INTRODUCTION — Glaucoma is a group of eye diseases traditionally characterized by increased intraocular pressure (IOP). However, glaucoma is more accurately defined as an optic neuropathy and may not always be associated with increased IOP. Angle-closure glaucoma is characterized by narrowing or closure of the anterior chamber angle.
This topic will discuss types of angle-closure glaucoma, diagnosis, and treatment. A discussion of open-angle glaucoma is presented separately. (See "Open-angle glaucoma: Epidemiology, clinical presentation, and diagnosis".)
DEFINITION AND TYPES
Glaucoma is defined as an optic neuropathy involving a characteristic atrophy of the optic nerve head, often accompanied with typical visual field defects [1]. Examination of a glaucomatous optic nerve reveals "cupping," which looks like a "hollowing out" of the optic nerve head (picture 1). Glaucoma is often, though not always, associated with increased intraocular pressure (IOP).
Angle-closure glaucoma is a form of glaucoma characterized by narrowing or closure of the anterior chamber angle [2]. The normal anterior chamber angle provides drainage for the aqueous humor, the fluid that fills the eyeball. When this drainage pathway is narrowed or closed, inadequate drainage of the aqueous humor leads to increased IOP and damage to the optic nerve (figure 1A-B). Normal IOP is 8 to 21 mmHg. In acute episodes of closed-angle glaucoma, pressures are often 30 mmHg or higher [3].
Angle-closure glaucoma is divided into two main groups:
●Primary angle-closure – Patients are anatomically predisposed to this type of glaucoma; there is no other identifiable cause.
●Secondary angle-closure – A primary process is responsible for narrowing or closure of the anterior chamber angle, which is secondary to that process. Examples of primary causes are a fibrovascular membrane that grows over the angle to pull it closed, as in neovascular glaucoma, or a mass or hemorrhage in the posterior segment of the eyeball that pushes the angle closed [4].
EPIDEMIOLOGY AND RISK FACTORS — After cataracts, glaucoma is the second leading cause of blindness in the world [5]. Angle-closure glaucoma is more prevalent in Asian populations, whereas open-angle glaucoma is more common in European or African populations [6]. In 2016, there were an estimated 20 million people with angle-closure glaucoma worldwide, with 75 percent in Asia [6,7]. This is projected to increase to 34 million worldwide in 2040 [7].
Risk factors that predispose to primary angle-closure glaucoma include [4,8-10]:
●Family history of angle-closure glaucoma
●Age >60 years
●Female
●Hyperopia (farsightedness)
●Certain medications (table 1)
●Pseudoexfoliation (a condition in which abnormal flaky deposits on eye surfaces can weaken the zonules that support the lens and cause it to shift forward)
●Race
The highest rates of angle-closure glaucoma are reported in Inuit and Asian populations [11-15], and lower rates are reported in African and European populations [2,13,16,17].
PATHOGENESIS
Primary angle-closure — Aqueous humor is produced by the ciliary body, flows through the pupil, reaches the anterior chamber angle, and exits the eye. The balance between fluid production and drainage determines the intraocular pressure.
In primary angle-closure, the lens is located too far forward anatomically and rests against the iris. This results in pupillary block, a condition in which aqueous humor can no longer flow normally through the pupil. Pressure builds up behind the iris, relative to the anterior chamber, causing the peripheral iris to bow forward and cover all or part of the anterior chamber angle.
Prolonged or repeated contact between the iris and the angle can lead to scarring and functional damage to the trabecular meshwork, the tissue in the angle that acts as a sieve through which the aqueous humor drains (figure 1A-B). Once the optic nerve shows damage from the high intraocular pressure (IOP), the disease is called primary angle-closure glaucoma.
If the entire angle is blocked suddenly, as occurs in complete pupillary block, the IOP rises rapidly, and acute symptoms can occur. These attacks of acute angle-closure glaucoma may resolve spontaneously and recur repeatedly if not treated. Without treatment, vision loss and even blindness can occur quickly during the attack (over hours to days), so acute angle-closure glaucoma is a true ophthalmic emergency.
Patients with anatomically narrow angles are at risk for future angle-closure [2]. The width of their anterior chamber angles is smaller than in normal eyes, and their peripheral iris is closer to their anterior chamber angle than normal.
