Preservative Benzalkonium Chloride Research Articles

A Preservative-Free Approach - Effects on Dry Eye Signs and Symptoms After Cataract Surgery.

To compare the effect of treatment with preservative-free dexamethasone, NSAIDs and trehalose/hyaluronic acid eye drops with the preservative benzalkonium chloride containing dexamethasone and NSAIDs after cataract surgery in dry versus non-dry eyes. In this prospective randomized intervention study, dry eye tests were performed before and 6 weeks after cataract surgery. Patients were considered as having dry eye, SDE (sign of dry eye), if at least one of the following dry eye tests were abnormal; corneal fluorescein staining (CFS), non-invasive keratograph breakup time (NIKBUT) or tear osmolarity. Patients with SDE were randomly assigned to one of two groups. Group 1 patients were treated with dexamethasone and bromfenac eye drops with the preservative benzalkonium chloride (BAC). Group 2 patients were treated with preservative-free dexamethasone and preservative-free diclofenac, as well as a preservative-free lubricant with trehalose and hyaluronic acid both before and after surgery. Patients with normal tear film status acted as the control group (group 3) and received same treatment as group 1. A total of 215 patients were enrolled six weeks after surgery, the number of patients with SDE decreased significantly in groups 1 and 2 (p <0.001). Subjective symptoms and objective measures including osmolarity, NIKBUT, CFS, and tear film thickness (TFT) improved after surgery, tear production remained unchanged, while corneal sensitivity and meibomian gland dysfunction (MGD) parameters worsened. In the control group with normal tear-film status, SDE increased significantly after the surgery (p <0.001). There were no statistically significant differences in tear film parameters between the three groups after surgery. After cataract surgery, patients with mild to moderate dry eyes may experience improved tear film status and reduced symptoms. However, we found no additional beneficial effect on dry eye parameters with treatment with preservative-free dexamethasone, NSAIDs, and lubricants compared to preservative-containing eye drops.

The Prevalence of Ocular Surface Disease in Glaucoma Patients

Introduction: Glaucoma is the third cause of blindness in developed countries after age-related macular degeneration (AMD) and diabetic retinopathy. The aim of this study was to determine the prevalence of ocular surface disease in patients treated for glaucoma or ocular hypertonia. Patients and methods: We conducted a one-year observational study including glaucoma patients older than 15 years, diagnosed and treated for more than six months. The impact of anti-glaucoma treatment on the ocular surface was assessed by a questionnaire derived from the Ocular Surface Disease Index (OSDI). Results: Antiglaucoma treatment caused an alteration of the ocular surface in 59% of patients. 61.7% of patients had a mean epithelial thickness below normal. Discussion: Several observational studies have shown a high prevalence of ocular surface disease in glaucoma patients. The prevalence of surface involvement in our study is close to most studies in the literature. The strong correlation between the number of eye drops prescribed and the severity of ocular surface involvement has been proven. This correlation is attributed to the preservative benzalkonium chloride (BAK). Among the cellular alterations, we noted a decrease in mucus cells with a decrease and instability of the thickness of the tear film, which was more important in patients under BAK preserved eye drops than in those without BAK. Conclusion: Our study allowed us to determine the frequency of ocular surface damage in patients treated long-term with hypotonizing eye drops. The mechanisms of this damage are multiple. Preservatives seem to play a central role in the genesis of these reactions.

Recombinant Human Clusterin Seals Damage to the Ocular Surface Barrier in a Mouse Model of Ophthalmic Preservative-Induced Epitheliopathy.

