Efficacy of indirect intense pulsed light irradiation on meibomian gland dysfunction: a randomized controlled study

Abstract

Aim: To investigate the efficacy and mechanisms of indirect intense pulsed light (IPL) irradiation on meibomian gland dysfunction (MGD).

Methods: A total of 60 MGD patients was included in this prospective randomized controlled trial. Patients were randomly assigned 1:1 into two groups (3-mm group and 10-mm group) in which IPL was applied at distances from the lower eyelid margin of 3 and 10 mm, respectively. Both groups received three times treatment with 3-week interval. Meibomian gland yield secretion score (MGYSS), standard patient evaluation of eye dryness (SPEED) questionnaire, tear break-up time (TBUT), corneal fluorescein staining (CFS), and in vivo confocal microscopy were performed at baseline and after every treatment.

Results: After three IPL treatments, both groups had significant improvement in MGYSS (both P<0.05). The non-inferiority test showed that improvement in 10-mm group was not inferior to that in 3-mm group (P<0.001). In both groups, temporal regions of both upper and lower eyelids showed significant improvement in MGYSS. Scores of SPEED questionnaire in both groups declined significantly (both P<0.001) and changes of SPEED had no difference between two groups (P=0.57). Density of central corneal subepithelial nerves and TBUTs showed no statistically significant changes. The 3-mm group had improvement on corneal fluorescein staining (P=0.048) and meibomian gland morphology (acini wall thickness P=0.003, hyperreflective points P=0.024) while the 10-mm group had not.

Conclusion: The efficacy of IPL indirect irradiation in improving meibomian gland secretion and alleviating dry eye symptoms remains unchanged with increase in treatment distance. IPL may primarily act on the functional improvement of the meibomian glands and corneal nerves.

Keywords: dry eye; intense pulsed light; meibomian gland disfunction; ocular surface.

Figure 1. Schematic diagram of the IPL intervention

Patients' eyes were protected with goggles. The blue rectangles in the diagram stand for the area where the IPL device was applied and 14-18 overlapping IPL irradiations were applied (35 mm×15 mm each irradiation area) on the forehead, bilateral temporal area, and 3 or 10 mm from the lower eyelid margin on the cheek. IPL: Intense pulsed light.

Figure 2. Measurements of parameters from in vivo confocal microscopy images

Image J software was applied for measurements of parameters from in vivo confocal microscopy images. The central corneal subepithelial nerves were tracked and measured by Neuron J plugin (A). Hyperreflective points in meibomian gland tissue were defined as points that have prominent higher reflectivity and can be distinguished from pyknotic meibocytes. Hyperreflective points were marked manually and counted by multicount function of Image J (B). Wall thicknesses of all the acini in one 400×400 µm² image were measured and averaged. Each clear acinus was measured at one spot that had good contrast and regular morphology, where the measuring short line was drawn in the direction perpendicular to the tangent of the spot (C). Scale bars: 50 µm.

Figure 3. MGYSS at different timepoints

MGYSSs of upper (A1, B1) and lower (A2, B2) eyelids at different timepoints. MGYSSs were evaluated at baseline (T0) and at 3wk after each treatment (T1-T3). ^aP<0.05, ^bP<0.01, ^cP<0.001 compared to baseline. MGYSS: Meibomian gland yield secretion score; u-MGYSS: MGYSS of upper eyelid; l-MGYSS: MGYSS of lower eyelid.

Figure 4. MGYSS trends in different regions of the eyelid

MGYSS trends (from T0 to T3) in different regions of the eyelids. A1-A3: MGYSS of upper eyelids; B1-B3: MGYSS of lower eyelids. ^aP<0.05, ^bP<0.01, ^cP<0.001 compared to baseline. MGYSS: Meibomian gland yield secretion score; u-MGYSS: MGYSS of upper eyelid; l-MGYSS: MGYSS of lower eyelid; t-MGYSS: MGYSS of temporal region of the eyelid; c-MGYSS: MGYSS of central region of the eyelid; n-MGYSS: MGYSS of nasal region of the eyelid; T0: Baseline; T1-T3: 3wk after each treatment.

Figure 5. Symptomatology scoring before and after IPL treatments

Both groups had significant decrease in scores of SPEED questionnaire (P<0.001 in both groups). ^cP<0.001 between groups. IPL: Intense pulsed light; SPEED: Standard patient evaluation of eye dryness; T0: Baseline; T3: 3wk after the 3^rd treatment.

Figure 6. Distribution of TBUTs at baseline and after the third IPL treatment

TBUTs at baseline (T0) and after the last IPL treatment (T3) were divided into three subgroups (TBUT<2s, 2s≤TBUT<5s, and TBUT≥5s). At baseline, most TBUT in both groups were under 5s. After the IPL treatments, numbers of TBUTs under 2s decreased, however this change was not statistically significant. IPL: Intense pulsed light; TBUT: Tear break-up time; T0: Baseline; T3: 3wk after the 3^rd treatment.

Figure 7. Typical case of wall thickness increase after IPL treatment

A: IVCM image of a patient's MG tissue at baseline; B: IVCM image of the same patient's 3wk after the third IPL treatment. Scale bars: 50 µm. IPL: Intense pulsed light; IVCM: In vivo cofocal microscopy; MG: Meibomian gland.

Figure 8. Typical case of hyperreflective points decrease after IPL treatment

A: IVCM image of a patient's MG tissue at baseline; B: IVCM image of the same patient's 3wk after the third IPL treatment. Scale bars: 50 µm. IPL: Intense pulsed light; IVCM: In vivo cofocal microscopy; MG: Meibomian gland.