NOV03 for Signs and Symptoms of Dry Eye Disease Associated With Meibomian Gland Dysfunction: The Randomized Phase 3 MOJAVE Study.

PURPOSE: To evaluate the efficacy and safety of NOV03 (perfluorohexyloctane) ophthalmic drop for the treatment of signs and symptoms of dry eye disease (DED) associated with meibomian gland dysfunction (MGD). DESIGN: Randomized, double-masked, controlled trial. METHODS: Patients ≥18 years of age with a history of DED and signs of MGD were randomly assigned 1:1 to treatment with NOV03 or hypotonic saline (0.6%) 4 times daily for 8 weeks. The primary sign and symptom endpoints were change from baseline to week 8 in total corneal fluorescein staining (tCFS; National Eye Institute scale) and eye dryness score (0-100 visual analog scale), respectively. RESULTS: A total of 620 patients (NOV03, n = 311; saline, n = 309) were randomized and treated. Least-squares (LS) mean change from baseline to week 8 was statistically significantly greater for NOV03 compared with saline for both tCFS (-2.3 vs -1.1; LS mean treatment difference, -1.2 [95% confidence interval -1.7 to -0.8]; P < .001) and visual analog scale dryness score (-29.4 vs -19.2; LS mean treatment difference, -10.2 [95% CI -14.4 to -6.1]; P < .001), with statistically significant between-group differences observed as early as week 2. The incidence of ocular adverse events was similar for NOV03 (12.9%) and saline (12.3%). There were no serious adverse events and no adverse events leading to treatment discontinuation. CONCLUSIONS: In this randomized controlled trial of patients with DED associated with MGD, NOV03 significantly reduced both signs and symptoms of DED compared with hypotonic saline control. NOV03 was well tolerated, with an adverse event profile similar to that of saline.

OC-01 (Varenicline Solution) Nasal Spray Demonstrates Consistency of Effect Regardless of Age, Race, Ethnicity, and Artificial Tear Use.

Purpose: To evaluate OC-01 [varenicline solution nasal spray (VNS)] tear production and symptom outcomes in patients with dry eye disease by age, gender, race, ethnicity, and artificial tear use status. Patients and Methods: Adults ≥22 years of age diagnosed with dry eye disease, with Ocular Surface Disease Index score ≥23, corneal fluorescein staining score ≥2 in ≥1 region or ≥4 for all regions, and baseline Schirmer Test Score (STS) ≤10 mm, with no restrictions on eye dryness score (EDS). Efficacy was assessed using integrated data from ONSET-1 and ONSET-2 [vehicle control (VC), n=294; OC-01 VNS 0.03 mg, n=308]. Subgroups included age (≤55, 56-65, >65 years), gender (male, female), race (White, Black or African American), ethnicity (Hispanic or Latino, Not Hispanic or Latino), and artificial tear use (yes, no). Analysis of covariance models, with the covariates treatment, study site, and baseline severity measures, were used to calculate treatment-VC differences. Consistency of effect among subgroups was evaluated by conducting interaction tests. Results: Consistency of treatment effect across subgroups was observed for all endpoints, with P value for all treatment-subgroup interaction terms >0.05. For % of patients with ≥10mm improvement in STS and least squares (LS) mean change from baseline in STS and EDS, there was improvement in tear production across demographic group categories. Artificial tear use did not change STS or EDS outcomes with OC-01 VNS. Conclusion: OC-01 VNS improved tear production and patient-reported symptom outcomes across a broad range of patients by age, gender, race, and ethnicity, and regardless of artificial tear use status at baseline. OC-01 VNS demonstrated a consistent benefit across an extensive range of patients with dry eye disease.

Topical human recombinant nerve growth factor for stage 1 Neurotrophic Keratitis: Retrospective case series of cenegermin treatment.

Purpose: To report on the management and effectiveness of treating patients with stage I Neurotrophic Keratitis using an 8-week course of topical recombinant human nerve growth factor (rhNGF, cenegermin). Observations: In this retrospective case series, punctate epithelial erosions (PEE), best corrected visual acuity (BCVA) and corneal sensation were followed and documented from 2 to 12 months in patients treated as per the standard of care. Clinical outcomes including changes in PEEs, corneal sensation and BCVA are reported. Most patients also had preexisting thyroid disease. Conclusions: All patients had clinically significant improvements in PEE, and corneal sensation. Three of the four patients had a significant improvement in BCVA, one patient had no change in their pre-treatment visual acuity (BCVA 20/20) The four patients studied also reported decreased photophobia and improvements in their quality of life. This case series provides real-world evidence of the safety and efficacy of cenegermin treatment of stage I NK for all four patients.

