Hot towels: The bedrock of Meibomian gland dysfunction treatment - A review.

BACKGROUND: Meibomian gland dysfunction (MGD) reduces quality-of-life and hinders work productivity of millions of patients, with high direct and indirect societal costs. Thickened meibum obstructs the glands and disrupts ocular surface health. Heating the eyelids to soften and express meibum from the glands can be beneficial. The most accessible method for eyelid warming uses heated, wet towels. However, the efficacy of this treatment is reliant on the methodology, and evidence-based best-practice recommendations are needed. PURPOSE: To evaluate the literature on hot towels in MGD treatment and recommend a best-practice protocol for future research and patient treatment. METHODS: Studies were identified through PubMed on the May 28, 2021, with the search terms: (warm* OR heat* OR thermal* OR towel OR wet towel) AND (meibomian OR MGD OR eyelid OR "dry eye" OR DED). All relevant original articles with English full-text were included. RESULTS: The search yielded 903 results, of which 22 met the inclusion criteria. Across studies, hot towels were found to be effective at reducing ocular symptoms. However, without reheating, the temperature quickly fell below the therapeutic range, which was deemed to be between 40 °C and 47 °C. Towels heated to around 45 °C and reheated every-two minutes were most effective at increasing eyelid temperature, comparable or better than several commercially available eyelid warming devices. No adverse effects were reported in the studies. CONCLUSION: Hot towel treatment effectively warms the eyelids and reduces ocular symptoms, but must be standardized, and towels reheated to achieve maximum benefit. Future research should assess patient satisfaction with different hot towel treatment methods that reheat or replace the towel at least every-two minutes, to establish which methods yield the greatest compliance. Guidelines or clinical recommendations that do not mention the need for regular reheating during hot towel compress treatment should be updated to include this.

Omega-3 polyunsaturated fatty acids and corneal nerve health: Current evidence and future directions.

Corneal nerves play a key role in maintaining ocular surface integrity. Corneal nerve damage, from local or systemic conditions, can lead to ocular discomfort, pain, and, if poorly managed, neurotrophic keratopathy. Omega-3 polyunsaturated fatty acids (PUFAs) are essential dietary components that play a key role in neural development, maintenance, and function. Their potential application in modulating ocular and systemic inflammation has been widely reported. Omega-3 PUFAs and their metabolites also have neuroprotective properties and can confer benefit in neurodegenerative disease. Several preclinical studies have shown that topical administration of omega-3 PUFA-derived lipid mediators promote corneal nerve recovery following corneal surgery. Dietary omega-3 PUFA supplementation can also reduce corneal epithelial nerve loss and promote corneal nerve regeneration in diabetes. Omega-3 PUFAs and their lipid mediators thus show promise as therapeutic approaches to modulate corneal nerve health in ocular and systemic disease. This review discusses the role of dietary omega-3 PUFAs in maintaining ocular surface health and summarizes the possible applications of omega-3 PUFAs in the management of ocular and systemic conditions that cause corneal nerve damage. In examining the current evidence, this review also highlights relatively underexplored applications of omega-3 PUFAs in conferring neuroprotection and addresses their therapeutic potential in mediating corneal nerve regeneration.

Investigating the Neuroprotective Effect of Oral Omega-3 Fatty Acid Supplementation in Type 1 Diabetes (nPROOFS1): A Randomized Placebo-Controlled Trial.

This randomized, double-masked, placebo-controlled trial evaluated the effects of oral omega-3 (n-3) fatty acid supplementation on peripheral nerves in type 1 diabetes. Participants with type 1 diabetes were assigned (1:1) to n-3 (1,800 mg/day fish oil) or placebo (600 mg/day olive oil) supplements for 180 days. The primary outcome was change from baseline in central corneal nerve fiber length (CNFL) at day 180. Secondary outcomes included change in other corneal nerve parameters, corneal sensitivity, peripheral small and large nerve fiber function, and ocular surface measures. Efficacy was analyzed according to the intention-to-treat principle. Safety assessments included diabetic retinopathy grade and adverse events. Between July 2017 and September 2019, 43 participants received n-3 (n = 21) or placebo (n = 22) supplements. All participants, except for two assigned to placebo, completed the trial. At day 180, the estimated increase in CNFL in the n-3 group, compared with placebo, was 2.70 mm/mm2 (95% CI 1.64, 3.75). The Omega-3 Index increased relative to placebo (3.3% [95% CI 2.4, 4.2]). There were no differences in most small or large nerve fiber functional parameters. Adverse events were similar between groups. In conclusion, we found in this randomized controlled trial that long-chain n-3 supplements impart corneal neuroregenerative effects in type 1 diabetes, indicating a role in modulating peripheral nerve health.

