Efficacy and safety of trigeminal parasympathetic pathway stimulation for dry eye: A systematic review and meta-analysis.

This study aimed to investigate the efficacy and safety of trigeminal parasympathetic pathway (TPP) stimulation in the treatment of dry eye. A comprehensive search for randomized clinical trials was performed in seven databases (MEDLINE, Embase, CENTRAL, etc.) up to 28 February 2023. After screening the suitable studies, the data were extracted and transformed as necessary. Data synthesis and analysis were performed using Review Manager 5.4, and the risk of bias and quality of evidence were evaluated with the recommended tools. Fourteen studies enrolling 1714 patients with two methods (electrical and chemical) of TPP stimulation were included. Overall findings indicate that TPP stimulation was effective in reducing subjective symptom score (standardized mean difference [SMD], -0.45; 95% confidence interval [CI], -0.63 to -0.28), corneal fluorescence staining (mean difference [MD], -0.78; 95% CI, -1.39 to -0.18), goblet cell area (MD, -32.10; 95% CI, -54.58 to -9.62) and perimeter (MD, -5.90; 95% CI, -10.27 to -1.53), and increasing Schirmer's test score (SMD, 0.98; 95% CI, 0.65 to 1.31) and tear film break-up time (SMD, 0.57; 95% CI, 0.19 to 0.95). Compared to inactive or low-activity stimulation controls, it has a higher incidence of adverse events. Therefore, TPP stimulation may be an effective treatment for dry eye, whether electrical or chemical. Adverse events are relatively mild and tolerable. Due to the high heterogeneity and low level of evidence, the current conclusions require to be further verified.

Quantum Molecular Resonance Effects on Patients With Dry Eye Disease: A Randomized Controlled Trial.

PURPOSE: The aim of the study was to evaluate the efficacy and safety of quantum molecular resonance in the treatment of dry eye disease. METHODS: This study was a double-blind randomized control trial in 1 academic medical center, for 2 years. Participants received treatment or a placebo with the Rexon-Eye device, once per week for 4 weeks. The primary outcome was the change in dry eye symptoms assessed by the Ocular Surface Disease Index (OSDI). Secondary outcomes were clinical findings associated with the dry eye such as meibomian gland dysfunction (MGD) score, tear break-up time (TBUT), corneal fluorescein staining, Schirmer test, and best-corrected visual acuity (BCVA). RESULTS: Forty patients were recruited, 20 in each arm. The mean age was 63.5 ± 15.1 years and 27 (67.5%) were female. The mean OSDI score significantly improved in the intervention group from 19.15 ± 10.3 to 10.5 ± 7.0 ( P < 0.001), whereas the control group showed no significant change (14.4 ± 8.4 to 15.5 ± 8.6, P = 0.830). MGD scores significantly improved in the intervention group (1.57 ± 1.2 to 0.8 ± 0.9, P = 0.006), whereas showing no significant change in the control group (1.60 ± 0.9 to 1.99 ± 1.0, P = 0.244). The corneal staining score also showed significant improvement in the intervention group ( P = 0.045) and a nonsignificant decline in the placebo group ( P = 0.50). No significant difference was seen in TBUT, visual acuity, and Schirmer scores between groups. No harm resulting from treatment was reported during the duration of the trial. CONCLUSIONS: High-frequency electrotherapy may have a positive effect on symptoms and signs of dry eye. This emerging technology may become part of the arsenal of therapeutic modalities for this condition.

Eliciting blinks by transcutaneous electric nerve stimulation improves tear fluid in healthy video display terminal users: A self-controlled study.

