The impact of Demodex blepharitis on patient symptoms and daily life.

SIGNIFICANCE: Patients with Demodex blepharitis have a considerable symptomatic burden that negatively impacts their daily activities and well-being. Despite chronic manifestations of and problems associated with blepharitis that resulted in multiple visits to eye care providers, Demodex blepharitis remained underdiagnosed or misdiagnosed. PURPOSE: This study aimed to evaluate the effect of Demodex blepharitis on patients' daily activities and well-being. METHODS: This prospective, multicenter, observational study recruited 524 patients with Demodex blepharitis from 20 U.S. ophthalmology and optometry practices. Demodex blepharitis was diagnosed based on the presence of the following clinical manifestations in at least one eye: >10 collarettes on the upper lashes, at least mild lid margin erythema of the upper eyelid, and mite density of ≥1.0 mite/lash (upper and lower combined). Patients were asked to complete a questionnaire related to their symptoms, daily activities, and management approaches. RESULTS: The proportion of patients who experienced blepharitis symptoms for ≥2 years was 67.8%, and for ≥4 years, it was 46.5%. The three most bothersome symptoms ranked were "itchy eyes," "dry eyes," and "foreign body sensation." Overall, 77.4% of patients reported that Demodex blepharitis negatively affected their daily life. One-third (32.3%) of patients had visited a doctor for blepharitis at least two times, including 19.6% who visited at least four times. Despite having clinical manifestations of Demodex blepharitis confirmed by an eye care provider, 58.7% had never been diagnosed with blepharitis. Commonly used management approaches were artificial tears, warm compresses, and lid wipes. Among those who discontinued their regimen, 45.9% had discontinued because of either tolerability issues or lack of effectiveness. Among contact lens wearers, 64.3% of the patients either were uncomfortable wearing contact lenses or experienced vision changes "sometimes" or "frequently." CONCLUSION: Demodex blepharitis results in a significant negative impact on daily activities, creating a psychosocial and symptomatic burden on patients.

Efficacy and Safety of the Melanocortin Pan-Agonist PL9643 in a Phase 2 Study of Patients with Dry Eye Disease.

Purpose: The melanocortin receptor pan-agonist PL9643, a potential therapy for ocular diseases, was investigated in a phase 2, 12-week study in patients with dry eye disease (DED). Methods: This was a placebo-controlled study evaluating efficacy and safety of thrice-daily PL9643. Placebo (vehicle) was similar to tears. Primary endpoints were intra-patient changes in inferior corneal fluorescein staining and ocular discomfort after 12 weeks. Secondary endpoints were changes in additional DED signs or symptoms. Multiple secondary endpoints were not adjusted for multiplicity. Patients with moderate or severe DED were analyzed in addition to the overall intent-to-treat (ITT) population. Results: In the ITT population (n = 160) the PL9643 group did not demonstrate significant treatment difference versus placebo at week 12/day 85 for the primary endpoints (P > 0.05). In patients with moderate or severe DED (n = 53), PL9643 treatment demonstrated either nominally significant (P < 0.05) or trending (P < 0.1) improvement over placebo in mean change from baseline at week 12/day 85 in several sign endpoints, including fluorescein staining in inferior, superior, corneal sum, and total sum regions; Lissamine Green staining in temporal, nasal, conjunctival sum, and total sum regions; and tear film breakup time. Conjunctival redness also showed (nonsignificant) improvement at week 12/day 85. There were no drug-related adverse events (AEs) and no drug-related discontinuations. Conclusions: PL9643 showed no significant efficacy for the ITT population; however, efficacy results across several signs and symptoms in the subpopulation of moderate to severe DED patients, the low number of ocular AEs, and no tolerability issues suggest that PL9643 shows promise as a therapeutic for DED. Clinical Trial Registration number: NCT04268069.

Lotilaner Ophthalmic Solution 0.25% for Demodex Blepharitis: Randomized, Vehicle-Controlled, Multicenter, Phase 3 Trial (Saturn-2).

