ONSET-1 Phase 2b Randomized Trial to Evaluate the Safety and Efficacy of OC-01 (Varenicline Solution) Nasal Spray on Signs and Symptoms of Dry Eye Disease.

PURPOSE: The purpose of this trial was to evaluate the safety and efficacy of OC-01 (varenicline solution), a nicotinic acetylcholine receptor agonist nasal spray, on signs and symptoms of dry eye disease. METHODS: A phase 2b, multicenter, randomized, double-masked, vehicle-controlled trial (ONSET-1; NCT03636061) was performed. Patients were aged 22 years or older with a physician's diagnosis of dry eye disease and previous use of artificial tears were randomized 1:1:1:1 to control (vehicle nasal spray twice daily [BID]), OC-01 0.006 mg BID, OC-01 0.03 mg BID, and OC-01 0.06 mg BID. The primary end point was the change in the anesthetized Schirmer test score from baseline to day 28 in the study eye. The secondary end points included the change in the eye dryness score from baseline to day 28. RESULTS: One hundred eighty-two patients were randomized. After 28 days, patients who received OC-01 0.03 or 0.06 mg showed a statistically significant improvement in tear film production relative to vehicle, with least squares mean differences from vehicle of 7.7 mm [95% confidence interval, 3.8-11.7; P < 0.001] with OC-01 0.03 mg and 7.5 mm (95% confidence interval, 3.4-11.6; P < 0.001) with OC-01 0.06 mg. Patients receiving OC-01 0.03 mg showed a significant reduction in the eye dryness score by day 28 versus vehicle (P = 0.021); those receiving the OC-01 0.06 mg dose showed a nonsignificant reduction versus vehicle. OC-01 administration was associated with sneezing (62%-84%) and cough (9%-25%); these were transient and predominantly mild in severity. CONCLUSIONS: OC-01 nasal spray administered BID at 0.03 and 0.06 mg resulted in significant improvements in signs and symptoms of dry eye disease, was well tolerated, and warrants further clinical investigation.

A Water-free 0.1% Cyclosporine A Solution for Treatment of Dry Eye Disease: Results of the Randomized Phase 2B/3 ESSENCE Study.

PURPOSE: To assess the efficacy, safety, and tolerability of a topical water-free cyclosporine A formulation (CyclASol 0.1% ophthalmic solution) in comparison with vehicle for the treatment of dry eye disease (DED). METHODS: Three hundred twenty-eight patients were enrolled in this prospective, 12-week, multicenter, randomized, double-masked, confirmatory, vehicle-controlled clinical study. After a 2-week run-in period, eligible DED patients were randomized 1:1 to either CyclASol 0.1% or vehicle twice daily. The primary efficacy endpoint was change from baseline in total corneal fluorescein staining (National Eye Institute scale), and the second hierarchical primary efficacy endpoint was change from baseline in the Ocular Surface Disease Index score, both at 4 weeks. Secondary efficacy and safety assessments included conjunctival lissamine green staining (Oxford scale), visual analog scales for dry eye symptoms, and adverse event. RESULTS: Treatment with CyclASol 0.1% was superior to vehicle in the primary endpoint: total corneal fluorescein staining at week 4 (Δ -0.8; 95% confidence interval, -1.3 to -0.4; P = 0.0002, analysis of covariance). This difference had already reached statistical significance after 2 weeks and was maintained throughout the study. The study did not statistically meet its second hierarchically tested primary endpoint: Ocular Surface Disease Index score (P = 0.2634). However, CyclASol 0.1% treatment showed statistically significant improvement compared with that of vehicle in the eye dryness score at week 4 (Δ -4.783; 95% confidence interval, -9.129 to -0.438; P = 0.0311). CONCLUSIONS: CyclASol 0.1% was effective in treating signs and symptoms of DED. It significantly reduced corneal and conjunctival staining and improved ocular dryness compared with vehicle. CyclASol 0.1% was safe and showed excellent tolerability.

Postoperative povidone-iodine prophylaxis in strabismus surgery.

PURPOSE: While antibiotic/steroid combinations are routinely administered during the first week after strabismus surgery, they can be costly and inconvenient and may be unnecessary. This study compares the use of single-dose 5% povidone-iodine drops versus a week-long course of antibiotic/steroid as a prophylaxis against postoperative infection in extraocular muscle surgery. METHODS: Retrospective chart review was performed of 1871 patients undergoing routine strabismus surgery. Patients received either a single application of 5% povidone-iodine solution to the operative eye(s) at the conclusion of the surgical procedure or a week-long course of topical antibiotic/steroid. Postoperative records were then reviewed to identify abnormalities or complications occurring during the first 2 months after surgery. RESULTS: Complete documentation was found for 1603 patients. Single-dose povidone-iodine prophylaxis was used in 953 cases (59.5%), and a postoperative course of topical antibiotic/steroid combination was used in 650 cases (40.5%). Of the 1603 cases, possible infection occurred in 46 patients (2.87%). Of the 46 possible infections, 20 (3.08%) occurred in 650 patients on an antibiotic/steroid combination and 26 (2.83%) occurred in the 953 patients treated with single-dose povidone-iodine prophylaxis. This difference was not statistically significant (p = 0.6815). No cases of orbital cellulitis or endophthalmitis occurred in either group. CONCLUSIONS: Single-dose povidone-iodine is an inexpensive alternative to postoperative antibiotic/steroid prophylaxis following routine strabismus surgery performed through a fornix incision. Patients who had reoperations and limbal incisions were more likely to have complicated postoperative courses: antibiotic/steroid use in these groups may be beneficial.