Recombinant Deoxyribonuclease I (DNase) Eye Drops for Ocular Graft vs Hosts Disease (oGVHD): Results of a Randomized Clinical Trial

Abstract

Purpose : We have previously shown that Neutrophil Extracellular Traps (NETs) are present on the ocular surface of oGVHD patients and they contribute 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 compare the safety and preliminary efficacy of DNase (0.1%) eye drops four times a day for 8 weeks in patients with oGVHD (n=51). Available data and intent-to-treat analyses were performed to determine the change in safety outcome measures (drug tolerability and proportion of adverse events) and efficacy outcome measures (OSDI score and corneal staining) between baseline and week 8. The clinical trial was performed under a IND assigned by the FDA and a protocol approved by UIC IRB.

Results : Tolerability and adverse events were similar in Vehicle group and DNase group. Within the DNase group (but not 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 significant median 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. Proportion of eyes that had improvement in Subjective global assessment (SGA) and mucous discharge were 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). Proportion of eyes that had improvement on CGI at week 8 were significantly greater in the DNase group (94.2%; p < 0.0001) as compared to the Vehicle group (22.0%).

Conclusions : Treatment of patients with oGVHD using DNase eye drops is safe and demonstrates a preliminary efficacy. DNase eye drops have the potential to reduce the severity of signs and symptoms of ocular surface disease in oGVHD patients.

This is a 2021 ARVO Annual Meeting abstract.