Continuing Education Activity

Acute angle-closure glaucoma is an ocular emergency that results from a rapid increase in intraocular pressure due to outflow obstruction of aqueous humor. Several factors lead to the obstruction in acute angle-closure glaucoma, but the major predisposing factor is the structural anatomy of the anterior chamber, leading to a shallower angle between the iris and the cornea. Acute angle-closure glaucoma presents as a sudden onset of severe unilateral eye pain or a headache associated with blurred vision, rainbow-colored halos around bright lights, nausea, and vomiting. This activity reviews the evaluation and treatment of patients with acute angle-closure glaucoma and highlights the role of the interprofessional team in managing patients with this condition.

Objectives:

• Identify patients at risk of acute closed-angle glaucoma through comprehensive medical history, ocular examination, and relevant diagnostic tests.

• Assess the severity and progression of acute closed-angle glaucoma using appropriate clinical and imaging modalities.

• Select and utilize appropriate pharmacological agents and procedures to manage acute closed-angle glaucoma.

• Collaborate with other healthcare professionals, such as ophthalmologists and optometrists, in managing and following up on patients with acute closed-angle glaucoma.

Introduction

Glaucoma, characterized by increased intraocular pressures (IOP), can result in optic neuropathy and vision loss if left untreated.[1] It is classified as open-angle or closed-angle and can be primary or secondary depending on the obstruction in the anterior chamber. The angle refers to the space between the iris and the cornea in the anterior chamber, which can become structurally obstructed.

Primary glaucomas are not associated with known ocular or systemic disorders and usually affect both eyes. In contrast, secondary glaucomas are often unilateral and linked to ocular or systemic diseases. Acute closed-angle glaucoma (ACAG) is a subset of primary angle-closure glaucoma. Acute angle-closure (AAC) is an ophthalmologic emergency with elevated IOP, posing a risk of irreversible damage and potential blindness not treated promptly.[2] 

AAC usually presents with significant and distressing symptoms such as unilateral intense periocular pain, redness in the eye, rapid vision loss, systemic symptoms, nausea, headache, multicolored halos around light sources, and vomiting.[3] Nonophthalmologic practitioners may misinterpret these symptoms as neurological conditions, leading to unnecessary cranial imaging and neurologic consultations before ophthalmologic examinations are conducted.[4]

The diagnosis of AAC is confirmed by elevated IOP measured using tonometry, which can range from 50 to 80 mm Hg.[5] Examination with a slit-lamp microscope usually reveals a shallow anterior chamber, corneal edema, fixed dilated pupil, conjunctival injection around the limbus (ciliary flush), and a closed angle on gonioscopy.[6] Treatment options include medical, laser, and surgical interventions to reduce IOP, relieve acute symptoms, and prevent future angle closures.[7]

The normal range for IOP measured by tonometry is 10 to 21 mm Hg.[8] IOP is influenced by the ciliary body's production rate of aqueous humor, the resistance to aqueous outflow through the trabecular meshwork and Schlemm's canal, and the episcleral venous pressure. Aqueous humor is produced in the ciliary body, passes through the pupil, and drains through the trabecular meshwork (TM) and Schlemm canal at the anterior chamber's angle. In ACAG, IOP increases rapidly due to outflow obstruction of the aqueous humor. The main predisposing factor for ACAG is the anterior chamber's structural anatomy, which can lead to a shallower angle.[9][10]

Etiology

Primary angle closure is characterized by a reversible (appositional) closure of the anterior chamber angle or an adhesional (synechial) closure. It can present in acute or chronic forms. Acute angle closure occurs when there is a sudden increase in IOP due to blockage of aqueous outflow from the trabecular meshwork (TM), resulting from a pupillary block of the iris that leads to complete closure of the angle.[11]

The subacute or intermittent form of primary angle closure is characterized by recurrent symptomatic episodes that are self-limiting.[12] In contrast, the chronic condition involves repeated episodes of angle closure, resulting in elevated IOP without symptoms and causing structural damage in the angle due to prolonged contact between the trabecular meshwork and peripheral iris.[13] This can lead to synechial closure and both structural and functional impairment in the angle over time.[14]