Effect of Cyclosporine 0.09% Treatment on Accuracy of Preoperative Biometry and Higher Order Aberrations in Dry Eye Patients Undergoing Cataract Surgery.

PURPOSE: To determine the effect of topical cyclosporine 0.09% on ocular surface regularity and the predictive accuracy of preoperative corneal power measurements in patients undergoing cataract surgery. SETTING: Private practice. DESIGN: Open-label, multicenter, prospective study. METHODS: Seventy-five patients (75 eyes) who presented for cataract surgery evaluation with signs of dry eye disease were prescribed topical cyclosporine 0.09% for 28 days BID. Corneal curvature measurements, slit lamp exam, and Standardized Patient Evaluation of Eye Dryness (SPEED) questionnaire were evaluated at the initial and follow-up visits. Cataract surgery occurred 1 to 3 weeks after the second biometry visit. Refraction and corrected distance visual acuity measurements were performed 1-month post-surgery. The primary outcome was the difference in absolute prediction error of 1-month spherical equivalent refractive outcome before and after cyclosporine treatment. Secondary outcomes included the effect of topical cyclosporine 0.09% on ocular surface irregularity. RESULTS: Sixty-four patients completed the study. The absolute prediction error of 1-month spherical equivalent refractive outcome was 0.39 ± 0.30 D vs 0.33 ± 0.25 D (P < 0.03) before and after treatment, respectively. The proportion of eyes that achieved the target refraction was greater based on measurements after topical cyclosporine 0.09% than would have occurred using pre-treatment measurements. CONCLUSION: Cataract surgery patients with dry eye who are prescribed topical cyclosporine 0.09% BID for 28 days pre-surgery showed a statistically significant improvement in the prediction error of the spherical equivalent outcome of surgery. Other measures of dry eye severity showed significant improvements after treatment.

Visible Meibomian Gland Structure Increases After Vectored Thermal Pulsation Treatment in Dry Eye Disease Patients with Meibomian Gland Dysfunction.

PURPOSE: To assess the effect of vectored thermal pulsation treatment (VTP) on visible meibomian gland structure (VGS) in patients with meibomian gland dysfunction (MGD). SETTING: Private group practice (A.T.E.). DESIGN: Retrospective, single-blinded cohort study. METHODS: Visible meibomian gland structure was evaluated at baseline and at 1-year in treatment (30 patients, 48 eyes) and control (13 patients, 22 eyes) groups. Meibography images were captured using dynamic meibomian imaging. Images were assessed using a novel morphometric analysis technique and analyzed for change in area of VGS (pixels). Additional outcomes measured include tear break up time, corneal staining, tear osmolarity, matrix metalloproteinase-9 (MMP-9), meibography grading, and meibomian gland evaluation. RESULTS: As high as 69% of eyes in the treatment group showed an improvement in VGS versus 27% of eyes in the control group. As high as 31% of eyes in the treatment group showed a decline in VGS versus 73% of eyes in the control group. TBUT (p = 0.0001), corneal staining (p = 0.0063), and meibomian gland evaluation scores (p = 0.0038) all significantly improved after VTP treatment. However, SPEED scores, MMP-9, tear osmolarity, and meiboscale scores were not significantly improved 1-year post treatment. CONCLUSION: A morphometric analysis protocol of meibography provides clinically meaningful information that is undetectable with the standard semiquantitative method of grading meibomian gland structure. This is the first report indicating that gland structure may increase post-VTP relative to untreated controls, thus presenting significant implications regarding benefits and timing of VTP therapy. The described protocol is currently more appropriate for research than for clinical practice.

The Effect of Lifitegrast on Refractive Accuracy and Symptoms in Dry Eye Patients Undergoing Cataract Surgery.

PURPOSE: To determine the effect of lifitegrast ophthalmic solution 5% on improving the tear film, biometry/keratometry, and refractive accuracy for dry eye patients scheduled for cataract surgery. PATIENTS AND METHODS: Multicenter, prospective, open-label study of 100 eyes of 100 patients undergoing cataract surgery who had a confirmed diagnosis of dry eye. Patients underwent biometry at baseline and again after a 28-day course of lifitegrast 5% BID. Primary outcome was an improvement in the accuracy of preoperative anterior corneal power measurements at predicting postoperative spherical equivalent (SE) pre- and post-lifitegrast treatment. Secondary outcomes included changes in dry eye symptoms and corneal staining. RESULTS: The accuracy of the biometry readings for the achieved refractive SE: within 0.25 D in 47% and 50% of eyes before and after the initial lifitegrast treatment, respectively; within 0.5 D in 71% and 79% of eyes before and after the initial lifitegrast treatment; and within 0.75 D in 81% and 91% of eyes before and after the initial lifitegrast treatment (p < 0.04). CONCLUSION: Lifitegrast 5% significantly improved preoperative corneal surface measurement accuracy in patients with confirmed dry eye who were scheduled for cataract surgery.

