|Year : 2021 | Volume
| Issue : 2 | Page : 91-96
Treatment of dry eye disease due to meibomian gland dysfunction using intense pulsed light and low-level light therapy
Ali A Khalifa, Mohamed M.A Ibrahim, Mahmoud S.A Abdelrahman
Department of Ophthalmology, Al Azhar University Hospitals, Al Azhar University, Cairo, Egypt
|Date of Submission||20-Sep-2020|
|Date of Decision||05-Dec-2020|
|Date of Acceptance||10-Mar-2021|
|Date of Web Publication||24-Jun-2021|
MBBCh Mahmoud S.A Abdelrahman
Department of Ophthalmology, Al Azhar University Hospitals, Al Azhar University, 75th, Lebanon Street, 7th District, El-Sheikh Zayed City 12588
Source of Support: None, Conflict of Interest: None
Background Meibomian gland dysfunction (MGD) is an abnormal chronic state of meibomian glands in which there is quality and quantity alternations in the meibum glandular secretion or terminal duct obstruction. Patients with MGD show imbalance in the tear film components because of the lipid layer deficiency.
Objectives The aim of this study was to assess the changes in the tear film after using intense pulsed light and low-level light therapy (IPL-LLLT) according to the Dry Eye Workshop classification.
Patients and methods The study enrolled 80 eyes of 40 patients of both sexes with dry eye disease caused by MGD, with age range from 23 to 74 years. They showed symptoms of unilateral or bilateral dryness, diagnosed as MGD, with a meibum grade more than or equal to 1 and with a Fitzpatrick skin type of two to five appearance dependent and sensitivities to sun light. They were studied by comparing the pretreatment and posttreatment session values.
Results The Dry Eye Workshop score showed a significant reduction after 4 weeks of the IPL-LLLT treatment in comparison with the baseline (P<0.001). The meibomian gland evaluation scores (meibum grade and meiboscale) showed a significant improvement after 4 weeks of treatment (P<0.001). Moreover, the Standard Patient Evaluation of Eye Dryness significantly decreased after the treatment (P<0.001). No undesirable events were observed except for four cases, all of which showed transient redness. In addition, one patient showed an obvious improvement in Schirmer test I, the second showed deterioration in the meibum grade, and the third showed deterioration in visual acuity, Schirmer test I, tear break-up time, corneal fluorescein staining, meibum grade, and Standard Patient Evaluation of Eye Dryness.
Conclusions IPL-LLLT combination could be used as a safe and efficient way for MGD treatment. However, it does not completely cure the MGD.
Keywords: dry eye, eye-light, intense pulsed light, low-level light therapy, meibomian gland dysfunction, meiboscale, Standard Patient Evaluation of Eye Dryness
|How to cite this article:|
Khalifa AA, Ibrahim MM, Abdelrahman MS. Treatment of dry eye disease due to meibomian gland dysfunction using intense pulsed light and low-level light therapy. Delta J Ophthalmol 2021;22:91-6
|How to cite this URL:|
Khalifa AA, Ibrahim MM, Abdelrahman MS. Treatment of dry eye disease due to meibomian gland dysfunction using intense pulsed light and low-level light therapy. Delta J Ophthalmol [serial online] 2021 [cited 2021 Sep 22];22:91-6. Available from: http://www.djo.eg.net/text.asp?2021/22/2/91/319184
| Introduction|| |
Patients with Meibomian gland More Details dysfunction (MGD) show imbalance in the tear film components owing to lipid layer deficiency. The aim of MGD treatment is to provide stable and long-term improvement of the symptoms of MGD by increasing the meibum quality or flow, regaining balance among the lipid, aqueous, and mucin layers of the tear film and improving stability of the tear film, in addition to reduction of inflammation .
Common treatment option varieties are available such as warm compresses application, lid hygiene practice, omega-3 fatty acids, expression of meibum , intraductal probing , autothermal pulsations , topical drugs, antibiotics, artificial tears, and topical diquafosol . However, many patients with MGD are resistant to therapy and do not show full or long-term symptom relief .
Intensive pulsed light (IPL) therapy is used for cosmetic and therapeutic treatment of hypertrichosis, vascular lesions such as benign cavernous hemangiomas, telangiectasises, venous malformations, and pigmented lesions . Corresponding trials have shown that in patients with mild to moderate MGD or dry eye, IPL therapy successfully enhanced subjective symptoms and objective results .
