UNASSIGNED: To prove non-inferiority of preservative-free (PF) latanoprost versus benzalkonium chloride (BAK) containing latanoprost in lowering intraocular pressure (IOP) in primary open-angle glaucoma (POAG) or ocular hypertension (OHT) patients.
UNASSIGNED: This phase III, randomized, investigator-masked trial primarily aimed to demonstrate non-inferiority of YSLT PF latanoprost 50 μg/ml (Yonsung GmbH) to latanoprost (Xalatan®) 50 μg/ml (Pfizer) in reducing IOP from Baseline to Week 12. Secondary aims included conjunctival hyperemia evaluation and difference in ocular comfort levels. Total 130 patients with POAG or OHT were enrolled and randomized (1:1 ratio) to receive YSLT or latanoprost, instilling eye drops daily for 12 weeks.
UNASSIGNED: At Week 12, mean diurnal IOP reduction was -7.67 ± 2.104 mmHg for YSLT PF latanoprost and -7.77 ± 2.500 for latanoprost. The 97.5% confidence interval of between-treatment group difference in IOP reduction from Baseline to Week 12 was [-0.846, +∞), not crossing the non-inferiority margin of -1.5 mmHg. A low incidence of mild topical treatment emergent adverse events (TEAEs) was observed in both groups, while no serious TEAEs were reported.
UNASSIGNED: YSLT eye drops demonstrated non-inferiority to latanoprost in reducing IOP. Both products were well tolerated without serious TEAEs reported.

OBJECTIVE: This multicenter prospective study (BZK40+) aims to determine the efficacy and tolerance of a benzalkonium chloride-containing spermicide as contraceptive among women aged 40 and over.
METHODS: Fertile women enrolled in this open single-arm study were instructed to systematically use the benzalkonium chloride spermicide before each intercourse. At the end of a 6-month mandatory period, participants were given the option of continuing the study for a further 6 months. The primary endpoint for contraceptive efficacy was the Pearl Index (PI) up to 12 months of typical use.
RESULTS: A total of 151 women (mean age: 45.9 years) were enrolled, 144 (95.4%) completed the initial 6-month period and 63 (41.7%) completed the optional 6-month period. The median number of intercourses ranged from 3 to 5 per month. The spermicide was applied before 96.3% of the 5,895 sexual intercourses. The PI up to 12 months of typical use was 0 pregnancies (95% confidence interval: 0-2.88). The cumulative treatment exposure was 1249.7 women-months.
CONCLUSIONS: This first study in women aged 40 years and over shows that benzalkonium chloride spermicide (Pharmatex®) is effective, well tolerated and well accepted in this population. Although very interesting, these results with a PI equal to zero are surprising and not in accordance with the low efficacy of spermicides in the overall population according to the WHO. So, our results should be interpreted with caution and confirmed by future research. Clinical trial registration number (EudraCT): 2016-004,188-38.

BACKGROUND: Different drugs have been approved to reduce the intraocular pressure. However, most of them contain preservatives to maintain sterility and these can be toxic to the ocular surface. The aim was to determine the patterns of use of antiglaucoma agents and ophthalmic preservatives in a group of patients from Colombia.
METHODS: A cross-sectional study that identified ophthalmic antiglaucoma agents from a population database of 9.2 million. Sociodemographic and pharmacological variables were considered. Descriptive and bivariate analyses were performed.
RESULTS: A total of 38,262 patients were identified, with a mean age of 69.2 ± 13.3 years, and 58.6% were women. A total of 98.8% were prescribed antiglaucoma drugs in multidose containers. The most widely used were prostaglandin analogs (59.9%), especially latanoprost (51.6%) and β-blockers (59.2%). A total of 54.7% of patients received combined management, especially with fixed-dose combination (FDC) drugs (41.3%). A total of 94.1% used antiglaucoma drugs with preservatives (benzalkonium chloride, 68.4%).
CONCLUSIONS: The pharmacological treatment of glaucoma was very heterogeneous, but the most commonly used therapeutic groups were in accordance with the recommendations of clinical practice guidelines but with differences by sex and age. Most of the patients were exposed to preservatives, especially benzalkonium chloride, but the wide use of FDC drugs can minimize toxicity on the ocular surface.