Clinical practice patterns in the management of dry eye disease: A TFOS international survey.

PURPOSE: To examine clinical management and prescribing patterns for dry eye disease (DED), in relation to severity and subtype, by eye care practitioners across the globe. METHODS: An online, anonymous cross-sectional survey (on Qualtrics) translated into 14 languages was distributed to eye care 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 independently 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 punctal occlusion, therapeutic contact lenses, secretagogues and biologics were more commonly recommended for aqueous deficient DED. CONCLUSIONS: DED management differs across continents and countries. A wide range of management strategies are utilised at each severity level and between subtypes. The survey results enable clinicians to benchmark their practice to that of their peers, indicate where further research is required to optimise patient management and inform industry on how best to target product development.

Developing evidence-based guidance for the treatment of dry eye disease with artificial tear supplements: A six-month multicentre, double-masked randomised controlled trial.

PURPOSE: To assess the six-month therapeutic profiles of lipid and non-lipid-based artificial tear supplements in managing dry eye disease (DED). METHODS: Ninety-nine participants fulfilling the TFOS DEWS II diagnostic criteria for DED (64% females; mean ± SD age, 44 ± 16 years) were enrolled in a prospective, multicentre, double-masked, parallel group, randomised controlled trial. Participants instilled lipid-based nanoemulsion drops or non-lipid-based aqueous drops for six months, at least four times daily. Symptomology, tear film and ocular surface characteristics were assessed at Days 0, 30, 60, 90, 120, 150 and 180. RESULTS: Sustained reductions in OSDI, DEQ-5, and SANDE symptom scores from baseline were observed from Day 30 onwards in both groups (all p < 0.05) and decreased superior lid wiper epitheliopathy grades from Day 60 onwards (all p ≤ 0.01). Improvements in non-invasive tear film breakup time, and sodium fluorescein and lissamine green staining scores followed from Day 120 onwards in both groups (all p < 0.05). Tear lipid layer grades increased from Day 90 onwards only with the lipid-based drops, and with significantly greater improvement in those with suboptimal lipid layer thickness at baseline (grade ≤3; p = 0.02). By Day 180, 19% of participants no longer fulfilled the diagnostic criteria for DED. CONCLUSIONS: Over a six-month treatment period, improvements in dry eye symptomology preceded tear film and ocular surface changes with regular use of both lipid and non-lipid-based artificial tear supplements. Both formulations addressed most mild-to-moderate forms of aqueous deficient and evaporative DED, while evaporative cases benefitted preferentially from lipid-based supplementation. This represents a first step towards mapping DED therapeutic strategies according to disease subtype and severity.

Randomized trial of topical periocular castor oil treatment for blepharitis.

PURPOSE: To evaluate the effects of topical castor oil application to the eyelids on ocular surface and tear film parameters in patients with blepharitis. METHODS: Twenty-six participants (14 females, 12 males; mean ± SD age, 38 ± 21 years) with clinical signs of blepharitis were enrolled in a prospective, investigator-masked, randomized, paired-eye trial. A 100% cold pressed castor oil formulation (Lotus Garden Botanicals, Biddeford, ME, USA) was applied to the eyelids of one eye (randomized), twice daily for 4 weeks. Ocular surface characteristics, symptoms, and tear film parameters were assessed at baseline and day 28. RESULTS: Baseline measurements did not differ between treated and control eyes (all p > 0.05). A significant reduction in OSDI symptomology score was observed following the four-week treatment period (p = 0.001). Clinical improvements in eyelid margin thickening, telangiectasia, eyelash matting, madarosis, cylindrical dandruff, and lid wiper epitheliopathy were limited to treated eyes (all p < 0.01), while greater decreases in staphylococcal and seborrheic eyelash crusting were observed in treated than control eyes (both p < 0.05). No adverse events were reported during the treatment period. CONCLUSION: Topical castor oil application effected significant improvements in ocular surface signs and symptoms in patients with blepharitis. The favourable therapeutic profile would suggest that castor oil demonstrates promise as a potential treatment for blepharitis, and support the conduct of further efficacy trials with longer follow up. TRIAL REGISTRATION NUMBER: ACTRN12618000856213.