We aimed to elicit strong blinks among healthy video display terminal (VDT) users by periorbital transcutaneous electric nerve stimulation (TENS) and evaluate its impact on the tear fluid and visual task. Appropriate TENS conditions were evaluated to evoke strong blinks under minimum discomfort. Seventeen healthy VDT users with noninvasive Keratograph first breakup time (NIKf-BUT) 5-15 s and Ocular Surface Disease Index (OSDI) scores < 15 were recruited in this study. Before the trial, noninvasive Keratograph average breakup time (NIKa-BUT), tear meniscus height (TMH) and OSDI scores were evaluated. Before each TENS session, the volunteers played Tetris while the corresponding blink rate and Tetris scores were recorded. Then, the participants underwent 30 minutes of TENS, which evoked blinking of their right eye 20 times per minute. Tetris scores were evaluated again during TENS. The Tetris scores and corresponding blink rate were assessed after each TENS session while NIKa-BUT, TMH and OSDI scores were recorded after the third and sixth TENS sessions. We found that OSDI scores declined significantly after the sixth TENS (P = .003). The NIKa-BUT of the right eye was promoted after the sixth TENS (P = .02), and the TMH was higher after the third and sixth TENS in both eyes (P = .03, P = .03 for right eyes respectively, P = .01, P = .01 for left eyes respectively). There was no significant difference between the adjusted Tetris scores before and during TENS (P = .12). The blink rate before and after TENS were unaffected after 6 sessions (P = .61). The results indicated that periorbital TENS effectively ameliorated ocular irritation and improved tear secretion and tear film stability by eliciting strong blinks in healthy VDT users without disturbing the visual task.

TearCare for the Treatment of Meibomian Gland Dysfunction in Adult Patients With Dry Eye Disease: A Masked Randomized Controlled Trial.

PURPOSE: The aim of this study was to demonstrate the safety and effectiveness of a single TearCare procedure compared with a single LipiFlow procedure in treatment of the dry eye disease associated with meibomian gland dysfunction. METHODS: In a multicenter, masked, randomized controlled trial, 135 subjects received a single TearCare (TC) treatment (n = 67) or a single LipiFlow (LF) treatment (n = 68) at baseline and were followed up for 1 month posttreatment. Tear film breakup time, meibomian gland function, and corneal and conjunctival staining scores were assessed as dry eye signs at baseline, 2 weeks, and 1 month; dry eye symptoms were assessed using the Ocular Surface Disease Index, Symptom Assessment in Dry Eye, and eye dryness questionnaires at baseline and 1 month. RESULTS: At 1 month posttreatment, both groups demonstrated significant improvements (P < 0.0001) in mean tear film breakup time and meibomian gland secretion score to 3.0 ± 4.4 and 11.2 ± 11.1 in the TC group and 2.6 ± 3.3 and 11.0 ± 10.4 in the LF group, respectively. The mean eye dryness, Symptom Assessment in Dry Eye, and Ocular Surface Disease Index scores were significantly reduced (P < 0.0001) by 35.4 ± 34.1, 38.2 ± 31.0, and 27.9 ± 20.5 in the TC group and 34.9 ± 26.9, 38.0 ± 25.9, and 23.4 ± 17.7 in the LF group, respectively. There were no statistically significant differences for any result between the groups. However, the TC group demonstrated numerically greater improvements consistently in all signs and symptoms. Device-related ocular adverse events were reported in 3 patients in the TC group (superficial punctate keratitis, chalazion, and blepharitis) and 4 patients in the LF group (blepharitis, 2 cases of foreign body sensation, and severe eye dryness). CONCLUSIONS: A single TearCare treatment significantly alleviates the signs and symptoms of dry eye disease in patients with meibomian gland dysfunction and is equivalent in its safety and effectiveness profile to LipiFlow treatment as shown in this 1-month follow-up study.

Preoperative Management of MGD with Vectored Thermal Pulsation before Cataract Surgery: A Prospective, Controlled Clinical Trial.

