RESUMEN
A clinical study of antimicrobial contact lenses containing the cationic peptide Mel4 was conducted. The few adverse events that occurred with this lens occurred on or after 13 nights of wear. The current study examined whether the Mel4 contact lenses lost activity during wear and the mechanism of this loss. Participants wore contact lenses for up to 13 nights. Lenses were tested for their ability to reduce the adhesion of Pseudomonas aeruginosa and Staphylococcus aureus. The amount of protein and lipid extracted from lenses was measured. The ability of trypsin to affect the antimicrobial activity of Mel4-coated contact lenses was measured. Mel4-coated contact lenses lost their antimicrobial activity at six nights of wear for both bacteria. The amount of lipids (13 ± 11 vs. 21 ± 14 µg/lens at 13 nights wear) and proteins (8 ± 4 vs. 10 ± 3 mg/lens at 13 nights of wear) extracted from lenses was not different between Mel4-coated and uncoated lenses, and was not different after three nights when antimicrobial activity was maintained and thirteen nights when they had lost activity (lipid: 25 ± 17 vs. 13 ± 11, p = 0.2; protein: 8 ± 1 vs. 8 ± 4 mg/lens, p = 0.4). Trypsin digestion eliminated the antimicrobial activity of Mel4-coated lenses. In summary, Mel4-coated contact lenses lost antibacterial activity at six nights of wear, and the most likely reason was proteolytic digestion of the peptide. Future studies will design and test proteolytically stable peptide mimics as coatings for contact lenses.
RESUMEN
(1) Purpose: This study aimed to investigate the effects of Mel4 antimicrobial contact lenses (MACL) on the ocular surface and comfort during extended wear. (2) Methods: A prospective, randomised, double-masked, contralateral clinical trial was conducted with 176 subjects to evaluate the biocompatibility of contralateral wear of MACL. The wearing modality was 14-day extended lens wear for three months. The participants were assessed at lens dispensing, after one night, two weeks, one month and three months of extended wear and one month after study completion. (3) Results: There were no significant differences (p > 0.05) in ocular redness or palpebral roughness between Mel4 and control eyes at any of the study visits. There was no significant difference (p > 0.05) in corneal staining between Mel4 and control eyes. There were no significant differences in front surface wettability or deposits or back surface debris (p > 0.05). No statistically significant differences (p > 0.05) were found in comfort, dryness, CLDEQ-8 scores lens or edge awareness. There was no evidence for delayed reactions on the ocular surface after cessation of lens wear. (4) Conclusion: The novel MACLs showed similar comfort to control lenses and were biocompatible during extended wear. Thus, these lenses were compatible with the ocular surface.
RESUMEN
PURPOSE: The purpose of this study was to investigate the effect of Mel4 antimicrobial peptide-coated contact lenses (MACL) on the microbiota of the conjunctiva and lenses during three months of extended wear. METHODS: One hundred and seventy-six participants were recruited into a randomised, contralateral, double masked, biweekly extended wear MACL and uncoated control lens trial. At the one month and 3-month visit, the conjunctival microbiota was sampled using sterile cotton swabs and contact lenses were collected aseptically. Standard microbiological procedures were employed for culture of the swabs and contact lenses and identification of the isolated microorganisms. RESULTS: Gram-positive bacteria (predominantly coagulase-negative staphylococci) were the most frequently isolated microbes from both contact lenses and conjunctiva. There was no difference in the frequency of isolation of most bacteria or fungi from the conjunctival swabs of eyes wearing either MACL or control lenses. The only exception was a higher frequency of eyes harbouring Staphylococcus arlettae when wearing control lenses (5%) versus MACL (<1%) (p = 0.002). There was no significant difference in the frequency of microbes isolated from MACL or control contact lenses. There were also no differences between lens types in the frequency of isolation of >1 microbial type per sampling occasion for either conjunctiva swabs or contact lenses. CONCLUSION: MACL wear did not change the conjunctival microbiota during extended wear, and the types of microbes isolated from MACL were similar to those isolated from control lenses.
