Purpose: Evaporation of the tear film is heavily discussed as one core reason for dry eye disease (DED). Subsequently, new artificial tear products are developed that specifically target this pathomechanism. Perfluorohexyloctane (F6H8, NovaTears®) from the family of semifluorinated alkanes is a novel substance that has been approved as a medical device, as a nonblurring wetting agent for the ocular surface.Methods: Thirty patients with hyperevaporative dry eye received F6H8 during a prospective, multicenter, observational 6-week study. Patients were advised to apply 1 drop 4 times daily in both eyes. Parameters assessed included best corrected visual acuity, intraocular pressure, Schirmer I test, tear fluid, tear film breakup time (TFBUT), corneal staining, meibum secretion, and Ocular Surface Disease Index (OSDI©).Results: From the 30 patients recruited, 25 completed the trial per protocol. Four patients discontinued F6H8 and 1 patient did not present for follow-up. F6H8 treatment led to significant reduction of corneal staining and significant increase of Schirmer I and TFBUT. In addition, OSDI score dropped significantly from a mean of 55 (±23.0) to 34 (±22.4). Visual acuity and ocular pressure did not change.Conclusions: This prospective observational study shows significant beneficial effects in patients suffering from evaporative DED, using F6H8 in all the relevant parameters tested. The decrease of the OSDI by a mean of 21 points was particularly remarkable and clearly exceeds minimal, clinical important differences for mild or moderate and severe disease. Overall, F6H8 (NovaTears) seems to be safe and effective in treating mild to moderate hyperevaporative DED.

To compare the efficacy, safety, and tolerability of waterfree cyclosporine formulation (CyclASol) at 2 concentrations (0.1% and 0.05% of cyclosporine [CsA]) to vehicle when applied twice daily for 16 weeks in patients with dry eye disease (DED). An open-label Restasis (Allergan, Irvine, CA) arm was included to allow a direct comparison with an approved therapy.Design: An exploratory phase II, multicenter, randomized, vehicle-controlled clinical trial, double-masked between CyclASol and vehicle with an open-label comparator.Participants: Two hundred and seven eligible patients with a history of dry eye disease were randomized 1:1:1:1 to 1 of 4 treatment arms (CyclASol 0.05%, n ¼ 51; CyclASol 0.1%, n ¼ 51; vehicle, n ¼ 52, and Restasis, n ¼ 53).Methods: After a 2-week run-in period with twice-daily dosing of Systane Balance (Alcon, Fort Worth, TX), patients were randomized to the respective treatment arm and dosed twice daily for 16 weeks.Main Outcome Measures: The study was set up to explore efficacy on a number of sign and symptom end points including total and subregion corneal fluorescein staining, conjunctival staining, visual analog scale (VAS) for dry eye symptoms VAS severity, and Ocular Surface Disease Index (OSDI) questionnaire.Results: CyclASol showed a consistent reduction in corneal and conjunctival staining compared with both vehicle and Restasis over the 16-week treatment period, with an early onset of effect (at day 14). A mixed-effects modelebased approach demonstrated that the CyclASol drug effect was statistically significant over vehicle (total corneal staining P < 0.1, central corneal staining P < 0.001, conjunctival staining P < 0.01). This model-based analysis suggests a significant CyclASol effect for OSDI as symptom parameter (P < 0.01). The numbers of ocular adverse events were low in all treatment groups.Conclusions: CyclASol showed efficacy, safety, and tolerability at 2 concentrations in moderate-to-severe DED. In a direct head-to-head against open-label Restasis, CyclASol was found to have an earlier onset of action, as early as after 2 weeks of treatment, in relieving the signs of DED, as measured by corneal and conjunctival staining. The central region of the cornea, an important area for visual function in dry eye sufferers, was shown to have the most benefit from treatment. Excellent safety, tolerability, and comfort profile supports this new CsA formulation as having a positive benefit-to-risk ratio.

