Promising new treatment for severe dry eye disease — clinical trial

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Participants in a phase I/II clinical trial of a new enzyme-based treatment for severe dry eye disease experienced reduced signs of disease and discomfort, according to a study. The trial compared eye drops containing a biosynthetic form of an enzyme called DNase with eye drops without the enzyme. DNase breaks up nucleic acid-based material on the surface of the eye.

“Participants in the trial who used the drops with DNase reported less eye discomfort and their corneas were healthier,” said Dr Sandeep Jain, professor of ophthalmology and visual sciences in the University of Illinois at Chicago College of Medicine and principal investigator of the clinical trial.

In dry eye disease, production of tears is dysregulated, and the cornea, the transparent outer layer of the eye, becomes inflamed. In severe dry eye disease, which often accompanies diseases such as Sjogren’s syndrome and ocular graft-versus-host disease, the inflammation in the corneal tissue can become extreme enough to cause disabling eye pain and sensitivity to light.

In previous research, Jain and colleagues discovered that strands of DNA form webs on the surface of eyes affected by severe dry eye disease. This material causes an inflammatory response that further irritates the eye. “In dry eye disease, several things happen,” Jain explained. “There is an increase in the number of white blood cells called neutrophils that gather on the surface of the eye. Neutrophils release DNA which forms webs on the cornea called neutrophil extracellular traps, which cause inflammation of the ocular surface and attract additional neutrophils in a vicious cycle.”

Normally, enzymes present in tears chop up and clear DNA and other debris on the cornea, but in patients with dry eye disease, there is not enough DNase to clear the material.

In the randomised, placebo-controlled phase I/II clinical trial, Jain and colleagues enrolled 47 participants with severe dry eye disease. About half the participants had a diagnosis of Sjogren’s syndrome and 17% had graft-versus-host disease – both of which are associated with significant deficits in tear production. Forty-one participants completed the trial.

Participants were given eye drops containing either DNase or a placebo formulation and instructed to administer one drop of the solution to each eye four times per day for eight weeks. The researchers evaluated patients’ symptoms through questionnaires and measured the degree of corneal damage and amount of DNA webs and other pro-inflammatory material on the surface of the eye before and for the duration of the study.

The researchers found that participants in the DNase group had a statistically significant and clinically meaningful reduction in corneal damage at eight weeks compared with the placebo group. Questionnaire scores related to symptoms also reflected significant improvement among patients in the DNase group compared with placebo, who also had reduced amounts of corneal DNA webs and other material on the surface of the eye.

“The data from this early clinical trial suggests that DNase eye drops may be safe and effective for treating severe dry eye, and we look forward to conducting larger randomized trials to definitively prove its efficacy,” Jain said.

DNase is currently approved by the US Food and Drug Administration to treat cystic fibrosis. Its use for treating severe dry eye that doesn’t respond to other medications is still considered experimental by the FDA.

“The burden of severe dry eye is much greater than just having an occasional feeling of dryness,” Jain said. “It can severely compromise quality of life to the point of disability and can compromise a person’s vision. There are currently only two approved drugs to treat dry eye, and they don’t work for everyone, especially those with severe disease, so having a new drug that can treat the disease is very important.”

Abstract
Purpose: To determine whether DNase eye drops have the potential to reduce signs and symptoms of dry eye disease (DED).
Methods: A placebo-controlled, randomized clinical trial was performed to compare the safety and efficacy of DNase eye drops 0.1% four times a day for 8 weeks in patients with severe tear deficient DED. The change in safety outcome measures (drug tolerability and proportion of adverse events) and efficacy outcome measures (Ocular Surface Disease Index [OSDI] score, corneal and conjunctival staining) were analyzed between baseline and week 8.
Results: Tolerability and adverse events were similar in placebo group and DNase group. Within the DNase group (but not placebo group), corneal staining showed a statistically significant and clinically meaningful reduction at week 8 compared with baseline. The OSDI score also showed a significant median reduction of 27.3 at week 8 compared with baseline within the DNase group. The median reduction in corneal staining and mucoid debris/strands was significantly greater in the DNase group as compared with the placebo group. In the DNase group, the median reduction in OSDI (−20.75) was more than placebo group (−8.43); however, the difference between groups was borderline significant.
Conclusions: In this pilot study, treatment of severe tear deficient DED patients with DNase eye drops appears safe, well tolerated, and has the potential to reduce the severity of signs and symptoms.

Authors
Christine Mun, Shilpa Gulati, Sapna Tibrewal, Yi-Fan Chen, Seungwon An, Bayasgalan Surenkhuu, Ilangovan Raju, Morgan Buwick, Anna Ahn, Ji-Eun Kwon, Nour Atassi, Anubhav Pradeep, Damiano Rondelli, Sandeep Jain

University of Illinois at Chicago material
Translational Vision and Science Technology abstract


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