Acute Angle-Closure Glaucoma in Emergency Medicine

Glaucoma refers to a range of ocular diseases that ultimately result in increased intraocular pressure (IOP) and decreased visual acuity. Acute angle-closure glaucoma (AACG) is an ocular emergency and is differentiated by its acute presentation, need for immediate treatment, and well-established anatomic pathology.[1] Rapid diagnosis, immediate intervention, and referral can have profound effects on patient outcome and morbidity.

The acute angle closure literature has been plagued by the lack of a uniform definition and specific diagnostic criteria. Only in recent years has there been a strong push to standardize the definitions of the various forms of angle closure disease. Primary angle closure, primary angle-closure glaucoma, acute angle closure, and acute angle-closure glaucoma were previously used interchangeably. Acute angle closure is defined as at least 2 of the following symptoms: ocular pain, nausea/vomiting, and a history of intermittent blurring of vision with halos; and at least 3 of the following signs: IOP greater than 21 mm Hg, conjunctival injection, corneal epithelial edema, mid-dilated nonreactive pupil, and shallower chamber in the presence of occlusion.

Primary angle closure is defined as the presence of signs of trabecular obstruction on physical exam in the setting of an occludable drainage angle. These signs include peripheral anterior synechiae, increased IOP, distortion of iris fibers [iris whorling], lens opacities, and excessive trabecular pigmentation deposits. Further, the term primary angle closure suspect refers to an eye in which there is contact between the peripheral iris and the posterior trabecular meshwork, or in which contact is considered possible based on ocular anatomy, and there is no evidence of acute disease. The term glaucoma is added if glaucomatous optic neuropathy is present.

AACG occurs as a result of the impaired drainage of aqueous humor and subsequent pathologic increase in IOP. Aqueous humor is produced by the ciliary body in the posterior chamber of the eye. It diffuses from the posterior chamber, through the pupil, and into the anterior chamber. From the anterior chamber, the fluid is drained into the vascular system via the trabecular meshwork and canal of Schlemm.

There exist several anatomic abnormalities which can lead to anterior chamber crowding, predisposing individuals to AACG. These include a shallow anterior chamber, thin ciliary body, thin iris, anteriorly-situated lens, thickened lens,[2] and short axial eye length. Studies have suggested that increased iris thickness and cross-sectional area are also associated with increased risk.[3] Of the many predisposing anatomical variations, a narrow angle has the most devastating consequences.

In the traditional model of AACG, the eye's physiologic pupillary dilation (as in response to environmental or chemical stimuli) contributes to a pathologic iris-lens apposition. When there is increased apposition or contact between the lens and the iris caused by this dilatory action, there is a risk of pupillary block (resistance in the aqueous flow from the posterior to anterior chamber). The increasing pressure in the posterior chamber then pushes the iris forward in an action termed "iris bombé," further narrowing the angle and obstructing aqueous drainage. Each step in this process can result in further increasing IOP, leading to a vicious cycle of ever increasing pressure.

Research has suggested an alternative pathway for AACG. Cronemberger et al propose that an acute increase in sympathetic tone is the underlying pathophysiology of AACG and this is compounded by excessively active or large iris dilatory muscles. Emotional distress, sympathomimetic drugs, or conditions of low light precipitate increased ocular sympathetic tone causing pupillary dilation, and thickening of the middle-peripheral iris. This thickening can lead to angle closure, thereby obstructing the outflow of aqueous humor.[4]

Other proposed mechanisms of AACG include plateau iris, lens swelling, and ciliary block. Plateau iris, thought to be less common than pupillary block, is an anatomic configuration in which the iris is flattened with an anterior attachment in the setting of a normal anterior chamber depth. The pathologic consequences are more or less due to the anterior insertion of the iris. The superfluous and crowded iris tissue blocks the trabecular meshwork thereby leading an increased IOP.

The remaining causes that will be discussed in this article, lens swelling and ciliary block, are extremely rare. Lens swelling is typically the result of lens necrosis secondary to cataracts. As the lens swells, it crowds the anterior chamber and, through mechanisms previously discussed at length, leads to an increase in IOP. Finally, when there is increasing force posterior to the lens (as can be seen in post-surgical inflammation or uveitis), both the lens and iris are pushed forward, termed ciliary block. 

