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Manal M Gabriel,1 Cynthia McAnally,2 Huagang Chen,2 Sruthi Srinivasan,1 Venkiteshwar Manoj,1 Renee Garofalo2 1Research and Development, Alcon Research, LLC, Johns Creek, GA, USA; 2Research and Development, Alcon Research, LLC, Fort Worth, TX, USACorrespondence: Renee Garofalo Research and DevelopmentAlcon Research, LLC, Fort Worth, TX, USATel +1 817 751 9321Email renee.garofalo@alcon.comAbstract: CLEAR CARE PLUS (CCP), also known as AOSEPT PLUS with HydraGlyde, is approved for use with gas permeable (GP) lenses, and the indication is supported by the scientific evidence that is reviewed in this article. Antimicrobial efficacy testing of CCP both as a stand-alone disinfectant and as part of a regimen shows that CCP exceeds the ISO 14729 criteria against bacteria, yeast, and mold. In real-world conditions, it is effective against clinically relevant bacterial strains isolated from adverse events and against the two forms, trophozoites and cysts, of resilient Acanthamoeba species. Compatibility tests of CCP with two types of GP lenses indicate that the physical and/or optical parameters of lenses are unaffected through 30 cycles of simulated use with CCP, and a clinical trial shows substantial equivalence of clinical performance with a commonly used GP multipurpose solution. These results indicate that CCP is well suited for cleaning and disinfection of GP contact lenses.Keywords: antimicrobial efficacy, CLEAR CARE PLUS, AOSEPT PLUS with HydraGlyde, gas permeable contact lenses, lens care

Abstract Background Proteolytic enzymes have been implicated in driving tumor progression by means of their cancer cell microenvironment activity where they promote proliferation, differentiation, apoptosis, migration, and invasion. Therapeutic strategies have focused on attenuating their activity using small molecule inhibitors, but the association of proteases with the cell surface during cancer progression opens up the possibility of targeting these using antibody dependent cellular cytotoxicity (ADCC). Cathepsin S is a lysosomal cysteine protease that promotes the growth and invasion of tumour and endothelial cells during cancer progression. Our analysis of colorectal cancer patient biopsies shows that cathepsin S associates with the cell membrane indicating a potential for ADCC targeting. Results Here we report the cell surface characterization of cathepsin S and the development of a humanized antibody (Fsn0503h) with immune effector function and a stable in vivo half-life of 274 hours. Cathepsin S is expressed on the surface of tumor cells representative of colorectal and pancreatic cancer (23%-79% positive expression). Furthermore the binding of Fsn0503h to surface associated cathepsin S results in natural killer (NK) cell targeted tumor killing. In a colorectal cancer model Fsn0503h elicits a 22% cytotoxic effect. Conclusions This data highlights the potential to target cell surface associated enzymes, such as cathepsin S, as therapeutic targets using antibodies capable of elicitingADCC in tumor cells.