Aqueous humor flow obstruction in primary angle closure is attributed to various anatomic factors, including a shallow anterior chamber, lens size, anterior positioning of the iris-lens diaphragm, and a narrow entrance to the anterior chamber angle.[15] The shallow anterior chamber angle causes extensive contact between the iris and lens, impeding the flow of aqueous humor from the posterior to the anterior chamber. This results in a pressure difference between the chambers, known as a pupillary block.[16] 

The pupillary block mechanism induces bowing of the iris, further narrowing the angle of the anterior chamber. This ongoing cycle perpetuates increasing IOP, leading to the clinical manifestation of ACAG.[17]

The American Academy of Ophthalmology guidelines classify primary angle closure based on specific criteria, including the presence of a narrow angle, more than 180° of iridotrabecular contact (ITC), presence of peripheral anterior synechiae (PAS), elevated IOP, and signs of optic nerve damage.[18] Primary angle closure suspect (PACS) refers to an eye with ITC but no elevated IOP or PAS. "Primary angle closure" (PAC) is diagnosed when there is ITC with either PAS, IOP, or both. The term "primary angle-closure glaucoma" (PACG) is used when there is evidence of a glaucomatous retinal nerve fiber layer with or without optic nerve damage.

Epidemiology

The number of people worldwide affected by glaucoma was reported to be approximately 65 million in 2013. However, incidence was estimated to have increased to as high as 76 million in 2020 and is projected to reach over 110 million by 2040.[19] Among these cases, one-third are due to PACG. Meta-analyses have consistently demonstrated that PACG is more likely to lead to blindness than primary open-angle glaucoma.[20]

Acute angle-closure (AAC) glaucoma is considered a rare occurrence. The incidence of AAC in white individuals has been reported to be approximately 2 to 4 cases per 100,000 people.[6] However, the incidence has been higher in certain populations, such as Singapore and Asia, ranging from 6 to 12 cases per 100,000 inhabitants.[21][22]

Identified risk factors associated with ACAG include the following:[23]

• Age: ACG tends to manifest between the ages of 55 and 65, and the condition's prevalence further increases with age. This is likely due to the increasing thickness of the lens with age and the decreasing depth of the anterior chamber.[24]
• Gender: Studies have indicated that females have a 2 to 4 times higher incidence rate of AAC than males.[22]
• Race: ACAG is commonly observed in Southeast Asian, Chinese, and Inuit peoples while remaining relatively uncommon in black populations. The variability in ethnicities could be due to anatomical differences in the ciliary body and iris.[2] In white people, ACAG accounts for 6% of all glaucoma diagnoses.[25]
• Family history: Predisposed ocular anatomic features at risk can be inherited.[26][27]
• Hyperopia: Certain ocular anatomical features associated with an increased risk of ACG can be inherited. The predisposition to develop ACG can be passed down through familial lines.[28]
• Medications: Over 60 drugs have been reported to be associated with AAC and are considered risk factors, particularly for individuals with ocular predispositions. These drugs include topical anticholinergic pupil dilators, such as atropine and cyclopentolate, and systemic medication, including topiramate, sulfonamides, duloxetine, and phenothiazines.[29] Patients using these medications should undergo regular ophthalmic examinations, especially if they possess AAC risk factors.[30]

Pathophysiology

AAC is precipitated by the blockage of aqueous outflow from the TM, resulting in a sudden and non—self-resolving increase in IOP. This elevated pressure leads to significant systemic and ophthalmologic signs and symptoms.

Primary AAC refers to cases where the angle closure arises in isolation without any causes or associated diseases.[31] It occurs due to anatomical factors such as a shallow anterior chamber or a narrow angle predisposing the individual to sudden angle closure. On the other hand, secondary AAC refers to cases where angle closure is a consequence of other underlying causes or diseases.[32] These underlying factors can include trauma, inflammation, tumors, or certain systemic conditions that affect the eye's structures or the flow of aqueous humor.

The most common causes of primary AAC are attributed to a mechanism called pupillary block.[33] In certain conditions like mydriasis and posterior synechiae in eyes at risk of AAC, increased apposition between the lens and iris can disrupt the normal movement of aqueous humor from the posterior chamber.

