Meibomian gland dysfunction (MGD: Meibomian Gland Dysfunction) is a chronic, diffuse functional abnormality of the meibomian glands. The MGD Working Group in Japan (2010) defined it as “a condition in which the function of the meibomian glands is diffusely impaired due to various causes, accompanied by chronic discomfort”4). The “Clinical Practice Guidelines for Meibomian Gland Dysfunction” (Journal of the Japanese Ophthalmological Society, Vol. 127, No. 2), published in 2023, positioned MGD as the main cause of evaporative dry eye and provided evidence-based, comprehensive clinical guidance3).
Internationally, the International Workshop on Meibomian Gland Dysfunction (IWMGD 2011) defines MGD as “a chronic, diffuse abnormality of the meibomian glands, commonly characterized by terminal duct obstruction and/or qualitative or quantitative changes in glandular secretion”1), 10). TFOS DEWS III (2025) also identifies MGD as a major contributing factor to dry eye disease, and treatments such as warm compresses, eyelid hygiene, IPL (intense pulsed light), and low-level laser therapy are included in its management algorithm8). The Dry Eye Society of Japan has established the “Dry Eye Clinical Practice Guidelines” (2019), which emphasizes MGD as a cause of evaporative dry eye9).
Meibomian glands are a type of large sebaceous gland located within the tarsal plates of the eyelids. When observed with non-contact meibography, normal eyes have 25–30 meibomian glands in the upper eyelid and 15–20 in the lower eyelid5). Each gland has numerous acini branching from a central duct, and meibocytes (acinar epithelial cells) produce meibum through holocrine secretion. Meibum contains over 100 types of lipids (mainly wax esters, cholesterol esters, polar phospholipids, and sphingolipids) and over 90 types of proteins, forming the lipid layer—the outermost layer of the tear film—which prevents evaporation of the aqueous layer and lowers surface tension to maintain tear film spread1). Normal lipid layer thickness (LLT) is 60–100 nm, and it becomes thinner in MGD1).
According to the Japanese Ophthalmological Society Guidelines 2023 BQ-4, which cites a population-based study in Japan (subjects aged 6–96 years), the age-specific prevalence of MGD is as follows3).
| Age group | MGD prevalence |
|---|---|
| ≤19 years | 0% |
| 20s | 11.8% |
| 30s | 5.6% |
| 40s | 21.6% |
| 50s | 32.8% |
| 60s | 41.9% |
| 70s | 48.4% |
| 80s | 63.9% |
Many studies have shown that MGD increases and worsens with age. By sex, it is more common in men and postmenopausal women3). Using non-contact meibography, Arita et al. reported that approximately 86% of dry eye patients have concurrent MGD5). Racial differences have also been noted, with higher prevalence rates (3.5–19.9%) reported in Asians than in Caucasians1). In Japan, the Dry Eye Society estimates that tens of millions of people, including potential patients, are affected, making it one of the most frequently encountered chronic diseases in daily clinical practice3).
The classification of MGD by the Japanese MGD Working Group is as follows4).
Clinically, the hyposecretory type is more common, among which obstructive MGD (oMGD) is the most prevalent. The Japanese Ophthalmological Society Guidelines 2023 BQ-1 summarizes the main pathophysiology of hyposecretory MGD as “hyperkeratinization of the ductal epithelium and atrophy of the acini”3). Atrophic MGD is a condition in which the acini are diffusely atrophied, and both mechanisms of secondary obstruction and primary acinar cell damage have been proposed.
The hypersecretory type of MGD includes seborrheic MGD (sMGD), which is recognized in contrast to obstructive MGD. When the tarsal portion of the upper eyelid is gently compressed, transparent meibum is released in normal individuals, but in seborrheic MGD, secretion is abnormally increased and foam formation is observed in the tear film along the lower eyelid margin. Related conditions include posterior blepharitis, meibomitis, and meibomitis-related keratoconjunctivitis (MRKC), and the Japanese Ophthalmological Society Guidelines 2023 BQ-3 emphasizes the importance of unifying these concepts3).
