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Glaucoma, Primary Open-Angle
Richard W. Allinson, MD
image BASICS
  • Primary open-angle glaucoma (POAG) is an optic neuropathy resulting in visual field loss frequently associated with increased intraocular pressure (IOP).
  • Normal IOP is 10 to 22 mm Hg. However, glaucomatous optic nerve damage also can occur with normal IOP and as a secondary manifestation of other disorders such as corticosteroid-induced glaucoma.
  • System(s) affected: nervous
  • Synonym(s): chronic open-angle glaucoma
Pregnancy Considerations
Prostaglandins should be avoided during pregnancy in the treatment of POAG.
  • Predominant age: usually >40 years
  • Increases with age
  • Predominant gender: male = female
Prevalence in persons >40 years of age is ˜1.8%.
Geriatric Considerations
Increasing prevalence with increasing age
  • Abnormal aqueous outflow resulting in increased IOP
  • Normally, aqueous is produced by the ciliary epithelium of the ciliary body and is secreted into the posterior chamber of the eye.
  • Aqueous then flows through the pupil and enters the anterior chamber to be drained by the trabecular meshwork in the iridocorneal angle of the eye into the Schlemm canal and into the venous system of the episclera.
  • 5-10% of the total aqueous outflow leaves via the uveoscleral pathway.
  • Impaired aqueous outflow through the trabecular meshwork
    • Increased resistance within the aqueous drainage system
A family history of glaucoma increases the risk for developing glaucoma.
  • Increased IOP
  • Myopia
  • Diabetes mellitus (DM)
  • African American
  • Elderly
  • Hypothyroidism
  • Positive family history
  • Central corneal thickness <550 &mgr;m
  • Larger vertical cup-to-disc ratio (CDR)
  • Larger horizontal CDR
  • CDR asymmetry
  • Disc hemorrhage
  • Prolonged use of topical, periocular, inhaled, or systemic corticosteroids
  • Obstructive sleep apnea
  • Hypertension (1)[B]
  • Corneal hysteresis (CH) (2)[B]
    • A measure of the viscoelastic damping of the cornea
    • Lower CH associated with faster rates of visual field loss
Possible reduced risk of open-angle glaucoma with long-term use of oral statins among persons with hyperlipidemia
  • Visual acuity and visual field assessment
  • Ophthalmoscopy to assess optic nerve for glaucomatous damage
  • Increased IOP
  • CDR >0.5: Normal eyes show a characteristic configuration for disc rim thickness of inferior ≥ superior ≥ nasal ≥ temporal (ISNT rule).
  • Earliest visual field defects are paracentral scotomas and peripheral nasal steps.
  • Normal-tension glaucoma
  • Optic nerve pits
  • Anterior ischemic optic neuropathy
  • Compressive lesions of the optic nerve or chiasm
  • Posthemorrhagic (shock optic neuropathy)
Initial Tests (lab, imaging)
Optical coherence tomography can be useful in the detection of glaucoma by measuring the thickness of the retinal nerve fiber layer (RNFL).
  • RNFL is thinner in patients with glaucoma.
  • RNFL tends to be thinner with older age, in Caucasians, greater axial length, and smaller optic disc area.
Diagnostic Procedures/Other
  • Visual field testing: perimetry
    • A multifocal intraocular lens may reduce visual sensitivity on standard automated perimetry.
  • Tonometry to measure IOP
Test Interpretation
  • Atrophy and cupping of optic nerve
  • Loss of retinal ganglion cells (RGCs) and their axons produces defects and thinning in the RNFL.
  • Significant RGC loss may occur at specific location before corresponding visual field loss is detected (3)[B].
  • Early Manifest Glaucoma Trial
    • Early treatment delays progression.
    • The magnitude of initial IOP reduction influences disease progression (4)[A].
  • Ocular Hypertension Treatment Study
    • Patients who only had increased IOP in the range of 24 to 32 mm Hg were treated with topical ocular hypotensive medication.
    • Treatment produced ˜20% reduction in IOP
    • At 5 years, treatment reduced the incidence of POAG by >50%: 9.5% in the observation group versus 4.4% in the medication-treated group (5)[A].
  • The Advanced Glaucoma Intervention Study
    • Eyes were randomized to laser trabeculoplasty or filtering surgery when medical therapy failed.
    • In follow-up, if IOP was always <18 mm Hg, visual fields tended to stabilize. When IOP was >17 mm Hg, >1/2 the time, patients tended to have worsening of visual fields (6)[A].
    • Whites did better with trabeculectomy first whereas African Americans did better with argon laser trabeculoplasty as the initial procedure.
  • Collaborative Initial Glaucoma Treatment Study
    • Both initial medical and surgical (trabeculectomy) treatment achieved significant IOP reduction, and both had little visual field loss over time (7)[A].
    • There was a 5-year risk of endophthalmitis of 1.1% after trabeculectomy (8)[A].
  • >1 medication, with different mechanisms of action, may be needed.