There is a significant unmet need for therapeutics to treat ocular surface barrier damage, also called epitheliopathy, due to dry eye and related diseases. We recently reported that the natural tear glycoprotein CLU (clusterin), a molecular chaperone and matrix metalloproteinase inhibitor, seals and heals epitheliopathy in mice subjected to desiccating stress in a model of aqueous-deficient/evaporative dry eye. Here we investigated CLU sealing using a second model with features of ophthalmic preservative-induced dry eye. The ocular surface was stressed by topical application of the ophthalmic preservative benzalkonium chloride (BAC). Then eyes were treated with CLU and sealing was evaluated immediately by quantification of clinical dye uptake. A commercial recombinant form of human CLU (rhCLU), as well as an rhCLU form produced in our laboratory, designed to be compatible with U.S. Food and Drug Administration guidelines on current Good Manufacturing Practices (cGMP), were as effective as natural plasma-derived human CLU (pCLU) in sealing the damaged ocular surface barrier. In contrast, two other proteins found in tears: TIMP1 and LCN1 (tear lipocalin), exhibited no sealing activity. The efficacy and selectivity of rhCLU for sealing of the damaged ocular surface epithelial barrier suggests that it could be of therapeutic value in treating BAC-induced epitheliopathy and related diseases.

Cell cultures - model object for experimental studies in ophthalmology

The article presents results obtained on several types of model cultures. Primary cultures of corneal epithelial cells and fibroblast-like cells from the limbus were obtained from the tissues of the anterior eye segment. Tests were performed on these cultures to determine the cytotoxicity of antiglaucoma drugs and to trial a protection method. In addition, a comparative analysis of the regenerative potential of various blood derivatives was carried out. An in vitro culture of endotheliocytes showed a correlation between the degree of damaging effects of antiglaucoma drugs of various groups and the content of the preservative benzalkonium chloride in their composition. Corneal keratocytes were used to create a cell sheet reflecting the main structural features of the stroma and suitable for biomechanical tests. The antifibrotic activity of the drugs was tested on the culture of fibroblasts from the nasolacrimal duct. The conducted studies demonstrate that cell cultures can be used as an informative model object for researching the pathogenesis of ophthalmic diseases and for testing drugs.

Benzalkonium chloride, a common ophthalmic preservative, compromises rat corneal cold sensitive nerve activity

PurposeCorneal nerves comprise the densest sensory network in the body. Dysfunction of the corneal cold sensitive neurons (CSN) is implicated in ophthalmic disorders, including Dry Eye Disease, the most common ocular surface disorder. The preservative Benzalkonium chloride (BAK) and the mydriatic agent Phenylephrine hydrochloride (PHE) are considered to be inactive at the level of the CSNs. The purpose of this study is to test the impacts of continuous exposures to BAK or PHE at their clinically used concentrations on corneal nerve structure and function. MethodsIn vivo extracellular electrophysiology of the rat trigeminal ganglion was used to monitor CSN functional response to stimuli mimicking physiological states and stressors of the cornea. Corneal nerve structure was evaluated by immunostaining. ResultsAmong the tested stimuli, cold probe receptive field stimulation and hyperosmolar stress were the most sensitive methods of detecting activity changes. CSN activity was attenuated after 30 min exposure to either PHE or BAK. After an hour-long washout period, BAK-treated neurons failed to recover activity while PHE-treated neurons showed signs of functional recovery. Intraepithelial nerve density was reduced and nerve fragmentation was increased in BAK-treated corneas, while PHE exposure left corneal nerves structurally intact. ConclusionsOur study suggests that prolonged ocular instillations of BAK or PHE alter CSN activity through two different processes — irreversible neuronal damage in the case of BAK vs. reversible attenuation in the case of PHE.

