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.

The Yin and Yang of non-immune and immune responses in meibomian gland dysfunction.

Meibomian gland dysfunction (MGD) is a leading cause of dry eye disease and one of the most common ophthalmic conditions encountered in eye clinics worldwide. These holocrine glands are situated in the eyelid, where they produce specialized lipids, or meibum, needed to lubricate the eye surface and slow tear film evaporation - functions which are critical to preserving high-resolution vision. MGD results in tear instability, rapid tear evaporation, changes in local microflora, and dry eye disease, amongst other pathological entities. While studies identifying the mechanisms of MGD have generally focused on gland obstruction, we now know that age is a major risk factor for MGD that is associated with abnormal cell differentiation and renewal. It is also now appreciated that immune-inflammatory disorders, such as certain autoimmune diseases and atopy, may trigger MGD, as demonstrated through a T cell-driven neutrophil response. Here, we independently discuss the underlying roles of gland and immune related factors in MGD, as well as the integration of these two distinct mechanisms into a unified perspective that may aid future studies. From this unique standpoint, we propose a revised model in which glandular dysfunction and immunopathogenic pathways are not primary versus secondary contributors in MGD, but are fluid, interactive, and dynamic, which we likened to the Yin and Yang of MGD.

Need to Increase the Number of Intense Pulsed Light (IPL) Treatment Sessions for Patients with Moderate to Severe Meibomian Gland Dysfunction (MGD) Patients.

PURPOSE: To evaluate whether patients with moderate-to-severe meibomian gland dysfunction (MGD) will benefit from increasing the number of intense pulsed light (IPL) treatment sessions. METHODS: Ninety Asian adult with MGD (stages 3-4) were enrolled in this retrospective study. In Group1, 30 patients completed the five-session IPL treatment, 63.33% of which also received meibomian gland expression (MGX). In Group 2, 60 patients received three-session IPL treatment, 60.0% of which also accepted MGX. Both intragroup and intergroup analyses were conducted. RESULTS: The population characteristics, clinical baseline characteristics and therapeutic regimen were comparable between Group1 and Group2. The symptoms and most clinical indices improved after IPL treatment finished in both two groups. No statistical difference was found in any improvement level of all symptomatic and physical indices, including the Ocular surface disease index, tear break-up time, Demodex, corneal staining, meibum quality, meibomian gland expressibility, and MGD stage (all p ≥ 0.05) between the two groups at any time, not only month by month, but also at the terminal visit. However, the response rate of Group1 after the five-session treatment (70.00%) was increased compared to that of Group2 after the three-session treatment (63.33%). CONCLUSIONS: Increasing the number of IPL sessions is beneficial for patients with moderate to severe MGD to increase the response rate of treatment, rather than the improvement level. However, there is no need for patients who respond well to a routine number of IPL treatments to undergo additional IPL sessions.

Efficacy of meibomian gland expression combined with Home-Based therapy in the management of dry eye Disease: A systematic review and Meta-Analysis.

PURPOSE: To compare the effectiveness of meibomian gland expression (MGX) combined with home-based therapy versus home-based therapy alone for the treatment of dry eye disease (DED) caused by meibomian gland dysfunction (MGD). METHODS: A systematic review of randomized controlled studies (RCTs), reporting the effects of MGX combined with home-based therapy in 2 databases, PubMed and Web of Science, was performed according to the PRISMA statement. The search period was until August 20, 2023. According to the heterogeneity, a random or fixed effects model was performed in the meta-analysis. The standardized mean difference (SMD) was calculated to analyze dry eye symptoms (DES) score, tear film break-up time (TBUT), total corneal fluorescein staining (tCFS) and meibomian glands expressibility (MGE). All analyses were performed by RevMan Web, version 5.7. The Cochrane risk of bias tool was used to analyze the quality of the studies selected. RESULTS: Two RCTs with a total of 99 patients were included. The studies reported that MGX combined with home-based therapy improves DES score, TBUT, tCFS and MGE compared to the home-based therapy. However, the meta-analysis indicated that MGX combined with home-based therapy only seems to be beneficial in reducing DES score (SMD -0.49; 95 % CI: -0.89 to -0.08; P = 0.02; I2 = 0 %). In addition, although TBUT, tCFS and MGE reported a slight trend in favor of MGX combined with home-based therapy, it was non-significant. CONCLUSIONS: While MGX combined with home-based therapy seem to show some evidence of alleviating dry eye symptoms, there is insufficient evidence to conclude the effects of this treatment definitively particularly in improving dry eye signs caused by MGD, such as TBUT, tCFS and MGE. Therefore, further RCTs are needed to elucidate these results.

