Article

Randomised controlled trial of topical antibacterial Manuka (Leptospermum species) honey for evaporative dry eye due to meibomian gland dysfunction

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Abstract

Background: The aim was to evaluate the efficacy of standardised Manuka (Leptospermum species) antibacterial honey as adjunctive twice daily treatment to conventional therapy (warm compresses, lid massage and preservative-free lubricant), in participants with evaporative dry eye due to moderate to advanced meibomian gland dysfunction. Methods: This prospective, open-label study involved 114 participants. After two weeks of conventional therapy participants were randomised to one of three treatment groups: Optimel Antibacterial Manuka Eye Gel (98 per cent Leptospermum species honey) plus conventional therapy (n = 37), Optimel Manuka plus Lubricant Eye Drops (16 per cent Leptospermum species honey) plus conventional therapy (n = 37) and a control (conventional therapy) (n = 40). Clinical evaluations performed at baseline and Week 8 included: symptom scores (Ocular Surface Disease Index, Ocular Comfort Index), daily lubricant use, tear assessments (break-up time, secretion, osmolarity and InflammaDry), corneal sensation, ocular surface staining, meibomian gland secretion quality and expressibility, bulbar conjunctival, limbal and lid marginal redness and eyelid marginal bacterial cultures and colony counts. Results: Significant improvements (p ≤ 0.05) occurred at Week 8 in symptoms, tear break-up time, staining, tear osmolarity, meibum quality and bulbar, limbal and lid margin redness for all treatments. Improvement in staining was significantly greater with Optimel 16 per cent drops (p = 0.035). Significant improvements (p < 0.05) in meibomian gland expressibility and InflammaDry occurred for both Optimel treatments. Optimel 98 per cent gel was significantly more effective in improving meibum quality (p = 0.005) and gland expressibility (p = 0.042). Total eyelid marginal bacterial colony counts reduced significantly with Optimel 16 per cent drops (p = 0.03) but not the other treatments. Staphylococcus epidermidis counts reduced significantly with Optimel 16 per cent drops (p = 0.041) and Optimel 98 per cent gel (p = 0.027). Both Optimel treatments significantly reduced the need for lubricants, with Optimel 16 per cent drops decreasing lubricant use most (p = 0.001). Temporary redness and stinging were the only adverse effects of Optimel use. Conclusions: Optimel antibacterial honey treatments are effective as adjunctive therapies for meibomian gland dysfunction.

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... honey, 980 mg/g, Melcare Biomedical Pty Ltd, Mt Cotton, Australia), are regulatory approved as medical devices for treating dry eye/eye discomfort, sore eyes, and irritated eyelids. 12,13 Although several clinical trials have investigated the treatment of dry eye using manuka honey, relevant metaanalyses have not been reported. Therefore, the aim of the present study was to perform a systematic review and metaanalysis of the studies that investigated the use of manuka honey for the treatment of dry eye. ...
... The characteristics of the five included studies are summarised in Table 1. The studies were conducted in Australia (n = 3), 12,22,23 New Zealand (n = 1) 21 and China (n = 1), 13 and were all published between 2017 and 2021. All were single-centre studies. ...
... All were single-centre studies. Three studies used a parallel-group design, 12,13,22 while the remaining two used a paired-eye 21 and a crossover 23 design. ...
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Dry eye has become an increasingly prevalent public health issue for which there is currently no cure. Manuka honey possesses anti-inflammatory and antioxidant properties that can be used to treat dry eye. The present study aimed to systematically review evidence supporting the treatment of dry eye with manuka honey and quantify this evidence via meta-analysis. Randomised clinical trials that fulfilled the inclusion criteria from database inception until 5 September 2021, were identified through online searches of seven databases, including but not limited to Embase, Medline, and Central. Changes between the point of longest follow-up and baseline subjective symptoms, tear film quality, ocular surface characteristics, adverse events, and compliance were selected for meta-analysis. A total of 288 adult participants with dry eye from five eligible randomised controlled trials were analysed. Compared with the control groups, treatment with manuka honey demonstrated a significant improvement in Ocular Surface Disease Index, Standard Patient Evaluation of Eye Dryness, tear evaporation rate, negative conversion rate of matrix metalloproteinase-9 levels, ocular surface staining, and daily use frequency of lubricant. No serious adverse events were reported, except for temporary stinging and redness, which were generally tolerated. This review found that manuka honey demonstrated promising results for the treatment of dry eye. However, limitations of the included studies and analytical methodology affect the reliability of this conclusion. Therefore, further high-quality randomised clinical trials are required to confirm the efficacy and safety of the use of manuka honey in the treatment of dry eye.
... In ophthalmology practice, Leptospermum honey has been previously used in the treatment of corneal edema and meibomian gland dysfunction. 4,5 Up to our knowledge, we used 100% Leptospermum medical grade Manuka honey (First Honey, Nashville, TN, United States) in the treatment of persistent CED in human eyes for the first time. ...
... Leptospermum honey gel and drops have lubricating effects and were found to reduce the number of lubricating drops used by patients with evaporative eye disease. 5 In both cases, conventional treatment with heavy, frequent lubrication drops, ointment and eyelid taping was tried for 2 weeks with no improvement. To isolate the effects of Leptospermum honey ointment, lubricating drops and ointments were held in both cases before starting Leptospermum honey ointment. ...
... However, in a study on meibomian gland dysfunction, no adverse effects were reported with 98% Leptospermum honey ointment and 16% Leptospermum honey drops other than redness and stinging. 5 The lack of animal studies supporting the use of Leptospermum 100% honey ointment in CEDs is considered a limitation of the study. Moreover, Leptospermum 100% medical grade Manuka honey ointment was used as off label in the present study. ...
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Background: To study the efficacy of 100% Leptospermum medical grade Manuka honey ointment in persistent corneal epithelial defects (CEDs). Methods: Case series. Results: Case 1 was a 25-year-old female patient who presented to the cornea clinic with a persistent CED (3.5 mm), following acanthamoeba keratitis, that had failed to respond to heavy, frequent lubrication drops and ointment. Two weeks later, after starting Leptospermum honey ointment (4 times per day), the CED healed totally. Case 2 was a 48-year diabatic, single-eyed female patient who presented with a persistent CED (1.5 × 1.5 mm) that had failed to respond to heavy, frequent lubrication drops and ointment. The CED healed three weeks after starting Leptospermum honey ointment (4 times per day). Conclusions: Leptospermum honey ointment can be a potential treatment for persistent epithelial defect.
... Promising results have been found using these drops for treatment of meibomian gland dysfunction-related dry eye disease. 13 We aimed to compare these eye-drops with conventional treatment for meibomian gland dysfunction in an Asian population. ...
... Systane Ultra was used as it is a currently available medication in our local pharmacy formulary and was also used as a control treatment in the study by Albietz and Schmid. 13 Patients in the intervention arm were also taught the usual lid hygiene and warm compress methods, but were given Optimel 16% eye-drops (approved in Australia (Australian Register of Therapeutic Goods identifier 199785) and Europe (CE-marked) for ocular use in meibomian gland dysfunction-related dry eye disease) and were instructed to use it two times per day. A diary card was given to patients of both groups to record and ensure compliance to the eye-drops. ...
... Significant improvement in subjective symptoms and objective signs was demonstrated. Similarly, in an open-label, randomised controlled trial by Albietz and Schmid, 13 Optimel 16% eye-drops were found to provide significant symptomatic and objective improvements in tear break-up time, staining, meibum quality, bulbar and lid margin redness, as well as other parameters such as bacterial colony count and InflammaDry levels. They also reported transient stinging and redness with the manuka honey eye-drops but no other adverse effects. ...
Article
Purpose To evaluate the effects of manuka honey eye-drops in the treatment of meibomian gland dysfunction. Methods This is an assessor-masked (single-blind), randomised controlled trial comparing conventional treatment group with interventional group using Optimel 16% manuka honey topical eye-drops. 59 patients were recruited to the study and randomised into two groups: one given regular lubricants and the other given Optimel 16% manuka honey eye-drops. The Standard Patient Evaluation of Eye Dryness (SPEED) score was measured at baseline and on follow-up. 4 patients were lost to follow-up. Multiple ocular surface parameters were graded from slit lamp examination by a masked assessor. Results were compared from baseline to follow-up date 3 weeks later. Results Patients in the conventional treatment group demonstrated minimal difference in SPEED score at 3-week follow-up (mean difference 1.087, p=0.183), which was not statistically significant. However, measurements of tear film break-up time, corneal surface stain (Oxford), lid margin, conjunctival redness, as well as meibum quality and expressibility showed significant improvements at 3 weeks (p<0.01). Patients in the manuka honey eye-drops group showed significant difference after 3 weeks in SPEED score (mean difference 2.53, p=0.006), as well as in lid margin redness, conjunctival redness, corneal surface stain (Oxford), and meibum quality and expressibility (p=0.000). Conclusions Optimel 16% manuka honey eye-drops showed significant improvement in symptoms and objective signs in meibomian gland dysfunction and are an effective alternative treatment for meibomian gland dysfunction. Trial registration number NCT04457648 .
... 12 Optimel Manuka+ Dry Eye Drops is a proprietary formulated eye drop with 16% Leptospermum spp honey and is at present, along with the gel form (98% Leptospermum spp honey), the only formulated eye drop with honey commercially available in either Australia or the UK. 13 Formulated eye drops with honey have been shown to improve ocular comfort when used twice daily in as little as 2 weeks in contact lens wearers 14 and after 8 weeks in subjects with meibomian gland dysfunction. 13 No significant differences were observed in objective measures of dry eye after 2 weeks of use, which may have been related to the short duration of treatment. ...
... 12 Optimel Manuka+ Dry Eye Drops is a proprietary formulated eye drop with 16% Leptospermum spp honey and is at present, along with the gel form (98% Leptospermum spp honey), the only formulated eye drop with honey commercially available in either Australia or the UK. 13 Formulated eye drops with honey have been shown to improve ocular comfort when used twice daily in as little as 2 weeks in contact lens wearers 14 and after 8 weeks in subjects with meibomian gland dysfunction. 13 No significant differences were observed in objective measures of dry eye after 2 weeks of use, which may have been related to the short duration of treatment. 14 However, measurable improvements in tear film break-up time, tear osmolarity and meibomian expressibility were observed after 8 weeks of treatment. ...
... 14 However, measurable improvements in tear film break-up time, tear osmolarity and meibomian expressibility were observed after 8 weeks of treatment. 13 Therefore, the purpose of this study was to evaluate the effects of a formulated eye drop with Leptospermum spp honey versus a conventional ocular lubricant on tear film properties, ocular surface staining and comfort in subjects with symptoms related to dry eye disease after 28 days of treatment, to determine whether measurable changes to objective tear film characteristics in particular can be detected earlier than after 8 weeks of treatment. ...
Article
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Aim To evaluate the effects of a proprietary formulated eye drop with Leptospermum spp honey versus a conventional lubricant eye drop on tear film properties in subjects with symptoms related to dry eye disease after 28 days of treatment. Methods Forty-six subjects with symptoms related to dry eye (Ocular Surface Disease Index (OSDI) score >12) were enrolled and randomly assigned to receive either the test formulated eye drop (Optimel by Melcare Biomedical Pty Ltd) or control eye drops (Alcon, USA) in this double-masked study. Inferior lipid layer thickness (LLT), tear film evaporation rate (TER), fluorescein tear film break-up time (TBUT), corneal staining and subjective symptoms (OSDI and visual analogue scales (VAS)) were measured before and after 28 days of instilling the eye drops. Results Forty-two subjects completed the study (21 subjects in each group). After 28 days of treatment, TER showed a significantly greater reduction with the formulated eye drop compared with the control (p=0.01). TBUT showed a slight but not statistically significant increase with the formulated eye drop compared with the control (p=0.06), and a significantly greater reduction (improvement) in OSDI scores was observed with the formulated eye drop compared with the control (p=0.01). No significant differences were found between the two groups for inferior LLT, corneal staining and any of the VAS scores. Conclusions The formulated eye drops were effective in reducing tear film evaporation rate and were more effective for improving symptoms of dry eye compared with the control eye drops after 28 days of treatment. Trial registration number NCT03622619 .
... Three papers related to non-antibiotic-containing topical treatments of MGD were identified and reviewed ( Table 6). The studies by Albietz and Schmid and Mihaltz et al. were RCTs,72,73 whereas the study by Steven et al. 74 was a multicenter uncontrolled study. Manuka (Leptospermum species) honey, lipid-containing eye drops, and perfluorohexyloctane eye drops were discussed in these papers respectively. ...