Therapeutic potential of castor oil in managing blepharitis, meibomian gland dysfunction and dry eye.

The multifactorial pathogenesis and interrelationship of blepharitis, meibomian gland dysfunction and dry eye disease poses challenges to any therapeutic approach. Current treatments are mostly palliative, with success limited by perceived inefficacy and poor patient compliance. Castor oil, a natural derivative of the Ricinus communis plant, is widely used as an emollient in cosmetics and personal care products, drug delivery systems and wound dressings. Castor oil is deemed safe and tolerable, with strong anti-microbial, anti-inflammatory, anti-nociceptive, analgesic, antioxidant, wound healing and vaso-constrictive properties. Its main constituent, ricinoleic acid, has a bipolar molecular structure that promotes the formation of esters, amides and polymers. These can supplement deficient physiological tear film lipids, enabling enhanced lipid spreading characteristics and reducing aqueous tear evaporation. Studies reveal that castor oil applied topically to the ocular surface has a prolonged residence time, facilitating increased tear film lipid layer thickness, stability, improved ocular surface staining and symptoms. This review summarises the properties, current uses of, and therapeutic potential of castor oil in managing ocular surface disease. The biochemical, medicinal actions of castor oil are explored from the perspective of ocular surface pathology, and include microbial and demodectic over-colonisation, inflammatory and oxidative processes, as well as clinical signs and symptoms of dryness and discomfort.

Omega-3 Fatty Acids and Eye Health: Opinions and Self-Reported Practice Behaviors of Optometrists in Australia and New Zealand.

This study investigated optometrists' attitudes and self-reported practice behaviors towards omega-3 fatty acids for eye health, and knowledge and understanding of their potential risks and benefits. An anonymous online survey was distributed to optometrists in Australia and New Zealand. Questions included practitioner demographics and practice modality; self-reported practices and recommendations relating to diet, nutritional supplements, and omega-3 fatty acids for age-related macular degeneration (AMD) and dry eye disease (DED); and practitioner knowledge about omega-3 fatty acids. Of 206 included surveys, most respondents (79%) indicated recommending for their patients to consume omega-3 fatty acids to improve their eye health. Sixty-eight percent of respondents indicated recommending omega-3-rich foods for AMD management, while 62% indicated recommending omega-3 supplements. Most respondents (78%) indicated recommending omega-3-rich foods or supplements for DED. For DED, recommended omega-3 supplement dosages were (median [inter-quartile range, IQR]) 2000 mg [1000-2750 mg] per day. The main sources of information reported by respondents to guide their clinical decision making were continuing education articles and conferences. In conclusion, optometrists routinely make clinical recommendations about diet and omega-3 fatty acids. Future education could target improving optometrists' knowledge of differences in the evidence for whole-food versus supplement sources of omega-3 fatty acids in AMD. Further research is needed to address uncertainties in the evidence regarding optimal omega-3 dosage and formulation composition in DED.

Randomised double-masked placebo-controlled trial of the cumulative treatment efficacy profile of intense pulsed light therapy for meibomian gland dysfunction.

