However, achieving this through prescribing topical antibiotic drops or ointment such as fusidic acid alone is not commonly recommended over the longer term, but is adopted by some practitioners  and a short dose of a topical antibiotic has been recommended in consensus-based reports . A recent Level 2 study demonstrated that an ofloxacin-based ointment was valuable in the management of patients with obstructive MGD.
Topical azithromycin a macrolide antibiotic has been used in the management of DED, but it is believed to have an anti-inflammatory action rather than simply reducing the bacteria lid flora see Section 4. More Level 1 studies are required to examine the potential for prescribing topical antibiotics alone in managing DED. Demodex infestation is a causative factor in many cases of intractable blepharitis and is often associated with dry eye symptoms , although there is currently no evidence to show a direct association with the development of MGD .
Historically, the treatment of ocular Demodex included a wide variety of products, most of which had no high level evidence to support their use. More recently, appropriate management has been found with the use of topical products containing tea-tree oil or oral ivermectin, as summarized in Table 6 [—].
Tea tree oil TTO is a natural, essential oil from steamed Melaleuca alternifolia leaves from the narrow-leaved Paperbark or Tea tree, which is native to Australia that exhibits antimicrobial, anti-inflammatory, antifungal, and antiviral properties , and is toxic to Demodex . However, TTO can be toxic to the eye and causes ocular stinging and irritation if used in its pure form. These reduce the risk of toxicity to the ocular surface compared with using stronger concentrations of TTO. Several studies have shown a considerable reduction in the number of Demodex on the eyelashes after treatment with TTO [,,,,].
To date, very limited information exists in relation to the positive impact of TTO on dry eye symptoms and signs , and more studies are needed on this topic. Ivermectin is a broad-spectrum antiparasitic drug primarily used to treat strongyloidiasis and control onchocerciasis. It is a low cost, single dose medication that is very well tolerated by patients.
One oral dose of ivermectin has been shown to successfully reduce the number of Demodex found adjacent to the lashes of patients with blepharitis [,]. Performance has been improved by combining the use of ivermectin with metronidazole , or with permethrin cream . More studies are needed to confirm the role of ivermectin for treating DED symptoms and signs. Thus, there exists a significant role for conventional treatments in the management of MGD, including ocular lubricants, lid hygiene and warm compresses. As MGD results in decreased lipid layer thickness, it may be beneficial to replace the lipids with ocular lubricant eye drops or sprays that contain lipids.
A number of studies have found an improvement in signs and symptoms with the use of lipid-based drops in dry eye Table 7 [65,,,,,—]. A Level 1 study has confirmed increased lipid layer thickness grade and NIBUT in normal eyes treated with a liposomal spray . To enhance the potential performance of lipid-based drops, nano-technology concepts have been incorporated into lipid emulsion eye drops [,]. Despite the proven efficacy of warm compresses in many clinical studies, compliance is often poor due to the time required and the difficulty in maintaining the temperature of the compress for an extended period of time [,,—].
One method to extend the length of time over which a facecloth can retain heat is to wrap several cloths around each other in a bundle format . The ability for heat from a warm compress to soften or liquefy the secretions in obstructed glands in the case of MGD is supported by Level 2 and 3 evidence [—]. The temperature and time required for melting obstructive material within the meibomian gland excretory duct has not been definitively established.
Meibomian gland material causing severe obstruction has a higher melting point than material from less obstructed glands [,,]. Arita and colleagues evaluated the impact of 5 commercially available eyelid-warming devices in 10 subjects with MGD and 10 controls over a 2—4 week period .
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The 5 devices consisted of 2 dry non-moist methods and 3 moist methods. A single application of all 5 devices improved symptom scores, increased TBUT and increased ocular surface temperatures, but only for up to 30 min. Their results showed that repeated eyelid warming with a non-moist device improved tear film function in normal individuals and may have beneficial effects on both tear film and meibomian gland function in MGD patients.
They concluded that repeated non-moist warming for 2 weeks or 4 weeks was required to achieve a stable improvement in normals and in those with MGD respectively . Optimal contact between the compress and eyelid should be achieved and the compresses should be replaced every 2 min to ensure the temperature is maintained .