Low-level light therapy (LLLT) uses red to near-infrared wavelengths of guided low power and high-fluence monochromatic, quasi-monochromatic lasers, or light-emitting diodes to change biological activity or to produce therapeutic effect of nondestructive and nonthermal ways . The LLLT causes conversion of light energy to metabolic energy, with a corresponding change of cell’s biological functions (photobiomodulation). LLLT depends on the target tissue physical and chemical characteristics, power and energy density, intensity, capacity, velocity, wavelengths, mode of contact, and energy source. The photostimulatory and photoinhibitory effects are achieved in LLLT applications with low (0.001–10 J/cm2) and high (>10 J/cm2) energy densities, respectively . The beneficial effects are likely to vary within this dosage range for a particular expected result. LLLT promotes cytochrome-C oxidation with the help of cytochrome oxidase, enhances oxygen uptake, with possible increase in mitochondrial membrane potential, and activation of mitochondrial permeability transition pore .
The aim of this study was to assess the changes in the tear film after using IPL and LLLT according to the Dry Eye Workshop (DEWS) classification.
| Patients and methods|| |
The study enrolled 80 eyes of 40 patients of both sexes with dry eye disease caused by MGD, with age range from 23 to 74 years, between June 2019 and January 2020. It included patients with symptoms of unilateral or bilateral dryness or who have undergone refractive surgery. They were diagnosed as having MGD, with a meibum grade more than or equal to 1, and with a Fitzpatrick skin type of 2–5 with appearance based and sensitivity to sun light ,. All patients signed a written informed consent to participate in the study and for publication of data before being enrolled in the study, and the study was approved by Al Azhar Medical Research Ethical Committee.
The pretreatment session evaluation included complete ophthalmic examination in the form of best-corrected and uncorrected visual acuity measured using Snellen’s chart and ocular adnexa and anterior segment examination by slit-lamp biomicroscopy. Special attention was directed to excluded any condition that can affect the ocular surface such as deforming lid abnormalities, severe lid margin vascularity, pterygium, or any corneal disease. The tear meniscus debris was observed, and the intraocular pressure was measured by an air puff tonometer (TOPCON CT-80; 75-1 Hasunuma-cho, Itabashi-ku, Tokyo, Japan).
The tear break-up time (TBUT) was measured by the Ocular Surface Analyzer which allows the evaluation of the stability and regularity of the tear film, using a noninvasive break-up time measurement. With the idra, which is an Ocular Surface Analyzer tool (SBM Sistemi, Strada Torino, Italy), we used auto-noninvasive break-up time, which was completely charged to the software .
For corneal and conjunctival fluorescein staining score, a drop of saline was applied on a fluorescein strip, and when saturated, the excess was shaken into a waste basket. The lower lid was then pulled down, and the strip was applied to the lower tarsal conjunctiva. After instillation, the optimum view is after 1–3 min. Each cornea was checked with the cobalt blue light by the slit lamp. The fluorescein pattern was usually estimated about 4–8 min after operation. Fluorescein-stained punctate epithelial erosions (PEE) were counted and scored as follows: more than 30 PEE was scored as 3; if 6–30 PEE was seen, it was scored as 2; if 1–5 PEE was seen, the corneal score was 1; and if no PEE, it was scored as 0 .
The tear film volume assessment was performed by Schirmer I test (no anesthesia). Regular graded Schirmer strips (Ophtechnics Unlimited, DLF City, Haryana, India) were folded and gently placed to the temporal angle as far as practicable over the lower lid edge. During the procedure, the patient was advised to hold his or her eyes closed. The strips were calculated using the millimeter scale of each strip after 5 min of wetting .
Meibum gland evaluation
The meibum was graded according to the quality of the expressed meibum as follows: 3=inspissated like toothpaste, 2=cloudy particulate fluid, 1=cloudy fluid, and 0=clear fluid. Meibomian glands were tested on the basis of the meiboscale for morphological features (1–4), as determined by noninvasive meibography to calculate the area of meibomian gland loss as 4 more than 75% loss, 3=51–75% loss, 2=25–50% loss, 1 less than 25% loss, and 0=0% loss ,.
The patient symptom assessment was described with the Standard Patient Evaluation of Eye Dryness (SPEED) validated questionnaire (0–28) .