Chronic angle-closure — Chronic angle-closure results if only a portion of the angle is blocked at a time and develops scarring. Over time, the angle may become progressively more closed. In this variation of the disease, the IOP may be normal or only slightly elevated, in which case symptoms will likely not occur. Patients with chronic angle-closure glaucoma may have more damage to the optic nerve and peripheral vision when the diagnosis is established, compared with patients with acute angle-closure glaucoma because of the absence of symptoms and thus delayed diagnosis.
Secondary angle-closure — Secondary angle-closure results when the anterior chamber angle becomes occluded as the result of conditions that push the iris or ciliary body forward ("pushing" conditions) or deform the iris so that it is retracted into the angle ("pulling" conditions).
Pushing conditions include:
●Fibrosis of the pupil to the anterior surface of the lens.
●Choroidal swelling or hemorrhage (due to types of ophthalmic surgery, retinal laser treatment, posterior scleritis, or drug reactions). Topiramate is the most common of the sulfa-based medications to cause this rare, idiosyncratic reaction.
●Plateau iris syndrome (a developmental anomaly).
●A large or anteriorly displaced lens.
●Aqueous misdirection (in which aqueous humor fills the vitreous cavity instead of flowing through the pupil, most commonly as a result of ophthalmic surgery).
●Choroidal hemorrhage or effusion.
●A space-occupying lesion in the posterior segment of the eyeball (such as a tumor or a gas bubble placed during retinal surgery).
●Developmental syndromes causing fibrosis in the posterior segment of the eyeball
Pulling conditions include:
●Inflammation or blood in the angle itself that fibroses and contracts
●Neovascularization of the iris with a resulting fibrovascular membrane (most commonly seen in poorly controlled diabetes mellitus or ophthalmic artery insufficiency)
●Abnormal corneal endothelial cell proliferation
●Prolonged shallowing of the anterior chamber resulting in iris-angle contact due to trauma or surgery
●Epithelial cell or fibroblast invasion of the angle [4]
CLINICAL PRESENTATION — The rapidity and degree of the intraocular pressure (IOP) elevation from angle-closure determines whether symptoms occur. If the IOP rises quickly, as is typical of acute primary angle-closure glaucoma, patients may experience some or all of the following symptoms:
●Decreased vision
●Halos around lights
●Headache
●Severe eye pain
●Nausea and vomiting
If the rise in IOP is slower and does not reach very high levels, the patient may be symptom-free. This occurs in chronic angle-closure glaucoma. The patient may not notice damage to the peripheral vision, which generally precedes decrease in central vision.
Signs that suggest a rapid rise in IOP include (picture 2):
●Conjunctival redness
●Corneal edema or cloudiness
●A shallow anterior chamber
●A mid-dilated pupil (4 to 6 mm) that reacts poorly to light
Symptoms and signs of acute glaucoma often occur in the evening, when lower light levels cause mydriasis and folds of the peripheral iris block the narrow angle [18].
DIAGNOSIS — Patients with the above symptoms or signs should undergo emergent examination of both eyes by an ophthalmologist, including:
●Visual acuity
●Evaluation of the pupils
●Intraocular pressure (IOP)
●Slit-lamp examination of the anterior segments
●Visual field testing (either by confrontation [finger testing] or by formal methods, depending on the acuity of the clinical situation)
●Gonioscopy (see 'Gonioscopy' below)
●Undilated fundus examination
Pupillary dilation should be deferred in untreated cases of suspected angle-closure glaucoma, as this may exacerbate the condition.
On eye examination, patients who have experienced prior acute attacks of high IOP may demonstrate iris irregularity due to ischemia during the attack, glaucomflecken (scattered opacities) in the anterior lens, normal or increased IOP, and cupping of the optic disc if narrow-angle glaucoma is present.
Although angle-closure often presents in just one eye, it is important to examine the other eye as well. The angle of the fellow eye may be similarly narrow, putting this eye at risk for future angle-closure attacks unless prophylactic treatment is instituted.
Diagnostic tests
Gonioscopy — Gonioscopy is the gold-standard method of diagnosing angle-closure glaucoma. This technique involves using a special lens for the slit lamp, which allows the ophthalmologist to visualize the angle (picture 3). Indentation gonioscopy refers to putting posterior pressure on the eyeball with the lens used for gonioscopy. The pressure will widen the angle if it is not scarred completely closed; the extent to which scarring has produced angle-closure helps to determine its severity and chronicity. Gonioscopy requires expertise and experience to perform reliably.