Prevalence

The prevalence of AACG worldwide is about 0.6% but varies with ethnicity.[5]

Mortality/Morbidity

Outcome after AACG is dependent on duration from onset to treatment, underlying ocular disease, and ethnicity. The degree of IOP elevation has been shown to have less impact on future visual acuity. Studies report that as many as two thirds of individuals with AACG had no visual field loss; however, Asians appear to be be less likely to respond to initial medical management, and are more likely to experience a progressive increase in IOP and deterioration in visual acuity even with definitive intervention.[6]

Race

AACG occurs in 1 of 1000 whites, about 1 in 100 Asians, and as many as 2-4 of 100 Eskimos.[7, 8]

Sex

Women are at increased risk for developing AACG and for developing subsequent blindness from AACG.[9]  

Age

Elderly patients in their sixth and seventh decades of life are at greatest risk.[9]

Decrease time to presentation is associated with a more favorable prognosis, as is prophylactic iridectomy on all fellow eyes. Surprisingly, degree of IOP elevation is not associated with a worse prognosis.[10]  

Classically, affected patients are in their sixth decade of life, suffer from hyperopia, and have no history of glaucoma. Most commonly, they present with periorbital pain and visual deficits.[11] The pain is described as piercing and is associated with an ipsilateral headache. Patients note blurry vision and see halos, or rings of light, around objects.

Careful investigation can elucidate a precipitating factor, such as dim light or medications (eg, anticholinergics, sympathomimetics).

It is not uncommon for patients with PACG to present with non-ocular complaints, such as an isolated headache, thereby increasing the likelihood that they are initially evaluated for a subarachnoid hemorrhage, or treated for migraines. Several case reports detail patients presenting with abdominal pain and vomiting, leading to a diagnosis of gastroenteritis and delayed definitive treatment.[12]

Initial evaluation of a patient with concern for AACG should include an exam of the external eye, the pupils, a direct or slit-lamp ophthalmoscopic exam, an assessment of ocular motility, visual fields, and visual acuity, and a measurement of the IOP. All of these tend to be affected in AACG.

Patients complaining of blurred vision may reveal to have decreased visual acuity in the affected eye, often with the ability to only detect hand movement. They may even be unable to identify numbers and letters on distance charts or near cards.

Slit-lamp evaluation may reveal corneal edema, synechiae, segmental iris atrophy, or an irregular pupillary shape or pupillary function, although the exam may be limited by the presence of a cloudy cornea, which is commonly present.

Other findings may include ciliary flush, or corneal and scleral injection.

Increased IOP (IOP > 21 mm Hg, but often 20 mm Hg and more) and ischemia result in pain on eye movement, a mid-dilated nonreactive pupil, and a firm globe. Clinicians must take a comprehensive history and perform a thorough physical examination to ensure that this time-sensitive diagnosis is not missed.

Anatomic variants with a higher propensity for the development of AACG include a shallow anterior chamber, anteriorly situated lens, short axial eye length, thick iris, overdeveloped iris dilator muscles, and a narrow angle.[3]

Precipitating factors include drugs (ie, sympathomimetics, anticholinergics, antidepressants [SSRIs], anticonvulsants, sulfonamides, cocaine, botulinum toxin),[13, 14, 15, 16, 17] dim light, and rapid correction of hyperglycemia (leading to lens swelling).

Case reports have identified AACG associated with carotid-cavernous sinus fistula, trauma, prone surgical positioning, and giant cell arteritis.[17, 18, 19]

The diagnosis of acute angle-closure glaucoma (AACG) is predicated upon the clinical presentation of painful vision loss and a physical examination revealing a fixed mid-dilated pupil. No definitive laboratory or imaging studies are available; however, tonometry must be performed and must demonstrate increased intraocular pressure (IOP).

The patient should be brought to the hospital in an expeditious manner to have intraocular pressure (IOP) reduced. The patient should remain in the supine position as long as possible. The urge to wear eye patches, covers, or blindfolds should be resisted. By maintaining the conditions that cause pupillary dilation, these articles help perpetuate the attack. Their potential negative effects outweigh any presumed benefit.

The treatment of acute angle-closure glaucoma (AACG) consists of IOP reduction, suppression of inflammation, and the reversal of angle closure. Once diagnosed, the initial intervention includes acetazolamide, a topical beta-blocker, and a topical steroid.