... Antibacterial Manuka (Leptospermum species) honey was delivered in two formulations, namely Optimel Manuka Eye Gel (with 98% Manuka honey) and Optimel Eye Drop (with 16% Manuka honey). 72 Despite all groups (including the control) showing significant improvements in dry eye metrics (e.g., TBUT, redness), increased MG expressibility and reduced MMP 9 counts were only observed in the two groups treated with Manuka honey, showing that Optimel Manuka is an effective adjunctive therapy for MGD. The two formulations had their respective advantages. ...
... Only temporary redness and stinging sensation were reported after the use of Optimel Manuka Gel and Eye Drops. 72 For lipidcontaining eye drops, some patients may not tolerate it well. In the study by Mihaltz et al., 73 two patients opted to terminate the use of lipid-containing eye drops because of local irritation, burning, and transient blurred vision. ...
Article
Objectives: To evaluate recent studies on available therapies for meibomian gland dysfunction (MGD). Methods: A literature search on recent publications, within the last five years, concerning treatment options for MGD was performed. Results: A total of 35 articles were reviewed after curation by the authors for relevance. In general, all modalities of treatments were shown to have clinical efficacy in alleviating dry eye signs and symptoms, although the extent of improvement and persistency of outcomes varied between the different treatments. Evidence from published studies demonstrate that thermal pulsation produces the longest lasting effect per treatment, but it also incurs the highest per-treatment cost. Reusable methods for warm compress with lipid/semi-fluorinated alkane-containing eye drops are recommended as first-line treatment for mild-to-moderate dry eye patients, because this option is most technically feasible and cost-effective in clinical practice. Intense pulsed light (IPL) therapy and thermal pulsation may be suitable as second line for patients unresponsive to warm compress therapy; however, their respective limitations need to be considered. For refractory MGD with features of periductal fibrosis or severe blepharitis, supplementary treatment with meibomian gland probing or oral antibiotics may be used. Conclusions: All eight forms of treatments, including self-applied eyelid warming, thermal pulsation, IPL, MG probing, antibiotics, lipid-containing eye drops, and perfluorohexyloctane, were effective against MGD, although with varying extent of clinical improvements. A better understanding on the mechanisms of actions may guide physicians to make better treatment decisions targeting the root causes.
... For instance, a long digital device exposure to the gland may cause lacrimal gland hypofunction, and normal aging has resulted in its malfunction, compromising the tear film integrity [164,165]. An evaporative dry eye disease caused by MGD increases tear evaporation and osmolarity, which subsequently extends the susceptibility to ocular surface inflammation and epithelial disruption [166]. ...
... Optimel eye gel significantly improved meibomian gland expressibility and meibum quality. On the other hand, the Optimel eye drop markedly reduced the growth of bacteria at the eyelid margin, whereas both Optimel treatments greatly suppressed S. epidermidis growth [166]. In a separate study, Tan J et al. demonstrated the comparison of the effects of an Optimel eye drop and conventional lubricant on the tear film properties in 42 participants with dry eye symptoms (Ocular Surface Disease Index score (ODSI) >12). ...
Article
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Honey and propolis have recently become the key target of attention for treating certain diseases and promoting overall health and well-being. A high content of flavonoids and phenolic acids found in both honey and propolis contributes to the antioxidant properties to scavenge free radicals. Honey and propolis also exhibited antibacterial effects where they act in two ways, namely the production of hydrogen peroxide (H2O2) and gluconic acids following the enzymatic activities of glucose oxidase, which exerts oxidative damage on the bacteria. Additionally, the anti-inflammatory effects of honey and propolis are mainly by reducing proinflammatory factors such as interleukins and tumor necrosis factor alpha (TNF-α). Their effects on pain were discovered through modulation at a peripheral nociceptive neuron or binding to an opioid receptor in the higher center. The aforementioned properties of honey have been reported to possess potential therapeutic topical application on the exterior parts of the eyes, particularly in treating conjunctivitis, keratitis, blepharitis, and corneal injury. In contrast, most of the medicinal values of propolis are beneficial in the internal ocular area, such as the retina, optic nerve, and uvea. This review aims to update the current discoveries of honey and propolis in treating various ocular diseases, including their antioxidant, anti-inflammatory, antibacterial, and anti-nociceptive properties. In conclusion, research has shown that propolis and honey have considerable therapeutic promise for treating various eye illnesses, although the present study designs are primarily animal and in vitro studies. Therefore, there is an urgent need to translate this finding into a clinical setting.
... Previous studies investigating management therapies for dry eye disease subtypes have tended to focus on evaporative dry eye disease [4][5][6][7][8][9][10][11][12]. In terms of subtype efficacy comparison, Alio and colleagues found little difference in the effectiveness of autologous platelet-rich plasma in the management of aqueous deficient compared to evaporative dry eye [13], whereas, while Essa and colleagues found the artificial tears they tested performed similarly, that osmolarity-balanced artificial tears were the preferred treatment in individuals with aqueous deficient dry eye and liposomal sprays/drops were more effective for individuals with evaporative dry eye [14,27]. ...
... Overgrowth of bacteria on the ocular surface is one of the factor that associated with tear deficiency. [27][28][29] Our limitation in this study is the short duration of honey cocktail supplementation. Longer duration of oral supplementation of honey cocktail is recommended to look for the beneficial effect of honey since honey has a slow effect. ...
... Recently, there has been a growing number of studies showing the effectiveness of eyelid hygiene with tea tree oil and manuka honey in MGD, blepharitis, Demodex mites, and Staphylococci infections which all cause dry eye disease. [46][47][48] Also, terpinen-4-ol, the main component of tea tree oil, has been demonstrated to be effective in bacterial, parasitic, and fungal ocular infections. 49 In our study, we used commercially available wet wipes containing terpinen-4-ol for eyelid hygiene and we were unable to evaluate microbial colonization in the base of the eyelashes which can be deemed as a limitation of the present study. ...
Article
Background: Dry eye disease is one of the most common pathologies of the ocular surface. In this study, we aimed to evaluate the impact of eyelid hygiene on tear film stability, ocular symptoms, and vision-related quality of life among operating room staff. Methods: This single-blind, randomized-controlled study included a total of 142 eyes of 71 operating room staff with at least Stage I dry eye disease. The participants were divided into two groups: the intervention group (n=34) and control group (n=37). Tear break-up time, Schirmer 1 test, corneal staining grading, Ocular Surface Diseases Index, McMonnies Questionnaire, Visual Function Questionnaire were used for data collection. The intervention group received eyelid hygiene consisting of warm compress, massage, cleaning. Results: The mean age was 35.73±5.38 years in the intervention group and 38.72±6.49 years in the control group. Of the participants, 79% and 78% were females in the intervention and control groups, respectively. In the intervention group, the ocular symptoms regressed, tear break-up time, and Ocular Surface Diseases Index scores increased, the corneal staining grading decreased, ocular pain scores decreased, and mental health scores increased in the Visual Function Questionnaire subscales (p<0.05). In the control group, the tear break-up time and Ocular Surface Diseases Index scores decreased, ocular pain and existing symptoms increased, and mental health decreased (p<0.05). Conclusion: The results suggest that eyelid hygiene improves the ocular surface and tear film quality with reduced ocular symptoms and better vision-related quality of life in this population.
... Previous studies investigating management therapies for dry eye disease subtypes have tended to focus on evaporative dry eye disease [4][5][6][7][8][9][10][11][12]. In terms of subtype efficacy comparison, Alio and colleagues found little difference in the effectiveness of autologous platelet-rich plasma in the management of aqueous deficient compared to evaporative dry eye [13], whereas, while Essa and colleagues found the artificial tears they tested performed similarly, that osmolarity-balanced artificial tears were the preferred treatment in individuals with aqueous deficient dry eye and liposomal sprays/drops were more effective for individuals with evaporative dry eye [14,27]. ...
Article
Purpose To examine clinical management and prescribing patterns for dry eye disease (DED), in relation to severity and subtype, by eyecare practitioners across the globe. Methods An online-anonymous cross-sectional survey (on Qualtrix) translated into 14 languages was distributed to eyecare practitioners across the globe. The survey included six questions around the management of DED, in relation to severity and subtype. Result The survey was completed by 1139 eyecare professionals (37% ophthalmologists and 58% optometrists) from 51 countries. Management varied significantly by continent and country (p < 0.01). The most commonly recommended management approaches internationally, included general advice (87%), low (85%) and high (80%) viscosity-enhancing unpreserved lubricants and lid wipes/scrubs (81%). Some treatments were prescribed largely independent of severity (e.g. artificial tears and nutritional supplements) while oral antibiotics, punctal occlusion, topical anti-inflammatory/immunosuppressants, secretagogues, biologics, therapeutic contact lenses and surgical approaches were prescribed by more practitioners as severity increased. Essential fatty acids, lipid sprays/drops, lid hygiene, warm compresses, intense pulsed light therapy and antibiotics (topical or oral) were more commonly recommended for evaporative DED, while artificial tears, moisture chamber goggles, punctal occlusion, therapeutic contact lenses, secretagogues and biologics were used more commonly for aqueous deficient DED. Conclusions DED management differs between continents and countries. A wide range of management strategies are utilised at each severity level and across subtypes. The survey results enable clinicians to benchmark their practice to their peers, indicate where further research is required to optimise patient management and to inform industry on how best to target product development.
... For example, manuka honey has recently been researched and commercialized as a treatment for dry eye disease and meibomian gland dysfunction with published reports detailing the benefits of this treatment. 33,34 The main limitation of this study was the search engines' ability to accurately identify Web sites with information on complementary and alternative therapies specifically for dry eye disease. Many of search engine results led to Web sites that described dry eye disease, complementary and alternative therapies in general, or therapies for dry eye disease that were not complementary and alternative therapies as defined by the Tear Film & Ocular Surface Society Dry Eye Workshop II Report Executive Summary. 1 This limited the number of Web sites that were able to be analyzed and may have prevented more complementary and alternative therapies for dry eye disease from being identified. ...
Article
Significance: Dry eye disease is a common condition with many complementary and alternative therapies promoted online. Patients may inquire about these therapies, and clinicians should be aware of the existence, safety, and efficacy of these therapies, as well as the quality of available online information. Purpose: Complementary and alternative medicine is a multibillion-dollar industry with increasing popularity. Dry eye disease is a chronic condition with many complementary and alternative therapies described online. Patients may inquire about and elect to forgo conventional treatments in favor of these therapies. This study identified alternative treatments for dry eye disease described online and evaluated the Web sites that described them. Methods: An Internet search algorithm identified Web sites describing complementary and alternative therapies for dry eye disease. Web site quality was assessed using the Sandvik score to evaluate Web site ownership, authorship, source, currency, interactivity, navigability, and balance. The potential risk of Web sites to patients was assessed using a risk scoring system. A list of described therapies was compiled. Results: Eight Web sites describing complementary and alternative therapies for dry eye disease were assessed. The Sandvik score classified more than half of the Web sites as "satisfactory" and none as "poor." The overall mean risk score was low at 0.9. One Web site displayed information that discouraged the use of conventional medicine, whereas no Web sites discouraged adhering to clinicians' advice. The Web sites listed 12 therapies with a further 32 found in Web site comments. The most common therapies were acupuncture, vitamin supplements, homeopathic eye drops, castor oil, coconut oil, and chamomile eye wash. Conclusions: The majority of analyzed Web sites were of satisfactory quality with a low potential risk to patients. However, some Web sites were biased toward their own therapies, lacked proper referencing, and/or did not identify authorship. Further research is required to ascertain the efficacy and safety of these therapies.
... 4 Macrolide therapy using azithromycin has also been used for its anti-inflammatory effects to help control bacterial flora and lid inflammation. 4 Topical Manuka honey is well-known for its anti-inflammatory effects, and the eye drop formulations have been shown to reduce the bacterial count from the eyelid and conjunctiva of patients with dry eye disease, 17,18 and to also improve clinical signs such as tear film stability, lipid layer thickness and lid margin staining, as well as comfort. 19 There is a lack of high-quality clinical trial evidence to support the use of topical Manuka honey as a first-line anti-inflammatory intervention, however this method was chosen to minimise the use of long-term corticosteroids. ...
... Manuka honey is also used in the therapy of other conditions, such as chronic rhinosinusitis and evaporative dry eye. Randomized controlled trials were performed by Albietz J. et al. [47] and Lee V.S. et al. [48]. ...
