**Background:** Dry eye is a prevalent chronic inflammatory ocular surface disease affecting 11.3% of people over 50, characterized by symptoms such as fatigue, tingling, and burning. It arises from multifactorial causes including rheumatic diseases, diabetes, hormone disorders, and contact lens wear, which activate inflammatory pathways like mitogen-activated protein kinases (MAPK) and nuclear factor-κB (NF-κB). These pathways promote macrophage and T cell activation and the release of inflammatory factors, perpetuating a vicious cycle. Traditional management with artificial tears (ATs) is often insufficient, making anti-inflammatory therapy a more suitable approach. This review aims to describe the inflammation mechanisms, associated inflammatory factors, and anti-inflammatory treatment options for dry eye.
**Methods:** This is a narrative review that synthesizes findings from published literature on dry eye inflammation mechanisms and anti-inflammatory therapies. The authors discuss inflammatory cells (neutrophils, macrophages, natural killer cells, dendritic cells, T cells) and their roles, inflammatory pathways (MAPK, NF-κB, TGF-β), and the involvement of blood and lymphatic vessels. They also cover common dry eye factors (diabetes, Sjögren's syndrome, sex hormones, contact lenses) and a wide range of anti-inflammatory treatments including cyclosporine, corticosteroids, NSAIDs, antibiotics, autologous serum, hormone therapy, IL-1 receptor antagonists, meibomian gland massage, intense pulsed light (IPL), mesenchymal stem cells (MSCs), dietary supplements (royal jelly, manuka honey, omega-3 fatty acids, vitamins), and other therapies (nerve stimulation, gabapentin). The review does not describe a specific systematic search strategy or inclusion criteria.
**Key Results:** The review highlights several key findings: (1) Inflammatory cells, particularly Th17 cells, are central to dry eye pathogenesis; Th17 cells secrete IL-17A, which promotes NF-κB and MAPK signaling, stimulates metalloproteinase production, and disrupts corneal barrier function. (2) The MAPK and NF-κB pathways are key drivers of inflammation, with p38 regulating Th1/2 cytokine secretion and NF-κB translocating to the nucleus to transcribe pro-inflammatory factors. (3) Diabetes exacerbates dry eye through neuropathy, metabolic disorders, and activation of NF-κB and ROS pathways; oral aldose reductase inhibitors can increase tear film evaporation time. (4) Sjögren's syndrome is associated with lymphocyte infiltration in the lacrimal gland and conjunctiva, with about 11% of dry eye patients diagnosed with this condition. (5) Sex hormones influence dry eye: androgens promote lipid production, while estrogens inhibit it; postmenopausal women are at higher risk due to decreased dehydroepiandrosterone (DHEA). (6) Contact lens wear increases levels of IL-6/17A, MMP-9, ICAM-1, and GM-CSF, and reduces conjunctival goblet cell density after 3 months. (7) Anti-inflammatory treatments: 0.05%–0.1% cyclosporine eye drops are recommended for 3–6 months; 0.1% cyclosporine improved dry eye indexes more than other concentrations. Corticosteroids like dexamethasone reduce MMP-9, TNF-α, and IL-1β levels in tears. NSAIDs combined with ATs are more effective than ATs alone. Azithromycin can inhibit bacterial lipase and block NF-κB activation. Autologous serum at 20% concentration is recommended for moderate dry eye, and 50% for severe dry eye. Omega-3 fatty acid supplementation for 3 months reduces tear osmolality and IL-17A levels. IPL therapy uses 500–1,200 nm wavelength light to induce superficial vascular coagulation and reduce inflammatory factor activity.
**Clinical Implications:** The review emphasizes that dry eye treatment should be multifaceted and personalized. For patients with primary diseases like Sjögren's syndrome or diabetes, active management of the underlying condition is crucial. Anti-inflammatory therapy combined with ATs appears more effective than ATs alone. Specific recommendations include: using 0.05% cyclosporine for moderate dry eye to avoid irritation; corticosteroids for postoperative dry eye; NSAIDs for contact lens-related dry eye with conjunctival papillae; and antibiotics (azithromycin, doxycycline) for meibomian gland dysfunction. Physical therapies like meibomian gland massage, hot compresses, and IPL can provide symptomatic relief. Dietary supplements (royal jelly, manuka honey, omega-3 fatty acids, vitamins A/B1/D) may be beneficial, especially for patients with deficiencies. The authors note that many anti-inflammatory drugs lack extensive clinical trials on dosage and treatment duration, highlighting the need for future research to clarify these parameters. Overall, a comprehensive approach combining anti-inflammatory drugs, ATs, and lifestyle modifications is recommended for optimal management of dry eye.