Acetazolamide should be given as a stat dose of 500 mg IV followed by 500 mg PO. A dose of a topical beta-blocker (ie, carteolol, timolol) will also aid in lowering IOP. Studies have not conclusively demonstrated the superior neuronal or visual field protectiveness of one beta-blocker over another. Both beta-blockers and acetazolamide are thought to decrease aqueous humor production and to enhance opening of the angle. An alpha-agonist can be added for a further decrease in IOP.

Inflammation is an important part of the pathophysiology and presenting symptomology. Topical steroids decrease the inflammatory reaction and reduce optic nerve damage. The current recommendation is for 1-2 doses of topical steroids.

Addressing the extraocular manifestations of the disease is critical. This includes analgesics for pain and antiemetics for nausea and vomiting, which can drastically increase IOP beyond its already elevated level. Placing the patient in the supine position may aid in comfort and reduce IOP. It is also believed that, while supine, the lens falls away from the iris decreasing pupillary block.

After the initial intervention, the patient should be reassessed. Reassessment includes evaluating IOP, evaluating adjunct drops, and considering the need for further intervention, such as osmotic agents and immediate iridotomy.

Approximately 1 hour after beginning treatment, pilocarpine, a miotic that leads to opening of the angle, should be administered every 15 minutes for 2 doses. In the initial attack, the elevated pressure in the anterior chamber causes a pressure-induced ischemic paralysis of the iris. At this time, pilocarpine would be ineffective. During the second evaluation, the initial agents have decreased the elevated IOP and hopefully have reduced the ischemic paralysis so pilocarpine becomes beneficial in relieving pupillary block.

Pilocarpine must be used with caution. Theoretical concerns exist about its mechanism of action. By constricting the ciliary muscle, it has been shown to increase the axial thickness of the lens and to induce anterior lens movement. This could result in reducing the depth of the anterior chamber and worsening the clinical situation in a paradoxical reaction. Despite this, pilocarpine is recommended to be used as an additional agent.[20]

No standard rate of reduction for IOP exists; however, Choong et el identified a satisfactory reduction as IOP less than 35 mm Hg or a reduction greater than 25% of presenting IOP.[19] If the IOP is not reduced 30 minutes after the second dose of pilocarpine, an osmotic agent must be considered. An oral agent like glycerol can be administered in nondiabetics. In diabetics, oral isosorbide is used to avoid the risk of hyperglycemia associated with glycerol. Patients who are unable to tolerate oral intake or do not experience a decrease in IOP despite oral therapy are candidates for IV mannitol.

Hyperosmotic agents are useful for several reasons. They reduce vitreous volume, which, in turn, decreases IOP. The decreased IOP reverses iris ischemia and improves its responsiveness to pilocarpine and other drugs. Osmotic agents cause an osmotic diuresis and total body fluid reduction. They should be administered with caution in cardiovascular and renal patients. Choong et el demonstrated that 44% of patients required the addition of an osmotic agent to decrease IOP.[21] Repeat doses may be necessary if no effect is seen and if tolerated by the patient.

If patients fail medical management, there are surgical options (briefly touched on below).The ophthalmologist will evaluate all patients via gonioscopy (with complete inspection of the angle) to further decide the treatment course. At institutions where ophthalmologic consultation is immediately available, initial treatment should be performed in conjunction with the specialist.

If ophthalmologic consultation is not immediately available, the emergency department physician must begin pharmacologic therapy as described above. After appropriate IOP-reducing therapy is administered, ophthalmologic evaluation must be ensured by transferring the patient, if necessary. If the IOP is unchanged or continues to increase in spite of appropriate pharmacologic therapy, the attack will most likely persist without surgical management. Because outcome is adversely affected by the duration of symptoms, expeditious evaluation by a specialist is required. Ocular massage through a closed eyelid may be performed while waiting for ophthalmology if no other treatment reduces IOP.

Ophthalmologic consultation should be obtained as soon as possible because acute-angle closure glaucoma is an ophthalmic emergency.