  • When ≥3 medications are required, compliance is difficult, and surgery may be needed. Ocular hypotensive agent categories
    • &bgr;-Adrenergic antagonists (nonselective and selective): decrease aqueous formation; best when used as an add-on therapy: timolol 0.25% (initial) to 0.5% one drop in affected eye q12h; gel-forming solution (0.35% or 0.5%) one drop in affected eye once daily; betaxolol 0.5% one drop in affected eye twice daily
    • Parasympathomimetics (miotic), including cholinergic (direct-acting) and anticholinesterase agents (indirect-acting parasympathomimetic): increase aqueous outflow
      • Pilocarpine 1-4%: one drop in affected eye BID to QID (cholinergic)
  • Carbonic anhydrase inhibitors (oral, topical): decrease aqueous formation
    • Acetazolamide: 250 mg PO 1 to 4 times per day
    • Dorzolamide 2%: one drop TID
    • Brinzolamide 1%: one drop TID
  • Adrenergic agonists (nonselective and selective &agr;2-adrenergic agonists)
    • Epinephrine 0.5-2%: One drop BID and Propine (dipivefrin) 0.1% one drop BID are both nonselective agents that increase aqueous outflow through the trabecular meshwork and increase uveoscleral outflow.
    • Brimonidine tartrate 0.1%: One drop TID (&agr;2-adrenergic agonist) decreases aqueous formation and increases uveoscleral outflow.
  • Prostaglandin analogues: enhance uveoscleral outflow and increase aqueous outflow through the trabecular meshwork: latanoprost 0.005% one drop at bedtime; travoprost 0.004% one drop at bedtime
  • Hyperosmotic agents: increase blood osmolality, drawing water from the vitreous cavity
    • Mannitol 20% solution: administered IV at 2 g/kg of body weight
    • Glycerin 50% solution: administered PO; dosage is usually 4 to 7 oz.
  • Contraindications/precautions
    • Nonselective &bgr;-adrenergic antagonists: Avoid in asthma, chronic obstructive pulmonary disease (COPD), 2nd- and 3rd-degree atrioventricular (A-V) block, and decompensated heart failure.

      Betaxolol is a selective &bgr;-adrenergic antagonist and is safer in pulmonary disease.
    • Parasympathomimetics (miotic): Indirect-acting parasympathomimetic agents increase risk of ocular and systemic side effects and are used rarely.
    • Carbonic anhydrase inhibitors
      • Do not use with sulfa drug allergies.
      • Do not use with cirrhosis because of the risk of hepatic encephalopathy.
  • Adrenergic agonists: Caution is recommended when using brimonidine and monoamine oxidase (MAO) inhibitor or tricyclic antidepressant (TCA) and in patients with vascular insufficiency. Brimonidine can cause excessive sleepiness and lethargy in children.
  • Prostaglandin analogues: caution with uveitis and avoided during pregnancy
  • Hyperosmotic agents
    • Glycerin can produce hyperglycemia or ketoacidosis in diabetic patients.
    • Can cause congestive heart failure
    • Do not use in patients with anuria.
  • Precautions
    • &bgr;-Adrenergic antagonists: caution with obstructive pulmonary disease, heart failure, and DM
    • Parasympathomimetics (miotic): cause pupillary constriction and may cause decreased vision in patients with a cataract; may cause eye pain or myopia due to increased accommodation. All miotics break down the blood-aqueous barrier and may induce chronic iridocyclitis.
    • Adrenergic agonists (e.g., brimonidine): caution with vascular insufficiency
    • Contact lens wearers: Many products contain benzalkonium chloride; remove contact lens prior to administration and wait 15 minutes before reinsertion.
    • Prostaglandin analogues may cause increased pigmentation of the iris and periorbital tissue (eyelid).
      • Increased pigmentation and growth of eyelashes
      • Should be used with caution in active intraocular inflammation (iritis/uveitis)
      • Caution is also advised in eyes with risk factors for herpes simplex, iritis, and cystoid macular edema.
      • Macular edema may be a complication associated with treatment.
  • Hyperosmotic agents: caution in diabetics; dehydrated patients; and those with cardiac, renal, and hepatic disease
  • Significant possible interactions: &bgr;-adrenergic antagonists: caution in patients taking calcium antagonists because of possible A-V conduction disturbances, left ventricular failure, or hypotension
  • Parasympathomimetics (miotic): Indirect-acting parasympathomimetic agents, anticholinesterase eye drops, can reduce serum pseudocholinesterase levels. If succinylcholine is used for induction of general anesthesia, prolonged apnea may result.
  • Argon laser trabeculoplasty (ALT)
    • Can be applied up to 180 degrees of the trabecular meshwork
    • Improves aqueous outflow
    • The Glaucoma Laser Trial Research Group showed in newly diagnosed, previously untreated patients with POAG that ALT was as effective as topical glaucoma medication within the first 2 years of follow-up.
    • Usually reserved for patients needing better IOP control while taking topical glaucoma drops
  • Selective laser trabeculoplasty (SLT)
    • 532-nm Nd:YAG laser
    • Appears to be as effective as ALT in lowering IOP
  • Trabeculectomy (glaucoma filtering surgery)
    • Usually reserved for patients needing better IOP control after maximal medical therapy and who may have previously undergone an ALT
    • Mitomycin C can be applied at the time of surgery to increase the chances of a surgical success.