PURPOSE: To assess long-term cumulative treatment effects of intense pulsed light (IPL) therapy in meibomian gland dysfunction (MGD). METHODS: Eighty-seven symptomatic participants (58 female, mean ± SD age, 53 ± 16 years) with clinical signs of MGD were enrolled in a prospective, double-masked, parallel-group, randomised, placebo-controlled trial. Participants were randomised to receive either four or five homogeneously sequenced light pulses or placebo treatment to both eyes, (E-Eye Intense Regulated Pulsed Light, E-Swin, France). Visual acuity, dry eye symptomology, tear film parameters, and ocular surface characteristics were assessed immediately before treatment on days 0, 15, 45, 75, and four weeks after treatment course completion on day 105. Inflammatory and goblet cell function marker expression, and eyelid swab microbiology cultures were evaluated at baseline and day 105. RESULTS: Significant decreases in OSDI, SPEED, and SANDE symptomology scores, and meibomian gland capping, accompanied by increased tear film lipid layer thickness, and inhibited Corynebacterium macginleyi growth were observed in both treatment groups (all p < 0.05). Sustained clinical improvements occurred in both treatment groups from day 75, although significant changes from day 45, in lipid layer quality, meibomian gland capping, OSDI and SANDE symptomology, were limited to the five-flash group (all p < 0.05). CONCLUSIONS: IPL therapy effected significant improvements in dry eye symptomology, tear film lipid layer thickness, and meibomian gland capping in MGD patients. Five-flash IPL treatment showed superior clinical efficacy to four-flash, and an initial course of at least four treatments is suggested to allow for establishment of sustained cumulative therapeutic benefits prior to evaluation of overall treatment efficacy. TRIAL REGISTRATION NUMBER: ACTRN12616000667415.

Omega-3 polyunsaturated fatty acid oral supplements for improving peripheral nerve health: a systematic review and meta-analysis.

CONTEXT: Peripheral nerve damage can occur in a variety of systemic conditions and can have a profound impact on functional and psychological health. Currently, therapeutic interventions for peripheral nerve damage are limited. OBJECTIVE: The aim of this systematic review, conducted in accordance with the Cochrane Collaboration's handbook and reported according to the PRISMA checklist, was to evaluate the efficacy and safety of omega-3 oral supplements for improving peripheral nerve structure and function. DATA SOURCES: PubMed, Embase, and Cochrane databases, along with clinical trial registries, were searched from inception to February 2019. Evidence was identified, critically appraised, and synthesized, and the certainty of evidence was appraised using the Grading of Recommendations Assessment, Development and Evaluation approach. STUDY SELECTION: Randomized controlled trials assessing the effects of omega-3 oral supplementation on outcomes of peripheral nerve structure, peripheral nerve function, or both were eligible for inclusion. Titles and abstracts of identified articles were independently assessed for potential eligibility by 2 review authors. For studies judged as eligible or potentially eligible, full text articles were retrieved and independently assessed by 2 review authors to determine eligibility; disagreements were resolved by consensus. DATA EXTRACTION: Fifteen trials were included. Two clinically similar studies that investigated the effect of omega-3 supplementation in individuals receiving chemotherapy were meta-analyzed. Pooled data showed a reduced incidence of peripheral neuropathy (RR = 0.58; 95%CI, 0.43-0.77) and a preservation of sensory nerve action potential amplitudes with omega-3 supplementation compared with placebo (MD = 4.19 µV; 95%CI; 2.19-6.19). CONCLUSION: This review finds, with low certainty, that omega-3 supplementation attenuates sensory loss and reduces the incidence of neuropathy secondary to oxaliplatin and paclitaxel treatment relative to placebo. There is currently limited evidence to ascertain whether omega-3 supplementation is beneficial in other systemic conditions characterized by peripheral nerve damage. SYSTEMATIC REVIEW REGISTRATION: PROSPERO registration number CRD 42018086297.

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

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

Therapeutic profile of a latent heat eyelid warming device with temperature setting variation.