When medical therapy proves to be ineffective, corneal indentation (CI) can be used as a temporizing measure to reduce IOP until definitive treatment is available. As the cornea is indented, aqueous humor is displaced to the periphery of the anterior chamber, which serves to temporarily open the angle. This leads to immediate reduction of IOP and occasionally may completely abort the attack. After applying topical anesthetic, any smooth instrument can be used to perform this procedure, including a gonioprism (ideal, if available), or a cotton-tipped applicator. Obviously, a concern with performing CI is the possibility for damage to the corneal epithelium, which may complicate the patient’s course.[22]

Laser peripheral iridotomy (LPI), performed 24-48 hours after IOP is controlled, is considered the definitive treatment for AACG. Furthermore, LPI may be offered prophylactically to individuals anatomically predisposed to AACG if identified before the first acute attack. While LPI is the current definitive treatment, evidence suggests that argon laser peripheral iridoplasty (ALPI) and anterior chamber paracentesis (ACP) may have increasing roles in the management of AACG.

In ALPI, burns are made in the peripheral iris resulting in iris contraction and opening of the angle. Some studies suggest ALPI causes a more immediate decrease in IOP, resulting in better outcomes with fewer side effects than systemic therapy[23] ; however, a recent randomized-controlled trial comparing LPI plus ALPI compared with ALI alone failed to show improved outcomes with ALPI as an adjunctive therapy.[24]  Systemic therapy must still be used with ACP, but ACP appears to instantaneously relieve symptoms.

An additional alternative is lens extraction. Although its role in AACG has not been completely established, it has been proven to effectively reduce IOP without the need for medication postoperatively. Furthermore, it offers a therapeutic advantage for individuals with coexisting cataracts.[25]

The goal in treatment of AACG is to reduce IOP. Medical management is the first step. A prompt reduction in IOP using topical and systemic medication decreases the duration of elevated IOP and the potential for a permanent reduction in visual acuity. IOP reduction is accomplished via suppressing aqueous humor production, eliminating pupillary block, and reversing inflammation. As with any medical intervention, intimate knowledge of the drugs, their indications, contraindications, and potential side effects can aid the physician in providing the best treatment and a favorable outcome.

Class Summary

These are first-line agents that should be used immediately during the initial intervention. They reduce bicarbonate production in the ciliary epithelium and therefore decrease aqueous formation.

Acetazolamide (Diamox)

Reduces rate of aqueous humor formation by direct inhibition of enzyme carbonic anhydrase (CA) on secretory ciliary epithelium, causing, in turn, a reduction in IOP. More than 90% of CA must be inhibited before IOP reduction can occur. May reduce IOP by 40-60%. Effects are seen in about an hour, they peak in 4 h, and trough in about 12 h. Derived chemically from sulfa drugs. If one form is not well tolerated, another form may be better or lower dose of the drug may better tolerated. IV administration of this medication may be used for rapid relief of increased IOP. A beneficial effect occurs when used with miotics or mydriatics.

Methazolamide (Neptazane)

Reduces aqueous humor formation by inhibiting enzyme carbonic anhydrase, which results in decreased IOP.

Class Summary

These agents may lower IOP via their suppression of aqueous humor production and probably not through any affects on the pupil.

Timolol ophthalmic (Timoptic, Timoptic XE)

Reduces elevated and normal IOP by reducing aqueous humor production or possibly the outflow.

Carteolol ophthalmic (Ocupress)

Nonselective beta-adrenergic receptor. Blocks beta1- and beta2-receptors and has mild intrinsic sympathomimetic activity (ISA), with possibly fewer cardiac and lipid profile adverse effects. Precise mechanism by which carteolol decreases IOP is thought to be through reduction of aqueous formation.

Levobunolol (AKBeta, Betagan)

Nonselective beta-adrenergic blocking agent that lowers IOP by reducing aqueous humor production and may increase outflow of aqueous humor.

Dosages of more than 1 gtt of 0.5% levobunolol twice daily have not been shown to be more effective. If IOP not at satisfactory level on this regimen, concomitant therapy can be instituted. However, do not administer 2 or more topical ophthalmic beta-adrenergic blocking agents simultaneously.

Class Summary

These agents are used as adjunct agents to further decrease IOP secondary to their affect on aqueous humor production.

Apraclonidine (Iopidine)

Potent alpha-adrenergic agent selective for alpha2-receptors with minimal cross-reactivity to alpha1-receptors. Suppresses aqueous production. Reduces elevated, as well as normal, IOP whether or not accompanied by glaucoma. Apraclonidine is relatively selective alpha-adrenergic agonist that does not have significant local anesthetic activity. Has minimal cardiovascular effects.