Therapeutic effects of low-color-temperature light-emitting diodes on dry eye.

BACKGROUND: As a new technology for treating dry eye diseases, phototherapy has attracted great attention, but the research on its safety and effectiveness is limited. In this study, the therapeutic effects of low-color-temperature light-emitting diodes on dry eye in humans, rabbits, and rats were investigated. METHODS: In clinical experiments, subjects in both groups read the same paper for 3 h under light sources of two color temperatures: 1900 K (low-color-temperature light-emitting diodes) or 4000 K (artificial fluorescent white light-emitting diodes). The differences in the non-invasive tear film breakup time, tear meniscus height, and conjunctival congestion scores before and after the experiment were compared between the two groups. In animal experiments, corneal epithelial barrier function and tear production of Sprague-Dawley rats and New Zealand white rabbits with dry eye were compared before and after low-color-temperature light-emitting diodes treatment. TUNEL staining and Western blotting were used to detect the apoptosis of corneal and conjunctival cells and the expression of inflammatory factor IL-1ß. RESULTS: Low-color-temperature light-emitting diodes prolonged tear film breakup time in patients with dry eye. Moreover, it increased tear secretion, decreased fluorescein sodium staining scores, corneal and conjunctival cell apoptosis, and inflammatory factor expression in rabbits and rats with dry eye. CONCLUSIONS: Low-color-temperature light-emitting diodes phototherapy can be used as an effective treatment for dry eye, reducing its symptoms and related ocular surface damage in humans, rabbits, and rats.

Novel treatment of chalazion using light-guided-tip intense pulsed light.

We assessed the effectiveness of light-guided-tip intense pulsed light (IPL) with meibomian gland expression (MGX) in chalazion treatment. Ninety-five eyes with chalazion received a light-guided-tip IPL-MGX treatment (IPL-MGX group), and another 95 eyes with chalazion received incision with curettage treatment (Control group). Prior to IPL or incision, as well as 1 month after the final treatment, data were gathered pertaining to the lesion location and size, hyperemia, lesions regression or recurrence, and a comprehensive ophthalmic examination. The total size of the chalazia in the IPL-MGX group was significantly reduced after the final treatment, with an average resolution rate of 70.5%, which is comparable to excision surgery. A significant decrease in chalazion recurrence rate was apparent after treatment in the IPL-MGX group compared with control. Moreover, the IPL-MGX demonstrated significant advancements throughout noninvasive tear film breakup time (NIBUT) as well as meibum grade in comparison to baseline and those in the the Control group. The use of IPL-MGX was found to be an efficient therapy for reducing the size and recurring frequency of chalazia, as well as for improving the meibomian gland function. It may be considered as a first-line treatment for cases of primary or recurrent chalazia with inflammation.

1,5-Dicaffeoylquinic acid from Pseudognaphalium affine ameliorates dry eye disease via suppression of inflammation and protection of the ocular surface.

PURPOSE: Pseudognaphalium affine (P. affine), a medicinal plant, has long been used to treat various diseases due to its astringent and vulnerary effects. These therapeutic benefits are largely attributed to high contents of phytochemicals, such as flavonoids and polyphenols, that have anti-inflammatory and tissue-protective activities. Herein, we investigated the potential of dicaffeoylquinic acids (diCQAs), polyphenols from P. affine, as a novel treatment for dry eye disease (DED). METHODS: We isolated 1,5-, 3,4-, 3,5- and 4,5-diCQAs from the P. affine methanol extract, and tested the effects of diCQA isomers in cultures of human corneal epithelial cells (CECs) under desiccating hyperosmolar stress and in two mouse models for DED: desiccating environmental stress-induced DED and the NOD.B10-H2b mouse model of ocular Sjögren's syndrome. RESULTS: Initial screening showed that, among the diCQAs, 1,5-diCQA significantly inhibited apoptosis and enhanced viability in cultures of CECs under hyperosmolar stress. Moreover, 1,5-diCQA protected CECs by promoting proliferation and downregulating inflammatory activation. Subsequent studies with two mouse models of DED revealed that topical 1,5-diCQA administration dose-dependently decreased corneal epithelial defects and increased tear production while repressing inflammatory cytokines and T cell infiltration on the ocular surface and in the lacrimal gland. 1,5-diCQA was more effective in alleviating DED, as compared with two commercially-available dry eye treatments, 0.05% cyclosporine and 0.1% sodium hyaluronate eye drops. CONCLUSIONS: Together, our results demonstrate that 1,5-diCQA isolated from P. affine ameliorates DED through protection of corneal epithelial cells and suppression of inflammation, thus suggesting a novel DED therapeutic strategy based on natural compounds.

