Intense pulsed light improves signs and symptoms of dry eye disease due to meibomian gland dysfunction: A randomized controlled study.

PURPOSE: To compare the safety and efficacy of intense pulsed light (IPL) followed by meibomian gland expression (MGX), against monotherapy of MGX. METHODS: Patients with moderate to severe meibomian gland dysfunction (MGD) were 1:1 randomized to 4 sessions of intense pulse light + MGX at 2-week intervals, or 4 sessions of Sham + MGX at 2-week intervals. Both patients and examiners were blinded to the allocation. Outcome measures, evaluated at the baseline (BL) and at a follow-up (FU) conducted 4 weeks after the last IPL session, included fluorescein tear breakup time (TBUT) as the primary outcome measure, OSDI (Ocular Surface Disease Index) questionnaire, Eye Dryness Score (EDS, a visual analog scale (VAS)-based questionnaire), Meibomian gland score (MGS, a score of meibum expressibility and quality in 15 glands on the lower eyelid), daily use of artificial tears, and daily use of warm compresses. In addition, during each treatment session, the number of expressible glands was counted in both eyelids, the predominant quality of meibum was estimated in both eyelids, and the level of pain/discomfort due to MGX and IPL was recorded. RESULTS: TBUT increased from 3.8±0.2 (µ±standard error of mean (SEM)) to 4.5±0.3 seconds in the control arm, and from 4.0±0.2 to 6.0±0.3 in the study arm. The difference between arms was statistically significant (P < .01). Other signs/symptoms which improved in both arms but were greater in the study arm included MGS (P < .001), EDS (P < .01), the number of expressible glands in the lower eyelids (P < .0001) and upper eyelid (P < .0001), the predominant meibum quality in the lower eyelid (P < .0001) and upper eyelid (P < .0001), and the level of pain due to MGX (P < .0001). Outcome measures which improved in both arms with no significant differences between the two were OSDI (P = .9984), and the daily use of artificial tears (P = .8216). Meibography, daily use of warm compresses, and severity of skin rosacea did not show statistically significant changes in either arm. No serious adverse events were observed. There was a slight tendency for more adverse events in the control group (P = 0.06). CONCLUSIONS: The results of this study suggest that, in patients with moderate to severe symptoms, combination therapy of intense pulse light (IPL) and meibomian gland expression (MGX) could be a safe and useful approach for improving signs of dry eye disease (DED) due to meibomian gland dysfunction (MGD). Future studies are needed to elucidate if and how such improvements can be generalized to different severity levels of MGD.

Results from a Prospective, Open-Label, Phase 4 Pilot Study of Repository Corticotropin Injection for Moderate and Severe Dry Eye Disease.

INTRODUCTION: There is a substantial unmet need for effective therapies to treat patients with refractory dry eye disease (DED). The goal of this open-label pilot study was to investigate the efficacy and safety of repository corticotropin injection (RCI; Acthar® Gel; Mallinckrodt Pharmaceuticals) in subjects with DED, most of whom did not experience adequate response to standard-of-care therapies. METHODS: Adults with moderate or severe-acute DED received 80 U of subcutaneous RCI twice weekly for 12 weeks. Primary efficacy outcomes were improvements in corneal fluorescein staining of superficial punctate keratitis (SPK) lesions and Symptom Assessment in Dry Eye (SANDE) scores. Secondary outcomes included changes in Schirmer's test scores, conjunctival lissamine green staining, erythema, intraocular pressure (IOP), and best corrected visual acuity (BCVA). Adverse events (AEs) were assessed continuously throughout the study. RESULTS: Fifteen subjects received at least 1 dose of RCI, and 12 subjects completed the study. Compared to baseline (day 1), significantly fewer fluorescein-stained SPK lesions were detected at day 14 (p = 0.0250) and day 84 (p = 0.0240) after RCI treatment. Mean SANDE scores progressively declined from 62.0 at baseline to 46.9 at day 84. Erythema (p = 0.0046), conjunctival lissamine green staining of SPK lesions (p = 0.0317), and IOP (p = 0.0052) were all significantly improved after 12 weeks of RCI therapy. Schirmer's test scores and BCVA showed no significant changes throughout the study. No ocular AEs or deaths occurred, and no new safety signals were identified for RCI. CONCLUSIONS: These results suggest that RCI may be a safe and effective treatment for moderate and severe DED. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03287635.

Evaluation of the Safety and Efficacy of Intense Pulsed Light Treatment with Meibomian Gland Expression of the Upper Eyelids for Dry Eye Disease.

Objective: To investigate the safety of and change from baseline of tear breakup time and visual analog pain scales in dry eye disease subjects with upper lid Meibomian gland dysfunction after intense pulsed light (IPL) treatment assessing global ocular pain severity, ocular pain frequency, and ocular pain in the previous 24 h. This is a prospective single-site study. Methods: All patients received active treatment consisting of four treatments spaced no fewer than 2 weeks apart and no longer than 4 weeks apart. The IPL therapy was performed with a Lumenis M22 (Lumenis Ltd., Yokneam, Israel) xenon-based micropulsed IPL utilizing a 590 nm filter with a 6 mm clear SapphireCool cylindrical lightguide for the upper lids with a fluence of 10 J/cm2 across the upper eyelids, including the tragus for two passes. Patients then received expression of their meibomian glands using two cotton-tipped applicators. Tear breakup data were collected as well as global ocular pain, ocular pain episodes in the past 24 h and frequency of ocular pain episodes. Results: All of the assessments for the treated eyes improved over the course of treatment. Statistically significant physician increases in measured tear breakup times were measured for each eye independently. Statistically significant decreases in global eye dryness scale, eye dryness in the preceding 24 h, and frequency of ocular pain episodes between treatments were observed. There were no serious or nonserious adverse events in the trial. Conclusions: This pilot study suggests that a new specialized 6 mm cylindrical handpiece for the M22 Lumenis IPL machine is safe and effective in increasing physician-measured tear breakup time as well as several scales of the symptoms of ocular dryness, including global symptoms, frequency of symptoms, and ocular dryness occurring within the previous 24 h before the study visit.

