The use of intense pulsed light therapy in the treatment of refractory meibomian gland dysfunction

KEYWORDS:

• Dry eye
• intense pulsed light
• lipid layer
• meibomian gland
• ocular surface
• tear film

1. Introduction

Meibomian gland dysfunction (MGD) is a leading contributor to evaporative dry eye disease [1,2], and is recognized to have significant impacts on ocular comfort, visual function, and quality of life [2–4]. In MGD, the increased viscosity of meibomian gland secretions can contribute to stasis, obstruction, bacterial proliferation, and inflammation of the ductal system. The ensuing reduction in the quality and quantity of meibomian gland secretions delivered to the tear film can impair the integrity of the surface lipid layer [5,6]. These pathophysiological changes can then predispose to a vicious circle of tear film instability, hyper-evaporation, hyper-osmolarity, and ocular surface inflammation, as well as the development and progression of dry eye symptoms [5,6].

Despite there being a myriad of therapeutic options currently available for the treatment of MGD, satisfactory long term symptomatic control is often difficult to sustain, reflecting an ongoing requirement for the development of alternative management strategies [7,8]. Warm compress therapy, mechanical meibum expression, eyelid hygiene regimens, lipid-based artificial tear lubricant eye drops, and omega-3 fatty acid supplementation are commonly recommended as first-line treatments, although their therapeutic efficacy can be limited by treatment adherence [7,8]. In more refractory and severe cases of MGD, intraductal probing, as well as antibiotic, tetracycline, anti-inflammatory and immunomodulatory agents might also be judiciously considered in balance with their potential adverse effects [7,8].

In the past decade, there has been growing interest in the potential of intense pulsed light (IPL) therapy for the treatment of MGD [7,9–11], after serendipitous accounts of improved tear film function following IPL therapy for cutaneous rosacea [9,12]. IPL therapy consists of the delivery of high-intensity polychromatic light, spanning the infrared to visible spectrum, with tailored selection of wavelength, energy delivery profile, and penetration depth to facilitate targeted application to specific structures within the lower eyelids [9–11]. The purpose of this literature review was to provide a brief overview of the current evidence for the efficacy of IPL therapy for the treatment of refractory MGD.

2. Mechanisms of action

The complex multifactorial mechanisms of action of IPL therapy for the treatment of MGD remain yet to be fully understood [9–11]. The delivery of thermal energy through IPL therapy is thought to promote the liquefaction of inspissated meibum and relieve ductal obstruction of the meibomian glands, thereby enhancing the integrity and thickness of the tear film lipid layer [7,9–11]. The potential antimicrobial effects of IPL therapy might dampen inflammatory triggers of the ocular surface [9–11]. It has been hypothesized that ocular Demodex might be targeted by the thermal energy delivered by IPL devices [9–11,13]. In addition, a recent randomized trial showed that a three-month course of IPL therapy inhibited periocular Corneybacterium macginleyi load [14]. Furthermore, the anti-inflammatory action of IPL therapy has also been demonstrated with the reduction of inflammatory markers in tear samples, including IL-4, IL-6, IL-10, IL-17A, TNF-α, and PGE2 [15,16].

IPL therapy has been shown in dermatological studies to induce localized thrombosis of abnormal superficial blood vessels that release inflammatory mediators, and it has been hypothesized that these effects might reduce inflammation in the eyelid tissues [9–11,17]. In addition, it has been postulated that IPL therapy might down-regulate epithelial turnover at the eyelid margin, which may serve to reduce debris accumulation that can obstruct the orifices of the meibomian glands [9–11]. In vitro studies have suggested that the photomodulatory effects of IPL therapy can activate fibroblasts and promote collagen synthesis, which might help to maintain the rigidity and elasticity of the periocular skin with aging, and promote lid apposition and meibum delivery during blinking [9–11,18]. Finally, the potential effects of IPL in reducing oxidative stress and thereby dampening inflammatory triggers of the ocular surface have also been raised [9–11].

3. Clinical safety

The clinical safety and tolerability of IPL therapy have been confirmed by numerous clinical studies which report no major adverse events following IPL therapy [14,16,19–28]. However, minor or transient side effects, including mild pain, light sensitivity, eyelash loss, eyelid erythema, crusting, hyperpigmentation, and blistering have been described [12,29–31].

Nevertheless, it is acknowledged that adequate protection of the globe during IPL application is required to prevent permanent intraocular damage [9–11]. Indeed, the pigmented iris is most susceptible to damage due to its absorbance of electromagnetic waves within the same spectrum as those emitted by IPL therapy [11]. Cases of pupillary defects, iris atrophy, anterior uveitis, posterior synechiae, pupillary block and secondary angle-closure glaucoma have been previously reported with inadequate eye protection [10,11,32,33], and highlight the importance of appropriate eye shield wear during IPL therapy [9–11].

4. Clinical efficacy

The efficacy of IPL therapy has been reported by a large number of clinical studies. Retrospective and prospective non-randomized studies have demonstrated that IPL therapy is associated with improvements in dry eye symptomology scores, tear film stability, tear osmolarity, lipid layer thickness, meibomian gland expressibility, meibum quality, eyelid margin vascularity and edema, conjunctival injection, corneal staining, and Schimer test values [12,16,19–27,29,30,34–37]. In addition, a recent prospective non-controlled study showed a reduction in tear inflammatory cytokines following IPL therapy [16], while another prospective controlled study reported significant improvement in tear protein and lipid content and composition [21].

