Ocular Antibiotic Utilisation across Aotearoa/New Zealand.

Ocular antibiotics are integral to the prevention and treatment of bacterial ocular infections. This study aimed to describe their utilisation across New Zealand according to patient and healthcare factors. Every subsidy-eligible community dispensing of ocular chloramphenicol, fusidic acid and ciprofloxacin in New Zealand, between 2010 and 2019, was included in this analysis. Number of dispensings/1000 population/year was quantified, stratified by patient age and urban/non-urban health districts. Dispensing rates by ethnicity were determined and were age adjusted. The proportion of dispensings by socioeconomic deprivation quintile was also determined. Chloramphenicol was the most commonly dispensed antibiotic; however, its utilisation decreased over time. Ciprofloxacin use was higher in children, while chloramphenicol use was higher in older patients. Ciprofloxacin usage was higher among Maori and Pasifika ethnicities, while fusidic acid use was lower. Chloramphenicol usage was higher among Pasifika. Antibiotic utilisation was higher in urban health districts, and in the most deprived quintile; both were most marked with ciprofloxacin. The utilisation of publicly funded ocular antibiotics across New Zealand varied between patient subgroups. These findings will help improve the prevention, management and outcomes of bacterial ocular infections, and support wider initiatives in antibiotic stewardship and medicine access equity.

Randomized masked trial of the clinical efficacy of MGO Manuka Honey microemulsion eye cream for the treatment of blepharitis.

PURPOSE: To assess the clinical efficacy of a novel MGO Manuka Honey microemulsion (MHME) eye cream for the management of blepharitis. METHODS: Fifty-three participants (32 females, 21 males; mean ± SD age, 60 ± 12 years) with clinical signs of blepharitis were enrolled in a prospective, investigator-masked, randomized, paired-eye trial. The MHME eye cream (Manuka Health New Zealand) was applied to the closed eyelids of one eye (randomized) overnight for 3 months. Visual acuity, ocular surface characteristics, symptoms and tear film parameters were assessed at baseline, day 30, and day 90. Eyelid swab microbiology cultures were evaluated at baseline and day 90. RESULTS: Baseline measurements did not differ between treated and control eyes (all p > 0.05). Significant reductions in SANDE and SPEED symptomology scores were detected in treated eyes on days 30 and 90 (all p < 0.05), while clinical improvements in non-invasive tear film breakup time, lipid layer thickness, and inferior lid wiper epitheliopathy were observed on day 90 (all p < 0.05). Following the 3-month treatment period, ocular Demodex, Corynebacterium macginleyi, Propionibacterium acnes, and Staphylococcus epidermidis load decreased significantly in treated eyes (all p ≤ 0.001). There were no changes in visual acuity during the 90-day period (all p > 0.05), and no major adverse events were reported. CONCLUSION: Topical overnight application of the MHME eye cream effected significant improvements in ocular surface symptomology, tear film stability and lipid layer thickness, and reduced lid margin staining, ocular Demodex and bacterial load. The favourable clinical efficacy and tolerability profile suggests promise for the MHME eye cream as a treatment for blepharitis management. TRIAL REGISTRATION NUMBER: ACTRN12616000539437.

Comparing the in vitro effects of MGO™ Manuka honey and tea tree oil on ocular Demodex viability.

PURPOSE: To compare the in vitro antiparasitic effects of MGO™ Manuka honey and tea tree oil against ocular Demodex. METHODS: Fifty-two viable Demodex mites were acquired from the epilated eyelashes of 9 participants with blepharitis and symptomatic dry eye. Viable mites were randomised to one of five treatment groups: cyclodextrin-complexed and uncomplexed Manuka Honey, 100% and 50% tea tree oil, and no treatment. Following treatment application, mite viability was assessed for 240 min, based on limb and body movement and/or the development of a crenated/translucent appearance. Kaplan-Meier survival analysis was then performed. RESULTS: The log-rank test demonstrated a significant treatment effect on the survival distribution of Demodex mites (p < 0.001). Bonferroni-corrected post-hoc pairwise analysis showed that all treatments except for uncomplexed honey effected lower survival probabilities than the untreated group (all p < 0.001). Among the four treatments, survival probabilities were lowest with 100% tea tree oil (all p < 0.001), and highest with uncomplexed honey (all p ≤ 0.001). No difference was observed between complexed honey and 50% tea tree oil (p = 0.81). CONCLUSIONS: The in vitro efficacy of cyclodextrin-complexed Manuka honey was comparable with 50% tea tree oil, an established treatment for ocular Demodex. The findings support future clinical trials investigating the therapeutic effects of complexed honey in demodectic blepharitis patients.

In vitro anti-demodectic effects and terpinen-4-ol content of commercial eyelid cleansers.

