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Gary Jerkins,1 Jack V Greiner,2,3 Louis Tong,4– 6 Jacqueline Tan,7 Joseph Tauber,8 Ali Mearza,9,10 Sruthi Srinivasan11 1Advancing Vision Research, LLC, Nashville, TN, USA; 2Clinical Eye Research of Boston, Boston, MA, USA; 3Department of Ophthalmology, Harvard Medical School, Boston, MA, USA; 4Singapore National Eye Center, National University of Singapore, Singapore; 5Singapore Eye Research Institute, Singapore; 6Duke-National University of Singapore Medical School, Singapore; 7University of New South Wales, Sydney, NSW, Australia; 8Tauber Eye Center, Kansas City, MO, USA; 9Imperial College Healthcare NHS Trust, London, UK; 10Ophthalmic Consultants of London, London, UK; 11Alcon Research, LLC, Johns Creek, GA, USACorrespondence: Gary JerkinsAdvancing Vision Research, LLC, Nashville, TN 37205, USATel +1 615-502-2871Fax +1 615-915-1825Email drjeyeguy@garyjerkins.comPurpose: The aim of this study was to compare the efficacy of two lipid-based lubricant eye drops in patients with lipid-deficient dry eye.Methods: This Phase IV, multicenter, prospective, double-masked study enrolled adults (aged ≥ 18 years) who had a tear film breakup time (TFBUT) of ≤ 15 seconds(s), and unanesthetized Schirmer I test of ≥ 3 mm to ≤ 12 mm in at least one eye, at both screening and baseline visits. Eligible patients (n=231) were randomized (1:1) and received either Systane® Balance (SYSB; n=117) or Refresh® Optive Advanced (RFO-Ad, n=114), four-times a day, for 35 days. The primary endpoint was non-inferiority for change from baseline in TFBUT at Day 35 (non-inferiority was established if the lower limit of the 95% confidence interval (CI) for the difference between the treatment groups was > – 1.0 s); secondary endpoints (test of superiority) were change in TFBUT and global ocular discomfort visual analog scale (VAS) score at Day 35. Other endpoints included the impact of dry eye on everyday life (IDEEL) treatment satisfaction scores (inconvenience and effectiveness) and safety.Results: At Day 35, the mean change from baseline in TFBUT was 0.998 s in the SYSB and 0.868 s in the RFO-Ad groups with a treatment difference: 0.130 s; (95% CI − 0.34, 0.60; P< 0.0001) demonstrating non-inferiority of SYSB to RFO-Ad. The global ocular discomfort VAS scores improved in both groups, with a mean change from baseline of – 9.7 and – 8.8 in SYSB and RFO-Ad groups (treatment difference – 0.8; P=0.62), respectively. No meaningful difference was observed in IDEEL treatment effectiveness and treatment inconvenience scores between SYSB vs RFO-Ad (P> 0.05 for treatment difference). Both treatments were well tolerated.Conclusion: SYSB lubricant eye drops were non-inferior to RFO-Ad for improvement in TFBUT in patients with lipid-deficient dry eye. Both lubricant eye drops improved TFBUT and ocular discomfort scores in patients with lipid-deficient dry eye.Keywords: dry eye, lipid-deficient, evaporative dry eye, lubricant eye drops, non-inferiority

Gary W Jerkins,1 Guruprasad R Pattar,2 Shane R Kannarr3 1Advancing Vision Research, Nashville, TN, USA; 2The Eye Care Institute, Louisville, KY, USA; 3Kannarr Eye Care, Pittsburg, KS, USACorrespondence: Gary W JerkinsAdvancing Vision Associates, 4306 Harding Pike, Nashville, TN 37205, USATel +1 615 502-2871Email drjeyeguy@garyjerkins.comAbstract: Keratoconjunctivitis sicca (KCS) is a multifactorial disease characterized by tear hyperosmolarity, inflammation, and ocular surface damage. Cyclosporine A (CsA) is used as an effective disease-modifying agent to improve the signs and symptoms of KCS by reducing inflammation, which interferes with tear production. This review provides an overview of efficacy, safety, and limitations of currently marketed topical CsA formulations—including CsA ophthalmic emulsion, cationic nanoemulsion, and aqueous nanomicelles—and highlights newer technologies for controlled ocular delivery of CsA and their clinical implications. Long available emulsion formulations of CsA are oil-based and have several limitations, including slow onset of efficacy and low intraocular penetration and bioavailability. Aqueous CsA nanomicelle carriers produce rapid improvement in objective signs of KCS such as corneal and conjunctival staining as early as 4 weeks and have acceptable safety profiles. CsA formulations using semifluorinated alkanes or polyaphrons are currently in clinical development, having recently completed Phase 2 studies. Other carriers for CsA currently in the preclinical phase include microemulsions, polymeric aqueous and lyophilized micelles, and hydrogels; these novel formulations have yet to undergo clinical trials. Formulations that improve tissue availability of CsA may be beneficial in clinical practice by providing faster onset of relief and improving patient adherence.Keywords: cyclosporine A, keratoconjunctivitis sicca, emulsion, nanomicelles, OTX-101

Pharmacogenetic (PGx) testing is a tool to identify patients at a higher risk of adverse events or treatment failure. The concern for unwanted side effects can limit medication adherence, particularly in children and adolescents. We conducted a pragmatic study to evaluate the acceptability and feasibility and gather pilot data on the utility of PGx testing in a child and adolescent psychiatry clinic. Both physicians and families participated in the study and answered pre-survey and post-survey questionnaires to examine their attitudes toward PGx testing. Patients were randomized into implementation (N = 25) and control groups (N = 24) and underwent PGx testing at the beginning or end of the study, respectively. Clinical consult notes with genotype-guided recommendations were provided to physicians for their consideration in clinical decisions. Patient-reported symptom severity and antidepressant-related side effects were assessed at baseline and for 12 weeks. Both participating physicians and families agreed that PGx testing is a useful tool to improve medication selection. The time from sample collection to having PGx test results was ~ 10 days and 15 days to having consult notes available, which may have impaired test utility in clinical decision making. There were no differences in any clinical end point between the implementation and control arms; however, there were higher antidepressant side effect scores for CYP2D6 poor and intermediate metabolizers after the eighth week of treatment. Our findings revealed benefits and pitfalls with the use of PGx testing in the real-world clinical setting, which may inform the methodology of a larger trial focused on outcomes., (© 2020 The Authors. Clinical and Translational Science published by Wiley Periodicals LLC on behalf of the American Society for Clinical Pharmacology and Therapeutics.)

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.).