Efficacy of intense pulsed light therapy on signs and symptoms of dry eye disease: A meta-analysis and systematic review.

This study reviewed the efficacy and safety of intense pulsed light (IPL) for the treatment of dry eye disease (DED). The PubMed database was used to conduct the literature search, which used the keywords "intense pulsed light" and "dry eye disease". After the authors evaluated the articles for relevancy, 49 articles were reviewed. In general, all treatment modalities were proven to be clinically effective in reducing dry eye (DE) signs and symptoms; however, the level of improvement and persistence of outcomes differed amongst them. Meta-analysis indicated significant improvement in the Ocular Surface Disease Index (OSDI) scores post-treatment with a standardized mean difference (SMD) = -1.63; confidence interval (CI): -2.42 to -0.84. Moreover, a meta-analysis indicated a significant improvement in tear break-up time (TBUT) test values with SMD = 1.77; CI: 0.49 to 3.05. Research suggests that additive therapies, such as meibomian gland expression (MGX), sodium hyaluronate eye drops, heated eye mask, warm compress, lid hygiene, lid margin scrub, eyelid massage, antibiotic drops, cyclosporine drops, omega-3 supplements, steroid drops, and warm compresses along with IPL, have been found to work in tandem for greater effectiveness; however, in clinical practice, its feasibility and cost-effectiveness have to be taken into consideration. Current findings suggest that IPL therapy is suitable when lifestyle modifications such as reducing or eliminating the use of contact lenses, lubricating eye drops/gels, and warm compresses/eye masks fail to improve signs and symptoms of DE. Moreover, patients with compliance issues have been shown to benefit well as the effects of IPL therapy is sustained for over several months. DED is a multifactorial disorder, and IPL therapy has been found to be safe and efficient in reducing its signs and symptoms of meibomian gland dysfunction (MGD)-related DE. Although the treatment protocol varies among authors, current findings suggest that IPL has a positive effect on the signs and symptoms of MGD-related DE. However, patients in the early stages can benefit more from IPL therapy. Moreover, IPL has a better maintenance impact when used in conjunction with other traditional therapies. Further research is needed to assess cost-utility analysis for IPL.

A randomized controlled study evaluating outcomes of intense pulsed light and low-level light therapy for treating meibomian gland dysfunction and evaporative dry eye.

Purpose: This randomized, controlled, blinded study evaluates the efficacy of intense pulsed light (IPL) therapy with low-level light therapy (LLLT) in the treatment of meibomian gland dysfunction (MGD) and evaporative dry eye (EDE) compared to a control group. Methods: Hundred patients with MGD and EDE were randomized into control (50 subjects, 100 eyes) and study group (50 subjects, 100 eyes). The study group underwent three sittings of IPL with LLLT 15 days apart and were followed up 1 month and 2 months after the last treatment sitting. The control group underwent sham treatment and was followed up at the same intervals. The patients were evaluated at baseline and 1 month and 3 months (post 1st treatment) for dry eye. Schirmer's test and tear breakup time (TBUT), OSDI, meibomian gland expression, and meibography. Results: The study group showed significant improvement in OSDI scores (P < 0.0001) compared to the control group and a significant improvement in TBUT (P < 0.005) compared to the control group. There was no change in schirmer's test and an improvement in the meibomian gland expression but not significant. Conclusion: The results show that a combined therapy of IPL with LLT is effective in treating MGD with EDE compared to controls, and repeated treatment sessions have a cumulative effect on the disease outcomes.

Intense pulsed-light treatment improves objective optical quality in patients with meibomian gland dysfunction.

