Mechanisms and Safety of Therapeutic Strategies in Meibomian Gland Dysfunction: A Narrative Review.

Understanding the Dual Dilemma of Dry Eye and Glaucoma: An International Review.

ABSTRACTPurpose: To observe (1) changes in meibomian gland (MG) after exposure to intense pulsed light (IPL) and (2) to understand the mechanism by which IPL treats meibomian gland dysfunction (MGD) in patients.Methods: A cohort study, including 35 MGD patients, was conducted. IPL treatment was administered in one group (IPL group; n = 18), and eyelid hygiene in another (control group; n = 17) for 3 months. All patients were given artificial tears during the treatment period. Associated ocular-surface indexes (ocular surface disease index, OSDI; tear breakup time, TBUT, Schirmer 1Test, corneal staining, and conjunctival staining), MG function, MG macro-morphology, and MG micro-morphology were examined before and after treatment. The relationships between the change in symptom score and the change in the other indexes (related ocular-surface indexes, MG functional indexes, and MG morphological indexes) were evaluated.Results: There was no statistical difference in pretreatment between the IPL and the control groups in terms of age, gender, related medical history, MGD stage, and all examined indexes, with the exception of conjunctival staining. OSDI, TBUT, meibum quality, MG expressibility, and MG dropout improved after treatment in both of the two groups (all P < 0.05). The MG microstructure indexes, including the MG acinar longest diameter (ALD), MG acinar unit density (AUD), and the positive rate of inflammatory cells (ICs) around glandular structures were significantly improved in the IPL group. No improvements of microstructure were found in the control group.Conclusion: IPL treatment improves the symptom score of patients, associated ocular-surface indexes, MG function, and MG macrostructure as well as eyelid hygiene. And IPL treatment particularly improves MG microstructure and decreases MG inflammation in MGD patients.

Meibomian gland dysfunction (MGD) is one of the common ocular surface diseases in clinics.The pathogenesis, diagnosis and treatment of MGD have been the clinical research focus and challenge over the years.The traditional physical treatments for MGD consist of lid hygiene, warm compress and massage.The traditional medical treatments for MGD consist of artificial tears, topical and systemic anti-inflammatory agents and antibiotics.However, each treatment above has its deficiency because of transient and limited curative effects.With people's further acknowledgement of MGD, different kinds of treatment options have emerged.The emerging physical treatments include the LipiFlow thermal pulsation system, intense pulsed light, intraductal meibomian gland probing.The emerging medical treatments include N-acetyl-cysteine, omega-3 essential fatty acids and hormone.This review focused on wide-used and current emerging treatment options above, aiming to help clinicians to select appropriate treatments and provide reference for further study on MGD. Key words: Meibomian gland dysfunction; Physical treatment; Medical treatment; Emerging treatment

Purpose: Meibomian gland dysfunction (MGD) may cause chronic ocular surface pain (COSP) with a neuropathic component that can significantly impact quality of life and be poorly responsive to conventional treatments of MGD. Intense pulsed light (IPL) is an emerging treatment already acknowledged as improving refractory MGD, potentially modulating inflammatory mediators on the ocular surface. This study aimed to assess the impact of IPL on COSP associated with unresponsive MGD. Methods: A monocentric prospective study has been conducted from 2021 to 2023 on patients presenting with moderate MGD and COSP non-responsive to conventional treatments of MGD. Neuropathic pain components were suspected when severe discomfort (OSDI score above 33/100) was observed despite moderate objective signs. Three sessions of IPL were performed at a two-week interval. The primary outcome was change in OSDI at day 60. Secondary outcomes included OSDI modification at D120, DEQ-5, and Pentascore results at D60/D120, together with changes in clinical [Schirmer I, Fluorescein Break-up time (BUT), fluorescein staining, and MGD classification] and paraclinical tests [noninvasive BUT, tear meniscus height (TMH), and meibography]. Results: A significant improvement of COSP (p < 0.05 for changes in OSDI and Pentascore results) was observed 2 and 4 months after the last IPL session, together with an improvement in tear film stability, corneal epitheliopathy, meibomian gland obstruction, and TMH. Conclusion: The results of this study suggest the beneficial effect of IPL on neuropathic component of COSP associated with MGD. The underlying mechanisms involved in that improvement, presumably related to downgrading of inflammatory effectors, remain however to be explored.