Article
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Chronic wound infections are difficult to manage because of the biofilm formation in the wound environment. New measures for eliminating infections are necessary to increase the chance of wound healing. Apitherapy may be the new solution. The aim of this study was to assess the prevalence of wound infection factors and to examine the impact of Manuka honey and ethanol extract of propolis on biofilm formation of Proteus mirabilis isolated from chronic wound infections. According to the findings, the most frequent factors of infection are Staphylococcus aureus (46.1%), Pseudomonas aeruginosa (35.0%), and Proteus mirabilis (10.6%). Minimal inhibitory concentration and minimal bactericidal concentration values were assigned using the microbroth dilution test according to the Clinical and Laboratory Standards Institute. Biofilm of Proteus mirabilis isolates was formed in 96-well polystyrene plates and treated with Manuka honey (concentrations from 1.88% to 30.0%) and ethanol extract of propolis (1.0% to 40.0%). After 24 h, the biofilm viability was expressed by formazan absorbance (λ = 470 nm). Manuka honey reduced the biofilm viability in all, and ethanol extract of propolis in most, of the concentrations tested. Ethanol extract of propolis at the concentrations of 20.0% and 40.0%, reduced biofilm viability stronger than ethanol itself. With these results comes the conclusion that these substances can reduce biofilm formation.
... In addition to the aforementioned, several other treatment options for MGD are in the pipeline, including the P2Y2 receptor agonist Diquafosol [28] and Manuka honey eye preparations [29] that have been shown to improve MGD however further studies are needed to establish effectiveness. ...
... Nevertheless, these symptoms generally resolved following aqueous irrigation of the ocular surface, and were avoided with subsequent application of a more modest amount of product further from the eyelash margin. These findings following application of the MHME cream to the eyelid contrast with the ocular redness and stinging reported following application of uncomplexed honey formulations directly onto the ocular surface [37]. ...
Article
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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.
... A report from Lithuania in 2007 showed improvement in DED with use of 20% honey solution eye drops [169]. There is also a growing body of work looking specifically at Manuka honey for use in Sjögren syndrome and non-Sjögren aqueous deficient dry eye and evaporative dry eye due to MGD [170]. ...
Article
Full-text available
Dry eye disease (DED) is one of the most frequent presentations to optometrists with over 16 million US adults (6.8% of adult population) diagnosed as having this disorder. The majority of associated marketed products offer relief from symptomatology but do not address aetiology. DED harbours many distinguishing features of a chronic inflammatory disorder. The recent explosion in human microbiome research has sparked interest in the ocular microbiome and its role in the preservation and extension of ocular surface health and in the contribution of the gut microbiome to chronic systemic inflammation and associated “Western life-style” diseases. With a significant lack of success for many patients using currently available DED treatments, in this era of the microbiome, we are interested in exploring potential novel therapies that aim to reconstitute healthy bacterial communities both locally and distally (in the gut) as a treatment for DED. Although this direction of investigation is in its infancy, burgeoning interest makes such a review timely. This paper considers a number of studies into the use functional foods and associated products to ameliorate dry eye.
... In contrast, a recently developed topical formulation of cyclodextrin-complexed MGO ™ Manuka Honey microemulsion (MHME) has successfully undergone safety and tolerability testing, with a two-week randomised masked clinical trial of healthy human subjects [37]. This demonstrated that, where applied carefully to the external eyelid surface, overnight topical application was not associated with major adverse events or changes in clinical ocular parameters, inflammatory and goblet cell function marker expression [37], contrary to the minor adverse effects of transient stinging and ocular redness reported for ocular surface application of uncomplexed honey formulations [38]. The results of the current study would therefore suggest that cyclodextrin-complexed Manuka honey shows the potential to offer an alternative non-irritating topical treatment for demodectic blepharitis [37]. ...
Article
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.
... The study found the honey products significantly improved meibomian gland expressibility and reduced the need for lubricants. The eye drop formulation significantly improved staining and reduced the bacterial colony count in those treated [15]. ...
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Natural products have been in use long before the introduction of modern drug therapies and are still used in various communities worldwide for the treatment of anterior eye disease. The aim of this review is to look at the current non-pharmaceutical modalities that have been tried and assess the body of existing evidence behind them. This includes alternative medicine, existing non-pharmaceutical therapy and more recent low and high tech solutions. A detailed search of all available databases including MEDLINE, Pubmed and Google was made to look for English-language studies for complementary and alternative treatment modalities (CAM), natural therapies and new modalities for anterior eye disease such as blepharitis, dry eye and microbial keratitis. We have included a broad discussion ranging from traditional treatments like honey and aloe vera which have been used for centuries, to the more recent technological advances like Intense Pulsed Light (IPL), LipiFlow and photoactivated chromophore for corneal cross linking in infectious keratitis (PACK-CXL). Alternative management strategies may have a role in anterior eye diseases and have a potential in changing the way we currently approach them. Some of the available CAM could play a role if incorporated in to current management practices of not only chronic diseases like blepharitis and dry eye, but also acute conditions with significant morbidity like microbial keratitis. Further large-scale randomized control trials stratified by disease severity are required to improve our understanding and to evaluate the use of non-pharmaceutical therapy against current practice.
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Introduction Eye drops play a prominent role in the treatment and/or management of many ocular diseases, however, they often have limitations. It is recognized that new therapies are needed in this area, to improve patient care. Areas covered This manuscript discusses a novel class of materials, known as fluid gels, for their ability to improve ocular care. The paper focuses on how the materials address several key limitations to eye drops, such as longevity, lubrication, and delivery. Expert opinion Eye drops are a common source of treatment/management for many ocular diseases. However, lacking the complexity of the native tear, they often fail to hit the mark in terms of performance. In particular, the longevity of many drops and ocular lubricants is insufficient to keep active compounds in situ and/or offer adequate treatment. Fluid gels have high prospects in this area; as careful control over their microstructures provides a platform that can be applied to the ocular surface for in the order of hours. Not only can retention be finely tuned, but such materials also offer highly lubricating properties. Excitingly, promising pre-clinical data, coupled with the means to manufacture at scale, offers a tantalizing new prospect for the future of ocular treatments.
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Hair loss is often distressing and can have a significant effect on the patient’s quality of life. Alopecia can be the result of temporary or permanent hair loss on a limited area or covering the entire scalp. Androgenetic alopecia affects 80% of the white male population and approximately 40% of the female population. Genetic factors and the activity of androgen hormones play a crucial role in the process of this type of baldness. The excessive sensitivity of the organism to dihydrotestosterone, (a testosterone derivative), is considered to be the direct cause of androgenetic alopecia. Although hair loss is not life threatening, it can be related to negative psychological effects, including lower self-esteem, depression, and a general dissatisfaction with the appearance of your body. Current treatment methods have been based on topical minoxidil and oral finasteride (male only). The therapy is effective only during the use of medications, after discontinuing the medications, the process of baldness progresses and is associated with the occurrence of undesirable side effects. Currently, there is a lot of research on the use of alternative methods in the treatment of alopecia based on the use of stem cells and platelet-rich plasma, which have a significant therapeutic potential. The test results confirm the effectiveness of the above-mentioned methods.
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Purpose of review: Dry eye disease (DED) is a multifactorial disease affecting approximately 5-50% of individuals in various populations. Contributors to DED include, but are not limited to, lacrimal gland hypofunction, meibomian gland dysfunction (MGD), ocular surface inflammation, and corneal nerve dysfunction. Current DED treatments target some facets of the disease, such as ocular surface inflammation, but not all individuals experience adequate symptom relief. As such, this review focuses on alternative and adjunct approaches that are being explored to target underlying contributors to DED. Recent findings: Neuromodulation, stem cell treatments, and oral royal jelly have all been studied in individuals with DED and lacrimal gland hypofunction, with promising results. In individuals with MGD, devices that provide eyelid warming or intense pulsed light therapy may reduce DED symptoms and signs, as may topical Manuka honey. For those with ocular surface inflammation, naturally derived anti-inflammatory agents may be helpful, with the compound trehalose being farthest along in the process of investigation. Nerve growth factor, blood-derived products, corneal neurotization, and to a lesser degree, fatty acids have been studied in individuals with DED and neurotrophic keratitis (i.e. corneal nerve hyposensitivity). Various adjuvant therapies have been investigated in individuals with DED with neuropathic pain (i.e. corneal nerve hypersensitivity) including nerve blocks, neurostimulation, botulinum toxin, and acupuncture, although study numbers and design are generally weaker than for the other DED sub-types. Summary: Several alternatives and adjunct DED therapies are being investigated that target various aspects of disease. For many, more robust studies are required to assess their sustainability and applicability.
Article
Aim: Contact lens induced dry eye affects approximately 50% of contact lens wearers. The aim was to assess the effects of Manuka (Leptospermum sp.) honey eye drops (Optimel, Melcare, Australia) on dry eye in contact lens wearers. The safety of the honey eye drops in contact lens wear and contact lens wearers' compliance were also evaluated. Design: Prospective, randomised, cross over study, examiner masked, pilot treatment trial. Methods: Twenty-four participants aged 20 to 55 years with contact lens related dry eye were recruited and randomised to two treatment groups; 20 completed the study. One group used Optimel eye drops twice a day for two weeks followed by conventional lubricant (Systane Ultra, Alcon) therapy for two weeks; the other group completed the treatments in the reverse order. Before and after each treatment dry eye symptomology, ocular surface inflammation, and tear quantity and quality were assessed. Participants completed a daily log detailing their usage of treatments and any issues. Results: Dry eye symptoms improved significantly after Optimel treatment. Patients with more severe symptoms at baseline showed a greater improvement in symptoms. No significant differences were observed in the objective signs of dry eye; presumably because of the short treatment duration. Seventy-five% of contact lens wearers reported good adherence to Optimel treatment and 95% reported no issues using this product. Conclusions: Optimel Eye Drops reduce the symptoms of dry eye in contact lens wearers and are safe to use. A longer treatment period to assess the effect on clinical signs of dry eye is required.
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The purpose of this work was to investigate the effect of 20% honey solution eye drops on human patients with dry eye syndrome. Thirty six patients (72 eyes) of mean age 44.7 years old were examined. Investigations were carried out before and after the treatment. Nineteen patients were treated with 20% honey solution eye drops three times a day, and 17 patients were treated with artificial tears three times a day as a control. After treatment with the honey eye drops, improvement of ocular changes was observed in most of the patients compared to the control treatment. We also found a positive effect of the honey eye drops on the state of the cornea.
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Meibomian gland dysfunction (MGD) is the most frequent cause of dry eye disease (DED). Eyelid inflammation, microbial growth, associated skin disorders as well as potentially severe corneal complications culminate to make MGD a complex multifactorial disorder. It is probable that MGD is a heterogeneous condition arising from any combination of the following five separate pathophysiological mechanisms: eyelid inflammation, conjunctival inflammation, corneal damage, microbiological changes and DED resulting from tear film instability. The pathogenesis of both MGD and DED can be described in terms of a ‘vicious circle’: the underlying pathophysiological mechanisms of DED and MGD interact, resulting in a double vicious circle. The MGD vicious circle is self-stimulated by microbiological changes, which results in increased melting temperature of meibum and subsequent meibomian gland blockage, reinforcing the vicious circle of MGD. Meibomian gland blockage, dropout and inflammation directly link the two vicious circles. MGD-associated tear film instability provides an entry point into the vicious circle of DED and leads to hyperosmolarity and inflammation, which are both a cause and consequence of DED. Here we propose a new pathophysiological scheme for MGD in order to better identify the pathological mechanisms involved and to allow more efficient targeting of therapeutics. Through better understanding of this scheme, MGD may gain true disease status rather than being viewed as a mere dysfunction.
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Objective: To evaluate the evidence in the peer-reviewed literature regarding the use of tear osmolarity as a physiological marker to diagnose, grade severity, and track therapeutic response in dry eye disease (DED). In addition, to review the evidence for the role of tear osmolarity in the pathophysiology of DED and ocular surface disease. Methods: A literature review of all publications after the year 2000, which included the keywords "tear osmolarity", was conducted. Relevant articles were graded according to quality of evidence and research, using the University of Michigan Practice Guideline and the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) rating systems. Articles were further categorized by the nature of any reported financial support and by the overall impression they provided related to tear osmolarity. Results: A total of 164 articles were identified as relevant to the search criteria, although some were editorials, and some were written in a foreign language. Of the total, it was possible to grade 159, and an overall impression was generated for 163. A positive impression of tear osmolarity in DED diagnosis was evident in 72% (117/163) of all articles, with a neutral impression in a further 21% (35/163); 7% had a negative impression. The percentage of positive impressions appeared independent of the quality of research; 73% (38/52) of articles graded high/moderate quality supported the use of tear film osmolarity measurement in DED diagnosis. Impressions were also independent of the source of financial support, with 72% (75/104) of independent studies positive. Conclusion: The literature broadly supports the use of tear film osmolarity as an objective numerical measure for diagnosing, grading severity, and managing treatment of DED.
