Efficacy and Safety of CSF-1 (0.4% Pilocarpine Hydrochloride) in Presbyopia: Pooled Results of the NEAR Phase 3 Randomized, Clinical Trials.

PURPOSE: This study was undertaken to evaluate the safety and efficacy of CSF-1 (0.4% pilocarpine hydrochloride ophthalmic solution) for use in individuals with presbyopia. METHODS: Two Phase 3 multicenter, randomized, double-masked, vehicle-controlled, parallel-group clinical trials were conducted in 35 private ophthalmology clinics in the United States from October 2020 to February 2022. Key inclusion criteria were the following: (1) age 45-64 years, (2) distance-corrected near visual acuity (DCNVA) at 40 cm ≥0.40 and ≤0.90 logarithm of the minimum angle of resolution (logMAR, approximately 20/50-20/160 Snellen) in at least 1 eye, (3) manifest refraction (MR) between -4.50 and +2.00 diopter (D) sphere in each eye with ≤2.00D difference between eyes, (4) <2.00D of cylinder MR in each eye, (5) ≤0.04 logMAR (20/20-2 or better) corrected distance visual acuity (CDVA) at 4 m in each eye. Key exclusion criteria were the following: (1) >0.14 logMAR (7 letters) improvement in post-vehicle treatment in monocular DCNVA in either eye at visit 1, (2) introcular pressure (IOP) <9 or >22 mm Hg, (3) average dark-adapted pupillometry <3.5 mm in either eye, (4) prior refractive surgery or intraocular lens (IOL) implantation. Participants applied CSF-1 or vehicle twice per day for 2 weeks. Efficacy and safety assessments were performed at several times on days 1, 8, and 15. Response was defined as ≥3-line gain in DCNVA without loss of ≥1-line in CDVA in the study eye under mesopic room lighting conditions. The primary efficacy endpoint was measured 1 hour post-dose 1 on day 8. Key secondary endpoints were 2 hours post-dose 1, and 1 and 2 hours post-dose 2, also on day 8. Safety endpoints were ocular and non-ocular treatment-related adverse events (TRAE), conjunctival redness, drop comfort, slit-lamp biomicroscopy, intraocular pressure, indirect fundoscopy, and CDVA at 4 m. FINDINGS: Six hundred thirteen participants were randomized to CSF-1 (n = 309) or vehicle (n = 304). Participants were predominantly White (80.8%) and female (62.0%), with mean age (standard deviation) of 54.7 (4.8). CSF-1 met the primary and key secondary endpoints. At the primary endpoint, 40.1% of the CSF-1 group achieved response versus 19.1% of the vehicle group (P < 0.0001). The percentage of responders was significantly greater in CSF-1 compared with vehicle at all tested times. Changes from baseline in all safety endpoints were comparable between groups. Most adverse events (AEs) were mild and transient. Neither serious nor severe AEs were reported with CSF-1. IMPLICATIONS: CSF-1, a low-dose pilocarpine ophthalmic solution, demonstrated superiority to vehicle in improving near vision in individuals with presbyopia without compromising distance vision. CSF-1 demonstrated a favorable safety profile. CLINICALTRIALS: gov identifier: NCT04599933 (NEAR-1), NCT04599972 (NEAR-2).

Magnitude of astigmatism - A comparison between eyes.