PURPOSE: To compare the in vitro anti-demodectic activity of four commercially available dedicated eyelid cleansers (Cliradex® towelette cleanser, Oust™ Demodex® cleanser, Blephadex™ eyelid foam, TheraTears® SteriLid® eyelid cleanser), tea tree oil, undiluted terpinen-4-ol and linalool; and to assess the terpinen-4-ol content of the commercial cleansers and tea tree oil. METHODS: In vitro anti-demodectic efficacy assessment: 93 viable Demodex mites were acquired from the epilated eyelashes of 10 participants, and were randomised to application with one of the four eyelid cleansers, 100% and 50% tea tree oil, undiluted terpinen-4-ol and linalool, or no treatment. Following treatment application, mite viability was assessed for 300 min, based on limb/body movement and/or the development of a crenated/translucent appearance. Kaplan-Meier survival analysis was then performed. MASS SPECTROMETRY ANALYSIS: The absolute concentration of terpinen-4-ol and the relative abundance of linalool in the four eyelid cleansers and tea tree oil were determined. RESULTS: In vitro anti-demodectic efficacy assessment: No significant differences were observed between undiluted tea tree oil, terpinen-4-ol and linalool (all p > 0.05). Although all commercial eyelid cleansers effected lower mite survival probabilities than the untreated group, Cliradex® was the only eyelid cleanser that demonstrated comparable antiparastic activity to 50% tea tree oil (p = 0.36). MASS SPECTROMETRY ANALYSIS: Among the four eyelid cleansers, Cliradex® contained the highest concentration of terpinen-4-ol, while linalool was present in TheraTears® SteriLid® only. CONCLUSIONS: Of the four commercial eyelid cleansers, Cliradex® demonstrated the highest levels of in vitro anti-demodectic activity and terpinen-4-ol content. Undiluted linalool and terpenin-4-ol showed comparable antiparasitic efficacy, and the use of linalool in the management of demodectic blepharitis warrants further investigation.

Randomized double-masked trial of eyelid cleansing treatments for blepharitis.

PURPOSE: To compare the efficacy of a dedicated eyelid cleanser and diluted baby shampoo in the management of blepharitis. METHODS: Forty-three participants with clinical blepharitis signs were enrolled in a prospective, randomized, double-masked, paired-eye trial. A dedicated eyelid cleanser (TheraTears® SteriLid®) was applied to the eyelids of one eye (randomized) and diluted baby shampoo (Johnson's® No More Tears®) to the fellow eye, twice daily for 4 weeks. Tear film parameters, ocular surface characteristics, symptomology and cytology markers were assessed at baseline and day 28. RESULTS: Baseline measurements did not differ between treatments (all p > 0.05). The eyelid cleanser was preferred over baby shampoo by the majority of participants (p < 0.001). Improvements in the tear lipid layer, inferior lid wiper epitheliopathy (LWE), cylindrical collarettes, and MMP-9 expression were limited to the dedicated eyelid cleanser (all p < 0.05), and a greater decrease in SANDE symptoms score was also observed (p = 0.04). Meibomian gland capping and MUC5AC expression worsened with baby shampoo treatment (both p < 0.05). SPEED symptoms score, superior LWE, seborrhoeic lash crusting, and trichiasis decreased significantly following application of both treatments (all p < 0.05), but did not differ between treatments (all p > 0.05). CONCLUSION: Clinical improvements in blepharitis occurred with both treatments. However, only the dedicated eyelid cleanser proved effective in reducing ocular surface inflammation, and was the preferred therapy. Long term impact of decreased goblet cell function secondary to baby shampoo treatment requires further exploration.

Preclinical development of MGO Manuka Honey microemulsion for blepharitis management.

OBJECTIVE: To evaluate the in vitro antimicrobial effects of cyclodextrin-complexed and uncomplexed Manuka honey on bacteria commonly associated with blepharitis, and in vivo rabbit eye tolerability of a cyclodextrin-complexed methylglyoxal (MGO) Manuka Honey microemulsion (MHME). METHODS AND ANALYSIS: In vitro phase: Bacterial growth inhibition was assessed by area under the growth curve (AUC) for Staphylococcus aureus, and the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) for S. aureus, Staphylococcus epidermidis and Pseudomonas aeruginosa with cyclodextrin-complexed and uncomplexed Manuka honey were determined. In vivo phase: Six rabbits were administered 20 µL of MHME (at 1:10 dilution) to the right eye (treated) and 20 µL of saline to the left eye (control) daily, for 5 days. Tear evaporation, production, osmolarity, lipid layer, conjunctival hyperaemia and fluorescein staining were assessed daily, before and 15 min after instillation. RESULTS: In vitro phase: The relative AUC for cyclodextrin-complexed Manuka honey was lower than that of uncomplexed honey at both 250 and 550 mg/kg of MGO (both p <0.05). Cyclodextrin-complexed honey had lower MIC and MBC than uncomplexed honey for both S. aureus and S. epidermidis, but not P. aeruginosa. In vivo phase: No significant changes were observed in the parameters assessed in either treated or control eyes (all p >0.05). CONCLUSION: Overall, antimicrobial potency of cyclodextrin-complexed Manuka honey was greater than uncomplexed honey. No significant immediate or cumulative adverse effects were observed with MHME application on rabbit eyes, supporting future conduct of clinical safety and tolerability trials in human subjects.