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To investigate the efficacy of topical 90% medical-grade kanuka honey and 10% glycerine (Honevo) as a treatment for rosacea. Randomised controlled trial with blinded assessment of primary outcome variable. Outpatient primary healthcare population from 5 New Zealand sites. 138 adults aged ≥16, with a diagnosis of rosacea, and a baseline blinded Investigator Global Assessment of Rosacea Severity Score (IGA-RSS) of ≥2. 69 participants were randomised to each treatment arm. 1 participant was excluded from the Honevo group, and 7 and 15 participants withdrew from the Honevo and control groups, respectively. Participants were randomly allocated 1:1 to Honevo or control cream (Cetomacrogol), applied twice daily for 8 weeks. The primary outcome measure was the proportion of participants who had a ≥2 improvement in the 7-point IGA-RSS at week 8 compared to baseline. Secondary outcomes included change in IGA-RSS and subject-rated visual analogue score of change in severity (VAS-CS) on a 100 mm scale (0 mm 'much worse', 100 mm 'much improved') at weeks 2 and 8. 24/68 (34.3%) in the Honevo group and 12/69 (17.4%) in the control group had a ≥2 improvement in IGA-RSS at week 8 compared to baseline (relative risk 2.03; 95% CI 1.11 to 3.72, p=0.020). The change in IGA-RSS for Honevo compared to control at week 2 minus baseline was -1 (Hodges-Lehman estimate, 95% CI -1 to 0, p=0.03), and at week 8 minus baseline was -1 (Hodges-Lehman estimate, 95% CI -1 to 0, p=0.005). The VAS-CS at week 2 was 9.1 (95% CI 3.5 to 14.7), p=0.002, and at week 8 was 12.3 (95% CI 5.7 to 18.9)¸ p<0.001 for Honevo compared to control. Honevo is an effective treatment for rosacea. This trial was registered in the Australian and New Zealand Clinical Trials Registry ACTRN12614000004662. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.
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Background Acacia honey (AH) has been proven to improve skin wound healing, but its therapeutic effects on corneal epithelium has not been elucidated to date. This study aimed to investigate the effects of AH on cultured corneal epithelial cells (CEC) on in vitro corneal abrasion wound healing model. Six New Zealand white rabbits’ CEC were isolated and cultured until passage 1. Circular wound area was created onto a confluent monolayer CEC using a corneal trephine which mimicked corneal abrasion and treated with 0.025% AH supplemented in basal medium (BM) and complete cornea medium (CCM). Wound healing was measured as the percentage of wound closure by the migration of CEC on day 0, day 3 and day 6, post wound creation. The morphological changes of CEC were assessed via phase contrast microscopy. Gene and protein expressions of cytokeratin (CK3), fibronectin and cluster of differentiation 44 (CD44) in AH treated groups and control groups were determined by real-time PCR and immunocytochemistry, respectively. Results Cultured CEC exhibited similar morphology of polygonal shaped cells in all culture media. CEC cultured in AH-supplemented media showed higher percentage of wound closure compared to the controls. Gene expression of CK3 increased in AH-supplemented groups throughout the study. Fibronectin expression was increased at the initial stage while CD44 expression was increased at day 3, post wound creation. The protein expression of CEC cultured in all media was in accordance to their respective gene expressions. Conclusion Supplementation of AH in BM and CCM media accelerates CEC wound closure of the in vitro corneal abrasion model by increasing the expression of genes and proteins associated with CEC wound healing.
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Meibomian gland dysfunction (MGD) appears to be the most common cause of evaporative dry eye, in which the meibum has an altered chemical structure that increases its melting point. Eyelid warming masks slowly transfer heat, preferably between 40 and 45°C to the inner meibomian glands, in an attempt to melt or soften the stagnant meibum. This ex vivo study evaluates the heat retention properties of commercially available masks over a 12-min interval. Five eyelid-warming masks (MGDRx EyeBag(®), EyeDoctor(®), Bruder(®), Tranquileyes™, Thera°Pearl(®)) were heated following manufacturer's instructions and heat retention was assessed at 1-min interval for 12min on a non-conductive surface. A facecloth warmed with hot tap water was used as comparison. All masks reached above 40°C within the first 2min after heating and remained so for 5min, with the exception of the facecloth, which lasted only 3min and quickly degraded to 30°C within 10min. The Bruder(®) and Tranquileyes™ reached >50°C, after heating and the Bruder(®) maintained >50°C for nearly 6min. The MGDRx EyeBag(®), and Thera°Pearl(®) had the most stable heat retention between 2 and 9min, remaining between the targeted temperature. Heat retention profiles are different for commercially available eyelid warming masks. This ex vivo study highlights that despite the popularity of the time-honored facecloth, it is poor at retaining the desired heat over a 5-10min interval. Clinical studies need to corroborate these results, remembering that ocular tissue parameters may be factors to consider. Copyright © 2015 British Contact Lens Association. Published by Elsevier Ltd. All rights reserved.
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Background/aims To investigate the efficacy and safety of the MGDRx EyeBag (The Eyebag Company, Halifax, UK) eyelid warming device. Methods Twenty-five patients with confirmed meibomian gland dysfunction (MGD)-related evaporative dry eye were enrolled into a randomised, single masked, contralateral clinical trial. Test eyes received a heated device; control eyes a non-heated device for 5 min twice a day for 2 weeks. Efficacy (ocular symptomology, non-invasive break-up time, lipid layer thickness, osmolarity, meibomian gland dropout and function) and safety (visual acuity, corneal topography, conjunctival hyperaemia and staining) measurements were taken at baseline and follow-up. Subsequent patient device usage and ocular comfort was ascertained at 6 months. Results Differences between test and control eyes at baseline were not statistically significant for all measurements (p>0.05). After 2 weeks, statistically significant improvements occurred in all efficacy measurements in test eyes (p<0.05). Visual acuity and corneal topography were unaffected (p>0.05). All patients maintained higher ocular comfort after 6 months (p<0.05), although the benefit was greater in those who continued usage 1–8 times a month (p<0.001). Conclusions The MGDRx EyeBag is a safe and effective device for the treatment of MGD-related evaporative dry eye. Subjective benefit lasts at least 6 months, aided by occasional retreatment. Trial registration number NCT01870180.
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Stem cells with enhanced resistance to oxidative stress after in vitro expansion have been shown to have improved engraftment and regenerative capacities. Such cells can be generated by preconditioning them with exposure to an antioxidant. In this study we evaluated the effects of Tualang honey (TH), an antioxidant-containing honey, on human corneal epithelial progenitor (HCEP) cells in culture. Cytotoxicity, gene expression, migration, and cellular resistance to oxidative stress were evaluated. Immunofluorescence staining revealed that HCEP cells were holoclonal and expressed epithelial stem cell marker p63 without corneal cytokeratin 3. Cell viability remained unchanged after cells were cultured with 0.004, 0.04, and 0.4% TH in the medium, but it was significantly reduced when the concentration was increased to 3.33%. Cell migration, tested using scratch migration assay, was significantly enhanced when cells were cultured with TH at 0.04% and 0.4%. We also found that TH has hydrogen peroxide (H2O2) scavenging ability, although a trace level of H2O2 was detected in the honey in its native form. Preconditioning HCEP cells with 0.4% TH for 48 h showed better survival following H2O2-induced oxidative stress at 50 µM than untreated group, with a significantly lower number of dead cells (15.3±0.4%) were observed compared to the untreated population (20.5±0.9%, p<0.01). Both TH and ascorbic acid improved HCEP viability following induction of 100 µM H2O2, but the benefit was greater with TH treatment than with ascorbic acid. However, no significant advantage was demonstrated using 5-hydroxymethyl-2-furancarboxaldehyde, a compound that was found abundant in TH using GC/MS analysis. This suggests that the cellular anti-oxidative capacity in HCEP cells was augmented by native TH and was attributed to its antioxidant properties. In conclusion, TH possesses antioxidant properties and can improve cell migration and cellular resistance to oxidative stress in HCEP cells in vitro.
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Purpose. This trial was designed to evaluate the efficacy and safety of topical honey eye drops in patients with diagnosed VKC. Methods. This clinical trial was conducted on 60 patients with diagnosed VKC. The patients were selected and randomly allocated between two groups of 30. Patients in two groups received honey eye drop (60% in artificial tear) or placebo, other than cromolyn and fluorometholone 1% eye drops, to be used topically in each eye, four times per day. The patients were examined with slit lamp and torch at baseline and the follow-up visits on the 1st, 3rd, and 6th months of the study for redness, limbal papillae, and intraocular pressure. Results. Out of 60 patients who completed the study, 19 patients (31.7%) were female. There was significant increase in eye pressure and reduction in redness as well as limbal papillae, following the consumption of the honey drop in honey group compared to placebo control group (P < 0.05). At the end of trial, one patient in honey group and 7 ones in placebo group had limbal papillae (P < 0.05). Conclusion. Topical honey eye drops, when used along with Cromolyn and Fluorometholone eye drops, might be beneficial for the treatment of VKC.
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The role of honey in wound healing continues to attract worldwide attention. This study examines the anti-inflammatory effect of four honeys on wound healing, to gauge its efficacy as a treatment option. Isolated phenolics and crude extracts from manuka (Leptospermum scoparium), kanuka (Kunzea ericoides), clover (Trifolium spp.), and a manuka/kanuka blend of honeys were examined. Anti-inflammatory assays were conducted in HEK-Blue™-2, HEK-Blue™-4, and nucleotide oligomerization domain (NOD)2-Wild Type (NOD2-WT) cell lines, to assess the extent to which honey treatment impacts on the inflammatory response and whether the effect was pathway-specific. Kanuka honey, and to a lesser extent manuka honey, produced a powerful anti-inflammatory effect related to their phenolic content. The effect was observed in HEK-Blue™-2 cells using the synthetic tripalmitoylated lipopeptide Pam3CysSerLys4 (Pam3CSK4) ligand, suggesting that honey acts specifically through the toll-like receptor (TLR)1/TLR2 signaling pathway. The manuka/kanuka blend and clover honeys had no significant anti-inflammatory effect in any cell line. The research found that kanuka and manuka honeys have an important role in modulating the inflammatory response associated with wound healing, through a pathway-specific effect. The phenolic content of honey correlates with its effectiveness, although the specific compounds involved remain to be determined.
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Meibomian gland dysfunction (MGD) is one of the most common diseases observed in clinics; it influences a great number of people, and is the leading cause of evaporative dry eye. Given the increased recognition of the importance of MGD, a great amount of attention has been paid to therapies targeting this condition. The traditional treatments of MGD consist of warm compresses and lid hygiene for removing an obstructed meibum, as well as antibiotics and anti-inflammatory agents to improve the quality of the meibum. However, each of these treatments has a different shortcoming and the treatment of MGD remains challenging. Despite the numerous possible treatment options for MGD, it is still difficult to obtain complete relief of signs and symptoms. This review focuses on current emerging treatment options for MGD including intraductal meibomian gland probing, emulsion eye drops containing lipids, the LipiFlow® thermal pulsation system, N-acetyl-cysteine, azithromycin, oral supplementation with omega-3 essential fatty acids, and cyclosporine A.
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Treatment of chronic wounds is becoming increasingly difficult due to antibiotic resistance. Complex natural products with antimicrobial activity, such as honey, are now under the spotlight as alternative treatments to antibiotics. Several studies have shown honey to have broad-spectrum antibacterial activity at concentrations present in honey dressings, and resistance to honey has not been attainable in the laboratory. However not all honeys are the same and few studies have used honey that is well defined both in geographic and chemical terms. Here we have used a range of concentrations of clover honey and a suite of manuka and kanuka honeys from known geographical locations, and for which the floral source and concentration of methylglyoxal and hydrogen peroxide potential were defined, to determine their effect on growth and cellular morphology of four bacteria: Bacillus subtilis, Escherichia coli, Staphylococcus aureus and Pseudomonas aeruginosa. While the general trend in effectiveness of growth inhibition was manuka>manuka-kanuka blend>kanuka>clover, the honeys had varying and diverse effects on the growth and cellular morphology of each bacterium, and each organism had a unique response profile to these honeys. P. aeruginosa showed a markedly different pattern of growth inhibition to the other three organisms when treated with sub-inhibitory concentrations of honey, being equally sensitive to all honeys, including clover, and the least sensitive to honey overall. While hydrogen peroxide potential contributed to the antibacterial activity of the manuka and kanuka honeys, it was never essential for complete growth inhibition. Cell morphology analysis also showed a varied and diverse set of responses to the honeys that included cell length changes, cell lysis, and alterations to DNA appearance. These changes are likely to reflect the different regulatory circuits of the organisms that are activated by the stress of honey treatment.
