Water-free cyclosporine eye drops a promising treatment for dry eye disease

Individuals with moderate-to-severe dry eye disease (DED) appear to obtain marked symptomatic improvements with a water-free cyclosporine 0.1% eye solution, according to the results of a phase III vehicle-controlled study from China.

After 29 days of treatment, the primary endpoint of the change from baseline in total corneal fluorescein staining (tCFS) was significantly greater among participants who received the cyclosporine eye drops than among those who received vehicle (−4.8 vs −3.0; difference, −1.8, 95 percent confidence interval [CI], −2.7 to −1.0; p<0.001). [JAMA Ophthalmol 2024;doi:10.1001/jamaophthalmol.2024.0101]

Meanwhile, the co-primary endpoint of dryness score on a visual analogue scale (VAS) decreased in both treatment groups, with no significant difference (−19.2 vs −15.4; difference, −3.8, 95 percent CI, −9.2 to 1.6; p=0.17).

“Cyclosporine is a highly hydrophobic molecule with large molecular weight, and the unique anatomy and physiology features of the eye further complicate the delivery of cyclosporine to the eye. The EyeSol delivery platform was developed to overcome this barrier,” the investigators explained, adding that the enhanced delivery allows cyclosporine to maintain its high bioavailability without compromising visual function. [Eur J Pharm Biopharm 2017;117:14-28]  

On the other hand, the vehicle already has low surface tension, enabling it to coat the ocular surface easily without triggering reflexes such as blinking and tearing that would wash the solution away, the investigators continued.

“The vehicle itself markedly alleviates symptoms and signs of DED, which partly explained why the between-group difference in dryness score did not reach statistical significance,” they said.

Study details

The study included participants with moderate-to-severe DED 206 (mean age 47.8 years, 90 percent women, 98.1 percent Han Chinese). Following a 14-day run-in period with an artificial tear, these participants were randomly assigned to receive treatment with water-free cyclosporine (n=103) or vehicle (n=103), with one drop administered to each eye twice daily for 29 days. After the treatment, participants in both groups were given the option to receive water-free cyclosporine for an additional 12 weeks for longer-term safety assessment.

At baseline, the mean tCFS score overall was 12.2, while the mean VAS dryness score overall was 73.0. The baseline characteristics were well balanced between groups.

Results for most secondary endpoints favoured cyclosporine over vehicle. Participants in the cyclosporine group showed significantly greater improvements in tCFS at week 15 (–4.0 vs –2.8; p=0.01), in central CFS at day 29 (–1.0 vs –0.6; p=0.01), total conjunctival staining at day 29 (–1.4 vs –0.8; p=0.003), and blurred vision at day 29 (–9.2 vs –2.8; p=0.01).

“After an additional 12-week treatment with cyclosporine, tCFS and dryness scores continued to improve,” the investigators said.

“In an ad hoc analysis, tCFS responders irrespective of treatment demonstrated higher improvements in various symptoms per the VAS at day 29 than nonresponders (Δ ranged from −0.2 to −9.4), and the improvement between responders and nonresponders reached nominal significance in frequency of dry eye, blurred vision, fluctuating vision, difficulty in reading, difficulty in looking at screens, and awareness of dry eye,” they added.

In terms of safety, treatment-related adverse events (TEAEs) were reported in 15 participants (14.6 percent) in the cyclosporine group and 11 participants (10.7 percent) in the vehicle group during the 29-day treatment. Over the 12-week follow-up duration, TEAEs were documented in 26.3 percent and 23.1 percent of participants in the respective treatment groups. None of the participants discontinued study treatment due to TEAEs or experienced serious TEAEs.