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ophtho.amd.core.v1PRODUCTION
ophtho.amd.core.v1

Age-related macular degeneration (dry, GA, and wet/neovascular)

general_internal_medicinechronicsubacuteadultgeriatric
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Encounter flow

12/12 authored

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

Current phase

Frame

Detailed

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).

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AMD framing set

Patient inputs (10)

Smoking is the strongest modifiable risk; current or former smokers must NOT receive beta-carotene-containing AREDS formulations — use the AREDS2 lutein/zeaxanthin formulation (PMID 23644932)

AMD is the leading cause of central vision loss >50; pretest probability rises steeply after 65 (AAO PPP AMD 2024)

Dilated fundus exam documents drusen size/extent, RPE changes, geographic atrophy, haemorrhage, exudate, pigment epithelial detachment (AAO PPP AMD 2024)

SD-OCT is the diagnostic centrepiece — drusen morphology, RPE/photoreceptor atrophy, intraretinal fluid, subretinal fluid, sub-RPE fluid/PED diagnose dry vs GA vs wet AMD and drive anti-VEGF / complement-inhibitor treatment (AAO PPP AMD 2024)

Baseline distance and reading VA drive treatment urgency and monitoring (AAO PPP AMD 2024)

FAF maps GA lesion area and growth (primary endpoint of complement-inhibitor trials); FA/OCT-A characterises MNV type and polypoidal CV (AAO PPP AMD 2024)

Family history (CFH and ARMS2 polymorphisms) raises risk substantially; influences screening cadence (AAO PPP AMD 2024)

Dietary lutein/zeaxanthin and omega-3 intake influences supplement decisions; document existing supplement use to avoid double-dosing of zinc/copper (AAO PPP AMD 2024)

Daily Amsler grid by the patient at home is the practical early-warning for wet conversion in intermediate AMD (AAO PPP AMD 2024)

Brolucizumab carries an intraocular-inflammation / retinal-vasculitis signal — avoid in patients with prior inflammation (HAWK/HARRIER post-hoc; FDA letter)

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

Severity triggers (5)

5 need judgement
  • informationallife_threateningpost_injection_endophthalmitis_amd
    Pain + hypopyon + visual loss after intravitreal injection
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalseverenew_wet_amd_metamorphopsia
    New metamorphopsia + IRF/SRF/PED on OCT in an AMD patient — wet conversion
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalseverebeta_carotene_in_smoker_areds_formulation
    Patient with current or former smoking history considered for an old (AREDS, not AREDS2) beta-carotene-containing formulation
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalseverebrolucizumab_prior_intraocular_inflammation
    Considering brolucizumab in a patient with prior intraocular inflammation
    Trigger could not be auto-evaluated — needs clinician judgement.
  • informationalseverega_complement_inhibitor_wet_conversion
    New wet conversion (IRF/SRF/PED) during pegcetacoplan or avacincaptad therapy
    Trigger could not be auto-evaluated — needs clinician judgement.

Workflow calculators

This dossier does not reference any calculators.

Recommended regimen

AMD — pathway-specific ladder (AREDS2 dry / complement-inhibitor GA / anti-VEGF wet)
axis: amd_pathway_specific_ladderstep 1 - Step 1 — Early / intermediate / advanced-in-one-eye DRY AMD: AREDS2 supplementation
Selected step "Step 1 — Early / intermediate / advanced-in-one-eye DRY AMD: AREDS2 supplementation" — Intermediate AMD (drusen >=125 microns or pigment changes) bilaterally, or advanced AMD in one eye
  • areds2_supplementation_no_beta_carotene
    first line
    antioxidant_mineral_supplement
    triggers: intermediate_amd, advanced_amd_in_one_eye
    AREDS2 — Age-Related Eye Disease Study 2 Research Group JAMA 2013 (PMID 23644932): substituting lutein 10 mg + zeaxanthin 2 mg for beta-carotene preserved efficacy and avoided the beta-carotene lung-cancer signal in former smokers (23 vs 11 lung-cancer cases in original AREDS).
  • smoking_cessation_and_mediterranean_diet
    first line
    lifestyle_modification
    triggers: any_amd_stage, current_or_former_smoker
    AAO PPP AMD 2024 — smoking is the strongest modifiable risk; Mediterranean dietary pattern (leafy greens, oily fish, nuts) associated with lower progression.

outpatient playbook — drug actions (5)