Randomised masked trial of the clinical safety and tolerability of MGO Manuka Honey eye cream for the management of blepharitis.

OBJECTIVE: To assess the clinical safety and tolerability of a novel MGO Manuka Honey microemulsion (MHME) eye cream for the management of blepharitis in human subjects. METHODS AND ANALYSIS: Twenty-five healthy subjects were enrolled in a prospective, randomised, paired-eye, investigator-masked trial. The MHME eye cream (Manuka Health New Zealand) was applied to the closed eyelids of one eye (randomised) overnight for 2 weeks. LogMAR visual acuity, eyelid irritation symptoms, ocular surface characteristics and tear film parameters were assessed at baseline, day 7 and day 14. Expression of markers of ocular surface inflammation (matrix metalloproteinase-9 and interleukin-6) and goblet cell function (MUC5AC) were quantified using impression cytology at baseline and day 14. RESULTS: There were no significant changes in visual acuity, eyelid irritation symptoms, ocular surface characteristics, tear film parameters and inflammatory marker expression during the 2-week treatment period in treated and control eyes (all p>0.05), and measurements did not differ significantly between eyes (all p>0.05). No major adverse events were reported. Two subjects experienced transient ocular stinging, presumably due to migration of the product into the eye, which resolved following aqueous irrigation. CONCLUSION: The MHME eye cream application was found to be well tolerated in healthy human subjects and was not associated with changes in visual acuity, ocular surface characteristics, tear film parameters, expression of markers of inflammation or goblet cell function. The findings support future clinical efficacy trials in patients with blepharitis. TRIAL REGISTRATION NUMBER: ACTRN12616000540415.

Beneficial effect of the antioxidant riboflavin on gene expression of extracellular matrix elements, antioxidants and oxidases in keratoconic stromal cells.

BACKGROUND: Keratoconus manifests as a conical protrusion of the cornea and is characterised by stromal thinning. This causes debilitating visual impairment which may necessitate corneal transplantation. Therapeutic targets related to disease mechanisms are currently lacking, as the pathobiology remains unclear. Many pathological features may be manifestations of defects in wound healing and reactive oxygen species (ROS)-associated functions. In a wide range of tissue and cell types, antioxidant exposure has beneficial effects on both of these pathways. This study investigated the effect of treatment with the antioxidant riboflavin on wound healing and ROS-associated functions in keratoconus. METHODS: Stromal cells were isolated from human central keratoconic (n = 3) and normal (n = 3) corneas. Total RNA was extracted and reverse-transcribed into complementary DNA. The gene expression of 22 genes involved in repair (eight normal and four repair-type extracellular matrix constituents) and ROS-associated processes (eight antioxidants and two ROS-synthesising oxidases) was quantified using quantitative polymerase chain reaction. This was also performed on keratoconic stromal cells treated in vitro with riboflavin (n = 3). RESULTS: In stromal cells from untreated keratoconic corneas (compared with untreated normal corneas), there was an up-regulation of 7/12 extracellular matrix elements. Four of eight antioxidants and two of two oxidases were also increased. In treated keratoconic corneas (compared with untreated keratoconic corneas), six out of eight normal extracellular matrix constituents were up-regulated and two of four repair-type molecules were reduced. An increase was also observed in seven out of eight antioxidants and there was a diminution in two out of two oxidases. CONCLUSION: Riboflavin encourages the synthesis of a normal extracellular matrix and reduces reactive oxygen species levels in keratoconus. This supports the occurrence of wound healing and ROS-associated abnormalities in keratoconus. By targeting the causative disease mechanisms, riboflavin may have therapeutic potential in the clinical management of keratoconus.

A new perspective on the pathobiology of keratoconus: interplay of stromal wound healing and reactive species-associated processes.

Severe loss of vision manifests from the corneal protrusion, thinning and distortion that characterises keratoconus, which in its most severe form is still treated primarily by lamellar or penetrating keratoplasty. Unfortunately, alternative therapeutic options targeting the underlying pathobiology remain limited, attributable to an incomplete understanding of the biological mechanisms instigating stromal deterioration and other disease processes. We postulate that underlying abnormalities in stromal repair and reactive species-linked activities and the interaction between these phenomena are implicated in the development of keratoconus. This revised interpretation of the pathophysiology may, with further investigation, advance our knowledge and the clinical management of this prevalent ectatic disorder.