Objective: Sight-threatening infections can be caused by pathogenic micro-organisms colonising the cornea, leading to microbial keratitis (MK). These micro-organisms can be introduced to the eye via improper contact lens use and care. MK can also result from ineffective contact lens care solutions (CLCs), even if the patient is following best practice guidelines. Therefore, it is critical to understand the differences between the effectiveness of popular CLCs on the global market., Methods and Analysis: Following the International Standards Organisation standards 14 729 and 18259, bacteria ( Pseudomonas aeruginosa, Serratia marcescens, Staphylococcus aureus ), fungi ( Candida albicans, Fusarium strains) and Acanthamoeba strains were inoculated into each CLC with and without contact lenses, and held for the manufacturer's stated disinfection time. Plate counts were conducted to determine the number of surviving micro-organisms., Results: All CLCs examined met the primary log reduction criteria during stand-alone testing for Pseudomonas, Staphylococcus, Candida and Fusarium . renu Multiplus, All Clean Soft, and Kombilösung Super did not meet the primary criteria when challenged with Serratia . Only OPTI-FREE Express exceeded 4 log reduction for both strains of Acanthamoeba tested. We noted a substantial reduction in disinfection efficacy when CLCs were challenged with Fusarium in the presence of lenses and cases versus stand-alone testing. OPTI-FREE Express demonstrated significantly less net log reduction loss than the other four CLCs tested., Conclusion: Of the popular CLCs on the global market, the product which relies on dual biocides polyquaternium-1 and myristamidopropyl dimethylamine demonstrated the highest disinfection efficacy in microbial disinfection challenges in the absence and presence of contact lenses., Competing Interests: Competing interests: All authors are/were employees of Alcon Research., (© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Microbial keratitis is a devastating disease that can cause eye damage and blindness and can be the result of infections by several common ocular pathogens. Importantly, some of these pathogens, such as Acanthamoeba , are particularly unsusceptible to biocides in common contact lens care solutions. Therefore, the disinfection efficacy of preservative-free (PF) disinfection systems against bacteria, fungi, and Acanthamoeba trophozoites and cysts should be assessed as products with the most potential to be efficacious against resistant organisms. PF disinfection systems were analyzed for antimicrobial efficacy. These were the one-step (hydrogen peroxide-based) Clear Care and Clear Care Plus systems and the two-step (povidone-iodine-based) Cleadew system. Stand-alone challenges using bacteria, fungi, and Acanthamoeba were prepared according to the International Standards Organization method 14729. These same challenges were also conducted in the presence of the following contact lenses: Boston RGP, Acuvue Oasys, Biofinity, Ultra, and 2-week PremiO. All challenges were performed at the manufacturer's recommended disinfection time. All preservative-free disinfection systems demonstrated similarly high rates of antimicrobial efficacy when challenged with bacteria or fungi, with or without lenses. However, both Clear Care and Clear Care Plus demonstrated significantly greater disinfection efficacy against Acanthamoeba trophozoites and cysts, with and without lenses ( P  < 0.05). Cleadew efficacy was impacted by the addition of contact lenses, whereas Clear Care/Clear Care Plus maintained similar efficacies in the absence or presence of lenses. While both hydrogen peroxide and povidone-iodine are highly effective against bacteria and fungi, hydrogen peroxide maintains significantly greater disinfection capabilities than povidone-iodine against all forms of Acanthamoeba . IMPORTANCE Understanding the most efficacious products will allow clinicians to best communicate to patients and consumers the safest products on the market to reduce adverse events, including microbial keratitis, during contact lens use.

Significance: This investigation examines the effectiveness of several common contact lens solutions in the disinfection of Acanthamoeba, which causes a serious eye infection most often resulting from dysfunctional or improper use of contact lens products., Purpose: Acanthamoeba keratitis is an eye infection caused by a free-living amoeba, which can lead to extensive corneal damage and frequently blindness. Acanthamoeba keratitis is linked with contact lens use combined with noncompliance with contact lens care cleaning regimens. The patient's choice and use of multipurpose solutions (MPSs) continue to be a risk factor for Acanthamoeba keratitis. Thus, it is critical that the Acanthamoeba disinfection efficacy of the popular MPSs be determined. Here we compare the efficacy of seven major MPSs on the global market., Methods: Using standard methods of Acanthamoeba disinfection and quantification, Acanthamoeba ATCC 30461, 30868, 50370, and 50676 trophozoites were inoculated into each MPS and held for the manufacturer's recommended disinfection time. Acanthamoeba recovery plates were incubated for 14 days, after which positive wells were identified and cell concentrations determined using the 50% endpoint method., Results: Members of the OPTI-FREE products (Express, Replenish, and Puremoist [Alcon, Fort Worth, TX]) demonstrated significantly higher percentages of antimicrobial activity compared with the renu Advanced Formula (Bausch + Lomb, Rochester, NY), Biotrue (Bausch + Lomb), Acuvue RevitaLens (Johnson & Johnson, Santa Ana, CA), and Lite products (Cooper Vision, Scottsville, NY) for four of the trophozoite strains tested., Conclusions: Many of the popular MPS biocides maintain little or no antimicrobial activity against Acanthamoeba trophozoites, and the number of biocides in an MPS does not necessarily indicate its antimicrobial activity., Competing Interests: Conflict of Interest Disclosure: All authors are employees of Alcon Research LLC. The authors have full access and control of the data reported in the study and take full responsibility for their presentation in this article. Alcon Research LLC funded the study., (Copyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Academy of Optometry.)

