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ophtho.dry-eye-disease.core.v1PRODUCTION
ophtho.dry-eye-disease.core.v1

Dry eye disease (aqueous-deficient and evaporative subtypes)

general_internal_medicinechronicadultgeriatric
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12/12 authored

Canonical 12-phase frame with authored status for this dossier.

Current phase

Frame

Detailed

Frame DED as a chronic multifactorial disease with two subtypes (aqueous-deficient and evaporative; most patients mixed). Engine drives TFOS DEWS II symptom-and-sign diagnosis, subtype identification with meibography + Schirmer, and a stepwise barrier + anti-inflammatory + secretagogue / anti-evaporative ladder. Sjögren syndrome and GVHD are recognised systemic causes routed by engine_id (TFOS DEWS II PMID 28736335).

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DED frame + subtype awareness set

Patient inputs (11)

Meibomian gland dropout / orifice plugging / lid-margin telangiectasia identifies the evaporative MGD subtype that dominates clinic DED (TFOS DEWS II PMID 28736335)

Antihistamines, anticholinergics, isotretinoin, oral contraceptives, hormone-replacement, diuretics, antidepressants worsen DED — counsel and substitute where possible (TFOS Lifestyle 2023)

Contact-lens wear, low-humidity environment, prolonged screen time, air travel, smoke exposure all worsen DED (TFOS Lifestyle 2023)

Validated symptom score (OSDI or DEQ-5) is the gateway diagnostic per TFOS DEWS II and the patient-reported-outcome that drives step-up decisions (PMID 28736342)

Non-invasive (preferred) or fluorescein TBUT under 10 seconds supports DED diagnosis per TFOS DEWS II Methodology (PMID 28736342)

Corneal fluorescein staining + conjunctival lissamine green + lid-margin staining quantify damage; staining without symptoms is "non-obvious DED" (TFOS DEWS II PMID 28736335)

Schirmer <=5 mm/5 min after anaesthesia points to aqueous-deficient subtype; >10 mm argues against (TFOS DEWS II Methodology PMID 28736342)

Sicca + arthralgia + parotid swelling triggers anti-SSA / anti-SSB serology + rheum referral; Sjögren carries lymphoma risk (TFOS DEWS II PMID 28736335)

GVHD ocular involvement and Stevens-Johnson Syndrome / TEN survivors carry severe cicatrising DED — different management arc (route to derm.sjs-ten and oncology engines)

Tear osmolarity >=308 mOsm/L or inter-eye difference >=8 supports DED diagnosis (TFOS DEWS II Methodology PMID 28736342)

Chronic benzalkonium-chloride (BAK) preserved eye-drop use (glaucoma, OTC tears) worsens ocular surface — counsel preservative-free (TFOS Lifestyle 2023)

* = hard-required. Engine cannot meaningfully run until these are filled.

Severity triggers (6)

6 need judgement
  • informationalseverepersistent_epithelial_defect_or_corneal_ulcer
    Persistent epithelial defect / filamentary keratitis / sterile ulcer on chronic-DED background
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalseveresjogrens_systemic_features
    Dry eyes + dry mouth + arthralgias / parotid swelling / anti-SSA or anti-SSB positive
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalseverecicatrising_conjunctivitis_mmp_sjs_gvhd
    Forniceal shortening, symblepharon, or unilateral progressive cicatrising changes
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalmoderatemedicamentosa_BAK_preservative_burden
    Chronic exposure to BAK-preserved drops (glaucoma drops, OTC tears) with worsening surface
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalmoderatesevere_evaporative_mgd_refractory_to_warm_compress
    Evaporative MGD-dominant DED unresponsive to 4-8 wk warm-compress + lid-hygiene + omega-3 + preservative-free tears
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalmoderateaqueous_deficient_severe_or_postmenopausal_sjogren_negative
    Schirmer <=5 with severe symptoms in postmenopausal woman, anti-SSA/SSB negative — non-Sjögren aqueous-deficient
    Trigger could not be auto-evaluated — needs clinician judgement.

Workflow calculators

This dossier does not reference any calculators.