Internationally, the IWMGD 2011 classifies MGD into low-delivery and high-delivery types, with the obstructive type being the most common among the low-delivery type1).
MGD is the most common cause of evaporative dry eye. When meibomian gland dysfunction thins the tear lipid layer, tear evaporation increases, tear osmolarity rises, and ocular surface inflammation develops. The Japanese Ophthalmological Society Guidelines 2023 also clearly state that MGD leads to dry eye and causes chronic ocular discomfort.
The Japanese Ophthalmological Society Guidelines 2023 CQ-2 lists the following subjective symptoms of MGD and strongly recommends eliciting them during history taking3).
A sticky sensation, often described as a “sticky or gooey feeling,” is also characteristic4). Symptoms are often more pronounced in the morning, and some patients report fluctuations in visual function. However, no specific subjective symptoms that reliably distinguish MGD from other ocular surface diseases have been identified to date3). The OSDI (Ocular Surface Disease Index) questionnaire is widely used to assess subjective symptoms. Since MGD symptoms significantly affect quality of life and cause not only ocular irritation but also decreased visual function, it is important to systematically evaluate the degree of impairment in daily activities1).
The Japanese Ophthalmological Society Guidelines 2023 CQ-3 recommends the following four findings as useful for diagnosing MGD: meibomian gland orifice obstruction, eyelid margin vascular dilation, displacement of the mucocutaneous junction, and eyelid margin irregularity3).
Eyelid Margin Findings
Orifice obstruction findings: plugging, pouting (pointed elevation around the orifice), and ridge (embankment-like structure covering multiple orifices) are observed.
Eyelid margin vascular dilation: Capillary dilation and telangiectasia around the orifices.
Displacement of the mucocutaneous junction (MCJ): Anterior or posterior deviation. Easily observed with fluorescein staining.
Eyelid margin irregularity: Irregularities of the line that contacts the cornea.
Meibomian gland assessment
Meibum appearance: Normally a clear oil. In MGD, it appears cloudy, granular, or toothpaste-like.
Shimazaki classification: Expressibility is graded 0–3 with moderate thumb pressure; grade 2 or higher is considered abnormal.
Meibography: An infrared camera is used to observe gland dropout, shortening, and distortion.
Thinning of the tear film lipid layer: Lipid layer thickness (LLT) can be assessed with an interferometer.
The Shimazaki meibum grade is evaluated in four grades as follows4), 12).
The non-contact meibography developed by Arita et al. in 2008 is a minimally invasive device that simply attaches an infrared transmission filter (700–850 nm) and a small infrared CCD camera to a slit lamp microscope5), 11). Infrared light passes through the tarsal plate and is reflected by meibum, allowing the meibomian glands to be observed as hyper-reflective (white) structures. In patients with MGD, various findings such as meibomian gland dropout, shortening, tortuosity, mottling, and dilation are observed in combination5).
The degree of gland dropout is classified into the following four grades according to the Arita meiboscore5).
| Meiboscore | Gland dropout area |
|---|---|
| grade 0 | No dropout |
| grade 1 | One-third or less of the total area |
| grade 2 | One-third to two-thirds |
| grade 3 | 2/3 or more |
It has been reported that contact lens wearers have more meibomian gland dropout than non-wearers. The changes become more pronounced with longer years of wear, and are observed with both soft and hard contact lenses16).
JOS Guidelines 2023 BQ-5 and BQ-6 systematically organize the factors related to the development of MGD3).
Aging and Hormonal Factors
Ocular factors and external factors
Systemic diseases
Demodex infection
Demodex folliculorum inhabits the eyelash roots, while Demodex brevis resides in the meibomian and sebaceous glands1). The infestation rate increases with age, reaching 100% in individuals aged 70 and older1). In a cohort study of 150 cases, Demodex was detected in 90% of patients with anterior blepharitis and 60% of patients with MGD1). D. folliculorum directly damages hair follicle basal cells, causing reactive hyperkeratinization and forming cylindrical dandruff. D. brevis physically obstructs the meibomian glands, induces granulomatous reactions, and promotes chalazion development1). Demodex also triggers inflammation as a bacterial vector and can cause delayed-type hypersensitivity reactions in patients with rosacea1). Zhang et al. reported a case of MGD in a 46-year-old man in whom 15 Demodex brevis organisms were detected in expressed meibum despite unremarkable external findings, demonstrating the utility of direct meibum microscopy6).