Improving Tolerance and Compliance with Topical Immunomodulators Using Micro-Emulsion Lipid Layer Artificial Tears.

PURPOSE: To investigate the efficacy of a micro-emulsion (ME) lipid layer artificial tear in improving tolerance of immunomodulator eye drops for the treatment of dry eye disease. PATIENTS AND METHODS: A total of 33 patients with previously diagnosed dry eye disease were given the micro-emulsion lipid layer artificial tear in conjunction with either lifitegrast or cyclosporine. Patients were queried on their tolerance of the regimen by reporting VAS scores before starting the adjunctive eye drop, immediately after starting, and 2-3 weeks later. Tolerance was statistically compared over time and with respect to previous medication compliance, timing of the adjunctive eye drop, age, gender, and ethnicity. RESULTS: Across all patients, the VAS pre-treatment score (6.8 ± 0.6) was significantly higher than both the VAS 1-day post ME lipid tear instillation time point (3.0 ± 0.7) (post hoc Bonferroni, p < 0.001) and the VAS 2-3-week post instillation time point (1.7 ± 0.7) (post hoc Bonferroni, p < 0.001), with the mean VAS score improving over time (post hoc Bonferroni, p < 0.028). Average VAS scores did not vary with respect to specific medical therapy or the timing of instillation of this artificial tear. Both the "at-risk" and "conversion" groups independently had significant improvements at both 1-day and 2-3-week time points compared to baseline. CONCLUSION: The micro-emulsion lipid layer artificial tear was effective as an adjunctive eye drop to improve tolerance of lifitegrast and cyclosporine for patients with dry eye disease who were at risk of failing or had previously failed immunomodulatory therapy.

Meibomian gland dysfunction patients with novel Sjögren's syndrome biomarkers benefit significantly from a single vectored thermal pulsation procedure: a retrospective analysis.

PURPOSE: To measure the effects from a single vectored thermal pulsation treatment of the meibomian glands on dry eye signs and symptoms in patients who tested positively versus negatively for novel Sjögren's syndrome (SS) biomarkers. METHODS: The retrospective study included the deidentified data of 102 eyes of 59 patients with dry eye and meibomian gland dysfunction (MGD), who were also tested for novel biomarkers for SS and underwent a single 12-minute LipiFlow thermal pulsation procedure. All patients were already being treated with individualized dry eye therapy but remained symptomatic. Meibomian gland secretion (MGS) scores, Standard Patient Evaluation of Eye Dryness (SPEED) questionnaire scores and tear breakup times (TBUTs) before and 8 weeks after thermal pulsation treatment were analyzed. RESULTS: Twenty-three patients tested positive for novel biomarkers of SS and 36 patients tested negative. At baseline, MGS, SPEED and TBUT of both SS-positive and SS-negative patients were equivalent. At 8 weeks' post-treatment, mean MGS score, SPEED and TBUT were 13.0±7.8, 12.5±6.8 and 9.6±4.6, respectively, in SS-positive patients and 15.9±7.9, 10.0±6.3 and 8.3±4.6, respectively, in SS-negative patients (P<0.001). While the post-treatment MGS was significantly better in SS-negative patients than SS-positive (P=0.021), no significant difference between post-treatment SPEED and TBUT was observed between the two groups (P>0.05). CONCLUSION: LipiFlow treatment in MGD patients who were SS-positive for novel biomarkers of SS demonstrated improvement in signs and symptoms of dry eye. While improvement in MGS scores in SS-negative patients was higher than that observed in SS-positive patients, SPEED and TBUT were equivalent between these two groups.

Effect of Oral Re-esterified Omega-3 Nutritional Supplementation on Dry Eyes.

