Meibomian gland dysfunction (MGD) is a chronic, diffuse condition caused by obstruction of glandular orifices and alterations in meibum quantity and/or quality.⁽¹⁾ It is the primary cause of evaporative dry eye (EDE) disease, with prevalence varying depending on diagnostic criteria and region. In 2024, Chen et al. identified an MGD prevalence of 86% in patients with dry eye disease.^(2,3)

Patients report symptoms such as burning, tearing, a sensation of a foreign body, and intermittent visual blurriness. Severe cases may lead to difficulties in everyday tasks, including reading, watching television, driving, and computer work, and may negatively affect quality of life and work performance.⁽⁴⁾

Current MGD treatments are divided into non-thermal (gland probing, topical/oral antibiotics, Manuka honey, emollient drops, therapeutic expression) and thermal (warm compresses, pulsed thermotherapy, and Intense Pulsed Light [IPL]).⁽⁵⁾

Intense Pulsed Light, initially used in dermatology for treating photoaging, rosacea, pigmented lesions, and telangiectasias, was found in 2002 by Toyos et al. to relieve symptoms of MGD in rosacea patients.^(6-8) Studies confirm its efficacy in treating DED and MGD, typically applied around the eyelids in conjunction with gland expression.^(9-11)

This study's primary objective is to describe the clinical benefits of IPL applied directly to the eyelids of patients with Meibomian gland dysfunction and without glandular expression.

This non-concurrent, paired cohort study included all 46 MGD patients treated with IPL at Santa Luzia Eye Center in Guarabira between August 2019 and December 2020. It adhered to the Helsinki Declaration guidelines, and informed consent was obtained from all participants. The study was approved by the Research Ethics Committee of the Clementino Fraga Filho University Hospital and the Faculty of Medicine of the Universidade Federal do Rio de Janeiro on December 22, 2023 (approval no. 76359123.4.0000.5257).

Among all patients with MGD and treated with IPL at the Santa Luzia Eye Center during the study period, 30 patients were not included in the analysis: 6 patients were asymptomatic, 4 had a NITBUT > 10 seconds, 1 patient was younger than 20 years, 9 patients had TMH < 0.25 mm, 2 patients had meibomyography < 25% and 8 patients answered a different questionnaire (Ocular Surface Disease Index [OSDI]).

This study included 16 eyes from 16 patients (10 women) with symptomatic MGD. The mean age was 60.4 ± 18.4 years, ranging from 27 to 85 (Table 3).

This study was the first to demonstrate the efficacy of standalone IPL therapy applied directly to the eyelids in improving symptoms and glandular function in patients with MGD. In 2020, Xue et al., when treating 87 patients with IPL without eyelid massage in the tragus region, achieved improvement in symptoms (OSDI) mean: 21 ± 17 and SPEED mean: 9 ± 5; p < 0.001), but without statistically significant differences in meibum quality (Mdn: 2; IQR: 1-2; p = 0.28) or meibography (Mdn: 1; IQR: 0-2; p = 0.29), with results inferior to this study.⁽¹⁰⁾

In 2021, Shin et al. ⁽¹²⁾ conducted a comparative study of patients treated with standalone IPL versus those with therapeutic expression, concluding that expression alone did not improve symptoms (p = 0.84) or Meibomian gland quality (p = 0.731). In 2022, Martínez-Hergueta et al. applied IPL directly to the eyelids, combined with glandular expression, and reported improvement in meibography (M: 1.40 ± 0.74; p = 0.024).⁽¹³⁾ Toyos et al. confirmed that IPL combined with glandular expression improved meibum quality (p < 0.0001).⁽¹⁴⁾

Meibomian gland dysfunction is characterized by obstruction and alterations in secretion quality, often accompanied by telangiectasias and secondary Demodex infestations. Treatments targeting these alterations, including IPL, are effective.^(5,15)

Intense Pulsed Light is a non-coherent, scattered, pulsed light beam with wavelengths between 400 and 1200 nm. Its tissue action is based on selective photothermolysis, targeting chromophores (hemoglobin, melanin, or water) using specific filters (Figure 7).⁽¹⁶⁾

In 2015, dermatologist Rolando Toyos et al. observed that his facial rosacea patients treated with IPL experienced improvement in dry eye symptoms. Since then, IPL has gained prominence in the treatment of dry eye.^(8,14)

The likely mechanisms of action of IPL therapy involve several processes. First, the local heat generated by the IPL flash raises tissue temperature to approximately 50ºC, sufficient to liquefy glandular secretions and facilitate drainage, thereby reducing gland dropout. However, many IPL devices lack small tips designed for direct eyelid application, resulting in protocols being applied to the face, as seen in rosacea treatment, even in patients with MGD alone. Some researchers have noted that IPL may not sufficiently elevate eyelid temperature to melt glandular secretions effectively.⁽¹⁴⁾

Another mechanism is the occlusion of small vessels at the eyelid margin. Meibomian glands function optimally in low-oxygen environments, and small ships at the eyelid margin increase oxygen delivery, impairing gland function. Intense Pulsed Light coagulates hemoglobin in these vessels, creating the anaerobic environment essential for gland efficiency.⁽¹⁷⁾