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Pseudomonas aeruginosa (PA) and Staphylococcus aureus (SA) biofilms are associated with poor chronic rhinosinusitis (CRS) disease control following surgery. Manuka honey (MH) has been shown to be both an effective in vitro treatment agent for SA and PA biofilms and nontoxic to sinonasal respiratory mucosa. Methylglyoxal (MGO) has been reported to be the major antibacterial agent in MH. The effect of this agent against SA and PA biofilms has yet to be reported. Our objective was to determine the in vitro effect of MGO against biofilms of SA and PA, via in vitro testing of MGO against bacterial biofilms. An established biofilm model was used to determine the effective concentration (EC) of MGO against 10 isolates of methicillin-resistant SA (MRSA) and PA. The EC of MGO was also determined against planktonic (free-swimming) MRSA and PA. For MRSA, the EC against planktonic organisms was a concentration of 0.08 mg/mL to 0.3 mg/mL whereas against the biofilm MRSA isolates, the EC ranged from 0.5 mg/mL to 3.6 mg/mL. For PA, the EC against planktonic organisms was a concentration of 0.15 mg/mL to 1.2 mg/mL for planktonic organisms whereas against the biofilm PA isolates, the EC ranged from 1.8 mg/mL to 7.3 mg/mL. MGO, a component of MH, is an effective antimicrobial agent against both planktonic and biofilm MRSA and PA organisms in vitro.
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Alkali injury is one of the most devastating injuries to the eye. It results in permanent unilateral or bilateral visual impairment. Chemical eye injury is accompanied by an increase in the oxidative stress. Anti-inflammatory and antioxidant agents play a major role in the treatment of chemical eye injuries. The purpose of this study is to evaluate the anti-inflammatory (clinical and histopathological) and antioxidant effects of Tualang honey versus conventional treatment in alkali injury on the eyes of rabbits. A preliminary study was carried out prior to the actual study to establish the alkali chemical injury on rabbit's cornea and we found that alkali chemical injury with 2 N NaOH showed severe clinical inflammatory features. In actual study, alkali injury with 2 N NaOH was induced in the right eye of 10 New Zealand White rabbits' cornea. The rabbits were divided into two groups, Group A was given conventional treatment and Group B was treated with both topical and oral Tualang honey. Clinical inflammatory features of the right eye were recorded at 12 hours, 24 hours, 72 hours, 5th day and 7th day post induction of alkali burn on the cornea. The histopathological inflammatory features of the right corneas of all rabbits were also evaluated on day-7. The level of total antioxidant status and lipid peroxidation products in the aqueous humour, vitreous humour and serum at day-7 were estimated biochemically. Fisher's Exact, Chi-Square and Mann-Whitney test were used to analyse the data. There was no statistically significant difference in clinical inflammatory features (p > 0.05) between honey treated and the conventional treated group at different times of examination. Histopathological examination of the cornea showed the number of polymorphonuclear leucocytes was below 50 for both groups (mild grade). There was also no significant difference in the level of total antioxidant status as well as lipid peroxidation products in aqueous humour (p = 0.117, p = 0.382 respectively), vitreous humour (p = 0.917, p = 0.248 respectively) and serum (p = 0.917, p = 0.332 respectively) between honey treated and the conventional treated group. Tualang honey has almost the equal effects when compared with the conventional treatment in treating alkali injury on rabbit's eye. Future research with more number of rabbits and control group is warranted to explore the anti-inflammatory and antioxidant effects of Tualang honey.
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Recent evidence suggests a potential role for honeys in mediating clinical inflammation and tissue damage. Here, we investigated the anti-inflammatory activity of a selection of previously untested indigenous New Zealand (NZ) honeys. We found that several, but not all, New Zealand rewarewa, manuka and kanuka honey samples exhibited potent, dose-dependent reduction of human neutrophil superoxide production in vitro. This inhibitory activity did not correlate with levels of known phenolic-based free radical scavengers. Furthermore, the active honeys did not scavenge superoxide generated in a cell-free xanthine/xanthine oxidase assay. In C57BL/6 J mice, topical application of manuka and rewarewa honey samples with the highest in vitro activity suppressed arachidonic acid-induced ear oedema, and rewarewa honey suppressed both oedema and leukocyte (monocyte and neutrophil) infiltration. Together, these findings demonstrate that some indigenous NZ honeys exhibit clinically relevant anti-inflammatory activity. Further investigation is warranted to identify the active component(s) and mechanisms responsible for these activities and to determine potential applications for anti-inflammatory honeys in the topical treatment of clinical inflammation.
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Chronic wound infections and antibiotic resistance are driving interest in antimicrobial treatments that have generally been considered complementary, including antimicrobially active honey. Australia has unique native flora and produces honey with a wide range of different physicochemical properties. In this study we surveyed 477 honey samples, derived from native and exotic plants from various regions of Australia, for their antibacterial activity using an established screening protocol. A level of activity considered potentially therapeutically useful was found in 274 (57%) of the honey samples, with exceptional activity seen in samples derived from marri (Corymbia calophylla), jarrah (Eucalyptus marginata) and jellybush (Leptospermum polygalifolium). In most cases the antibacterial activity was attributable to hydrogen peroxide produced by the bee-derived enzyme glucose oxidase. Non-hydrogen peroxide activity was detected in 80 (16.8%) samples, and was most consistently seen in honey produced from Leptospermum spp. Testing over time found the hydrogen peroxide-dependent activity in honey decreased, in some cases by 100%, and this activity was more stable at 4 °C than at 25 °C. In contrast, the non-hydrogen peroxide activity of Leptospermum honey samples increased, and this was greatest in samples stored at 25 °C. The stability of non-peroxide activity from other honeys was more variable, suggesting this activity may have a different cause. We conclude that many Australian honeys have clinical potential, and that further studies into the composition and stability of their active constituents are warranted.
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The goals of the subcommittee were to review the current practice and published evidence of medical and surgical treatment options for meibomian gland dysfunction (MGD) and to identify areas with conflicting, or lack of, evidence, observations, concepts, or even mechanisms where further research is required. To achieve these goals, a comprehensive review of clinical textbooks and the scientific literature was performed and the quality of published evidence graded according to an agreed on standard, using objective criteria for clinical and basic research studies adapted from the American Academy of Ophthalmology Practice Guidelines1 (Table 1). It should be noted that, in many of the clinical textbooks and previous reports, terminology is often interchanged and the management of anterior and posterior blepharitis and/or meibomitis is often considered concurrently. Thus, a broad scope of documents was reviewed in this process. Consistency in terminology and global adoption of the term “meibomian gland dysfunction” would significantly aid clinical research and clinical care in MGD going forward.
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D iagnostic tests of meibomian gland dysfunction (MGD) and of MGD-related disorders are based on the demonstration of abnormal anatomy and physiology of the glands and the detection of specific pathologic events. For this reason, this subcommittee report is divided into two sections. In part I, those aspects of meibomian anatomy and physiology that are relevant to currently available tests are described; a fuller account of the anatomy and physiology is provided in the report of the Anatomy Subcommittee of this workshop. In part II, each test and its performance is described in detail. In part III, the practical application of selected tests is summarized and recommendations for future approaches are made. Additional recommendations and a summary of pertinent literature and concepts are presented in Appendices 1 to 17.
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Scientists have been interested in studying the secretions of the meibomian glands for many years, 1– 8 and diseases associated with the meibomian glands (e.g., cancers, posterior blepharitis) have been noted in the medical literature since at least the early part of the 20th Century. 9 –13 However, the term “meibomian gland dysfunction” (MGD) was only introduced by Korb and Henriquez in 1980. 14 The terminology “meibomian gland disease” was later introduced by Bron et al. 15 as an umbrella term to indicate any disease affecting the meibomian glands (see Definition and Classification). Although the etiology of MGD may differ from that of aqueous-deficient dry eye disease (which is due to insufficient lacrimal gland production), the two conditions share many clinical features, including symptoms of ocular surface irritation and visual fluctuation, altered tear film stability, and potential ocular surface compromise. When MGD is of sufficient degree, it may give rise to the second major subtype of dry eye disease, evaporative dry eye. 16 These subtypes are not mutually exclusive, as has been acknowledged. 16
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National Natural Science Foundation of China (NSFC) [30872806, 30872809]; Ministry of Public Health of China; Ministry of Science and Technology of China [2006AA02A131]; Natural Science Foundation of Fujian Province [2009J06023]
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Supported by the Tear Film and Ocular Surface Society (TFOS; http://www.tearfilm.org); individual author support is listed in the Appendix of the Introduction. Disclosure: Each Workshop Participant's disclosure data can be found in the Appendix of the Introduction.
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The purpose of this study was to investigate the effects of manuka honey on the structural integrity of Pseudomonas aeruginosa ATCC 27853. The minimum inhibitory concentration (MIC) and the minimum bactericidal concentration (MBC) of manuka honey for P. aeruginosa were determined by a microtitre plate method, and the survival of bacteria exposed to a bactericidal concentration of manuka honey was monitored. The effect of manuka honey on the structure of the bacteria was investigated using scanning and transmission electron microscopy (SEM and TEM, respectively). The MIC and MBC values of manuka honey against P. aeruginosa were 9.5% (w/v) and 12% (w/v) respectively; a time-kill curve demonstrated a bactericidal rather than a bacteriostatic effect, with a 5 log reduction estimated within 257 min. Using SEM, loss of structural integrity and marked changes in cell shape and surface were observed in honey-treated cultures. With TEM, these changes were confirmed, and evidence of extensive cell disruption and lysis was found. Manuka honey does not induce the same structural changes in P. aeruginosa as those observed in staphylococci. Our results indicate that manuka honey has the potential to be an effective inhibitor of P. aeruginosa.
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Honey has potent activity against both antibiotic-sensitive and -resistant bacteria, and is an interesting agent for topical antimicrobial application to wounds. As honey is diluted by wound exudate, rapid bactericidal activity up to high dilution is a prerequisite for its successful application. We investigated the kinetics of the killing of antibiotic-resistant bacteria by RS honey, the source for the production of Revamil® medical-grade honey, and we aimed to enhance the rapid bactericidal activity of RS honey by enrichment with its endogenous compounds or the addition of antimicrobial peptides (AMPs). RS honey killed antibiotic-resistant isolates of Pseudomonas aeruginosa, Staphylococcus epidermidis, Enterococcus faecium, and Burkholderia cepacia within 2 h, but lacked such rapid activity against methicillin-resistant S. aureus (MRSA) and extended-spectrum beta-lactamase (ESBL)-producing Escherichia coli. It was not feasible to enhance the rapid activity of RS honey by enrichment with endogenous compounds, but RS honey enriched with 75 μM of the synthetic peptide Bactericidal Peptide 2 (BP2) showed rapid bactericidal activity against all species tested, including MRSA and ESBL E. coli, at up to 10-20-fold dilution. RS honey enriched with BP2 rapidly killed all bacteria tested and had a broader spectrum of bactericidal activity than either BP2 or honey alone.
Article
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Clinical use of honey in the topical treatment of wounds has increased in Europe and North America since licensed wound care products became available in 2004 and 2007, respectively. Honey-resistant bacteria have not been isolated from wounds, but there is a need to investigate whether honey has the potential to select for honey resistance. Two cultures of bacteria from reference collections (Staphylococcus aureus NCTC 10017 and Pseudomonas aeruginosa ATCC 27853) and four cultures isolated from wounds (Escherichia coli, methicillin-resistant S. aureus (MRSA), Pseudomonas aeruginosa and S. epidermidis) were exposed to sub-lethal concentrations of manuka honey in continuous and stepwise training experiments to determine whether the susceptibility to honey diminished. Reduced susceptibilities to manuka honey in the test organisms during long-term stepwise resistance training were found, but these changes were not permanent and honey-resistant mutants were not detected. The risk of bacteria acquiring resistance to honey will be low if high concentrations are maintained clinically.
