12-phase flow (12)

1. 1FRAME
   Frame as a microvascular complication of diabetes producing capillary dropout, microaneurysms, IRMA, macular oedema, and (proliferative) neovascularisation with risk of vitreous haemorrhage and tractional detachment. Engine drives ETDRS / ICDR staging, OCT-based DME assessment, and a tiered anti-VEGF / PRP / steroid / vitrectomy ladder. Early-worsening with rapid glycemic correction or pregnancy is the over-arching guardrail (ADA Standards 2026; AAO PPP DR 2025).
   advance: DR framing + early-worsening guardrail set
2. 2ENTRY
   Most entries are routine screening per ADA cadence; minority arrive with painless central blur (DME) or sudden vision loss with floaters (PDR vitreous haemorrhage). Establish diabetes type, duration, latest HbA1c, BP, lipids, and recent therapy intensification.
   inputs: diabetes_type_duration_a1c, hba1c_and_glycemic_trend
   advance: diabetes baseline + entry trigger documented
3. 3CONTEXT
   Calibrate disease-acceleration risk: BP, lipid panel, eGFR, pregnancy / pre-conception status, recent SGLT2/GLP-1 start, bariatric surgery, recent insulin intensification. ACCORD-Eye signal: intensive glycaemic + fenofibrate adjunct slowed DR progression. Pregnancy + rapid-correction = early-worsening risk → shorter follow-up interval (ADA Standards 2026).
   inputs: blood_pressure_and_lipid_profile, pregnancy_or_planning_conception, recent_intensification_sglt2_glp1_insulin
   advance: systemic risk + early-worsening triggers captured
4. 4RED_FLAGS
   Sudden visual loss + dense floaters + known PDR → vitreous haemorrhage / tractional RD — same-day vitreoretinal referral. Pain + redness + hypopyon after recent intravitreal injection → endophthalmitis — route OUT to ophtho.endophthalmitis.core.v1 (vitreous tap + intravitreal antibiotics).
   advance: red flag routes confirmed
5. 5INITIAL_WORKUP
   Dilated fundus / ultra-widefield examination — stage by ICDR (no DR / mild NPDR / moderate / severe NPDR by 4-2-1 / PDR). SD-OCT macula — centre-involving vs non-centre-involving DME with central subfield thickness; intraretinal cysts / subretinal fluid / DRIL. Fundus photography for baseline documentation (AAO PPP DR 2025).
   inputs: dilated_fundus_examination_or_widefield, oct_macula_center_subfield_thickness
   advance: ICDR stage + DME centre-involvement documented
6. 6BRANCHING_WORKUP
   FA / OCT-A to characterise capillary non-perfusion and neovascularisation, especially in severe NPDR → PDR transition and when planning targeted PRP vs anti-VEGF (Protocol S). B-scan ultrasonography if vitreous haemorrhage obscures the fundus (rule out tractional detachment behind the blood).
   inputs: fluorescein_angiography_or_oct_a
   advance: NV / non-perfusion mapped; ischaemia-guided plan set
7. 7DIFFERENTIAL
   Terminal differential: diabetic retinopathy (microaneurysms, dot/blot haemorrhages, exudates, NV in a diabetic) vs retinal vein occlusion (sectoral haemorrhage + cotton-wool spots in the venous territory) vs hypertensive retinopathy (arteriolar narrowing, AV nicking, no microaneurysms early) vs radiation retinopathy (history) vs OIS (carotid stenosis with mid-peripheral haemorrhages and pain) vs sickle retinopathy (sea-fan NV) (AAO PPP DR 2025).
   advance: DR confirmed and look-alikes excluded
8. 8RISK_STRATIFICATION
   ICDR stage + DME centre-involvement + HbA1c trend + BP / lipids + pregnancy + visual acuity together set treatment urgency. Severe NPDR has ~50% 1-year progression to PDR by ICDR/ETDRS; pregnancy + rapid HbA1c drop accelerates. Centre-involving DME with vision loss triggers anti-VEGF.
   inputs: hba1c_and_glycemic_trend, pregnancy_or_planning_conception
   advance: risk tier + treatment urgency set
9. 9TREATMENT
   (A) SYSTEMIC: optimise HbA1c, BP (<130/80), and lipids (statin; consider fenofibrate adjunct per ACCORD-Eye if eligible). Avoid abrupt large HbA1c drops where DR already severe; co-manage pregnancy with maternal-fetal medicine. (B) MILD-MODERATE NPDR without DME: observation + systemic optimisation + return per cadence. (C) SEVERE NPDR: consider intravitreal anti-VEGF (PANORAMA-class signal) or PRP if poor adherence to anti-VEGF visits; tighten follow-up. (D) CENTRE-INVOLVING DME with vision loss: first-line intravitreal anti-VEGF (faricimab YOSEMITE/RHINE PMID 35085503 with q4 to q16-wk personalised treatment interval; aflibercept 2 mg or 8 mg PHOTON; ranibizumab; bevacizumab off-label per Protocol T). Intravitreal corticosteroid implants (dexamethasone Ozurdex / fluocinolone Iluvien) for anti-VEGF-incomplete-response or pseudophakic patients — cataract and IOP risk. (E) PDR: intravitreal anti-VEGF (Protocol S Gross JAMA 2015 PMID 26565927 — ranibizumab non-inferior to PRP at 2 y with less peripheral VF loss, less DME, more visits) OR PRP (DRS / ETDRS); vitrectomy for non-clearing vitreous haemorrhage or tractional detachment.
   inputs: lens_status_phakic_pseudophakic, baseline_iop_for_steroid_implant
   advance: stage-appropriate tier started; systemic optimisation co-engaged
10. 10DISPOSITION
    Routine outpatient ophthalmology. Same-day vitreoretinal referral for: PDR with vitreous haemorrhage or tractional RD; suspected post-injection endophthalmitis (→ ophtho.endophthalmitis.core.v1). Pregnant patient with severe NPDR / PDR → expedited treatment + maternal-fetal-medicine co-management (ADA Standards 2026).
    advance: disposition + referral pathway set
11. 11MONITORING
    OCT central subfield thickness and visual acuity at each anti-VEGF visit; ICDR stage and presence/extent of NV at each examination. After PRP: monitor regression of NV at 4-6 weeks then 3-monthly. After steroid implant: IOP at 2-6 weeks and 3-monthly (steroid-responder IOP rise / open-angle glaucoma risk). HbA1c, BP, lipids per ADA cadence.
    advance: visit-by-visit OCT + VA + IOP + ICDR re-grade running
12. 12FOLLOWUP
    Lifelong screening + treatment arc. Adjust cadence by ICDR stage: q12-24 mo no DR, q12 mo mild, q6-12 mo moderate/severe NPDR, q1-4 mo PDR / DME on therapy. Pregnancy: pre-conception baseline then q1-3 months. Co-manage cataract surgery (DME can worsen post-op — peri-operative anti-VEGF or steroid). Low-vision rehabilitation for irreversible field loss / advanced disease (AAO PPP DR 2025; ADA Standards 2026).
    advance: stage-appropriate cadence + cataract / pregnancy / low-vision planning documented