Slit lamp grading of anterior chamber depth — In this technique, the width of the angle is estimated by shining a light beam from the slit lamp on the peripheral anterior chamber. It is not as reliable as gonioscopy for diagnosing angle-closure glaucoma.
Ultrasound biomicroscopy — Specialized ultrasound of the anterior chamber can show angle-closure and help to define the mechanism. The ultrasound biomicroscope instrument is costly and thus not widely available. This technique also requires specialized interpretation of the results.
Anterior segment optical coherence tomography — High-definition anterior segment optical coherence tomography is being used as a modality to image the drainage angle and detect eyes at risk for angle-closure [19]. Findings suggest that eyes prone to developing angle-closure do not merely differ anatomically from normal eyes but may also respond differently to light stimuli [20]. As an example, when dilated to the same degree, the iris of an angle-closure eye tends to be thicker than the iris of a normal eye [21].
Provocative tests — Provocative tests most often do not provide additional information beyond the clinical examination and are not widely used because they are time-consuming, not definitive, and potentially risky. In the dark room provocation test, a patient rests (awake) in a dark room for 30 minutes with his or her head in the prone position to encourage pupillary dilation and forward displacement of the lens. Angle-closure is suggested if the IOP rises significantly or if the angle appears more closed on gonioscopy. Clinical applicability is unknown.
In pharmacologic tests, the pupil is dilated with phenylephrine or parasympatholytic mydriatic eye drops and pilocarpine is instilled in an attempt to provoke an attack of angle-closure glaucoma. This procedure involves risk and a negative result does not absolutely rule out angle-closure [4]. Both eyes should not be tested simultaneously. We do not recommend this test.
DIFFERENTIAL DIAGNOSIS
Other causes of a red eye may mimic acute primary angle-closure glaucoma. These include iritis, traumatic hyphema, conjunctivitis, episcleritis, subconjunctival hemorrhage, corneal abrasion, and infectious keratitis. (See "The red eye: Evaluation and management".)
The primary care clinician may be able to distinguish acute primary closure from these conditions by the presence of severe eye pain, headache, nausea and vomiting, a mid-dilated pupil, and possibly decreased vision. However, not every patient with acute angle-closure glaucoma will demonstrate all of these symptoms and signs.
Secondary angle-closure is best differentiated from primary angle-closure by an ophthalmologist (see 'Secondary angle-closure' above). The management of these disorders differs from treatment of primary angle-closure.
MANAGEMENT — Management of angle-closure glaucoma involves medical control of elevated intraocular pressure (IOP) followed by reversal of angle-closure by laser peripheral iridotomy or other surgical treatments. The patient should be referred urgently to an ophthalmologist for care (table 2).
Acute primary angle-closure glaucoma
Medical therapy — There are no available trials comparing medical options for treatment of acute angle-closure glaucoma, and treatment recommendations are based on clinical experience [22]. When an ophthalmologist is available for consultation within one hour of patient presentation, patients with signs or symptoms suggesting possible acute angle-closure should be referred for emergency assessment and treatment.
When there is likely to be an hour or more delay before a patient can be seen by an ophthalmologist, and the suspicion of an acute attack is high, empiric treatment should be initiated. If the vision is normal, but other symptoms and signs suggest an acute angle-closure attack, empiric treatment should only be given if the intraocular pressure is significantly elevated (eg, >40 mmHg). For an acute primary angle-closure attack, initial management involves prompt administration of pressure-lowering eye drops. A possible regimen would be one drop each, one minute apart, of [22]:
●0.5% timolol maleate;
●1% apraclonidine; and
●2% pilocarpine, especially immediately prior to laser peripheral iridotomy [2]
We also suggest giving the patient 500 mg of oral or intravenous (IV) acetazolamide. The eye pressure should be checked 30 to 60 minutes after giving pressure-lowering drops and acetazolamide. If the eye pressure is still significantly elevated, the same drops could be given again, but the patient should also be examined immediately by an ophthalmologist. Systemic medications other than acetazolamide (such as IV mannitol) should be administered under the guidance of an ophthalmologist, since angle-closure should be confirmed before they are given.