Article
Honey has been used as a medicine for thousands of years and its curative properties are well documented. However, modern medicine turned its back on honey and it is only now, with the advent of multi-resistant bacteria, that the antibiotic properties of honey are being rediscovered.
Article
Purpose: To compare dry eye (DE) symptoms and signs in subjects who tested positive versus those who tested negative for ocular surface matrix metalloproteinase 9 (MMP-9) using the InflammaDry point of care test (RPS, Sarasota, FL). Methods: In this cross-sectional study, individuals seen in the Miami Veterans Affairs eye clinic with DE symptoms, as evidenced by DE questionnaire 5 (DEQ5) ≥6, were given standardized questionnaires to assess DE symptoms and ocular and non-ocular pain complaints. Also, a complete evaluation was conducted to measure ocular surface signs of DE. MMP-9 testing was performed using the InflammaDry once in each eye, per the manufacturer's instructions. The main outcome measure was a comparison of DE symptoms and signs in MMP-9 positive versus negative subjects. Results: Of 128 subjects, 50 (39%) were positive for MMP-9 for InflammaDry testing in either eye. No statistically significant differences in mental health indices, DE symptoms, or ocular surface signs were seen in subjects based on MMP-9 status. Conclusion: In our population, there was no difference in the DE profile by both symptoms and signs between those testing positive versus negative for MMP-9 on the ocular surface. This suggests that clinical exam alone cannot predict patients with clinically significant inflammation.
Article
Purpose: To assess the improvement in meibomian gland function and dry eye symptoms in patients with refractory dry eye treated with a combination therapy of intense pulsed light (IPL) and meibomian gland expression (MGX). Methods: Medical records of 81 consecutive patients with dry eye treated with serial IPL/MGX were retrospectively examined to determine the outcome. All patients had a minimum of 6 months of follow-up after the first IPL/MGX treatment. Patients typically received 1 to 4 IPL treatments spaced 4 to 6 weeks apart. Each IPL session included MGX. Thirty-five charts had complete data for inclusion in analysis. We reviewed demographics, ocular histories, Standard Patient Evaluation of Eye Dryness 2 (SPEED2) symptom survey scores, slit-lamp examinations, and meibomian gland evaluations (MGE) at baseline and at each visit before IPL/MGX treatments. Results: The paired t test showed a significant (P < 0.0001) decrease in SPEED2 with IPL/MGX therapy. Of the 35 patients, 8 (23%) had a ≥50% decrease in SPEED2, 23 (66%) had a 1% to 49% decrease in SPEED2, 1 (3%) had no change in SPEED2, and 3 (9%) had an increase in SPEED2. The Paired t test showed a significant increase in MGE in the left eye but not in the right eye (OD P = 0.163 and OS P = 0.0002). Thirteen patients (37%) had improved MGE bilaterally. Eight patients (23%) had either a decrease in MGE bilaterally or a decrease in 1 eye with no change in the other eye. Conclusions: This retrospective analysis shows that the combination of IPL and MGX can significantly improve dry eye symptoms (in 89% of patients) and meibomian gland function (in 77% of patients in at least 1 eye).
Article
Background Corneal oedema is a common post-operative problem that delays or prevents visual recovery from ocular surgery. Honey is a supersaturated solution of sugars with an acidic pH, high osmolarity and low water content. These characteristics inhibit the growth of micro-organisms, reduce oedema and promote epithelialisation. This clinical case series describes the use of a regulatory approved Leptospermum species honey ophthalmic product, in the management of post-operative corneal oedema and bullous keratopathy.MethodsA retrospective review of 18 consecutive cases (30 eyes) with corneal oedema persisting beyond one month after single or multiple ocular surgical procedures (phacoemulsification cataract surgery and additional procedures) treated with Optimel Antibacterial Manuka Eye Drops twice to three times daily as an adjunctive therapy to conventional topical management with corticosteroid, aqueous suppressants, hypertonic sodium chloride five per cent, eyelid hygiene and artificial tears. Visual acuity and central corneal thickness were measured before and at the conclusion of Optimel treatment.ResultsA temporary reduction in corneal epithelial oedema lasting up to several hours was observed after the initial Optimel instillation and was associated with a reduction in central corneal thickness, resolution of epithelial microcysts, collapse of epithelial bullae, improved corneal clarity, improved visualisation of the intraocular structures and improved visual acuity. Additionally, with chronic use, reduction in punctate epitheliopathy, reduction in central corneal thickness and improvement in visual acuity were achieved. Temporary stinging after Optimel instillation was experienced. No adverse infectious or inflammatory events occurred during treatment with Optimel.Conclusions Optimel was a safe and effective adjunctive therapeutic strategy in the management of persistent post-operative corneal oedema and warrants further investigation in clinical trials.
Article
Meibomian gland (MG) dysfunction (MGD) is a multifactorial, chronic condition of the eyelids, leading to eye irritation, inflammation and ocular surface disease. Initial conservative therapy often includes a combination of warm compresses in addition to baby shampoo or eyelid wipes. The practice of lid hygiene dates back to the 1950s, when selenium sulfide-based shampoo was first used to treat seborrhoeic dermatitis of the eyelids. Today, tear-free baby shampoo has replaced dandruff shampoo for MGD treatment and offers symptom relief in selected patients. However, many will not achieve significant improvement on this therapy alone; some may even develop an allergy to the added dyes and fragrances in these products. Other manual and mechanical techniques to treat MGD include MG expression and massage, MG probing and LipiFlow(®). While potentially effective in patients with moderate MGD, these procedures are more invasive and may be cost prohibitive. Pharmacological treatments are another course of action. Supplements rich in omega-3 fatty acids have been shown to improve both MGD and dry eye symptoms. Tea tree oil, specifically the terpenin-4-ol component, is especially effective in treating MGD associated with Demodex mites. Topical antibiotics, such as azithromycin, or systemic antibiotics, such as doxycycline or azithromycin, can improve MGD symptoms both by altering the ocular flora and through anti-inflammatory mechanisms. Addressing and treating concurrent ocular allergy is integral to symptom management. Topical N-acetylcysteine and topical cyclosporine can both be effective therapeutic adjuncts in patients with concurrent dry eye. A short course of topical steroid may be used in some severe cases, with monitoring for steroid-induced glaucoma and cataracts. While the standard method to treat MGD is simply warm compresses and baby shampoo, a more tailored approach to address the multiple aetiologies of the disease is suggested.
Article
Objective To evaluate the validity and reliability of the Ocular Surface Disease Index (OSDI) questionnaire.Methods Participants (109 patients with dry eye and 30 normal controls) completed the OSDI, the National Eye Institute Visual Functioning Questionnaire (NEI VFQ-25), the McMonnies Dry Eye Questionnaire, the Short Form-12 (SF-12) Health Status Questionnaire, and an ophthalmic examination including Schirmer tests, tear breakup time, and fluorescein and lissamine green staining.Results Factor analysis identified 3 subscales of the OSDI: vision-related function, ocular symptoms, and environmental triggers. Reliability (measured by Cronbach α) ranged from good to excellent for the overall instrument and each subscale, and test-retest reliability was good to excellent. The OSDI was valid, effectively discriminating between normal, mild to moderate, and severe dry eye disease as defined by both physician's assessment and a composite disease severity score. The OSDI also correlated significantly with the McMonnies questionnaire, the National Eye Institute Visual Functioning Questionnaire, the physical component summary score of the Short Form-12, patient perception of symptoms, and artificial tear usage.Conclusions The OSDI is a valid and reliable instrument for measuring the severity of dry eye disease, and it possesses the necessary psychometric properties to be used as an end point in clinical trials.
Article
Purpose:To evaluate the effect of intense pulsed light (IPL) applied to the periocular area for meibomian gland dysfunction (MGD) in a prospective, double-masked, placebo-controlled, paired-eye study. Methods:Twenty-eight participants underwent IPL treatment (E>Eye, E-Swin, France), with homogeneously sequenced light pulses delivered to one eye and placebo treatment to the partner control eye at 1, 15, and 45 days following baseline (BL) evaluation. Lipid layer grade (LLG), non-invasive tear breakup time (NIBUT), tear evaporation rate (TER), tear meniscus height (TMH) and subjective symptom score (SPEED) were compared to BL and control values at each visit. Results:LLG improved significantly from BL to Day 45 in the treated eye (p<0.001), but not the control eye (p=0.714) with 82% of treated eyes improving by at least one LLG. NIBUT also improved significantly from BL to Day 45 in the treated (p<0.001), but not control eye (p=0.056), and was significantly longer than in the treated eye at Day 45 (14.1 ± 9.8s vs 8.6 ± 8.2s, p<0.001). TER was not significantly lower at Day 45 compared to BL in the control eye (p=0.165), but approached significance in the treated eye (p = 0.080). TMH does not change from BL in either eye (p>0.05). SPEED scores improved at each visit in both the treated (p<0.001) and control eye (p=0.002), with 86% of participants noting reduced symptoms in the treated eye by Day 45. Conclusions:IPL with multiple sculpted pulses shows therapeutic potential for MGD, improving tear film quality and reducing symptoms of dry eye. Copyright © 2015 by Association for Research in Vision and Ophthalmology.
Article
The aim of this study was to report the complementary use of honey for treatment of a contact lens-induced corneal ulcer. A 23-year-old contact lens user presented with a corneal ulcer in her left eye. She had visual acuity reduced to hand movement. There was a history of wearing contact lenses while swimming in a lake seven days before presentation. The cultures from corneal scrapings and contact lenses were positive for Klebsiella oxytoca, Pseudomonas aeruginosa, Stenotrophomonas maltophilia and Pseudomonas spp. The treatment with topical levofloxacin and 25% (w/v) γ-irradiated honeydew honey solution was effective and the patient achieved final best corrected visual acuity of affected eye. In addition to positive clinical outcome, honeydew honey was shown to be highly effective in vitro against ocular isolates, in particular S. maltophilia. The minimal inhibitory concentrations for honeydew honey ranged from 5% to 10%. These results demonstrate that honey is a promising antibacterial agent in management of corneal ulcers. Moreover, honey exhibits anti-biofilm and anti-inflammatory properties, and thus becomes an interesting ophthalmologic agent.
Article
Objective To evaluate the expression of matrix metalloproteinase 9 (MMP9) and transglutaminase 2 (TG2) in different forms of dry eye. Design Case control study. Participants Seventy-five female subjects divided into 3 groups: group 1, 15 healthy controls; group 2, 30 subjects with Sjögren syndrome (SS); and group 3, 30 subjects with Meibomian gland dysfunction (MGD). Methods A clinical assessment was carried out and impression cytologic specimens were processed for immunoperoxidase staining for MMP9 and TG2 and real-time polymerase chain reaction analyses were carried out for MMP9, TG2, interleukin-6, interferon-γ, B-cell lymphoma 2, and caspase 3. To study MMP9 and TG2 expression after anti-inflammatory treatment, patients were divided into 2 subgroups, one treated with saline and the other treated with saline plus topical corticosteroid eye drops (0.5% loteprednol etabonate) 4 times daily for 15 days. For statistical analysis, Student t test, Mann–Whitney U test, and Spearman's correlation coefficient were used as appropriate. Main Outcome Measures Conjunctival expression of MMP9 and TG2. Results MMP9 and TG2 expression were higher in both patient groups than in controls (P < 0.0001). Group 2 patients showed higher expression than group 3 (P < 0.0001). The Spearman's correlation coefficient showed in group 2 a positive correlation between MMP9 and TG2 expression (ρ = 0.437; P = 0.01), but no correlation in group 3 (ρ = 0.143; P = 0.45). Corticosteroid treatment significantly reduced MMP9 and TG2 expression in both groups, ameliorating symptoms and signs. A much higher percentage reduction was observed in SS. Conclusions The pathogenic mechanisms of the 2 forms of dry eye give an account for the different MMP9 and TG2 expressions in the 2 groups of patients. The higher expression in SS is determined by the direct autoimmune insult to the ocular surface epithelia, whereas in MGD patients, with an epithelial damage due to an unbalanced tear secretion, the molecules expression is significantly lower, although higher than in controls. The corticosteroid treatment induced a reduction of both molecules, although higher in SS than in MGD, because of its direct inhibitory effect on inflammation.
