Primary Angle-Closure Glaucoma

Updated: Nov 19, 2021
  • Author: Clement Chee-yung Tham, MBBCh, MA, FRCS(Glasg); Chief Editor: Hampton Roy, Sr, MD  more...
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Overview

Practice Essentials

Overview

Background

Variable and sometimes conflicting terminology was used to describe different forms of angle-closure glaucoma before the advent of indentation gonioscopy and laser iridotomy, when the mechanisms of angle-closure glaucoma were poorly understood. [1, 2]

In the era of surgical iridectomy, an attack of acute angle-closure glaucoma (AACG) could arise in an eye that had developed peripheral anterior synechiae (PAS) as a result of gradual angle closure before the attack. Conversely, a prolonged acute attack or a series of subacute attacks could lead to progressive PAS formation. Patients undergoing surgical iridectomy were dilated routinely after surgery, and shallow anterior chambers were not uncommon. Patients undergoing surgical iridectomy for AACG who were dilated postoperatively and had shallow anterior chambers not infrequently formed PAS. [3, 4]  Prolonged apposition or repeated subacute attacks lead to gradual PAS formation. These usually begin in the superior angle, which is narrower than the inferior angle, as pinpoint synechiae, reaching to the midtrabecular meshwork and gradually expanding in width. [5]

Primary angle-closure suspect (PACS) was defined as nonvisibility of the filtering trabecular meshwork for 180° or more in the absence of PAS with normal intraocular pressure (IOP). Primary angle closure (PAC) can be further classified as synechial or appositional. Primary (appositional) angle closure refers to an eye with raised IOP (>21 mm Hg) associated with obstructed filtering trabecular meshwork of more than 180° in the absence of PAS, disc damage, or field changes. On the other hand, primary (synechial) angle closure (PAC) refers to an eye in which portions of the anterior chamber angle are closed permanently by PAS with more than 180° of iridotrabecular contact with or without raised IOP. The term primary angle-closure glaucoma (PACG) is used to denote PAC eyes with glaucomatous optic nerve damage or visual field loss. [6]

Pathophysiology

Combined mechanism glaucoma refers to situations in which both open-angle and angle-closure components are present.

The term mixed mechanism glaucoma often is used interchangeably with combined mechanism glaucoma, but it should not be, because it creates additional confusion. It is better to reserve this term to describe an eye with angle closure due to more than one contributory mechanism. 

Plateau iris refers to an anatomic configuration in which the iris root angulates forward and then centrally. Two subtypes have been differentiated. In the complete syndrome, which is rare, IOP rises when the angle closes with pupillary dilation. In the incomplete syndrome, IOP does not rise. 

Miotic-induced angle-closure glaucoma may result from prolonged miotic treatment in eyes with open-angle glaucoma and narrow angles.

Epidemiology

The global prevalence of PACG is 0.6%. The prevalence is highest in Asia (12.30 million), and risk factors include Asian race, female sex, and advancing age. [7]  

Mortality/Morbidity

If IOP is not controlled, glaucomatous optic neuropathy and visual field loss may progress.

Race

The prevalence of PACG is highest among Chinese (1.26% among those ≥40 years), 0.25% among Whites of European ancestry, and 0.16% among those of African and Middle Eastern ancestry, according to a review of worldwide statistics. [7]  

Creeping angle closure is uncommon in Whites, but it is much more prevalent in Asians, in whom it ranks high as a cause of blindness. Black patients with angle closure also tend to have this form.

Sex

Patients with PACG and plateau iris tend to be female.

Age

Those with PACG tend to be elderly and often have coexisting cataract or at least lens thickening. 

Patients with plateau iris tend to be in their fourth to sixth decade of age.

Prognosis 

The prognosis is favorable with control of the IOP. [8]

Factors associated with disease progression in PACG eyes include large IOP fluctuations [9]  and a thin central corneal thickness. [10]

Patient education

For excellent patient education resources, visit eMedicineHealth's Eye and Vision Center. Also, see eMedicineHealth's patient education articles Glaucoma OverviewGlaucoma FAQsGlaucoma Medications, and How to Instill Your Eyedrops.