The Japanese Ophthalmological Society Guidelines GL 2023 clearly state that soft contact lens wear is a risk factor for MGD. Mechanical friction during blinking may cause shortening and loss of meibomian glands and obstruction of the gland openings. MGD may also be a cause of CL intolerance, and MGD treatment may improve wearing comfort.
The diagnostic criteria for hyposecretory MGD proposed by the Japanese MGD Working Group in 2010 require all three of the following items to be positive4). The Japanese Ophthalmological Society Guidelines GL 2023 CQ-1 also state that these criteria are widely used in Japan3).
| Item | Content |
|---|---|
| 1. Subjective symptoms | Ocular discomfort, foreign body sensation, dryness, feeling of pressure, etc. |
| 2. Abnormal findings around the orifice | One or more positive findings among vascular dilation, displacement of the mucocutaneous junction, and irregularity of the eyelid margin |
| 3. Findings of orifice obstruction | Satisfies both obstructive findings such as plugging/pouting/ridge and reduced expressibility of Shimazaki grade 2 or higher |
The examinations recommended by the Japanese Ophthalmological Society Guideline 2023 are as follows3).
In vivo confocal microscopy (CQ-11), tear evaporation rate measurement (CQ-10), tear inflammatory biomarkers (CQ-15), bacteriological examination (CQ-16), and biochemical analysis of meibum (CQ-14) have not yet been recommended as routine tests3). Elevated tear levels of IL-1α, IL-1β, and MMP-9 are important in terms of pathophysiology, but standardized testing equipment and conditions are lacking, preventing clinical application1).
In outpatient clinics in Japan, incorporating non-contact meibography into the slit-lamp microscope workflow is recommended5).
This series of tests is usually completed within 3–5 minutes and places little burden on the patient. Meibography provides visual feedback to the patient, which helps improve motivation for treatment5).
In the 2023 JOS Guideline, 13 CQs (CQ-18 to CQ-30) evaluate MGD treatment based on evidence 3). There is no single gold-standard treatment; a stepwise and combined approach is fundamental 1). The Japanese Dry Eye Clinical Practice Guideline 2019 also identifies MGD as the main cause of evaporative dry eye and presents a treatment algorithm with warm compresses and lid hygiene as first-line therapy 9). The TFOS DEWS III Management and Treatment Report (2025) proposes stepwise management for MGD combining warm compresses, in-office device treatments, IPL, low-level light therapy (LLLT), lid scrub, anti-Demodex therapy, and blepharoexfoliation 8).
Conservative Treatment (First-Line)
Warm compress therapy: Strongly recommended in Japanese Ophthalmological Society Guidelines 2023 CQ-18. Raises eyelid temperature above the meibum melting point to promote secretion. It is recommended to use a commercially available warm eye mask for 5 minutes or more twice daily.
Eyelid hygiene: Weakly recommended in CQ-19. Clean the eyelid margins with a water-moistened cotton ball or a commercially available eyelid cleansing product. Daily continuation is the general principle.
Meibum expression: Weakly recommended in CQ-20. Performed as an outpatient procedure using Arita-style meibomian gland expression forceps at intervals of 10 days to 1 month. Obstructive MGD is a good indication.
Artificial tears: Used for tear supplementation and ocular surface moisturization.
Pharmacotherapy (note insurance coverage)
Azithromycin hydrate ophthalmic solution: Weakly recommended in CQ-22, but not covered by insurance in Japan. Improves subjective symptoms, eyelid margin findings, and meibum grade.
Tetracycline oral therapy: Weakly recommended in CQ-27, not covered by insurance. The regimen used is doxycycline 100 mg twice daily, tapered over 3–4 months.
