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Mucin stimulator improves dry eye signs, symptoms
Rebamipide, a quinolinone derivative, promotes the production of mucins in goblet cells and corneal epithelial cells.
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A novel mucin-stimulating agent treated various objective and subjective symptoms of dry eye, according to a study.
The study authors elucidated the action of rebamipide, a quinolinone derivative that stimulates production of mucins in goblet cells and corneal epithelial cells.
“The most significant finding from this study was that rebamipide was effective for the treatment of dry eye in both objective signs and subjective symptoms,” Shigeru Kinoshita, MD, PhD, the corresponding author, said in an email interview with Ocular Surgery News. “It is noteworthy that 2% rebamipide showed significant improvements of all five dry eye-related ocular symptoms: foreign body sensation, dryness, photophobia, eye pain and blurred vision, compared to the placebo group in this study.”
Clinicians are increasingly aware of the role that mucins play in maintaining the aqueous layer, Kinoshita said.
“Recently, the role of ocular mucins has been attracting increased attention for the treatment of dry eye, because the mucin layer has an important function in retention of the aqueous layer, and its disruption may lead to further damage to the cornea-conjunctiva,” he said.
Shigeru Kinoshita
Mucins are secreted by goblet cells and the membranes of ocular surface epithelia, Kinoshita said.
“In dry eye, reduced goblet cell density and changes in mucin amount, distribution and glycosylation have been reported, and therapeutic improvements have reportedly occurred when mucin instillation is administered in patients with dry eye,” he said. “Since decreased mucin levels on the surface of the cornea and a decreased density of goblet cells have been observed in patients with dry eye, the mode of action of rebamipide is expected to be beneficial for this disease.”
Patients and methods
The randomized, double-masked, multicenter, placebo-controlled phase 2 clinical study, published in Ophthalmology, included 308 patients with a mean age of 55.2 years whose dry eye symptoms did not respond to conventional treatment and persisted for more than 20 months.
Patients were randomized to receive placebo or topical 1% or 2% rebamipide administered in each eye four times daily for 4 weeks.
The primary outcome measure was change in fluorescein corneal staining score from baseline to last observation carried forward. Secondary measures were lissamine green conjunctival staining score, tear film breakup time and Schirmer testing scores.
Secondary subjective measures were dry eye-related ocular symptoms, such as foreign body sensation, dryness, photophobia, ocular pain, blurred vision and patients’ overall treatment impression scores.
Patient selection was critical in terms of evaluating objective and subjective symptoms of dry eye, Kinoshita said.
“Dry eye is a multifactorial disease of the tears and ocular surface that results in symptoms of discomfort, visual disturbance and tear film instability with potential damage to the ocular surface,” he said. “Therefore, we selected the patients having symptoms of discomfort and visual disturbance (score of 2 or more for one or more dry eye-related ocular symptoms), tear film instability (unanesthetized Schirmer test value at 5 minutes of 5 mm or less) and damage of ocular surface (fluorescein corneal staining score of 4 or more and lissamine green conjunctival staining score of 5 or more) for this study.”
Outcomes and observations
Study results showed that a rebamipide dose response was seen in fluorescein corneal staining, lissamine green conjunctival staining and tear film breakup time scores.
“With regard to the objective signs, both 1% and 2% rebamipide groups were significantly more effective than placebo group in terms of the change from baseline to last observation carried forward for not only fluorescein corneal staining, but also lissamine green conjunctival staining and tear film breakup time scores,” Kinoshita said. “Rebamipide showed significant improvement of ocular damage, fluorescein corneal staining and lissamine green conjunctival staining scores compared to the placebo group in this study.”
However, there was no significant difference in baseline to last observation carried forward in Schirmer’s test values; no dose response was reported.
All five subjective symptoms of dry eye improved in the 1% and 2% rebamipide groups from baseline to last observation carried forward. However, photophobia symptoms did not improve in the 1% rebamipide group, the results showed.
“Although 1% and 2% rebamipide were both efficacious, 2% rebamipide may be more effective than 1% rebamipide,” Kinoshita said.
Results showed a statistically significant improvement in patients’ overall impressions of treatment in the 1% and 2% rebamipide groups (both P < .001).
Data showed that 64.1% and 54.9% of patients in the 1% and 2% rebamipide groups, respectively, and 28.1% of patients in the placebo group reported some improvement in dry eye symptoms. – by Matt Hasson