Microbial keratitis (MK) is an eye infection caused by opportunistic bacteria or fungi, which may lead to sight-threatening corneal ulcers. These microorganisms can be introduced to the eye via improper contact lens usage or hygiene, or ineffective multipurpose solutions (MPSs) to disinfect daily wear contact lenses. Thus, the patient's choice and use of these MPSs is a known risk factor for the development of MK. It is then critical to determine the efficacy of popular MPSs against ubiquitous ocular microorganisms. Therefore, we compare the efficacy of nine major MPSs on the global market against four different microorganism species, and with four different common contact lenses. In accordance with International Standards Organization protocol 14729 and 18259, the microorganisms were inoculated into each MPS with and without contact lenses, and held for the manufacturer's disinfection time, 24 h, and 7 days after challenge with Serratia marcescens or Fusarium spp. Plates were incubated for 2-7 days and plate counts were conducted to determine the number of surviving microorganisms. The majority of MPSs demonstrated significantly higher disinfection efficacies without contact lenses. Broadly, among the microorganisms tested, the OPTI-FREE products (Puremoist, Express, and Replenish) maintained the highest disinfection efficacies at the manufacturer's stated disinfection time when paired with any contact lens, compared with other MPSs. These were followed closely by RevitaLens and renu Advanced. MPSs containing dual biocides polyquaternium-1 and myristamidopropyl dimethylamine possessed the highest disinfection efficacy against multiple ocular pathogens.

Purpose: To compare the antimicrobial effects of CLEAR CARE, a 3% hydrogen peroxide (H2O2) solution formulated for simultaneous cleaning, daily protein removal, disinfection, and storage of soft (hydrophilic) hydrogel, silicone hydrogel, and gas-permeable contact lenses, and CLEAR CARE PLUS, consisting of the 3% H2O2 solution plus a novel wetting agent, polyoxyethylene-polyoxybutylene (EOBO-21)., Methods: Three lots each of the 2 solutions were incubated with 5 compendial microorganisms required by the Food and Drug Administration (FDA) 510(k) and International Organization for Standardization (ISO) 14729 stand-alone procedures, 4 clinical isolates of Gram-positive and Gram-negative bacteria, and trophozoites and cysts of 2 Acanthamoeba strains that are associated with microbial keratitis. Microbial loads were evaluated after disinfection and neutralization., Results: Both solutions exceeded the FDA/ISO stand-alone primary criteria against Gram-positive and Gram-negative compendial bacteria, yeast, and mold after only 1.5-hr disinfection/neutralization. At the recommended minimum disinfection time, bacteria were reduced by 4.4 to 5.1 logs, yeast by 4.4 to 4.9 logs, and mold by 2.9 to 3.5 logs with and without organic soil. In addition, both solutions eliminated or effectively reduced populations of clinically relevant ocular bacterial isolates (4.5-5.0 logs), Acanthamoeba trophozoites (3.4-4.2 logs), and cysts (1.5-2.1 logs)., Conclusion: Both solutions eliminated or reduced populations of FDA/ISO compendial bacteria and fungi as well as clinically relevant microorganisms and Acanthamoeba trophozoites and cysts. The addition of EOBO-21 to the 3% H2O2 lens care solution had no impact on antimicrobial activity.

Objective: The aim of this study was to use antimicrobial efficacy endpoint methodology to determine compatibility of multipurpose disinfecting solutions (MPSs), lens cases, and hydrogel lenses for disinfection (AEEMC) against International Organization for Standardization (ISO)-specified microorganisms and clinical ocular isolates of Stenotrophomonas maltophilia., Methods: Six MPSs (PQ/Aldox 1, 2, and 3; PQ/Alexidine; PQ/PHMB; and PHMB) were challenged against ISO-specified microorganisms and S. maltophilia using the AEEMC test. AEEMC tests were performed with and without balafilcon A, etafilcon A, and senofilcon A lenses in lens cases with organic soil. Exposure times included disinfection time (DT) and 24 hr. Additionally, all six MPSs were challenged with two strains of S. maltophilia, based on the ISO Stand-alone test., Results: The efficacy against bacteria for PQ/Aldox and PQ/Alexidine MPSs was not diminished by the presence of lenses. The efficacy of PQ/PHMB and PHMB MPSs against Serratia marcescens was significantly reduced compared with the no-lens control at DT for at least one lens type. The PHMB MPS with lenses present also demonstrated reduced efficacy against Staphylococcus aureus at DT versus the control. PQ/Aldox MPSs retained activity against Fusarium solani with lenses present; however, all other test MPSs demonstrated reduced F. solani efficacy at DT with lenses present. With lenses, all MPSs showed reduced efficacy against Candida albicans., Conclusions: AEEMC antimicrobial efficacy test results vary based on challenge microorganism, contact lenses, and MPS biocide systems. This study highlights the importance of evaluating MPSs for compatibility with lenses and lens cases.