Demodex folliculorum infestation is an important contributor to meibomian gland dysfunction (MGD) and chronic ocular surface disease. This study evaluated and compared the therapeutic efficacy of intense pulsed light (IPL) and eyelid hygiene (ELH) for Demodex-associated MGD. In this prospective, randomized comparative trial, 50 patients (100 eyes) with Demodex-associated MGD were allocated to two arms. Group A (n = 25) received three Eyesis IPL sessions at baseline, week 2, and week 4. Group B (n = 25) performed daily eyelid hygiene with OCuSOFT Lid Scrub for 6 weeks. Ocular surface parameters, including ocular surface disease index (OSDI), tear film lipid layer thickness (TFLL), noninvasive tear film break-up time (NITBUT), meibomian gland dropout, meibum quality and expressibility, corneal fluorescein staining (CFS), Schirmer's I, and Demodex count, were assessed from baseline to week 6. Best-corrected visual acuity (BCVA) and intraocular pressure (IOP) were recorded at each visit. Both treatments significantly improved OSDI, NITBUT, TFLL, Schirmer's I, and CFS over 6 weeks (all p < 0.001). Compared with ELH, IPL achieved larger and earlier reductions in symptoms, greater increases in TFLL, and superior improvements in meibum quality and expressibility from week 4 onward (between-group p ≤ 0.021). Demodex counts decreased significantly in both groups with no between-group difference at week 6. BCVA, IOP, and adverse events remained stable, indicating a favorable short-term safety profile. IPL and ELH are effective for Demodex-related MGD, but IPL provides faster and more pronounced improvements in meibomian gland function, tear film stability, and patient-reported symptoms over 6 weeks.

Objective: To evaluate the short-term therapeutic effect of intense pulsed light combined with meibomian gland expression (IPL/MGX) for the treatment of meibomian gland dysfunction (MGD). Methods: This was a prospective single-arm clinical study that included 55 MGD patients, in which 48 patients (96 eyes) finished the follow-up. IPL/MGX treatment was administered in both eyes, once every 3 weeks for 3 sessions. Testing was performed before treatment and 1 week after treatment and included the ocular surface disease index (OSDI), a questionnaire survey, tear film break-up time, corneal staining, meibomian gland function and imaging, conjunctival bulbar redness, confocal microscope examination of the meibomian gland and mites, etc. A paired t test, Wilcoxon rank sum test and Spearman rank correlation were used for statistical analysis. Results: Ocular surface disease index (t=2.300, P=0.024) meibomian gland expression score and meibum quality score (Z=-3.617, P<0.001; t=2.472, P=0.017), corneal staining score and bulbar redness score (Z=-2.757, P=0.006; t=2.040, P=0.044), inflammatory cell density (t=4.765, P<0.001), and total number of demodex mites in the follicle (t=2.121, P=0.037) were all improved after treatment. The patients with a meibomian gland dropout area of less than 50% had significant improvement of subjective symptoms, ocular surface inflammation and meibomian gland function after treatment. Patients with a meibomian gland dropout area of more than 70% showed no significant improvement before and after treatment. Conclusion: IPL/MGX can significantly improve the subjective symptoms and meibomian gland function of MGD patients with mild atrophy of the meibomian gland, alleviate the inflammation of the ocular surface, reduce the number of demodex mites, and relieve damage onthe ocular surface. Key words: intense pulsed light; meibomian gland expression; meibomian gland dysfunction; in vivo confocal microscopy

Meibomian gland (MG) dysfunction (MGD) is a multifactorial, chronic condition of the eyelids, leading to eye irritation, inflammation and ocular surface disease. Initial conservative therapy often includes a combination of warm compresses in addition to baby shampoo or eyelid wipes. The practice of lid hygiene dates back to the 1950s, when selenium sulfide-based shampoo was first used to treat seborrhoeic dermatitis of the eyelids. Today, tear-free baby shampoo has replaced dandruff shampoo for MGD treatment and offers symptom relief in selected patients. However, many will not achieve significant improvement on this therapy alone; some may even develop an allergy to the added dyes and fragrances in these products. Other manual and mechanical techniques to treat MGD include MG expression and massage, MG probing and LipiFlow(®). While potentially effective in patients with moderate MGD, these procedures are more invasive and may be cost prohibitive. Pharmacological treatments are another course of action. Supplements rich in omega-3 fatty acids have been shown to improve both MGD and dry eye symptoms. Tea tree oil, specifically the terpenin-4-ol component, is especially effective in treating MGD associated with Demodex mites. Topical antibiotics, such as azithromycin, or systemic antibiotics, such as doxycycline or azithromycin, can improve MGD symptoms both by altering the ocular flora and through anti-inflammatory mechanisms. Addressing and treating concurrent ocular allergy is integral to symptom management. Topical N-acetylcysteine and topical cyclosporine can both be effective therapeutic adjuncts in patients with concurrent dry eye. A short course of topical steroid may be used in some severe cases, with monitoring for steroid-induced glaucoma and cataracts. While the standard method to treat MGD is simply warm compresses and baby shampoo, a more tailored approach to address the multiple aetiologies of the disease is suggested.