Intense Pulsed Light also aids in the elimination of Demodex folliculorum and Demodex brevis, which contribute to the inflammatory cycle in dry eye syndrome by releasing toxins on the ocular surface. The IPL treatment increases porphyrin production in the mitochondria of Demodex mites, leading to their destruction.⁽¹⁸⁾

Furthermore, IPL reduces pro-inflammatory mediators such as interleukin (IL) 17A, IL-6, and prostaglandin E2 while combating blepharitis.⁽¹⁹⁾ It also induces photobiomodulation by altering intracellular gene and protein expression, which improves cellular function. IPL's effect on fibroblasts enhances collagen synthesis, improving eyelid tone and elasticity. This results in more efficient blinking, improved Meibomian gland expression, reduced tear evaporation, enhanced ductal gland architecture, and activation of germinative cells, thereby improving secretion quality.⁽²⁰⁾

Lastly, IPL exerts neurological effects by stimulating two branches of the parasympathetic nerve in the lower eyelid, improving the function of the Meibomian and lacrimal glands. These combined mechanisms contribute to the therapeutic efficacy of IPL in treating MGD and associated conditions.⁽²¹⁾

In this study, IPL treatment was performed on the lower eyelid, as in most studies, and on the upper eyelid.^(8,13,21-23) Meibomian gland dysfunction is not exclusive to the lower eyelid. Unfortunately, the initial indication for this therapy was for dermatological patients with dry eyes and facial rosacea. The initial machines had large tips, which made it impossible to treat the upper eyelid without causing harmful effects, leading many doctors to avoid treating it.

The upper eyelid has an average of 30 Meibomian glands, while the lower has 25. These glands produce an average of 26 and 13 µL of secretion, respectively.⁽²⁴⁾ Thus, the upper eyelid's reservoir of meibum is significant and should not be neglected.

Unfortunately, most IPL machines have large tips, typically 35 mm x 15 mm, which are unsuitable for eyelid dimensions. This mismatch can cause burns, loss of eyebrows and eyelashes, uveitis, and iris transillumination defects.^{(7,13,15,25,26)}

Despite treatment on the upper and lower eyelids, meibomography and meibum evaluation were performed only on the lower eyelid due to technical limitations, as they already represent the disease.

Direct IPL treatment on the eyelids did not increase gland dropout percentages, a significant concern for proponents of pulsed thermotherapy, given that eyelid temperature can exceed 50°C.^(13,26,27) Improvements in meibography averages (Figure 6C) may be attributed to the photobiomodulatory effects of IPL on the acinar units of Meibomian glands, which liquefy meibum, facilitate drainage, reduce ductal pressure, and slow down acinar apoptosis and gland dropout.^(13,20)

The therapy resulted in symptom improvement, with 75% of patients becoming asymptomatic or reporting mild symptoms, achieving statistical significance (p<0.001) and a substantial effect size (d = 1.44). In 2024, Elbakary et al. treated 15 patients with moderate-to-severe EDE using IPL and achieved 73% of asymptomatic and mild cases, which is similar to the values we found. A significant improvement in patients’ quality of life (QOL) was noticed in all patients treated with IPL, with a reduction of the mean OSDI score from 56.9 ± 11.1(moderate-to-severe) to 22.9 ± 16.4(asymptomatic-to-mild).⁽²⁸⁾

Additionally, 68.8% exhibited clear or yellowish meibum, with an important effect size (rpb 0.889). These results demonstrate clinical relevance and justify the standalone use of IPL for treating patients with refractory MGD.

Neither sex nor age influenced treatment response as they did not meet the assumptions for the initial multiple linear regression model. This was unexpected, given that age and sex are significant risk factors for MGD, likely due to glandular loss with age and hormonal changes.^(29-31)

This study employed a retrospective cohort design, with data collected from medical records. This led to information loss. Another limitation was the transformation of numerical data into ordinal variables for statistical analysis, which reduced the study's power.

The treatment period coincided with the COVID-19 pandemic, which discouraged patient follow-up. Several patients reported significant symptom improvement but did not attend the post-therapy control examinations, affecting the sample size. Adverse effects included eyelash loss in two patients and localized burning sensation for a few hours.^(7,31,32)

The sample size was small, and follow-up was short, only 30 days post-treatment. Longer follow-up would be necessary to assess the duration of the therapy's effects on glandular secretion, symptom improvement, and glandular loss.

An interesting observation was made in patients using prostaglandin analogs for the management of glaucoma. Long-term use of these medications leads to orbital fat atrophy, eyelid stiffening, and darkening. Following IPL sessions, skin lightening and improved eyelid tone were observed, thereby enhancing periocular aesthetics.^(6,33)

Our findings suggest that concomitant treatment of the upper and lower eyelids was associated with statistically and clinically significant improvements in symptoms, demonstrating the possible irrelevance of associating glandular expression with Intense Pulsed Light. The quality of meibum secretion also enhanced, with no worsening of gland dropout in meibography, thereby, contributing to the reduction of the disease's progression.