Topical Anti-TNFα Agent Licaminlimab (OCS-02) Relieves Persistent Ocular Discomfort in Severe Dry Eye Disease: A Randomized Phase II Study.

Purpose: To assess the efficacy, safety, and pharmacokinetics of new topical ocular anti-TNFα antibody fragment licaminlimab in the relief of persistent ocular discomfort in severe dry eye disease (DED). Patients and Methods: Patients with ≥6-month history of DED, regular use of artificial tears, and best-corrected visual acuity (BCVA) of ≥55 letters in each eye (Early Treatment Diabetic Retinopathy Score) at baseline were included in this multicenter, randomized, vehicle-controlled, double masked study. A total of 514 patients were screened. After a 2-week run-in with Vehicle, all qualifying patients received Vehicle eye drops for 4 weeks. Patients with global ocular discomfort score ≥50 at the end of this 4-week period were randomized to receive licaminlimab (60 mg/mL ophthalmic solution) (69 patients) or Vehicle (65 patients) for 6 weeks. The primary efficacy endpoint was change from baseline in global ocular discomfort score at Day 29. Safety assessments included adverse events and ophthalmology examination including intraocular pressure (IOP). Serum licaminlimab levels were also determined. Results: Change from baseline to Day 29 in global ocular discomfort score was statistically significantly greater for licaminlimab than for Vehicle (p = 0.041). No safety issues were identified. Serum licaminlimab was undetectable in most patients; the maximum concentration observed was 8.47 ng/mL. Conclusion: Topical ocular licaminlimab demonstrated statistically significant improvement in global ocular discomfort score compared to Vehicle in patients with severe DED, with good tolerability, no increase in IOP, and minimal systemic drug exposure.

Effect of OTX-101, a Novel Nanomicellar Formulation of Cyclosporine A, on Corneal Staining in Patients With Keratoconjunctivitis Sicca: A Pooled Analysis of Phase 2b/3 and Phase 3 Studies.

BACKGROUND: Keratoconjunctivitis sicca affects 5% to 33% of the population and is often accompanied by symptoms such as burning and dryness. This pooled analysis evaluated total and central corneal fluorescein staining (CFS) in patients receiving OTX-101 0.09% or vehicle in phase 2b/3 and 3 studies and whether improvements in corneal staining correlated with improved visual acuity. METHODS: In these randomized, vehicle-controlled studies, patients received 1 drop of OTX-101 or vehicle in both eyes twice daily. Corneal staining was performed at baseline and days 28, 56, and 84. CFS was evaluated in each zone (0-to-4 scale); total corneal staining (0-to-20 scale per eye) was averaged over both eyes. Pooled safety assessments included adverse event monitoring. RESULTS: Mean baseline CFS total scores (SD) were 4.2 (2.5) and 4.3 (2.6) for the OTX-101 (n = 523) and vehicle (n = 525) groups, respectively. For total corneal staining, least squares mean changes from baseline (standard error) were -0.9 (0.08) versus -0.5 (0.08) for OTX-101 and vehicle, respectively (P = 0.0008), on day 28 and -1.4 (0.09) versus -0.9 (0.09) on day 84 (P = 0.0002). There was a significantly high correlation (P = 0.0117) between reduced central corneal staining and improved visual acuity on day 84. Treatment-related adverse events were mostly mild, with instillation site pain reported by 21.8% and 4.0% of patients receiving OTX-101 and vehicle, respectively. CONCLUSIONS: Treatment with OTX-101 led to greater improvements versus vehicle in corneal surface staining as early as 4 weeks, and further improvements were seen up to 12 weeks. OTX-101 was well tolerated in patients with keratoconjunctivitis sicca.

Clinical Outcomes of Fixed Versus As-Needed Use of Artificial Tears in Dry Eye Disease: A 6-Week, Observer-Masked Phase 4 Clinical Trial.

Purpose: To evaluate the clinical effects of using fixed (four times daily [QID]) versus as-needed (PRN) dosing of an artificial tear product (polyethylene glycol/propylene glycol [PEG/PG]; Systane Ultra) in individuals with dry eye disease. Methods: In this prospective, multicenter, observer-masked, active-control, parallel-group trial, participants were randomized (1:2 allocation) to receive 1 drop of PEG/PG QID (n = 34) or PRN (n = 63) for 28 days. The primary endpoint was change from baseline in the total ocular surface staining (TOSS) score (according to the Oxford scale) at day 28. Results: At day 28, the change from baseline in least squares mean (LSM) TOSS scores for QID and PRN groups were -1.19 and -0.94, respectively (treatment difference [TD]: -0.26; 95% confidence interval [CI]: -∞ to 0.21; P = 0.184); superiority of QID versus PRN dosing was not established, as the upper limit of one-sided 95% CI for TD was not <0 (prespecified limit). At day 28, for QID and PRN groups, the LSM change from baseline in Impact of Dry Eye on Everyday Life (IDEEL) scores was symptom-bother, -7.0 and -2.94 (TD: -4.06, P = 0.037); treatment effectiveness, 2.43 and 0.16 (TD: 2.28, P = 0.278); and treatment-related inconvenience, -11.56 and -2.77 (TD: -8.8, P = 0.996), respectively. Incidence of adverse events was low (≤3.2%) in both the groups; no serious adverse events were reported. Conclusions: QID dosing of PEG/PG was not superior to PRN dosing in terms of ocular staining. The IDEEL symptom-bother score favored QID dosing, suggesting that regular use of artificial tears may provide better symptomatic relief than PRN use. (ClinicalTrials.gov number, NCT02446015.).