Экспериментальная модель хронического воспаления тканей глазной поверхности, ассоциированного с медикаментозным лечением глаукомы

Purpose. To study experimental model of eye surface chronic inflammation, associated with glaucoma medication. Material and methods. 40 rabbits received glaucoma medication containing prostaglandin analogue (PGA), beta-blocker (BB) and preservative benzalkonium chloride (PGA + BB group) for 3 months. Rabbits of control group (n=12) received drops of normal saline for the same period of time. All the rabbits underwent regular ophthalmic examination including biomicroscopy, conjunctival hyperemia scoring, corneal examination involving fluorescein staining as well as Shirmer's test I. In 3 months tissues of conjunctiva, Tenon's capsule and cornea were histologically investigated by means of microscopy. Results. Median score of conjunctival hyperemia was significantly higher at PGA + BB group by the end of the study: 2.0 (1.0; 2.0) vs 0.0 (0.0; 0.5) points in control group. Corneal epithelium damage score according to Efron grading scales was 2.0 (1.0; 2.0) points in PGA+BB group, while corneas of control group rabbits didn't show signs of fluorescein staining. Rabbits under topical glaucoma medication had lower results of Shirmer's test I: 10.0 (9.5; 11.0) mm vs 14.0 (14.0; 15.0) mm at animals of control group by the end of experiment. Histological examination revealed thickened conjunctiva, thickened conjunctival epithelium with disorganization of its layers, lesions of monocyte infiltration, fibrosis and neoangiogenesis in conjunctiva and Tenon's capsule, as well as local detachment of upper layers of corneal epithelium in PGA + BB group. Conclusion. We received experimental model of eye surface disease, associated with glaucoma medication, as a result of daily 3-months administration of fixed combination of PGA and BB containing preservative in rabbit eyes. Eye surface disorder was characterized by morphological signs of chronic inflammation of conjunctiva and Tenon's capsule with clinical manifestations of dry eye disease. Key words: glaucoma medication, preservatives, experimental model, dr y eye disease, inflammation, conjunctiva

Advances in the management of Acanthamoeba keratitis: A review of the literature and synthesized algorithmic approach

Acanthamoeba keratitis (AK) is a severe cause of infectious keratitis and represents a significant clinical challenge. Recent literature regarding AK epidemiology, diagnosis, treatment modalities, and prognosis is reviewed and synthesized to propose an algorithmic protocol for AK management. Globally, AK outbreaks in developed countries are ongoing, and AK rates have increased. Moreover, current outbreaks may carry a worse prognosis than prior outbreaks. Despite identification of contact lens solutions implicated in AK outbreaks and the consequent market recall of these products, outbreaks persist. Acanthamoeba keratitis afflicts not only refractive soft contact lens users but also cosmetic contact lens users and gas permeable (especially orthokeratology) lens users. Innovations in in vivo confocal microscopy and PCR assays have increased the role for these adjuvant tests alongside corneal smear and culture in a multimodal diagnostic approach to suspected AK. Biguanides (such as chlorhexidine and polyhexamethylene biguanide) and diamidines (propamidine isethionate and hexamidine) remain cornerstones of AK management, and evidence for other treatment modalities continues to evolve. Voriconazole in topical and systemic forms may be useful as adjuvant therapy. The anti-leishmaniasis drug miltefosine, recently given orphan drug status by the United States Food and Drug Administration, has increasing evidence supporting a role in patients with severe/refractory disease. Prior topical corticosteroids have been consistently shown to be associated with worse outcomes in AK. Although not historically thought of as a treatment modality, benzalkonium chloride preservative may be leveraged for its anti-Acanthamoebal properties. The role of Rose-Bengal photodynamic antimicrobial therapy is evolving in selected cases of AK.

Effect of the Preservative Benzalkonium Chloride in Prostaglandin Analogues on Corneal Sensitivity