BACKGROUND: To evaluate changes in objective optical quality following intense pulsed light (IPL) treatment combined with meibomian gland (MG) expression (MGX) in patients with MG dysfunction (MGD). METHODS: This retrospective cross-sectional study included MGD-related dry eye disease (DED) patients who received IPL treatment between March and December 2021 at Kim's Eye Hospital, Seoul, Republic of Korea. Each patient underwent four sessions of IPL treatment using Lumenis M22 (Lumenis Ltd., Yokneam, Israel) and MGX at three-week intervals. RESULTS: This study included 90 eyes from 45 patients with MGD. The mean age was 52.3 ± 16.1 years (range, 20-75 years), and 53.3% (24/45) of patients were female. Compared with the baseline, all clinical symptoms and signs significantly improved after IPL treatment combined with MGX. All optical quality parameters obtained with an optical quality analysis system (OQAS: Visiometrics, Castelldefels, Spain) have improved significantly over the baseline (p < 0.001). CONCLUSIONS: In patients with MGD, IPL treatment combined with MGX improved the objective optical quality and clinical signs and symptoms of DED.

Comparison of clinical outcomes between intense pulsed light therapy using two different filters in meibomian gland dysfunction: prospective randomized study.

Our study compared treatment efficacy between cut-off and notch filters in intense pulsed light (IPL) therapy for meibomian gland dysfunction (MGD) through a prospective, randomized paired-eye trial. Additionally, the efficacy of IPL treatment alone was investigated by restricting other conventional treatments. One eye was randomly selected for an acne filter and the other for a 590-nm filter. Identical four regimens of IPL treatments were administered. The tear break-up time (TBUT), Oxford scale, Sjögren's International Clinical Collaborative Alliance (SICCA) staining score, tear matrix metalloproteinase-9 (MMP-9) expression, tear osmolarity, and Ocular Surface Disease Index (OSDI) questionnaires were evaluated before and after IPL. Meibomian gland (MG) parameters were measured. When combining the results from both filters, the TBUT, SICCA staining score, OSDI score, and upper and lower lid meibum expressibility were improved after IPL. No significant differences were found between the two filters in the TBUT, Oxford scale, SICCA staining score, MMP-9 expression, tear osmolarity, and MG parameters. Although not significant, the acne filter showed better treatment efficacy than that in the 590-nm filter. IPL alone is efficacious in terms of ocular surface parameters, MG function, and subjective symptoms. Regarding filter selection, both acne and 590-nm filters are promising options for MGD treatment.

The Approach of Intense Pulsed Light Treatment in Patients with Different Severities of Meibomian Gland Dysfunction.

PURPOSE: To make appropriate therapeutic decisions of intense pulsed light (IPL) for meibomian gland dysfunction (MGD) patients. METHODS: Sixty patients with MGD stage 2-3 were enrolled in IPL Group1 and Self-hygiene Group; 110 patients with MGD stage 3-4 were included in IPL + MGX Group and IPL Group2. Patients in IPL groups received IPL treatment once a month for three times. Meibomian gland expression (MGX) was combined with IPL treatment in IPL + MGX Group. Meibomian gland (MG) functions, MGD stage, associated ocular-surface indexes, and response rate were evaluated. RESULTS: Population characteristics and clinical conditions were comparable between groups. In patients with MGD stage 2-3, both IPL Group1 and Self-hygiene Group improved in MG functions, ocular surface disease index (OSDI) and tear break-up time (TBUT). No statistical difference was found in improvements. Posttreatment response rate was 64.3-66.7% in two groups. In patients with MGD stage 3-4, IPL + MGX Group achieved better improvements in MG expressibility and higher response rate (75.5%) than IPL Group2 (63.3%). Referring to IPL treatment, no statistical difference in MG functions and OSDI improvements was found among MGD patients with different ages, genders, and IPL energy exposure. Patients with higher Fitzpatrick scale improved more in MG expressibility. CONCLUSION: Self-eyelid hygiene is cost-effective for milder MGD stages. Combining MGX with IPL is necessary in more severe stages. Adult patients with all age and different genders can benefit from IPL treatment. Patients with darker skin can benefit more in expressiblity.

Effect of Intense Pulsed Light Therapy in Dry Eye Disease Caused by Meibomian Gland Dysfunction: A Systematic Review and Meta-Analysis.