Purpose: There has been increasing awareness of the need for more powerful contact lens disinfectants, ideally having low toxicity and allergenicity to ocular tissue. Opti-Free Express with ALDOX Multi-Purpose Disinfecting Solution (MPDS) was recently marketed as a new multi-purpose disinfecting solution for soft contact lenses. MPDS contains two antimicrobial agents, polyquaternium-1 and myristamidopropyl dimethylamine, to broaden the range of antimicrobial activity. The purpose of this study was to evaluate the antimicrobial activity of MPDS against microorganisms that have been reported as contact lens and lens case contaminants and causative agents of microbial keratitis., Methods: MPDS was challenged with high numbers of gram-positive and gram-negative bacteria, yeast, mold, and Acanthamoeba. Several lots of product were challenged with at least three separate inocula of each isolate. After exposure to the disinfecting solution, a sample was removed from the product and plated for survivors by suitable recovery methods. The plates were incubated and the number of survivors was enumerated., Results: The results showed that MPDS was bactericidal, fungicidal and amoebicidal against an extensive variety of environmental contaminants of lens care accessories and ocular pathogens. MPDS was capable of killing a broad spectrum of microorganisms. The log reduction exceeded the primary criteria for disinfecting products and produced a notable reduction of other clinical and environmental isolates as well., Conclusions: Opti-Free Express MPDS contains antimicrobial agents that can kill an extensive spectrum of many different types of microorganisms that may contaminate contact lenses and solutions.

Purpose: We compared the antimicrobial activity of a new multi-purpose disinfection solution (OPTI-FREE EXPRESS with ALDOX) to a 3% hydrogen peroxide disinfecting system. The antimicrobial ingredients in the new solution are polyquaternium-1 and myristamidopropyl dimethylamine., Methods: The solutions were tested for antimicrobial activity against Staphylococcus sp.., Pseudomonas aeruginosa, Serratia marcescens, Candida albicans, Fusarium solani, and two Acanthamoeba species and were evaluated according to the primary criteria of the FDA and ISO contact lens disinfection procedures., Results and Conclusions: OPTI-FREE EXPRESS with ALDOX (EXPRESS MPDS) Multi-Purpose Disinfecting Solution provided a multiple spectrum of antimicrobial activity and met the FDA and ISO primary Stand Alone Test criteria for disinfection of contact lenses. EXPRESS MPDS showed disinfection activity in the range of a 3% hydrogen peroxide system. Unlike the 3% hydrogen peroxide system, it retarded contamination during storage.

We evaluated the antimicrobial activity of chemical and hydrogen peroxide-neutralizer contact lens disinfection systems. The acute activity, storage, and recontamination potential of the two disinfection methods were compared by challenging the disinfectants with Staphylococcus spp., Pseudomonas aeruginosa, Serratia marcescens, Candida spp., and Aspergillus fumigatus. Chemical disinfectants preserved with polyquaternium-1 and polyhexamethylene biguanide and hydrogen peroxide-neutralizer systems with no additional preservatives were tested. Additionally, lens cases from patients using both systems were evaluated. Lens cases from patients using peroxide-neutralizer systems tended toward heavier contamination (31.8%) than the cases disinfected with a chemical system (20.3%, P = 0.16). The laboratory results showed that the differences in activity of chemical and peroxide-neutralizer systems was not statistically significant at the disinfection times against Staphylococcus epidermidis, S. marcescens, Candida parapsilosis, and A. fumigatus (P = 0.1037 to P = 0.5412). A statistical difference was shown against C. albicans (P = 0.0176) in favor of the peroxide-neutralizer systems. The reverse was true during storage. Although the chemical disinfectants maintained the population of microorganisms, the bacteria and yeast increased to over 10(7) CFU/mL in neutralized peroxide systems. Overall, the results emphasize the importance of contact lens products containing preservatives for lasting protection from microorganisms.