Presentation

History 

Primary angle-closure glaucoma (PACG) usually is asymptomatic because of its slow onset, as opposed to acute angle-closure glaucoma (AACG), which presents with pain and nausea due to the rapid intraocular pressure (IOP) increase. However, patients with PACG may report transient eye pain, headache, and/or halo visualization.

Physical

Insertion of the iris at or anterior to the scleral spur is rare in young individuals, and, in many eyes with angle-closure glaucoma that have such an insertion, creeping angle closure is the underlying reason. The IOP in eyes with primary angle closure (PAC) may be normal or elevated. PACG eyes have greater IOP fluctuations than PAC or PACS eyes and higher baseline IOP, glaucoma medication requirements, previous trabeculectomy and current smoking status are associated with larger IOP fluctuations. [11]  IOP fluctuation was a significant and independent predictor for subsequent VF deterioration in eyes with PACD. [12]

Blotches of pigment on the meshwork, particularly in the superior angle, or deposits of black pigment in the angle of a lightly pigmented iris are highly suggestive of previous appositional closure. If the angle opens, this deposited line of pigment shows the extent of previous angle closure and sometimes can be a helpful diagnostic feature.

The anterior chamber is quiet and usually deeper than in eyes with AACG.

The pupil is normal.

The gradual elevation of IOP does not result in corneal endothelial decompensation, and corneal edema is rare. The IOP is usually less than 40 mm Hg and does not reach the levels found in AACG. Symptoms are absent until the pressure rises high enough to affect the cornea or until extensive visual field damage has occurred. Although iridotomy will eliminate the pupillary block, IOP often remains elevated, and further medical treatment or surgery is required.

Causes

Causes of PACG include PAS formation, plateau iris, combined mechanism glaucoma, mixed mechanism glaucoma, and miotic-induced glaucoma.

Workup

Imaging studies

In patients with glaucoma, analysis of serial retinal nerve fiber layer thickness (RNFL) maps generated with spectral-domain optical coherence tomography (OCT) can aid in the detection of RNFL progression. [13]  

Other tests

Goldmann applanation tonometry remains the gold standard for IOP assessment.

Static and dynamic (indentation) gonioscopy is used to evaluate and document the extent, the nature (appositional versus synechial), and the cause of the angle closure.

Slit-lamp biomicroscopy examination using noncontact lenses (eg, 90-D lens) or contact lenses (eg, central lens in Goldmann 3-mirror lens) may utilize green filter (red-free light) to aid in the identification of RNFL thinning; fundus photography can be used for documentation (stereoscopic or nonstereoscopic).

A GDx VCC nerve fiber analyzer, Heidelberg retinal tomography (HRT), and OCT can be used for quantitative assessment.

Assessments of the optic nerve head and retinal nerve fiber layer thickness 

Visual field assessment can include threshold testing by automated perimetry. S; special programs, such as SWAP, may help identify early visual field losses.

Further investigations to delineate the mechanism of angle closure can include ultrasound biomicroscopy examination and anterior segment OCT (AS-OCT).

Treatment

Medical care

It is important to recognize early stages of appositional angle closure in the absence of peripheral anterior synechiae (PAS) and to recognize deep, circumferential angle closure.

Laser iridotomy is indicated for primary angle closure (PAC) and primary angle-closure glaucoma (PACG). Laser iridotomy involves the creation of a hole in the peripheral iris by laser.

Miotic treatment may enhance the development of PACG in the absence of an iridotomy. When miotic-induced angle closure occurs, the approach to treatment should be determined by assessing the medications necessary to control the glaucoma.

Argon laser trabeculoplasty (ALT) has been reported to be both successful and unsuccessful after iridotomy in combined-mechanism glaucoma; however, overall, it has been found to be reasonably successful. [14, 15]  Selective laser trabeculoplasty (SLT) delivers laser energy to pigmented cells in the trabecular meshwork avoiding thermal damage to adjacent cells.

Surgical care

The two main challenges in the management of PACG are, firstly, to prevent progression of the angle closure and, secondly, to prevent progression of the glaucomatous optic neuropathy by controlling IOP. Various surgical procedures have different roles in meeting these challenges.