Corticosteroid eye drops: Weakly recommended in CQ-24. In Japan, insurance coverage applies only when complicated by blepharitis. 0.1% fluorometholone or similar is used concomitantly for a short period.
Omega-3 fatty acid oral supplementation: Weakly recommended in CQ-26. Treated as a supplement in Japan and not covered by insurance.
| Treatment | CQ | Strength of recommendation | Japanese insurance coverage |
|---|---|---|---|
| Warm compress | CQ-18 | Strongly recommended | Covered |
| Eyelid cleansing | CQ-19 | Weakly recommended | Applicable |
| Meibum expression | CQ-20 | Weakly recommended | Eye procedure |
| Diquafosol eye drops | CQ-21 | Not recommended (weak) | Not applicable |
| Azithromycin eye drops | CQ-22 | Weakly recommended | Off-label |
| Steroid eye drops | CQ-24 | Weakly recommended | Only when accompanied by blepharitis |
| Cyclosporine A eye drops | CQ-25 | Do not perform (weak) | Not indicated |
| Oral omega-3 | CQ-26 | Weakly recommended | Supplement |
| Oral antibiotics | CQ-27 | Weakly recommended | Not indicated |
| IPL | CQ-28 | Weakly recommended | Unapproved |
| Thermal pulsation | CQ-29 | Weakly recommended | Off-label |
| Probing | CQ-30 | Not performed (weak) | Not applicable |
Intense pulsed light (IPL) therapy (Japanese Ophthalmological Society Guidelines 2023 CQ-28): A broadband high-intensity non-laser light of 500–1200 nm is applied around the eyelids1), 8). Light energy absorbed by oxyhemoglobin in blood vessels on the skin surface generates heat, inducing thermal coagulation of abnormal blood vessels, bacterial reduction, Demodex elimination, meibum liquefaction, suppression of epithelial turnover, fibroblast activation, and promotion of collagen synthesis1). An RCT of 88 eyes reported that three consecutive sessions (at 4-week intervals) significantly reduced tear fluid IL-17α and IL-6 levels1). Multiple RCTs have shown improvement in subjective symptoms, meibomian gland orifice findings, meibum grade, BUT, and corneal epithelial damage. Although the evidence strongly supports its use, it is unapproved and not covered by insurance in Japan at the time of manuscript preparation, so Japanese Ophthalmological Society Guidelines 2023 gives only a weak recommendation3). Adverse events include eyelid redness and swelling in up to 13%, all mild and reversible1).
Thermal pulsation therapy (LipiFlow, etc.) (CQ-29): LipiFlow® (TearScience) is a vectored thermal pulsation (VTP) device that simultaneously applies 42.5°C heating from the palpebral conjunctival side and distal-to-proximal pulsatile compression from the external eyelid side for 12 minutes1). It is the only device that applies heat directly to the inner surface of the tarsal plate, raising upper eyelid temperature from 36.9°C to 41.1°C and lower eyelid temperature from 37.0°C to 42.0°C1). A single treatment significantly improves meibum secretion score, OSDI, SPEED, and TBUT at 1 month, with long-term results persisting for 3 years1). In an RCT of 400 eyes, a single LipiFlow treatment was significantly superior to warm compress twice daily for 10 minutes plus eyelid hygiene, and 86% required no additional treatment at 12 months1). Its efficacy has been confirmed to be equal or superior to a 3-month course of oral doxycycline1). The new semi-transparent activator (Activator Clear) facilitates confirmation of placement position, with a reported 100% treatment completion rate2). In Japan, this treatment is not covered by insurance. A similar device, MiBo Thermoflo®, heats via an external paddle at 42.2°C but has a smaller effect on eyelid temperature elevation1).
Intraductal probing (CQ-30): A Maskin probe (1 mm → 4/6 mm, stepwise) is inserted into the obstructed duct to mechanically reopen it1). In a cohort of 25 patients, 96% obtained immediate symptom relief, but in a 49-patient RCT, improvement in objective findings was limited1). Because the procedure is invasive and offers little improvement in objective findings, the Japanese Ophthalmological Society Guideline 2023 gives a “weak recommendation against performing” this procedure3).
