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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 occur late and involve visual field loss. Diagnosis is by ophthalmoscopy, gonioscopy, visual field examination, and measurement of IOP. Treatment includes topical drugs (eg, prostaglandin analogs, β-blockers) and often requires laser or incisional surgery to increase aqueous drainage.
Etiology
Although open-angle glaucomas can have numerous causes (see Table 1: Glaucoma: Open-Angle Glaucoma: Classification Based on Mechanisms of Outflow Obstruction* ), 60 to 70% of cases 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.
Pathophysiology
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. These 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's syndrome) than the general population, suggesting that a vascular disorder compromising blood flow to the optic nerve may play a role.
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.
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
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
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
Diagnosis 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, and other ocular or neurologic disorders that cause similar visual field defects.
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.
Treatment
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.
Drug therapy:
Multiple drugs are available (see Table 4: Glaucoma: Drugs Used to Treat Glaucoma). Topical agents are preferred. The most popular are prostaglandin analogs, followed by β-blockers (particularly timolol). Other drugs include α2-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.
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Table 4
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| Drugs Used to Treat Glaucoma |
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Drug
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Dose/Frequency
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Mechanism of Action on Eye
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Comments
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Miotics, direct-acting (cholinergic agonists; topical)
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Carbachol
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1 drop bid–tid
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Cause miosis, increase aqueous outflow
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Less effective as monotherapy than β-blockers
Possible need for higher strengths in patients with darker-pigmented pupils
Hinder dark adaptation
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Pilocarpine
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1 drop bid–qid
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Miotics, indirect-acting (cholinesterase inhibitors; topical)
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Demecarium
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1 drop once/day–bid*
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Cause miosis, increase aqueous outflow
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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
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Echothiophate iodide
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1 drop once/day–bid*
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Isoflurophate
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1 drop once/day–bid*
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Neostigmine
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1 drop once/day–bid†
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Physostigmine
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1 drop once/day–bid†
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Carbonic anhydrase inhibitors (oral or IV)
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Acetazolamide
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125–250 mg po qid (or 500 mg po bid using extended-release capsules) or 500 mg IV single dose
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Decrease aqueous production
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Used as adjunctive therapy
Cause fatigue, altered taste, anorexia, depression, paresthesias, electrolyte abnormalities, kidney calculi, and blood dyscrasias
Possibly nausea, diarrhea, weight loss
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Methazolamide
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25–50 mg po bid–tid
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Carbonic anhydrase inhibitors (topical)
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Brinzolamide
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1 drop bid–qid
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Low risk of systemic effects, but may cause bad taste in mouth
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Dorzolamide
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1 drop bid–tid
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Nonselective adrenergic agonists (topical)
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Dipivefrin
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1 drop bid
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Cause mydriasis, increase aqueous outflow, and decrease aqueous production
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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)
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Epinephrine
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1 drop bid
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α 2-Selective adrenergic agonists (topical)
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Apraclonidine
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1 drop bid–tid
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Decrease aqueous production; may increase uveoscleral aqueous outflow; may cause mydriasis
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With apraclonidine, high rate of allergic reactions and tachyphylaxis; less common with brimonidine, which may cause dry mouth
Systemic effects (eg, hypertension, tachycardia) less common than with nonselective agonists
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Brimonidine
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1 drop bid–tid‡
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β-Blockers (topical)
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Timolol
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1 drop once/day–bid
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Decrease aqueous production; do not affect pupil size
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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
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Betaxolol
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1 drop once/day–bid§
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Carteolol
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1 drop once/day–bid
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Levobetaxolol
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1 drop bid
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Levobunolol
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1 drop once/day–bid
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Metipranolol
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1 drop once/day–bid
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Prostaglandin analogs (topical)
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Bimatoprost
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1 drop at bedtime
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Increase uveoscleral outflow rather than altering conventional (trabeculocanalicular) aqueous outflow
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Increased pigmentation of the iris and skin; possible worsening of uveitis
Elongated and thickened eyelashes; muscle, joint, and back pain; skin rash
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Latanoprost
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1 drop at bedtime
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Travoprost
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1 drop at bedtime
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Unoprostone
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1 drop at bedtime
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Osmotic diuretics (oral, IV)
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Glycerin
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1–1.5 g/kg body weight po (may repeat 8–12 h later)
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Cause increased serum osmolarity, which draws fluid from eye
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Used for acute angle closure
Have adverse systemic effects
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Mannitol
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0.5–2.0 g/kg body weight IV over 30–45 min (may repeat 8–12 h later)
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*Irreversible; may be cataractogenic; increased risk of retinal detachment.
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†Reversible.
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‡More α2-selective than apraclonidine.
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§
β 1-Selective.
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Surgery:
Surgery for primary open-angle and normal-pressure glaucoma includes laser trabeculoplasty, a guarded filtration procedure, and possibly tube shunts or ciliodestructive procedures.
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.
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 swelling 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 immediately.
Viscocanalostomy, canaloplasty, and Trabectome® surgery are newer filtration procedures that do not involve creating a fistula between the anterior chamber and subconjunctival space. Viscocanalostomy and canaloplasty involve dilating Schlemm's canal. Trabectome® surgery uses a proprietary device to remove a portion of the inner aspect of one of the drains of the eye (trabecular meshwork). More long-term studies with these procedures are needed and are on-going. Currently, these new procedures do not appear as effective as trabeculectomy but seem to offer greater safety.
Last full review/revision August 2008 by Douglas J. Rhee, MD
Content last modified February 2012
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