  1. 1. AREDS2 supplementation (no beta-carotene)
    Vit C 500 mg + Vit E 400 IU + Lutein 10 mg + Zeaxanthin 2 mg + Zinc 80 mg [or 25 mg] + Cupric oxide 2 mg • PO • daily
    trigger: Intermediate or advanced-in-one-eye AMD (PMID 23644932)
    AREDS2 lutein/zeaxanthin substitution maintains efficacy and avoids smoker lung-cancer signal
  2. 2. pegcetacoplan intravitreal (GA)
    rxcui 2557372
    15 mg / 0.1 mL • intravitreal • q25-60 d
    trigger: Geographic atrophy with growing or foveal-threatening lesion (OAKS/DERBY PMID 37865470)
    Slows GA lesion growth 18-22% at 24 m; monitor for new wet conversion
  3. 3. avacincaptad pegol intravitreal (GA)
    rxcui 2645108
    2 mg / 0.1 mL • intravitreal • q28 d
    trigger: Geographic atrophy (GATHER1/GATHER2 PMID 38719191)
    Reduces GA growth and delays >=15-letter loss
  4. 4. faricimab intravitreal (wet AMD)
    rxcui 2591519
    6 mg / 0.05 mL • intravitreal • q4 wk x4 then q8-16 wk per activity
    trigger: Active MNV on OCT (TENAYA/LUCERNE PMID 35085502)
    Non-inferior to aflibercept with up-to-q16 wk durability in many patients
  5. 5. aflibercept 2 mg / 8 mg intravitreal (wet AMD)
    rxcui 1232150
    2 mg / 0.05 mL standard or 8 mg q12-16 wk • intravitreal • q4 wk x3 then q8-16 wk
    trigger: Active MNV (VIEW; PULSAR)
    Established and high-dose extended-interval options

Auto-drafted A&P note

outpatient

Subjective

- Possible entry pathways: Distorted straight lines (metamorphopsia) on Amsler grid or in daily life in a patient >50 — wet AMD until proven otherwise (AAO PPP AMD 2024); Sudden central blur, scotoma, or visual loss in an older adult — possible new wet AMD or progression of GA (AAO PPP AMD 2024); Drusen, pigment changes, or geographic atrophy noted on routine eye examination >50 years — entry to AREDS staging and prophylaxis (PMID 23644932).

Objective

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

Assessment

**Age-related macular degeneration (dry, GA, and wet/neovascular)** (ophtho.amd.core.v1).
Phenotype framing: 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).
Scope: 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).

No severity triggers fired against current inputs.

Plan

Regimen axis: **AMD — pathway-specific ladder (AREDS2 dry / complement-inhibitor GA / anti-VEGF wet)** — step "Step 1 — Early / intermediate / advanced-in-one-eye DRY AMD: AREDS2 supplementation".
1. areds2_supplementation_no_beta_carotene (antioxidant_mineral_supplement, first line) — AREDS2 — Age-Related Eye Disease Study 2 Research Group JAMA 2013 (PMID 23644932): substituting lutein 10 mg + zeaxanthin 2 mg for beta-carotene preserved efficacy and avoided the beta-carotene lung-cancer signal in former smokers (23 vs 11 lung-cancer cases in original AREDS).
2. smoking_cessation_and_mediterranean_diet (lifestyle_modification, first line) — AAO PPP AMD 2024 — smoking is the strongest modifiable risk; Mediterranean dietary pattern (leafy greens, oily fish, nuts) associated with lower progression.

Setting playbook (outpatient) — Stage by AREDS, select smoking-aware AREDS2 supplementation for intermediate/advanced-in-one-eye dry AMD, deploy complement inhibitor for GA, deliver intravitreal anti-VEGF for wet AMD within 2 weeks of diagnosis, and run lifelong OCT-based monitoring with home Amsler grid (AAO PPP AMD 2024; AREDS2 PMID 23644932; OAKS/DERBY PMID 37865470; TENAYA/LUCERNE PMID 35085502)
3. AREDS2 supplementation (no beta-carotene) Vit C 500 mg + Vit E 400 IU + Lutein 10 mg + Zeaxanthin 2 mg + Zinc 80 mg [or 25 mg] + Cupric oxide 2 mg PO daily — Intermediate or advanced-in-one-eye AMD (PMID 23644932) (AREDS2 lutein/zeaxanthin substitution maintains efficacy and avoids smoker lung-cancer signal)
4. pegcetacoplan intravitreal (GA) 15 mg / 0.1 mL intravitreal q25-60 d — Geographic atrophy with growing or foveal-threatening lesion (OAKS/DERBY PMID 37865470) (Slows GA lesion growth 18-22% at 24 m; monitor for new wet conversion)
5. avacincaptad pegol intravitreal (GA) 2 mg / 0.1 mL intravitreal q28 d — Geographic atrophy (GATHER1/GATHER2 PMID 38719191) (Reduces GA growth and delays >=15-letter loss)
6. faricimab intravitreal (wet AMD) 6 mg / 0.05 mL intravitreal q4 wk x4 then q8-16 wk per activity — Active MNV on OCT (TENAYA/LUCERNE PMID 35085502) (Non-inferior to aflibercept with up-to-q16 wk durability in many patients)
7. aflibercept 2 mg / 8 mg intravitreal (wet AMD) 2 mg / 0.05 mL standard or 8 mg q12-16 wk intravitreal q4 wk x3 then q8-16 wk — Active MNV (VIEW; PULSAR) (Established and high-dose extended-interval options)

Non-pharmacologic actions:
- Smoking cessation counselling at every visit (AAO PPP AMD 2024)
- Home Amsler grid daily for intermediate/advanced-in-one-eye AMD
- Mediterranean-style diet (leafy greens, oily fish, nuts) + UV protection
- Low-vision rehabilitation referral for advanced bilateral disease + driving-vision counsel
- Cataract surgery is appropriate in AMD when visually significant (do not defer without reason)