Purpose: To investigate the effect of a prostaglandin (PG) analogue with or without preservative benzalkonium chloride (BAK) on corneal sensitivity.Methods: Central corneal sensitivity was measured prospectively with a Cochet–Bonnet esthesiometer in patients with normal tension glaucoma (NTG) or primary open angle glaucoma (POAG) before and 1 and 3 months after treatment. All patients began treatment with PG monotherapy with or without BAK preservative.Results: The study enrolled 84 patients: 52 NTG and 32 POAG. The treatment was PG with BAK preservative in 45 eyes and without BAK preservative in 39 eyes. Without BAK, the mean corneal sensitivity was 58.22 ± 3.56, 57.77 ± 4.59, and 56.33 ± 5.47 mm before and after 1 and 3 months, respectively; with BAK the mean corneal sensitivity was 58.20 ± 4.51, 56.31 ± 6.22, and 55.52 ± 6.23 mm. Corneal sensitivity was reduced significantly in patients using PG with the preservative BAK after 3 months (p = 0.033). Co-administration of artificial tears did not affect this reduction in corneal sensitivity.Conclusions: PG with the preservative BAK reduced corneal sensitivity and artificial tears did not improve this reduction. Reduced corneal sensitivity and accompanying side effects should be considered in the long-term use of PG with the preservative BAK.

Effect of preservative-free and preserved prostaglandin analogues on the histology of cornea of adult male guinea pigs following repeated exposure.

Glaucoma is a group of eye diseases that can cause vision loss. Prostaglandin analogues (PGAs) are known to be first-line treatment for patients with glaucoma. Latanoprost is a good, efficient and well-tolerated PGA that is currently available as latanoprost with benzalkonium chloride (BAC) (Xalatan) and preservative-free (PF) prostaglandin analogue latanoprost (Monopost). Lately, using PF anti-glaucoma agents has been considered an essential procedure for enhancing glaucoma care. This study aimed to analyse the histological changes within the corneal tissue with the use of currently available preserved prostaglandins-derived eye drops and PF prostaglandin analogue. In this study, 40 male guinea pigs were divided into four equal groups. Control group, Latanoprost with 0.02% BAC-treated group, Recovery group and PF latanoprost-treated group. After 2 months, the corneal tissues of guinea pigs were prepared for light and electron microscopic studies; morphometric and statistical studies were performed. Our results indicated that guinea pigs treated with latanoprost with BAC exhibited ocular surface changes: there was epithelial thinning with desquamation, the stroma showed irregularly arranged collagen fibres and small keratocytes. Morphometrically, there was a marked decrease in the thickness of epithelium and number of keratocytes. Negative periodic acid Schiff (PAS) reaction was observed in some parts of the epithelial basement membrane. The epithelium gave a strong positive immunoreactivity for Bcl-2-associated X protein (BAX). Guinea pigs left to recover exhibited improvement, while treatment of animals with PF latanoprost resulted in nearly normal corneal structure. In conclusion, PF prostaglandin anti-glaucoma medication seems to be better and have protective effect on cornea of male guinea pigs than prostaglandins with BAC preservative.

Rupture and chemical accumulation in contact lenses with dexamethasone eye drop administration after congenital cataract surgery.

To investigate whether contact lenses used after surgery for congenital cataracts act as a depot for dexamethasone, which would allow the prescribed amount of drops to be reduced, and to examine whether the preservative benzalkonium chloride accumulates in the contact lens matrix, which would suggest a need for more frequent replacements. Contact lenses (n = 10) worn by infants treated with dexamethasone eye drops after congenital cataract surgery were analysed with scanning electron microscopy, UV-vis, 1 H-NMR and LDI-MS for chemical deposits and for changes on the contact lens surface. Unused lenses (n = 5) and lenses (n = 4) from patients with no eye drop treatment were analysed as reference. The treated contact lenses displayed ruptured surfaces in comparison with unused and reference lenses. Dexamethasone and BAK were not detected in any of the lenses. A polyethylene oxide component was found in the treated lenses, likely originating from the dexamethasone eye drops or the contact lens solution. Dexamethasone and BAK do not accumulate in the contact lenses, and a depot effect of any clinical significance is unlikely. Therefore, the number of drops given after surgery should remain the same regardless of whether the child has contact lenses. The ruptured surface may both decrease the child's comfort and increase the risk of microbial adhesion, and so it is recommended that contact lenses should be replaced once a month throughout the course of anti-inflammatory eye drop treatment after surgery for congenital cataract.