Asunto(s)
Lentes de Contacto de Uso Prolongado , Lentes de Contacto Hidrofílicos , Lentes de Contacto , Microbiota , Antibacterianos , Péptidos Antimicrobianos , Bacterias , HumanosRESUMEN
Contact lens wear is generally safe and provides excellent vision. However, contact lens wear is often associated with the risk of developing ocular surface infection and inflammation, and in severe cases, the infection can result in loss of vision. Antimicrobial peptide-coated contact lenses have been made to help reduce the incidence of infection and inflammation. This paper reviews the research progress from conception, through the laboratory and preclinical tests to the latest information on clinical testing of an antimicrobial contact lens. We provide insights into the pathways followed and pitfalls that have been encountered. The journey has not always been linear or smooth, but has resulted in some of the first published clinical testing of antimicrobial peptide-coated contact lenses in humans. We hope this may help lead to the development and commercialisation of antimicrobial contact lenses in the future.
Asunto(s)
Antiinfecciosos/farmacología , Péptidos Catiónicos Antimicrobianos/farmacología , Infecciones Bacterianas/prevención & control , Materiales Biocompatibles Revestidos/farmacología , Lentes de Contacto/microbiología , Queratitis/prevención & control , Micosis/prevención & control , Secuencia de Aminoácidos , Animales , Infecciones Bacterianas/etiología , Infecciones Bacterianas/microbiología , Infecciones Bacterianas/patología , Ensayos Clínicos como Asunto , Lentes de Contacto/efectos adversos , Evaluación Preclínica de Medicamentos , Humanos , Queratitis/etiología , Queratitis/microbiología , Queratitis/patología , Pruebas de Sensibilidad Microbiana , Micosis/etiología , Micosis/microbiología , Micosis/patología , Pseudomonas aeruginosa/efectos de los fármacos , Pseudomonas aeruginosa/crecimiento & desarrollo , Pseudomonas aeruginosa/patogenicidad , Conejos , Serratia marcescens/efectos de los fármacos , Serratia marcescens/crecimiento & desarrollo , Serratia marcescens/patogenicidad , Staphylococcus aureus/efectos de los fármacos , Staphylococcus aureus/crecimiento & desarrollo , Staphylococcus aureus/patogenicidadRESUMEN
PURPOSE: To determine the antimicrobial activity of the melimine derived peptide Mel4 against Delftia, Stenotrophomonas, Elizabethkingia, Burkholderia and to investigate biocompatibility of Mel4 as an antimicrobial coating on contact lenses in animals and humans. METHODS: In vitro antimicrobial activity of Mel4 was determined against the four Gram negative bacteria by investigating growth curves for 24h followed by viable counts to determine the minimum inhibitory concentration (MIC). Contact lenses were coated by covalently binding Mel4, characterized by amino acid analysis, and were investigated for changes in lens parameters. Safety of Mel-4 coated lenses were determined in a rabbit model of daily contralateral wear. A prospective, randomised, double-masked, contralateral, 1week daily wear human clinical trial was used to evaluate subjective responses and ocular physiology. RESULTS: Mel4 was active against all the bacteria tested (MIC50 ranged from 31-1000µgml-1) and produced an antimicrobial surface on contact lenses. Mel4-coating resulted hydrophilic surface without any significant change in contact lens parameters, and showed no signs of cytotoxicity or ocular irritation during rabbit wear. During human clinical trial, there were no differences between Mel4 coated and uncoated contact lenses in lens performance indicators and ocular signs such as corneal fluorescein staining. Mel4 and control uncoated lenses had no differences in ocular symptoms during lens wear. CONCLUSION: Mel4 has achieved antimicrobial activity against variety of Gram negative bacteria that are often resistant to the action of cationic peptides and have been implicated in contact lens related adverse events. Mel4-coated contact lenses were safe to wear.