Patient treatment sessions
The patients received benoxinate HCl 0.4% (EIPICO, Tenth of Ramadan City, Egypt) eye drops that were used as a topical anesthetic before each session. Every patient had a series of one to four treatment sessions with 2-week intervals guided by the meiboscale (1, 2, 3, or 4 sessions for degrees 1, 2, 3, and 4, respectively). Each case was fully assessed, as shown above, both before treatment, at each session, and a month after the last session. The patients were instructed to keep on their eye medications. No new therapy (topical or systemic) was allowed for any patient during the treatment course. Eye-light, including IPL and LLLT (Espansione Group, Funo, Bologna, Italy), as shown in [Figure 1], was used.
The operator wore protective goggles provided by the instrument. In each treatment session, both eyes of the patient were closed and shielded with IPL-Aid eye shields. The patient received five flashes after selecting the Optimal Power Energy button, starting on the lower lid from the nasal to the temporal side (four flashes) and the fifth flash horizontally by overlapping the others. By selecting light modulation button, the patient wore light modulation mask for 15 min.
All studied eyes received between one and four sessions of eye-light − IPL and . Then the tear film changes were evaluated, and we compared the pretreatment and posttreatment session values according to the DEWS classification.
Data were analyzed using IBM SPSS software package, version 20.0. (IBM Corp, Armonk, New York, USA). Shapiro–Wilk test was used to verify the normality of distribution. Quantitative data were described using range (minimum and maximum), mean, SD, median, and interquartile range. Paired t test was used for normally distributed quantitative variables to compare between two periods. Wilcoxon signed-rank test was used for abnormally distributed quantitative variables to compare between two periods. Significance of the obtained results was judged at the 5% level, with p value equal to or less than 0.05 being considered statistically significant.
| Results|| |
Abnormal findings were found in four cases; all of them showed transient redness. In addition, the first case showed an obvious improvement in Schirmer I test, the second showed deterioration in meibum grade, and the third showed deterioration in visual acuity, Schirmer I test, TBUT, corneal fluorescein staining (CFS), meibum grade, and SPEED.
The meibum grade ranged from 1 to 3 (mean=1.93±0.64) before treatment and from 1 to 2 (mean=1.21±0.41) after treatment, with a statistically significant difference (P<0.001). The SPEED value ranged from 15 to 28 (mean=22.53±3.32) before treatment and became 9–27 (mean=18.62±4.75) after treatment, with a statistically significant difference (P<0.001). The meiboscale ranged from 1 to 4 (mean=1.79±0.88) and from 1 to 4 (mean=1.51±0.75) for pretreatment and posttreatment values, respectively, with a statistically significant difference (P<0.001). The DEWS % ranged from 36.11 to 91.67% (mean=54.16±11.41%) before treatment and became 33.0–94.0% (mean=49.93±11.59%) after treatment, with a statistically significant difference (P<0.001). The CFS ranged from 0.0 to 9.0 (mean=4.03±2.05) and 2.0 to 7.0 (mean=3.56 ±1.42) pretreatment and posttreatment, respectively, with a statistically insignificant difference (P=0.078). The Schirmer’s test ranged from 0.0 to 23.0 mm (mean=8.84±5.31 mm) before treatment and improved to 0.0–30.0 mm (mean=12.52±5.52 mm) after treatment, with a statistically significant difference (P<0.001) ([Table 1]).
|Table 1 Descriptive analysis of the studied cases before and after treatment|
Click here to view
| Discussion|| |
MGD is a common disease. However, efficient treatment is not yet clear and is widely disappointing. This may be as a result of its mixed etiopathology and restricted treatment choices, which alleviate symptoms rather than treat the pathology .
Kam and Sullivan  reported that IPL stimulates the meibomian gland epithelial cells which have receptors for parasympathetic neurons and can therefore produce meibum again. Many mechanisms were proposed to explain how IPL treats MGD. They included thrombosis of abnormal blood vessels, meibum liquefaction, decreasing inflammatory mediators, and photo-modulation. Photo-modulation modulates cell metabolism through photon absorption by photoreceptors, including cytochrome-C oxidase in the mitochondria and calcium ion channels . Photo-modulation is distinguished by counter-inflammatory results, such as pain control, enhancement of healing, and reduction of inflammatory factors . The reduced inflammation and reactive oxygen species might improve the corneal nerve regeneration . In previous studies, the function of low-level lasers in improving regenerative processes in damaged nerves may be attributed to photo-modulation ,,. Hence, neurotropism could be a mechanism when using IPL treatment for MGD.