PURPOSE: To evaluate the safety and efficacy of lotilaner ophthalmic solution 0.25% compared with vehicle for the treatment of Demodex blepharitis. DESIGN: Prospective, randomized, double-masked, vehicle-controlled, multicenter, phase 3 clinical trial. PARTICIPANTS: Four hundred twelve patients with Demodex blepharitis were assigned randomly in a 1:1 ratio to receive either lotilaner ophthalmic solution 0.25% (study group) or vehicle without lotilaner (control group). METHODS: Patients with Demodex blepharitis treated at 21 United States clinical sites were assigned either to the study group (n = 203) to receive lotilaner ophthalmic solution 0.25% or to the control group (n = 209) to receive vehicle without lotilaner bilaterally twice daily for 6 weeks. Collarettes and erythema were graded for each eyelid at screening and at all visits after baseline. At screening and on days 15, 22, and 43, 4 or more eyelashes were epilated from each eye, and the number of Demodex mites present on the lashes was counted with a microscope. Mite density was calculated as the number of mites per lash. MAIN OUTCOME MEASURES: Outcome measures included collarette cure (collarette grade 0), clinically meaningful collarette reduction to 10 collarettes or fewer (grade 0 or 1), mite eradication (0 mites/lash), erythema cure (grade 0), composite cure (grade 0 for collarettes as well as erythema), compliance with the drop regimen, drop comfort, and adverse events. RESULTS: At day 43, the study group achieved a statistically significant (P < 0.0001) higher proportion of patients with collarette cure (56.0% vs. 12.5%), clinically meaningful collarette reduction to 10 collarettes or fewer (89.1% vs. 33.0%), mite eradication (51.8% vs. 14.6%), erythema cure (31.1% vs. 9.0%), and composite cure (19.2% vs. 4.0%) than the control group. High compliance with the drop regimen (mean ± standard deviation, 98.7 ± 5.3%) in the study group was observed, and 90.7% of patients found the drops to be neutral to very comfortable. CONCLUSIONS: Twice-daily treatment with lotilaner ophthalmic solution 0.25% for 6 weeks generally was safe and well tolerated and met the primary end point and all secondary end points for the treatment of Demodex blepharitis compared with vehicle control. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Real-World Use of Loteprednol Etabonate 0.5%/Tobramycin 0.3% Ophthalmic Suspension for the Treatment of Ocular Surface Inflammatory Conditions.

Purpose: Use of a combination corticosteroid/antibiotic product is common in ocular surface inflammatory conditions for which corticosteroid therapy is indicated and there exists a risk of superficial bacterial infection. Combination loteprednol etabonate 0.5% and tobramycin 0.3% (LE/T) has been evaluated for blepharokeratoconjunctivitis in two trials, but there has been limited reporting on its real-world use. Patients and Methods: This was a retrospective chart review conducted at three optometry practices in the USA. Data were collected from cases in which LE/T was used and data were recorded for the period commencing with therapy with a minimum of one follow-up visit (within 2 months). Data abstracted included patient demographics, diagnosis, LE/T dosing regimen, pre- and post-treatment ocular signs and symptoms, intraocular pressure (IOP) measurements, adverse event (AE) reports, visual acuity (VA), and any notations as to resolution of baseline condition. Primary outcomes of interest included IOP changes and AEs. Results: Ninety-six patient charts were extracted, and data from 87 charts (115 LE/T-treated eyes) were included. Mean (SD) years of age was 45.6 (19.7), most patients were white (83.9%), and just over half were female (58.6%). Common baseline conditions were conjunctival injury/corneal abrasion (25.3%), keratitis (18.4%), viral conjunctivitis (16.1%), and blepharitis/eyelid inflammation/MGD (11.5%). The most common LE/T dosing regimen was one drop QID. Mean (SD) IOP was 15.2 (4.4) mm Hg at baseline and 15.7 (4.4) mm Hg at the first follow-up visit (p = 0.2467). No AEs were recorded, and there were no significant changes in mean VA. Where recorded, most patients (83%) were noted as having their condition resolved/resolving at the first or second follow-up visit. Conclusion: LE/T appears to have a high level of safety when used for the management of various ocular surface inflammatory conditions encountered in optometric practice.

Efficacy and Safety of OC-01 (Varenicline Solution) Nasal Spray on Signs and Symptoms of Dry Eye Disease: The ONSET-2 Phase 3 Randomized Trial.