Purpose: To investigate the efficacy of preoperative monocular treatment in elderly cataract patients with Meibomian Gland Dysfunction (MGD) utilizing vectored thermal pulsation treatment.Materials and Methods: This study was a prospective, examiner-masked contralateral eye clinical trial. Patients previously diagnosed with MGD undergoing uncomplicated cataract surgery in two eyes were enrolled. The eye perceived by the patient to be more symptomatic of MGD received a 12 min vectored thermal pulsation treatment using the LipiFlow Thermal Pulsation System, and was referred to as the LipiFlow-surgery eye. The contralateral eye then served as the nonLipiFlow-surgery eye. Patients with MGD not undergoing cataract surgery were enrolled as the control group. Within the control group, the eye that received LipiFlow treatment was considered the LipiFlow-nonsurgery eye, while the contralateral eye served as the nonLipiFlow-nonsurgery eye. All patients were examined before treatment and at one-week, one-month, and three-month intervals after treatment. Clinical parameters included dry eye symptoms, average lipid layer thickness (LLT-ave), tear breakup time (TBUT), corneal staining, Schirmer I tests, Meibomian glands yielding liquid secretion (MGYLS), and meibomian gland dropout.Results: A total of 32 patients (64 eyes) were examined during the three-month follow-up. There was a significant reduction in dry eye symptoms in non-surgery patients with monocular treatment of MGD, while no change in surgery patients was observed. Significant improvement of MGYLS in LipiFlow-surgery and LipiFlow-nonsurgery eyes during the follow-up time (p < .001) was reported, while no difference was observed in nonLipiFlow-surgery and nonLipiFlow-nonsurgery eyes. A statistically significant difference was seen in TBUT between LipiFlow-surgery and nonLipiFlow-surgery eyes at one-week and one-month intervals (p = .019 and 0.019, respectively). Differences in other clinical parameters were not statistically significant.Conclusions: Our findings suggest that although subjective symptoms were not alleviated, a single application of LipiFlow treatment before cataract surgery is effective in alleviating blockage of meibomian glands and preventing the decline of TBUT after cataract surgery.

Comparative Evaluation in Intense Pulsed Light Therapy Combined with or without Meibomian Gland Expression for the Treatment of Meibomian Gland Dysfunction.

OBJECTIVE: To determine whether the combination of meibomian gland expression (MGX) with intense-pulsed light (IPL) has a better efficacy to treat meibomian gland dysfunction (MGD) than IPL alone. METHODS: One hundred patients with MGD were randomly divided into three groups: MGX, IPL, and IPL+ MGX. Clinical parameters included the Ocular Surface Disease Index (OSDI), tear meniscus height (TMH), noninvasive keratograph tear breakup time (NIBUT), redness, meibomian gland dropout, tear breakup time (TBUT), corneal fluorescent staining (CFS), eyelid margin score, meibomian gland secretion function, and Schirmer I tests were collected before treatment and at 1 and 3 months after treatment. Compare the indexes of each group before and after treatment and also compare the differences of each group on follow-up. RESULTS: Compared to the baseline, OSDI, TBUT, and meibomian gland secretion function in IPL group improved throughout the follow-up period (all P < .05) and part of the meibomian gland secretion function increased continuously. OSDI, TBUT, lower eyelid margin scores, and meibomian gland secretion function in IPL + MGX group improved at the both follow-up visits (all P < .05), and continued improvement in meibomian gland secretion function can be observed. Lower meibomian gland dropout and CFS reduced at 1 month and 3 months respectively in IPL ± MGX group (P = .001,P = .001).Compared to IPL group, only CFS has reduction in IPL + MGX group at 1-month (P < .001), CFS, upper and lower MGYCS were improved at the 3 months (P = .037,P = .014, P = .049). CONCLUSIONS: MGX may have synergistic effect when combined with IPL therapy, and the effect can last at least 3 months.

Effect of 808-nm Laser Photobiomodulation Treatment in Blepharitis Rat Model.

PURPOSE: Blepharitis, simply defined as eyelid inflammation, is one of the common ocular conditions associated with discomfort and irritation. Because blepharitis causes meibomian gland dysfunction and dry eye, this study aimed to confirm the effect of photobiomodulation (PBM) on blepharitis. METHODS: A total of 20 rats were randomly assigned to 4 equal groups, including control, blepharitis, PBM, and eye drop. Blepharitis was induced in rats by injecting complete Freund's adjuvant in the eyelid margins. PBM intervention was given every 3 days after blepharitis induction. Clinical signs including tear volume, tear breakup time (TBUT), meibomian gland swelling, fluorescein, telangiectasia, and meibomian gland secretion scores were measured every week, and the rats were killed for histological analysis after 4 weeks. Immunohistochemistry was performed to compare the level of inflammatory cytokines, interleukin-1ß and tumor necrosis factor-α, and terminal deoxynucleotidyl transferase dUTP nick end labeling staining on retina was performed to observe any retinal damage. RESULTS: Tear volume and TBUT increased with PBM intervention, and with improved eyelid swelling, corneal staining, telangiectasia, and meibomian gland secretion scores increased. Hematoxylin and eosin staining showed no structural abnormalities of meibomian gland caused by blepharitis induction. Immunohistochemistry revealed that the levels of inflammatory cytokines interleukin-1ß and tumor necrosis factor-α were lowered with PBM treatment in both eyelid and conjunctiva. Terminal deoxynucleotidyl transferase dUTP nick end labeling staining showed no retinal damage. CONCLUSIONS: Laser PBM at 808 nm was effective in alleviating ocular signs and controlling inflammation in blepharitis rat model. The in vivo results suggest that PBM has the potential to be used in treating blepharitis patients.