Intense Pulsed Light Applied Directly on Eyelids Combined with Meibomian Gland Expression to Treat Meibomian Gland Dysfunction.

OBJECTIVE: To determine the efficacy and safety of intense pulsed light (IPL) applied directly on the eyelids and meibomian gland expression (MGX) in treating meibomian gland dysfunction (MGD). BACKGROUND: IPL application on the periocular skin effectively improves meibomian gland secretion and tear film break-up time (TBUT) in patients with MGD/dry eye. METHODS: This prospective, randomized, double-masked, controlled study involved 44 patients. One eye was randomly selected for IPL treatment; the other served as a control. Study eyes received three IPL treatments at 4-week intervals; IPL was applied directly on the eyelids, and the eye was protected with a Jaeger lid plate. Control eyes received sham IPL treatments. Both eyes received MGX and artificial tears. Meibomian gland yielding secretion score (MGYSS), TBUT, Standard Patient Evaluation of Eye Dryness (SPEED), cornea fluorescein staining (CFS), meibography, best corrected visual acuity (BCVA), intraocular pressure (IOP), and fundus examination were performed. RESULTS: Compared to the baseline, MGYSS, TBUT, and SPEED and CFS scores improved in the study eyes, while only SPEED and CFS scores improved in the control eyes (p < 0.001 for all). Changes in MGYSS and TBUT were higher in the study eyes than in the control eyes (p < 0.05), but changes in SPEED and CFS scores were similar (p > 0.05). BCVA and IOP improved in both the study and control eyes (p < 0.05). Five patients experienced mild pain and burning during IPL treatment. One patient suffered partial eyelash loss. CONCLUSIONS: IPL combined with MGX safely and effectively treated MGD.

Analysis of Cytokine Levels in Tears and Clinical Correlations After Intense Pulsed Light Treating Meibomian Gland Dysfunction.

PURPOSE: To investigate the change from baseline of inflammatory markers in tears of dry eye disease (DED) subjects owing to meibomian gland dysfunction (MGD) after intense pulsed light (IPL) treatment and meibomian gland expression (MGE) compared to sham treatment, and the correlations with ocular surface parameters. DESIGN: Randomized, double-masked, controlled study. METHODS: Those randomized into the active treatment arm received 3 consecutive treatments (14∼16 J/cm2) approximately 4 weeks apart in the periocular region. Control eyes received 3 treatments in the same intervals of 0 J/cm2. Tear samples in all eyes were collected and analyzed at baseline, week 12, and/or week 4 for interleukin (IL)-17A, IL-6, and prostaglandin E2 (PGE2). The correlations between cytokines and ocular surface parameters were analyzed before and after IPL treatment. RESULTS: All of the inflammatory markers declined in value compared to baselines. IL-17A and IL-6 showed statistically significant decreases compared to sham treatment at each measured time point. PGE2 showed statistically significant decreases compared to sham at week 12. Results showed that the expressions of IL-17A and IL-6 correlated well with ocular surface parameters of the lower eyelid before IPL. The changed values of IL-6 and PGE2 in tears correlated with the changed values of partial ocular surface parameters after IPL treatment in study eyes, respectively. CONCLUSIONS: The study results suggest that IPL can significantly reduce inflammatory markers in tears of patients suffering with DED owing to MGD after IPL treatment. These findings indicate that IL-17A and IL-6 play roles in the pathogenesis of DED owing to MGD, and the reduction of the inflammatory factors is consistent with the improvement of partial clinical symptoms and signs.

Intense pulsed light treatment for dry eye disease due to meibomian gland dysfunction; a 3-year retrospective study.

OBJECTIVE: The purpose of this study was to determine the clinical benefits of intense-pulsed-light therapy for the treatment of dry-eye disease caused by meibomian gland dysfunction (MGD). BACKGROUND DATA: MGD is the leading cause of evaporative dry eye disease. It is currently treated with a range of methods that have been shown to be only somewhat effective, leading to the need for advanced treatment options. METHODS: A retrospective noncomparative interventional case series was conducted with 91 patients presenting with severe dry eye syndrome. Treatment included intense-pulsed-light therapy and gland expression at a single outpatient clinic over a 30-month study. Pre/post tear breakup time data were available for a subset of 78 patients. For all patients, a specially developed technique for the treatment of dry eye syndrome was applied as a series of monthly treatments until there was adequate improvement in dry eye syndrome symptoms by physician judgment, or until patient discontinuation. RESULTS: Primary outcomes included change in tear breakup time, self-reported patient satisfaction, and adverse events. Physician-judged improvement in dry eye tear breakup time was found for 68 of 78 patients (87%) with seven treatment visits and four maintenance visits on average (medians), and 93% of patients reported post-treatment satisfaction with degree of dry eye syndrome symptoms. Adverse events, most typically redness or swelling, were found for 13% of patients. No serious adverse events were found. CONCLUSIONS: Although preliminary, study results of intense-pulsed-light therapy treatment for dry eye syndrome caused by meibomian gland dysfunction are promising. A multisite clinical trial with a larger sample, treatment comparison groups, and randomized controlled trials is currently underway.