To prevent progression of the angle closure, all eyes with angle closure or very narrow drainage angles should undergo iridectomy or iridotomy to eliminate pupillary block. Laser iridotomy has largely succeeded surgical iridectomy, other than in exceptional circumstances. [16, 17]

Trabeculectomy is effective for PACG. [18, 19, 20, 21, 22]  Trabeculectomy has an overall success rate of 68% in controlling IOP. However, compared with primary open-angle glaucoma (POAG), any aqueous-draining procedure in an eye with a shallow anterior chamber and a chronic closed angle poses the risk of further shallowing the anterior chamber or precipitating malignant glaucoma. Trabeculectomy in PACG is associated with a higher risk of filtration failure, shallow anterior chamber, and malignant glaucoma/aqueous misdirection.

Lens position and thickness both play important roles in the etiology of angle-closure glaucoma.52 Lens extraction significantly increases anterior chamber depth and width of the drainage angle. Lens extraction has been actively studied and reported in recent years in the treatment of PACG. The lens may narrow the angle by pushing the peripheral iris anteriorly, and this effect will be more marked if the lens is cataractous. Both traditional extracapsular cataract extraction and phacoemulsification have been reported to lower IOP in PACG. Phacoemulsification alone has also been shown to normalize IOP in PACG.

Goniosynechialysis (GSL) is a surgical technique performed to strip the PAS from the trabecular surface in the angle and provide aqueous renewed access to the trabecular meshwork. [23, 24, 25]  In eyes with minimal PAS, trabeculectomy is preferred because trabecular function in these eyes is expected to be poor and a fistula procedure would be more appropriate. On the other hand, there may be spikes of raised IOP during and after the GSL procedure leading to loss of vision. GSL is more suitable for eyes with a minimal to moderate degree of neuronal damage.

Consultations

Consult a glaucoma specialist.

Complications

Cataract can occur with steroid and laser treatment.

Medication

The first step in the management of primary angle-closure glaucoma (PACG) is often a surgical procedure to open, as far as possible, those segments of the drainage angle that are appositionally closed or narrow. Options may include laser peripheral iridotomy, argon laser peripheral iridoplasty, and lens extraction, depending on the mechanism(s) of angle closure. Intraocular pressure (IOP) may, however, remain elevated after these procedures, which may be the result of extensive residual synechial angle closure. IOP-lowering medications are indicated if a safe IOP level cannot be reached after angle-opening procedures.80

In the past, timolol and pilocarpine were extensively used in PACG. Recent studies have demonstrated the superior IOP-lowering efficacy of prostaglandin analogue monotherapy over these conventional drugs, and even some combination therapies, in PACG. The IOP-lowering effect of prostaglandin analogues does not appear to be related to the degree of angle closure or to the extent of peripheral anterior synechiae (PAS). Once-daily prostaglandin analogue regimes are generally well tolerated by patients with PACG. Prostaglandin analogues have become an important member in the medical arsenal against PACG.81

Miotic agents

These agents directly stimulate cholinergic receptors in the eye, decreasing resistance to aqueous humor outflow.

Beta-adrenergic Blocker

Thought to decrease IOP by reducing aqueous formation; however, some studies observed increased outflow.

Prostaglandin, ophthalmic

Reduces IOP by increasing uveoscleral outflow.

Carbonic anhydrase inhibitor

Inhibits aqueous humor formation by inhibiting carbonic anhydrase 2 (CA-II).

Alpha2-adrenergic agonist agent, ophthalmic

Reduces aqueous humor production and increases uveoscleral outflow.

Brimonidine (Alphagan P)

Diuretic, Osmotic

These agents elevate glomerular filtrate osmolarity, resulting in decreased tubular reabsorption of water, thereby inducing diuresis.

Mannitol (Osmitrol)

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Background

In the past, variable and sometimes conflicting terminology has been used to describe different forms of angle-closure glaucoma. The problem arose from the fact that terminology was developed before the advent of indentation gonioscopy and laser iridotomy, when the mechanisms of angle-closure glaucoma were poorly understood. [1, 2]

In the era of surgical iridectomy, an attack of acute angle-closure glaucoma (AACG) could arise in an eye that had developed peripheral anterior synechiae (PAS) because of gradual angle closure before the attack. Conversely, a prolonged acute attack or a series of subacute attacks could lead to progressive PAS formation. Patients undergoing surgical iridectomy were dilated routinely after surgery, and shallow anterior chambers were not uncommon. Patients undergoing surgical iridectomy for AACG who were dilated postoperatively and had shallow anterior chambers not infrequently formed PAS. [3, 4] Prolonged apposition or repeated subacute attacks lead to gradual PAS formation. These usually begin in the superior angle, which is narrower than the inferior angle, as pinpoint synechiae, reaching to the midtrabecular meshwork and gradually expanding in width. [5]