As a result of this disruption, fluid forces are built behind the iris, pushing and bulging the peripheral iris. This bulging causes the iris to come in contact with the TM, leading to the acute closure of the angle between the iris and cornea.[34] This mechanism obstructs aqueous humor outflow, resulting in an acute and abrupt rise in IOP.[35] 

Nonpupillary block mechanisms can also cause angle closure and obstruct aqueous outflow from the TM. These conditions include plateau iris syndrome, ciliary body edema, anteriorly displaced or enlarged lens, and malignant glaucoma.[36]

History and Physical

AAC typically presents with sudden and severe symptoms, which may include:

• Eye pain or headache
• Blurred vision and reduced visual acuity
• Rainbow-colored halos
• Nausea and vomiting

During a physical examination, the following findings may be observed:

• Fixed midpoint dilated pupil
• Engorged conjunctival vessels
• Hazy or cloudy cornea
• Marked conjunctival injection
• Elevated intraocular pressure: Intraocular pressure is significantly increased during an acute attack and can reach high levels, ranging from 60 to 80 mm Hg.
• Mild aqueous flare and cells: Examination of the anterior chamber may reveal a slight amount of aqueous flare (haziness) and cells, indicating inflammation.
• Angle-closure on gonioscopy: Gonioscopy will reveal angle closure for 360 degrees, confirming the diagnosis of AAC.
• Swollen optic nerve: The optic nerve may appear swollen during an acute attack, indicating optic nerve head edema.[37][38]

Evaluation

Several diagnostic procedures are commonly performed in evaluating a patient with suspected AAC and include the following: 

Slit-lamp examination: Slit-lamp examination is essential for a detailed assessment of the anterior segment of the eye. It allows for a close examination of the cornea, iris, and anterior chamber to observe any abnormalities, such as corneal edema, conjunctival injection, or an anatomically narrow angle.

Measurement of intraocular pressure (IOP): Elevated intraocular pressure is a hallmark of AAC. Measuring the IOP using tonometry is a critical diagnostic step. Elevated IOP levels are typically observed in AAC, and values can be markedly high during an acute attack.

Imaging studies: In the acute phase of AAC, imaging studies are generally unnecessary for diagnosis. The clinical signs and symptoms, along with the findings obtained from the slit-lamp examination and IOP measurement, are usually sufficient to establish a diagnosis.

Basic metabolic panel: If osmotic agents, such as mannitol or glycerin, are used as part of the treatment regimen, checking a basic metabolic panel can help monitor electrolyte levels and renal function due to the potential systemic effects of these agents.

Gonioscopic examination: A gonioscopic examination, performed by an ophthalmologist, is crucial for verifying angle closure and making a definitive diagnosis of AAC. It involves evaluating the angle between the iris and cornea to determine the extent of closure. Gonioscopy of the unaffected eye may reveal a narrow, almost occluded angle, considering the anatomic predisposing factors for angle-closure glaucoma.

Glaucomflecken: Glaucomflecken refers to grey-white opacities that may be visible on the anterior lens capsule, typically following previous episodes of angle-closure glaucoma. These opacities can be observed during a slit-lamp examination, providing evidence of past attacks.[39]

Visual field testing with automated static perimetry and Optical Coherence Tomography (OCT) is crucial in managing patients with acute angle-closure glaucoma (AAC) to assess various aspects of the condition and guide treatment decisions.

Visual field testing: Automated static perimetry helps evaluate the extent and severity of glaucomatous visual field loss caused by AAC. It measures the patient's ability to perceive visual stimuli at different locations within their visual field. Serial visual field testing over time can provide valuable information about the condition's progression and the treatment's effectiveness.

Optical Coherence Tomography (OCT): OCT is a noninvasive imaging technique that provides detailed cross-sectional images of the retina and optic nerve head. It is useful in assessing retinal nerve fiber layer (RNFL) thickness, indicating damage caused by AAC. OCT can also help detect structural abnormalities and optic nerve head changes characteristic of glaucoma. Serial OCT scans allow for monitoring changes over time and assessing the response to treatment.

Anterior segment OCT and ultrasound biomicroscopy: In patients with risk factors for AAC, such as hyperopia, shallow anterior chamber, or a history of AAC in the fellow eye, anterior segment OCT and ultrasound biomicroscopy can be helpful. These imaging modalities provide detailed visualization of the anterior segment structures, including the angle, iris, and ciliary body. They can help assess anatomical features associated with angle closure and aid in decision-making for preventive measures or further interventions. 