Recommended regimen

Dry eye disease — TFOS DEWS II + TFOS Lifestyle 2023 stepwise ladder
axis: ded_stepwise_dews_ii_ladderstep 1 - Step 1 — Foundation: education, environment, lid hygiene, preservative-free tears (all patients)
Selected step "Step 1 — Foundation: education, environment, lid hygiene, preservative-free tears (all patients)" — All severities, continuously — the substrate beneath every higher tier
  • patient_education_and_environment_modification
    first line
    lifestyle_modification
    TFOS Lifestyle 2023 + DEWS II (PMID 28736335) — humidity, 20-20-20 screen rule, hydration, smoke avoidance, contact-lens wear-time reduction.
  • warm_compress_and_lid_hygiene_for_mgd
    first line
    mgd_management
    triggers: evaporative_subtype_dominant, meibomian_gland_dropout, lid_margin_telangiectasia
    TFOS DEWS II (PMID 28736335) — warm compress 5-10 min + gentle lid massage + commercial lid scrub for evaporative MGD-DED, the commonest subtype.
  • preservative_free_artificial_tears_q1_4h
    first line
    lubricant
    TFOS DEWS II (PMID 28736335) — preservative-free PRN to as often as q1-2h for symptom relief; avoid BAK-preserved drops in chronic use (TFOS Lifestyle 2023).
  • cessation_of_BAK_preserved_drops
    first line
    deprescribing
    triggers: chronic_glaucoma_drop_burden, frequent_OTC_preserved_tear_use
    TFOS Lifestyle 2023 — chronic BAK exposure worsens ocular surface; switch glaucoma drops to preservative-free where available.
  • omega_3_dietary_or_supplement
    add on
    nutritional
    triggers: mgd_dominant, high_inflammatory_burden
    TFOS DEWS II (PMID 28736335) — mixed evidence; reasonable adjunct in MGD; DREAM trial neutral but TFOS retained as conditional.

outpatient playbook — drug actions (5)

  1. 1. preservative-free artificial tears + warm compress + lid hygiene (foundation)
    PRN to q1-4h • topical / non-drug • daily
    trigger: Any DED (PMID 28736335)
    Step 1 substrate beneath every higher tier; cessation of BAK-preserved drops counselled
  2. 2. cyclosporine ophthalmic 0.05% (Restasis) BID
    rxcui 1156187
    BID • topical • BID
    trigger: Persistent moderate DED after step 1 (PMID 28736335)
    Anti-inflammatory; effect at 3-6 months; transient burning
  3. 3. lifitegrast 5% (Xiidan) BID
    rxcui 1801820
    1 drop • topical • BID
    trigger: Moderate symptom-dominant DED (PMID 28736335)
    LFA-1/ICAM-1 antagonist; symptom benefit by 6-12 weeks; dysgeusia
  4. 4. perfluorohexyloctane (Miebo) QID
    rxcui 2637547
    1 drop • topical • QID
    trigger: Evaporative MGD-dominant DED (GOBI/MOJAVE PMID 39564145)
    First anti-evaporative drop; tCFS LSM difference -1.1 vs control
  5. 5. varenicline nasal spray 0.03 mg (Tyrvaya) BID
    rxcui 591622
    one spray each nostril • intranasal • BID
    trigger: Aqueous-deficient or symptom-dominant DED inadequately controlled (ONSET-2 PMID 34767866)
    Trigeminal-lacrimal reflex neurostimulation; sneeze/cough mild/transient

Auto-drafted A&P note

outpatient

Subjective

- Possible entry pathways: Gritty / burning / foreign-body sensation, fluctuating vision, eyes tire with reading or screens (TFOS DEWS II PMID 28736335); Paradoxical reflex tearing in dry eye — tear-film instability triggers reflex aqueous secretion (TFOS DEWS II PMID 28736335); High screen-time, low humidity, contact-lens wear, frequent air-travel, autoimmune disease, anti-cholinergic or systemic-retinoid drugs (TFOS Lifestyle 2023).

Objective

- No vitals, labs, or imaging entered for this encounter.

Assessment

**Dry eye disease (aqueous-deficient and evaporative subtypes)** (ophtho.dry-eye-disease.core.v1).
Phenotype framing: Terminal differential: aqueous-deficient DED (Sjögren / non-Sjögren) vs evaporative DED (MGD-dominant) vs neuropathic ocular pain (symptoms-without-signs) vs allergic conjunctivitis (itch dominant) vs blepharitis with secondary DED (route to ophtho.blepharitis-stye-chalazion) vs medicamentosa from BAK / vasoconstrictor overuse vs cicatrising conjunctivitis (MMP / SJS / GVHD).
Scope: Frame DED as a chronic multifactorial disease with two subtypes (aqueous-deficient and evaporative; most patients mixed). Engine drives TFOS DEWS II symptom-and-sign diagnosis, subtype identification with meibography + Schirmer, and a stepwise barrier + anti-inflammatory + secretagogue / anti-evaporative ladder. Sjögren syndrome and GVHD are recognised systemic causes routed by engine_id (TFOS DEWS II PMID 28736335).