Article
Background: For the diagnosis of dry eye, taking an accurate medical history of the patient is critical. For this purpose the ocular surface disease index (OSDI) can be regarded as the established standard questionnaire but the standard patient evaluation of eye dryness (SPEED) questionnaire has recently been developed. The advantages of the SPEED questionnaire are the lower number of questions and easier interpretability. Material and methods: In a retrospective analysis of 153 patients of our special clinic for dry eyes we performed a comparison of the SPEED with the established OSDI questionnaire regarding the evaluation of the severity of dry eye. In addition, we analyzed possible correlations with various objective parameters for classification of dry eye syndrome. Results: There was a highly significant correlation between OSDI and SPEED values with a correlation coefficient of 0.47 (p < 0.001). In addition, significant correlations between OSDI values and the tear meniscus height (r = - 0.1374, p = 0.0226), Schirmer values (r = - 0.26, p < 0.0001) and lid margins parallel conjunctival folds (r = 0.1261, p = 0.034) were observed. The SPEED values showed a significant correlation with age (r = - 0.2106, p = 0.0107) and lipid layer thickness (r = - 0.159, p = 0.0081). Discussion: The OSDI and SPEED questionnaires are both suitable for detecting the symptoms of dry eye; however the results of the questionnaires cannot be used interchangeably. While the SPEED levels seemed to correlate more with the parameters of evaporative dry eye, the OSDI values were more correlated with parameters of aqueous tear-deficient dry eye. However, a distinction between evaporative and aqueous tear-deficient dry eye is not possible based only on the results of the questionnaires.
Article
To report an unusual case of a late-stage reactivation of immune stromal keratitis associated with herpes zoster ophthalmicus (HZO), occurring without any apparent predisposing factors, more than 4 years after an acute zoster dermatomal rash. Significant corneal hypoesthesia and a central band keratopathy developed within 6 months of the late-stage reactivation. The clinical case management, issues associated with management, and management options are discussed, including the use of standardized, regulatory approved, antibacterial medical honey. An 83-year-old woman presented for routine review with a reactivation of right anterior stromal keratitis and mild anterior uveitis, occurring more than 4 years after an acute HZO dermatomal rash and an associated initial episode of anterior stromal keratitis. Corneal sensation became markedly impaired, and over the subsequent 6 months, a right central band keratopathy developed despite oral antiviral and topical steroid therapy. Visual acuity with pinhole was reduced to 20/100 in the affected eye and moderate irritation and epiphora were experienced. The patient declined the surgical intervention options of chelation, lamellar keratectomy, and phototherapeutic keratectomy to treat the band keratopathy. Longer-term management has involved preservative-free artificial tears, eyelid hygiene, standardized antibacterial medical honey, topical nonpreserved steroid, and UV-protective wraparound sunglasses. The clinical condition has improved over 14 months with this ocular surface management regimen, and visual acuity of 20/30 is currently achieved in a comfortable eye. The chronic and recurrent nature of HZO can be associated with significant corneal morbidity, even many years after the initial zoster episode. Long-term review and management of patients with a history of herpes zoster stromal keratitis are indicated following the initial corneal involvement. Standardized antibacterial medical honey can be considered in the management of the chronic ocular surface disease associated with HZO and warrants further evaluation in clinical trials.
Article
Honey is a popular natural product that is used in the treatment of burns and a broad spectrum of injuries, in particular chronic wounds. The antibacterial potential of honey has been considered the exclusive criterion for its wound healing properties. The antibacterial activity of honey has recently been fully characterized in medical-grade honeys. Recently, the multifunctional immunomodulatory properties of honey have attracted much attention. The aim of this review is to provide closer insight into the potential immunomodulatory effects of honey in wound healing. Honey and its components are able to either stimulate or inhibit the release of certain cytokines (tumor necrosis factor-α, interleukin-1β, interleukin-6) from human monocytes and macrophages, depending on wound condition. Similarly, honey seems to either reduce or activate the production of reactive oxygen species from neutrophils, also depending on the wound microenvironment. The honey-induced activation of both types of immune cells could promote debridement of a wound and speed up the repair process. Similarly, human keratinocytes, fibroblasts, and endothelial cell responses (e.g., cell migration and proliferation, collagen matrix production, chemotaxis) are positively affected in the presence of honey; thus, honey may accelerate reepithelization and wound closure. The immunomodulatory activity of honey is highly complex because of the involvement of multiple quantitatively variable compounds among honeys of different origins. The identification of these individual compounds and their contributions to wound healing is crucial for a better understanding of the mechanisms behind honey-mediated healing of chronic wounds.
Article
Purpose To compare the effectiveness of a single LipiFlow® treatment with combined lid warming and massage in patients with meibomian gland dysfunction (MGD). Methods In this prospective, randomized, crossover, observer-masked clinical trial, subjects were randomized to receive either a single 12-min LipiFlow-LipiFlow Thermal Pulsation (LTP) system treatment or to perform combined twice-daily lid warming and massage for 3 months. All subjects were examined before, and 1 and 3 months after initiation of treatments. Investigated parameters included subjective symptoms, lipid layer thickness, meibomian gland assessment, tear break-up time, tear osmolarity, corneal and conjunctival staining, Schirmer test values, and tear meniscus height. Results A total of 31 subjects completed the 3-month follow-up. At 1 and 3 months, patients in the LipiFlow treatment group had a significant reduction in Ocular Surface Disease Index (OSDI) scores compared with those in the lid-margin hygiene group. Both treatments produced a significant improvement in expressible meibomian glands compared to the baseline parameters, but no significant difference was noted between the two groups. The other investigated objective parameters did not show a significant difference. Conclusion Results of our study show that a single LipiFlow treatment is as least as effective as a 3-month, twice-daily lid margin hygiene regimen for MGD. However, the present study was observer-masked only, and therefore a placebo effect may have confounded any improvements in subjective symptoms and other parameters in both groups.
Article
Objectives To determine the clinical sensitivity, specificity, negative predictive value, and positive predictive value of a rapid point-of-care diagnostic test to detect elevated matrix metalloproteinase 9 levels (InflammaDry). Methods In a prospective, sequential, masked, multicenter clinical trial, InflammaDry was performed on 206 patients: 143 patients with clinical signs and symptoms of dysfunctional tear syndrome (dry eyes) and 63 healthy individuals serving as controls. Participants were assessed as healthy controls or for a clinical diagnosis of dry eye using the Ocular Surface Disease Index, Schirmer tear test, tear breakup time, and keratoconjunctival staining. Main Outcome Measures The sensitivity and specificity of InflammaDry were compared with clinical assessment. Results InflammaDry showed sensitivity of 85% (in 121 of 143 patients), specificity of 94% (59 of 63), negative predictive value of 73% (59 of 81), and positive predictive value of 97% (121 of 125). Conclusion Compared with clinical assessment, InflammaDry is sensitive and specific in diagnosing dry eye. Application to Clinical Practice Dry eye is often underdiagnosed resulting from poor communication between the clinical assessment of dry eye severity between clinicians and patients. This often leads to a lack of effective treatment. Matrix metalloproteinase 9 is an inflammatory biomarker that has been shown to be elevated in the tears of patients with dry eyes. The ability to accurately detect elevated matrix metalloproteinase 9 levels may lead to earlier diagnosis, more appropriate treatment, and better management of ocular surface disease. Preoperative and perioperative management of inflammation related to dry eyes may reduce dry eyes that develop after laser in situ keratomileusis, improve wound healing, and reduce flap complications. Recognition of inflammation may allow for targeted perioperative therapeutic management of care for patients who undergo cataract and refractive surgery and improve outcomes. Trial Registration clinicaltrials.gov Identifier: NCT01313351
Article
: To compare the efficacy of topical cyclosporine [0.05% cyclosporine A (CsA)] and preservative-free artificial tears in the treatment of meibomian gland dysfunction (MGD). : A 3-month prospective, randomized, double-masked, parallel-group controlled trial enrolled 70 patients with symptomatic MGD and unstable tear film [tear breakup time (TBUT) <8 seconds]. Patients were randomized to topical CsA (0.05%; group A) and 0.5% carboxymethylcellulose (control; group B) instilled twice daily for 3 months. Ocular Surface Disease Index (OSDI), lid margin inflammation, meibomian gland expression, conjunctival injection, corneal and interpalpebral dye staining, noninvasive tear breakup time (NIBUT) using the Tearscope Plus and invasive fluorescein tear breakup time (FBUT), and Schirmer I test were performed. : At the 3-month evaluation, mean OSDI, NIBUT and FBUT, lid margin inflammation, meibomian gland expressibility, and tarsal injection showed significant improvement from baseline in group A (P < 0.01, P < 0.01, P < 0.001, P < 0.05, and P < 0.001, respectively). In group B, only the OSDI improved significantly from baseline at 3 months (P = 0.003). TBUTs (NIBUT and FBUT) were significantly longer in group A at all visits, and the mean change of TBUTs from baseline was also significantly greater in group A at 3 months (P < 0.001). : Topical CsA 0.05% twice daily may be helpful in the treatment of MGD mainly by improving tear film stability.
Article
Ocular surface disorders-and dry eye, in particular-is a leading reason for visits to eye care professionals. It has been generally accepted that meibomian gland dysfunction (MGD) is a leading cause of evaporative dry eye, as well as being associated with aqueous-deficient dry eye. Yet, researchers and clinicians have lacked a global consensus on the definition of MGD, its epidemiology, pathophysiology, and management. Various systemic diseases and medications have been associated with the progression of both dry eye and MGD, as have several ocular disorders beyond those directly affecting the surface. It is in the best interest of patients for clinicians to be able to better identify and diagnose MGD, differentiating it from other ocular surface disorders, and to recognize the effects of MGD on the ocular surface, and thus initiate appropriate therapy. This CME activity provides expert insight into the Tear Film and Ocular Surface Society's International Workshop on MGD consensus report, offering practical application of its findings to better manage MGD patient care, particularly for those patients facing or undergoing ocular surgery.
Article
Background: Blepharitis, an inflammatory condition associated with itchiness, redness, flaking, and crusting of the eyelids, is a common eye condition that affects both children and adults. It is common in all ethnic groups and across all ages. Although infrequent, blepharitis can lead to permanent alterations to the eyelid margin or vision loss from superficial keratopathy (abnormality of the cornea), corneal neovascularization, and ulceration. Most importantly, blepharitis frequently causes significant ocular symptoms such as burning sensation, irritation, tearing, and red eyes as well as visual problems such as photophobia and blurred vision. The exact etiopathogenesis is unknown, but suspected to be multifactorial, including chronic low-grade infections of the ocular surface with bacteria, infestations with certain parasites such as demodex, and inflammatory skin conditions such as atopy and seborrhea. Blepharitis can be categorized in several different ways. First, categorization is based on the length of disease process: acute or chronic blepharitis. Second, categorization is based on the anatomical location of disease: anterior, or front of the eye (e.g. staphylococcal and seborrheic blepharitis), and posterior, or back of the eye (e.g. meibomian gland dysfunction (MGD)). This review focuses on chronic blepharitis and stratifies anterior and posterior blepharitis. Objectives: To examine the effectiveness of interventions in the treatment of chronic blepharitis. Search methods: We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2012, Issue 1), MEDLINE (January 1950 to February 2012), EMBASE (January 1980 to February 2012), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov) and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We searched the reference lists of included studies for any additional studies not identified by the electronic searches. There were no date or language restrictions in the electronic searches for trials. The electronic databases were last searched on 9 February 2012. Selection criteria: We included randomized controlled trials (RCTs) and quasi-randomized controlled trials (CCTs) in which participants were adults aged 16 years or older and clinically diagnosed with chronic blepharitis. We also included trials where participants with chronic blepharitis were a subset of the participants included in the study and data were reported separately for these participants. Interventions within the scope of this review included medical treatment and lid hygiene measures. Data collection and analysis: Two authors independently assessed search results, reviewed full-text copies for eligibility, examined risk of bias, and extracted data. Data were meta-analyzed for studies comparing similar interventions and reporting comparable outcomes with the same timing. Otherwise, results for included studies were summarized in the text. Main results: There were 34 studies (2169 participants with blepharitis) included in this review: 20 studies (14 RCTs and 6 CCTs) included 1661 participants with anterior or mixed blepharitis and 14 studies (12 RCTs and 2 CCTs) included 508 participants with posterior blepharitis (MGD). Due to the heterogeneity of study characteristics among the included studies, with respect to follow-up periods and types of interventions, comparisons, and condition of participants, our ability to perform meta-analyses was limited. Topical antibiotics were shown to provide some symptomatic relief and were effective in eradicating bacteria from the eyelid margin for anterior blepharitis. Lid hygiene may provide symptomatic relief for anterior and posterior blepharitis. The effectiveness of other treatments for blepharitis, such as topical steroids and oral antibiotics, were inconclusive. Authors' conclusions: Despite identifying 34 trials related to treatments for blepharitis, there is no strong evidence for any of the treatments in terms of curing chronic blepharitis. Commercial products are marketed to consumers and prescribed to patients without substantial evidence of effectiveness. Further research is needed to evaluate the effectiveness of such treatments. Any RCT designed for this purpose should separate participants by type of condition (e.g. staphylococcal blepharitis or MGD) in order to minimize imbalances between groups (type I errors) and to achieve statistical power for analyses (prevent type II errors). Medical interventions and commercial products should be compared with conventional lid hygiene measures, such as warm compresses and eyelid margin washing, to determine effectiveness, as well as head-to-head to show comparative effectiveness between treatments. Outcomes of interest should be patient-centered and measured using validated questionnaires or scales. It is important that participants be followed long-term, at least one year, to assess chronic outcomes properly.
