12-phase flow (12)

1. 1FRAME
   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).
   advance: DED frame + subtype awareness set
2. 2ENTRY
   Recognise the classic gritty/burning/fluctuating-vision presentation; capture validated symptom score (OSDI or DEQ-5) up front as the gateway PRO that drives step-up decisions (TFOS DEWS II Methodology PMID 28736342).
   inputs: symptom_severity_oder_deq5_or_osdi
   advance: entry trigger present; symptom score recorded
3. 3CONTEXT
   Build context: meibography / lid-margin signs (MGD is the commonest evaporative driver), systemic drugs (antihistamines / isotretinoin / antidepressants / diuretics / HRT), environment (screen time, humidity, air travel), contact-lens use, autoimmune-disease history, prior cataract/refractive surgery (TFOS Lifestyle 2023).
   inputs: meibography_or_lid_margin_assessment, systemic_drugs_anticholinergic_isotretinoin_diuretic, contact_lens_use_and_environment
   advance: subtype dominance + modifiable-driver inventory done
4. 4RED_FLAGS
   Acute red eye + photophobia + decreased vision = not simple DED — route to ophtho.acute-red-eye.core.v1; corneal ulcer / dendritic keratitis → microbial keratitis engine; persistent unilateral DED with cicatrising changes → consider mucous membrane pemphigoid / SJS survivor / GVHD.
   advance: mimics screened; routes confirmed
5. 5INITIAL_WORKUP
   TFOS DEWS II diagnostic ladder: symptom score positive (DEQ-5 >=6 / OSDI >=13) plus one of (NIBUT <10 s, tear osmolarity >=308 mOsm/L or inter-eye diff >=8, positive ocular-surface staining) confirms DED. Document subtype-defining tests (PMID 28736342).
   inputs: tear_break_up_time_nibut_or_fbut, ocular_surface_staining_fluorescein_lissamine, tear_osmolarity
   advance: DED diagnosis confirmed; subtype dominance recorded
6. 6BRANCHING_WORKUP
   Schirmer <=5 → aqueous-deficient → screen Sjögren (anti-SSA / anti-SSB + ANA + RF + SSC criteria) and refer rheum if positive systemic features; meibography dropout + lid-margin signs → evaporative MGD-dominant DED; cicatrising changes / forniceal shortening → MMP / SJS / GVHD; ocular-rosacea features → derm route (TFOS DEWS II PMID 28736335).
   inputs: schirmer_test_with_anaesthesia, sjogren_features_anti_ssa_anti_ssb, graft_vs_host_or_sjs_history
   advance: subtype + systemic cause assigned (or routed)
7. 7DIFFERENTIAL
   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).
   advance: single best DED subtype assigned; mimics routed
8. 8RISK_STRATIFICATION
   Stage severity by combining symptom score + staining + TBUT + osmolarity. Mild: symptom-dominant with minimal staining → tier 1; moderate: persistent staining despite tier 1 → tier 2; severe: filamentary keratitis / persistent epithelial defect / sterile ulcer → tier 3-4 with corneal-rescue measures (TFOS DEWS II PMID 28736335).
   advance: severity tier + treatment urgency set
9. 9TREATMENT
   Stepwise ladder per TFOS DEWS II + Lifestyle 2023. STEP 1 (all patients): education + environment (humidity, 20-20-20 screen rule, hydration), warm compress + lid hygiene (foundation for MGD-evaporative), omega-3 (mixed evidence; consider for MGD), preservative-free artificial tears, cessation of preserved drops. STEP 2 (persistent inflammation): cyclosporine ophthalmic emulsion 0.05% (Restasis BID) or 0.09% (Cequa BID), lifitegrast 5% (Xiidan BID), perfluorohexyloctane (Miebo q.i.d. — evaporative MGD-DED first anti-evaporative drop, GOBI/MOJAVE PMID 39564145), punctal plugs (silicone preferred), therapeutic in-office MGD procedures (LipiFlow, IPL). STEP 3 (inadequate response): short-course (2-4 wk) topical corticosteroid PRESERVATIVE-FREE (loteprednol / fluorometholone — IOP monitoring), autologous serum tears, varenicline nasal spray 0.03 mg BID (Tyrvaya — ONSET-2 PMID 34767866). STEP 4 (severe): amniotic membrane (Prokera) for persistent epithelial defect, scleral lenses, permanent punctal occlusion, tarsorrhaphy. Co-engage rheum.sjogrens by engine_id if confirmed Sjögren (TFOS DEWS II PMID 28736335).
   inputs: preservative_drop_burden_BAK
   advance: step-appropriate therapy started; preservative-free principle applied
10. 10DISPOSITION
    Almost entirely outpatient ophthalmology / optometry. Same-day referral for: persistent epithelial defect / corneal ulcer; new severe cicatrising changes; signs of microbial keratitis on a chronic-DED substrate (TFOS DEWS II PMID 28736335).
    advance: disposition + referral pathway documented
11. 11MONITORING
    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).
    advance: step-appropriate monitoring cadence + IOP surveillance running
12. 12FOLLOWUP
    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).
    advance: long-term + systemic-disease + perioperative planning documented