No severity triggers fired against current inputs.

Plan

Regimen axis: **Dry eye disease — TFOS DEWS II + TFOS Lifestyle 2023 stepwise ladder** — step "Step 1 — Foundation: education, environment, lid hygiene, preservative-free tears (all patients)".
1. patient_education_and_environment_modification (lifestyle_modification, first line) — TFOS Lifestyle 2023 + DEWS II (PMID 28736335) — humidity, 20-20-20 screen rule, hydration, smoke avoidance, contact-lens wear-time reduction.
2. warm_compress_and_lid_hygiene_for_mgd (mgd_management, first line) — TFOS DEWS II (PMID 28736335) — warm compress 5-10 min + gentle lid massage + commercial lid scrub for evaporative MGD-DED, the commonest subtype.
3. preservative_free_artificial_tears_q1_4h (lubricant, first line) — TFOS DEWS II (PMID 28736335) — preservative-free PRN to as often as q1-2h for symptom relief; avoid BAK-preserved drops in chronic use (TFOS Lifestyle 2023).
4. cessation_of_BAK_preserved_drops (deprescribing, first line) — TFOS Lifestyle 2023 — chronic BAK exposure worsens ocular surface; switch glaucoma drops to preservative-free where available.
5. omega_3_dietary_or_supplement (nutritional, add on) — TFOS DEWS II (PMID 28736335) — mixed evidence; reasonable adjunct in MGD; DREAM trial neutral but TFOS retained as conditional.

Setting playbook (outpatient) — Confirm DED by TFOS DEWS II criteria, identify dominant subtype (aqueous-deficient vs evaporative-MGD), exclude Sjögren / GVHD / cicatrising mimics, and walk the stepwise ladder with preservative-free principle (TFOS DEWS II PMID 28736335 + 28736342; GOBI/MOJAVE PMID 39564145; ONSET-2 PMID 34767866)
6. preservative-free artificial tears + warm compress + lid hygiene (foundation) PRN to q1-4h topical / non-drug daily — Any DED (PMID 28736335) (Step 1 substrate beneath every higher tier; cessation of BAK-preserved drops counselled)
7. cyclosporine ophthalmic 0.05% (Restasis) BID BID topical BID — Persistent moderate DED after step 1 (PMID 28736335) (Anti-inflammatory; effect at 3-6 months; transient burning)
8. lifitegrast 5% (Xiidan) BID 1 drop topical BID — Moderate symptom-dominant DED (PMID 28736335) (LFA-1/ICAM-1 antagonist; symptom benefit by 6-12 weeks; dysgeusia)
9. perfluorohexyloctane (Miebo) QID 1 drop topical QID — Evaporative MGD-dominant DED (GOBI/MOJAVE PMID 39564145) (First anti-evaporative drop; tCFS LSM difference -1.1 vs control)
10. varenicline nasal spray 0.03 mg (Tyrvaya) BID one spray each nostril intranasal BID — Aqueous-deficient or symptom-dominant DED inadequately controlled (ONSET-2 PMID 34767866) (Trigeminal-lacrimal reflex neurostimulation; sneeze/cough mild/transient)

Non-pharmacologic actions:
- Punctal plugs (silicone then permanent) for aqueous-deficient persistent DED (PMID 28736335)
- In-office MGD thermal pulsation (LipiFlow) / IPL for MGD refractory to warm compress
- Amniotic membrane (Prokera) for persistent epithelial defect
- Scleral lens fitting in severe evaporative / GVHD / SJS-survivor DED
- Counsel cataract / refractive surgeons on pre-op surface optimisation (TFOS Lifestyle 2023)

AVOID / contraindication checks:
- Avoid chronic benzalkonium chloride BAK preserved eye drops (TFOS Lifestyle 2023 — worsens ocular surface)
- Topical corticosteroid use requires IOP and cataract surveillance (TFOS DEWS II PMID 28736335)
- Do not use vasoconstrictor decongestant drops chronically (rebound and medicamentosa)
- Cyclosporine and lifitegrast cause transient burning on instillation counsel adherence (TFOS DEWS II PMID 28736335)
- Exclude microbial keratitis before attributing corneal staining to DED alone (route to microbial keratitis engine if dendrite / infiltrate)

Monitoring

Regimen monitoring:
- OSDI or DEQ5 symptom score at 4 to 12 weeks per step (TFOS DEWS II PMID 28736342)
- ocular surface staining TBUT at each visit (TFOS DEWS II PMID 28736342)
- IOP every 2 to 6 weeks then 3 monthly on topical steroid (TFOS DEWS II PMID 28736335)
- Schirmer re check after neurostimulator or secretagogue at 4 weeks
- adherence and preservative free principle reinforced every visit