    • Subconjunctival bevacizumab may be a beneficial adjunctive therapy for reducing late surgical failure after trabeculectomy.
  • Shunt (tube) surgery
    • For example, Molteno and Ahmed devices
    • Generally reserved for difficult glaucoma cases in which conventional filtering surgery has failed or is likely to fail
  • Tube Versus Trabeculectomy (TVT) Study
    • After 5 years of follow-up, both procedures were associated with similar IOP reduction and the number of glaucoma medications needed (9)[A].
  • Ciliary body ablation: indicated to lower IOP in patients with poor visual potential or those who are poor candidates for filtering or shunt procedures
  • Canaloplasty can control IOP in patients with POAG. Canaloplasty involves the placement of a microcatheter circumferentially through Schlemm canal, vasodilation of the canal, and placement of a nylon tensioning suture.
  • Cataract extraction can decrease IOP in patients with ocular hypertension (10)[A].
Patient Monitoring
  • Monitor vision and IOP every 3 to 6 months.
  • Visual field testing every 6 to 18 months
  • Optic nerve evaluation every 3 to 18 months, depending on POAG control
  • A worsening of the mean deviation by 2 dB on the Humphrey field analyzer and confirmed by a single test after 6 months had a 72% probability of progression.
  • The IOP response to ocular hypotensive agents tends to be reduced in persons with thicker corneas.
POAG is a silent robber of vision, and patients may not appreciate the significance of their disease until much of their visual field is lost.
  • With standard glaucoma therapy, the rate of visual field loss in POAG is slow.
  • Patients still may lose vision and develop blindness, even when treated appropriately.
  • The rate of legal blindness from POAG over a follow-up of 22 years is 19%.
  • The rate of progression of visual field loss increases with older age.
1. Zhao D, Cho J, Kim MH, et al. The association of blood pressure and primary open-angle glaucoma: a meta-analysis. Am J Ophthalmol. 2014;158(3):615.e9-627.e9.
2. Medeiros FA, Meira-Freitas D, Lisboa R, et al. Corneal hysteresis as a risk factor for glaucoma progression: a prospective longitudinal study. Ophthalmology. 2013;120(8):1533-1540.
3. Alasil T, Wang K, Yu F, et al. Correlation of retinal nerve fiber layer thickness and visual fields in glaucoma: a broken stick model. Am J Ophthalmol. 2014;157(5):953-959.
4. Heijl A, Leske MC, Bengtsson B, et al. Reduction of intraocular pressure and glaucoma progression: results from the Early Manifest Glaucoma Trial. Arch Ophthalmol. 2002;120(10):1268-1279.
5. Kass MA, Heuer DK, Higginbotham EJ, et al. The Ocular Hypertension Treatment Study: a randomized trial determines that topical ocular hypotensive medication delays or prevents the onset of primary open-angle glaucoma. Arch Ophthalmol. 2002;120(6):701-713.
6. The Advanced Glaucoma Intervention Study (AGIS): 7. The relationship between control of intraocular pressure and visual field deterioration. Am J Ophthalmol. 2000;130(4):429-440.
7. Lichter PR, Musch DC, Gillespie BW, et al. Interim clinical outcomes in the Collaborative Initial Glaucoma Treatment Study comparing initial treatment randomized to medications or surgery. Ophthalmology. 2001;108(11):1943-1953.
8. Zahid S, Musch DC, Nizol LM, et al. Risk of endophthalmitis and other long-term complications of trabeculectomy in the Collaborative Initial Glaucoma Treatment Study (CIGTS). Am J Ophthalmol. 2013;155(4):674-680, 680.e1.
9. Gedde SJ, Schiffman JC, Feuer WJ, et al. Treatment outcomes in the Tube Versus Trabeculectomy (TVT) Study after five years of follow-up. Am J Ophthalmol. 2012;153(5):789.e2-803.e2.
10. Mansberger SL, Gordon MO, Jampel H, et al. Reduction in intraocular pressure after cataract extraction: the Ocular Hypertension Treatment Study. Ophthalmology. 2012;119(9):1826-1831.
Additional Reading
  • Aychoua N, Junoy Montolio FG, Jansonius NM. Influence of multifocal intraocular lenses on standard automated perimetry test results. JAMA Ophthalmol. 2013;131(4):481-485.
  • Lin CC, Hu CC, Ho JD, et al. Obstructive sleep apnea and increased risk of glaucoma: a population-based matched-cohort study. Ophthalmology. 2013;120(8):1559-1564.
  • H40.11X0 Primary open-angle glaucoma, stage unspecified
  • H40.11X1 Primary open-angle glaucoma, mild stage
  • H40.11X2 Primary open-angle glaucoma, moderate stage
Clinical Pearls
  • Topical or systemic steroids can cause the IOP to increase.
  • Pain is not a frequent symptom of POAG.
  • Painless, slowly progressive visual loss; patients generally are unaware of the visual loss until late in the disease. Central visual acuity remains unaffected until late in the disease.
  • Patients still may lose vision and develop blindness, even when treated appropriately.