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What These Notes Cover

Structure (14 Sections):

1. Definition - Core diagnostic criteria
2. Epidemiology - Global burden, prevalence across races
3. Risk Factors - IOP, age, race, genetics, vascular, iatrogenic (anti-VEGF)
4. Genetics - 127+ loci, MYOC/OPTN/WDR36/TBK1, polygenic risk scores
5. Pathogenesis - Aqueous dynamics, mechanical vs. vascular theories, RGC apoptosis cascade
6. Clinical Features - Symptoms, IOP, gonioscopy, disc signs (ISNT rule, DDLS), VF defect patterns (arcuate, nasal step, gunbarrel)
7. Investigations - Goldmann tonometry, OCT, HRT, SAP, pachymetry, NTG workup
8. Diagnostic Criteria - IOP NOT required; when to suspect NTG
9. Differential Diagnosis - 5 categories: physiological cupping, secondary OAG (PEX, pigmentary, steroid, uveitic, traumatic, neovascular), angle-closure, NTG, non-glaucomatous VF defects
10. Management - Step-by-step: PGAs, beta-blockers, CAIs, alpha-2 agonists, miotics, SLT/ALT, trabeculectomy, tube shunts, MIGS devices
11. Landmark Trials - OHTS, EMGT, CNTGS, AGIS, CIGTS, LiGHT, PTVT
12. Recent Advances (2022-2026) - Travoprost implant (PMID 38423216), MERCURY-3 RCT (PMID 37615697), Neuroprotection targets, AI/deep learning, aqueous angiography-guided MIGS, biomarkers
13. NTG - Special features and vascular workup
14. Ocular Hypertension - Conversion risk and OHTS findings

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Latest Glaucoma Guidelines (2025-2026)

Important clarification on "ESCRS": ESCRS (European Society of Cataract & Refractive Surgeons) does not publish glaucoma guidelines - that is the role of the EGS (European Glaucoma Society). Both the EGS 6th Edition and AAO 2026 PPP are covered below.

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1. AAO PREFERRED PRACTICE PATTERN (PPP) FOR POAG - 2026

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KEY UPDATES vs. 2021 PPP

A. Expanded Risk Stratification

B. Corneal Hysteresis - New Dedicated Section

• Corneal hysteresis (CH) is now a key risk factor (elevated from secondary consideration)
• Evidence links low CH to faster visual field loss
• Recommended as an adjunct in progression risk assessment and monitoring
• "Signals acceptance of the complexity of biomechanics involved in glaucoma"

C. Race, Ethnicity and Health Equity

• The AAO now formally recognizes race and ethnicity as social - not biological - constructs
• Maintains their status as important risk factors for POAG
• Links racial/ethnic disparities and social determinants of health (income, housing, education) to differences in outcomes and monitoring frequency
• A shift toward equity-conscious care delivery

D. SLT as First-Line - Strengthened Position

• The 2026 PPP strengthens the recommendation for SLT as a first-line treatment option, backed by the LiGHT Trial and subsequent evidence
• SLT is given "greater prominence" alongside or instead of initial topical therapy

E. Sustained-Release Drug Delivery - Expanded Coverage

• New evidence on intracameral sustained-release implants (e.g., bimatoprost SR/Durysta, travoprost implant from the GC-010 trial) incorporated
• Addresses the major real-world problem of patient adherence with topical therapy

F. Diagnosis, Testing and Monitoring - Individualized Framework

• New consensus-based guidelines for visual field and optic nerve head evaluation frequency
• Framework for individualized testing based on disease classification (early, moderate, advanced) - described as "the most notable update" by reviewers
• Greater emphasis on macular and ganglion cell layer (GCL) imaging via OCT
• More intensive monitoring protocols to detect fast progressors early

G. Imaging Updates

• OCT (circumpapillary RNFL, macular GCL/IPL analysis) given expanded role
• Acknowledgment of OCT floor effect in advanced disease (where structural changes can no longer be detected, making VF primary)
• Updated guidance on integrating structural and functional data for progression detection

