EENT · PANCE / PANRE

Primary Open-Angle Glaucoma (POAG)

Chronic painless optic neuropathy with progressive visual field loss — leading cause of irreversible blindness worldwide.

Also known as: POAG, open-angle glaucoma, primary open-angle glaucoma, chronic glaucoma

Overview

Chronic, progressive, typically bilateral optic neuropathy characterized by retinal nerve fiber layer loss, characteristic optic disc cupping, and corresponding visual field defects, occurring in the presence of an open anterior chamber angle. Elevated intraocular pressure (IOP) is the most important modifiable risk factor, although normal-tension glaucoma occurs with IOP in the statistically normal range (<21 mmHg).

Epidemiology

Leading cause of irreversible blindness worldwide. Prevalence rises sharply with age — ~1% at age 40, ~10% by age 80. African ancestry: 3-4× risk and earlier onset; Hispanic ancestry also elevated. Approximately half of affected patients are undiagnosed.

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Risk factors

  • Age >40 (>60 for highest risk)
  • African or Hispanic ancestry
  • Family history of glaucoma in first-degree relative
  • Elevated IOP
  • Thin central corneal thickness
  • High myopia
  • Diabetes mellitus, hypertension, sleep apnea
  • Long-term topical or systemic corticosteroid use
  • Pseudoexfoliation syndrome, pigment dispersion syndrome

Pathophysiology

Imbalance between aqueous humor production by the ciliary body and outflow through the trabecular meshwork/Schlemm canal increases IOP, which damages retinal ganglion cell axons at the lamina cribrosa. Ischemic and mechanical factors contribute. The optic disc develops progressive cupping (loss of neuroretinal rim) and the visual field loses peripheral and arcuate function before central vision. In normal-tension glaucoma, vascular dysregulation and lower CSF pressure may produce the same end-organ damage at lower IOP.

Clinical presentation

Symptoms

  • Asymptomatic in early disease — vision loss is painless and gradual
  • Patients rarely notice peripheral field defects until advanced
  • Trouble with night driving, missing steps, or bumping into things
  • Central vision preserved until late
  • Frequently detected on screening exam or as 'large cup' on routine fundoscopy

Signs / physical exam

  • Elevated IOP on tonometry (most have IOP >21, but normal-tension subgroup does not)
  • Open angle on gonioscopy
  • Optic disc cupping: cup-to-disc ratio >0.6, asymmetric C/D between eyes >0.2, notching of the rim, disc hemorrhages (Drance hemorrhages)
  • Loss of retinal nerve fiber layer on OCT
  • Visual field defects: nasal step, paracentral or arcuate scotoma, eventually tunnel vision
  • Pupils equal with no RAPD until advanced asymmetric disease

Classic findings

Progressive optic disc cupping with corresponding nerve fiber bundle visual field defects in a patient with elevated IOP.

Differential diagnosis

  • Normal-tension glaucoma — POAG phenotype with IOP <21; consider vascular dysregulation; treat to lower IOP and address risk factors
  • Angle-closure glaucoma — Acute or subacute pain, halos; gonioscopy shows closed angle; laser iridotomy
  • Secondary glaucomas (pigmentary, pseudoexfoliative, steroid-induced, neovascular, uveitic, traumatic) — Findings on slit lamp/gonioscopy; treat underlying cause
  • Non-glaucomatous optic neuropathy (ischemic, compressive, inflammatory) — Pale rather than cupped disc, RAPD, sudden vision change, neuroimaging
  • Optic disc drusen / physiologic cupping — Stable disc and field over time; B-scan or OCT shows drusen
  • Retinal disease causing field loss — Macular or peripheral retinal pathology; normal disc

Diagnostic workup

Diagnostic criteria

Characteristic optic disc and/or nerve fiber layer damage with corresponding visual field defect in an eye with open angle, after exclusion of secondary causes.

Labs

  • Not routinely indicated for diagnosis
  • Targeted workup (B12, ESR, ACE, syphilis, etc.) if optic neuropathy appears non-glaucomatous

Imaging

  • Goldmann applanation tonometry (gold standard) — multiple readings, diurnal variation
  • Pachymetry — central corneal thickness influences IOP measurement and is an independent risk factor (OHTS)
  • Gonioscopy — confirms open angle and rules out angle closure and secondary causes
  • Dilated fundus exam and stereoscopic optic disc photography
  • Optical coherence tomography (OCT) of retinal nerve fiber layer and ganglion cell complex
  • Automated perimetry (Humphrey 24-2 or 30-2) — functional assessment; baseline and serial

