Abstract
Purpose :
We have previously shown that Neutrophil Extracellular Traps (NETs) are present on the ocular surface of oGVHD patients, contributing to inflammation and surface disease. Therefore, we performed a clinical trial using DNase eye drops to test the hypothesis that reducing the abundance of NETs from the ocular surface will reduce signs and symptoms of oGVHD.
Methods :
A prospective, phase I/II, randomized, placebo-controlled, double-masked clinical trial was performed to determine the safety and preliminary efficacy of DNase (0.1%) eye drops four times daily for eight weeks in patients with oGVHD (n=58). Intent-to-treat analysis was performed to determine the change in safety outcome measures (drug tolerability and proportion of adverse events) and efficacy outcome measures (Ocular Surface Disease Index [OSDI] score and corneal staining) between baseline and week 8.
Results :
Tolerability and adverse events were similar in the Vehicle and DNase groups. Within the DNase group (but not the Vehicle group), corneal staining showed a statistically significant and clinically meaningful reduction at week 8 (3.50 [2.75; 5.00]) compared to baseline (5.00 [3.00; 7.00]). The OSDI score also showed a statistically significant clinically meaningful reduction of 18.4 [9.16; 33.1] (p<0.001) at week 8 compared to baseline (45.5 [31.8; 50.0]) within the DNase group. The proportion of eyes that had improvement in Subjective global assessment (SGA) and mucous discharge was significantly greater in the DNase group (55.6% and 57.7% at weeks 4 and 8, respectively; p < 0.0001 at both time points) as compared to the Vehicle group (35.7% and 34.0% at weeks 4 and 8, respectively).
Conclusions :
Treatment of patients with oGVHD using DNase eye drops is safe and demonstrates preliminary efficacy. DNase eye drops can potentially reduce the severity of signs and symptoms of ocular surface disease in oGVHD patients.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.