Lipid-based eye drop formulations for the management of evaporative dry eyes.

Dry eye disease is a progressive prevalent ocular surface disorder that arises from various factors and is characterized by insufficient quality and/or quantity of tears. The underlying pathophysiology is intricate and can progress to chronic, difficult-to-treat conditions. Multiple strategies and therapeutic approaches are utilized in its management that target one or more etiopathological components of dry eyes, which may include aqueous tear deficiency or evaporative dry eyes. The primary focus of this paper is on treatment alternatives that utilize lipids for the treatment of evaporative dry eyes. This may arise from either abnormal lipid production or inadequate lipid spreading caused by meibomian gland dysfunction. The hypothesis behind the development of these lipid-containing eye drops is that if they can imitate the lipid layer, they may be able to help in the management of the signs and symptoms of evaporative dry eyes. The lipids used in commercial formulations for dry eyes are mineral oil, castor oil, phospholipids, omega-3 fatty acid, and medium-chain triglycerides. The literature suggests the potential of lipid-containing eye drops to alleviate some of the signs and symptoms and enhance the quality of life for individuals suffering from evaporative dry eyes.

The activity of antimicrobial peptoids against multidrug-resistant ocular pathogens.

BACKGROUND: Ocular infections caused by antibiotic-resistant pathogens can result in partial or complete vision loss. The development of pan-resistant microbial strains poses a significant challenge for clinicians as there are limited antimicrobial options available. Synthetic peptoids, which are sequence-specific oligo-N-substituted glycines, offer potential as alternative antimicrobial agents to target multidrug-resistant bacteria. METHODS: The antimicrobial activity of synthesised peptoids against multidrug-resistant (MDR) ocular pathogens was evaluated using the microbroth dilution method. Hemolytic propensity was assessed using mammalian erythrocytes. Peptoids were also incubated with proteolytic enzymes, after which their minimum inhibitory activity against bacteria was re-evaluated. RESULTS: Several alkylated and brominated peptoids showed good inhibitory activity against multidrug-resistant Pseudomonas aeruginosa strains at concentrations of ≤15 µg mL-1 (≤12 µM). Similarly, most brominated compounds inhibited the growth of methicillin-resistant Staphylococcus aureus at 1.9 to 15 µg mL-1 (12 µM). The N-terminally alkylated peptoids caused less toxicity to erythrocytes. The peptoid denoted as TM5 had a high therapeutic index, being non-toxic to either erythrocytes or corneal epithelial cells, even at 15 to 22 times its MIC. Additionally, the peptoids were resistant to protease activity. CONCLUSIONS: Peptoids studied here demonstrated potent activity against various multidrug-resistant ocular pathogens. Their properties make them promising candidates for controlling vision-related morbidity associated with eye infections by antibiotic-resistant strains.

Effect of Deposition and Protease Digestion on the Ex Vivo Activity of Antimicrobial Peptide-Coated Contact Lenses.

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.

Longevity of hand sanitisers on fingers.

CLINICAL RELEVANCE: Hand hygiene is important to reduce the spread of microbes in clinical settings. Hand sanitisers that last longer may be beneficial. BACKGROUND: Longevity of hand sanitisation products on fingers and hands may be important to help reduce microbial transmission. The current study evaluated the persistence of disinfection of three hand sanitisers. METHODS: Initially the minimum inhibitory concentrations of the hand sanitisers were determined using strains of Staphylococcus epidermidis and S. aureus. Then a cross-over study with participants randomly assigned to use three different hand sanitisers for 30 seconds was undertaken. The number of bacteria and fungi on fingers was assessed 10 and 20 minutes and 4 hours after use. The type of microbial inhibition of the capric acid sanitiser was studied by examining the effects of adding Tween 80 and lecithin to microbial agar. RESULTS: The minimum inhibitory concentration of an alcohol-based sanitiser (AS) was 10%, for the capric acid-based (CS) sanitiser was 70%, and for the quaternary ammonium-based (QS) sanitiser was < 10%. AS significantly reduced the number of microbes on fingers 10 minutes after hand washing (18.2 cfu/mL) compared to CS (59.7 cfu/mL; p < 0.0001) or QS (64.5 cfu/mL; p < 0.0001). Twenty minutes after use, microbes on fingers after AS (23 cfu/mL) or CS (16.7 cfu/mL) were significantly reduced compared to QS (72.2  cfu/mL; p < 0.0001) and the numbers on fingers after CS was significantly less than after AS (p = 0.002). Four hours after use of any hand sanitiser, the number of microbes increased to near baseline levels. The reduction in bacterial numbers was not affected by the use of neutralisers in agar (48 ± 28% reduction with, 47 ± 49% reduction without; p = 0.876). CONCLUSIONS: Hand sanitisers containing capric acid or alcohol out-performed one containing quaternary ammonium in the clinical trial and may help reduce the spread of microbes.