PurposeTo make appropriate therapeutic decisions of intense pulsed light (IPL) for meibomian gland dysfunction (MGD) patients.MethodsSixty patients with MGD stage 2–3 were enrolled in IPL Group1 and Self-hygiene Group; 110 patients with MGD stage 3–4 were included in IPL + MGX Group and IPL Group2. Patients in IPL groups received IPL treatment once a month for three times. Meibomian gland expression (MGX) was combined with IPL treatment in IPL + MGX Group. Meibomian gland (MG) functions, MGD stage, associated ocular-surface indexes, and response rate were evaluated.ResultsPopulation characteristics and clinical conditions were comparable between groups. In patients with MGD stage 2–3, both IPL Group1 and Self-hygiene Group improved in MG functions, ocular surface disease index (OSDI) and tear break-up time (TBUT). No statistical difference was found in improvements. Posttreatment response rate was 64.3–66.7% in two groups. In patients with MGD stage 3–4, IPL + MGX Group achieved better improvements in MG expressibility and higher response rate (75.5%) than IPL Group2 (63.3%). Referring to IPL treatment, no statistical difference in MG functions and OSDI improvements was found among MGD patients with different ages, genders, and IPL energy exposure. Patients with higher Fitzpatrick scale improved more in MG expressibility.ConclusionSelf-eyelid hygiene is cost-effective for milder MGD stages. Combining MGX with IPL is necessary in more severe stages. Adult patients with all age and different genders can benefit from IPL treatment. Patients with darker skin can benefit more in expressiblity.

Purpose:To assess the therapeutic efficacy of a combinational therapy, including conventional treatment and intense pulsed light (IPL) technique on sleep quality of patients with meibomian gland dysfunction (MGD).Methods:Fifty participants with a clinical diagnosis of MGD were enrolled in this study. Participants underwent three sessions of IPL therapy. There was a 2-week interval between IPL sessions 1 and 2 and 1 month between sessions 2 and 3. Treatment was supplemented with conventional home-based therapy (including lid hygiene, warm compress, eyelid massage, and lid margin scrub) for MGD. Dry eye symptomatology, tear film, and ocular surface parameters were evaluated at baseline (day 0) and days 15, 45, and 75. Sleep quality was assessed before and after the study using Pittsburgh Sleep Quality Index (PSQI).Results:PSQI components improved significantly at day 75 in comparison with the baseline (all P < 0.05). Ocular Surface Disease Index (OSDI) score, noninvasive Keratograph tear break-up time (NIKBUT), fluorescein tear break-up time (FTBUT), meibomian gland expressibility, meibum quality score, and tear osmolarity improved at follow-up visits (P < 0.05). Younger patients showed more improvement in NIKBUT, sleep quality, and duration (P = 0.024, P = 0.047, and P = 0.008). Sleep latency decreased with increased NIKBUT and FTBUT and decreased OSDI score (P = 0.001, P = 0.005, and P = 0.041).Conclusions:The treatment of MGD is effective for improving sleep quality. Younger patients may preferentially benefit from the treatment.