Article
Endophthalmitis following eye surgery remains a rare but serious complication. Topical fluoroquinolones have been used as prophylactic agents against endophthalmitis. However, the emerging resistance of ocular pathogens to fluoroquinolones may preclude their routine use. Honey, a natural antimicrobial product with wound healing properties, is a promising candidate for the prophylaxis of endophthalmitis. The goal of this study was to determine whether 25% (w/v) honey solution is effective in eradicating bacterial ocular pathogens in the perioperative period in patients scheduled for cataract surgery or vitrectomy, and to compare its efficacy to 0.3% ofloxacin. In this pilot study, 101 patients were randomized to honey (n = 49) or ofloxacin (n = 52) treatment. In both groups, eye drops were administered five times a day for 7 days before and 5 days after surgery. Before administration of the antibacterial agents, 18 and 25 isolates were detected in the ofloxacin and honey group, respectively. After 7 days of administration, four isolates (coagulase-negative Staphylococcus) were detected in each therapeutic group. No significant difference in antibacterial effect was found between groups. These results indicate that honey may act as a prophylactic agent of endophthalmitis; however, further studies are needed to characterize its ocular penetration properties.
Article
To evaluate in a general clinic-based cohort of patients with dry eye disease (DED) the distribution of patients with aqueous-deficient or evaporative subtype of DED. Schirmer tests and meibomian gland dysfunction (MGD) (Foulks-Bron scoring) were evaluated in both eyes of 299 normal subjects and DED patients (218 women and 81 men) across 10 sites in the European Union and the United States. Using the more severe measurement of the 2 eyes, subjects were considered to have pure aqueous-deficient dry eye (ADDE) with Schirmer values of <7 mm and MGD grades of ≤5. Patients were classified as purely evaporative dry eye with MGD grades of >5 and Schirmer values of ≥7 mm. Subjects were placed into the mixed (hybrid) category if they exhibited both a low Schirmer value of <7 and evidence of MGD with a grade >5. Of the 224 subjects classified with DED using an objective, composite, disease severity scale, 159 were classified into 1 of 3 categories: 79 were classified with only MGD, whereas only 23 were classified as purely aqueous deficient, and 57 showed evidence of both MGD and aqueous deficiency. Overall, 86% of these qualified DED patients demonstrated signs of MGD. The remaining 65 patients showed evidence of DED through other clinical signs, without overt evidence of MGD or ADDE, possibly because of the inherent variability of these signs. The proportion of subjects exhibiting signs of evaporative dry eye resulting from MGD far outweighs that of subjects with pure ADDE in a general clinic-based patient cohort.
Article
 To investigate the effect of topically applied honey on intact corneas, surgically induced corneal abrasions and endotoxin induced keratitis. The effect of honey on the cornea was investigated by application of honey on intact corneas, wounded corneas and endotoxin-induced keratitis in Lewis rats. The corneas were wounded by creating an epithelial defect using a surgical blade, and the keratitis was induced by topically applying Pseudomonas aeruginosa endotoxin to scarified corneas. After treatment rats were sacrificed and cornea harvested in each case. Corneas were processed for paraffin embedding for histological and immuno-fluorescence staining. Corneas were also harvested and processed for total ribonucleic acid (RNA) isolation for reverse transcriptase-polymerase chain reaction (RT-PCR) analysis for various growth factors and inflammatory chemokines/cytokines).  Histological analysis revealed that no inflammation or morphological changes occurred after honey treatment in naive intact corneas. Vascular endothelial growth factor (VEGF) levels were also not altered after honey treatment. Topical application of honey to injured corneas resulted in faster epithelial healing and decreased expression of VEGF, transforming growth factor beta (TGF-β), interferon gamma (IFN-γ), interleukin 12 (IL-12) and tumor necrosis factor alpha (TNF-α) in injured corneas. Our results also established that honey treatment reduced the inflammation in endotoxin-induced keratitis by reducing the levels of angiogenic factors (VEGF and TGF-β), inflammatory cytokines (IL-12) and chemokines (CC chemokine receptor 5(CCR-5)).  Short term use of honey on intact corneas can be safe. Honey has anti-angiogenic and anti-inflammatory properties that can be explored in several corneal inflammatory and infectious conditions.
Article
Low pH, hydrogen peroxide generation, and the hyperosmolarity mechanisms of antimicrobial action are ubiquitous for all honeys. In addition, manuka honey has been shown to contain high concentrations of methylglyoxal (MGO), contributing the relatively superior antimicrobial activity of manuka honey compared to non-MGO honeys. In high concentrations, manuka honey is effective in killing Staphylococcus aureus biofilms in vitro. Lower concentrations of honey, however, are desirable for clinical use as a topical rinse in chronic rhinosinusitis in order to maximize the tolerability and practicality of the delivery technique. This study, therefore, was designed to evaluate the contribution of MGO to the biofilm-cidal activity of manuka honey, and furthermore determine whether the antibiofilm activity of low-dose honey can be augmented by the addition of exogenous MGO. In vitro microbiology experiment. Five S. aureus strains (four clinical isolates and one reference strain) were incubated to form biofilms using a previously established in vitro dynamic peg model. First, the biofilm-cidal activities of 1) manuka honey (790 mg/kg MGO), 2) non-MGO honey supplemented with 790 mg/kg MGO, and 3) MGO-only solutions were assessed. Second, the experiment was repeated using honey solutions supplemented with sufficient MGO to achieve concentrations exceeding those seen in commercially available manuka honey preparations. All honey solutions containing a MGO concentration of 0.53 mg/mL or greater demonstrated biofilm-cidal activity; equivalent activity was achieved with ≥1.05 mg/mL MGO solution. MGO is only partially responsible for the antibiofilm activity of manuka honey. Infusion of MGO-negative honey with MGO, however, achieves similar cidality to the equivalent MGO-rich manuka honey.
Article
Assessment of corneal sensory function is commonly carried out using the Cochet-Bonnet aesthesiometer. The limitations of this instrument have lead to development of newer instruments, such as the CRCERT-Belmonte aesthesiometer, which utilise a jet of air as their stimulus. Recent work, however, has demonstrated contradictory effects on ocular surface sensitivity when measured with different types of aesthesiometer. The purpose of the present study was to compare clinical measurements of corneal sensitivity obtained with the CRCERT-Belmonte and the Cochet-Bonnet aesthesiometers and to examine their stimulus characteristics in terms of force exerted. No association was found between central corneal sensitivity measured with the two aesthesiometers in a group of normal subjects. Sensitivity was measured to be lower with the Cochet-Bonnet aesthesiometer than with the CRCERT-Belmonte. Over half of the subjects could not be assessed with the standard Cochet-Bonnet filament and 11% could not be assessed with either filament, as their corneal sensitivity was outside of the range of the instrument. In contrast, all subjects were within the stimulus range of the CRCERT-Belmonte aesthesiometer. Corneal sensitivity measurements made with the non-contact CRCERT-Belmonte aesthesiometer and the Cochet-Bonnet aesthesiometer are not comparable. Due to dissimilarities in the composition of their stimuli, and thus mode of stimulation, it is possible that the two instruments measure different aspects of the neural response. The underestimation of corneal sensitivity by the Cochet-Bonnet aesthesiometer and its inability to measure sensitivity of some subjects at all are important considerations in the assessment of sensitivity loss. Subtle changes are unlikely to be detected with this instrument, particularly at higher sensitivity levels. The Cochet-Bonnet should therefore be used with caution and the 0.08 mm diameter used as the filament of choice. Adoption of a non-contact aesthesiometer as standard for ocular sensitivity measurement should be considered. The non-contact instrument allows superior stimulus reproducibility and better control over stimulus characteristics, in addition to the ability for exploration of the response of all three types of neuro-receptors on the ocular surface.
Article
To summarize the key literature and our research experience regarding Demodex infestation as a potential cause of ocular inflammatory diseases with a special emphasis on Demodex blepharitis. Two distinct Demodex species have been confirmed as a cause of blepharitis: Demodex folliculorum can cause anterior blepharitis associated with disorders of eyelashes, and D. brevis can cause posterior blepharitis with meibomian gland dysfunction and keratoconjunctivitis. Tea tree oil treatments with either 50% lid scrubs or 5% lid massages are effective in eradicating mites and reducing ocular surface inflammation. Demodex blepharitis is a common but overlooked external eye disease. The pathogenesis of Demodex blepharitis in eliciting ocular surface inflammation has been further clarified. The modified eyelash sampling and counting method makes it easier and more accurate to diagnose Demodex infestation. Tea tree oil shows promising potential to treat Demodex blepharitis by reducing Demodex counts with additional antibacterial, antifungal, and anti-inflammatory actions.
Article
Tear hyperosmolarity is diagnostic of dry eye disease (DED), yet difficulty in measurement has limited its utility; development of new instruments could facilitate its clinical application. This study compares the new OcuSense TearLab osmometer (OcuSense, Inc, San Diego, CA), based on electrical impedance "lab-on-a-chip" nanoliter technology, with the freezing point depression Clifton Osmometer (Clifton Technical Physics, Hartford, NY). Thirty-six subjects were recruited: 15 DED (9 women, 6 men age: 41 +/- 16 years) and 21 controls (12 women, 9 men age: 35 +/- 12 years); criteria for DED were noninvasive tear breakup time <10 seconds, Schirmer I test <5 mm, and positive symptoms. Samples were collected from the inferior tear meniscus for testing with both osmometers. Osmolarity values measured with OcuSense TearLab were 308 +/- 6 and 321 +/- 16 mOsm/L for controls and dry eye, respectively, and those measured with Clifton were 310 +/- 7 and 323 +/- 14 mOsm/L for controls and dry eye, respectively; these values were significantly different. Significant correlation was found between OcuSense and Clifton measurements (r = 0.904; P = 0.006). Bland-Altman analysis revealed agreement between techniques; the majority of points fell within the 95% confidence limits, and actual values differed by less than 1%. A cutoff value of >316 mOsm/L, derived from the distribution of osmolarity values, was used to diagnose DED with an effectiveness of 73% sensitivity, 90% specificity, and 85% positive predictive value for the OcuSense and 73% sensitivity, 71% specificity, and 65% positive predictive value for the Clifton in the study samples. Tear film osmolarity measured with the OcuSense TearLab system correlates well with the Clifton Osmometer. The new instrument has the potential to provide clinicians with a readily available clinically applicable measure, which could become the gold standard in DED.
Article
With the rise in prevalence of antibiotic-resistant bacteria, honey is increasingly valued for its antibacterial activity. To characterize all bactericidal factors in a medical-grade honey, we used a novel approach of successive neutralization of individual honey bactericidal factors. All bacteria tested, including Bacillus subtilis, methicillin-resistant Staphylococcus aureus, extended-spectrum beta-lactamase producing Escherichia coli, ciprofloxacin-resistant Pseudomonas aeruginosa, and vancomycin-resistant Enterococcus faecium, were killed by 10-20% (v/v) honey, whereas > or = 40% (v/v) of a honey-equivalent sugar solution was required for similar activity. Honey accumulated up to 5.62 +/- 0.54 mM H(2)O(2) and contained 0.25 +/- 0.01 mM methylglyoxal (MGO). After enzymatic neutralization of these two compounds, honey retained substantial activity. Using B. subtilis for activity-guided isolation of the additional antimicrobial factors, we discovered bee defensin-1 in honey. After combined neutralization of H(2)O(2), MGO, and bee defensin-1, 20% honey had only minimal activity left, and subsequent adjustment of the pH of this honey from 3.3 to 7.0 reduced the activity to that of sugar alone. Activity against all other bacteria tested depended on sugar, H(2)O(2), MGO, and bee defensin-1. Thus, we fully characterized the antibacterial activity of medical-grade honey.