Diagnostic algorithm

Drug ClassExamplesMechanismKey Side Effects
Prostaglandin analogLatanoprost, bimatoprost, travoprost, tafluprost↑ uveoscleral outflowIris darkening, lash growth, periorbital atrophy, hyperemia
Beta-blockerTimolol, betaxolol↓ aqueous productionBronchospasm, bradycardia; avoid in asthma/COPD/heart block
Alpha-2 agonistBrimonidine, apraclonidine↓ aqueous production, ↑ uveoscleral outflowAllergy, fatigue, dry mouth; CNS depression in infants
Carbonic anhydrase inhibitor (topical)Dorzolamide, brinzolamide↓ aqueous productionBitter taste, stinging; sulfa caution
Carbonic anhydrase inhibitor (oral)Acetazolamide, methazolamide↓ aqueous productionParesthesias, kidney stones, metabolic acidosis
Rho kinase inhibitorNetarsudil↑ trabecular outflowConjunctival hyperemia, corneal verticillata
Cholinergic (miotic)Pilocarpine↑ trabecular outflow via ciliary contractionBrow ache, miosis, retinal detachment risk
Topical and systemic agents used to lower intraocular pressure in POAG.

Treatment

First-line

  • Target IOP reduction of 20-30% from baseline; lower targets for advanced disease (EMGT, AGIS data)
  • Prostaglandin analog (POAG) — latanoprost, bimatoprost, travoprost, tafluprost — once daily at bedtime; most effective IOP-lowering class; side effects: iris darkening, periorbital pigmentation/atrophy, lash growth, conjunctival hyperemia
  • Selective laser trabeculoplasty (SLT) — increasingly used as first-line based on LiGHT trial; comparable or superior to drops
  • Patient education on adherence — chronic, asymptomatic disease

Second-line / adjunct

  • Topical beta-blocker — timolol 0.25-0.5%, betaxolol 0.25% (cardioselective); avoid in asthma/COPD, bradyarrhythmia, decompensated HF
  • Topical alpha-2 agonist — brimonidine 0.1-0.2%, apraclonidine; avoid in young children (CNS depression)
  • Topical carbonic anhydrase inhibitor — dorzolamide 2%, brinzolamide 1%; caution in sulfa allergy
  • Topical rho kinase inhibitor — netarsudil 0.02% (newer class); side effect: conjunctival hyperemia, corneal verticillata
  • Cholinergic (pilocarpine) — rarely used today; miosis and brow ache
  • Combination drops to reduce dosing burden (e.g., dorzolamide-timolol, brimonidine-timolol)
  • Oral acetazolamide — short-term bridge; long-term side effects (paresthesias, kidney stones, metabolic acidosis)
  • Trabeculectomy or glaucoma drainage device (tube shunt) for refractory disease
  • Minimally invasive glaucoma surgery (MIGS) — iStent, Hydrus, XEN gel stent — often combined with cataract surgery in mild-moderate disease
  • Cyclophotocoagulation for advanced refractory disease

Complications

  • Irreversible blindness if untreated or undertreated
  • Severely constricted visual fields with preserved central acuity (tunnel vision)
  • Side effects of topical therapy: ocular surface disease, allergy, systemic absorption
  • Surgical complications: hypotony, bleb infection, endophthalmitis, cataract

PANCE pearls

  • POAG is painless and asymptomatic until advanced — screening of high-risk groups (African ancestry ≥40, family history) is essential.
  • Cup-to-disc ratio asymmetry >0.2 between eyes is suspicious for glaucoma even with normal IOP.
  • Disc (Drance) hemorrhages at the rim are a strong sign of progression.
  • Central corneal thickness influences applanation tonometry — thin corneas under-read IOP and confer independent risk (OHTS).
  • Prostaglandin analogs are the most powerful single-agent IOP lowerers and are once-daily — first-line pharmacotherapy.
  • Selective laser trabeculoplasty (SLT) is now considered a reasonable first-line option per the LiGHT trial — fewer drops, fewer side effects.
  • Normal-tension glaucoma still benefits from IOP lowering (CNTGS) — do not dismiss because IOP is 'normal.'

References

  • AAO 2020 — American Academy of Ophthalmology. Primary Open-Angle Glaucoma Preferred Practice Pattern. Ophthalmology 2021;128(1):P71-P150
  • OHTS — Kass MA et al. The Ocular Hypertension Treatment Study. Arch Ophthalmol 2002;120(6):701-713
  • EMGT — Heijl A et al. Reduction of intraocular pressure and glaucoma progression: Early Manifest Glaucoma Trial. Arch Ophthalmol 2002;120(10):1268-1279
  • LiGHT — Gazzard G et al. Selective laser trabeculoplasty versus eye drops for first-line treatment of ocular hypertension and glaucoma (LiGHT): a multicentre randomised controlled trial. Lancet 2019;393(10180):1505-1516
  • CNTGS — Collaborative Normal-Tension Glaucoma Study Group. Comparison of glaucomatous progression between untreated patients with normal-tension glaucoma and patients with therapeutically reduced intraocular pressures. Am J Ophthalmol 1998;126(4):487-497

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