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Primary Open-Angle Glaucoma


Douglas J. Rhee

, MD, University Hospitals/Case Western Reserve University

Last full review/revision Mar 2021| Content last modified Mar 2021
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Primary open-angle glaucoma is a syndrome of optic nerve damage associated with an open anterior chamber angle and an elevated or sometimes average intraocular pressure (IOP). Symptoms are a result of visual field loss. Diagnosis is by ophthalmoscopy, gonioscopy, visual field examination, and measurement of central corneal thickness and IOP. Treatment includes topical drugs (eg, prostaglandin analogs, beta-blockers) and often requires laser or incisional surgery to increase aqueous drainage.

(See also Overview of Glaucoma.)

Etiology of Primary Open-Angle Glaucoma

Although open-angle glaucomas can have numerous causes (see table Open-Angle Glaucoma: Classification), 60 to 70% of cases in the US have no identifiable cause and are termed primary open-angle glaucoma. Both eyes usually are affected, but typically not equally.


Open-Angle Glaucoma: Classification Based on Mechanisms of Outflow Obstruction*






Disorder of extracellular matrix

Corticosteroid-induced glaucoma

Juvenile glaucoma

Pseudoexfoliation glaucoma

Primary open-angle glaucoma


By red blood cells

Ghost cell glaucoma

Hemorrhagic glaucoma

By macrophages

Hemolytic glaucoma

Melanomalytic glaucoma

Phacolytic glaucoma

By neoplastic cells

Juvenile xanthogranuloma

Malignant tumors

Nevus of Ota

By pigment particles

Exfoliation syndrome (glaucoma capsulare)

Pigmentary glaucoma


By protein

Lens-induced glaucoma

Due to other means

Viscoelastic agents

Vitreous hemorrhage


Due to edema

Alkali burns

Iritis or uveitis causing trabeculitis

Due to trauma

Angle recession

Due to intraocular foreign bodies



Obstruction of the Schlemm canal

By particulate matter or collapse of canal walls

Age-related changes in canal wall

Sickled red blood cells


Reduced flow in aqueous veins

Due to elevated episcleral venous pressure

Carotid-cavernous fistula

Idiopathic episcleral venous pressure elevation

Mediastinal tumors

Infiltrative ophthalmopathy (thyrotropic exophthalmos)

Retrobulbar tumors

Superior vena cava obstruction

* Clinical examples cited; not an inclusive list of glaucomas.

Adapted from Ritch R, Shields MB, Krupin T: The Glaucomas, ed. 2. St. Louis, Mosby, 1996, p. 720; with permission.

Risk factors for primary open-angle glaucoma include

In people of African ethnicity, glaucoma is more severe and develops at an earlier age, and blindness is 6 to 8 times more likely.

Pathophysiology of Primary Open-Angle Glaucoma

Intraocular pressure (IOP) can be elevated or within the average range.

In primary open-angle glaucoma, there is an abnormality of extracellular matrix in the part of the trabecular meshwork (TM) that is immediately adjacent to the Schlemm canal (called the juxtacanalicular TM) similar to accelerated aging; trabecular meshwork cellularity may also decrease.

Elevated-pressure glaucoma

Two thirds of patients with glaucoma have elevated (> 21 mm Hg) IOP. Aqueous humor drainage is inadequate, whereas production by the ciliary body is normal. Identifiable mechanisms (ie, secondary open-angle glaucomas) are not present. Secondary mechanisms include developmental anomalies, scarring caused by trauma or infection, and plugging of channels by detached iris pigment (ie, pigment dispersion syndrome) or abnormal protein deposits (eg, pseudoexfoliation syndrome).

Normal-pressure glaucoma or low-tension (low-pressure) glaucoma

In at least one third of patients with glaucoma, IOP is within the average range, but optic nerve damage and visual field loss typical of glaucoma are present. These patients have a higher incidence of vasospastic diseases (eg, migraines, Raynaud syndrome) than the general population, suggesting that a vascular disorder compromising blood flow to the optic nerve may play a role. Glaucoma occurring with average-range IOP is more common among Asians.