The main procedures performed in the outpatient setting are as follows.
Tetracyclines: Doxycycline and minocycline are more lipophilic than tetracycline and accumulate in ocular tissues and eyelids at low doses1). They are used primarily for anti-inflammatory rather than antimicrobial effects, controlling inflammation through suppression of MMP-8, MMP-9, TNF-α, inhibition of lipase production, and reduction of free fatty acid production1). A 60-patient RCT reported that the minocycline combination group showed significant improvement in all clinical parameters and in IL-6, IL-1β, IL-17α, TNF-α, and IL-12p70 compared to the control group1), 13). Side effects include photosensitivity and gastrointestinal symptoms; it is contraindicated in pregnant women and children14).
Azithromycin: A macrolide that binds to the 50S ribosomal 23S rRNA and inhibits bacterial protein synthesis. In addition to antimicrobial effects, it suppresses expression of NF-κB, IL-6, IL-8, TNF-α, and MMP-9 and induces anti-inflammatory TGF-β11). A 1% ophthalmic formulation (AzaSite®, United States) is available for topical use, with reported therapeutic effects persisting for 3 months after short-term administration. Oral azithromycin regimens include 500 mg daily for 3 days, repeated for 3 cycles (7-day intervals), or 1 g once weekly for 3 weeks. However, there is a risk of QT prolongation, requiring caution in patients with a history of cardiac disease1).
Cyclosporine A 0.05% ophthalmic solution: Approved in the United States as Restasis® for aqueous-deficient dry eye. It exerts anti-inflammatory effects by inhibiting T-cell IL-2 production1). Efficacy for MGD alone is limited, and the JOS Guideline 2023 weakly recommends against its use3).
Lifitegrast 5.0% ophthalmic solution: An LFA-1 antagonist approved by the US FDA for dry eye. Dedicated evidence for MGD has not been established1).
Oral omega-3 fatty acids: Supplementation with EPA/DHA alters the fatty acid composition of meibum1). The DREAM study (n=499) reported in 2018 that there were no significant differences in OSDI, Schirmer test, or tear break-up time between the omega-3 and control groups, and the evidence is conflicting1). The JOS Guideline 2023 weakly recommends their use, considering that omega-3 fatty acids are classified as supplements in Japan3).
Demodex infection increases with age and reaches 100% in those aged 70 and older1). Demodex folliculorum parasitizes the eyelash roots, while Demodex brevis parasitizes the meibomian glands and sebaceous glands. The former causes reactive hyperkeratinization and forms cylindrical dandruff, while the latter causes gland obstruction and granulomatous reactions1).
Tea tree oil (TTO: derived from Melaleuca alternifolia) is effective for demodicidal treatment1). Specifically, a protocol using 50% TTO lid scrub in the clinic once a week and 10% TTO at home daily for one month has been reported to reduce eyelid margin inflammation, decrease tear fluid IL-1β and IL-17 levels, and improve ocular surface irritation symptoms1). The primary acaricidal component of TTO is terpinen-4-ol, and commercial products such as Cliradex® are available1). A single oral dose of ivermectin 200 μg/kg (day 0 and day 7) has also been reported to improve Demodex counts, Schirmer test, and BUT in refractory posterior blepharitis1).
Zhang et al. reported a case of a 46-year-old male with MGD who had few external findings and no Demodex detected by eyelash epilation testing, in which 15 D. brevis organisms were directly detected in expressed meibum after lid margin disinfection, and symptoms improved with TTO lid scrub6). This is an important case demonstrating that direct meibum microscopy is useful for detecting Demodex.
The diagnostic criteria of the Japanese MGD Working Group 2010 require all three of the following items to be positive: (1) subjective symptoms such as ocular discomfort, (2) abnormal findings around the orifices (one or more of vascular dilation, MCJ migration, and irregular lid margin), and (3) findings of orifice obstruction (both plugging and reduced meibum expression of grade 2 or higher on the Shimazaki scale). The Journal of the Japanese Ophthalmological Society Guideline 2023 recommends performing meibography and meibum observation.
