The randomized placebo controlled phase I/II clinical trial compares eye drops containing a biosynthetic form of the enzyme DNase to eye drops without the enzyme in human subjects with severe dry eye disease; DNase breaks up nucleic acid based materials on the surface of the eye as production of tears is dysregulated in dry eye disease. Dysregulated production of tears leads to the cornea becoming inflamed, with severe dry eye disease inflammation in corneal tissue can become extreme enough to cause disabling eye pain and sensitivity to light.
“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 the University of Illinois at Chicago and principal investigator of the clinical trial.
Strands of DNA form webs on the surface of the eyes affected by severe dry eye disease, this material causes an inflammatory response that further irritates the eye; typically enzymes present in tears would clear debris on the cornea, but in those with the disease there is not enough DNase to clear the materials due to dysregulated production of tears.
“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.”
47 patients with severe dry eye were enrolled to participate in the trial, close to half of which had been diagnosed with Sjogren’s syndrome, and 17% had graft versus host disease; 41% of the enrolled participants completed the trial.
Participants were either given a placebo formulation or a DNase formulation and were instructed to administer one drop of solution to each eye 4 times a day for 8 week; patient symptoms were evaluated through questionnaires along with measurements of the degree of corneal damage and amount of DNA webs as well as other proinflammatory materials that were on their eyes surface before and during the study.
Those in the DNase group were found to have statistically significant and clinically meaningful reduction in corneal damage at 8 weeks; questionnaires scores related to symptoms reflected significant improvement; and amounts of corneal DNA webs and other materials on the surface of the eye were also reduced.
“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.“The burden of severe dry eye is much greater than just having an occasional feeling of dryness. 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.”
The US FDA has previously approved DNase to treat cystic fibrosis; use for treating severe dry eye not responsive to other medications is still considered to be experimental by the FDA, which will hopefully change pending further positive results from additional studies.