Primary angle-closure suspect (PACS) was defined as nonvisibility of the filtering trabecular meshwork for 180° or more in the absence of PAS with normal intraocular pressure (IOP). Primary angle closure (PAC) can be further classified as synechial or appositional. Primary (appositional) angle closure refers to an eye with raised IOP (>21 mm Hg) associated with obstructed filtering trabecular meshwork of more than 180° in the absence of PAS, disc damage, or field changes. On the other hand, primary (synechial) angle closure (PAC) refers to an eye in which portions of the anterior chamber angle are closed permanently by PAS with more than 180° of iridotrabecular contact with or without raised IOP. The term primary angle-closure glaucoma (PACG) is used to denote PAC eyes with glaucomatous optic nerve damage or visual field loss. [6]

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Pathophysiology

Eyes with progressive PAS formation eventually may develop AACG when pupillary block results in closure of the remaining portions of the angle unaffected by PAS. However, many patients develop gradual angle closure, elevated IOP, and glaucomatous damage in the absence of symptoms. The presentation is similar to that of PACG, with progression of glaucomatous cupping and visual field loss. [26]

PAS also may form during an acute attack, remaining after iridotomy has opened the unaffected portions of the angle. These PAS are usually high and broad. When first observed at this stage, it is impossible to determine whether the PAS formed before or during the attack, or at both times.

In eyes with darker irides, a second mechanism of progressive angle closure is more common. The closure is circumferential and begins in the deepest portion of the angle. Closure occurs more evenly in all quadrants, so that the angle progressively becomes shallower. The appearance over time is of a progressively more anterior iris insertion. Lowe has termed this creeping angle closure. [27] The PAS gradually creep up the ciliary face to the scleral spur and then to the trabecular meshwork.

Combined mechanism glaucoma

Combined mechanism glaucoma refers to situations in which both open-angle and angle-closure components are present. Most commonly, angle-closure glaucoma is treated successfully with iridotomy, eliminating all appositional closure, and IOP still remains elevated, with or without the presence of PAS of any extent.

Conversely, an eye with open-angle glaucoma may later develop angle closure, either because of the natural development of pupillary block or because of exacerbation by miotic therapy.

Exfoliation syndrome commonly predisposes to combined mechanism glaucoma. [28] In this case, open-angle glaucoma can develop independently years after iridotomy for angle closure, with progressive blockage of the trabecular network. In all of these cases, the residual open-angle component is treated as open-angle glaucoma.

Mixed mechanism glaucoma

This term often is used interchangeably with combined mechanism glaucoma, but should not be, because it creates additional confusion. It is better to reserve this term to describe an eye with angle closure due to more than one contributory mechanism. When pupillary block is eliminated by iridotomy and the angle opens to a greater degree than before the iridotomy, an appositional closure remains on the basis of plateau iris, phacomorphic glaucoma, or malignant glaucoma, a mixed mechanism may be present.

Plateau iris

Plateau iris refers to an anatomic configuration in which the iris root angulates forward and then centrally. [29, 30, 31] The iris root often is short and inserted anteriorly on the ciliary face, so that the angle is shallow and narrow, with a sharp drop-off of the peripheral iris at the inner aspect of the angle. The iris surface is relatively flat and the anterior chamber is not unusually shallow.

When appositional angle closure develops in the presence of a patent iridotomy or iridectomy, either spontaneously or after pupillary dilation, in an eye with this anatomic configuration, plateau iris syndrome is present. [32] Some patients may develop AACG. The risk for postoperative pupillary dilation after iridectomy or iridotomy frequently is realized.

Until recently, plateau iris syndrome was considered rare. Two subtypes have been differentiated. In the complete syndrome, which is rare, IOP rises when the angle closes with pupillary dilation. In the incomplete syndrome, IOP does not rise. The differentiating factor is the height of the plateau with respect to the angle structures. If the angle closes to the upper meshwork or Schwalbe line, IOP rises because aqueous outflow is blocked completely, whereas, if the angle closes partially, leaving the upper portion of the filtering meshwork open, aqueous humor still exit the eye. This condition is far more common, and its detection is important; these patients can develop PAS up to years after a successful iridotomy produces what appears as a well-positioned angle.