Wet a clean towel and warm it in the microwave, or apply a commercially available heated eye mask to both eyes for 5–10 minutes. It is important to keep the eyelid temperature at around 40°C; note that a hot towel tends to cool down due to evaporative heat loss. The Japanese Ophthalmological Society Guidelines 2023 (CQ-18) recommend continuing this for 5 minutes or more twice daily. Gently massaging the eyelids after warming promotes the expression of liquefied meibum.
The Japanese Ophthalmological Society Guidelines 2023 (BQ-1) summarizes the main pathophysiology of hyposecretory MGD as “hyperkeratinization of the ductal epithelium and atrophy of the acini”3). It states that acinar atrophy can occur not only secondary to meibomian gland obstruction but also as a result of primary damage to acinar cells due to aging and other factors.
Progression from Ductal Obstruction to Acinar Atrophy
Hyperkeratinization of the ductal epithelium and increased viscosity of meibum cause obstruction of the terminal ducts1). Obstruction leads to increased intra-acinar pressure, which progresses to acinar atrophy and loss. The loss of acini reduces lipid secretion, resulting in thinning of the tear film lipid layer.
Elevated Melting Point of Meibum
Normal meibum has a melting point of approximately 19–32°C and remains fluid at ocular surface temperatures of 33–37°C1). In MGD, increased sphingolipids such as ceramide raise the melting point of meibum, and in severe cases, it will not liquefy unless heated above 40°C1). This is the therapeutic rationale for warm compresses and thermal pulsation.
Influence of sex hormones
Androgens activate lipid synthesis genes and suppress keratinization-related genes in meibocytes (meibomian gland cells)1). Androgen deficiency, receptor dysfunction, and anti-androgen drug use are associated with obstructive MGD. Estrogen, on the other hand, promotes lipid catabolism and stimulates the production of inflammatory cytokines such as IL-6 and TNF-α1). The association between postmenopausal hormone replacement therapy and dry eye is partially explained by reduced adrenal androgen production due to suppression of the hypothalamic-pituitary-adrenal axis1).
Contribution of bacteria and inflammation
Lipases produced by commensal bacteria (mainly Staphylococcus) on the eyelid margin degrade meibum lipids, and the increase in free fatty acids triggers inflammation1). Increased lipase activity and matrix metalloproteinase (MMP) production have been confirmed in patients with blepharitis. In the tear fluid of MGD patients, concentrations of IL-1α, mature IL-1β, MMP-9, IL-6, IL-8, and TNF-α are elevated and correlate with the severity of ocular surface epithelial damage1). IL-1 promotes epithelial cell proliferation and hyperkeratinization, forming a vicious cycle in obstructive MGD.
PPAR-γ (peroxisome proliferator-activated receptor γ) belongs to the nuclear receptor superfamily and, as a transcription factor, is involved in lipid synthesis and meibocyte differentiation. It is thought to play an important role in cell differentiation and lipid synthesis in meibocytes and is attracting attention as a target for elucidating the pathophysiology of MGD3).
Sphingolipids and Melting Point
In MGD, the proportion of ceramides and sphingolipids in meibum increases, reducing the stability of the meibum lipid film1). The elevated ceramide content directly raises the melting point of meibum, creating a state where it does not liquefy unless heated to 40°C or above. Sphingolipids not only alter the physicochemical properties of meibum but also regulate cellular processes including cell proliferation, differentiation, apoptosis, and inflammation, further complicating the pathology of MGD1).
Diabetes and Ocular Surface Changes
Type 2 diabetes is an exacerbating factor for MGD. A cross-sectional study of 302 eyes by Hao et al. reported that the DED-DM group showed significantly worse upper lid margin irregularity, lid margin vascular dilation, orifice plugging grade, lid margin thickening, upper meibomian gland dropout, ciliary injection, and noninvasive tear breakup time (NIBUT) compared to the DED-only group, and that blood glucose levels showed a significant correlation with NIBUT, lid margin thickening, and lid margin irregularity7). A pathological mechanism involving chronic inflammation and microvascular damage affecting the lid margin and glandular tissue has been proposed.