Purpose: Meibomian gland disease is generally accepted as the leading cause for evaporative dry eye disease (DED). In a previous study, perfluorohexyloctane, a semifluorinated alkane, has been demonstrated to significantly increase tear film breakup time and to reduce corneal fluorescein staining in patients with evaporative DED, thereby vastly reducing dry eye-related symptoms. This study was set up to evaluate perfluorohexyloctane in a larger population of patients with Meibomian gland dysfunction.Methods: Seventy-two patients with Meibomian gland disease and associated dry eye received 1 drop of perfluorohexyloctane 4 times daily during an observational, prospective, multicenter, 6–8-week study. Clinical assessment included best-corrected visual acuity, intraocular pressure, Schirmer test I, tear film breakup time, anterior and posterior blepharitis assessment, number of expressible Meibomian glands, meibum quality and quantity, ocular surface fluorescein staining, lid margin and symptom assessment, and Ocular Surface Disease Index (OSDI©).Results: From the 72 patients recruited, 61 completed the trial per protocol. Nine patients did not apply the medication as recommended and 2 patients were lost to follow-up. Tear film breakup time, corneal and conjunctival fluorescein staining, number of expressible Meibomian glands, and severity of anterior and posterior blepharitis significantly improved after 6–8 weeks of perfluorohexyloctane application. In addition, symptoms improved as demonstrated by a significant decrease of OSDI-values from 37 (±13) to 26 (±16).Conclusions: In concordance with previous findings, 6–8 weeks of topical application of perfluorohexyloctane significantly improves clinical signs of Meibomian gland disease and associated mild to moderate DED.

This randomized, double-blind, placebo-controlled, 6-arm, parallel-design study investigated cardiac and hematological pharmacodynamic effects of ceralifimod (ONO-4641), a selective sphingosine-1-phosphate (S1P) receptor modulator, over a broad dose range in direct comparison with the nonselective S1P modulator fingolimod. Healthy subjects were assigned to ceralifimod (0.01, 0.025, 0.05, or 0.10 mg), fingolimod (0.5 mg), or placebo once daily for 14 days (n = 24 per group). After 14 days of treatment, mean absolute lymphocyte count percentage change from baseline was greatest in the fingolimod (-62%) and ceralifimod 0.10 mg (-56%) groups. On treatment cessation, lymphocyte recovery was faster in the ceralifimod versus the fingolimod group. Ceralifimod showed dose- and concentration-dependent chronotropic effect. Cardiac effects in the fingolimod group were dependent on fingolimod-P concentrations. Maximum mean heart rate (HR) effect on day 1 was larger with fingolimod (placebo-adjusted change from time-matched baseline HR [ΔΔHR], -14.9 beats per minute [bpm]) versus ceralifimod (ΔΔHR, -6.2 and -12.0 bpm for the 0.05- and 0.10-mg doses, respectively). Ceralifimod's effect on the PR interval was minor. Safety biomarker results suggest that potential therapeutic doses of ceralifimod, in particular the 0.05-mg dose, might result in reduced occurrence of bradycardia, atrioventricular block absolute lymphocyte count and grade 3/4 lymphopenia compared with fingolimod 0.5 mg.

The purpose of this mechanistic drug interaction study was to investigate the effects of ketoconazole on the pharmacokinetics of safinamide. Ketoconazole was applied as a potent prototypic inhibitor of cytochrome CYP3A4, to determine the role of CYP3A4 in the metabolic clearance of safinamide. In an open-label, randomized, two-period, two-sequence cross-over study, 14 healthy adult subjects (7 males/7 females) received two single doses of 100 mg safinamide: alone and on top of multiple doses of ketoconazole (200 mg b.i.d.) given over 6 days. Serial blood samples were collected over 240 h post dose to quantify safinamide parent drug and metabolite concentrations for pharmacokinetic evaluation. Safinamide exposure was essentially unchanged when administered with and without ketoconazole: C(max) and AUC(0-∞) point estimates (90% CIs) for the treatment comparison were 106.6 (101.0; 112.4) and 112.9 (109.8; 116.03), respectively. Similarly, ketoconazole did not influence the formation and clearance of safinamide metabolites to a clinically relevant extent. Overall, the study shows that CYP3A4 plays a minor role in the metabolism of safinamide in vivo. Therefore, safinamide can be administered together with potent CYP3A4 inhibitors without any requirement for dose adjustment.