To date, a total of five randomized trials investigating the efficacy of IPL therapy for the treatment of MGD have been published [14,15,28,31,38], as summarized in Table 1, and ongoing randomized trials are highlighted in Table 2. Improvements in dry eye symptomology scores, tear film stability, lipid layer thickness, meibomian gland expressibility and capping, and corneal fluorescein staining have been reported following three to four sessions of IPL therapy in these randomized studies [14,15,28,31,38]. Furthermore, reductions in the expression of IL-6, IL-17A, and PGE2 was observed to be associated with improvements in clinical ocular surface parameters in a recent double-masked, paired eye, randomized, sham-controlled trial [15]. Another double-masked, parallel-group, randomized, sham-controlled trial reported inhibition of periocular Corneybacterium macginleyi load following four sessions of IPL therapy [14].

Table 1. Published randomized controlled trials investigating the efficacy of intense pulsed light therapy for the treatment of meibomian gland dysfunction.

Study	Design	Sample size	Treatment course	Outcomes
Craig et al, [38]	Double-masked, paired eye, randomized, sham-controlled eye trial	28	E-Eye device (9–13 J/cm^2) at weeks 0, 2, and 6	Improved dry eye symptomology, lipid layer thickness, and tear film stability following treatment course
Liu et al, [15]	Double-masked, paired eye, randomized, sham-controlled eye trial	44	Lumenis device (14–16 J/cm^2) at weeks 0, 4, and 8	Reduced IL-17A, IL-6, PGE-2 tear inflammatory marker expression following treatment course
Rong et al, [28]	Double-masked, paired eye, randomized, sham-controlled eye trial	44	Lumenis device (14–16 J/cm^2) at weeks 0, 4, and 8	Improved dry eye symptomology, meibomian gland expressibility, tear film stability, and corneal staining following treatment course
Rong et al, [31]	Double-masked, paired eye, randomized, sham-controlled eye trial	28	Lumenis device (14–16 J/cm^2) at weeks 0, 4, and 8	Improved meibomian gland expressibility and tear film stability 6 months following completion of treatment course
Xue et al, [14]	Double-masked, parallel-group, randomized, sham-controlled eye trial	87	E-Eye device (9–13 J/cm^2) at weeks 0, 2, 6, 10	Improved dry eye symptomology, lipid layer thickness, meibomian gland capping, and inhibition of periocular Corneybacterium macginleyi load 1 month following completion of treatment course

Table 2. Ongoing randomized controlled trials investigating the efficacy of intense pulsed light therapy for the treatment of meibomian gland dysfunction.

Study	Design	Sample size	Treatment course	Outcome measures
Dell et al, 2018 [39]	Single-masked, parallel-group, randomized, sham-controlled eye trial	88	Lumenis device (14–16 J/cm^2) at weeks 0, 2, 4, and 6	Tear film stability, dry eye symptomology, meibomian gland dropout, eyelid appearance and biomicroscopy, adverse events
Piyacomn et al, 2018 [40]	Double-masked, parallel-group, randomized, sham-controlled eye trial	114	E-Eye device (9–13 J/cm^2) at weeks 0, 2, and 6	Tear film stability, dry eye symptomology, tear osmolarity, corneal staining, lipid layer thickness, meibomian gland dropout and expressibility, Schirmer’s test, tear cytokine levels
Wood et al, 2017 [41]	Double-masked, paired eye, randomized, sham-controlled eye trial	14	Details regarding device and frequency not available. Course of 4 treatment sessions.	Tear film stability, dry eye symptomology
Zadok et al, 2017 [42]	Double-masked, parallel-group, randomized, sham-controlled eye trial	24	Lumenis device (14–16 J/cm^2) at weeks 0, 2, 4, and 6	Tear film stability, dry eye symptomology, tear osmolarity, meibomian gland dropout and expressibility, eyelid appearance

5. Limitations

Although the safety and efficacy of IPL therapy for the treatment of MGD has been confirmed by several clinical trials, a number of limitations are acknowledged. The use of IPL therapy in patients with Fitzpatrick scores of IV or greater is generally not recommended, due the increased risk of skin damage secondary to greater absorbance of light energy with deeper pigmentation [9–11]. In addition, IPL therapy is currently mainly limited to the treatment of the lower eyelids, as concerns of broad-spectrum light energy penetration to intraocular structures with direct application to the upper eyelids [9–11] necessitate the fitting of scleral shields during treatment.

6. Future directions

The potential for individual patient factors, including demographic characteristics, baseline ocular surface parameters, and MGD severity, in predicting treatment outcome warrants investigation in future studies, in order to provide evidence-based guidance for selecting patients who might benefit most from IPL therapy. Future research is also required to establish the optimal length, frequency, and energy delivery profile of treatment courses for maximal therapeutic benefit.

In addition, the long term effects of IPL therapy require further investigation in studies with extended follow-up periods, and it remains unclear whether the therapeutic benefits can be sustained over months to years following the completion of the treatment course. To date, only a limited number of studies have investigated treatment outcomes beyond the completion of the IPL treatment course. As summarized in Table 1, two randomized trials reported sustained improvements in ocular surface parameters at one and six months following the completion of the IPL treatment course, respectively [14,28]. Another prospective non-randomized study reported sustained improvements in dry eye symptomology and meibomian gland expressibility up to 12 months post-treatment, but not tear film stability or corneal staining [26].

7. Conclusions

Recent studies have suggested that IPL therapy demonstrates promise as a safe and effective treatment for refractive MGD. However, the exact mechanisms of action of IPL therapy in MGD remain yet to be fully understood. Future research is also required to investigate whether individual patient factors might predict the treatment outcomes of IPL therapy, and to determine the optimal length and frequency of treatment courses.

Declaration of interest

JP Craig serves as a consultant to Azura Ophthalmics and reports unrestricted grants to the university research fund from Alcon, Manuka Health NZ, E-Swin France, and Théa France. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer Disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose

Additional information

Funding

This paper was not funded.