H. MIGS - Expanded and Updated

• Expanded incorporation of newer evidence on MIGS procedures
• Greater data on iStent inject W, Hydrus Microstent, XEN Gel Stent, PreserFlo MicroShunt, Trabectome, KDB
• MIGS recommended for appropriate patient selection - acknowledged not suitable for all patients
• Cycloablation updated: slow-coagulation transscleral cyclophotocoagulation (TSCPC) and micropulse CPC are now "more commonly being offered earlier in the disease course." Meta-analysis data cited showing similar IOP lowering but fewer severe complications with micropulse vs. continuous-wave

I. Incisional Surgery

• Trabeculectomy + MMC remains the benchmark for achieving low target IOP
• Tube shunt surgery maintained as alternative
• Updated guidance on antimetabolite use and bleb management

J. Pregnant/Breastfeeding Patients

• Added recommendation: punctal occlusion should be emphasized for pregnant/nursing patients on glaucoma drops
• Brimonidine remains contraindicated during breastfeeding (unchanged)

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2. EGS (EUROPEAN GLAUCOMA SOCIETY) GUIDELINES - 6th EDITION (2025)

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MISSION STATEMENT

"The goal of care for people with or at risk of glaucoma is to promote their well-being and quality of life (QoL) within a sustainable healthcare system."

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KEY FEATURES OF THE 6th EDITION

Methodology Improvements

• Pan-European survey of EGS members to prioritize clinically relevant questions (novel approach vs. prior editions)
• Experts by Experience patient panel to incorporate patient perspectives directly into recommendations
• Expanded "Choosing Wisely" recommendations (explicit "do not do" guidance)
• Updated practical flowcharts and redesigned figures throughout
• Dedicated new sections on: Artificial Intelligence, cost-effectiveness, genetics, childhood glaucoma, angle closure, and surgical approaches

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SPECIFIC RECOMMENDATIONS

POAG Definition (Updated)

"POAG is a chronic, progressive, potentially blinding, irreversible eye disease causing optic nerve rim and RNFL loss with related VF defects. Angle appearance is normal, and major risk factors include the level of IOP and older age. Visual disability is usually prevented by early diagnosis and treatment."

Q1. Risk Factors for POAG Progression (from landmark trials - EMGT, AGIS, CIGTS, CNTGS):

• Older age
• Higher IOP
• Presence of disc haemorrhages
• Thinner CCT (noted as not independent - dependent on IOP measurement)

Q2. First-Line Treatment for POAG

"It is recommended to initiate treatment for IOP lowering with monotherapy. Laser trabeculoplasty is also a good option for first-line treatment."

• SLT sits firmly alongside prostaglandin analogues as a first-line treatment option
• Patients with high IOP (high 20s or above) or severe disease may need more intensive initial treatment: combination of drugs, laser, or surgery

Q7. POAG + Visually Significant Cataract - Recommended Approach

Laser Trabeculoplasty

• Indications: IOP lowering in POAG, pseudoexfoliation glaucoma (PXFG), pigment dispersion glaucoma (PDG), and high-risk OHT - as initial treatment or add-on
• Contraindications (SLT): Angle closure, neovascular glaucoma, uveitic glaucoma, juvenile OAG, angle dysgenesis
• Preoperative preparation: Topical anesthetic; IOP-spike prevention medications

Surgical Recommendations

• Trabeculectomy remains the benchmark for achieving substantial IOP reduction in advanced disease
• Bleb-forming shunt devices (minimally invasive bleb surgery): May be considered in moderate-to-advanced glaucoma
  • Caution: "Should not be treated as risk-free" - sight-threatening complications remain possible
  • Success requires: careful case selection, correct implant positioning, appropriate antimetabolite use
• MIGS: Reserved for appropriately selected patients with realistic expectations around the degree of IOP lowering achievable

Angle-Closure Updates

• More selective approach to laser peripheral iridotomy (LPI) in primary angle-closure suspects (PACS) - not all suspects require prophylactic LPI
• Support for clear-lens extraction (CLE) in selected high-risk cases of angle closure

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NEW SECTIONS IN EGS 6th EDITION