PURPOSE: To compare the effects on ocular temperature and tear film parameters following a single application of a latent heat eyelid warming device at a range of temperature settings. METHODS: Fifteen subjects were enrolled in a prospective, investigator-masked, randomised, cross-over trial. On separate days, participants were randomised to 10-minute application of a research latent heat device (Laboratoires Théa) at device temperature settings of 45 °C, 50 °C and 55 °C. Outer eyelid and corneal temperatures, tear film lipid layer grade, and non-invasive tear film breakup time (NIBUT) were measured at baseline and immediately after 10 min of device application. RESULTS: Baseline measurements did not differ between treatment groups (all p > 0.05). Ocular temperatures, lipid layer grade and non-invasive tear film stability rose significantly following device application in all treatment groups (all p < 0.05). The 55 °C setting effected a mean ocular surface temperature rise in the order of +4 °C from baseline, which was 1.46 and 1.26 times greater than at the 45 °C and 50 °C temperature settings, respectively (all p < 0.05). Similarly, improvements in mean non-invasive tear film stability from baseline in the order of +7 s were observed, which were 2.43 and 1.66 times greater than those at the lower temperature settings of 45 °C and 50 °C, respectively (all p < 0.05). CONCLUSIONS: At all temperature settings, the latent heat device resulted in clinically and statistically significant increases in ocular temperature, lipid layer grade, and non-invasive tear film stability. However, the 55 °C setting proved to be most effective at raising ocular temperature (in the order of +4 °C from baseline) and improving tear film stability.

Randomised trial of the clinical utility of an eyelid massage device for the management of meibomian gland dysfunction.

PURPOSE: To compare the single application and two week treatment effects of device-applied (Eyepeace) and manually-applied eyelid massage techniques, as an adjunct to warm compress therapy, on ocular surface and tear film parameters. METHODS: Twenty participants (11 females, 9 males; mean age, 27 ±â€¯11 years) with dry eye symptoms were recruited in a two week, investigator-masked, randomised, contralateral-eye trial. Following 10 min of warm compress therapy application (MGDRx EyeBag®) on both eyes, eyelid massage therapy was applied to one eye (randomised) by device, and to the fellow eye by manual eyelid massage, once daily for 14 days. Ocular surface and tear film measurements were conducted at baseline, and 15 min post-application by a clinician, then again after 14 days of self-administered daily treatment at home. RESULTS: Baseline clinical measurements did not differ between the treatment groups (all p > 0.05). Following two weeks of treatment, tear film lipid layer grade improved significantly with device massage (p = 0.008), and was marginally greater than manual massage by less than 1 grade (p = 0.03). Although immediate post-treatment improvements in tear film stability were observed in both groups (both p < 0.05), no significant long-term cumulative effects or inter-treatment differences in stability measures were detected (all p > 0.05). Visual acuity, tear meniscus height, conjunctival hyperaemia, ocular surface staining, and meibomian gland dropout did not change during the treatment period (all p > 0.05). CONCLUSIONS: Two weeks of treatment with the eyelid massage device, as an adjunct to warm compress therapy, effected marginally greater improvements in tear film lipid layer thickness than the conventional manual technique, which were statistically but not clinically significant. Future parallel group trials with longer treatment periods and a greater range of disease severity are required.

Randomized, Controlled, Double-Masked, Multicenter, Pilot Study Evaluating Safety and Efficacy of Intranasal Neurostimulation for Dry Eye Disease.

Purpose: We assess the safety and effectiveness of intranasal neurostimulation to promote tear production via the nasolacrimal pathway in subjects with dry eye disease. Methods: A multicenter, randomized, controlled, double-masked pilot study was conducted in adults with dry eye diagnosis and at least one eye with corneal fluorescein staining ≥2 in at least one region or a sum of all regions ≥5 (National Eye Institute grading), basal Schirmer test score ≤10 mm, a cotton-swab stimulated Schirmer score ≥7 mm higher, and an Ocular Surface Disease Index score ≥23. Subjects were randomized to receive active intranasal neurostimulation or sham control intranasal stimulation 4 to 8 times per day. Assessments were scheduled before (unstimulated) and during (stimulated) device application at days 0, 7, 14, 30, and 90. The primary effectiveness endpoint was stimulation-induced change in Schirmer test (with anesthesia) score. Primary safety measure was incidence of device-related adverse events (AEs). Results: Fifty-eight subjects were randomized at nine sites in Australia and New Zealand; 56 completed the 90-day study. Stimulation-induced change in Schirmer score was significantly greater with active intranasal (mean ± SEM, 9.0 ± 2.0) than sham control intranasal stimulation (0.4 ± 0.6; P < 0.001) at day 90. Similar results were observed at days 0, 7, 14, and 30 (P < 0.001). No serious device-related AEs were observed. Mild nosebleed, the most common device-related AE, was reported in five (16.7%) subjects. Conclusions: Intranasal neurostimulation was effective in inducing acute tear production after 90 days of use and generally was well tolerated in subjects with dry eye disease.