PURPOSE: To assess the effect of oral re-esterified omega-3 fatty acids on tear osmolarity, matrix metalloproteinase-9 (MMP-9), tear break-up time (TBUT), Ocular Surface Disease Index (OSDI), fluorescein corneal staining, Schirmer score, meibomian gland dysfunction (MGD) stage and omega-3 index in subjects with dry eyes and confirmed MGD. METHODS: This was a multicenter, prospective, interventional, placebo-controlled, double-masked study. Subjects were randomized to receive 4 softgels containing a total of 1680 mg of eicosapentaenoic acid/560 mg of docosahexaenoic acid or a control of 3136 mg of linoleic acid, daily for 12 weeks. Subjects were measured at baseline, week 6, and week 12 for tear osmolarity, TBUT, OSDI, fluorescein corneal staining, and Schirmer test with anesthesia. MMP-9 testing and omega-3 index were done at baseline and at 12 weeks. RESULTS: One hundred five subjects completed the study. They were randomized to omega-3 (n = 54) and control group (n = 51). Statistically significant reduction in tear osmolarity was observed in the omega-3 group versus control group at week 6 (-16.8 ± 2.6 vs. -9.0 ± 2.7 mOsm/L, P = 0.042) and week 12 (-19.4 ± 2.7 vs. -8.3 ± 2.8 mOsm/L, P = 0.004). At 12 weeks, a statistically significant increase in omega-3 index levels (P < 0.001) and TBUT (3.5 ± 0.5 s vs. 1.2 ± 0.5 s, P = 0.002) was also observed. Omega-3 group experienced a significant reduction in MMP-9 positivity versus control group (67.9% vs. 35.0%, P = 0.024) and OSDI scores decreased significantly in omega-3 (-17.0 ± 2.6) versus control group (-5.0 ± 2.7, P = 0.002). CONCLUSIONS: Oral consumption of re-esterified omega-3 fatty acids is associated with statistically significant improvement in tear osmolarity, omega-3 index levels, TBUT, MMP-9, and OSDI symptom scores.

Visual and Refractive Outcomes of a Toric Presbyopia-Correcting Intraocular Lens.

Purpose. To evaluate outcomes in astigmatic patients implanted with the Trulign (Bausch + Lomb) toric presbyopia-correcting intraocular lens (IOL) during cataract surgery in a clinical practice setting. Methods. Retrospective study in 40 eyes (31 patients) that underwent cataract extraction and IOL implantation in a procedure using intraoperative wavefront aberrometry guidance (ORA system). Endpoints included uncorrected visual acuity (VA), reduction in refractive cylinder, accuracy to target, axis orientation, and safety. Results. At postoperative month 1, refractive cylinder was ≤0.50 D in 97.5% of eyes (≤1.00 D in 100%), uncorrected distance VA was 20/25 or better in 95%, uncorrected intermediate VA was 20/25 or better in 95%, and uncorrected near VA was 20/40 (J3 equivalent) or better in 92.5%. Manifest refraction spherical equivalent was within 1.00 D of target in 95% of eyes and within 0.50 D in 82.5%. Lens rotation was <5° and best-corrected VA was 20/25 or better in all eyes. Conclusion. The IOL effectively reduced refractive cylinder and provided excellent uncorrected distance and intermediate vision and functional near vision. Refractive predictability and rotational stability were exceptional. Implantation of this toric presbyopia-correcting IOL using ORA intraoperative aberrometry provides excellent refractive and visual outcomes in a standard of care setting.

Effect of tear osmolarity on repeatability of keratometry for cataract surgery planning.

PURPOSE: To evaluate the effects of tear osmolarity on the repeatability of keratometry (K) measurements in patients presenting for cataract surgery. SETTING: Three clinical practices. DESIGN: Observational prospective nonrandomized study. METHODS: Subjects were prospectively recruited based on tear osmolarity (Tearlab Osmolarity System); that is, osmolarity more than 316 mOsm/L in at least 1 eye (hyperosmolar) and osmolarity less than 308 mOsm/L in both eyes (normal). The baseline K value was measured, and a second measurement was taken on the same instrument (IOLMaster) within 3 weeks of the first. Variability in average K, calculated corneal astigmatism using vector analysis, and intraocular lens (IOL) sphere power calculations were compared between groups. RESULTS: The hyperosmolar group (50 subjects) had a statistically significantly higher variability in the average K reading (P = .05) than the normal group (25 subjects) and a statistically significantly higher percentage of eyes with a 1.0 diopter (D) or greater difference in the measured corneal astigmatism (P = .02). A statistically significantly higher percentage of eyes in the hyperosmolar group had an IOL power difference of more than 0.5 D (P = .02). No statistically significant differences were present when the subjects were grouped by self-reported dry eye. CONCLUSIONS: Significantly more variability in average K and anterior corneal astigmatism was observed in the hyperosmolar group, with significant resultant differences in IOL power calculations. Variability was not significantly different when subjects were grouped by self-reported dry eye. Measurement of tear osmolarity at the time of cataract surgery planning can effectively identify patients with a higher likelihood of high unexpected refractive error resulting from inaccurate keratometry. FINANCIAL DISCLOSURE: Drs. Epitropoulos, Matossian, Berdy, and Malhotra received compensation from Tearlab for participating in the study. No author has a financial or proprietary interest in any material or method mentioned.