Purpose: The aim of this study was to evaluate the different approaches used in the treatment of meibomian gland dysfunction (MGD). Materials and Methods: This open-label, single-center, prospective pilot study with a parallel-group design was conducted in February 2025. Ninety-two patients presenting to our clinic with symptoms and signs of MGD were enrolled and diagnosed according to Japanese MGD diagnostic criteria. Patients were assigned to five treatment groups: conservative management alone, conservative management plus intense pulsed light (IPL) therapy, conservative management plus oral azithromycin, conservative management plus oral doxycycline, and conservative management plus topical cyclosporine. Conservative management consisted of preservative-free artificial tears containing polyvinyl alcohol and povidone, warm compresses, and eyelid hygiene. Primary outcome measures included ocular surface parameters such as the Ocular Surface Disease Index (OSDI), tear break-up time (TBUT), Standard Patient Evaluation of Eye Dryness (SPEED) scores, and meibomian gland parameters evaluated using a slit-lamp examination. All parameters were assessed at baseline and during follow-up examinations after treatment initiation to observe changes in symptoms and signs. Results: A statistically significant increase was determined in meibum grade plugging (grades 0–3; higher = greater obstruction) and Marx line scores with IPL therapy (p < 0.05). The group receiving doxycycline treatment exhibited a significant improvement in OSDI and SPEED scores, plugging, TBUT, and meibum grades. The group receiving cyclosporine registered a significant improvement in OSDI and SPEED scores, plugging, TBUT, and meibum grades. A statistically significant increase was observed in the conservative treatment group in terms of lid margin irregularity, Marx line score, and OSDI and SPEED scores. In the group receiving azithromycin treatment, plugging, lid margin irregularity, TBUT, and OSDI and SPEED scores increased significantly. Compared with conservative care, the doxycycline group exhibited lengthened TBUT and lowered meibomian gland plugging and symptoms (p < 0.05), and the oral azithromycin group achieved a similar TBUT gain with slightly greater symptom relief. The topical cyclosporine group principally registered improved lid vascularity and meibum quality (p < 0.05), while the IPL group achieved the greatest overall improvements, reducing plugging and Marx line scores and adding ≈3 s to TBUT (p < 0.05 for all endpoints). Doxycycline exhibited notable short-term improvements, with 35.26% meibum grade improvement and a 40.48% foaming response, while IPL therapy demonstrated substantial OSDI improvements at 54.06%, with traditional parameters indicating limited treatment responsiveness. Conclusions: Various methods can be used in the treatment of MGD. All the conservative treatment methods used in this study were successful.

This systematic review finds a scarcity of RCT evidence relating to the effectiveness and safety of IPL as a treatment for MGD. Whether IPL is of value for modifying the symptoms or signs of evaporative dry eye disease is currently uncertain. Due to a lack of comprehensive reporting of adverse events, the safety profile of IPL in this patient population is also unclear. The current limitations in the evidence base should be considered by clinicians using this intervention to treat MGD, and outlined to individuals potentially undergoing this procedure with the intent of treating dry eye disease. The results of the 14 RCTs currently in progress will be of major importance for establishing a more definitive answer regarding the effectiveness and safety of IPL for treating MGD. We intend to update this review when results from these trials become available.

This study aimed to study the clinical effects and safety in terms of symptoms and signs and to evaluate the change in tear inflammatory cytokines in meibomian gland dysfunction (MGD) after 3 sessions of Intense Pulsed Light (IPL) in a prospective randomized double-masked sham-controlled clinical trial.� Patients with MGD who met all criteria were randomly assigned into IPL and sham-IPL group.�The stratified blocked randomization was�done using the�MGD gradeas a stratum�by�computer-generated assistance. Each patient in IPL group underwent 3 sessions of IPL on day 0, 15 and 45. The other group underwent sham-IPL. Both group received conventional treatment as warm compression, lid scrub and artificial tears. Primary outcome was tear film break-up time. Other clinical parameters included Ocular Surface Disease Index (OSDI), symptoms of dry eyes in visual analog scale score (VAS), tear film lipid layer thickness, meibography grade, ocular surface staining using NEI grading system, meibomian gland expressibility, meibum quality, tear osmoloarity, Schirmer's test and tear cytokines (IL-1Ra and IL-6). The parameters were evaluated on day 0, 15, 45, month 3 and 6. Subgroup analysis according to stage and patient's compliance to conventional treatment were analyzed. One hundred and fourteen patients were randomized and allocated into IPL and sham-IPL group. The tear film break-up time in IPL group was significantly more than that in sham-IPL group in all visits, in any stages and in any kinds of compliance (p&lt;0.001). The tear film break-up time increased at day 15, reached its maximum at day 45 and persisted at least six months. The meibum quality score and meibum expressibility in IPL group was significantly better than that in sham-IPL group in all visits (p&lt;0.001). Patients who were not strictly complied with the warm compression and lid scrub could have their meibum qualities and expressibilities improved by IPL. Ocular surface staining and meibography grade in IPL group significantly improved more than that in sham-IPL group in stage 4 (p&lt;0.05). However, tear osmolarity, Schirmer's test, IL-1Ra and IL-6 levels were not statistically different between two groups. No adverse event occurred in IPL group. In conclusion, our study suggests that IPL is effective and safe to manage patients with meibomian gland dysfunction especially in stage 4 of the disease.