PURPOSE: Astigmatism is a highly prevalent refractive error and while studies typically focus to describe the axis symmetry between eyes, little is known about the refractive symmetry. Therefore, this study determined the astigmatic power symmetry between eyes in a large clinic population. METHODS: A clinical chart review was conducted at three optometric practices in the United States, the United Kingdom and Canada and subjective refraction data from 88,891 patients 14-70 years of age who presented with at least -0.25DC refractive astigmatism in at least one eye were included in the analysis. Data were obtained at these practices between January 2014 and March 2017. The overall distribution (%) and magnitude (DC) of astigmatism was determined and refractive differences between eyes were identified. RESULTS: The mean age of the patients was 42.1 ± 15.9 years and included 51,685 (58%) female and 37,206 (42%) male patients. In this data pool of 177,782 eyes, 10.9% required zero astigmatic correction, while 56.2% had astigmatism of -0.25 to -0.75DC. In total 23.9% of patients presented with astigmatism of at least -0.75DC in only one eye, while the other eye had 0 to -0.50DC. Overall, the difference in astigmatism between eyes was less than -0.75DC for 82.1% of astigmatic patients. For patients who presented with astigmatism of -1.00DC in the right eye, 80.8% of them had an astigmatic prescription of -1.00 ± 0.50DC in the left eye. For an astigmatic prescription of -4.00DC in the right eye, only 40.6% of patients exhibited astigmatism of -4.00DC ± 0.50DC in the left eye. CONCLUSIONS: The majority of patients exhibited a difference in astigmatism between eyes of less than -0.75DC, however the refractive cylinder power symmetry was significantly lower in patients with higher refractive astigmatism.

Spectacle prescriptions review to determine prevalence of ametropia and coverage of frequent replacement soft toric contact lenses.

PURPOSE: To determine the prevalence of ametropia and astigmatism in a clinic population and to estimate the coverage of frequent replacement soft toric lenses. METHODS: A review of patient files was conducted at three clinical sites. Prescription data collected between January 2014 and March 2017 in a patient cohort 14 to 70 years of age inclusive were analyzed to determine prevalence of ametropia and astigmatism. The percent coverage of frequent replacement soft toric contact lenses has further been estimated using different ranges for sphere, cylinder and axis availability. RESULTS: In total 101,973 patients were included in the analysis of which 69.5% were considered myopic, 26.9% hyperopic and 3.5% emmetropic as determined by the eye with the larger absolute value of the spherical equivalent refraction. Astigmatism in at least one eye was found in 87.2% of the population, with 37.0% of the patients exhibiting astigmatism of at least -1.00DC in at least one eye. With-the-rule astigmatism was most prevalent in the 14 to 20 year-olds (53.0%), while against-the-rule astigmatism was most prevalent in the 41 to 70 year-olds (50.7%). For astigmatic eyes with a cylinder of at least -0.75DC (n = 83,540; 41% of all eyes), the coverage with toric soft lenses varied greatly depending on parameter availability and ranged between 30.7% (sphere: Plano to -3.00D, cylinder: up to -1.75DC, axes: 90 ±â€¯10° and 180 ±â€¯10°) and 96.4% (sphere: + 6.00D to -10.00D, cylinders: up to -2.75DC, 18 axes). CONCLUSION: Currently available frequent replacement soft toric contact lenses provide coverage for up to 96.4% of potential patients.

Treating allergic conjunctivitis: A once-daily medication that provides 24-hour symptom relief.

BACKGROUND: Allergic conjunctivitis (AC) is a common ocular inflammatory manifestation of allergen exposure in sensitized individuals. Signs and symptoms of AC can decrease quality of life, interfere with productivity, and lead to considerable economic burden. Consistent suppression of conjunctival inflammation is necessary for managing AC, but currently available medications require frequent administration and exhibit limited duration of action. METHODS: In this review, we summarized AC pathogenesis, diagnosis, and current treatment options as well as their limitations. Findings from the literature were discussed in the context of the unmet need for a once-daily medication with sustained 24-hour effectiveness. RESULTS: Topical pharmacologic treatments are the most common approach for managing extant AC; however, most available medications require multiple daily instillations. Dual-acting antihistamine-mast cell stabilizing agents are currently considered first-line therapeutics for AC because they provide acute relief of signs and symptoms and block persistent inflammation to promote regression of AC. Recent studies of a newly-developed, higher-concentration formulation of a dual-acting antihistamine-mast cell stabilizer have demonstrated that this formulation provides a 24-hour duration of action with once-daily dosing. CONCLUSIONS: Dual-acting AC medications exhibit a high degree of overall effectiveness and are well tolerated for chronic use. A newly available once-daily medication that manages signs and symptoms of AC for a full 24 hours may be considered a treatment of choice for patients experiencing seasonal or perennial AC. ClinicalTrials.gov NCT01743027 and NCT01479374.