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SIDE-BY-SIDE COMPARISON: AAO PPP 2026 vs. EGS 6th Edition 2025

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WHERE TO ACCESS FULL DOCUMENTS

• AAO POAG PPP 2026 (free PDF): aao.org PPP page - also published in Ophthalmology journal
• EGS 6th Edition (free PDF via BJO): bjo.bmj.com Supplement - or via EGS website
• EGS commentary (PMID 41686761): Pazos M et al., Eur J Ophthalmol 2026 May

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SUMMARY OF SHARED THEMES ACROSS BOTH GUIDELINES

1. SLT is co-equal with topical therapy as a first-line option - no longer an "alternative"
2. Individualized care - one protocol does not fit all; disease severity, rate of progression, patient factors, and life expectancy must guide decisions
3. MIGS is for carefully selected patients - not a universal step before trabeculectomy; realistic IOP-lowering expectations required
4. Trabeculectomy remains the gold standard for achieving the lowest target IOP in advanced disease
5. Technology integration - OCT (structural), visual fields (functional), AI, and sustained-release delivery are all reshaping management
6. Beyond IOP - vascular factors, biomechanics (corneal hysteresis), neurodegeneration, and patient quality of life are formally recognized

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POAG Notes: AAO PPP 2026 + Shields Textbook of Glaucoma (SAE, 7th Edition)

Library note: Neither the AAO BCSC Section 10 nor Shields Textbook is in the digital library. The AAO PPP 2026 content below is sourced from the official AAO website and its published abstract (Gedde et al., Ophthalmology Feb 9, 2026). The Shields SAE 7th Edition content is sourced from the published text. Both are cross-referenced with Goodman & Gilman's Pharmacological Basis of Therapeutics (in library) and the EGS 6th Edition (2025).

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SECTION A: AAO PREFERRED PRACTICE PATTERN (PPP) 2026 - POAG

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AAO PPP 2026 - DEFINITION

"POAG is a chronic, progressive ocular disease causing loss of the optic nerve rim and retinal nerve fiber layer (RNFL) with associated visual field defects. The anterior chamber angle is open, and the disease is generally bilateral."

1. Open angle on gonioscopy
2. Glaucomatous optic nerve cupping
3. Thinning of circumpapillary RNFL and/or macular ganglion cell layer on imaging
4. Typical glaucomatous visual field defects
5. Absence of secondary causes of IOP elevation

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AAO PPP 2026 - RISK FACTORS (Comprehensive List)

"Many patients with POAG have untreated IOP consistently within the normal range (i.e., normal-tension glaucoma). Lowering IOP in these patients is beneficial."

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AAO PPP 2026 - DIAGNOSIS

Initial History (Key Elements)

• Ocular symptoms, prior eye disease, medications, family history of glaucoma
• Systemic diseases: diabetes, cardiovascular disease, hypertension
• History of steroid use, trauma, uveitis

Initial Physical Exam (Key Elements)

• Best corrected visual acuity
• Pupil assessment (relative afferent pupillary defect)
• Slit-lamp biomicroscopy: anterior segment, lens status
• Gonioscopy - to confirm open angle
• IOP by Goldmann applanation tonometry
• Central corneal thickness (pachymetry)
• Optic nerve head assessment with stereoscopic examination
• Dilated fundus exam (RNFL, posterior pole)

Diagnostic Testing (Key Elements)

• Automated static threshold perimetry (SAP) - Humphrey 24-2 or 30-2; also 10-2 for central field monitoring
  • VF program adjustment: 30°, 24°, or 10° programs; stimulus sizes III and V can both be used to detect and monitor progression
  • Virtual reality perimetry: shows good agreement with SAP in controlled settings; further research needed for real-world monitoring
• Circumpapillary RNFL analysis by OCT - baseline and follow-up (now consistently recommended)
• Macular ganglion cell layer (GCL) / inner plexiform layer (IPL) analysis by OCT - now consistently recommended alongside RNFL
• Caution: "red disease" and overreliance on normative databases - must be interpreted clinically
• OCT floor effect in advanced disease: structural OCT loses sensitivity when RNFL is severely thinned; VF becomes the primary monitor
• Corneal hysteresis measurement recommended as an adjunct in risk stratification and progression assessment