Aqueous humor pharmacokinetics of Benzalkonium chloride free bimatoprost formulated in tight junction modulation technology compared to Benzalkonium chloride preserved bimatoprost 0.01% ophthalmic solution in rabbit eyes

This study was undertaken with an objective to compare the aqueous humor pharmacokinetics (PKs) of bimatoprost and bimatoprost free acid of innovator bimatoprost 0.01% (BAK-Bimatoprost) and the novel formulation, Tight Junction Modulation technology based bimatoprost 0.01% (TJM-bimatoprost) containing polyhexamethylene Biguanide hydrochloride (PHMB) as a preservative.All animals in the study were assigned to one of two treatment arms: either a single dose of BAK-Bimatoprost (n=28) or a TJM-bimatoprost ophthalmic solution (n=28). Time points for aqueous humor collection were 0.5, 1, 2, 4, 8, 12 and 24 Hrs after drug administration. The mean Cmax of 11.93± 2.70 vs 10.92± 3.84 ng/ml was comparable (P&amp;#62;0.05, one-way ANOVA) across TJM bimatoprost and BAK-bimatoprost treatment arms. Results of other PK parameters pertaining to bimatoprost+ bimatoprost free acid concentration were as follows: time to maximum concentration (T_max) was 1.75± 2.0 vs 1.50 ± 1.16 hr and half-live (T_half) was 2.13 ± 0.58 vs 2.47 ± 0.79 hr in the TJM- bimatoprost and BAK-bimatoprost treatment arms respectively. Overall, there was no difference between TJM-bimatoprost and BAK-bimatoprost treatment arms in the PK end points. The results taken in totality support the hypothesis that pharmacokinetics TJM-bimatoprost 0.01%, containing PHMB preservative, is comparable to BAK-bimatoprost 0.01%. A new formulation of bimatoprost 0.01% using Tight Junction Modulation technology is pharmacokinetically comparable to marketed formulation of bimatoprost containing benzalkonium chloride preservative.

Use of Preservatives in Vegetable Protein-Based Food Attractants for Monitoring Anastrepha fraterculus (Diptera: Tephritidae) in Peach Orchards.

Studies have demonstrated that the addition of preservatives mixed with food attractants have provided a more expressive attractiveness for fruit fly adults. The objective of the study was to evaluate the capture of Anastrepha fraterculus (Wiedemann, 1830) adults when the addition of borax and/or benzalkonium chloride preservative in BioAnastrephaTM and Isca Samaritá TradicionalTM food attractants compared to CeraTrapTM (control, no preservatives added) in peach orchards. As well as, verifying the effect over non-target insects. BioAnastrephaTM, Isca Samaritá TradicionalTM and CeraTrapTM attractants enabled the capture of A. fraterculus adults when used by themselves in McPhail traps. However, by adding borax and benzalkonium chloride, BioAnastrephaTM and Isca Samaritá TradicionalTM food attractants significantly increased the number of adults captured. Additionally, the number of A. fraterculus adults captured by BioAnastrephaTM attractant + borax was similar to CeraTrapTM attractant over time. Regarding non-target insects, the highest percentages of subjects captured belong to the Coleoptera (4.4 to 11%) and Diptera orders (24.1 to 34.6%) (Drosophilidae family). Nevertheless, insects from the Hymenoptera order [(Formicidae (0.14 to 0.96%), Vespidae (0.02 to 0.3%), and Apidae (0.04 to 0.9%)] families. Neuroptera (0.02 to 0.98%) and Lepidoptera (0.09 to 0.7%) were also captured, although those amounted to less than 1% of the A. fraterculus total. Adding borax and benzalkonium chloride to BioAnastrephaTM and Isca Samaritá TradicionalTM food attractants potentialize the effect of A. fraterculus capture in monitoring traps. Also, adding preservatives made attractants more durable, consequently, the need to replace attractants was not as frequent.