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Several preliminary studies on non-dry eye participants have investigated the effect of different warm compresses on eyelid temperature [,]. All of the compresses showed an increase in temperature at the lower lid conjunctival surface and none caused any damage to the eyelids. This study concluded that a wet surface improved heat transmission through the lid and should be used versus dry treatments .
Fortunately, a safeguard is the individual's pain response, that protects against extensive thermal damage to the eyelid skin as a patient will not tolerate a cloth that is excessively hot . If eye rubbing occurs when the corneal temperature is elevated, corneal deformation and visual blur can result . The risks of ocular massage with elevated corneal temperature have been deemed to require patient instruction on how to optimally perform the procedure [,].
A study of subjects with MGD showed that 12 weeks of lid warming therapy resulted in a therapeutic benefit, with excess ocular surface phospholipase activity which is detrimental to tear film stability being reduced . In addition to homemade compresses, a wide variety of devices are now commercially available for the management of lid anomalies that will raise the lid temperature for a longer period of time [,].
A moistened insert is placed into each sealed watertight chamber to provide a warm, high humidity environment over each eye. Decreased acinar diameter and area were also observed in individuals unresponsive to warm compress treatment . The benefits lasted for up to 6 months, with occasional retreatment sessions leading to greater comfort. The infrared warm compression device consists of an eye mask with two rigid patches over the eyes.
Each patch has 19 light emitting diodes, emitting near infrared radiation from to nm, with a peak at nm. The infrared warm compression device was used to treat 37 subjects with obstructive MGD in a prospective, non-comparative interventional case series for 5 min, twice a day, for 2 weeks with closed eyelids.
Total subjective symptom scores improved and there was also significant improvement in tear evaporation rates during forced blinking, fluorescein and rose bengal staining and meibomian gland orifice obstruction score . Physical expression for therapeutic amelioration of obstructive material should not be confused with diagnostic expression, where minimal forces are used to determine if the gland is functional .
There are three established methods for physically treating ductal obstruction; warm compresses and various heating devices use heat to raise the temperature to soften or preferably liquefy the obstructive material, physical force is used to compress the glands to physically express the material from the obstructed gland, and intraductal probing introduces a thin wire into the obstructed orifice and then uses force to expel the obstructive material.
There is a long history describing a variety of methods for forceful expression of the meibomian glands without the application of heat [—]. These methods include isolating the eyelid to be expressed between the examiner's fingers and applying force by squeezing the eyelids against each other, or utilizing a rigid object on the inner surface of the eyelid and the thumb or finger or another rigid object on the outer lid to apply force [,].
However, a limiting factor with all these methods is pain experienced by the patient, which is only minimally relieved by topical anesthetics. The amount of pain increases rapidly as the force of expression exceeds 5 pounds per square inch PSI . The usual maximal tolerable force is 15 PSI, which is frequently marginal or inadequate to express obstructive material .
A study investigated the efficacy of four in-office forceful expressions over a period of 6 months in conjunction with daily warm compress therapy . The number of expressible glands, quality of secretion and lipid layer thickness significantly improved and all patients reported improved comfort and decreased symptoms associated with DED . After receiving the crossover treatment, the warm compress group also demonstrated significant improvement in gland function and TBUT. An uncontrolled single center, observational study found significant and sustained improvement in meibomian gland function and symptoms for up to 3 years after a single treatment .
Intense pulsed light IPL has been used in dermatology to deliver intense pulses of non-coherent light from nm to nm in wavelength to treat various conditions, including skin pigmentation, sun damage and acne . A hand held computer-controlled flashgun delivers the appropriate light, which is filtered for specific action. A more recent prospective, double-masked, placebo-controlled, paired-eye study compared the effect of multiple pulses of IPL on one eye while the other eye received a sham treatment.
