The treatment of meibomian gland dysfunction (MGD) first requires both proper diagnosis of the condition and identification of contributory ocular surfaces disorders that may confuse proper attribution of both patient symptoms and signs. Nomenclature remains confusing as many clinicians alternate between diagnosing patients with dry eye, evaporative dry eye, MGD, ocular rosacea, or, more generically, ocular surface disease. While all of these terms are valid descriptors of ocular surface disease, this chapter will focus on treatment of MGD, to be understood as the evaporative dry eye caused by the tear film dysfunction created by stagnant and/or dysfunctional meibum as well as ocular surface inflammation, whether present within occluded glands in the eyelid, conjunctival and corneal epithelium, and the tear film itself. Of course, it is well recognized that most patients with MGD have some degree of concomitant aqueous tear production deficiency, conjunctivochalasis, , and/or allergic eye disease, and these also require their own distinct therapeutic interventions. The value of clinical skills on the part of the eye care provider in differentiating the relative contributions of these overlapping conditions is crucial to success in addressing patient complaints. Clinicians can be loosely divided into categories of lumpers (all ocular surface disease is one pool) and splitters (subgrouping ocular surface disease matters). The clinical management recommendations of this chapter focus on the treatment of MGD in isolation and follow the thinking of a splitter-style clinician, cognizant of the need to also treat all the contributory causes of ocular surface disease. The comprehensive treatment approach for ocular surface disease is beyond the scope of this chapter.
Optimum treatment addresses disease pathophysiology, but our understanding of what truly underlies MGD is incomplete. The etiologies of MGD have been reviewed extensively in the TFOS MGD Workshop Report and other publications and will not be repeated here. Of note, significant basic science research provides growing evidence that meibomian gland senescence and altered meibocyte differentiation related to PPAR-γ–mediated pathways are critical to the development of clinical MGD. Understanding of the role of meibomian gland periductal fibrosis has also grown in past years. As our understanding of meibocyte physiology and of additional mechanisms of MGD pathogenesis evolve, it is likely that novel treatment strategies will emerge.
At present, most clinicians believe that MGD is a result of hyperkeratinization of ductal epithelium and abnormal thickening of meibum secretions with consequent gland obstruction, atrophy, and dropout as well as variable degrees of secondary inflammation and secondary microbial colonization or superinfection. Optimum treatment, in theory, would prevent or resolve hyperkeratinization (whether on the eyelid margin or within the gland ducts), “normalize” meibum, suppress or eliminate inflammation and superinfection, restore normal meibum output, and prevent functional loss of gland tissue. Some clinicians distinguish between lipid-deficient or hyposecretory MGD (in which a decreased tear lipid layer allows increased evaporation of tears) and oil retentive or obstructive MGD as different conditions based on the presence/degree of meibomian gland obstruction, and possibly in the degree of inflammation in the eyelid margin tissues. This may be relevant in constructing a treatment algorithm for MGD patients, depending on whether the main driver of symptoms is tear overevaporation or tissue-based inflammation within the eyelids. Compared with aqueous deficient dry eye, most clinicians underestimate (and undertreat) inflammation as a pathogenic mechanism (and thus target for therapy) in MGD.
Replacement or normalization (restoring homeostasis) of the meibum layer of the tear film represents a significant challenge to clinicians. At present, it must be said that we do not have reproducible methods to either reliably quantitate or characterize meibum in the tear film or even to quantitate gland orifice obstruction. In cases where significant loss of functioning glands precludes restoration of a normal meibum component to the tear, a “substitute” component delivered topically might serve the physiologic role of meibum, that is, to stabilize the tear film and prevent evaporative loss of tears. Perfluorohexyloctanes have been shown to do this in clinical trials and are in development as a treatment for evaporative dry eye. ,
“If you can’t measure it, you can’t manage it” is a quote (famously incorrectly attributed to economist W. Edward Deming) relevant to the difficulty of assessing treatment efficacy in MGD. There is no standardized methodology to clinically (at the slit lamp) assess the viscosity or the quantity of secreted meibum beyond simple mild–moderate–severe scales. There is debate over whether the patency of gland orifices is best inferred from vigorous compression of the eyelid using a finger, forceps, or various mechanical squeezers versus tools that exert mild or “physiologic blink” force (the Korb MGE). , Debate also exists as to the irreversibility of gland “dropout” as diagnosed by meibography (defined as nonvisualization of “normal white stripes” thought to represent normally functioning glands). , Each of these issues has important relevance in determining an appropriate metric (orifice patency vs. meibum consistency) with which to measure efficacy of our treatments for MGD. Further, it may be necessary to treat tissue-based inflammation in addition to restoring the normal meibum component to the tear film.
Currently available treatment options do not address each of the pathogenic processes involved in MGD. Prior to managing the disease, clinicians who treat patients with MGD must be cognizant of the contributory role of medicamentosa (e.g., isotretinoin and others) , in MGD and the existence of high-risk patient subgroups (atopy, OCP, prostate cancer, etc.). , While it may not be possible to improve the function of meibomian glands by discontinuing systemic medications such as isotretinoin, the benefits of eliminating preservatives from topical medications is well known. Controlling atopy with appropriate antiallergy medications and controlling the immunologic activity of diseases such as OCP is likewise important, highlighting the benefits of thorough history taking.
