Does Dry Eye Disease Severity Impact Efficacy of Varenicline Solution Nasal Spray on Sign and Symptom Treatment Outcomes?

SIGNIFICANCE: There is a clinical necessity for dry eye disease treatments that perform across a broad range of presenting patient severities. Varenicline solution nasal spray (VNS), a unique cholinergic agonist ocular surface-sparing nasal spray therapy, demonstrated significant improvement in both signs and symptoms of dry eye disease in subjects with mild, moderate, and severe symptoms as the clinical studies enrolled a more real-world patient population. PURPOSE: This study evaluated efficacy outcomes for VNS in patients with mild-moderate and severe dry eye disease. METHODS: An analysis of integrated data from two randomized clinical trials, ONSET-1 (NCT03636061) and ONSET-2 (NCT04036292) (vehicle control [VC], n = 294; VNS 0.03 mg, n = 308), was performed. Adults 22 years or older with dry eye disease, Ocular Surface Disease Index score of ≥23, corneal fluorescein staining score of ≥2 in ≥1 regions/≥4 all regions, and Schirmer Test Score (STS) of ≤10 mm (no restrictions on Eye Dryness Score [EDS]) were included in this study. Efficacy was evaluated using analysis of covariance among pre-specified subgroups of mild-moderate and severe baseline disease severity defined by STS (≤5 vs. >5) and EDS (<60 vs. ≥60). Consistency of effect was evaluated by interaction tests. RESULTS: No treatment-subgroup interactions were observed for all end points ( P > .05). The odds of achieving a ≥10-mm improvement in STS for VNS versus VC for patients with baseline STS ≤5 and >5 were 3.4(95% confidence interval, 2.0 to 5.6) and 2.3(1.3 to 4.0) and for EDS of <60 and ≥60 were 3.4(1.9 to 6.1) and 2.5(1.5 to 4.0). Least-squares mean treatment/VC differences in change from baseline in EDS for patients with baseline STS ≤5 or >5 were -7.4(95% confidence interval, -12.5 to -2.4) and -2.8(-8.7 to 3.1); EDS of <60 and ≥60 were -2.9(-8.3 to 2.5) and -8.1(-13.6 to -2.6). CONCLUSIONS: Compared with VC, VNS improved tear production and patient-reported symptoms in patients with dry eye disease, demonstrating consistency of effect regardless of initial presenting severity.

Psychosocial Impact of Demodex Blepharitis.

Purpose: To evaluate the impact of Demodex blepharitis on patients' daily activities and quality of life. Patients and Methods: In this multicenter, observational, prospective, IRB-approved study, 311 Demodex blepharitis patients aged ≥18 years were included. Demodex blepharitis was diagnosed based on the presence of ≥1.0 mite per lash (upper and lower eyelids combined), >10 collarettes on the upper lashes, and at least mild lid margin erythema of the upper eyelid in at least one eye. All patients were asked to complete a questionnaire about their symptoms, daily activities, quality of life, and management approaches, and descriptive statistics were used to analyze the responses. Results: More than half the patients had been experiencing symptoms of blepharitis for ≥4 years. The three most frequent and bothersome symptoms experienced by patients were dry eyes, itchiness, and irritation. Nearly half the patients (47%) responded that they were conscious of their eyes all day, and 23% said that they were constantly worrying about their eyes. Other activities that were negatively affected included difficulty driving at night (47%), additional time needed for daily hygiene routine (30%), and difficulty in wearing eye make-up (in 34% of females). While all subjects had objective signs of Demodex blepharitis confirmed by an eye care provider, 58% said they had never previously been diagnosed with blepharitis. The most commonly used management approaches for Demodex blepharitis were artificial tears (47%), warm compresses (32%), and lid wipes (14%). Conclusion: Demodex blepharitis has a significant negative impact on daily activities and the mental and physical well-being of afflicted patients.