The clinical efficiency of lycium-rehmannia pills in treating dry eye symptom: A meta-analysis.

BACKGROUND: Dry eye symptom threatens human health and causes a larger burden of disease, the study aims to systematically compare the therapeutic effect of Lycium-rehmannia pills combined with topical eye drops and pure western medicine (western medicine eye drops) on dry eye symptom, to provide a reflection and enlightenment for clinical treatment. METHOD: PubMed, The Cochrane Library, EMbase, MEDLINE, CBM, WanFang, VIP, and CNKI databases were searched manually and automatically by the computer until March 2019 and relevant randomized controlled trials (RCTs) were selected. Article selection and data extraction were conducted by 2 researchers independently, then RevMan 5.3 was applied for meta-analysis. RESULT: Fifteen randomized controlled trials were included, including 1222 patients (eyes = 2382). The meta-analysis results showed that Lycium-rehmannia pills combined with western medicine were superior to the control group in terms of therapeutic efficiency [OR = 4.38, 95% confidence interval (CI) (3.26, 5.89), P < .00001]. There were controversial results that the study group was better than the control group in Basic Schirmer test [MD, 2.46, 95% CI (1.49, 3.44), P < .00001], tear break up time [MD, 3.79, 95% CI (3.57, 4.01), P < .00001], and Fluorescein test [MD, -1.29, 95% CI (-1.42, -1.15), P < .00001], but Lycium-rehmannia pills combined with western medicine could not reduce the incidence of adverse reactions, including eyelid inflammation [OR = 1.00, 95% CI (0.37, 2.72), P = 1.00] and congestion symptom [OR = 0.55, 95% CI (0.18, 1.65), P = .28]. CONCLUSION: Lycium-rehmannia pills combined with western medicine is better than the control group of therapeutic efficiency in the treatment of dry eye symptom. Due to the quantity and quality limitations of the literature, there were controversial results that the study group was better than the control group in Basic Schirmer test, Tear break up time, Fluorescein test, and reduced adverse reactions, including inflammation of the eyelids and congestion. The above conclusion needs more clinical trials to test and verify.

Intense Pulsed Light for Meibomian Gland Disease: A Report by the American Academy of Ophthalmology.

PURPOSE: To review the literature on the efficacy of intense pulsed light (IPL) on the eyelids in the management of meibomian gland disease (MGD) and meibomian gland-related ocular surface disease. METHODS: A literature search was last conducted on May 15, 2019, in the PubMed and Cochrane Library databases for English-language original research that assessed the effect of IPL on MGD in adult patients. Thirty-three articles were identified, and 12 studies were determined to be relevant to the criteria outlined for assessment. The panel methodologist (V.K.A.) assigned a level of evidence rating to each study; 4 studies were rated level II, and 8 studies were rated level III. Five studies had potential conflicts of interest and design limitations that affected interpretation of results. RESULTS: All studies documented improvement in clinically meaningful metrics, including tear breakup time (TBUT), corneal staining and eyelid margin measurements, meibum quality, meibomian gland expressability, ocular surface disease index (OSDI), and standard patient evaluation of eye dryness (SPEED) questionnaire scores. Side effects were relatively uncommon but included discomfort, cutaneous erythema, blistering, eyelash loss, and floaters; these were uniformly self-limited. CONCLUSIONS: Although methodological limitations and potential conflicts of interest in some studies raised concern, the existing body of literature demonstrates improvements in the signs and symptoms of MGD after IPL therapy.