A pilot comparison of phospolipidated lutein to conventional lutein for effects on plasma lutein concentrations in adult people.

BACKGROUND: The percent absorption of lutein from supplements falls well below that from lutein enriched egg yolk, a rich source of phospholipids. Therefore, a supplement of lutein plus phospholipids was tested for effects on serum accumulation. METHODS: A 10 day supplementation with a solid-lipid particle (SLP) lutein complex or conventional lutein ester was done in apparently healthy people (both supplement types taken with fat containing meals). Plasma lutein was measured pre- and post-supplementation as well as 7 days after supplementation stopped. Changes within each supplement group were analyzed by paired t-test; group comparisons were done by unpaired t-test. RESULTS: The solid-lipid particle complex lutein gave much higher plasma lutein values than conventional lutein ester. The lutein complex showed superior effects based on absolute mean value after 10 days of supplementation, change in value from baseline to 10 days, and value at 7 days after supplement discontinuation. CONCLUSIONS: A solid lipid lutein complex strongly increased plasma lutein levels compared to a conventional form.

Evaluation of a New Controlled Point Source LED Glare Tester for Disability Glare Detection in Participants With and Without Cataracts.

PURPOSE: To determine glare-induced change during visual acuity testing in patients with and without cataract using the controlled point source light-emitting diode (LED) glare tester (EpiGlare Tester; Epico, LLC, Columbus, OH), a new medical device for identification of glare disability. METHODS: This prospective, multicenter study enrolled 40 patients (80 eyes with cataracts) and 49 control subjects (98 eyes without cataracts). Corrected distance visual acuity (CDVA) was measured with and without glare using the EpiGlare Tester as a glare source. Functional visual ability was evaluated using driving and glare subscales from the Refractive Status Vision Profile questionnaire. The primary efficacy measure was change in CDVA measurement with and without glare in patients with senile cataract compared to participants without cataract. Secondary efficacy measures included correlation of the CDVA change caused by functional glare disability and subjective patient and investigator assessments. RESULTS: CDVA reduction was greater for patients with cataract, with a mean reduction of -0.49 ± 0.3 logMAR, than for participants without cataracts at -0.13 ± 0.2 logMAR (P < .001). This equates to a 5-line Snellen reduction (0.49 logMAR) in patients with cataracts and a 1-line reduction (-0.13 logMAR) in patients without cataracts. Among patients with cataracts, 83% stated the device accurately represented the difficulty experienced while driving at night (P < .001); among participants without cataracts, 71% reported being minimally affected by glare from the device (P = .003). CONCLUSIONS: A new controlled point source LED glare tester demonstrated the adverse effect on visual acuity due to glare in patients with cataract, accurately simulated night driving glare issues for patients with cataracts, and was rated as easy to use and useful by investigators.

Axial length measurement acquisition rates of two optical biometers in cataractous eyes.

PURPOSE: To compare the ability of two optical biometers to acquire the axial length (AL) measurement in cataractous eyes. METHODS: This prospective, comparative, single-center study comprised 105 eyes (63 patients). AL was acquired by the composite mean value of 20 measurements (composite-20 IM) and five measurements (composite-5 IM) (IOLMaster(®) 500 version 7.1 software), and the standard mean value of the first five measurements (standard-5 LS, Lenstar LS 900(®)). Anterior chamber depth (ACD) and average keratometry (K) readings were acquired. RESULTS: AL was acquired in 83.8%, 92.4%, and 84.8% of eyes for the composite-5 IM, composite-20 IM, and standard-5 LS, respectively. Standard-5 LS AL measurements were significantly shorter (P<0.001). IOLMaster(®) 500-acquired ACD (corneal epithelium to lens) measurements were significantly shorter (P<0.001). IOLMaster(®) 500 average K measurements were significantly steeper (P<0.001). CONCLUSION: The composite-20 IM had the highest AL acquisition success rate of the three versions evaluated. AL, ACD, and average Ks were statistically different between the two biometers, although the differences were clinically insignificant.