12-phase flow (12)

1. 1FRAME
   Frame AMD as a leading-cause-of-blindness chronic disease with two distinct pathways (dry/GA and wet/neovascular) and increasingly disease-modifying therapies for both. Engine drives AREDS staging, dry-AMD nutritional prophylaxis (AREDS2; NO beta-carotene), GA-targeting complement inhibitors (pegcetacoplan / avacincaptad), and wet-AMD intravitreal anti-VEGF / anti-Ang2. Smoking + family history are the dominant non-disease-modifiable risk factors (AAO PPP AMD 2024).
   advance: AMD framing set
2. 2ENTRY
   Most entries are routine screening (drusen / RPE changes >50) or distorted-vision / sudden scotoma signalling wet conversion. Establish age, smoking status, family history, fellow-eye status (advanced AMD in one eye is the highest-risk single signal).
   inputs: age_over_50, smoking_status_current_former_never
   advance: baseline demographic + smoking documented
3. 3CONTEXT
   Calibrate the pretest: family history, smoking (current/former vs never decides AREDS formulation), dietary lutein/zeaxanthin/omega-3, existing supplements, cardiovascular co-morbidity (anti-VEGF systemic exposure concerns in selected patients).
   inputs: family_history_amd, dietary_and_supplement_use
   advance: risk profile + AREDS formulation pre-selected
4. 4RED_FLAGS
   Sudden central scotoma + metamorphopsia + intraretinal/subretinal fluid on OCT — new wet AMD requires urgent anti-VEGF (within 2 weeks). Pain + redness + hypopyon after intravitreal injection → ophtho.endophthalmitis.core.v1.
   advance: wet conversion and post-injection complications routed
5. 5INITIAL_WORKUP
   Dilated fundus examination + SD-OCT macula (both eyes — fellow-eye risk dominates). Stage by AREDS: no AMD / early (small drusen <63 microns) / intermediate (drusen >=125 microns or pigment changes) / advanced (GA or active wet). Baseline VA both eyes. Fundus autofluorescence to baseline GA lesion area (AAO PPP AMD 2024).
   inputs: dilated_fundus_examination, sd_oct_macula, baseline_visual_acuity
   advance: AREDS stage + dry vs GA vs wet pathway assigned
6. 6BRANCHING_WORKUP
   Suspected wet AMD on OCT (intraretinal fluid / SRF / PED) → FA / OCT-A to characterise MNV type 1 (sub-RPE) / type 2 (subretinal) / type 3 (intraretinal); polypoidal choroidal vasculopathy in Asian / pigmented patients (ICGA helps). GA growth tracked by serial fundus autofluorescence (AAO PPP AMD 2024).
   inputs: fundus_autofluorescence_fa_octa
   advance: MNV / PCV / type 3 / GA characterised
7. 7DIFFERENTIAL
   Terminal differential: AMD vs central serous chorioretinopathy (younger patient, no drusen, focal RPE leak on FA) vs diabetic maculopathy (route to ophtho.diabetic-retinopathy) vs myopic CNV (high myopia, peripapillary atrophy) vs Stargardt / pattern dystrophy (younger, family history, characteristic FAF) vs vitelliform lesion vs central retinal vein occlusion (sectoral haemorrhages) (AAO PPP AMD 2024).
   advance: AMD confirmed and look-alikes excluded
8. 8RISK_STRATIFICATION
   AREDS stage + fellow-eye status + family history + smoking sets 5-year progression risk. Advanced AMD in one eye → ~50% 5-year risk in the fellow eye → AREDS2 + monthly Amsler self-monitoring + low-vision plan. Intermediate bilateral → AREDS2 candidate. GA growth rate on FAF + foveal proximity drives complement-inhibitor decision (AAO PPP AMD 2024).
   advance: risk tier + treatment urgency set
9. 9TREATMENT
   (A) EARLY AMD: no specific therapy beyond modifiable-risk control (smoking cessation, Mediterranean-style diet with leafy greens and oily fish, UV protection, hypertension/lipid control). (B) INTERMEDIATE OR ADVANCED-IN-ONE-EYE DRY AMD: AREDS2 oral supplementation (Vitamin C 500 mg + Vitamin E 400 IU + Lutein 10 mg + Zeaxanthin 2 mg + Zinc 80 mg [or 25 mg low-zinc variant] + Cupric oxide 2 mg). NO beta-carotene — substituted because of lung-cancer signal in current/former smokers per AREDS2 (PMID 23644932). (C) GEOGRAPHIC ATROPHY: intravitreal complement inhibitor — pegcetacoplan 15 mg q25-60 d (Apellis SYFOVRE; OAKS/DERBY Lancet 2023 PMID 37865470 — 22% / 18% reduction in lesion growth at 24 months) OR avacincaptad pegol 2 mg q28 d (Iveric IZERVAY; GATHER1 + GATHER2; PMID 38719191 — reduced lesion growth + delayed BCVA loss). Slows GA growth; does not restore lost atrophy. New-onset exudative AMD is a known adverse event of pegcetacoplan (~11-13% by 24 months vs 2-4% sham). (D) WET AMD: intravitreal anti-VEGF — first-line faricimab 6 mg (TENAYA/LUCERNE Lancet 2022 PMID 35085502 — non-inferior to aflibercept at up to q16 wk in many patients), aflibercept 2 mg, aflibercept 8 mg (PULSAR — q12-16 wk), ranibizumab 0.5 mg, bevacizumab 1.25 mg off-label (CATT-equivalent), brolucizumab 6 mg (avoid in prior inflammation). Induction 3 monthly then treat-and-extend (T&E) per response.
   inputs: smoking_status_current_former_never, intraocular_inflammation_history_for_brolucizumab
   advance: pathway-appropriate tier started; smoking-aware AREDS formulation selected
10. 10DISPOSITION
    Routine outpatient retina co-management. Urgent (within 2 weeks) retina referral for new wet AMD signs (metamorphopsia + OCT fluid). Same-day vitreoretinal referral for post-injection endophthalmitis → ophtho.endophthalmitis.core.v1.
    advance: disposition + referral pathway documented
11. 11MONITORING
    Wet AMD: OCT + VA at each anti-VEGF visit; T&E interval driven by anatomic dryness. GA: fundus autofluorescence + OCT 6-monthly; watch for new-onset wet conversion (especially while on pegcetacoplan). Dry AMD on AREDS2: yearly OCT + Amsler self-monitoring at home (AAO PPP AMD 2024).
    advance: visit-by-visit OCT + VA + side-effect screen running
12. 12FOLLOWUP
    Lifelong arc. Reassess AREDS stage and fellow-eye risk yearly. Counsel smoking cessation (largest modifiable lever). Co-manage cataract surgery: do not defer in patients with concurrent intermediate AMD — better functional outcome generally outweighs theoretical AMD-progression concern (AREDS data reassuring). Low-vision rehabilitation for irreversible central loss; driving-vision regulations; depression and falls-screen in advanced bilateral disease (AAO PPP AMD 2024).
    inputs: amsler_grid_self_monitoring
    advance: long-term + low-vision + cataract co-planning documented