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Primary Open-Angle Glaucoma

by Douglas J. Rhee, MD


Although open-angle glaucomas can have numerous causes (see Open-Angle Glaucoma: Classification Based on Mechanisms of Outflow Obstruction*), 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.

Risk factors include older age, positive family history, black race, thinner central corneal thickness, systemic hypertension, diabetes, and myopia. In blacks, glaucoma is more severe and develops at an earlier age, and blindness is 6 to 8 times more likely.


IOP can be elevated or within the average range.

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- or 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

Early 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. 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 (including 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

Thinning of the neurosensory rim over time alone can be diagnostic of glaucoma regardless of the IOP or visual field. However, most initial diagnoses of glaucoma involve some visual field change.

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.


  • Visual field testing

  • Ophthalmoscopy

  • Measurement of central corneal thickness and IOP

  • Exclusion of other optic neuropathies

Diagnosis is suggested by the examination, but similar findings can result from other optic neuropathies (eg, caused by ischemia, cytomegalovirus infection, or vitamin B 12 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, and 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 years, depending on the patient’s reliability, severity of the glaucoma, and response to treatment.


  • Decreasing IOP 20 to 40%

  • Initially, drugs (eg, prostaglandin analogs such latanoprost or tafluprost, β-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. 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. 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 Drugs Used to Treat Glaucoma). Topical agents are preferred. The most popular are prostaglandin analogs, followed by β-blockers (particularly timolol). Other drugs include α 2 -selective adrenergic agonists, cholinergic agonists, and carbonic anhydrase inhibitors. Oral carbonic anhydrase inhibitors are effective, but adverse effects limit their use.

Patients taking topical glaucoma drugs should be taught passive lid 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 only one eye (one-eye trial); once improvement in the treated eye has been confirmed at a subsequent visit (typically 1 to 4 wk later), both eyes are treated.

Drugs Used to Treat Glaucoma



Mechanism of Action on Eye


Miotics, direct-acting (cholinergic agonists; topical)


1 drop bid–tid

Cause miosis, increase aqueous outflow

Less effective as monotherapy than β-blockers

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

Hinder dark adaptation


1 drop bid–qid

Miotics, indirect-acting (cholinesterase inhibitors; topical)


1 drop once/day–bid*

Cause miosis, increase aqueous outflow

Shorter acting (neostimine, physostigmine): Reversible inhibition

Very long acting (demecarium, echothiophate, isoflurophate): Irreversible inhibition; can cause cataracts and retinal detachment; should be avoided in angle-closure glaucoma because of the extreme miosis; hinder 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 excellent choices in pseudophakic patients

Echothiophate iodide

1 drop once/day–bid*


1 drop once/day–bid*


1 drop once/day–bid


1 drop once/day–bid

Carbonic anhydrase inhibitors (oral or IV)


125–250 mg po qid (or 500 mg po bid using extended-release capsules) or 500 mg IV single dose

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 po bid–tid

Carbonic anhydrase inhibitors (topical)


1 drop bid–qid

Low risk of systemic effects, but may cause bad taste in mouth


1 drop bid–tid

Nonselective adrenergic agonists (topical)


1 drop bid

Cause mydriasis, increase aqueous outflow, and decrease aqueous production

Often combined with a miotic (dipivefrin, a prodrug, is metabolized to epinephrine)

Less reliable than selective adrenergic agonists and higher incidence of allergic and toxic reactions (eg, hypertension, tachycardia)


1 drop bid

α 2 -Selective adrenergic agonists (topical)


1 drop bid–tid

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 yr

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


1 drop bid–tid

β-Blockers (topical)


1 drop once/day–bid

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/day–bid


1 drop once/day–bid


1 drop bid


1 drop once/day–bid


1 drop once/day–bid

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; rash


1 drop at bedtime


1 drop at bedtime


1 drop at bedtime


1 drop bid

Osmotic diuretics (oral, IV)


1–1.5 g/kg body weight po (may repeat 8–12 h later)

Cause increased serum osmolarity, which draws fluid from eye

Used for acute angle closure

Have adverse systemic effects


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

*Irreversible; may be cataractogenic; increased risk of retinal detachment.


More α 2 -selective than apraclonidine.

β 1 -Selective.


Surgery for primary open-angle and normal-pressure glaucoma includes laser trabeculoplasty, a guarded filtration procedure, and possibly procedures that create only a partial-thickness drainage pathway.

Argon laser trabeculoplasty (ALT) may be the initial treatment for patients who do not respond to or who cannot tolerate drug therapy. Laser energy is applied to either 180º or 360º of the trabecular meshwork to improve the drainage of aqueous humor. Within 2 to 5 yr, about 50% of patients require additional drug therapy or surgery because of insufficient IOP control.

Selective laser trabeculoplasty (SLT) uses a pulsed double-frequency neodymium:yttrium-aluminum-garnet laser. SLT and ALT are equally effective initially, but SLT may have greater effectiveness in subsequent treatments. SLT may also be considered for initial treatment.

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.

In partial thickness procedures, the fistula or drainage pathway created between the anterior chamber and subconjunctival space is only partial thickness.

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

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.

Although these procedures are still under study, they do appear to be safer but less effective than trabeculectomy.

Key Points

  • Primary open-angle glaucoma is usually related to elevated 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 latanoprost or tafluprost, β-blockers such as timolol).

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

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Drugs Mentioned In This Article

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* This is a professional Version *