Recombinant Deoxyribonuclease I Eye Drops for Ocular Graft Versus Host Disease: Results of a Randomized Clinical Trial.
Journal
Eye & contact lens
ISSN: 1542-233X
Titre abrégé: Eye Contact Lens
Pays: United States
ID NLM: 101160941
Informations de publication
Date de publication:
23 Feb 2024
23 Feb 2024
Historique:
accepted:
07
12
2023
medline:
26
2
2024
pubmed:
26
2
2024
entrez:
26
2
2024
Statut:
aheadofprint
Résumé
We have previously shown that neutrophil extracellular traps (NETs) are present on the ocular surface of patients with ocular graft versus host disease (oGVHD), contributing to inflammation and surface disease. Therefore, we performed a clinical trial using deoxyribonuclease I (DNAase) eye drops to test the hypothesis that reducing the abundance of NETs from the ocular surface will reduce signs and symptoms of oGVHD. A prospective, phase I or II, randomized, placebo-controlled, double-masked clinical trial was performed to determine the safety and preliminary efficacy of DNAase (0.1%) eye drops four times daily for 8 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. Tolerability and adverse events were similar in the vehicle and DNAase groups. Within the DNAase 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 with 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 with baseline (45.5 [31.8; 50.0]) within the DNAase group. The proportion of eyes that had improvement in subjective global assessment (SGA) and mucous discharge was significantly greater in the DNAase group (55.6% and 57.7% at weeks 4 and 8, respectively; P<0.0001 at both time points) as compared with the vehicle group (35.7% and 34.0% at weeks 4 and 8, respectively). Treatment of patients with oGVHD using DNAase eye drops is safe and demonstrates preliminary efficacy. Deoxyribonuclease I eye drops can potentially reduce the severity of signs and symptoms of ocular surface disease in patients with oGVHD.
Identifiants
pubmed: 38407974
doi: 10.1097/ICL.0000000000001078
pii: 00140068-990000000-00182
doi:
Banques de données
ClinicalTrials.gov
['NCT02702518']
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : CSR NIH HHS
ID : R24EY032440
Pays : United States
Organisme : CSR NIH HHS
ID : R01EY024966
Pays : United States
Organisme : CSR NIH HHS
ID : P30EY001792
Pays : United States
Organisme : CSR NIH HHS
ID : UL1TR002003
Pays : United States
Informations de copyright
Copyright © 2024 Contact Lens Association of Ophthalmologists.
Déclaration de conflit d'intérêts
S. Jain, MD: Consultant, Ocugen, Inc., Neutrolis, Inc., GlaxoSmithKline; Stock Ownership, Advaite Inc., Selagine Inc.; Patent application, UIC. Other authors have no funding or conflicts of interest to disclose.
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