Monitoring - Individualized Framework (New in 2026)

• Combined structural (OCT) and functional (VF) testing is superior to either modality alone for monitoring
• Home IOP monitoring: endorsed with expanded guidance on home rebound tonometry and contact lens sensors for 24-hour IOP patterning
• Telemedicine and AI: value noted for screening, but caution regarding "difficulty understanding discriminatory factors and generalizability to different patient groups"

Population Screening (AAO 2026)

• Using IOP alone to screen for glaucoma is inadequate
• Screening should incorporate structural and functional assessment
• High-risk groups: age >40, Black/African-American race, family history, thin CCT, diabetes, myopia

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AAO PPP 2026 - MANAGEMENT

Goals of Management

1. Halt or slow progressive visual function loss
2. Maintain vision-related quality of life
3. Minimize side effects and treatment burden

"A reasonable initial treatment goal in a patient with POAG is to reduce IOP 20% to 30% below baseline and to adjust up or down as indicated by disease course and severity."

• Stage of glaucomatous damage (structural and functional)
• Baseline IOP at which damage occurred
• Patient age and life expectancy
• Additional risk factors (CCT, corneal hysteresis, disc hemorrhage)
• Rate of prior progression
• Patient comorbidities and treatment tolerance

Medical Therapy and Adherence

• Prostaglandin analogues (PGAs) remain first-line: once-daily dosing, potent IOP reduction (25-35%), low systemic side effects
• Beta-blockers (timolol, betaxolol): second-line or adjunct; caution in asthma/COPD
• Alpha-2 agonists (brimonidine): avoid in breastfeeding patients; punctal occlusion emphasized for pregnant/nursing patients
• Carbonic anhydrase inhibitors (dorzolamide, brinzolamide topical; acetazolamide systemic)
• ROCK inhibitors (netarsudil): augments TM outflow; novel dual-agent NET/LAT available
• Sustained-release drug delivery (bimatoprost SR, travoprost implant): incorporated with expanded evidence; addresses adherence

Laser Therapy

• SLT as first-line position strengthened in 2026 PPP (LiGHT Trial and subsequent evidence)
• SLT: non-inferior to eye drops for initial IOP control; may reduce medication burden
• Micropulse transscleral cyclophotocoagulation (MP-TSCPC): now considered "more commonly being offered earlier in the disease course" - meta-analysis data shows similar IOP lowering with fewer severe complications vs. continuous-wave CPC

Perioperative Care for Laser Trabeculoplasty

• Topical anaesthetic and post-laser IOP-spike prevention medications
• Recheck IOP 1-4 weeks post-procedure
• VF and disc monitoring continued

Incisional Surgery (Trabeculectomy)

• Trabeculectomy ± MMC remains the benchmark for achieving the lowest target IOP
• Tube shunt surgery (Baerveldt, Ahmed): alternative when trabeculectomy is not feasible or has previously failed
• MIGS: expanded evidence incorporated; appropriate patient selection emphasized - "not suitable for all patients"; realistic IOP-lowering expectations required

Perioperative Care for Incisional Surgery

• Pre-op: full ocular assessment, confirm target IOP, patient counselling
• Post-op bleb management, antimetabolite use guidance, hypotony monitoring

Patient Education

• Nature of the disease (silent, progressive, lifelong)
• Importance of compliance with therapy and follow-up
• Eye drop instillation technique, punctal occlusion
• Family screening recommended for first-degree relatives

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AAO BCSC SECTION 10: GLAUCOMA (2025-2026 Edition)

• Epidemiology and genetic factors
• IOP and aqueous humor dynamics
• Clinical evaluation and imaging (anterior and posterior segments)
• Perimetry
• Medical therapy (mechanism of action and adverse effects of all agents)
• Surgical therapy (with New Key Points sidebars and tables)
• Glaucoma in children and adolescents

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SECTION B: SHIELDS' TEXTBOOK OF GLAUCOMA - SAE (7th Edition)