Symptoms and Signs of Primary Open-Angle Glaucoma

Early primary open-angle glaucoma symptoms are uncommon. Usually, the patient becomes aware of visual field loss only when optic nerve atrophy is marked; the typically asymmetric deficits contribute to delay in recognition. However, some patients have complaints, such as missing stairs if their inferior visual field has been lost, noticing portions of words missing when reading, or having difficulty with driving earlier in the course of the disease.

Examination findings include an unobstructed open angle on gonioscopy and characteristic optic nerve appearance and visual field defects. Intraocular pressure (IOP) may be normal or high but is almost always higher in the eye with more optic nerve damage.

Optic nerve appearance

The optic nerve head (ie, disk) is normally a slightly vertically elongated circle with a centrally located depression called the cup. The neurosensory rim is the tissue between the margin of the cup and the edge of the disk, and is composed of the ganglion cell axons from the retina.

Characteristic optic nerve changes include

  • Increased cup:disk ratio (particularly an increasing ratio over time)

  • Thinning of the neurosensory rim

  • Pitting or notching of the rim

  • Nerve fiber layer hemorrhage that crosses the disk margin (ie, Drance hemorrhage or splinter hemorrhages)

  • Vertical elongation of the cup

  • Quick angulations in the course of the exiting blood vessels (called bayoneting)

Thinning of the neurosensory rim (optic nerve or retinal nerve fiber layer) over time alone can be diagnostic of glaucoma regardless of the IOP or visual field and is the initial sign of damage in 40 to 60% of cases. In other cases, the initial sign of damage is some visual field change.

Wedge-shaped dark areas may develop, reflecting damage to the retinal nerve fiber layer.

Visual field defects

Visual field changes caused by lesions of the optic nerve include

  • Nasal step defects (which do not cross the horizontal meridian—an imaginary horizontal line between the upper and lower parts of the visual field)

  • Arcuate (arc-shaped) scotomata extending nasally from the blind spot

  • Temporal wedge defects

  • Paracentral scotomata

In contrast, deficits of the more proximal visual pathways (ie, from the lateral geniculate nucleus to the occipital lobe) involve quadrants or hemispheres of the visual field; thus, deficits do not cross the vertical meridian.

Diagnosis of Primary Open-Angle Glaucoma

  • Visual field testing

  • Ophthalmoscopy

  • Measurement of central corneal thickness and intraocular pressure (IOP)

  • Exclusion of other optic neuropathies

Diagnosis of primary open-angle glaucoma is suggested by the examination, but similar findings can result from other optic neuropathies (eg, caused by ischemia, cytomegalovirus infection, or vitamin B12 deficiency).

Before a diagnosis of normal-pressure glaucoma can be established, the following factors may need to be ruled out:

  • Inaccurate IOP readings

  • Large diurnal fluctuations (causing intermittent normal readings)

  • Optic nerve damage caused by previously resolved glaucoma (eg, a previously elevated IOP due to corticosteroid use or uveitis)

  • Intermittent angle-closure glaucoma

  • Other ocular or neurologic disorders that cause similar visual field defects

Central corneal thickness is measured to help interpret the result of IOP measurement.

Optic disk photography or a detailed optic disk drawing is helpful for future comparison. The frequency of follow-up examinations varies from weeks to months, depending on the patient’s reliability, severity of the glaucoma, and response to treatment.

Treatment of Primary Open-Angle Glaucoma

  • Decreasing intraocular pressure (IOP) 20 to 40%

  • Initially, drugs (eg, prostaglandin analogs such as latanoprost or tafluprost, beta-blockers such as timolol)

  • Sometimes surgery, such as laser trabeculoplasty or guarded filtration procedure

Vision lost by glaucoma cannot be recovered. The goal is to prevent further optic nerve and visual field damage by lowering IOP. The target level is 20 to 40% below pretreatment readings or the IOP at which damage is known to have occurred. In general, the greater the damage caused by glaucoma, the lower the IOP must be to prevent further damage. If damage progresses, the IOP goal is lowered further and additional therapy is initiated.