Treatment / Management

The medical treatment of acute angle-closure glaucoma focuses on rapidly lowering IOP by blocking the production of aqueous humor, increasing the outflow of aqueous humor, and reducing the volume of aqueous humor.[18][40]

Initial medical therapy typically involves a combination of medications to reduce IOP and relieve symptoms rapidly. The following medications are commonly used:

• Oral or intravenous acetazolamide: Acetazolamide, a carbonic anhydrase inhibitor, is administered orally or intravenously to reduce aqueous humor production. It helps lower IOP by inhibiting the enzyme responsible for forming bicarbonate ions, reducing the aqueous humor secretion.[41] The dose is oral or IV 500 mg.
• Intravenous mannitol: Mannitol, an osmotic diuretic, is given intravenously to decrease the volume of aqueous humor and lower IOP rapidly. It draws fluid out of the eye, thereby reducing intraocular pressure.[42] The dosage is typically 1 to 2 grams per kilogram of body weight.
• Topical beta-blocker: A topical beta-blocker, such as timolol 0.5%, is applied as eye drops to block aqueous humor production. Beta-blockers reduce IOP by inhibiting the beta-adrenergic receptors in the ciliary body, thereby decreasing aqueous humor production.[43] The dose is timolol 0.5%; apply 1 drop on the affected eye.
• Topical alpha 2-agonist: An alpha 2-agonist, like apraclonidine 1%, is used as eye drops to block aqueous humor production. These medications reduce the production of aqueous humor and enhance the outflow of aqueous humor through the trabecular meshwork.[44] The dose is apraclonidine 1%; apply 1 drop to the affected eye.
• Topical pilocarpine: Pilocarpine, a miotic agent, is instilled as eye drops to increase the outflow of aqueous humor. It works by constricting the pupil and tightening the tension of the iris, which helps open the angle between the iris and cornea, facilitating aqueous humor drainage. Pilocarpine is usually administered once the intraocular pressure is below 40 mm Hg. The dose is pilocarpine 1% to 2%; apply 1 drop every 15 minutes for 2 doses once IOP is below 40 mm Hg.[45]

During the acute phase of AAC, it is crucial to closely monitor IOP to assess the effectiveness of treatment and ensure that it returns to normal values. Frequent IOP measurements are necessary to evaluate the response to therapy and make any necessary adjustments. The recommended frequency of IOP checks may vary depending on the specific situation and the response to treatment. Still, generally, it is advised to measure IOP at least every hour after the initial onset of symptoms until the IOP stabilizes.

After the acute episode of AAC subsides, definitive treatment focuses on preventing future angle-closure attacks and managing the underlying anatomical risk factors. The following treatment options are commonly employed:

Laser peripheral iridotomy (LPI) is the treatment of choice.[46] LPI involves using a laser to create a small hole in the peripheral iris, allowing for the flow of aqueous humor from the posterior chamber to the anterior chamber, bypassing the blocked angle. LPI helps to relieve pupillary block and prevent future angle-closure episodes. LPI is a minimally invasive procedure performed on an outpatient basis.

Surgical iridectomy is indicated when laser iridectomy cannot be performed or is insufficient.[47] This involves surgically removing a portion of the iris to create a permanent opening and relieve the pupillary block. Surgical iridectomy is typically reserved for situations where laser treatment is not feasible or unsuccessful.

Iridectomy or iridotomy relieves the pupillary block as the pressure between the posterior and anterior chamber approaches zero by allowing the flow of aqueous humor through a different route. Iridectomy/iridotomy should be as peripheral as possible and covered by the eyelid to avoid monocular diplopia through this second hole in the pupil.[48]

Lens extraction can be considered when there are significant anatomical risk factors. In these cases, lens extraction may be considered as a first-line treatment.[49] Lens extraction involves removing the crystalline lens, which can relieve the anatomical factors contributing to angle closure. This approach is often beneficial in eyes with advanced AAC.

If elevated IOP persists after the acute phase of AAC, treatment strategies similar to those used in open-angle glaucoma can be employed. These include topical medical therapy, laser treatment, and surgical interventions.

Routine ophthalmologic examinations, visual field testing, and OCT should be considered if the patient shows risks of developing elevated IOP and future glaucomatous damage.