AVOID / contraindication checks:
- NO beta carotene AREDS formulation in current or former smokers (PMID 23644932; CARET lung cancer signal)
- Complement inhibitors increase new onset exudative AMD incidence — MNV surveillance during treatment (PMID 37865470)
- Brolucizumab intraocular inflammation and retinal vasculitis signal — avoid in prior inflammation (HAWK/HARRIER; FDA letter)
- Post intravitreal injection endophthalmitis routes OUT to ophtho.endophthalmitis.core.v1
- Do not defer cataract surgery in AMD without clear reason (AAO PPP AMD 2024; AREDS reassuring)

Monitoring

Regimen monitoring:
- Wet AMD: OCT + VA at each visit; T&E interval per anatomic response (AAO PPP AMD 2024)
- GA on complement inhibitor: FAF + OCT q3-6 mo; vigilant for new MNV (~10-13% at 24 m on pegcetacoplan) (PMID 37865470)
- AREDS2 dry AMD: annual exam + OCT; home Amsler grid daily (PMID 23644932)
- Smoking cessation reinforcement at every visit

Setting (outpatient) monitoring:
- Wet AMD: OCT + VA at each anti-VEGF visit, T&E interval (AAO PPP AMD 2024)
- GA on complement inhibitor: FAF + OCT q3-6 mo, MNV surveillance (PMID 37865470)
- Dry AMD on AREDS2: annual OCT + home Amsler grid
- Brolucizumab patients: intraocular-inflammation surveillance every visit

Follow-up plan: 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).
- Close-out criterion: long-term + low-vision + cataract co-planning documented

Monitoring phase: 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).

Disposition

Current setting: outpatient — Stage by AREDS, select smoking-aware AREDS2 supplementation for intermediate/advanced-in-one-eye dry AMD, deploy complement inhibitor for GA, deliver intravitreal anti-VEGF for wet AMD within 2 weeks of diagnosis, and run lifelong OCT-based monitoring with home Amsler grid (AAO PPP AMD 2024; AREDS2 PMID 23644932; OAKS/DERBY PMID 37865470; TENAYA/LUCERNE PMID 35085502)

Disposition criteria:
- Continue outpatient retina co-management with stage-appropriate cadence (AAO PPP AMD 2024)
- Low-vision and depression screen for advanced bilateral disease

Escalation triggers (move to higher acuity):
- New metamorphopsia + IRF/SRF/PED on OCT → urgent retina referral for anti-VEGF within 2 weeks
- Post-injection pain + redness + hypopyon → ophtho.endophthalmitis.core.v1
- New wet conversion during complement-inhibitor therapy → add anti-VEGF

Earlier-Return Triggers

Return-precaution thresholds (watch for):
- [LIFE_THREATENING] Pain + hypopyon + visual loss after intravitreal injection
- [SEVERE] New metamorphopsia + IRF/SRF/PED on OCT in an AMD patient — wet conversion
- [SEVERE] Patient with current or former smoking history considered for an old (AREDS, not AREDS2) beta-carotene-containing formulation

Citations

- AAO Preferred Practice Pattern AMD 2024 cycle + AREDS2 (Age-Related Eye Disease Study 2 Research Group, JAMA 2013, PMID 23644932) + OAKS & DERBY pegcetacoplan (Heier et al, Lancet 2023, PMID 37865470) + GATHER1 & GATHER2 avacincaptad pegol vision-loss analysis (Danzig/Khanani et al, Ophthalmol Retina 2024, PMID 38719191) + TENAYA & LUCERNE faricimab nAMD (Heier et al, Lancet 2022, PMID 35085502) [PMID:23644932](https://pubmed.ncbi.nlm.nih.gov/23644932/)
- Cited evidence (PMID 37865470) [PMID:37865470](https://pubmed.ncbi.nlm.nih.gov/37865470/)
- Cited evidence (PMID 38719191) [PMID:38719191](https://pubmed.ncbi.nlm.nih.gov/38719191/)
- Cited evidence (PMID 35085502) [PMID:35085502](https://pubmed.ncbi.nlm.nih.gov/35085502/)

Last reconciled with current guidelines: 2026-05-26.
References
  • AAO Preferred Practice Pattern AMD 2024 cycle + AREDS2 (Age-Related Eye Disease Study 2 Research Group, JAMA 2013, PMID 23644932) + OAKS & DERBY pegcetacoplan (Heier et al, Lancet 2023, PMID 37865470) + GATHER1 & GATHER2 avacincaptad pegol vision-loss analysis (Danzig/Khanani et al, Ophthalmol Retina 2024, PMID 38719191) + TENAYA & LUCERNE faricimab nAMD (Heier et al, Lancet 2022, PMID 35085502) — PMID:23644932
  • Cited evidence (PMID 37865470) — PMID:37865470
  • Cited evidence (PMID 38719191) — PMID:38719191
  • Cited evidence (PMID 35085502) — PMID:35085502