**Background:** Dry eye disease (DED) is a multifactorial ocular surface disorder characterized by tear film instability, hyperosmolarity, inflammation, and damage. It is broadly classified into aqueous-deficient dry eye (10–15% of cases) and evaporative dry eye, with over 85% of DED cases having an evaporative component. Meibomian gland dysfunction (MGD) is the primary cause of evaporative DED, with a pooled prevalence of 35.9% in population-based studies and signs of MGD observed in 70–90% of DED patients. MGD involves chronic abnormalities of meibomian glands, including terminal duct obstruction and altered meibum secretion, leading to disruption of the tear film lipid layer and increased evaporation. This triggers a cycle of tear film instability, hyperosmolarity, inflammation, and ocular surface cell apoptosis. The tear film lipid layer, composed of nonpolar lipids (cholesteryl esters, wax esters, triglycerides >80%) and amphiphilic polar lipids (phospholipids, omega-hydroxyl fatty acids), serves as an evaporation barrier. In MGD, meibum changes (e.g., increased viscosity, loss of OAHFAs) worsen evaporation. Diagnosis involves a two-tiered approach: first establishing DED via symptoms, slit-lamp exam, and tests (corneal fluorescein staining, Schirmer test, tear osmolarity, TFBUT), then evaluating meibomian gland function (lid morphology, meibum expressibility, gland dropout via meibography). The primary treatment goal is to restore the lipid layer and reduce evaporation.
**Methods:** A review of the MEDLINE database was conducted in April 2022 for English-language articles with no date restriction. Searches used terms "dry eye," "meibomian gland," and "tear film" for overall pathophysiology. Specific treatments were identified using keywords "evaporative dry eye" or "meibomian" combined with terms for individual treatments (e.g., lid hygiene, warming, artificial tears, omega-3, thermal pulsation, IPL, antibiotics, cyclosporine, lifitegrast, varenicline, diquafosol). Outputs were reviewed for prospective, randomized, placebo- or active-controlled clinical trials in patients with DED associated with MGD. Article bibliographies were also reviewed. Emerging therapies were identified via clinical trial registries, conference presentations, and press releases, focusing on phase 2 or 3 products.
**Key Results:** Home-care options include eyelid hygiene (twice daily, often with warm compresses; one randomized trial showed an eyelid cleanser improved lipid layer and reduced inflammatory markers vs. baby shampoo), warming eye masks (melting point of meibum is ~4°C higher in MGD patients; warming alters tear lipidome, reduces evaporation, and improves symptoms in randomized trials), ocular lubricants (lipid-based drops superior to aqueous for evaporative DED in a randomized trial of 99 patients; retention time limited to 22.4–40.8 min), and omega-3 fatty acids (a meta-analysis showed significant improvements in TFBUT and Schirmer test; however, a large randomized trial of 535 patients found no significant difference vs. olive oil placebo over 12 months). Office-based treatments include manual expression (small randomized trials show greater improvement in OSDI, TFBUT, meibum quality when added to conventional treatment), microblepharoexfoliation (one trial of 81 patients showed reduced Demodex counts and OSDI vs. scrubs alone; another of 50 patients showed no OSDI improvement), thermal pulsation (LipiFlow: a meta-analysis of 10 RCTs with 761 patients found significant improvements in symptoms and signs vs. control, but quality of evidence low; iLux, TearCare, MiBo Thermoflo showed noninferiority to LipiFlow in randomized trials), intense pulsed light (IPL: a meta-analysis of 9 studies with 539 patients found IPL plus meibomian gland expression superior to expression alone for TFBUT and OSDI, but not SPEED; efficacy correlated with number of treatments), and intraductal probing (small randomized trials show improved TFBUT and meibum grade vs. control). Prescription medications: No FDA-approved drugs are specifically indicated for MGD-associated DED. Cyclosporine 0.05% emulsion showed significantly greater reduction in meibomian gland blockage and fluorescein staining vs. artificial tears in a randomized study of 33 patients. Lifitegrast showed significantly better corneal staining and eye dryness vs. one thermal pulsation treatment in 50 patients. Loteprednol etabonate 0.5% plus heat/hygiene significantly decreased inflammatory tear cytokines and improved TFBUT, meibum quality, and MGD stage vs. heat/hygiene alone in 60 patients. Emerging therapies: NOV03 (perfluorohexyloctane) is the most advanced. In phase 2 (SEECASE, n=336) and two phase 3 trials (GOBI, n=597; MOJAVE, n=620), NOV03 demonstrated statistically significant improvements in both primary sign (total corneal fluorescein staining at week 8) and primary symptom (VAS dryness score at week 8) vs. saline control. In GOBI, NOV03 reduced tCFS by a mean of 1.5 units vs. 0.9 units for control (p<0.001) and VAS dryness by 25.3 mm vs. 18.5 mm (p<0.001). Adverse event rates were similar between groups (8.3% vs. 5.1% in GOBI; 9.6% vs. 9.7% in MOJAVE). AZR-MD-001 (selenium sulfide) in a phase 2 trial of 22 patients significantly decreased tear evaporation rate and increased TFBUT and meibomian gland secretion vs. vehicle. Other phase 2 agents include AXR-270 (selective glucocorticoid receptor agonist), CBT-006 (cholesterol sequestration), and HY-02 (minocycline ointment).
**Clinical Implications:** MGD is highly prevalent and the leading cause of evaporative DED, yet current treatments are limited. Home-care and office-based therapies provide symptomatic relief but often require long-term compliance and may not address the underlying pathophysiology. No FDA-approved pharmacologic treatments specifically target excessive evaporation, the key driver of MGD-associated DED. NOV03, a novel semifluorinated alkane that forms a protective layer on the tear film to reduce evaporation, has shown consistent efficacy in phase 3 trials and may fill this gap. Other emerging therapies targeting meibomian gland function (e.g., keratolytic, anti-inflammatory) are in development. Larger, well-designed randomized controlled trials are needed to confirm efficacy and safety of existing and emerging treatments, and to enable a more individualized approach to managing this common condition.