Differential Diagnosis

Numerous conditions can lead to elevated IOP, corneal haze, inflammation of the conjunctiva and the anterior segment, and similar signs and symptoms seen in patients with AAC. When evaluating a patient presenting with these manifestations, the following differential diagnosis should be considered:

• Allergic conjunctivitis
• Bacterial conjunctivitis (pink eye)
• Viral conjunctivitis
• Keratitis
• Episcleritis or scleritis
• Eye trauma
• Chemical injury
• Corneal ulcer
• Open-angle glaucoma
• Drug-induced glaucoma
• Malignant glaucoma
• Neovascular glaucoma
• Phacomorphic glaucoma
• Senile cataract (age-related cataract)
• Lens subluxation[50]
• Migraine headache[51]
• Cluster headache
• Suprachoroidal hemorrhage

Prognosis

The prognosis of AAC is significantly influenced by early detection and prompt treatment. A study involving 116 cases of ACAG found that the timing of presentation and the duration of the acute episode were crucial factors in determining these patients' outcomes. High IOP was found to have less impact on the long-term prognosis of this condition.[52]

Complications

If ACAG goes undetected and untreated in its early stages, it can result in temporary vision loss or blindness. The condition's progression typically involves a sequential loss of peripheral vision followed by a loss of central vision. However, in some cases, ACAG can develop into a more severe and challenging-to-treat form known as malignant glaucoma.

A significant increase in IOP characterizes malignant glaucoma despite a patent iridotomy. In this condition, the eye's anterior chamber becomes flat due to a fluid imbalance, leading to further elevation of IOP. Malignant glaucoma is also called aqueous misdirection syndrome or ciliary block glaucoma. This condition is challenging to treat and progressively leads to blindness.[53]

Deterrence and Patient Education

Patients with a history of acute angle-closure glaucoma should be advised to avoid dim lighting conditions. Dim light can cause pupils to dilate, further narrowing the iridocorneal angle.

Patients with hypermetropia are at an increased risk of developing angle-closure glaucoma. This is because hypermetropia is often associated with specific anatomical predispositions that can contribute to angle closure, such as a shallow anterior chamber depth or a more anterior lens position. LPI is a recommended preventative measure in individuals with AAC risk factors.[48]

Pearls and Other Issues

In patients with an AAC, an untreated opposite eye shares the same anatomic predisposing factors as the first eye. The untreated eye has a 40% to 80% chance of developing an AAC glaucoma within 5 to 10 years.[54] Therefore, it is recommended to perform LPI not only in the affected eye but also in the other eye to reduce the risk of such an attack.

The presence of gender and ethnicity as predisposing factors for AAC glaucoma suggests a genetic predisposition to the disease in specific populations. Recent large-scale studies have provided strong evidence linking several genes and genetic loci to primary open-angle glaucoma. However, evidence for acute angle-closure glaucoma is sparse. Only 1 study has identified a genetic locus on chromosome 11 that can contribute to the development of AAC glaucoma.

Research has been conducted to explore potential therapeutic targets for patients with early-onset glaucoma, focusing on molecular and cellular events triggered by mutations in genes myocilin (MYOC), optineurin (OPTN), and TANK-binding kinase 1 (TBK1).[55]

Enhancing Healthcare Team Outcomes

The optimal management of acute angle-closure glaucoma requires a collaborative approach involving an interprofessional team comprising an ophthalmologist, a family practitioner, an ophthalmology nurse, and a pharmacist. In initial emergency management, the administration of appropriate eye drops is crucial. However, it is essential to note that this is typically a temporary measure.

Following the emergency intervention, it is essential to schedule the patient for an iridectomy. Healthcare practitioners should be mindful that the contralateral eye is susceptible to AAC glaucoma. Thus, prophylactic surgery, such as laser peripheral iridotomy, is also recommended to reduce the risk in that eye.

Patients with acute angle-closure glaucoma generally have favorable outcomes if timely treatment is provided. However, it is crucial to emphasize that any delay in treatment can have serious consequences, including potential damage to the optic nerve and resulting vision loss. Swift intervention is essential to alleviate intraocular pressure and preserve visual function. Therefore, prompt recognition and appropriate management are paramount to optimize the prognosis for individuals with acute angle-closure glaucoma.