BACKGROUND: This study aimed to systematically evaluate the effect of intense pulsed light (IPL) therapy in patients harboring dry eye disease caused by meibomian gland dysfunction (MGD) based on qualified studies. METHODS: The electronic databases, including PubMed, Cochrane, and Embase, were searched using keywords to identify available publications updated to November 2021. Relative risk or weighted mean difference combined with 95% confidence interval was used to synthesize the outcomes of included studies. The meta-analysis included 15 randomized controlled trials with 1,142 patients (2,284 eyes). RESULTS: The results revealed that IPL could significantly decrease the ocular surface disease index (OSDI), standard patient evaluation of eye dryness (SPEED), artificial tear usage, tear film lipid layer, meibomian gland quality (MGQ), meibomian gland expression (MGX), and corneal fluorescein staining (CFS) while increase tear break-up time (TBUT) and noninvasive tear break-up time (NIBUT) compared with sham. Compared with MGX, IPL+MGX markedly decreased the SPEED, CFS, and tear meniscus height (TMH), but with increased TBUT. Compared with MGX, IPL showed significant effect in increasing the OSDI and TBUT, but decreasing the TMH and NIBUT. However, no significant differences were seen between IP+MGX and MGX in OSDI, MGQ, and MGX, nor between IPL and MGX in OSDI, SPEED, and TBUT. CONCLUSION: We identified that the application of IPL alone or IPL combined with MGX elicited superior clinical effect for improving the eye function and symptoms in the treatment of MGD-related dry eye disease, which is considered available for wide clinical application.

An Oral Polyphenol Formulation to Modulate the Ocular Surface Inflammatory Process and to Improve the Symptomatology Associated with Dry Eye Disease.

Due to their antioxidant, anti-inflammatory, neuroprotective, and anti-angiogenic effects, polyphenols are first-rate candidates to prevent or treat chronic diseases in which oxidative stress-induced inflammation plays a role in disease pathogenesis. Dry eye disease (DED) is a common pathology, on which novel phenolic compound formulations have been tested as an adjuvant therapeutic approach. However, polyphenols are characterized by limited stability and solubility, insolubility in water, very rapid metabolism, and a very short half-life. Thus, they show poor bioavailability. To overcome these limitations and improve their stability and bioavailability, we evaluated the safety and efficacy of an oral formulation containing among other compounds, polyphenols and omega-3 fatty acids, with the addition of a surfactant in patients with DED. Subjects were randomly assigned to one of four study groups including the study formulation (A), placebo (P), the study formulation + eye lubricant (A + L), and placebo + eye lubricant (P + L). Patients from the A and P groups were instructed to take two capsules every 24 h, while patients in the L groups also added one drop of lubricant twice a day for 12 weeks as well. Regarding safety, non-ocular abnormalities were observed during study formulation therapy. Liver function tests did not show any statistically significant difference (baseline vs. week 4). Concerning efficacy, there was a statistically significant difference between baseline, month 1, and month 3 in the OSDI (Ocular Surface Disease Index) test results in both treatment groups (group A and group A + L). Furthermore, both groups showed statistically significant differences between baseline and month 3 regarding the non-invasive film tear breakup time (NIF-BUT) score and a positive trend related to Shirmer's test at month 3. The non-invasive average breakup time (NIAvg-BUT) score showed a statistically significant difference at month 3 when compared with baseline in the A + L group. The P + L group showed a statistically significant difference in terms of the OSDI questionary between baseline and month 3. Regarding the lissamine green staining, the A + L group showed a statistical difference between baseline and month 3 (p = 0.0367). The placebo + lubricant group did not show statistically significant differences. Finally, the placebo group did not show any data with statistically significant differences. Consequently, this polyphenol formulation as a primary treatment outperformed the placebo alone, and the polyphenol oral formulation used as an adjuvant to artificial tears was superior to the combination of the placebo and the artificial tears. Thus, our data strongly suggest that this polyphenol oral formulation improves visual strain symptoms and tear film status in patients with mild to moderate DED.

Effect of Omega-3 on HLA-DR Expression by Conjunctival Cells and Tear Cytokine Concentrations in the Dry Eye Assessment and Management Study.