Ability of Essential Oil Vapours to Reduce Numbers of Culturable Aerosolised Coronavirus, Bacteria and Fungi.

Transmission of pathogens present in the indoor air can occur through aerosols. This study evaluated the efficacy of an evaporated mix of essential oils to reduce the numbers of culturable aerosolized coronavirus, bacterium and fungus. The essential oil-containing gel was allowed to vaporize inside a glass chamber for 10 or 20 min. Aerosols of a surrogate of SARS-CoV-2, murine hepatitis coronavirus MHV-1, Escherichia coli or Aspergillus flavus spores were produced using a collision nebuliser and passed through the essential oil vapours, then collected on a six-stage Andersen sampler. The six-stages of the impact sampler capture aerosols in sizes ranging from 7 to 0.65 µm. The number of culturable microbes present in the aerosols collected in the different stages were enumerated and compared to the number of culturable microbes in control microbial aerosols that were not exposed to the evaporated essential oils. After 10 and 20 min evaporation, the essential oils reduced the numbers of culturable aerosolized coronavirus by 48% (log10 reduction = 0.3; p = 0.002 vs. control) and 53% (log10 reduction = 0.3; p = 0.001 vs. control), respectively. The essential oils vaporised for 10 min, reduced the number of viable E. coli by 51% (log10 reduction = 0.3; p = 0.032 vs. control). The Aspergillus flavus spores were mostly observed in the larger aerosols (7.00 µm to 2.10 µm) and the essential oils vaporised for 10 min reduced the number of viable spores by 72% (log10 reduction = 0.6; p = 0.008 vs. control). The vapours produced by a gel containing naturally occurring essential oils were able to significantly reduce the viable numbers of aerosolized coronavirus, bacteria and fungal spores. The antimicrobial gel containing the essential oils may be able to reduce aerosol transmission of microbes when used in domestic and workplace settings.

Biocompatibility and Comfort during Extended Wear of Mel4 Peptide-Coated Antimicrobial Contact Lenses.

(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.

Ocular microbiota and lens contamination following Mel4 peptide-coated antimicrobial contact lens (MACL) extended wear.

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.

The ability of face masks to reduce transmission of microbes.

CLINICAL RELEVANCE: Optometrists have been advised to wear face masks during the COVID-19 pandemic. This study examined whether face masks were equally protective against transmission of microbes. BACKGROUND: The aim of the current study was to examine the ability of face masks to reduce transmission of microbes in aerosols and during speech. METHODS: Different face masks, surgical, medical 3-ply and cloth masks with different layers were used. The masks were tested under the ASTM standard F2101-1 to measure their ability to reduce the transmission of aerosolised Staphylococcus aureus. Bacterial cells in different sized aerosols were captured on agar plates. The ability of masks to reduce the transmission of bacteria during speech over 30 cm was measured. Bacteria were captured in masks or on agar plates at a distance of 30 cm during the speech. RESULTS: All masks reduced the transmission of aerosolised S. aureus (p ≤ 0.007). The medical 3-ply and cloth masks with three layers reduced the transmission of S. aureus aerosols (3.3 µm) by 98% and surgical and seven-layer masks reduced this by 100%. An antibacterial silver mask showed significantly greater transmission of S. aureus in aerosols of 4.7 µm (16 ± 6 cells) and 3.3 µm (122 ± 66 cells) compared to all other masks (0-3 cells and 0-15 cells, respectively; p ≤ 0.016). Surgical and three-layer masks had significantly worse filtration of 1.1 µm aerosols than for other aerosol sizes. Wearing a mask reduced the transmission of bacteria during speech, but the inner surface of these masks became contaminated with 528-3060 bacterial cells. CONCLUSIONS: Face masks effectively reduce the transmission of microbes in laboratory tests. Face masks made with seven layers were very effective at stopping transmission of S. aureus in all aerosol particle sizes. However, face masks become rapidly contaminated during wear. If masks are to be re-used, they should be regularly replaced or appropriately washed.