Effect of a formulated eye drop with Leptospermum spp honey on tear film properties.

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.

Intense regulated pulse light for the meibomian gland dysfunction.

PURPOSE: To assess the effect of intense regulated pulse light (E-Eye; E-Swin, France) on the treatment of meibomian gland dysfunction. SETTING: Health Sciences University, Ankara Numune Training and Research Hospital, Department of Ophthalmology. METHODS: A total of 26 patients underwent intense pulsed light treatment (E-Eye; E-Swin), with homogeneously sequenced five light pulses delivered to one eye at 1, 15, and 45 days following baseline evaluation. At each visit, subjective clinical parameters (ocular surface disease index questionnaire and standard patient evaluation of eye dryness questionnaire) and objective clinical parameters (Schirmer I test scores, tear break-up times, Oxford grading, lid margin abnormality score, secretion quality and expressibility degree) were recorded. The subjective and objective parameters at Days 15 and 45 were compared with baseline values. RESULTS: Patients underwent three sessions of intense pulsed light treatment. Schirmer test and tear break-up time improved significantly from baseline to Day (D) 45 (8.53 ± 4.31 mm vs 12.6 ± 3.14 mm, 4.53 ± 1.33 sn vs 11.07 ± 2.87 sn, p = 0.003 and p < 0.001). Ocular surface disease index and standard patient evaluation of eye dryness scores improved from baseline to D15 and baseline to D45 (all with p < 0.05). All the subjects reported reduced symptoms by D45. There were no cases of adverse ocular effects. There was no significant change in Oxford grading, lid margin abnormality score, secretion quality, and expressibility degree. CONCLUSIONS: Intense regulated pulse light seems a safe treatment procedure for meibomian gland dysfunction, improving tear film quality and reducing symptoms of dry eye.

Hypothalamic activation discriminates painful and non-painful initiation of the trigeminal autonomic reflex - an fMRI study.

BACKGROUND: The role of the trigeminal autonomic reflex in headache syndromes, such as cluster headache, is undisputed but sparsely investigated. The aim of the present study was therefore, to identify neural correlates that play a role in the initiation of the trigeminal autonomic reflex. We further aimed to discriminate between components of the reflex that are involved in nociceptive compared to non-nociceptive processing. METHODS: Kinetic Oscillation Stimulation (KOS) in the left nostril was applied in order to provoke autonomic symptoms (e.g. lacrimation) via the trigeminal autonomic reflex in 26 healthy participants using functional magnetic resonance imaging. Unpleasantness and painfulness were assessed on a visual analog scale (VAS), in order to assess the quality of the stimulus (e.g. pain or no pain). RESULTS: During non-painful activation, specific regions involved in the trigeminal autonomic reflex became activated, including several brainstem nuclei but also cerebellar and bilateral insular regions. However, when the input leading to activation of the trigeminal autonomic reflex was perceived as painful, activation of the anterior hypothalamus, the locus coeruleus (LC), the ventral posteriomedial nucleus of the thalamus (VPM), as well as an activation of ipsilateral insular regions, was observed. CONCLUSION: Our results suggest the anterior hypothalamus, besides the thalamus and specific brain stem regions, play a significant role in networks that mediate autonomic output (e.g. lacrimation) following trigeminal input, but only if the trigeminal system is activated by a stimulus comprising a painful component.

The Efficacy of Warm Compresses in the Treatment of Meibomian Gland Dysfunction and Demodex Folliculorum Blepharitis.