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

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

Omega-3 polyunsaturated fatty acid supplementation for improving peripheral nerve health: protocol for a systematic review.

INTRODUCTION: Damage to peripheral nerves occurs in a variety of health conditions. Preserving nerve integrity, to prevent progressive nerve damage, remains a clinical challenge. Omega-3 polyunsaturated fatty acids (PUFAs) are implicated in the development and maintenance of healthy nerves and may be beneficial for promoting peripheral nerve health. The aim of this systematic review is to assess the effects of oral omega-3 PUFA supplementation on peripheral nerve integrity, including both subjective and objective measures of peripheral nerve structure and/or function. METHODS AND ANALYSIS: A systematic review of randomised controlled trials that have evaluated the effects of omega-3 PUFA supplementation on peripheral nerve assessments will be conducted. Comprehensive electronic database searches will be performed in Ovid MEDLINE, Embase, the Cochrane Central Register of Controlled Trials (CENTRAL), US National Institutes of Health Clinical Trials Registry and the WHO International Clinical Trials Registry Platform. The title, abstract and keywords of identified articles will be assessed for eligibility by two reviewers. Full-text articles will be obtained for all studies judged as eligible or potentially eligible; these studies will be independently assessed by two reviewers to determine eligibility. Disagreements will be resolved by consensus. Risk of bias assessment will be performed using the Cochrane Collaboration risk of bias tool to appraise the quality of included studies. If clinically meaningful, and there are a sufficient number of eligible studies, a meta-analysis will be conducted and a summary of findings table will be provided. ETHICS AND DISSEMINATION: This is a systematic review that will involve the analysis of previously published data, and therefore ethics approval is not required. A manuscript reporting the results of this systematic review will be published in a peer-reviewed journal and may also be presented at relevant scientific conferences. PROSPERO REGISTRATION NUMBER: CRD42018086297.

Comparison of treatment effect across varying severities of meibomian gland dropout.

PURPOSE: Better understanding of the pathophysiology of meibomian gland dysfunction (MGD) has provided the opportunity to develop treatments which could be tailored for specific presentations of MGD. This study sought to directly compare treatment effectiveness for three current therapies across differing levels of MG dropout. METHODS: Subjects (n=81), grouped by infrared meibography dropout proportions, into either no (control), mild, or pronounced MG dropout, were randomised to receive treatment with a latent heat device (n=25), liposomal spray (n=28), or heated warm compress (n=28). A battery of tear film measures was performed, pre- and post-application of treatment, and compared by treatment type and MG severity. RESULTS: Symptoms correlated with MG dropout proportions (r=0.618, p<0.001). Following treatment, non-invasive tear breakup time improved (p=0.010), independent of treatment type (p=0.131). The improvement was significant only in the pronounced MGD group (+4.32 ±1.15s, p=0.008), however, following treatment, the mild group was no longer distinct from the control group (p=0.843). Lipid layer grade (LLG) also improved following treatment (p<0.009), but again was not specific to treatment type (p=0.349). All three severity groups showed an improvement in LLG, with 49.3% of participants showing an improvement of at least one grade, and none showing decreased LLG. CONCLUSIONS: Increased LLG across all three treatment groups suggests that all methods increase meibum outflow to the tear film, resulting in a thicker lipid layer after treatment. These results suggest that all three treatments are effective in improving tear film quality, independent of MGD severity based either on symptoms or based on gland dropout.

TFOS DEWS II Management and Therapy Report.