Virtually all patients self-treat symptoms of ocular surface disease with topical artificial lubricants as a first step. Despite limited published studies of efficacy, many clinicians recommend lubricants, intended either as general supplementation of tear volume or for a presumed rinsing effect on the ocular surface. The purported benefits of lipid-containing or higher viscosity lubricants , , have not yet been confirmed in large, randomized clinical trials. Nonetheless, there is rationale justification for choosing an artificial lubricant that replaces the deficient component in tears or one that behaves physiologically like tears.
Most clinicians initiate mechanical treatment of MGD with some form of home-based lid hygiene (combinations of heat/warm compress plus massage/expression of meibum). Heating the eyelids usually is perceived as soothing or comforting, but compression or expression of gland contents is the more therapeutic aspect of the procedure. This point needs to be highlighted in instructing patients. Despite published, peer-reviewed studies regarding the required temperature/time needed to melt meibum and estimates of the force required to express meibum, no standardization of home eyelid hygiene method exists. , Even the methods of patient instruction (e.g., written handouts, videos, personal hands-on instruction) and assessment of patient compliance are not standardized and not validated in a statistical sense. Nonetheless, numerous published studies have shown lid hygiene to be effective in relieving both symptoms and signs of MGD and this is generally the first treatment intervention selected by most eye care providers, including corneal specialists. , ,
Pharmaceutical treatment using orally administered agents is often the next prescribed therapy for patients whose symptoms are uncontrolled with eyelid hygiene. , Rather than antibiosis (which may be an ancillary side benefit), these agents are primarily prescribed for their antiinflammatory and oil-thinning effects. Tetracycline derivatives, azithromycin and/or omega-3 supplementation, are widely prescribed at varied dosing schedules in hopes of reducing tear film inflammation. Potential side effects are real and can be serious, including tetracycline-induced esophageal erosions, gastric cramping, vaginal yeast infections, and cardiac arrythmias. Omega-3 supplementation can cause anticoagulation issues, particularly in combination with other medications. Patients must be educated about these potential side effects at the time of drug prescription. Published reports support the efficacy of doxycycline or minocycline over other tetracyclines including low doses of these drugs, believed to be antiinflammatory but not antibacterial, , particularly in patients with rosacea. Azithromycin has been reported to be more efficacious than doxycycline in MGD, , though a variety of dosing regimens have been reported.
Other topical therapies in common use for MGD include antibiotics, steroids, antibiotic-steroid combinations, and even topical hormonal agents. There is no consensus on whether bacterial colonization of the eyelid is causal or secondary to crust accumulation and whether chronic topical antibiotic treatment is appropriate for MGD. Of course, chronic topical antibiotic therapy should be avoided because of the risks of emergence of resistant organisms. Despite their rapid and significant efficacy in controlling acute inflammation or flare ups, topical steroids or steroid/antibiotic combinations generate concerns about ocular hypertension and cataract progression associated with chronic use. While appropriate to treat short-term flares of lid inflammation, these agents should be avoided as chronic therapy.
Thermal pulsation procedures have been widely adopted as a treatment to more completely “express” secretions from stagnated and occluded glands, and numerous published studies have shown the effectiveness and longevity of some of these treatments. , It is not known if the benefit of such procedures is related to the simultaneous heating and compression or to the vectored nature of the compression. While LipiFlow was the first procedure to gain widespread use based on numerous reports of durable efficacy and symptom improvement, iLux is a handheld heating/compression method that has been shown to provide comparable efficacy. Posttreatment mechanical gland expression and posttreatment topical steroids have been reported to improve outcomes following thermal pulsation procedures. A variety of other, less studied mechanical heating/expression procedures (e.g., MiboFlo and TearCare) are also available, with limited published data. , While heating the MG secretions can melt some enough to make them expressible, it is clinically apparent that not all gland occlusions can be relieved in this way. Meibomian gland duct probing, first reported by Maskin in 2009 (Maskin 2010), is a method designed to reopen clogged duct orifices and central ducts and break adhesions attributed to periductal fibrosis. Probing has been reported as effective for as long as 4–12 months in clearing obstructions, relieving symptoms, and improving TBUT and may be a preferred therapeutic intervention in cases where obstruction is advanced or when prior thermal pulsation has been insufficient. , Debridement of the eyelid margin has been reported to have efficacy as a stand-alone procedure , and may be performed at the same time as duct probing.
Light-based therapies (including intense pulsed light or IPL) have gained popularity as a treatment for MGD and several studies support their efficacy, though most published studies include MG expression as a cotreatment with IPL, obscuring a clear evaluation of the light-based therapy itself. Review of published metaanalyses, , individual unblinded or open-label reports and reviews suggest potential benefit but a scarcity of RCT evidence for significant improvement in either symptoms, TBUT or corneal staining in MGD patients. Further study is certainly warranted and multiple trials are said to be in progress. The purported mechanisms by which IPL improves symptoms and signs in MGD remain speculative but may include eyelid warming, vascular thrombosis, decreased epithelial cell turnover, photomodulation (at a genetic or protein level), fibroblast activation, increased collagen synthesis, and MMP suppression or impact on inflammatory cytokines or reactive oxygen species.