We tested a total of nine variables including tear film-related and meibomian gland parameters before and 4 weeks after therapy. The IPL-LLLT combination demonstrated a substantial progress over the pretreatment values in several calculated parameters. The progress of meibomian gland scores such as meibum level has shown that an increased local temperature, with increased melting and liquidation of meibum, is a possible pathway for IPL therapy. In the current study, also, abnormalities of eyelid margin (telangiectasias and irregularities) were improved. This agreed with previous studies ,,.
In the current study, the SPEED score markedly improved from a mean value of 22.5–18.6. In addition, the Schirmer’s test improved from a mean value of 8.84 mm. before treatment to 12.52 mm 4 weeks after treatment. Although the CFS showed improvement from a mean value of 4.03–3.56, yet it was statistically insignificant. The study by Arita et al.  showed marked improvement of SPEED score from a mean value of 14.7 before treatment to 5.9 after 24 weeks of treatment of IPL-meibomian gland expression (MGX). In addition, the CFS significantly improved from a mean value of 1.1–0.2 (P˂0.001), and the Schirmer’s test significantly improved from a mean value of 8.5–8.8 mm, respectively (P>0.05). Similarly, in a study by Rong et al. , the SPEED and CFS scores significantly improved with IPL treatment (P<0.001), whereas the meiboscale in the studied eyes (1.48±0.76, lower eyelid) remained constant at the baseline and after 12 months following treatment. So, it agreed with the present study in terms of improvement of SPEED score and Schirmer’s test, whereas the CFS and meiboscale results in both studies disagreed with the current study; although they had the same inclusion criteria of patients, they used IPL treatment and meibomian gland expression ,.
Craig et al.  evaluated the changes in SPEED score. It was lower at the 45th day compared with the baseline. The median SPEED score decreased over the time period between the first and the 45th day in the treated eyes, which was statistically significantly better (P<0.001). This agreed with the current study results, as the patients in both groups had mild–moderate clinical signs of MGD and the period of treatment and follow-up was largely close.
In 2020, Karaca et al.  showed a statistically significant improvement in SPEED score (P<0.05) when they assessed the effect of intense regulated pulse light on the treatment of MGD.
The study by Jiang et al.  showed a statistically significant improvement in the meibum grade among other things (P<0.05) after the second treatment. In addition, it was shown to be an effective therapy for MGD, with an improvement in symptoms such as foreign body sensation, burning and blindness (P<0.05). This also agreed with the present study results.
The study by Yin et al.  showed differences in meibomian gland morphological changes before and after IPL treatment. Regarding the meibomian gland macrostructure, the patients in the IPL group had notable meibomian gland dropout before therapy (45.72±12.93%). The dropout level decreased after treatment by 4–5%, with a statistically significant difference (P˂0.002). In addition, the study showed a change in the meibum grade (quality) in the IPL group before and after treatment, which was statistically significant (mean=2.78±2.34 and 1.17±1.86, respectively, P˂0.014). These results were in agreement with the lowered degree of meibomian gland dropout documented in the current study. However, the study by Yin et al.  showed a change in the Schirmer test results in IPL group before and after treatment from a mean value of 10.44±8.74 to 7.61±7.35 mm, respectively, which was statistically insignificant (P>0.05), which disagreed with the present study results. However, they used IPL only without LLLT.
Dell et al.  used the SPEED questionnaire for evaluating the subjective symptoms. It was conducted independently for each eye. The overall SPEED score decreased from the baseline compared with each of the three follow-up visits, with statistically meaningful changes from a mean value of 12.9±4.9 to 5.8±4.2 (P˂0.0001). This agreed with our study results.
