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.

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.

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.

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.

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.

Press releases issued by supplements industry organisations and non-industry organisations in response to publication of clinical research findings: a case-control study.

BACKGROUND: Dietary supplement use is increasing despite lack of evidence of benefits, or evidence of harm. Press releases issued by the supplements industry might contribute to this situation by using 'spin' (strategies to hype or denigrate findings) to distort the results of clinical studies. We assessed press releases issued in response to publication of clinical studies on dietary supplements. METHODS AND FINDINGS: We analyzed 47 supplements industry press releases and 91 non-industry press releases and news stories, generated in response to 46 clinical studies of dietary supplements published between 1/1/2005 and 5/31/2013. The primary outcome was 'spin' content and direction. We also assessed disposition towards use of dietary supplements, reporting of study information, and dissemination of industry press releases. More supplements industry press releases (100%) contained 'spin' than non-industry media documents (55%, P<0.001). Hyping 'spin' scores were higher in industry than non-industry media documents for studies reporting benefit of supplements (median 'spin' score 3.3, 95% CI 1.0-5.5 vs 0.5, 0-1.0; P<0.001). Denigratory 'spin' scores were higher in industry than non-industry media documents for studies reporting no effect (6.0, 5.0-7.0 vs 0, 0-0; P<0.001) or harm (6.0, 5.5-7.5 vs 0, 0-0.5; P<0.001) from a supplement. Industry press releases advocated supplement use in response to >90% of studies that reported no benefit, or harm, of the supplement. Industry press releases less frequently reported study outcomes, sample size, and estimates of effect size than non-industry media documents (all P<0.001), particularly for studies that reported no benefit of supplements. Industry press releases were referenced by 148 news stories on the websites of 6 organizations that inform manufacturers, retailers and consumers of supplements. CONCLUSIONS: Dietary supplements industry press releases issued in response to clinical research findings are characterized by 'spin' that hypes results that are favourable to supplement use and denigrates results that are not.