The members of the Management and Therapy Subcommittee undertook an evidence-based review of current dry eye therapies and management options. Management options reviewed in detail included treatments for tear insufficiency and lid abnormalities, as well as anti-inflammatory medications, surgical approaches, dietary modifications, environmental considerations and complementary therapies. Following this extensive review it became clear that many of the treatments available for the management of dry eye disease lack the necessary Level 1 evidence to support their recommendation, often due to a lack of appropriate masking, randomization or controls and in some cases due to issues with selection bias or inadequate sample size. Reflecting on all available evidence, a staged management algorithm was derived that presents a step-wise approach to implementing the various management and therapeutic options according to disease severity. While this exercise indicated that differentiating between aqueous-deficient and evaporative dry eye disease was critical in selecting the most appropriate management strategy, it also highlighted challenges, based on the limited evidence currently available, in predicting relative benefits of specific management options, in managing the two dry eye disease subtypes. Further evidence is required to support the introduction, and continued use, of many of the treatment options currently available to manage dry eye disease, as well as to inform appropriate treatment starting points and understand treatment specificity in relation to dry eye disease subtype.

Temperature profiles of patient-applied eyelid warming therapies.

PURPOSE: To compare temperature profile characteristics (on and off eye) of two patient-applied heat therapies for meibomian gland dysfunction (MGD): an eye mask containing disposable warming units (EyeGiene(®)) and a microwave-heated flaxseed eye bag(®) (MGDRx EyeBag(®)). METHODS: In vitro evaluation: surface temperature profiles of activated eye masks and heated eye bags(®) (both n=10), were tracked every 10s until return to ambient temperature. Heat-transfer assessment: outer and inner eyelid temperature profiles throughout the eye mask and eye bag(®) treatment application period (10min) were investigated in triplicate. The devices were applied for 12 different time intervals in a randomised order, with a cool-down period in between to ensure ocular temperatures returned to baseline. Temperature measurements were taken before and immediately after each application. RESULTS: In vitro evaluation: on profile, the eye bag(®) surface temperature peaked earlier (0±0 s vs. 100±20 s, p<0.001), cooled more slowly and displayed less variability than the eye mask (all p<0.05). Heat-transfer assessment: the eye bag(®) effected higher peak inner eyelid temperatures (38.1±0.4°C vs. 37.4±0.2°C, p=0.04), as well as larger inner eyelid temperature increases over the first 2 min, and between 9 and 10 min (all p<0.05). CONCLUSIONS: The eye bag(®) surface temperature profile displayed greater uniformity and slower cooling than the eye mask, and was demonstrated to be significantly more effective in raising ocular temperatures than the eye mask, both statistically and clinically. This has implications for MGD treatment, where the melting points of meibomian secretions are likely to be higher with increasing disease severity.

Comparison of Self-applied Heat Therapy for Meibomian Gland Dysfunction.

PURPOSE: To compare the effects on ocular temperature, lipid layer grade, tear film stability, and tear meniscus height after a single application of two commercially available warm compresses in mild-to-moderate dry eye and to report participant treatment preference. METHODS: Forty-one subjects with mild-to-moderate dry eye symptoms were enrolled in a randomized, paired-eye, investigator-masked trial. Heat was applied simultaneously to one eye (randomized) with a portable eye mask (EyeGiene) and to the contralateral eye with a microwave-heated flaxseed eye bag (MGDRx Eye Bag). Outer and inner eyelid temperatures, tear film lipid layer grade (LLG), and noninvasive tear film breakup time (NIBUT) were measured at baseline and immediately after 10 minutes of device application. RESULTS: Outer and inner eyelid temperatures, LLG, and NIBUT did not differ before treatment between eyes assigned to eye mask and eye bag therapy. All measurements were significantly increased from baseline, after warming with both devices (all p < 0.05). Outer and inner eyelid temperature changes were significantly greater with the eye bag than with the eye mask (outer eyelid, +3.5 ± 1.0°C vs. +2.4 ± 0.8°C; inner eyelid, +3.5 ± 1.0°C vs. +2.5 ± 0.9°C; all p < 0.001), although there was no significant difference in LLG and NIBUT improvement between treatments (all p > 0.05). A majority of subjects (78%) preferred the application of heat with the eye bag over the eye mask. CONCLUSIONS: Both the EyeGiene mask and the MGDRx Eye Bag are convenient eyelid warming devices that result in clinically and statistically significant increases in NIBUT and LLG in patients with mild-to-moderate dry eye symptoms. The MGDRx Eye Bag is more effective in raising ocular temperature and is the preferred treatment method among subjects.