The treatment imparted an improvement in tear film quality and a reduction in symptoms . Intraductal meibomian gland probing was first described in . This initial publication reported data from a retrospective chart review of 25 consecutive patients who all had signs and symptoms of obstructive MGD. Immediate post-probing relief was experienced by 24 of the 25 patients and all patients had relief from symptoms by 4 weeks after the procedure.
Five patients required one or two retreatment sessions. The patients who underwent a single treatment were followed up on average at All of the patients were symptom free at their last follow-up visit . A prospective, longitudinal study performed probing on one eye of 16 individuals presenting with MGD, while the fellow eye was used as a control.
Break-up time, vision, pain and photophobia all improved at one week and 6 months post-treatment . A study of three patients with refractory obstructive MGD investigated the amount and change in meibum viscosity after probing. All patients showed improvements in lipid levels and viscosity and 2 of the 3 showed improved TBUT . A study also reported improvement in symptoms after probing for 10 patients with ocular rosacea, MGD, and surface disease refractory to conventional management.
While further research is indicated, especially in view of the invasive nature of the procedure, the possibility of damage to a complex ductal system and the small sample of subjects thus far reported on, the data reported suggest that intraductal probing may offer relief to MGD patients who are unresponsive to conventional treatment.
One of the primary mechanisms driving obstruction of the meibomian glands is hyperkeratinization of the eyelid margin and duct orifices .
As keratinized material is built up around and within the orifice, the gland is obstructed and meibum cannot be delivered from the gland to the tear film. Debridement of the line of Marx, which marks the mucocutaneous junction and the keratinized lid margin, was first reported in . It is believed that this technique works by mechanically removing accumulated debris and keratinized cells from the eyelid margin to allow increased flow of meibum into the tear film.
The prospective, investigator-masked study by Korb and colleagues included a test group of 16 subjects and a control group of 12 subjects, all presenting with symptoms of dry eye and visible changes to the line of Marx . The stained line of Marx and the entire width of the keratinized lower lid margin were debrided in the test group using a stainless steel golf spud. All 14 subjects were female, seven were randomized to the treatment group and seven were controls. One month after debridement scaling subjects reported improved symptoms, ocular staining was reduced, and re-establishment of meibomian gland function was demonstrated .
A lack of sham treatment and masking in both reported studies [,] must be considered. Larger studies and additional study designs are needed to confirm the mechanisms of action to explain the positive results reported to date.
Incomplete blinking or an inability to close the eyes fully during sleep can result in drying of the ocular surface [—], and thus appropriate measures to address any blink or lid closure abnormalities are worthy of consideration in the management of the patient with signs or symptoms of DED. Studies investigating treatments for any form of inadequate lid closure are mostly Level 3 [,—], and include the evaluation of tear supplements, ointments typically instilled at night , moisture goggles, night time eyeshields that achieve mechanical closure of the lids, and forced temporary closure of the lids by patching or taping.
For those unwilling or unable to perform eyelid physical taping overnight, such as those with contact dermatitis or those concerned with iatrogenic lash epilation [,], alternative methods exist. These methods include eyecups of a variety of different designs and materials, and the use of thin polymer films such as plastic food wrap.
Level 1 evidence suggests that films provide better protection to the exposed cornea, with fewer complications, than lubricants . Mechanical closure of the eyelids by various methods in critically ill populations is reported to equally, or better, protect the exposed cornea, with fewer complications, than lubricants [,]. However, although it is universally accepted that mechanical closure of the eyelids is mandatory in the management of severe exposure keratopathy, there are no randomized prospective controlled clinical studies to establish the efficacy or superiority of different treatments.
Rigid gas permeable scleral lenses can also be an option in cases of exposure keratitis, as detailed in section 3. Entropion and ectropion result in ocular surface exposure and entropion often results in concurrent trichiasis, causing symptoms of dry eye . Facial nerve palsy results in a paralytic lower lid ectropion and upper eyelid retraction due to reduced activity of the orbicularis oculi.
Other causes include trauma, tumors, facial surgery and age-related lid laxity. Management of both entropion and ectropion is usually surgical and techniques include tightening the canthal tendons and removing a cicatrix or other mechanical reason for eyelid malposition [—].
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