New tear formulation provides additional option for ocular surface disease

May 1, 2008

Carboxymethylcellulose 0.5% with compatible solutes (CMC-solutes) (Optive, Allergan), a new artificial tear formulation, when used with topical cyclosporine 0.05% (Restasis, Allergan) in patients with ocular surface disease, improved the objective signs and subjective symptoms of the disease when compared with the patients' previously used artificial tears.

Key Points

Minneapolis-Carboxymethylcellulose 0.5% with compatible solutes (CMC-solutes) (Optive, Allergan), a new artificial tear formulation, when used with topical cyclosporine 0.05% (Restasis, Allergan) in patients with ocular surface disease, improves the objective signs and subjective symptoms of dry eye when compared with the patients' previously used artificial tears, according to David Hardten, MD.

The CMC-solutes formula contains two molecular weights of CMC, which results in a solution with a viscosity that is thicker than some other artificial tear formulations. But it is not as thick as a gel.

"The enhanced viscosity is designed to increase retention on the ocular surface and extend the immediate lubricating and moisturizing benefits of the product," said the investigators. They reported their findings in Current Medical Research and Opinion (2007;23:2083-2091).

Topical cyclosporine 0.05% is the only ophthalmic medical solution that has received FDA approval for the treatment of chronic dry eye. It addresses the inflammatory component of dry eye and results in increased production of the patients' natural tears, said Dr. Hardten, director, refractive surgery services, Minnesota Eye Consultants, and adjunct associate professor of ophthalmology, University of Minnesota, Minneapolis. The drug does this by inhibiting T lymph cells, increasing goblet cells, and increasing the expression of aquaporin-3 in the conjunctiva, he said.

Because those two products exhibited previously proven therapeutic effects, Dr. Hardten and colleagues theorized that "the increased retention of the lubricant of CMC-solutes and the addition of compatible solutes may improve the signs and symptoms of ocular surface disease in patients already using cyclosporine and other artificial tears."

For the prospective study, the authors enrolled 19 patients (average age, 56.4 years) with dry eye who were being treated with cyclosporine 0.05% for a minimum of 3 months and who had used other tear products simultaneously. The other tear products were discontinued, and the patients were given CMC-solutes and continued with their topical cyclosporine 0.05%. No patient took antihistamine or anticholinergic drugs. Patients were instructed to use CMC-solutes as needed but at least twice daily.

Patients were examined at baseline and 1 and 3 months after the start of the study. Testing included tear break-up time, corneal and conjunctival fluorescein staining, conjunctival lissamine green staining, and Schirmer testing.

The patients also completed Ocular Surface Disease Index (OSDI) and lubricant satisfaction questionnaires. The OSDI questionnaire used a scale of 0 to 4 to rate ocular discomfort caused by dryness; a score of 0 indicated no dry eye symptoms, and a score of 4 indicated that dry eye symptoms were exhibited all the time for multiple items.

Patients also were asked to rate the effectiveness of the drops and about other factors, such as limitations of activities, symptoms, emotions, and quality of life.

At each time point, patients were asked whether they complied with the treatment regimen and if they tolerated the drops.

Study findings

Most patients (58%) had been using 0.4% polyethylene glycol 400 (PEG-400)/0.3% propylene glycol/hydroxypropyl (HP)-guar (Systane, Alcon Laboratories) prior to the start of the study. Other tear products used included 0.5% CMC (Refresh Tears, Allergan), 21%; preservative-free 0.4% PEG-400/0.3% propylene glycol (Systane PF, Alcon), 5%; 0.6% glycerin/0.6% propylene glycol (Soothe, Bausch & Lomb) and 0.4% PEG-400/0.3% propylene glycol/HP-guar, 5%; 1% glycerin/1% polysorbate 80 (Refresh Endura, Allergan), 5%; and 0.25% PEG-400 (Blink, Advanced Medical Optics), 5%.

Only one patient missed one follow-up visit at month 1. No adverse treatment effects were reported. All patients were compliant with the study regimen.

Dr. Hardten reported improvements in lissamine green staining from 3.4 at baseline to 1.9 by month 3 (p = 0.004) and tear break-up time from 4.6 seconds at baseline to 5.3 seconds after treatment (p = 0.049). The OSDI scores also improved from 16.2 at baseline to 11.5 at month 3 (p = 0.007), and improvement was seen as early as month 1. Patients rated their ocular discomfort as 2.7 at baseline and 2.3 at month 3 (p = 0.049).

The results of Schirmer testing did not change significantly from baseline to month 3.

When asked about their preferences, the investigators reported, "At month 1, 61% of the patients said they liked CMC-solutes better than previous drops, and 83% said they liked CMC-solutes as much as or better than previous drops. At month 3, 63% said they preferred CMC-solutes to previous drops, and 89% said they liked CMC-solutes as much as or better than previous drops. All patients said CMC-solutes provided similar or improved relief of symptoms of dry eye compared with previous eye drops."

Dr. Hardten said, "This study showed that using CMC-solutes tears (Optive) was able to make further improvement in the signs and symptoms of dry eye patients in what most of the time we thought was pretty good treatment already-the use of cyclosporine and an over-the-counter artificial tear product. Some patients may benefit from changing their lubricant from their current product to a tear with compatible solutes like [CMC-solutes]."