Continuous Albuterol With Benzalkonium in Children Hospitalized With Severe Asthma

MC Pertzborn, S Prabhakaran, M Abu-Hasan. Pediatrics. 2020;145(4):e20190107 The albuterol dropper bottle used to prepare solutions for continuous nebulization contains the chemical preservative benzalkonium chloride (BAC). BAC, by itself, has been shown to cause bronchospasm. BAC is contained in the 0.5% multidose 20-mL dropper bottle of albuterol. All other albuterol products for nebulization are single-dose sterile, preservative-free vials of concentrate or varying dilutions with saline. The authors hypothesize that BAC would decrease the therapeutic efficacy of albuterol in patients with acute asthma exacerbations. Patients treated at the University of …

Efflux Pump-Driven Antibiotic and Biocide Cross-Resistance in Pseudomonas aeruginosa Isolated from Different Ecological Niches: A Case Study in the Development of Multidrug Resistance in Environmental Hotspots.

Pseudomonas aeruginosa is an opportunistic pathogen displaying high intrinsic antimicrobial resistance and the ability to thrive in different ecological environments. In this study, the ability of P. aeruginosa to develop simultaneous resistance to multiple antibiotics and disinfectants in different natural niches were investigated using strains collected from clinical samples, veterinary samples, and wastewater. The correlation between biocide and antimicrobial resistance was determined by employing principal component analysis. Molecular mechanisms linking biocide and antimicrobial resistance were interrogated by determining gene expression using RT-qPCR and identifying a potential genetic determinant for co- and cross-resistance using whole-genome sequencing. A subpopulation of P. aeruginosa isolates belonging to three sequence types was resistant against the common preservative benzalkonium chloride and showed cross-resistance to fluoroquinolones, cephalosporins, aminoglycosides, and multidrug resistance. Of these, the epidemiological high-risk ST235 clone was the most abundant. The overexpression of the MexAB-OprM drug efflux pump resulting from amino acid mutations in regulators MexR, NalC, or NalD was the major contributing factor for cross-resistance that could be reversed by an efflux pump inhibitor. This is the first comparison of antibiotic-biocide cross-resistance in samples isolated from different ecological niches and serves as a confirmation of laboratory-based studies on biocide adapted isolates. The isolates from wastewater had a higher incidence of multidrug resistance and biocide-antibiotic cross-resistance than those from clinical and veterinary settings.

Adaptation and Survival of Burkholderia cepacia and B. contaminans During Long-Term Incubation in Saline Solutions Containing Benzalkonium Chloride

The Burkholderia cepacia complex (Bcc) is a group of opportunistic pathogenic bacteria with a remarkable metabolic capacity and broad genotypic/phenotypic plasticity, allowing their adaptation to hostile conditions, including nutrient depleted solutions containing antimicrobial agents. Bcc bacteria are feared contaminants in pharmaceutical industries and cause nosocomial outbreaks, posing health threats to immunocompromised individuals and cystic fibrosis (CF) patients. In this study, the adaptation and survival of B. cepacia and B. contaminans isolates was investigated after long-term incubation in nutrient depleted saline solutions supplemented with increasing concentrations of the biocidal preservative benzalkonium chloride (BZK), recreating the storage conditions of pharmaceutical products. These epidemiologically related isolates were recovered from intrinsically contaminated saline solutions for nasal application and from two CF patients. Long-term incubation in saline solutions containing BZK led to the development of bacterial sub-populations that survived for at least 16 months, despite an initial 2–3 log decrease in viability, displaying a progressive dose-dependent decrease of colony and cell size, including the appearance of small colony variants (SCVs). Bacterial colonies lost pigmentation, changed the morphotype from rough to smooth and produced more spherical cells during extended incubation with BZK. The development of macroscopically visible cellular aggregates, rich in polysaccharide and harboring viable cells in their interior was triggered by BZK. The existence of a metabolic pathway for BZK degradation was confirmed through genome analysis. This study reveals mechanisms underlying the prevalence of Bcc bacteria as contaminants of pharmaceutical products containing BZK, which often lead to false-negative results during quality control and routine testing.

