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.

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.

Periplocin ameliorates mouse age-related meibomian gland dysfunction through up-regulation of Na/K-ATPase via SRC pathway.

Age-related meibomian gland dysfunction (MGD) is the main cause of evaporative dry eye disease in an aging population. Decreased meibocyte cell renewal and lipid synthesis are associated with age-related MGD. Here, we found an obvious decline of Ki67, ΔNp63, and Na+/K+ ATPase expression in aged meibomian glands. Potential Na+/K+ ATPase agonist periplocin, a naturally occurring compound extracted from the traditional herbal medicine cortex periplocae, could promote the proliferation and stem cell activity of meibocyte cells in vitro. Moreover, we observed that periplocin treatment effectively increased the expression of Na+ /K+ ATPase, accompanied with the enhanced expression of Ki67 and ΔNp63 in aged meibomian glands, indicating that periplocin may accelerate meibocyte cell renewal in aged mice. LipidTox staining showed increased lipid accumulation after periplocin treatment in cultured meibomian gland cells and aged meibomian glands. Furthermore, we demonstrated that the SRC pathway was inhibited in aged meibomian glands; however, it was activated by periplocin. Accordingly, the inhibition of the SRC signaling pathway by saracatinib blocked periplocin-induced proliferation and lipid accumulation in meibomian gland cells. In sum, we suggest periplocin-ameliorated meibocyte cell renewal and lipid synthesis in aged meibomian glands via the SRC pathway, which could be a promising candidate for age-related MGD.

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.

Intense pulsed light plus meibomian gland expression versus intense pulsed light alone for meibomian gland dysfunction: A randomized crossover study.

PURPOSE: To investigate the comparative efficacy of intense pulsed light (IPL) therapy alone with that of IPL plus meibomian gland expression (MGX) for meibomian gland dysfunction (MGD). METHODS: This is a prospective randomized crossover clinical trial. Sixty patients were enrolled and randomly assigned to two groups. All of patients underwent four treatment sessions in total, which were two weeks apart. Group 1 underwent two sessions of IPL therapy with MGX, as well as two sessions of IPL alone. Group 2 received two sessions of IPL therapy alone, and two sessions of IPL therapy with MGX. The following parameters were measured at baseline (BL), 2 weeks after the second treatment session (FU1), and 2 weeks after the fourth treatment session (FU2): tearfilm break-up time (BUT), Oxford grade for corneal staining, meibomian gland expressibility (MGE), meibum quality (MQ), and ocular surface disease index (OSDI). The separate effect of MGX on improvement of MGD parameters was evaluated using generalized estimating equation (GEE). RESULTS: The mean age of the participants was 57.52 ± 10.50 years. The BUT, Oxford grade, MGE, MQ, and OSDI of both groups improved significantly (from baseline) by the end of four treatment sessions (FU2 compared to BL; all p-values <0.05). The MGE and MQ significantly improved after the first and second treatment sessions (FU1 compare to BL; all p-values < 0.001). However, the improvement was not statistically significant after the third and fourth treatment sessions (FU2 compared to FU1; p-value of 0.388 for MGE and 0.645 for MQ in group 1, 0.333 for MGE and 0.333 for MQ in group 2). The IPL plus MGX therapy produced greater improvements in the BUT scores than did IPL therapy alone (p = 0.003 by GEE). In contrast, the Oxford grade, MGE, MQ, and OSDI were not influenced by the addition of MGX to IPL (p = 0.642, 0.663, 0.731, and 0.840, respectively by GEE). CONCLUSION: IPL therapy effectively improves the subjective symptoms and objective ocular findings of MGD. MGX enhanced the improvement of BUT driven by IPL therapy. The meibomian gland function (MGE and MQ) recovers faster in response to IPL therapy than did the other parameters.

The Effect of Therapeutic Meibomian Glands Expression on Evaporative Dry Eye: A Prospective Randomized Controlled Trial.