BACKGROUND: Allergic contact dermatitis (ACD) from topical ophthalmic medications (TOMs) poses an additional disease burden to patients who already suffer from eye problems.
OBJECTIVE: To investigate the epidemiological/clinical profile of patients with periorbital ACD from TOMs in Turkey.
METHODS: This was a retrospective, cross-sectional, single tertiary centre study based on files of 75 patch tested patients with suspected periorbital ACD from TOMs among a total of 2801 consecutively patch tested patients with suspected ACD of any origin between 1996 and 2019.
RESULTS: Periorbital ACD was diagnosed in 25 of 75 (33.3%) patients (female:male = 1.8:1; age range: 6-85 years) with suspected ACD from TOMs showing an overall prevalence of 0.9% (25/2801) among the whole patch test population. Atopy was not present. Tobramycin-containing TOMs were the most frequent culprits, followed by antiglaucoma preparations. Their frequency increased, whereas no new cases of neomycin-induced ACD were observed after 2011. Positivities with thimerosal were of unknown clinical relevance, while benzalkonium chloride (BAC) caused ACD in two patients. The diagnosis would be missed in each 20% of patients without performing day (D) 4 and D7 readings and strip-patch testing. Ten culprits were identified only by testing with patients\' own TOMs in eight (32%) patients.
CONCLUSIONS: Aminoglycosides, particularly tobramycin, were the leading cause of ACD from TOMs. The frequency of ACD from tobramycin and antiglaucoma medications increased after 2011. BAC was a rare but important allergen. Additional D4 and D7 readings, strip-patch testing, and testing with patients\' own TOMs seem essential when patch testing with eye medications.

The behavior of a new 1,3-dioctadecyl-1H-imidazol-3-ium tetraphenylborate (DODI-TPB) surfactant sensor was studied in single and complex mixtures of technical grade QACs-benzalkonium chloride (BAC), N,N-didecyl-N,N-dimethylammonium chloride (DDAC), and N,N-dioctyl-N,N-dimethylammonium chloride (DOAC) usually used in COVID-19 disinfecting agents formulations. The results obtained with the new DODI-TPB sensor were in good agreement with data measured by a 1,3-dihexadecyl-1H-benzo[d]imidazol-3-ium-tetraphenylborate (DMI-TPB) surfactant sensor, as well as two-phase titration used as a reference method. The quantitative titrations of a two-component mixture of the cationic homologs (a) DDAC and DOAC; and (b) BAC and DOAC showed that the new DODI-TPB surfactant sensor can clearly distinguish two separate mixture components in a single potentiometric titration curve with two characteristic inflexion points. The consumption of SDS (used as a titrant) in the end-point 1 (EP 1) corresponded to the content of DDAC (or BAC), whereas the consumption in the end-point 2 (EP 2) corresponded to the total content of both cationic surfactants in the mixture. DOAC content in both mixtures can be calculated from the difference of the titrant used to achieve EP1 and EP2. The addition of nonionic surfactants resulted in the signal change decrease from 333.2 mV (1:0; no nonionic surfactant added) to 243.0 mV (1:10, w/w). The sensor was successfully tested in ten two-component COVID-19 disinfecting formulations.

This survey study of ophthalmologists investigated the prevalence and clinical manifestations of ocular surface disease (OSD) in glaucoma patients, assessment methods used, risk factors, glaucoma drugs considered responsible, and treatment approaches.
A questionnaire prepared jointly by the Turkish Ophthalmological Association Cornea and Ocular Surface Society and Glaucoma Society using SurveyMonkey was sent to ophthalmologists via e-mail. The distribution of parameters was compared with chi-square test and p<0.05 was considered statistically significant.
Forty-five percent of the ophthalmologists reported that OSD was evident in least 25% of their patients. The most common symptom was redness (91.9%), while the most common ocular surface finding was conjunctival hyperemia (75.6%). The tests considered to be the most important in ocular surface assessment were ocular staining (38.7%) and tear film break-up time (TBUT) (21.9%). Ninety percent of the physicians stated that the main cause of OSD was benzalkonium chloride (BAC) in medications. Prostaglandin analogs and alpha-2 agonists were reported to be the most common medications causing OSD. In case of OSD, the ophthalmologists often switch to a glaucoma drug from a different group (38%), a non-preservative glaucoma drug (33.7%) or a drug with a preservative other than BAC (20.4%). Most physicians prescribed artificial tears (84.6%).
In this cross-sectional survey study, ophthalmologists detected varying rates of OSD in glaucoma patients depending on chronic drug use and BAC exposure. Although ocular surface examination was performed by physicians, tests such as TBUT and ocular surface staining were rarely used. Detecting OSD in glaucoma patients and planning personalized treatment increase patient comfort, drug compliance, and treatment effectiveness. For this reason, it is important to prepare an algorithm for the management of comorbid OSD in glaucoma patients.

OBJECTIVE: To evaluate the noninferiority of intraocular pressure (IOP)-lowering latanoprost without benzalkonium chloride (BAK) versus latanoprost with BAK (for treatment of open-angle glaucoma or ocular hypertension).
METHODS: Overall, 578 patients were randomized 1:1 to latanoprost without BAK or latanoprost with BAK once daily in the affected eye(s) for 12 weeks. The primary efficacy endpoint was IOP, measured on days 0, 7, 28, 56, and 84 (8 am, 10 am, and 4 pm). Noninferiority was established if the following criteria were met: 95% confidence interval (CI) of the mean difference between treatments included 0 mm Hg for all time points (N1), 95% CI upper limit less than 1.5 mm Hg (N2), and less than 1 mm Hg for≥7 of 12 time points (N3). Primary efficacy analysis was performed on the intent-to-treat population. Safety measurements included ocular and systemic adverse event (AE).
RESULTS: The 95% CI included 0 mm Hg for 7/12 time points (N1), 95% CI upper limit was less than 1.5 mm Hg for 12/12 time points (N2), and less than 1.0 mm Hg for 4/7 time points (N3). AEs were mild and similarly distributed between groups.
CONCLUSIONS: Latanoprost without BAK did not meet two of three criteria for noninferiority and showed a similar safety profile relative to latanoprost with BAK.