Initial treatment is usually drug therapy, proceeding to laser therapy and then incisional surgery if the target IOP is not met; however, recent evidence suggests that initial treatment with laser trabeculoplasty is at least as efficacious as drug therapy. Surgery may be the initial treatment if IOP is extremely high, the patient does not wish to use or has trouble adhering to drug therapy, or if there is significant visual field damage at presentation.

Drug therapy

Multiple drugs are available (see table Drugs Used to Treat Glaucoma). Topical agents are preferred. The most popular are prostaglandin analogs, followed by beta-blockers (particularly timolol). Other drugs include alpha-2-selective adrenergic agonists, carbonic anhydrase inhibitors, rho kinase inhibitors, and cholinergic agonists. Oral carbonic anhydrase inhibitors are effective, but adverse effects limit their use.

Patients taking topical glaucoma drugs should be taught passive eyelid closure with punctal occlusion to help reduce systemic absorption and associated adverse effects, although the effectiveness of these maneuvers is controversial. Patients who have difficulty instilling drops directly onto the conjunctiva may place the drop on the nose just medial to the medial canthus, then roll the head slightly toward the eye so that the liquid flows into the eye.

Typically, to gauge effectiveness, clinicians start drugs in one (one-eye trial) or both eyes.


Drugs Used to Treat Glaucoma



Mechanism of Action on Eye


Prostaglandin analogs (topical)


1 drop at bedtime

Increase uveoscleral outflow rather than altering conventional (trabeculocanalicular) aqueous outflow

Increased pigmentation of the iris and skin

Possible worsening of uveitis

Elongated and thickened eyelashes

Muscle, joint, and back pain



1 drop at bedtime


1 drop at bedtime


1 drop at bedtime

Beta-blockers (topical)


1 drop once or twice a day

Decrease aqueous production; do not affect pupil size

Systemic adverse effects (eg, bronchospasm, depression, fatigue, confusion, erectile dysfunction, hair loss, bradycardia)

May develop insidiously and be attributed by patients to aging or other processes


1 drop once or twice a day*


1 drop once or twice a day


1 drop twice a day*


1 drop once or twice a day


1 drop once or twice a day

Carbonic anhydrase inhibitors (oral or IV)


125–250 mg orally four times a day (or 500 mg orally twice a day using extended-release capsules) or 500 mg IV single dose for acute lowering

Decrease aqueous production

Used as adjunctive therapy

Cause fatigue, altered taste, anorexia, depression, paresthesias, electrolyte abnormalities, kidney calculi, and blood dyscrasias

Possibly nausea, diarrhea, weight loss


25–50 mg orally two or three times a day

Carbonic anhydrase inhibitors (topical)


1 drop two or three times a day

Decrease aqueous production

Low risk of systemic effects, but may cause bad taste in mouth and/or rash


1 drop two or three times a day

Rho kinase inhibitor 


1 drop at bedtime

Increases conventional aqueous outflow

May develop conjunctival hyperemia (redness), corneal verticillata, subconjunctival petechial hemorrhages

Miotics, direct-acting (cholinergic agonists; topical)†


1 drop two or three times a day

Cause miosis, increase aqueous outflow

Less effective as monotherapy than beta-blockers

Possible need for higher strengths in patients with darker-pigmented pupils

Hinder dark adaptation


1 drop two to four times a day

Miotic, indirect-acting (cholinesterase inhibitors; topical)†

Echothiophate iodide

1 drop once or twice a day

Causes miosis, increases aqueous outflow

Very long acting: Irreversible inhibition; can cause cataracts and retinal detachment; should be avoided in angle-closure glaucoma because of the extreme miosis; hinders dark adaptation

Systemic effects (eg, sweating, headache, tremor, excess saliva production, diarrhea, abdominal cramps, nausea) more likely than with direct-acting miotics

May still be an option in pseudophakic patients

Osmotic diuretics (oral, IV)‡


1–1.5 g/kg body weight orally (may repeat 8–12 hours later)