In 2020, the study by Yan et al.  showed an improvement in CFS, which was statistically significant, with a decrease in the mean value from 1.56±1.7 to 0.96±1.5 (N=60, P˂0.0001). Similarly, the current study showed a decrease in the mean value of CFS, but it was statistically insignificant. This disagreement may be attributed to the fact that each of their patients was treated three times within 3-week intervals.In addition, in the study by Albietz and Schmid , the CFS was reduced over the 12 weeks from 4.0±3.1 to 1.8±2.5, with a statistically significant improvement (P<0.001), whereas the Schirmer I test was reduced from a mean value of 17.3±11.0–14.9±6.0 mm (P>0.05). Contrary to this, the present study showed a statistically insignificant improvement in the CFS and an increase in Schirmer I test mean value. This disagreement could be owing to their study involving 26 participants only, and they also used IPL treatment and meibomian gland expression for moderate to advanced MGD .
In the study by Yurttaser Ocak et al. , the Schirmer test results showed no changes in any group (mild, moderate, or severe) at any time point (1, 3, or 12 months), which was statistically insignificant (P>0.05), whereas the CFS results showed improvement in the mild and moderate groups at all time points (1, 3, and 12 months), which was statistically significant (P˂0.001), whereas the severe group did not show any improvement. This totally disagrees with the current study results, which may be attributed to the longer follow-up periods, as they followed up their patients at 1, 3, and 12 months .
The current study is limited by the short follow-up period (4 weeks). We need more observation to assess the long-term efficacy of the IPL treatment. In addition, the ocular surface evaluation was performed by one investigator. If more than one patient performed the mentioned tests and their average readings were taken, it could have improved the accuracy of results.
| Conclusion|| |
IPL-LLLT is a new highly developed treatment option for MGD patients. Abnormal findings were found in four cases; all of them showed transient redness. In addition, the first case showed an obvious improvement in Schirmer I test, the second showed deterioration in meibum grade, and the third showed deterioration in visual acuity, Schirmer I test, TBUT, CFS, meibum grade, and SPEED. IPL-LLLT was able to improve both symptoms and signs of MGD in a safe and efficient manner, so it can be used as a new MGD treatment option. However, it does not completely cure the MGD.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest
| References|| |
Mizoguchi T, Arita R, Fukuoka S, Morishige N. Morphology and function of meibomian glands and other tear film parameters in junior high school students. Cornea 2017; 36:922–926.
Arita R, Mizoguchi T, Fukuoka S, Morishige N. Multicenter study of intense pulsed light therapy for patients with refractory meibomian gland dysfunction. Cornea 2018; 37:1566–1571.
Maskin SL. Intraductal meibomian gland probing relieves symptoms of obstructive meibomian gland dysfunction. Cornea 2010; 29:1145–1152.
Greiner JV. A single LipiFlow® thermal pulsation system treatment improves meibomian gland function and reduces dry eye symptoms for 9 months. Curr Eye Res 2012; 37:272–278.
Arita R, Suehiro J, Haraguchi T, Maeda S, Maeda K, Tokoro H, Amano S. Topical diquafosol for patients with obstructive meibomian gland dysfunction. Br J Ophthalmol 2013; 97:725–729.
Choi M, Han SJ, Ji YW, Choi YJ, Jun I, Alotaibi MH et al.
Meibum expressibility improvement as a therapeutic target of intense pulsed light treatment in meibomian gland dysfunction and its association with tear inflammatory cytokines. Sci Rep 2019; 9:7648.
Toyos R, McGill W, Briscoe D. Intense pulsed light treatment for dry eye disease due to meibomian gland dysfunction; a 3-year retrospective study. Photomed Laser Surg 2015; 33:41–46.
Rojas JC, Gonzalez-Lima F. Low-level light therapy of the eye and brain. Eye Brain 2011; 3:49–67.
Rohringer S, Holnthoner W, Chaudary S, Slezak P, Priglinger E, Strassl M et al.
The impact of wavelengths of LED light-therapy on endothelial cells. Sci Rep 2017; 7:10700.
Hamblin MR. Mechanisms and mitochondrial redox signaling in photobiomodulation. Photochem Photobiol 2018; 94:199–212.
Eom Y, Choi KE, Kang SY, Lee HK, Kim HM, Song JS. Comparison of meibomian gland loss and expressed meibum grade between the upper and lower eyelids in patients with obstructive meibomian gland dysfunction. Cornea 2014; 33:448–452.
Knight JM. Combined 400-600nm and 800-1200nm intense pulsed phototherapy of facial acne vulgaris. J Drugs Dermatol 2019; 18:1116–1122.