OBJECTIVES: To determine effect of omega-3 supplementation on conjunctival cell HLA-DR expression and tear concentrations of interleukin (IL)-1ß, IL-6, IL-8, IL-10, IL-17A, interferon-γ, and tumor necrosis factor-α in dry eye disease patients in the Dry Eye Assessment and Management study. METHODS: Patients were randomized to receive a daily dose of eicosapentaenoic and docosahexaenoic acids (ω3) or refined olive oil (placebo) for 12 months. At baseline, 6 and 12 months, HLA-DR expression in conjunctival total, epithelial, and white blood cells and cytokine concentration in tears were determined. Differences in change from baseline between treatment groups were assessed using generalized estimating equations (HLA-DR) or Wilcoxon rank-sum test (cytokines). RESULTS: No differences were observed in HLA-DR expression in total, epithelial, or white blood cells between ω3 and placebo groups at 6 months (n=435) or 12 months (n=436). The median concentration percent change differed between ω3 and placebo groups at 6 months for IL-6 (-36.6 vs. 24.5%, P =0.02, n=75) and for IL-8 (3.7% vs. 72.6%, P =0.02, n=68); at 12 months, they did not differ ( P ≥0.18). No other differences between the treatment groups were detected. CONCLUSIONS: ω3 supplementation did not consistently affect ocular inflammatory status as measured by the frequency of HLA-DR expressing conjunctival cells or tear cytokines.

Combination treatment with intense pulsed light, thermal pulsation (LipiFlow), and meibomian gland expression for refractory meibomian gland dysfunction.

PURPOSE: To evaluate the clinical efficacy and safety of combination treatment with intense pulsed light (IPL), LipiFlow thermal pulsation, and manual meibomian gland expression (MGX) for patients with refractory meibomian gland dysfunction (MGD). METHODS: A total of 23 eyes from 23 patients who underwent combination treatment with IPL, LipiFlow, and MGX for refractory MGD were included in the study. All patients were followed up for 12 months after the first treatment. All patients were examined prior to treatment and underwent three sessions of IPL, LipiFlow, and MGX, a subsequent three sessions of IPL and MGX, and six subsequent sessions of MGX. Patients were examined 10 weeks, 6 months, and 12 months after the first treatment. The ophthalmologic examination included ocular surface disease index (OSDI), non-invasive tearfilm break-up time (NIBUT), lipid layer thickness (LLT), meibomian gland expressibility (MGE), meibomian gland morphology (meiboscore), and tear meniscus height (TMH). RESULTS: OSDI, NIBUT, LLT, and MGE significantly improved with treatment, which was maintained during the follow-up period. TMH and meiboscore remained unchanged throughout follow-up. No serious adverse events occurred during follow-up. CONCLUSIONS: Combination therapy with IPL, LipiFlow, and MGX was clinically effective and safe for the treatment of refractory MGD. Combination treatment could be considered for patients with insufficient improvement despite conventional MGD treatments, including IPL treatment with MGX.

Effect of meibomian gland morphology on functionality with applied treatment.

PURPOSE: To determine how Meibomian gland (MG) morphology affects MG function by means of gland expression with the effect of treatment. METHODS: Fifteen patients (aged 31.6 ± 13.1 years) from a dry eye clinic diagnosed with MG dysfunction had their 365 lower lid MGs visualised with a slit-lamp biomicroscopy. Using infrared meibography (Oculus K5m), MG length, width and tortuosity were objectively measured. Each MG was expressed and the meibum graded (0=clear fluid, 1=cloudy fluid, 2= particulate fluid, 3=inspissated, or 4 = no expression) to determine its functionality. Participants had functionality repeated each time following a sequence of a warm compress, debridement, and forcible expression after 5 min. RESULTS: Just over 10 % of complete length MGs gave clear expression, while about 5% did not express at all, with most expressed meibum being particulate in nature. In contrast, the majority of partial length glands gave inspissated expression (38 %), with 32 % not expressing at all. No MG of <10 % length expressed. MG gland length was correlated with gland expression (r=-0.507, p < 0.001) and MG tortuosity (r=-0.129, p < 0.001), but not MG width (r=-0.090, p = 0.167). Regardless of MG length, warm compress increased the quality of expression (p < 0.002). Debridement further improved expression in partial MGs (p = 0.003), but not forcible expression (p = 0.529). CONCLUSIONS: Length is the key functional morphology metric of lower lid MGs. Warm compress and massage increase the quality of expression in all, but the shortest glands and patients with partial length glands also benefit from debridement.

Treatment Effect and Pain During Treatment With Intense Pulsed-Light Therapy According to the Light Guide in Patients With Meibomian Gland Dysfunction.

