Dry eye, blepharitis and meibomian dysfunction

Dry eye disease (DED) is common in anterior-segment practice and can impair comfort and visual quality. TFOS DEWS III, published in 2025, updates the earlier 2017 consensus. It describes symptomatic, multifactorial loss of tear-film and/or ocular-surface homeostasis, involving instability, hyperosmolarity, inflammation, surface damage and neurosensory factors.

The diagnostic task is to establish symptoms and evidence of lost homeostasis, then identify the contributing drivers. Treating all patients as though they have one identical inflammatory process misses lid, tear, anatomical and sensory abnormalities.

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1. Anatomy of the Precorneal Tear Film

Historical models conceptualised the tear film as a distinct trilaminar sandwich (lipid, aqueous, and mucin). Contemporary biophysical research demonstrates that the tear film consists of a superficial lipid layer overlying a blended, continuous muco-aqueous gradient ($3–5\,\mu\text{m}$ thickness):

1. Lipid layer: Meibomian glands provide lipids that contribute to tear-film stability and resistance to evaporation. The effect depends on composition and structure; one universal percentage reduction is not a clinical law.
2. Muco-Aqueous Layer ($3–5\,\mu\text{m}$): Secreted predominantly by the main lacrimal gland and accessory lacrimal glands of Krause (fornices) and Wolfring (tarsus). Contains water, essential electrolytes ($\text{Na}^+, \text{K}^+, \text{Cl}^-, \text{HCO}_3^-$), and antimicrobial/trophic proteins:
   • Lysozyme: Cleaves peptidoglycan cell walls of Gram-positive bacteria.
   • Lactoferrin: Chelates free iron, arresting bacterial replication.
   • Secretory IgA (sIgA): Neutralises bacterial and viral adhesion.
   • Lipocalin: Chelates fatty acids and stabilises the lipid-water interface.
   • Epidermal Growth Factor (EGF) and Nerve Growth Factor (NGF): Maintain epithelial and neurosensory homeostasis.
3. Mucin Component: Divided into soluble gel-forming mucins (predominantly MUC5AC synthesised by conjunctival goblet cells) that lubricate and clear debris, and membrane-associated mucins (MUC1, MUC4, MUC16) expressed by the microvilli of corneal and conjunctival epithelial cells forming the glycocalyx, converting a naturally hydrophobic lipid-rich epithelial cell membrane into a hydrophilic wettable surface.

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2. The Pathophysiological "Vicious Circle" of Dry Eye

The central mechanism driving all forms of DED is tear film hyperosmolarity, which triggers a self-perpetuating inflammatory cascade:

1. Initiating Stress: Evaporative excess (MGD) or aqueous deficiency leads to excessive water loss from the ocular surface.
2. Tear Hyperosmolarity: Evaporation concentrates electrolytes, driving tear osmolarity above physiological levels ($> 308\text{ mOsm/L}$). Hyperosmolarity imposes osmotic stress on corneal and conjunctival epithelial cells.
3. Pro-Inflammatory Signaling: Hyperosmolar stress activates mitogen-activated protein kinases (p38 MAPK, JNK) and the nuclear transcription factor NF-$\kappa$B within epithelial cells.
4. Inflammatory mediators and proteases: Stimulated cells release pro-inflammatory cytokines (IL-1$\beta$, TNF-$\alpha$, IL-6), chemokines, and matrix metalloproteinases (MMP-9).
5. Goblet Cell Apoptosis & Epithelial Damage: Inflammatory mediators trigger apoptosis of conjunctival goblet cells (reducing MUC5AC) and disrupt epithelial tight junctions (claudins, occludins).
6. Tear Instability & Amplification: Loss of mucin and irregular epithelia further destabilise the tear film, accelerating evaporation and worsening hyperosmolarity.
7. Neurosensory Dysregulation: Chronic inflammation damages peripheral corneal nerve terminals, leading to either neuropathic pain (hyperalgesia/allodynia: severe symptoms with minimal signs) or neurotrophic hypoesthesia (blunted reflex tearing and blink rate).

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3. Classify the Drivers

Aqueous deficiency and evaporation remain useful concepts but often overlap. TFOS DEWS III groups drivers involving tears, lids, ocular surface and systemic factors. Assess gland secretion, lipid/tear stability, blink and exposure, mucin/surface disease, medications, allergy and neuropathic symptoms. Sjögren disease can involve severe aqueous deficiency and needs systemic assessment. Do not assign a universal percentage of all dry-eye patients to one subtype. Symptoms without signs and signs without symptoms require careful differential assessment rather than automatic escalation of anti-inflammatory drops.

4. Symptoms and Homeostasis Testing

TFOS DEWS III uses compatible symptoms together with at least one marker of lost homeostasis after considering mimics. The abbreviated OSDI-6 symptom questionnaire uses a cutoff of at least 4. Perform less invasive tests before dye and contact tests alter the tear film.

Examples of diagnostic markers are non-invasive breakup time below 10 seconds, fluorescein breakup below 5 seconds, osmolarity at least 308 mOsm/L in the higher eye or an inter-eye difference above 8, and specified surface-staining patterns. Thresholds depend on protocol and do not independently define severity or the treatment needed. Record corneal, conjunctival and lid-margin staining separately. Schirmer testing and secretion/lid assessment help identify drivers; a positive MMP-9 test alone does not mandate treatment.