PURPOSE: To determine the clinical benefits of Meibomian gland expression therapy for the treatment of dry-eye disease caused by Meibomian gland dysfunction (MGD). METHODS: In a prospective randomized controlled double-masked trial, 87 eyes of 44 patients with MGD and dry-eye symptoms were enrolled. Patients were randomly assigned into two groups; a study group that received therapeutic Meibomian gland expression once every month, and a control group that received sham treatment. All patients received treatment with artificial tears. RESULTS: One week after the first treatment, the Ocular Surface Disease Index (OSDI) score improved significantly in the study group (mean change -18.5 ± 21.2, p = .01) but not in the control group (-3.8 ± 15.8, p = .16); after 1 month, both groups improved significantly (-20.5 ± 19 p = .001 in the study group and -6.5 ± 11, p = .016 in the control group). The improvement continued at 2 months in the study group (-28.4 ± 26.1, P < .0001) and in the control group (-9.6 ± 9.9, p = .007). The blepharitis questionnaire score improved in the study group compared to controls after 1 week (-9.95 ± 12.52 versus -1.77 ± 9.1, p = .03) 1 month (-11.5 ± 10.9 versus -1.1 ± 9.4, p = .02) and 2 months (-16.5 ± 8.0 versus -8.8 ± 11.7, p = .02). Burning sensation was significantly reduced only in the study group. Mean change after 2-month treatment was -2.00 ± 1.2583 (p < .0001) vs -0.67 ± 1.44 (p = .08). The trend was similar in Eyelid scales. Conjunctival hyperemia improved only in the study group 1 week after the treatment (-0.12 ± 0.32 p = .03). CONCLUSION: Therapeutic Meibomian gland expression improves dry-eye symptoms in subjects with MGD, compared to conventional treatment with artificial tears.

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.

Clinical Efficacy of Immediate Manual Meibomian Gland Expression After Thermal Pulsation (LipiFlow) for Obstructive Meibomian Gland Dysfunction: Comparison With Thermal Pulsation.

PURPOSE: To evaluate the clinical efficacy and safety of immediate manual meibomian gland expression (MGX) after LipiFlow thermal pulsation (TearScience Inc, Morrisville, NC) for obstructive meibomian gland dysfunction and to compare the LipiFlow only and MGX after LipiFlow. METHODS: Patients who underwent immediate manual MGX after LipiFlow or who received only LipiFlow treatment were included. Thirty eyes from 15 patients were enrolled in each group. All patients underwent 3 treatments at monthly intervals. All patients were followed up for 6 months after treatment. All patients were examined before and at 3 and 6 months after treatment. Examinations included the Ocular Surface Disease Index score, noninvasive tear film breakup time (NIBUT), lipid layer thickness (LLT), corneal and conjunctival staining, and tear meniscus height. RESULTS: The Ocular Surface Disease Index scores improved in both groups during the follow-up periods (P = 0.001 and P = 0.001). In the LipiFlow-only group, the NIBUT and LLT significantly improved at 3 months (P < 0.001 and P = 0.006) but deteriorated at 6 months. In the MGX after LipiFlow group, the NIBUT and LLT improved at 3 months (P < 0.001 and P < 0.001), and this improvement was maintained at 6 months. The improvement of NIBUT at 3 months was greater in the MGX after LipiFlow group (3.24 ± 1.16 to 9.25 ± 1.36 s) than in the LipiFlow-only group (3.78 ± 1.75 to 7.18 ± 2.70 s), and the improvements of the LLT at 6 months were greater in the MGX after LipiFlow group (30.27 ± 10.74 to 46.93 ± 20.81 µm) than in the LipiFlow-only group (34.70 ± 10.79 to 38.73 ± 14.70 µm). CONCLUSIONS: Both LipiFlow only and MGX after LipiFlow were clinically effective for obstructive meibomian gland dysfunction. However, the efficacy and persistence of treatment were greater in patients who received MGX after LipiFlow.