Purpose: To investigate and compare the effect of warm compresses on meibomian gland dysfunction and Demodex folliculorum blepharitis.Methods: Forty-two subjects (13 males, 29 females; mean age of 56.45 years) enrolled and completed the two-month warm compress treatment study. Three warm compress therapies were compared: Warm face cloth, MGDRx EyeBag® and OPTASETM Moist Heat Mask. Subjects attended for four visits: baseline, two weeks, four weeks, and eight weeks. Subjective symptoms, osmolarity, non-invasive tear break-up time, ocular surface staining, Schirmer I test, meibum expressibility and clarity, and eyelash manipulation and epilation to assess for the presence of Demodex folliculorum, were measured at each visit.Results: Meibomian gland dysfunction, based on a composite score of meibum quality and expressibility, reduced significantly with the MGDRx EyeBag® and the OPTASETM Moist Heat Mask (p < .05). There was no significant difference in efficacy for treating meibomian gland dysfunction between the two devices (p = .29). No improvement in meibomian gland dysfunction was detected with the warm face cloth. Only the OPTASETM Moist Heat Mask significantly reduced the quantity of Demodex folliculorum over eight-weeks of treatment (p = .036, only baseline to week eight significant p = .008). Symptoms and ocular surface staining improved significantly in all three groups (p < .05). There was no significant change observed in osmolarity, non-invasive tear break-up time or Schirmer I test within each group (p > .05, respectively).Conclusion: The MGDRx EyeBag® and the OPTASETM Moist Heat Mask exhibited superior efficacy in treating signs and symptoms of meibomian gland dysfunction, compared to the use of a warm face cloth, over the eight-week period. The OPTASETM Moist Heat Mask demonstrated dual therapeutic abilities, treating both meibomian gland dysfunction and Demodex folliculorum blepharitis. Repeated application of heat for the treatment of meibomian gland dysfunction may continue to present a good home-remedy option for patients.

Effect of the Bruder moist heat eye compress on contact lens discomfort in contact lens wearers: An open-label randomized clinical trial.

The purpose of this study was to investigate the effect of the Bruder Moist Heat Compress on contact lens (CL) discomfort in subjects with contact lens-related dry eye (CLDE). This was a 4-week, single-center, three-arm, randomized, open-label clinical trial in subjects diagnosed with CLDE using the Contact Lens Dry Eye Questionnaire. Fifty-one CL wearers were randomized to one of three treatment groups: application of the Bruder Compress twice a day, Bruder Compress once a day, or warm washcloth used for ten minutes twice a day without reheating. Subject diaries were monitored for compliance and collected data on daily CL comfort upon awakening and throughout the afternoon. Clinical assessments included tear film break-up time (TBUT), lipid layer thickness (LLT), and meibomian gland evaluation. Statistical tests included a generalized linear model and one-way analysis of variance (ANOVA) to investigate treatment effect on comfortable wear time. Fifty-one subjects (98% female) completed the study. After treatment, subjects using a washcloth reported more uncomfortable contact lens wear time on average (mean = 5.1 ± 2.8 h) when compared with subjects who had used the Bruder Compress in Group 1 (mean = 2.8 ± 1.6 h) (p = 0.02). In the Bruder Compress groups, there was a significant reduction in the blockage of meibomian glands (p < 0.01). No significant difference in uncomfortable wear time was found between subjects using the Bruder Compress twice daily versus once daily (p = 0.48). Subjects using the Bruder Compress once daily had the highest rate of compliance at 90.2% (p < 0.01). No significant improvements were observed in TBUT (p = 0.76) or LLT (p = 0.78). The Bruder Moist Heat Compress resulted in a significant improvement in comfortable CL wear time in subjects with CLDE.

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.

Efficacy of Omega-3 Fatty Acid Supplementation for Treatment of Dry Eye Disease: A Meta-Analysis of Randomized Clinical Trials.

PURPOSE: To assess whether omega-3 fatty acid (FA) supplementation is more efficacious than placebo in amelioration of signs and symptoms of dry eye disease. METHODS: We performed a systematic literature search in PubMed, Scopus, Web of Science, and Cochrane Central Register of Controlled Trials databases. We included randomized clinical trials comparing omega-3 FA supplementation with placebo in patients with dry eye disease. The outcome measures were dry eye symptoms, breakup time (BUT), Schirmer test, and corneal fluorescein staining. The pooled effect sizes were estimated using a random-effects model. Heterogeneity was evaluated using the Q and I tests. Sensitivity analysis and assessment of publication bias were performed. Meta-regression was performed to evaluate the source of heterogeneity. RESULTS: Seventeen randomized clinical trials involving 3363 patients were included. Compared with placebo, omega-3 FA supplementation decreased dry eye symptoms [standardized difference in mean values (SDM) = 0.968; 95% confidence interval (CI) 0.554-1.383; P < 0.001] and corneal fluorescein staining (SDM = 0.517; 95% CI, 0.043-0.991; P = 0.032), whereas it increased the BUT (SDM = 0.905; 95% CI, 0.564-1.246; P < 0.001) and Schirmer test values (SDM = 0.905; 95% CI, 0.564-1.246; P < 0.001). No evidence of publication bias was observed, and sensitivity analyses indicated the robustness of results obtained. Meta-regression analysis showed a higher improvement of dry eye symptoms and BUT in studies conducted in India. CONCLUSIONS: This meta-analysis provides evidence that omega-3 FA supplementation significantly improves dry eye symptoms and signs in patients with dry eye disease. Therefore, our findings indicate that omega-3 FA supplementation may be an effective treatment for dry eye disease.