Continuous Albuterol With Benzalkonium in Children Hospitalized With Severe Asthma

The albuterol dropper bottle used to prepare solutions for continuous nebulization contains the preservative benzalkonium chloride (BAC). BAC, by itself, has been shown to cause bronchospasm. We hypothesized that BAC would decrease the therapeutic efficacy of albuterol in patients with acute asthma exacerbations. We performed a retrospective cohort study comparing the clinical outcomes of patients <18 years of age receiving continuous nebulized albuterol with and without BAC. For the primary end point (duration of continuous albuterol nebulization), we compared the 2 groups with Kaplan-Meier estimate of survival curves, conducted a log-rank test of difference, and adjusted for baseline characteristics using multivariable Cox regression. A P value <.05 was considered significant. A total of 477 patients were included in the analysis (236 exposed to BAC and 241 controls). The duration of continuous nebulization was significantly longer in the BAC group than in the control group (median of 9 vs 6 hours; 15.7% required continuous nebulization compared to 5.8% of controls at 24 hours). The control group was 79% more likely to stop continuous nebulization at any particular point in time (hazard ratio 1.79; 95% confidence interval: 1.45 to 2.22; P < .001) and 43% more likely to stop additional respiratory support (hazard ratio 1.43; 95% confidence interval: 1.16 to 1.75; P < .001). BAC is a functional albuterol antagonist associated with a longer duration of continuous albuterol nebulization treatment and additional respiratory support, suggesting that preservative-free albuterol formulations are safer for use in continuous nebulization.

Dose-dependent benzalkonium chloride toxicity imparts ocular surface epithelial changes with features of dry eye disease

PurposeInclusion of the preservative benzalkonium chloride (BAC) in ophthalmic solutions is prevalent, despite the noted potential for exacerbating dry eye disease (DED). Whilst studies incorporating BAC have assessed its’ effects as a mouse model of DED, the impact on limbal epithelia is under-studied. Our investigation aimed to comprehensively assess the impact of different BAC dosing regimens and their suitability as a mouse model of DED. MethodsC57BL/6J mice (n = 72) were administered topical BAC (0.05–0.2%) over 7 days. Fluorescein staining, corneal smoothness index, and immuno-histological analyses were applied to determine architectural and cellular changes on the ocular surface following BAC treatment. The effect of BAC (0.0001–0.01%) on cultivated primary mouse corneo-limbal epithelial cells (CLECs) (n = 6) was examined using morphological and functional assays. ResultsWhilst 0.2% BAC induced severe corneal epithelial defects, 0.1% BAC dispensed once daily over 7 days, induced punctate fluorescein staining without detriment to corneal smoothness. Histochemical staining revealed disorganized basal corneal epithelial cells with enlarged cytoplasmic halos. Furthermore, PAS+ goblet cells were decreased. BAC treatment also modulated K14 expression and distribution within the limbus. In cultured CLEC, BAC triggered cell contraction and vacuolation, increased LDH release and elevated cell necrosis by 4.1-fold. Concentrations of BAC as low as 0.0001% decreased colony formation. ConclusionsThis study describes how exposing C57BL/6 mice to BAC induce some clinicopathological features of DED seen in humans, and therefore provides the foundations to explore the consequences on the ocular surface, particularly on limbal epithelia and its’ stem cells.

Extracellular MMP-9-Based Assessment of Ocular Surface Inflammation in Patients with Primary Open-Angle Glaucoma.