LipiFlow Translucent Activator: LipiFlow’s new semi-transparent activator (Activator Clear) uses a translucent material that makes it easier to confirm the positioning, and Hu et al. reported a 100% treatment completion rate2). Improvements in subjective symptoms and meibum scores were confirmed up to 3 months after treatment. In a long-term observational study by Blackie et al., a single LipiFlow treatment sustained improvements in meibum secretion and dry eye symptoms for 12 months, with 86% not requiring additional treatment15).
Intranasal neurostimulation: Pulsed stimulation of the anterior ethmoidal nerve in the nasal cavity induces lacrimal gland secretion via the nasolacrimal reflex pathway. In animal experiments, daily stimulation for 3 minutes per day over 3 weeks increased tear volume, lipid and protein concentrations, and decreased tear osmolarity1). In human RCTs, the Allergan TrueTear® Intranasal Tear Neurostimulator (ITN) has been reported to induce conjunctival goblet cell degranulation, elevation of tear meniscus height, elevation of meibomian gland temperature in the central lower eyelid, and increased tear film lipid layer thickness1). A non-randomized open-label study also reported improvements in Schirmer values, keratoconjunctival staining, and subjective symptoms with use 4 or more times daily for 180 days1). Findings also show that intranasal stimulation induces immediate changes in meibomian gland morphology (area and perimeter), suggesting a new therapeutic strategy for promoting meibum secretion through neuromodulation1).
Sex hormone therapy: Schiffman et al.’s multicenter randomized trial reported at the ARVO abstract stage that topical testosterone ophthalmic solution (0.03%) significantly improved meibomian gland secretion viscosity compared to the control group after 6 months of treatment1). Some studies have shown that topical androgens increase tear lipid layer thickness and tear break-up time, but currently no approved ophthalmic product exists in Japan, the United States, or elsewhere1). The application of 5% testosterone cream in menopausal women (improving OSDI), transdermal DHEA in postmenopausal patients, and ophthalmic applications of hormone replacement therapy have also been discussed, but all lack sufficient evidence and have not been introduced into routine clinical practice1).
IL-1 receptor antagonist (Anakinra): Recombinant human IL-1RA (Kineret™) is a biologic agent approved for rheumatoid arthritis and has shown efficacy in off-label use for dry eye disease1). Since IL-1 in the tears of MGD patients plays a central role in pathogenesis, it represents a promising therapeutic target, but clinical trial results for MGD have not yet been published1).
IPL-Induced Changes in Gland Morphology: A 35-patient cohort study reported that IPL induced an increase in acinar longest diameter and unit density, and reduced inflammatory cells around the glands1). This suggests a potential tissue repair effect beyond mere symptomatic treatment.
Meibomian Gland Gene Expression Profile: Over 400 gene expression changes have been reported in the meibomian glands of patients with MGD. Androgen-responsive genes, keratinization-related genes, and lipid synthesis-related genes are considered major targets, and the potential for molecular-targeted therapy is being explored1).
Mibo Thermoflo®, IRPL, and Low-Level Laser: Comparative trials of novel devices such as external heating devices, IRPL (broadband light), and low-level laser are ongoing, but no device has been reported to demonstrate superior efficacy compared to LipiFlow at this time1).
The 2023 Japanese Ophthalmological Society Clinical Guidelines also pointed out the limitations of evidence across many clinical questions, and accumulating evidence through Japan-led RCTs is considered a future challenge3). In particular, there is a need for: establishing standardized protocols for conservative treatments feasible in Japan (warm compresses, eyelid hygiene, meibum expression); domestic trials to expand insurance coverage for doxycycline, azithromycin, and other drugs; and multicenter trials toward regulatory approval of IPL and LipiFlow.
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Hu JG, Dang VT, Chang DH, et al. Performance of a Translucent Activator for LipiFlow Vectored Thermal Pulse (VTP) Treatment of Meibomian Gland Dysfunction. Clin Ophthalmol. 2022;16:963-971.
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