Effect of Antimicrobial Contact Lenses on Corneal Infiltrative Events: A Randomized Clinical Trial.

Purpose: To determine whether Mel4-coated antimicrobial contact lenses (MACLs) can reduce the incidence of corneal infiltrative events (CIEs) during extended wear. Methods: A prospective, randomized, double-masked, single-center, contralateral, extended contact lens wear clinical trial was conducted with 176 subjects. Each participant was randomly assigned to wear a MACL in one eye and an uncoated control contact lens in the contralateral eye or an extended-wear biweekly disposable modality for 3 months. The main outcome measures were the incidence of CIEs per 100 eye-months, identification of the microbial types colonizing the contact lenses or eyes at the time of the CIEs, and their susceptibility to Mel4. Results: Nine participants (5.1%) experienced unilateral CIEs; six participants had contact lens acute red eye, and three participants had infiltrative keratitis. The incidence rate for CIEs (0.4 events per 100 participant months; 1.7%) in the Mel4-coated lenses (test) was 69% less than that of the control lenses (1.3 events per 100 participant months; 3.4%; P = 0.29). All Gram-negative bacteria isolated from lenses and lids of participants with CIEs (Citrobacter diversus, Acinetobacter haemolyticus, and Acinetobacter lwoffii) were susceptible to Mel4 peptide; minimum inhibitory concentrations ranged from 15.6 to 62.5 µg/mL. Reduction of adhesion of these bacteria by Mel4-coated lenses ranged from 2.1 to 2.2 log10 colony-forming units/lens. Conclusions: MACLs had the capacity to reduce CIEs by at least 50% compared with uncoated control lenses during extended wear over 3 months; however, due to the relatively low rates of CIEs, the reduction was not statistically different compared with control lenses. Translational Relevance: This study provides evidence that antimicrobial contact lenses have the potential to reduce the incidence of corneal infiltrative events during extended wear.

Contact lens fitting after corneal collagen cross-linking.

BACKGROUND: Contact lenses (CLs) remain the mainstay in improving vision in patients having keratoconus. With corneal collagen cross-linking (CXL) performed worldwide, whether the same CLs can be used or needs replacement needed to be assessed and considered. AIMS: The aim of this study was to evaluate the changes in CL fitting following CXL. SETTINGS AND DESIGN: This is a retrospective study conducted at a tertiary center. SUBJECTS AND METHODS: We analyzed the medical records of patients who underwent CXL and used CL. Data collected included demographics, pre- and post-CXL refraction, corneal topography, anterior-segment examination, and CL [rigid gas permeable(RGP)] fitting details and duration between CXL and RGP fitting. STATISTICAL ANALYSIS: Descriptive analysis and paired t-test were used to compare the pre- and post-CXL data on refraction, visual acuity, and CL parameters. The statistical significance was kept at P < 0.05. RESULTS: Thirty-four eyes (keratoconus = 32, pellucid marginal degeneration = 1, and post-LASIK ectasia = 1) of 27 patients who used CL before and after undergoing CXL were analyzed. Mean duration between CXL and RGP lens use was 2.53 months. Mean sphere and cylinder post-CXL was -4.11 ± 4.32 D and -3.54 ± 2.51 D, respectively. A mean change of 0.75 ± 3.72 D sphere and 0.71 ± 3.39 D cylinder was noted post-CXL. The post-CXL best spectacle-corrected visual acuity (CVA) was 0.52 ± 0.36 and with RGP lens it was 0.09 ± 0.18. There was no significant difference in pre- and post-CXL RGP lens CVA (0.07 ± 0.09 and 0.09 ± 0.18, respectively; P = 0.556). Pre-CXL, 3-point-touch fitting was in 24 eyes (70.59%) and central fluorescein pooling was in 10 eyes (29.41%). Post-CXL, 30 eyes (88.24%) had 3-point-touch and central fluorescein pooling was found in four eyes (11.76%). One patient had CL intolerance after CXL. Of the 32 keratoconus eyes, 62.5% (n = 20 eyes) were prescribed new lenses; 37.5% (n = 12 eyes) continued using own lenses. CONCLUSIONS: There was no significant difference in refraction, topography indices, and RGP lens parameters pre- and post-CXL. However, changes in RGP lens fitting characteristics suggest a possible change in shape or apex location of the cornea after CXL. RGP lenses remain the best option to improve visual acuity after CXL in corneal ectasia.