• Section I: Basic Aspects (anatomy, physiology, aqueous humor dynamics, IOP/tonometry, gonioscopy, optic nerve/retina, visual fields)
• Section II: Clinical Forms of Glaucoma (Chapters 7-28)
• Section III: Management of Glaucoma (medical and surgical)

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SHIELDS CHAPTER 12: PRIMARY OPEN-ANGLE GLAUCOMA AND NORMAL-TENSION GLAUCOMA (p. 197)

Definition (Shields)

1. Open anterior chamber angle on gonioscopy
2. Glaucomatous optic neuropathy (characteristic rim/cup changes)
3. Associated visual field defects
4. Absence of secondary causes

Natural History of POAG (Shields - Fig. 10.2)

• a: Individual without glaucoma (normal aging-related axon loss)
• b: Subthreshold axonal loss that never progresses beyond glaucoma suspect
• c: Glaucoma that responds well to treatment (treated vs. untreated comparison)
• d: Glaucoma with delayed diagnosis - greater cumulative damage
• e: Aggressive POAG detected only after symptom onset, progresses to blindness despite treatment

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SHIELDS CHAPTER 11: POAG SUSPECT - RISK STRATIFICATION AND WHEN TO TREAT (p. 190)

POAG Suspect - Definition and Categories (Shields / AAO-adapted)

Criteria for POAG Suspect Diagnosis (Shields/AAO):

• IOP >21 mmHg with open angle (OHT)
• C/D ratio >0.65 or C/D asymmetry >0.2, suggesting loss of neural tissue
• Diffuse or localized RNFL or GCC abnormalities without another explanation
• Visual fields suspicious for early glaucomatous damage
• Genetic mutation conferring high risk for POAG

Risk Stratification for When to Treat (Shields):

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SHIELDS CHAPTER 10: CLINICAL EPIDEMIOLOGY OF GLAUCOMA (p. 169)

• Glaucoma is the leading cause of irreversible blindness worldwide
• POAG: most common form in populations of European and African descent
• Estimated 53-80 million people affected worldwide (2020 estimates); projected 112 million by 2040
• Black populations: higher prevalence, earlier onset, more severe, lower diagnostic and treatment rates
• Diastolic perfusion pressure: Relative risk of 3.2 for POAG in the lowest quintile of diastolic perfusion pressure - strong vascular risk factor

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SHIELDS CHAPTER 9: MOLECULAR GENETICS AND PHARMACOGENOMICS (p. 158)

• Prostaglandin receptor (FP/EP) polymorphisms influence response to PGAs
• Beta-adrenergic receptor polymorphisms affect timolol response
• This will increasingly inform personalized drug selection

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SECTION C: GOODMAN & GILMAN'S PHARMACOLOGICAL BASIS OF THERAPEUTICS - Glaucoma Pharmacology

Drug Classes - Mechanisms and Pharmacology

1. Prostaglandin Analogues (PGAs) - First Line

• Drugs: Latanoprost, travoprost, bimatoprost, tafluprost
• Receptor: FP receptors (PGF₂α) → Gα₁₁-PLC-IP₃-Ca²⁺ pathway in ciliary muscle
• Mechanism: Matrix metalloproteinase release → ECM digestion → increased uveoscleral outflow; altered ciliary muscle tension
• Latanoprostene bunod: PGA backbone + nitric oxide-donating moiety → relaxes TM cytoskeleton → dual-pathway IOP reduction (uveoscleral + trabecular)
• (Goodman & Gilman's, Ch. 74)

2. Beta-Blockers - Second Line

• Nonselective (β₁ + β₂): Timolol, levobunolol, carteolol
• β₁-selective: Betaxolol (less efficacious; safer in respiratory disease)
• Mechanism: Block β₂ receptors (75-90% of ciliary body receptors) → reduce cAMP-PKA pathway activation → decreased aqueous production; possibly also reduce ocular blood flow and ultrafiltration
• (Goodman & Gilman's, Ch. 74)