BACKGROUND: Benzalkonium chloride (BAK), the most commonly used preservative in anti-glaucoma eye drops, inflicts damage to the ocular surface. A novel anti-glaucoma formulation that avoids the use of BAK has been developed. The aim of this study was to evaluate the cytotoxicity of this formulation and to compare it with an ophthalmic solution containing BAK.
METHODS: Two different latanoprost eye drops were used: one ophthalmic solution (LSc) containing BAK 0.02% and one ophthalmic nanoemulsion (LNe) with a soft preservative (potassium sorbate 0.18%). Human epithelial conjunctival cells were incubated for 15, 30, and 60 min with either LSc or LNe. The cytotoxicity was determined by MTT assay. Cell death was measured by flow cytometry using annexin V-FITC and propidium iodide.
RESULTS: The values of cell viability and proliferation obtained from cells exposed to LNe were between 80 and 90% relative to the control group, whereas values obtained from cells exposed to LSc were around 30% at all study times (p < 0.05 at 15 and 30 min; p < 0.01 at 60 min). The percentage of viable cells decreased significantly when cells were incubated with LSc compared with cells incubated with LNe at all the study times, while the percentage of cells in late apoptosis/necrosis increased significantly in cells exposed to LSc compared to LNe.
CONCLUSIONS: The new latanoprost nanoemulsion is significantly less cytotoxic on human conjunctival cells than LSc. These results suggest that the new formulation might be gentler on the eye surface than currently available BAK-preserved latanoprost solutions.

UNASSIGNED: Spermicides have been identified as a potentially attractive alternative to hormonal contraceptives and/or intrauterine devices. Thus, this study aimed evaluating the efficacy and local tolerance of benzalkonium chloride (BKC) and myristalkonium chloride (MKC) contained in Pharmatex® vaginal formulations and compare them with nonoxynol-9 (N-9), the most common active ingredient in topical vaginal contraceptives.
UNASSIGNED: Human normozoospermic samples were assessed for motility, viability, acrosome status and penetration ability after exposure to control, N-9 or different BKC and MKC doses for 0 and 10 minutes. Local tolerance on HeLa cells was evaluated by the Trypan-blue and MTT assays.
UNASSIGNED: Exposure to BKC and MKC reduced acrosome integrity while promoting total immobilisation and complete loss of sperm viability (p < .001, n = 15). Both compounds also compromised sperm penetration ability upon exposure (p < .001, n = 15). N-9 induced the same outcomes (p < .001, n = 15); nevertheless, it was more toxic to HeLa cells than BKC and MKC (p < .05, n = 14).
UNASSIGNED: BKC and MKC present strong in vitro spermicidal activity at lower doses than N-9 and were better tolerated after immediate exposure than N-9. Available Pharmatex® galenic formulations were as effective as products based on N-9.

OBJECTIVE: To prospectively evaluate the effect of benzalkonium chloride (BAK)-preserved latanoprost on ocular surface damage and identify the associated risk factors among treatment-naive glaucoma patients.
METHODS: The basal Schirmer\'s test results, corneal Oxford staining score, non-invasive keratograph tear-breakup time, oculus hyperemia index score (objective metrics), and ocular surface disease index (OSDI) questionnaire (subjective metric) were evaluated at baseline, 1 month, and 4 months after receiving latanoprost eye drops. Associated risk factors were assessed by multivariate linear regression.
RESULTS: Seventy-four eyes (44 patients) were enrolled. Basal Schirmer\'s test tear-flow and Oxford scores gradually deteriorated (β = -0.14, P = 0.001 and β = 0.1, P < 0.001, respectively). The percentage of unstable tear-film (breakup time < 10 s) increased significantly at 4 months (6.21% vs 9.11%, P = 0.042). Hyperemic scores increased significantly at 1 month and normalized at 4 months (P = 0.01 and P = 0.16, respectively); total OSDI scores tended to improve (β = -0.76, P = 0.06). Older age was associated with additional corneal Oxford staining (P = 0.005); female sex was associated with increased unstable tear-film scores (P = 0.01). Artificial tear use was associated with a smaller decrease in basal Schirmer\'s test values (P = 0.01) and a smaller increase in unstable tear-film scores (P = 0.02).
CONCLUSIONS: Preserved latanoprost eye drops affected ocular surface changes in glaucoma patients through decreased basal tear secretion. Artificial tears represent an early intervention in vulnerable glaucoma patients with reduced tear secretion and impaired tear-film stability.