If medical treatment is successful in reducing IOP, as is most often the case, corneal edema and eye pain will typically lessen or resolve. In refractory cases, the ophthalmologist may consider performing an anterior chamber paracentesis to remove some aqueous humor and immediately lower the eye pressure temporarily, which may help to break the attack. Once the attack is broken, the treatment of choice is a peripheral iridotomy. If laser peripheral iridotomy fails to remain patent, or the cornea is too cloudy to visualize the iris, surgical peripheral iridectomy may be necessary.
Laser peripheral iridotomy — This procedure creates a tiny hole in the peripheral iris through which aqueous humor can flow and reach the angle [23]. Once the iridotomy is patent, pupillary block is bypassed. A peripheral iridotomy is usually created with a laser.
The IOP is rechecked 30 to 120 minutes after the iridotomy is performed, and mild steroid drops are given for several days. Repeat gonioscopy is then performed to determine if the angle is wider. The pupil is dilated to ensure that the IOP does not rise significantly and to better assess any glaucoma damage to the optic nerve.
Possible complications of laser peripheral iridotomy include:
●Increased IOP
●Inflammation
●Laser burns to the cornea, lens, or retina
●A ghost image in the vision
●Increased rate of cataract formation [24,25]
●Need for repeat treatment if the hole were to shrink or close spontaneously
The fellow eye should be examined. If a narrow angle is found, prophylactic laser peripheral iridotomy should be performed to prevent future attacks of angle-closure glaucoma [24]. Untreated, approximately 50 percent of fellow eyes in acute angle-closure glaucoma patients will have another attack within five years [24,26].
Surgical peripheral iridectomy — In this procedure, the ophthalmologist makes an incision into the anterior chamber and surgically excises a small amount of iris tissue to create a passage for aqueous humor to reach the angle.
Other surgery — In a few cases of angle-closure glaucoma, goniosynechialysis may be performed in the operating room at some point after a peripheral iridotomy is in place. In goniosynechialysis, adhesions that result in scarring of the angle are mechanically lysed in an attempt to restore some drainage function. Results tend to be better if the scarring has been present for less than one year [27].
Cataract surgery (phacoemulsification) with an intraocular lens implant may resolve the issue of acute or chronic primary angle-closure glaucoma in some patients by removing the lens that may be crowding the angle [24,28-30]. A randomized trial of 62 Chinese patients with cataracts who had been medically treated for acute primary angle-closure glaucoma found that early phacoemulsification was more effective than laser peripheral iridotomy in preventing recurrence of IOP rise [31]. In a 2017 meta-analysis, patients with angle-closure glaucoma experienced a 6.4 mmHg (95% CI, -9.4 to -3.4 mmHg) lowering of IOP after cataract surgery at 12 months’ or longer follow-up [32]. A multicenter study randomizing angle-closure patients to either clear lens extraction (ie, lens removal without significant cataract) or laser peripheral iridotomy found that clear lens extraction was more efficacious, with IOP 1.18 mmHg lower than after iridotomy (95% CI -1.99 to -0.38), as well as more cost-effective [7].
Chronic angle-closure glaucoma — Laser peripheral iridotomy is the first step in treatment of patients with chronic angle-closure glaucoma, to relieve any pupillary block component. The IOP may remain elevated, however, if scarring has already damaged the drainage angle. In this case, the remaining glaucoma is treated medically and surgically much as in open-angle glaucoma. (See "Open-angle glaucoma: Epidemiology, clinical presentation, and diagnosis".)
Secondary angle-closure glaucoma — Secondary angle-closure glaucoma is managed by treating the primary cause if possible. Controlling the IOP medically and surgically afterwards is the next step, much as in open-angle glaucoma. (See "Open-angle glaucoma: Epidemiology, clinical presentation, and diagnosis".)
MEDICATIONS WITH GLAUCOMA WARNINGS — There are many medications that carry warnings or contraindications regarding use in patients with glaucoma. These warnings and contraindications are relevant regardless of whether or not the patient is taking glaucoma medications; they are not drug-drug interactions.
These warnings can pose difficulties for clinicians, as potential adverse outcomes vary according to the type of glaucoma (open versus narrow-angle) and the type of laser treatment (iridotomy versus trabeculoplasty). Iridotomy may protect against certain medication effects, but its protective effect varies among patients and over time and requires ophthalmological confirmation. (See "Open-angle glaucoma: Epidemiology, clinical presentation, and diagnosis".)