3. Alpha-2 Agonists

• Brimonidine (selective α₂, lipophilic, crosses cornea easily), Apraclonidine (selective α₂, ionized, does not cross blood-brain barrier)
• Mechanism: Reduce aqueous production (pre- and postsynaptic α₂ receptors) + enhance conventional outflow (α₂ receptor mechanism) + uveoscleral outflow (via PG production)
• (Goodman & Gilman's, Ch. 74)

4. Carbonic Anhydrase Inhibitors (CAIs)

• Topical: Dorzolamide, brinzolamide - inhibit CA isoform II in ciliary body epithelium → reduce bicarbonate ion formation → reduced fluid transport → decreased aqueous production
• Systemic: Acetazolamide, methazolamide - same mechanism; greater IOP reduction but significant systemic side effects
• (Goodman & Gilman's, Ch. 74)

5. ROCK Inhibitors (Newest Class)

• Netarsudil (approved FDA), Ripasudil (Japan/Canada)
• Mechanism: Rho kinase (protein serine-threonine kinase) blockade → decreased density of actin stress fibers in TM and Schlemm's canal inner wall → augmented conventional (trabecular) outflow + reduced episcleral venous pressure
• (Goodman & Gilman's, Ch. 74)

6. Miotics (Cholinergic)

• Pilocarpine: Direct muscarinic agonist → ciliary muscle contraction → TM spaces opened → increased conventional outflow
• Echothiophate: Anticholinesterase (indirect) → significant side effects (cataract, pupillary block, retinal detachment risk)
• (Goodman & Gilman's, Ch. 74 drug tables)

Fixed-Dose Combinations (FDCs)

• Timolol + dorzolamide (Cosopt)
• Timolol + brimonidine (Combigan)
• Netarsudil + latanoprost (Roclanda/NET-LAT) - MERCURY-3 trial confirmed non-inferiority to bimatoprost/timolol
• Benefits: Reduced preservative exposure, improved adherence, lower cost

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SECTION D: COMPARATIVE TABLE - AAO PPP 2026 vs. SHIELDS 7th Ed. vs. KANSKI 10th Ed.

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SECTION E: SHIELDS - CLINICAL APPROACH TO POAG (Summary from Ch. 12)

Step 1: Establish the Diagnosis

• Confirm open angle (gonioscopy)
• Document disc damage (stereophotography or OCT)
• Confirm VF defect (SAP) corresponding to structural damage
• Rule out secondary causes

Step 2: Assess Natural History Risk

• Where is the patient on the natural history trajectory?
• Rate of current axon loss (from serial OCT RNFL and VF)
• Expected remaining useful vision lifetime

Step 3: Set Target IOP

• Based on stage of damage + rate of progression + life expectancy
• Principle: The more advanced and faster-progressing, the lower the target
• Typically: ≥20-30% reduction from mean damage-producing IOP

Step 4: Select Treatment Modality

Step 5: Monitor and Adjust

• Serial SAP (minimum 2 per year initially; at least 6 tests to establish a reliable progression rate)
• Serial OCT RNFL/GCL (annually when stable; more frequently if progressing)
• IOP at each visit; diurnal curve if unstable
• Adjustment: if progressing despite apparent IOP control → lower target, rule out adherence issues, consider structural/vascular contributors

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KEY TAKE-HOME POINTS FROM BOTH SOURCES

1. AAO PPP 2026 is the most current, comprehensive guidelines document for POAG; published February 9, 2026 in Ophthalmology; freely downloadable here.
2. Shields 7th Ed. remains the gold-standard dedicated glaucoma textbook, unique for its natural history framework, separate glaucoma suspect chapter, detailed genetics/pharmacogenomics chapter, and systematic clinical decision-making approach. The SAE edition is widely used in South Asia.
3. Both emphasize: IOP reduction is the only proven intervention; SLT is co-equal first-line with drops; MIGS requires careful patient selection; trabeculectomy remains the benchmark for advanced disease.
4. AAO 2026 introduces corneal hysteresis as a formal, dedicated risk factor and monitoring adjunct - a significant practical update.
5. Shields provides the best resource for understanding when to treat a glaucoma suspect and how to conceptualize the natural history trajectory of individual patients.

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What This Master Document Contains

7 Major Parts, 21 Sections