LogMAR and Stereoacuity in Keratoconus Corrected with Spectacles and Rigid Gas-permeable Contact Lenses.

SIGNIFICANCE: This study showed an improvement in three-dimensional depth perception of subjects with bilateral and unilateral keratoconus with rigid gas-permeable (RGP) contact lens wear, relative to spectacles. This novel information will aid clinicians to consider RGP contact lenses as a management modality in keratoconic patients complaining of depth-related difficulties with their spectacles. PURPOSE: The aim of this study was to systematically compare changes in logMAR acuity and stereoacuity from best-corrected spherocylindrical spectacles to RGP contact lenses in bilateral and unilateral keratoconus vis-à-vis age-matched control subjects. METHODS: Monocular and binocular logMAR acuity and random-dot stereoacuity were determined in subjects with bilateral (n = 30; 18 to 24 years) and unilateral (n = 10; 18 to 24 years) keratoconus and 20 control subjects using standard psychophysical protocols. RESULTS: Median (25th to 75th interquartile range) monocular (right eye) and binocular logMAR acuity and stereoacuity improved significantly from spectacles to RGP contact lenses in the bilateral keratoconus cohort (P < .001). Only monocular logMAR acuity of affected eye and stereoacuity improved from spectacles to RGP contact lenses in the unilateral keratoconus cohort (P < .001). There was no significant change in the binocular logMAR acuity from spectacles to RGP contact lenses in the unilateral keratoconus cohort. The magnitude of improvement in binocular logMAR acuity and stereoacuity was also greater for the bilateral compared with the unilateral keratoconus cohort. All outcome measures of cases with RGP contact lenses remained poorer than control subjects (P < .001). CONCLUSIONS: Binocular resolution and stereoacuity improve from spectacles to RGP contact lenses in bilateral keratoconus, whereas only stereoacuity improves from spectacles to RGP contact lenses in unilateral keratoconus. The magnitude of improvement in visual performance is greater for the binocular compared with the unilateral keratoconus cohort.

Boston keratoprosthesis for visual rehabilitation in porphyria cutanea tarda.

A 56-year-old man, presented with bilateral chronic visual loss associated with generalised skin lesions. He had undergone multiple penetrating keratoplasties in his right eye for recurrent corneal infections and perforations. On ocular examination, his left eye was phthisical and his right eye had light perception vision owing to a failed and vascularised corneal graft. Dermatological evaluation revealed multiple hyperpigmented and hypopigmented lesions along with thickening of skin on nose, scalp and dorsum of hands. Skin biopsy showed focal areas of deposition of faint periodic acid Schiff-positive diastase-resistant perivascular material. The high-performance liquid chromatography assessment revealed increased presence of porphyrins in blood and urine, thus confirming a diagnosis of porphyria cutanea tarda. The patient's vision in the right eye improved after undergoing Boston type 1 keratoprosthesis along with general photoprotective measures for the exposed parts of the body.