The Prevalence of Demodex Blepharitis in US Eye Care Clinic Patients as Determined by Collarettes: A Pathognomonic Sign.

Purpose: To evaluate the prevalence of Demodex blepharitis by its pathognomonic sign, collarettes, in patients presenting for any reason to eye care clinics in the United States. Patients and Methods: In this retrospective study by 7 investigators at 6 eye care clinics, case records of consecutive patients who underwent a slit-lamp examination, regardless of chief complaint, were reviewed for Demodex blepharitis, as identified by the presence of collarettes. Patient characteristics, including age, gender, race, relevant ocular and systemic diagnoses, ocular medications, lid hygiene practices and contact lens wear, were also recorded. Results: Of 1032 patients (mean age: 60.2 ± 17.8 years), 57.7% had Demodex blepharitis. While the prevalence of Demodex blepharitis in patients with dry eye disease (DED) (58.9%) and cataract (55.7%) was similar to the overall prevalence of Demodex blepharitis, it was higher in patients with blepharitis (69.1%) and glaucoma (64.8%). Among patients with collarettes, 44.0% had never been diagnosed with blepharitis. Among those on anti-inflammatory DED treatment, 60.0% had Demodex blepharitis. Demodex blepharitis prevalence was significantly higher among those using topical tea tree oil versus those who were not (74.5% versus 56.7% p = 0.014); prevalence was comparable among those using/not using lid wipes (56.9% versus 55.5%). Conclusion: Demodex blepharitis, based on the pathognomonic finding of collarettes, is common and likely underdiagnosed among patients seeking eye care. These collarettes are still found in patients using over-the-counter treatments for blepharitis. The present study highlights the importance of screening patients for collarettes and Demodex blepharitis as part of every slit-lamp examination.

Topical Review: An Update of Diagnostic and Management Algorithms for Acquired Blepharoptosis.

SIGNIFICANCE: Acquired ptosis is a condition of the upper eyelid that has negative cosmetic and functional effects but is likely underdiagnosed and undertreated. Given the evolving understanding of the condition and expanding therapeutic options, this review reappraised published evidence and clinical experience regarding diagnosis and treatment of acquired ptosis.The authors met over two structured virtual working sessions to review current evidence and develop timely recommendations for acquired ptosis identification, differential diagnosis, characterization, and treatment selection. Diagnostic algorithms, plus management and referral guidelines, are presented. Eyelid evaluation and, when needed, ptosis diagnostic workup are essential in the comprehensive eye examination. Acquired ptosis can be efficiently identified via patient questionnaire, history, and photograph review combined with assessment of eyelid position and symmetry using established methods. When ptosis is present, it is essential to evaluate onset, symptoms, pupil diameter, and extraocular muscle function to identify or rule out serious underlying conditions. If signs of serious underlying etiology are present, immediate referral/follow-up testing is required. After ruling out serious underlying causes, masquerade conditions, and pseudoptosis, pharmacologic or surgical treatment should be selected based on the clinical evidence. Effectively managing acquired ptosis requires practice-wide commitment to thorough eyelid evaluation, accurate diagnosis, and adoption of new treatment modalities. Aided by evolving pharmacologic therapeutic options, shifting from a "detect and refer" to a "diagnose and manage" approach can support identification and treatment of more patients with acquired ptosis, particularly mild-to-moderate cases.

Lifitegrast clinical efficacy for treatment of signs and symptoms of dry eye disease across three randomized controlled trials.