Efficacy and Safety of Intense Pulsed Light in Patients With Meibomian Gland Dysfunction-A Randomized, Double-Masked, Sham-Controlled Clinical Trial.

PURPOSE: To study the efficacy and safety of intense pulsed light (IPL) in patients with meibomian gland dysfunction (MGD). METHODS: This prospective randomized double-masked sham-controlled trial included 114 patients with MGD. Patients were randomized into the IPL or sham group. Either the IPL or sham procedure was performed on days 0, 15, and 45. Ocular Surface Disease Index (OSDI), visual analog scale, visual acuity, tear breakup time, meibum quality and expressibility, meibography grade, ocular surface staining, tear film lipid layer thickness, tear osmolarity, Schirmer test, tear interleukin-1 receptor agonist, and interleukin-6 levels were examined on days 0, 15, and 45 and at months 3 and 6. Subgroup analysis according to stage and the patient's compliance to conventional treatment were also analyzed. Any adverse events during the study were recorded. A multilevel mixed-effect linear regression model was used. P value less than 0.05 was considered statistically significant. RESULTS: At 6 months, tear breakup time, meibum quality grades, expressibility grades, and OSDI were better in the IPL group (5.23 ± 2.91 vs. 3.11 ± 0.99 seconds, P < 0.001; 8.74 ± 4.74 vs. 13.19 ± 5.01, P < 0.001; 0.50 ± 0.67 vs. 1.12 ± 0.70, P < 0.001; 24.29 ± 16.92 vs. 32.71 ± 20.07, P < 0.05). OSDI, meibum quality, and expressibility in the IPL group began to improve at day 15 (P < 0.001), whereas the results in the sham group began to improve at day 45 (P < 0001). No adverse event occurred after IPL. CONCLUSIONS: IPL is effective and safe for MGD treatment in all stages regardless of compliance.

High Frequency Electrotherapy for the Treatment of Meibomian Gland Dysfunction.

PURPOSE: To test the safety and efficacy of high frequency electrotherapy (ET) on the clinical signs and symptoms of patients affected by dry eye and meibomian gland dysfunction (MGD). METHODS: Twenty-five patients affected by MGD were enrolled. Quantum Molecular Resonance ET was administered by means of the Rexon-Eye device 4 times, once per week for 4 weeks. Patients were reexamined 1 month after the last treatment. The primary endpoint was reduction in corneal fluorescein staining. Additional endpoints were tear break-up time, Ocular Surface Disease Index score, meibomian gland secretion score, and the number of expressible meibomian glands. Safety endpoints were Logarithm of the Minimum Angle of Resolution (LogMar) best spectacle-corrected visual acuity and intraocular pressure. RESULTS: Corneal fluorescein staining improved by 62.5% (P < 0.0001), tear breakup time increased by 30.9% (P < 0.0001), and the Ocular Surface Disease Index score improved by 37% (P < 0.001). The meibum quality and the number of expressible meibomian glands also increased (35.7% and 12%, P < 0.001 and P < 0.0001, respectively). Schirmer test scores increased after treatment by 16.5% (P = 0.01). No adverse events were observed. CONCLUSIONS: Quantum Molecular Resonance ET appears to be safe and significantly reduces symptoms and signs associated with MGD. It may have a relevant role in the treatment of evaporative dry eye disease.

Meibum Expressibility Improvement as a Therapeutic Target of Intense Pulsed Light Treatment in Meibomian Gland Dysfunction and Its Association with Tear Inflammatory Cytokines.