PURPOSE: To evaluate the efficacy and safety of OC-01 (varenicline solution) nasal spray for treatment of patients with dry eye disease. DESIGN: Randomized, multicenter, double-masked, vehicle-controlled, phase 3 study. PARTICIPANTS: Adults 22 years of age or older with a diagnosis of dry eye disease, artificial tear use, Ocular Surface Disease Index score of 23 or more, and Schirmer test score (STS) of 10 mm or less. Eligibility was not restricted by eye dryness score (EDS). METHODS: Patients (N = 758) were randomized in a 1:1:1 ratio to twice-daily treatment with 50-µl intranasal spray in each nostril of OC-01 0.03 mg (n = 260), OC-01 0.06 mg (n = 246), or vehicle (control; n = 252) for 4 weeks (ClinicalTrials.gov identifier, NCT04036292). MAIN OUTCOME MEASURES: The primary efficacy end point was the percentage of patients achieving a 10-mm improvement or more in STS at week 4. Secondary end points included change from baseline to week 4 in STS and EDS in a controlled adverse environment (CAE) chamber and in the clinic. Treatment-emergent adverse events (TEAEs) were assessed. RESULTS: A statistically significantly greater percentage of patients achieved the primary end point in both OC-01 treatment groups compared with the vehicle group (OC-01 0.03 mg, 47.3%; OC-01 0.06 mg, 49.2%; vehicle, 27.8%; P < 0.0001 for both doses). Change from baseline in STS at week 4 was statistically significantly greater for patients receiving OC-01 than vehicle (P < 0.0001 for both doses). Eye dryness score assessed at week 4 improved with OC-01 treatment compared with vehicle, although the difference was not significant for EDS measured in the CAE chamber and showed (nominal) significance in the clinic. Overall, 86.5% of patients (654/756) reported at least 1 TEAE during the treatment period; most were mild, nonocular (sneezing, cough, throat irritation, and instillation site irritation) and were reported by fewer patients in the vehicle group than in the OC-01 treatment groups (OC-01 0.03 mg, 97.3%; OC-01 0.06 mg, 99.2%; vehicle, 57%). CONCLUSIONS: OC-01 nasal spray was well tolerated and showed a clinically meaningful effect on signs and symptoms of dry eye disease.

In Vitro Antibiotic Resistance among Bacteria from the Cornea in the Antibiotic Resistance Monitoring in Ocular MicRoorganisms Surveillance Study.

PURPOSE: This study aimed to report on in vitro susceptibility patterns among corneal isolates collected in the Antibiotic Resistance Monitoring in Ocular micRoorganisms (ARMOR) study. METHODS: Each year, from 2009 to 2019, Staphylococcus aureus, coagulase-negative staphylococci (CoNS), Streptococcus pneumoniae, Pseudomonas aeruginosa, and Haemophilus influenzae isolates cultured from patients with ocular infections at participating ARMOR sites were submitted to a central laboratory for species confirmation and antibiotic susceptibility testing. In this analysis of corneal isolates, odds ratios for concurrent resistance were based on sample proportions, one-way ANOVA was used to evaluate resistance by patient age, and Cochran-Armitage tests were used to examine changes in antibiotic resistance over time. RESULTS: A total of 1499 corneal isolates were collected from 61 sites over the 11-year period. Overall, 34.5% (148 of 429) of S. aureus and 41.9% (220 of 525) of CoNS isolates were methicillin resistant and had higher odds ratios for concurrent resistance to azithromycin (17.44 and 5.67), ciprofloxacin (39.63 and 12.81), and tobramycin (19.56 and 19.95), respectively, relative to methicillin-susceptible isolates (P < .001, all); also, a high proportion of methicillin-resistant S. aureus (85.1%) and methicillin-resistant CoNS (81.8%) were multidrug resistant (at least three classes of antibiotics). Resistance among S. pneumoniae isolates was highest for azithromycin (33.1%), whereas P. aeruginosa and H. influenzae isolates demonstrated low resistance overall. Among staphylococci, antibiotic resistance differed by patient age (S. aureus: F = 6.46, P < .001; CoNS: F = 4.82, P < .001), and few small changes in resistance (≤3.60% per year), mostly decreases, were observed over time. CONCLUSIONS: Although rates of in vitro antibiotic resistance among presumed keratitis isolates obtained in ARMOR seemed stable between 2009 and 2019, resistance among staphylococci and pneumococci remains high (and should be considered when treating keratitis).