OBJECTIVE: Report efficacy findings from three clinical trials (one phase 2 and two phase 3 [OPUS-1, OPUS-2]) of lifitegrast ophthalmic solution 5.0% for treatment of dry eye disease (DED). RESEARCH DESIGN AND METHODS: Three 84-day, randomized, double-masked, placebo-controlled trials. Adults (≥18 years) with DED were randomized (1:1) to lifitegrast 5.0% or matching placebo. Changes from baseline to day 84 in signs and symptoms of DED were analyzed. MAIN OUTCOME MEASURES: Phase 2, pre-specified endpoint: inferior corneal staining score (ICSS; 0-4); OPUS-1, coprimary endpoints: ICSS and visual-related function subscale (0-4 scale); OPUS-2, coprimary endpoints: ICSS and eye dryness score (EDS, VAS; 0-100). RESULTS: Fifty-eight participants were randomized to lifitegrast 5.0% and 58 to placebo in the phase 2 trial; 293 to lifitegrast and 295 to placebo in OPUS-1; 358 to lifitegrast and 360 to placebo in OPUS-2. In participants with mild-to-moderate baseline DED symptomatology, lifitegrast improved ICSS versus placebo in the phase 2 study (treatment effect, 0.35; 95% CI, 0.05-0.65; p = 0.0209) and OPUS-1 (effect, 0.24; 95% CI, 0.10-0.38; p = 0.0007). Among more symptomatic participants (baseline EDS ≥40, recent artificial tear use), lifitegrast improved EDS versus placebo in a post hoc analysis of OPUS-1 (effect, 13.34; 95% CI, 2.35-24.33; nominal p = 0.0178) and in OPUS-2 (effect, 12.61; 95% CI, 8.51-16.70; p < 0.0001). LIMITATIONS: Trials were conducted over 12 weeks; efficacy beyond this period was not assessed. CONCLUSIONS: Across three trials, lifitegrast improved ICSS in participants with mild-to-moderate baseline symptomatology in two studies, and EDS in participants with moderate-to-severe baseline symptomatology in two studies. Based on the overall findings from these trials, lifitegrast shows promise as a new treatment option for signs and symptoms of DED.

Long-term Supplementation With n-6 and n-3 PUFAs Improves Moderate-to-Severe Keratoconjunctivitis Sicca: A Randomized Double-Blind Clinical Trial.

PURPOSE: Supplementation with gamma-linolenic acid (GLA) and omega-3 (n-3) polyunsaturated fatty acids (PUFAs) has been found to decrease the production of disease-relevant inflammatory mediators that are implicated in the pathogenesis of chronic dry eye. This study evaluated the effect of a supplement containing both GLA and n-3 PUFAs on signs and symptoms of moderate-to-severe keratoconjunctivitis sicca in postmenopausal patients. METHODS: This multicenter, double-masked placebo-controlled clinical trial enrolled 38 patients (both eyes) with tear dysfunction who were randomized to supplemental GLA + n-3 PUFAs or placebo for 6 months. Disease parameters, including Ocular Surface Disease Index, Schirmer test, tear breakup time, conjunctival fluorescein and lissamine green staining, and topographic corneal smoothness indexes (surface asymmetry index and surface regularity index), were assessed at baseline and at 4, 12, and 24 weeks. The intensity of dendritic cell CD11c integrin and HLA-DR expression was measured in conjunctival impression cytologies. RESULTS: The Ocular Surface Disease Index score improved with supplementation and was significantly lower than placebo (21 ± 4 vs. 34 ± 5) after 24 weeks (P = 0.05, n = 19 per group). The surface asymmetry index was significantly lower in supplement-treated subjects (0.37 ± 0.03, n = 15) than placebo (0.51 ± 0.03, n = 16) at 24 weeks (P = 0.005). Placebo treatment also significantly increased HLA-DR intensity by 36% ± 9% and CD11c by 34% ± 7% when compared with supplement treatment (n = 19 per group, P = 0.001, 24 weeks). Neither treatment had any effect on tear production, tear breakup time, or corneal or conjunctival staining. CONCLUSIONS: Supplemental GLA and n-3 PUFAs for 6 months improved ocular irritation symptoms, maintained corneal surface smoothness, and inhibited conjunctival dendritic cell maturation in patients with postmenopausal keratoconjunctivitis sicca.Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT00883649.