PURPOSE: We investigated whether there is a difference in the treatment effect and pain during the treatment of meibomian gland dysfunction (MGD) with intense pulsed-light (IPL) between new light guide and conventional light guide. METHODS: We retrospectively reviewed medical records of 85 patients (170 eyes) who underwent IPL treatment of the upper and lower eyelids 3 times, at 3-week intervals, for MGD. Patients treated with the 6-mm or 8 × 15-mm cylindrical light guide were designated as group A or group B, respectively. The ocular surface disease index (OSDI), dry eye (DE), and MGD parameters were obtained before the first and after the third IPL treatments. Visual analog scale (VAS) scores were obtained at every IPL treatment. OSDI, DE, and MGD parameters and VAS scores were compared between the groups. RESULTS: VAS scores at the first, second, and third IPL treatments were lower in group A than in group B. OSDI, DE, and MGD parameters were improved after 3 IPL treatments in both groups. There were no significant differences in OSDI, DE symptoms, and MGD parameters between before the first IPL treatment and after the third IPL treatment between the groups. CONCLUSIONS: Using the new 6-mm cylindrical light guide for IPL treatment in patients with MGD induced less pain during treatment and had similar treatment effects to the conventional 8 × 15-mm light guide. The new 6-mm cylindrical light guide can be useful when treating patients with dark or hyperpigmented skin and for pediatric patients with low compliance.

Efficacy of Artificial Tears Based on an Extract of Artemia salina Containing Dinucleotides in a Rabbit Dry Eye Model.

(1) Background: Artemia salina is a brine shrimp containing high concentrations of dinucleotides, molecules with properties for dry eye treatment. For this reason, the purpose of the study was to evaluate the effect of the artificial tears based on an extract of Artemia salina in a rabbit dry eye model. (2) Methods: A prospective and randomized study was carried out. Twenty rabbits were divided into 4 groups (n = 5, each group): healthy rabbits, dry eye rabbits, dry eye rabbits treated with hypromellose (HPMC), and dry eye rabbits treated with Artemia salina. Dry eye was induced by the topical instillation of 0.2% benzalkonium chloride. The measurements were performed before and after the treatment for 5 consecutive days. (3) Results: The topical instillation of artificial tears containing Artemia salina showed beneficial effects on tear secretion, tear break-up time, corneal staining, the density of Goblet cells, heigh of mucin cloud secreted by these cells, and mRNA levels of IL-1ß and MMP9 in conjunctival cells. Compared with the HPMC, there was a statistically significant improvement (p < 0.05) with the Artemia salina in all the variables under study, except for the conjunctival hyperemia, density of Goblet cells, and mRNA levels of IL-6. (4) Conclusions: The potential of artificial tears based on Artemia salina as a secretagogue agent for dry eye treatment was confirmed, opening the door for future clinical trials and studies to extrapolate the findings for dry eye patients.

Aquaporin5-Targeted Treatment for Dry Eye Through Bioactive Compounds and Gut Microbiota.

Dry eye and dry mouth are the principal sources of morbidity for patients with Sjögren's syndrome (SS). There are few effective treatments, particularly systemic ones. Targeting aquaprin-5 (AQP5)-mediated tear secretion has been tested as a novel ancillary strategy and has proved promising. Patients have a great interest in using complementary medicine, including nutraceuticals and bioactive compounds to alleviate their symptoms. Potential mechanisms by which phytocompounds and bioactive compounds may benefit SS ocular and mouth symptoms through modulation of AQP5 activity are presented within this review. Supplementation with prebiotics (such as polyphenols with high bioavailability) in SS patients with lower Firmicutes/Bacteroides (F/B) community ratio phenotype, through administration of butyrate-producing diets, is proposed as ancillary strategy for dry eye and mouth. The potential use of natural bioactive compounds to treat dry eye could also apply to dry mouth occurring in the context of aging and SS. This novel hypothesis could have implications with respect to planning a successful dietary regimen for achieving and maintaining a normal gut microbiota in SS patients. This regimen would include augmenting butyrate-producing foodstuffs and/or polyphenol-rich syrups, and high amounts of some specific probiotic-rich foodstuffs such as yogurt, soy yogurt, or as probiotic supplements. There are applications for pharmaceutical and nutraceutical products aiming to relieve dry eye and mouth.