Cause increased serum osmolarity, which draws fluid from eye

Used for acute angle closure

Has adverse systemic effects

Can rarely cause cerebral hemorrhage and acute, decompensated heart failure

Ineffective in patients with moderate to severe renal failure


0.5–2.0 g/kg body weight IV over 30–45 minutes (may repeat 8–12 hours later)

Alpha-2-selective adrenergic agonists (topical)


1 drop two to three times a day

Decrease aqueous production; may increase uveoscleral aqueous outflow; may cause mydriasis

With apraclonidine, high rate of allergic reactions and tachyphylaxis; less common with brimonidine, which may cause dry mouth and is contraindicated in children < 2 years

Systemic effects (eg, hypertension, tachycardia) less common than with nonselective agonists


1 drop two to three times a day§‡

* Beta-1-selective.

† Miotics are rarely used.

‡ For acute use only.

§ More alpha-2-selective than apraclonidine.


Surgery for primary open-angle glaucoma and normal-pressure glaucoma includes laser trabeculoplasty, a guarded filtration procedure, and procedures that enhance only a portion of the drainage pathway.

Selective laser trabeculoplasty (SLT) uses a pulsed double-frequency neodymium:yttrium-aluminum-garnet laser. SLT and argon laser trabeculoplasty (ALT) are equally effective initially, but SLT may have greater effectiveness in subsequent treatments. SLT is usually the initial treatment for patients who do not respond to or who cannot tolerate drug therapy.

Argon laser trabeculoplasty (ALT) may also be considered for surgical treatment of glaucoma. Laser energy is applied to either 180º or 360º of the trabecular meshwork to improve the drainage of aqueous humor. Within 2 to 5 years, about 50% of patients require additional drug therapy or surgery because of insufficient IOP control.

A guarded filtration procedure is the most commonly used filtration procedure. A hole is made in the limbal sclera (trabeculectomy), which is covered by a partial-thickness scleral flap that controls egress of aqueous from the eye to the subconjunctival space, forming a filtration bleb. Adverse effects of glaucoma filtration surgery include acceleration of cataract growth, pressures that are too low, and transient accumulation of fluid in the choroidal space (ie, choroidal effusion) during the perioperative period. Patients with trabeculectomies are at increased risk of bacterial endophthalmitis and should be instructed to report any symptoms or signs of bleb infection (blebitis) or endophthalmitis (eg, worsening vision, conjunctival hyperemia, pain) immediately.

Partial-thickness procedures bypass portions of the outflow pathways, unlike full-thickness procedures, even if guarded, that create a direct conduit between the anterior chamber and subconjunctival space.

The ab externo approach (an approach from outside the eye), including viscocanalostomy, deep sclerectomy, and canaloplasty, involves a deep dissection of greater than >98% thickness of the scleral passage, leaving a window of Descemet membrane and/or the inner wall of the Schlemm canal and trabecular meshwork. The canal is dilated by using a viscoelastic solution (in viscocanalostomy) or a microcatheter (in canaloplasty). Deep sclerectomy generally relies on the formation of a conjunctival bleb.

In the ab interno approach (an approach from inside the eye), a device is used to remove (eg, with ab interno trabeculectomy) or bypass (eg, with some stent procedures) the trabecular meshwork, creating direct communication between the anterior chamber and collecting channels. No bleb is formed.

In general, these procedures appear to be safer but less effective than trabeculectomy.

Key Points about Primary Open-Angle Glaucoma

  • Primary open-angle glaucoma is usually related to elevated intraocular pressure (IOP) but may occur with normal IOP.

  • Vision loss due to glaucoma cannot be recovered.

  • Begin diagnostic evaluation with ophthalmoscopy, measurement of IOP, and visual field testing.

  • Aim to decrease IOP by 20 to 40%.

  • Begin treatment with topical drugs (eg, prostaglandin analogs such as latanoprost or tafluprost, beta-blockers such as timolol).

  • Consider surgical treatment if drugs are not effective or if visual loss is severe.

Drugs Mentioned In This Article

Drug Name Select Trade
No US brand name
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