Topical pharmaceuticals approved for dry eye (cyclosporin and lifitegrast) may have efficacy in the treatment of MGD independent from their efficacy in treating the frequently coexistent aqueous tear deficiency. The presence of inflammation within meibomian glands and within eyelid tissue is difficult to demonstrate but is likely an important cause of eyelid redness, swelling, and induration. Published studies of treatment with topical immunomodulators in MGD populations (small series) have shown efficacy for both cyclosporine , and lifitegrast in these subgroups of dry eye. Large, randomized trials of treatment in MGD have not been reported. However, given the frequent presence of aqueous deficiency in patients with MGD, the use of immunomodulatory eyedrops in these patients often is reasonable.
Hypochlorous acid is increasingly included in treatment plans for patients with eyelid inflammation and has efficacy as an antimicrobial (bacteria, fungi, and viruses) and possibly as an antiinflammatory agent. There is a paucity of data related to the use of these agents for MGD, but because the treatment is well tolerated, even with direct spray onto the ocular surface, hypochlorous acid is used by increasing numbers of patients.
Demodex has been discussed as a pathogenic commensal organism that is present in many patients with MGD, though there is uncertainty and debate regarding how frequently this is the actual cause of patient symptoms. Treatment for Demodex blepharitis includes a stepladder style escalation of therapy from topical agents (tea tree oil, terpinol-9) prepared as disposable wipes followed (for incomplete eradication) by an in-office tea tree oil cream for a more intense treatment. Soolantra cream is sometimes prescribed for recalcitrant cases and oral ivermectin has been reported as effective in resistant cases. ,
A number of algorithms have been published for the treatment of dry eye disease, with significant similarities between them as well as one for MGD that includes broader recommendations including treatment of aqueous deficiency. No published data are available comparing patient outcomes between these treatment approaches, leaving many clinicians uncertain of how to tailor their sequencing of treatments in patients with uncontrolled symptoms (or signs). Providing yet another algorithm for the treatment of MGD is unlikely to bring consensus, but this author’s thirty-plus years of experience treating ocular surface disease in a corneal specialty/clinical research practice yielding very high patient satisfaction has led to a “stepladder” approach that may help others. This sequence of treatments is recommended for addressing the MGD component that is only one (significant) part of ocular surface disease, and other contributory factors need to be addressed as well.
- 1.
Diagnosis before treatment! Begin with an accurate diagnosis of MGD and intercurrent ocular surface disease using risk factor assessment, patient history, meibography, and tear measurements (aqueous production and lipid layer thickness).
- 2.
Identify patient risk factors and other pathogenic processes (exposure, allergy, conjunctivochalasis, epithelial dystrophy, corneal anesthesia, significant Demodex infestation, etc.) that may be contributory. Treat each as appropriate and as necessary.
- 3.
Exclude medicamentosa contribution from both topical and systemic agents whenever possible.
- 4.
Rehabilitate the tear film using preservative-free lubricants (escalating toward thicker or lipid-containing products including ointment) and effective and regular eyelid hygiene/expression BID. Develop a specific hygiene regimen for your patients based on the results you observe from the method you provide.
- 5.
Address thickened meibum pharmaceutically (omega-3 supplements, doxycycline, azithromycin) especially in cases where meibum appears thickened, viscous, or waxy.
- 6.
Use topical antiinflammatory agents (steroids, azithromycin) judiciously, avoiding long-term therapy. Consider serum tear administration and/or amniotic membrane treatment in resistant cases and for flare-ups of chronic disease.
- 7.
If orifices are patent, thermal pulsation procedures (e.g., LipiFlow or iLux) can augment patient home lid compression, but are not a replacement for home therapy.
- 8.
If orifices are closed or if clinical responses to thermal pulsation procedures are insufficient, consider meibomian gland probing to restore orifice patency.
Management and treatment of MGD requires a full set of clinician skills, including thorough history taking, differential diagnosis, proper diagnosis including coexistent/contributory conditions and knowledge of the many therapeutic options available today. Delivering effective care for each patient requires balancing issues such as choosing between treatments covered by insurance versus self-pay procedures, addressing compliance in an effective way and maintaining patient engagement in plans of ongoing treatment for this chronic and progressive condition. Patient dissatisfaction with inadequate symptom improvement following self-pay procedures can interfere with ongoing care, and clinicians need to properly set patient expectations and explain the need for continued treatment of MGD.
Ongoing research is likely to bring new tools to clinicians, including topical agents that provide the same antievaporative effect that meibum does, agents that reverse abnormal keratinization within the MG and hormonal therapies that maintain the function of meibocytes even as we age.
References
Stay updated, free articles. Join our Telegram channel
Full access? Get Clinical Tree