Seek alternative explanations such as allergy, infection, exposure, medication toxicity or neuropathic pain. Compare symptoms with function and explain uncertainty. See the TFOS DEWS III summaries.

5. Blepharitis & Meibomian Gland Dysfunction (MGD)

Blepharitis is an inflammatory condition of the eyelid margins, categorised anatomically into anterior and posterior disease.

Anterior Blepharitis

Involves the base of the eyelashes and lash follicles:

• Staphylococcal Blepharitis: Chronic colonization by Staphylococcus aureus or S. epidermidis. Slit-lamp biomicroscopy reveals hard, brittle, fibrinous collarettes encasing the lash shafts, ulcerative lash margins, madarosis (loss of eyelashes), trichiasis, and poliosis (whitening of lashes).
• Seborrhoeic Blepharitis: Strongly associated with seborrhoeic dermatitis. Features soft, greasy, oily scales along the eyelid margins and lashes without ulceration.
• Demodex blepharitis: Collarettes at the lash bases support mite-associated disease. Assess symptoms and concurrent lid/surface problems. Treatment depends on the locally available, appropriately authorized product and its evidence. Tea-tree-derived products can irritate or injure the ocular surface; avoid concentrated home preparations and do not routinely place skin ivermectin cream in the eye. Clinician-directed lid care and selected anti-mite treatment require monitoring of tolerability.

Posterior Blepharitis & Meibomian Gland Dysfunction (MGD)

MGD is a chronic, diffuse abnormality of the meibomian glands characterised by terminal duct obstruction and qualitative/quantitative alterations in glandular lipid secretion.

• Pathophysiology: Hyperkeratinisation of ductal epithelium $\rightarrow$ thick, turbid meibum with elevated melting temperature ($> 35^\circ\text{C}$) $\rightarrow$ ductal plugging $\rightarrow$ cystic dilatation and eventual intraglandular atrophy.
• Biomicroscopic Signs: Telangiectatic blood vessels crossing the mucocutaneous junction, plugging and pouting of meibomian orifices, thickened "toothpaste-like" meibum upon digital expression, irregular lid margin, and foamy tear meniscus (lipid saponification by bacterial lipases).
• Non-Contact Infrared Meibography: Direct imaging of glandular silhouettes in the everted tarsus. Documents gland dropout, shortening, and tortuosity, quantified via the meiboscore (Grade 0: no dropout; Grade 1: $< 33\%$ loss; Grade 2: $33–66\%$ loss; Grade 3: $> 66\%$ loss).

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6. Management Matched to the Drivers of Disease

TFOS DEWS III (2025) updates the earlier report and emphasises treatment selected for tear deficiencies, eyelid abnormalities, ocular surface changes and systemic contributors. A patient often has several drivers. Review symptoms and functional priorities as well as objective findings; a single test does not mandate one drug.

Begin with education, appropriate tear supplementation and feasible environmental or blink changes. For meibomian dysfunction, use safe lid warming and hygiene, then select further treatment according to gland function, inflammation, tolerance and evidence. Avoid excessive heat or undiluted irritating cleansers. Persistent unilateral pain, photophobia or reduced vision requires evaluation for other pathology.

Punctal occlusion is one option for tear conservation. Consider the degree of inflammation and treat it appropriately, but evidence does not establish that plugs invariably worsen inflammation unless all anti-inflammatory therapy precedes insertion. Explain extrusion, irritation, epiphora and infection risks and reassess the response.

Availability of ciclosporin formulations, lifitegrast, secretagogues and Demodex treatments differs by country and authorisation. Lotilaner has a US indication for Demodex blepharitis; do not infer EU access from that approval. Tea-tree formulations may irritate or damage the surface and should not be treated as a harmless universal first-line remedy. Selected systemic antibiotics for rosacea/MGD require assessment of contraindications and an appropriate protocol.

Nutritional supplementation is not a guaranteed dry-eye treatment. The DREAM trial did not find a significant advantage of the tested omega-3 supplement over its comparator. Correct a demonstrated deficiency when indicated and distinguish uncertain adjuncts from established treatment for severe ocular disease.

Measure outcomes meaningful to the patient, such as reading fluctuation and comfort, and recheck the relevant surface signs. Persistent symptoms with minimal signs may require assessment of neuropathic pain, while marked staining with little pain raises concern for reduced sensation. Severe epithelial disease may require serum drops, amnion or protective surgery under specialist care.

Source: TFOS DEWS III reports and summaries.

DEWS III recommends symptom screening with OSDI-6, whose six items refer to the preceding month; a summed score of at least 4 is the symptom cutoff. Confirm loss of homeostasis using tear stability or osmolarity and comprehensive surface staining, starting with the least invasive tests. Non-invasive breakup time below 10 seconds and fluorescein breakup time below 5 seconds are different measures and are not interchangeable. An isolated MMP-9 result does not itself select or mandate anti-inflammatory treatment.