Many recent studies have demonstrated the efficacy of intense pulsed light (IPL) for the treatment of meibomian gland dysfunction (MGD); however, its effective treatment targets have not yet been elucidated. This study aimed to investigate the baseline characteristics associated with an improvement in symptoms after IPL treatment; to examine the course of change in inflammatory tear cytokines, meibomian gland function, and tear stability; and to investigate the correlation between cytokines and ocular surface parameters. Thirty participants underwent three sessions of IPL treatment. During each examination, tear film lipid layer interferometry, meibography, tear meniscus height measurement, tear sampling, and slit-lamp examination were performed, and the Ocular Surface Disease Index (OSDI) questionnaire was administered. Meibum quality, meibum expressibility, lid margin abnormality, tear film break-up time (TBUT), ocular surface staining, and the OSDI significantly improved after treatment. Poor meibum expressibility and short TBUT were associated with greater recovery in the OSDI after IPL. Tear levels of IL-4, IL-6, IL-10, IL-17A, and TNF-α decreased after IPL, and IL-6, and TNF-α were correlated with the improvement in meibum expressibility. Therefore, IPL treatment improved meibomian gland function, stabilized the tear film, and decreased ocular surface inflammation. Patients with obstructive MGD and tear instability were more likely to experience an improvement in ocular discomfort after IPL treatment.

The optimum temperature for the heat therapy for meibomian gland dysfunction.

PURPOSE: Numerous devices have been developed to warm the eyelid as a therapy for Meibomian gland dysfunction. The optimum temperature for such therapy was determined. METHODS: Meibum lipid disorder versus temperature was calculated from previously published phase transition parameters measured using infrared spectroscopy. Phase transitions parameters were calculated from meibum obtained from donors with Meibomian gland dysfunction (MMGD), donors who were susceptible to dry eye after hematopoietic stem cell transplantations (MHSCT) and meibum from donors without dry eye (Mn). RESULTS: Heating Mn to 40 °C increases the lipid disorder by 20.4%-90%. Heating the meibum another 4° increases the disorder to 95%. MMGD is 73.2% disordered with no heating. Heating MMGD to 41.5 °C increases the disorder by 26.8%-90% disordered. Heating MMGD another 5.1 °C increases the disorder to 95%. As MHSCT is much more ordered, 56.9% disordered compared with Mn and MMGD, a higher temperature above safety limits, 52 and 59 °C is need to disorder MHSCT to 90 and 95% disorder. CONCLUSIONS: Heating the eye lid above the phase transition temperature of meibum increases the disorder of meibum lipid which could ameliorate dry eye symptoms. The optimum temperature for disordering Mn and MMGD to 90% maximum disorder is 40 and 41.5 °C, respectively. Safety issues and discomfort should be considered in obtaining an optimal level of disorder, especially for severe cases of dry eye.

Therapeutic efficacy of intense pulsed light in patients with refractory meibomian gland dysfunction.

PURPOSE: To evaluate the efficacy and safety of intense pulsed light (IPL) combined with meibomian gland expression (MGX) for treatment of refractory meibomian gland dysfunction (MGD). METHODS: Ninety eyes of 45 patients were randomly assigned to receive either the combination of IPL and MGX or MGX alone (control). Each eye underwent eight treatment sessions at 3-week intervals. Parameters were evaluated before and during treatment as well as at 3-11 weeks after the last treatment session. Measured parameters included the Standard Patient Evaluation of Eye Dryness (SPEED) questionnaire score, noninvasive breakup time (NIBUT), fluorescein breakup time (BUT), lipid layer grade, lipid layer thickness (LLT), lid margin abnormalities, corneal and conjunctival fluorescein staining (CFS) score, meibum grade, and meiboscore. RESULTS: A significant improvement in lipid layer grade was apparent in the IPL-MGX group from 6 to 32 weeks after treatment onset (adjusted P < 0.001) but was not observed in the control group. The IPL-MGX group also showed significant improvements in LLT, NIBUT, BUT, lid margin abnormalities, and meibum grade compared with the control group at 24 and 32 weeks (adjusted P < 0.001) as well as significant improvements in the SPEED score at 32 weeks (adjusted P = 0.044) and in CFS score at 24 (adjusted P = 0.015) and 32 (adjusted P = 0.006) weeks. CONCLUSIONS: The combination of IPL and MGX improved homeostasis of the tear film and ameliorated ocular symptoms in patients with refractory MGD and is thus a promising modality for treatment of this condition.