (p<0.05 being significant).

Results : Mean±SD age of LE and AT arm was 57.22±12.07 and 55.35±15.58 years, respectively (p>0.05). Clinical and DC parameters were comparable at baseline (p>0.05 for all, except lissamine green staining). Corneal fluorescein staining decreased (mean difference±SD) from baseline in LE arm at 2 weeks (-1.48± 2.58, p=0.003) and 6 weeks (-1.22± 2.67, p=0.025) but not in the AT arm at 2 weeks (-0.56± 2.70, p=0.225) and 6 weeks (mean -0.36± 0.42, p=0.400). Mean(±SD) OSDI scores showed improvement in symptoms in LE arm from baseline [53.53±29.7) at 2 weeks (44.9±6.29, p=0.015) and 6 weeks (45.12±28.91, p=0.006), but not in the AT arm [34.46±20.33 at baseline, 33.16±23.55 at 2 weeks (p=0.109) and 36.05±23.30 at 6 weeks (p=0.478)].

Conclusions : Long-term topical steroids demonstrate increased treatment efficacy, if used in DED population that has been enriched with increased DCs using IVCM. Our study highlights the utility of IVCM in DED as an adjunct tool for patient enrichment or treatment stratification.

This abstract was presented at the 2019 ARVO Annual Meeting, held in Vancouver, Canada, April 28 - May 2, 2019.