To investigate the changes in meibomian gland dysfunction (MGD) and tear matrix metalloproteinase-9 (MMP-9) levels in patients with moderate-to-severe MGD after combined treatment with intense pulsed light (IPL) therapy and cyclosporine 0.05%. Thirty-six patients concurrently treated with IPL and cyclosporine 0.05% ophthalmic drops were retrospectively enrolled. Tear break up time (TBUT), corneal and conjunctival staining scores, Schirmer test, and ocular surface disease index (OSDI) questionnaire responses were recorded. Meibum quality, consistency, and eyelid margin telangiectasia were evaluated. MMP-9 levels were examined by the positivity and signal intensity of red lines (scored 0-4). IPL was performed four times with a vascular filter at 2-week intervals, followed by a 1-month follow-up after treatment cessation. Immediately after each IPL treatment, gentle meibomian gland expression was performed in both the upper and lower eyelids using meibomian gland expressor forceps. TBUT (1.88 ± 1.02s to 3.12 ± 1.08s, p < 0.001), corneal and conjunctival staining (6.19 ± 2.11 to 3.12 ± 1.89, p < 0.001), Oxford staining grade (2.66 ± 0.89 to 1.35 ± 0.76, p < 0.001), and OSDI (52.97 ± 21.86 to 36.36 ± 22.45, p < 0.001) scores significantly improved after the combined treatment. Meibum quality, consistency and lid margin telangiectasia showed significant post-treatment improvement in both the upper and lower eyelids. MMP-9 positivity showed a significant decrease (97-69%, p = 0.026) with a reduction in signal intensity (2.72 ± 0.87 to 2.09 ± 0.95, p = 0.011). The combination of IPL therapy and 0.05% cyclosporine eye drops effectively treats moderate-to-severe MGD by reducing symptoms and signs of MGD and by decreasing ocular surface MMP-9-associated inflammation.

Purpose:To compare the efficacy of physiological, non-detergent eyelid wipes with conventional lid hygiene in patients with meibomian gland dysfunction (MGD).Methods:Fifty participants with MGD were recruited and randomized into two groups. Participants in group I used Evolve Pure™ Eyewipes twice a day to clean the eyelid debris along with standard therapy (antibiotic and lubricants) and participants in group II followed lid hygiene with warm compresses along with standard therapy. Symptoms, ocular surface assessment (lipid layer thickness, tear meniscus height, non-invasive tear film breakup time, and meibography), slit-lamp biomicroscopy (eyelash contamination, meibomian gland blockage, meibomian gland secretion, and meibomian gland telangiectasia) and tear film osmolarity were noted at baseline and 90 days after therapy.Results:Significant improvement in symptoms and signs of MGD was observed in both groups after treatment (P < 0.001); however, the clinical improvement was better with the use of eyelid wipes. Lipid layer thickness increased significantly in group I (P = 0.0006) and group II (P = 0.0002), which was maintained even after adjusting for sociodemographic variables such as age, sex, and severity score of symptoms and signs.Conclusion:Lipid layer thickness of the tear film is a sensitive marker in monitoring response to treatment in patients with MGD. The use of physiological detergent-free eyelid wipes is non-inferior to lid hygiene and warm compresses, which remains the mainstay for treatment of MGD; the clinical improvement with eyelid wipes was noted to be better.

To compare the anti-inflammatory effects of intense pulsed light (IPL) with tobramycin/dexamethasone plus warm compress through clinical signs and cytokines in tears. Eighty-two patients with dry eye disease (DED) associated meibomian gland dysfunction (MGD) were divided into two groups. Group A was treated with IPL, and Group B was treated with tobramycin/dexamethasone plus warm compress. Ocular Surface Disease Index (OSDI), tear film breakup time (TBUT), corneal fluorescein staining (CFS), meibomian gland expressibility (MGE), meibum quality, gland dropout and tear cytokine levels were evaluated before treatment, 1wk and 1mo after treatment. TBUT in Group A was higher (P=0.035), and MGE score was lower than Group B at 1mo (P=0.001). The changes of interleukin (IL)-17A and IL-1β levels in tears were lower in Group A compared with that in Group B at 1wk after treatment (P=0.05, P=0.005). Treatment with IPL can improve TBUT and MGE and downregulate levels of IL-17A and IL-1β in tears of patients with DED associated MGD better than treatment with tobramycin/dexamethasone plus warm compress in one-month treatment period.