Brimonidine (Alphagan, Alphagan-P)

Selective alpha2 receptor that may reduce aqueous humor formation, may decrease inflow, or may increase uveoscleral outflow.

Class Summary

These agents reduce ocular inflammation thereby providing symptomatic relief and augmenting the affects of other medications.

Prednisolone ophthalmic (AK-Pred, Econopred)

Used in treatment of acute inflammations following eye surgery or other insults to the eye.

In cases of bacterial infections, concomitant use of anti-infective agents is mandatory. If signs and symptoms do not improve after 2 d, reevaluate the patient. Dosing may be reduced, but advise patients not to discontinue therapy prematurely.

Class Summary

These agents pull the peripheral iris tissue away from the trabecular meshwork helping to eliminate obstructed aqueous humor flow. They are ineffective during the initial period due to the ischemic paralysis of the iris. Miotics should be used after the immediate management and initial reduction of IOP.

Pilocarpine ophthalmic (Pilagan, Pilocar, Pilostat)

Patients may be maintained on pilocarpine as long as IOP is controlled and no deterioration in visual fields is present. May be used alone or in combination with other miotics, beta-adrenergic blocking agents, epinephrine, carbonic anhydrase inhibitors, or hyperosmotic agents to decrease IOP.

Frequency of instillation and concentration are determined by patient's response. Individuals with heavily pigmented irides may require higher strengths.

Class Summary

Hyperosmotic agents increase serum osmolarity and cause a fluid shift from the eye into the vascular space. The subsequent osmotic diuresis reduces IOP.

Glycerin (Osmoglyn)

Used in glaucoma to interrupt acute attacks. Reduces IOP through its diuretic effects. Adds to tonicity of blood until metabolized and eliminated by kidneys. Maximal reduction of IOP occurs 1 h after glycerin administration. The effect lasts approximately 5 h.

Isosorbide dinitrate (Dilatrate-SR, ISDN, Isordil)

In the eyes, creates an osmotic gradient between plasma and ocular fluids. Induces diuresis by elevating osmolarity of glomerular filtrate, thereby hindering tubular reabsorption of water. May be used to interrupt an acute attack of glaucoma. Use when less risk of nausea and vomiting, compared with other oral hyperosmotic agents, is needed.

Mannitol (Osmitrol)

Reduces elevated IOP when pressure cannot be lowered by other means.

Initially assess for adequate renal function in adults by administering a test dose of 200 mg/kg IV over 3-5 min. Should produce a urine flow of at least 30-50 mL/h of urine over 2-3 h.

In children, assess for adequate renal function by administering a test dose of 200 mg/kg IV over 3-5 min. Should produce a urine flow of at least 1 mL/h over 1-3 h.

Patients remain on oral acetazolamide, pilocarpine, and beta-blockers or alpha-agonists until definitive treatment. After laser peripheral iridotomy (LPI), 33% of patients require topical medication to maintain lower intraocular pressure (IOP).

A low threshold for admission should be used with acute angle-closure glaucoma (AACG) patients. Immediate ophthalmologic consultation must be arranged and admission may be required based on their treatment protocol and the patient's response to therapy. Patients who received osmotic agents may require electrolyte and volume status monitoring, particularly those with co-morbid illnesses.

Fellow eye surgery.

Complications may include the following:

• Permanent decrease in visual acuity

• Repeat episode

• Malignant glaucoma

• Fellow eye attack

• Central retinal artery occlusion

• Central retinal vein occlusion

Several studies evaluated patients after treatment for AACG and demonstrated favorable outcomes. With adequate treatment, most patients recover their lost vision. In whites, IOP was controlled with LPI alone in 65-76%. Asians more often have medically refractory initial attacks and require medications after LPI.[6] They also have higher rates of vision loss and subsequent increases in IOP.[6] It has been hypothesized that the initial attack is often more severe in Asians resulting in greater trabecular damage. Another possibility is the formation of peripheral synechiae (adhesions) causing a creeping angle reclosure.

For patient education resources, see the Glaucoma Center, as well as Acute Angle-Closure Glaucoma, Glaucoma FAQs, Glaucoma Overview, and Understanding Glaucoma Medications.