Giannaccare G, Vigo L, Pellegrini M, Sebastiani S, Carones F. Ocular surface workup with automated noninvasive measurements for the diagnosis of meibomian gland dysfunction. Cornea 2018; 37:740–745.
Pellegrini M, Bernabei F, Moscardelli F, Vagge A, Scotto R, Bovone C et al.
Assessment of corneal fluorescein staining in different dry eye subtypes using digital image analysis. Transl Vis Sci Technol 2019; 8:34.
Li N, Deng XG, He MF. Comparison of the Schirmer I test with and without topical anesthesia for diagnosing dry eye. Int J Ophthalmol 2012; 5:478–481.
Osae EA, Ablorddepey RK, Horstmann J, Kumah DB, Steven P. Assessment of meibomian glands using a custom-made meibographer in dry eye patients in Ghana. BMC Ophthalmol 2018; 18:201.
Asiedu K. Rasch analysis of the standard patient evaluation of eye dryness questionnaire. Eye Contact Lens 2017; 43:394–398.
Dell SJ, Gaster RN, Barbarino SC, Cunningham DN. Prospective evaluation of intense pulsed light and meibomian gland expression efficacy on relieving signs and symptoms of dry eye disease due to meibomian gland dysfunction. Clin Ophthalmol 2017; 11:817–827.
Kam WR, Sullivan DA. Neurotransmitter influence on human meibomian gland epithelial cells. Invest Ophthalmol Vis Sci 2011; 52:8543–8548.
Hamblin MR. Mechanisms and applications of the anti-inflammatory effects of photobiomodulation. AIMS Biophys 2017; 4:337–361.
Katagiri W, Lee G, Tanushi A, Tsukada K, Choi HS, Kashiwagi S. High-throughput single-cell live imaging of photobiomodulation with multispectral near-infrared lasers in cultured T cells. J Biomed Opt 2020; 25:1–18.
Zhang J, Dai Y, Wei C, Zhao X, Zhou Q, Xie L. DNase I improves corneal epithelial and nerve regeneration in diabetic mice. J Cell Mol Med 2020; 24:4547–4556.
Andreo L, Ribeiro BG, Alves AN, Martinelli ASA, Soldera CB, Horliana ACRT et al.
Effects of photobiomodulation with low-level laser therapy on muscle repair following a peripheral nerve injury in Wistar rats. Photochem Photobiol 2020; 96:1124–1132.
Jiang X, Lv H, Song H, Zhang M, Liu Y, Hu X et al.
Evaluation of the safety and effectiveness of intense pulsed light in the treatment of meibomian gland dysfunction. J Ophthalmol 2016; 2016:6.
Yin Y, Liu N, Gong L, Song N. Changes in the meibomian gland after exposure to intense pulsed light in meibomian gland dysfunction (MGD) patients. Curr Eye Res 2018; 43:308–313.
Arita R, Fukuoka S, Morishige N. Therapeutic efficacy of intense pulsed light in patients with refractory meibomian gland dysfunction. Ocul Surf 2019; 17:104–110.
Rong B, Tang Y, Tu P, Liu R, Qiao J, Song W et al.
Intense pulsed light applied directly on eyelids combined with meibomian gland expression to treat meibomian gland dysfunction. Photomed Laser Surg 2018; 36:326–332.
Craig JP, Chen YH, Turnbull PR. Prospective trial of intense pulsed light for the treatment of meibomian gland dysfunction. Invest Ophthalmol Vis Sci 2015; 56:1965–1970.
Karaca EE, Evren Kemer Ö, Özek D. Intense regulated pulse light for the meibomian gland dysfunction. Eur J Ophthalmol 2020; 30:289–292.
Yan X, Hong J, Jin X, Chen W, Rong B, Feng Y et al.
The efficacy of intense pulsed light combined with meibomian gland expression for the treatment of dry eye disease due to meibomian gland dysfunction: a multicenter, randomized controlled trial. Eye Contact Lens 2021; 47:45–53.
Albietz JM, Schmid KL. Intense pulsed light treatment and meibomian gland expression for moderate to advanced meibomian gland dysfunction. Clin Exp Optom 2018; 101:23–33.
Yurttaser Ocak S, Karakus S, Ocak OB, Cakir A, Bolukbasi S, Erden B et al.
Intense pulse light therapy treatment for refractory dry eye disease due to meibomian gland dysfunction. Int Ophthalmol 2020; 40:1135–1141.