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.

Effects of a sea buckthorn oil spray emulsion on dry eye.

PURPOSE: To investigate the effects of a sea buckthorn oil and sodium hyaluronate-containing eyelid spray emulsion (SB spray) on dry eye. METHODS: A randomized controlled study was carried out. Adults (25-70 years) with Ocular Surface Disease Index (OSDI) ≥20 and moderate or severe dryness, burning or grittiness of the eyes were included. In study part one (n = 2), SB spray was used on both closed eyelids four times in one day. In part two (n = 10), SB spray was used on one randomized eyelid, and a commercial reference spray on the other for nine days. In part three (n = 40), eyes were randomized to one eye receiving SB spray and an untreated control for 1.5 months. Dry eye tests were carried out at baseline, during, and at the end of each study section. Symptoms were recorded in questionnaires and daily logs. RESULTS: In part one, the SB spray was well tolerated. In part two, OSDI decreased significantly (P = 0.022) in the SB spray eye compared to the reference spray, indicating a beneficial effect on symptoms. In part three, OSDI in the SB spray eye decreased significantly compared to the untreated control (P = 0.0007). The scores for dryness at the study end were lower in the SB spray eye compared to control (P = 0.0070). Symptom sums and frequencies of dryness (sum P = 0.0046, frequency P = 0.0016) and watering (sum P = 0.0003, frequency P = 0.013) in the daily logs were lower in the eye treated with SB spray. CONCLUSIONS: SB spray on closed eyelids relieved the symptoms of dry eye.

An Eyelid Warming Device for the Management of Meibomian Gland Dysfunction.

PURPOSE: To determine the effectiveness of the MGDRx EyeBag in managing meibomian gland dysfunction. METHODS: This was a prospective, randomized, controlled, observer-masked, bilateral eye study that enrolled 29 participants. Participants were randomized into either the EyeBag group or the control group. The EyeBag group used the EyeBag 10minutes 2x/day, and the control group remained on their own dry eye treatment regimen (if applicable). All participants were observed at baseline, 2 weeks (2wk) and 4 weeks (4wk). At 4wk, participants in the EyeBag group were asked to stop using the EyeBag. All participants were seen again at 8 weeks (8wk). Primary outcomes were the Ocular Surface Disease Index (OSDI), Current Symptoms Questionnaire (CSQ), meibomian gland score (MG score), and non-invasive tear breakup time (NIBUT). RESULTS: Twenty-five participants completed the study (mean age 38±15 years, 7 male). There was a significant change in OSDI over time for the EyeBag group (mean[lower 95% CI, upper 95% CI], baseline: 39.1[31.1,47.0], 2wk: 26.8[19.7,33.9], 4wk: 26.6[16.5,36.7], 8wk: 27.7[18.4,37.0]; p=0.01), but not in the control group (p=0.22), but no significant difference between groups at all time points (all p>0.27). Symptoms immediately improved after conducting the EyeBag based on at-home CSQ scores (Δ=-5.0 points, p<0.01), but not in the control group. For both groups, there was no significant change (p-value EyeBag,p-value control) in MG score (0.21,0.17) and NIBUT (0.49,0.06) over time. CONCLUSIONS: The EyeBag may relieve symptoms of dry eye, but the effect on meibomian gland function and tear stability when used for only 4 weeks was undetectable.