Setting (outpatient) monitoring:
- OSDI/DEQ-5 + staining + TBUT at 4-12 weeks per step (PMID 28736342)
- IOP every 2-6 weeks then 3-monthly on topical corticosteroid (PMID 28736335)
- Adherence + preservative-free reinforcement every visit

Follow-up plan: Lifelong chronic-disease care. Quarterly to biannual review at stable disease; tighter on therapy initiation or flare. Co-manage Sjögren systemic disease via rheum engine; monitor for lymphoma in Sjögren long-term. Counsel cataract / refractive surgeons on patient pre-existing DED — optimise surface pre-op to avoid postoperative deterioration (TFOS Lifestyle 2023; TFOS DEWS II PMID 28736335).
- Close-out criterion: long-term + systemic-disease + perioperative planning documented

Monitoring phase: Reassess symptom score + staining + TBUT + tolerance at 4-12 wk per step (cyclosporine effect at 3-6 m; lifitegrast at 6-12 wk; PFHO at 2-8 wk; varenicline nasal spray at 4 wk). IOP at 2-6 wk + 3-monthly if on topical corticosteroid. Adherence audit and preservative-free reinforcement at every visit (TFOS DEWS II PMID 28736335).

Disposition

Current setting: outpatient — Confirm DED by TFOS DEWS II criteria, identify dominant subtype (aqueous-deficient vs evaporative-MGD), exclude Sjögren / GVHD / cicatrising mimics, and walk the stepwise ladder with preservative-free principle (TFOS DEWS II PMID 28736335 + 28736342; GOBI/MOJAVE PMID 39564145; ONSET-2 PMID 34767866)

Disposition criteria:
- Continue outpatient ophthalmology / optometry co-management (TFOS DEWS II PMID 28736335)
- Cornea referral for severe refractory cases
- Rheum referral for Sjögren systemic management

Escalation triggers (move to higher acuity):
- Persistent epithelial defect / corneal ulcer → urgent cornea referral and amniotic membrane (PMID 28736335)
- Sjögren features + positive anti-SSA/SSB → route to rheum.sjogrens engine for systemic management
- Cicatrising changes / forniceal shortening → MMP / SJS / GVHD work-up

Earlier-Return Triggers

Return-precaution thresholds (watch for):
- [SEVERE] Persistent epithelial defect / filamentary keratitis / sterile ulcer on chronic-DED background
- [SEVERE] Dry eyes + dry mouth + arthralgias / parotid swelling / anti-SSA or anti-SSB positive
- [SEVERE] Forniceal shortening, symblepharon, or unilateral progressive cicatrising changes

Citations

- TFOS DEWS II Definition and Classification (Craig et al, Ocul Surf 2017, PMID 28736335) + TFOS DEWS II Diagnostic Methodology (Wolffsohn et al, Ocul Surf 2017, PMID 28736342) + TFOS Lifestyle Reports 2023 series + GOBI + MOJAVE pooled perfluorohexyloctane (Fahmy et al, Front Ophthalmol 2024, PMID 39564145) + ONSET-2 varenicline nasal spray (Wirta et al, Ophthalmology 2021, PMID 34767866) [PMID:28736335](https://pubmed.ncbi.nlm.nih.gov/28736335/)
- Cited evidence (PMID 28736342) [PMID:28736342](https://pubmed.ncbi.nlm.nih.gov/28736342/)
- Cited evidence (PMID 39564145) [PMID:39564145](https://pubmed.ncbi.nlm.nih.gov/39564145/)
- Cited evidence (PMID 34767866) [PMID:34767866](https://pubmed.ncbi.nlm.nih.gov/34767866/)

Last reconciled with current guidelines: 2026-05-26.
References
  • TFOS DEWS II Definition and Classification (Craig et al, Ocul Surf 2017, PMID 28736335) + TFOS DEWS II Diagnostic Methodology (Wolffsohn et al, Ocul Surf 2017, PMID 28736342) + TFOS Lifestyle Reports 2023 series + GOBI + MOJAVE pooled perfluorohexyloctane (Fahmy et al, Front Ophthalmol 2024, PMID 39564145) + ONSET-2 varenicline nasal spray (Wirta et al, Ophthalmology 2021, PMID 34767866) — PMID:28736335
  • Cited evidence (PMID 28736342) — PMID:28736342
  • Cited evidence (PMID 39564145) — PMID:39564145
  • Cited evidence (PMID 34767866) — PMID:34767866