Impact of Dry Eye Disease on Work Productivity, and Patients' Satisfaction With Over-the-Counter Dry Eye Treatments.

PURPOSE: To assess the effect of dry eye disease on work productivity and performance of non-work-related activities, and patients' satisfaction with over-the-counter (OTC) dry eye treatments. METHODS: In this prospective, noninterventional, cross-sectional study, conducted at 10 U.S. optometry/ophthalmology practices, 158 symptomatic dry eye patients naïve to prescription medication underwent standard dry eye diagnostic tests and completed Work Productivity and Activity Impairment (WPAI) and Ocular Surface Disease Index (OSDI) questionnaires. Use of OTC dry eye medication, and satisfaction with OTC medication and symptom relief were also assessed. RESULTS: On average, dry eye resulted in loss of 0.36% of work time (∼5 minutes over 7 days) and ∼30% impairment of workplace performance (presenteeism), work productivity, and non-job-related activities. Presenteeism and productivity impairment scores showed significant correlation with OSDI total (r = 0.55) and symptom domain (r = 0.50) scores, but not with dry eye clinical signs. Activity impairment score showed stronger correlation with OSDI total (r = 0.61) and symptom domain (r = 0.53) scores than with clinical signs (r ≤ 0.20). Almost 75% of patients used OTC dry eye medication. Levels of patient satisfaction with OTC medication (64.2%) and symptom relief from OTC (37.3%) were unaffected by administration frequency (≥3 vs. ≤2 times daily). CONCLUSIONS: Dry eye causes negligible absenteeism, but markedly reduces workplace and non-job-related performances. Impairment of work performance is more closely linked to dry eye symptoms than to clinical signs. Patients' perceptions of OTC dry eye medication tend to be more positive than their perceptions of symptom relief.

Conjunctival concentrations of a new ophthalmic solution formulation of moxifloxacin 0.5% in cataract surgery patients.

PURPOSE: To compare the conjunctival concentrations of moxifloxacin after instillation of a single drop of moxifloxacin ophthalmic solution, 0.5% (Moxi) or a new 0.5% ophthalmic solution formulation (MAF) containing a retention-enhancing agent in patients undergoing cataract surgery. METHODS: This was a randomized, double-masked, parallel-group study. One hundred thirty patients scheduled for routine phacoemulsification and intraocular lens implantation were randomized to both treatment and post-dose sample collection time points. A single topical drop of Moxi or MAF was instilled in the study eye. At the designated time (0.25, 0.5, 1, 3, or 5 h post-dose), 2 conjunctival biopsy samples were obtained (N = 11-13 per treatment condition). Concentrations of moxifloxacin were determined using a validated ultra-performance liquid chromatography method. Moxifloxacin exposure [maximum mean moxifloxacin concentrations (C(max)) and area under the concentration-time curve (AUC)] was estimated from the observed concentration-time data. RESULTS: The conjunctival moxifloxacin C(max), 43.8 µg/g, for MAF was achieved at 0.25 h. This was 1.8-fold higher than the C(max) for Moxi (24.1 µg/g), which was reached at 0.5 h post-dose. MAF AUC(0-3) was significantly greater than the AUC(0-3) of Moxi [50.5 (µg·h)/g vs. 27.1 (µg·h)/g; P < 0.05]. The conjunctival moxifloxacin C(max) for MAF was 337- to 730-fold greater than the reported minimum inhibitory concentration (MIC(90)) values for Staphylococcus aureus, Streptococcus pneumoniae, and Haemophilus influenzae. The C(max):MIC(90) ratios for Moxi ranged from 185 to 402. Conjunctival AUC(0-24):MIC(90) ratios ranged from 777 to 1,683 for MAF and from 625 to 1,355 for Moxi. CONCLUSIONS: The new MAF ophthalmic formulation of moxifloxacin provided higher peak levels of moxifloxacin in the conjunctiva tissue, and larger total tissue exposure than the current, commercially available formulation. The superior penetration of MAF observed in this study could translate into greater eradication of bacteria.