These potential adverse effects are discussed separately. (See "Open-angle glaucoma: Treatment", section on 'Use of medications with glaucoma warnings'.)
PATIENT INSTRUCTIONS — Patients who are known to have narrow angles but who have not yet undergone laser peripheral iridotomy should avoid medicines that induce pupillary dilation and might provoke an angle-closure attack. Such medicines include over-the-counter decongestants, motion sickness medications, adrenergic agents, antipsychotics, antidepressants, and anticholinergic agents (table 1) [2]. Once laser peripheral iridotomy has been performed, these medications are no longer contraindicated.
People with a family history of primary angle-closure glaucoma should undergo regular screening eye examinations for this condition, particularly as they reach middle age. The examining ophthalmologist should perform gonioscopy to assess for narrow angles, and evidence of prior angle-closure glaucoma; laser peripheral iridotomy should be performed if these are found.
PROGNOSIS — The outcomes of patients with angle-closure glaucoma depend on how early the disease is detected. Because glaucoma damage to the optic nerve is generally not reversible and can occur within a matter of hours in the case of an acute angle-closure attack, it is important that an ophthalmologist see these patients urgently to provide prompt diagnosis and treatment.
The fellow eye also must be evaluated as prophylactic treatment with laser peripheral iridotomy can prevent future angle-closure. The outcome for patients with secondary angle-closure depends on its cause.
INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)
●Basics topic (see "Patient education: Angle-closure glaucoma (The Basics)" and "Patient education: Anesthesia for elective eye surgery (The Basics)")
SUMMARY AND RECOMMENDATIONS
●Definitions – Glaucoma involves a characteristic atrophy of the optic nerve head ("cupping"), often with peripheral vision defects. Angle-closure glaucoma is characterized by narrowing or closure of the anterior chamber angle, leading to increased intraocular pressure (IOP) and damage to the optic nerve. (See 'Definition and types' above.)
●Risk factors – Several risk factors that predispose to primary angle-closure glaucoma have been identified, including certain medications (table 1).
●Primary-angle closure – In primary angle-closure glaucoma, drainage of aqueous humor through the anterior angle is blocked by anatomic narrowing of the angle.
•Acute angle-closure glaucoma – Acute blockage is an ophthalmic emergency, since vision loss and blindness may occur quickly. (See 'Primary angle-closure' above.)
•Chronic angle-closure – Patients with chronic angle-closure glaucoma may not develop increased IOP and symptoms, and diagnosis may be delayed resulting in more vision loss than patients with acute angle-closure glaucoma. (See 'Chronic angle-closure' above.)
●Secondary angle-closure – Secondary angle-closure is caused by a variety of processes that either push or pull the anterior chamber angle closed. These may include fibrosis and scarring, drug reactions, neovascularization, or mass. (See 'Secondary angle-closure' above.)
●Clinical presentation
•Symptoms – Patients with acute angle-closure glaucoma present with vision loss, headache, severe eye pain, light halos, nausea, and vomiting.
•Examination findings – Ocular exam reveals a red eye, corneal cloudiness or edema, a shallow anterior chamber, and poorly reactive mid-dilated pupil. Urgent referral for ophthalmology consultation is necessary in this setting. (See 'Clinical presentation' above.)
●Diagnosis – Diagnosis of angle-closure glaucoma is established by gonioscopy. Provocative tests are not recommended. The fellow eye should be examined as well as the affected eye. (See 'Diagnostic tests' above.)
●Management of acute angle-closure – Patients with symptoms and signs suggesting an acute attack of angle-closure glaucoma require emergency care by an ophthalmologist (table 2). We recommend emergency use of topical ophthalmic medications to reduce IOP (Grade 1C). These drugs may include a beta-blocker, an alpha agonist, and an agent to produce miosis. We also suggest systemic medication to decrease IOP, which may include oral or intravenous (IV) acetazolamide or IV mannitol (Grade 2C). Once the acute attack is controlled, definitive treatment for angle-closure glaucoma is a laser peripheral iridotomy, to provide a small drainage hole through the iris, or cataract surgery. (See 'Acute primary angle-closure glaucoma' above.)
●Patient instructions – Patients with narrow anterior chamber angles who are awaiting surgery should be advised to avoid decongestants and anticholinergic medications, which may precipitate an attack. (See 'Patient instructions' above.)