Purpose Objective assessment of dry eye disease (DED) severity and ocular inflammation using the InflammaDry® test for extracellular matrix metalloproteinase-9 (MMP-9) and the impact of antiglaucoma eye drops in people with primary open-angle glaucoma (POAG). Methods Overall, 90 adults (180 eyes) were included: 60 had been diagnosed with POAG and were treated with prostaglandin analogue monotherapy and 30 were suspected of having POAG but did not receive any treatment (control group). Of those treated with prostaglandin eye drops, 30 received a preservative-free formulation (tafluprost) and 30 were treated with a formulation containing the preservative benzalkonium chloride (BAK) (latanoprost). Measurement of extracellular MMP-9 levels (InflammaDry test) provided a marker for ocular surface inflammation. Further assessments of disease severity and inflammation comprised Goldmann applanation tonometry for intraocular pressure (IOP), Schirmer's test with anesthesia, ocular surface staining with unpreserved fluorescein (Oxford scale index), tear breakup time (TBUT), McMonnies questionnaire, and the Ocular Surface Disease index (OSDI). Results Clinically significant MMP-9 levels (>40 ng/mL) were detected in tear film from 46.7% of subjects treated with BAK-containing medication. In contrast, only 16.7% of subjects treated with preservative-free medication or untreated individuals demonstrated similar MMP-9 levels. This difference was statistically significant (p < 0.05). MMP-9 results correlated with other indicators of inflammation and disease severity. BAK-containing medication was associated with rapid TBUT (<5 seconds) in 50% of cases, while only 10% of untreated subjects and individuals using preservative-free medication demonstrated comparable TBUT results. Conclusion Measurement of ocular surface MMP-9 level provides a useful marker for inflammation and DED in POAG. Use of a preservative-free topical prostaglandin formulation results in lower levels of ocular inflammation, compared with BAK-containing medication.

Safety and effectiveness of albuterol solutions with and without benzalkonium chloride when administered by continuous nebulization.

The results of a study to determine if rates of poor response differ in patients receiving continuous nebulized albuterol (CNA) therapy with or without the preservative benzalkonium chloride are presented. A retrospective analysis of the records of all patients who received CNA therapy at a large academic medical center from July 2015 to January 2016 was conducted. Data from patient evaluations performed before and after a change to benzalkonium chloride-containing albuterol were collected. The primary outcome was the rate of poor patient response, defined as a composite endpoint. Secondary outcomes included duration of therapy, dosing requirements, and duration of supplemental oxygen therapy. There was no significant difference in rates of poor response between patients exposed (n = 80) and patients not exposed (n = 48) to benzalkonium chloride (16% and 17%, respectively; p = 0.95). The cohort not exposed to benzalkonium chloride had a median CNA duration of 7.0 hours, as compared with 10.5 hours for the cohort exposed to benzalkonium chloride, but this difference was not significant (p = 0.19). There were no significant differences between the benzalkonium chloride-exposed and nonexposed cohorts in the maximum dosing requirement (12.6 mg/hr versus 12.8 mg/hr, p = 0.89) or median duration of supplemental oxygen use (27.5 hours versus 16.5 hours, p = 0.77). A study of hospitalized patients receiving CNA detected no significant difference in the frequency of poor response to therapy between groups receiving benzalkonium chloride-free versus benzalkonium chloride-containing albuterol products.

FORMULATION AND DEVELOPMENT OF KETOROLAC TROMETHAMINE OPHTHALMIC SOLUTION

An acetic acid derivative ketorolac tromethmine has found its applicability in both gram positive and gram negative bacterial ocular infection and used commonly associated with multiple doses. Ophthalmic medication stored in multiple dose containers is required by the U.S. Food and Drug Administration to contain a preservative so that patients are provided with microbe free medication. Benzalkonium chloride in concentrations from 0.1% to 0.0001% induced dose-dependent growth arrest and conjunctiva epithelial cell death, either delayed or immediately after administration. In such case, a preservative Benzalkonium chloride must be used within reasonable bound. Benzalkonium chloride can provide more help than harm. Hence the present study focusing on to formulate a formulation for ketorolac tromethmine (0.5%) ophthalmic solution using different concentration of Benzalkonium chloride as preservative. Keywords: Ketorolac tromethamine, Ophthalmic, benzalkonium chloride, conjunctiva