Plateau iris occurs because large and/or anteriorly positioned ciliary processes hold the peripheral iris up against the trabecular meshwork. [33, 34] Iris cysts also may cause a situation equivalent to plateau iris. When dynamic gonioscopy is performed in such an eye, the ciliary processes prevent posterior movement of the peripheral iris. As a result, a sinuous configuration results (ie, double hump sign), in which the iris follows the curvature of the lens, reaches its deepest point at the lens equator, and then rises again over the ciliary processes before dropping peripherally. Much more force is needed during gonioscopy to open the angle than in pupillary block because the ciliary processes must be displaced, and the angle does not open as widely. In a morphometric study of the ciliary sulcus, Orgul et al proposed that the displacement of the pars plicata from the peripheral iris to the iris root during embryogenesis may be incomplete in eyes of shorter axial length. [35]

Patients with plateau iris tend to be female, younger (30s-50s), and less hyperopic than those with relative pupillary block. They often have a family history of angle-closure glaucoma. Except in the rare younger patients (20s-30s), some element of pupillary block also is present. If plateau iris was not diagnosed before iridotomy and IOP is elevated postlaser, careful gonioscopy should be performed. If the angle is open, secondary damage to the trabecular meshwork or pigment liberation with dilation are the most likely causes. If the angle is closed, the differential diagnosis, besides plateau iris, should include malignant glaucoma, in which the anterior chamber is extremely shallow; PAS, which can be ruled out by dynamic gonioscopy; or incomplete iridectomy.

Miotic-induced angle-closure glaucoma

Prolonged miotic treatment in eyes with open-angle glaucoma and narrow angles may lead to pupillary block and angle-closure glaucoma. [36] PACG has developed after several years of miotic therapy in eyes that initially had wide-open angles. In some eyes, zonular relaxation occurs more readily than in other eyes, so that anterior lens movement and an increase in axial lens thickness may facilitate pupillary block and angle closure.

In other eyes, little change in the lens occurs, but progressively increasing pressure in the posterior chamber gradually pushes the peripheral iris against the trabecular meshwork. It is believed that eyes with exfoliation syndrome are particularly prone to develop miotic-induced angle closure. In these eyes, the iris is thicker and stiffer than normal because of deposition of exfoliation material within the stroma. In addition, zonular weakness allows the lens to move forward, leading to pupillary block.

Less commonly, miotic therapy can have a pronounced effect on lens position and trigger malignant glaucoma. [37, 38, 39] Unequal anterior chamber depths, a progressive increase in myopia, or progressive shallowing of the anterior chamber are clues to the correct diagnosis.

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Epidemiology

Frequency

Worldwide

The worldwide prevalence of PACG was 0.6% in a meta-analysis of 20 years of data from 144,354 participants. The risk for PACG increases with age; the disease is estimated to affect approximately 17.14 million individuals older than 40 years, 20.73 million in 2030, 23.73 million in 2040, and 26.26 million in 2050.

The prevalence is highest in Asia (12.30 million), and risk factors include Asian race, female sex, and advancing age. [7]  

Europe and  United States

In European-derived populations, an estimated 130,000 people in the United Kingdom have PACG, compared with 1.60 million people in Europe, and 581,000 people in the United States. Accounting for aging population structures, cases are predicted to increase by 19% in the United Kingdom, 9% in Europe, and 18% in the United States from 2012 to 2022. [40]

Asia

The overall pooled prevalence of PACG among adult Asians was 0.75%. Ethnicity-specific pooled prevalence estimates were 0.97% in the Middle East group, 0.66% in the Southeast Asia group, 0.46% in the India group, 1.10% in the China group, and 1.19% in the Japan group. [41]

Mortality/Morbidity

If IOP is not controlled, glaucomatous optic neuropathy and visual field loss may progress.

Race

The prevalence of PACG appears to be highest among Chinese (1.26% among those ≥40 years), according to a review of worldwide statistics. The prevalence of PACG in whites of European ancestry is around 0.25%. The prevalence of PACG appears to be lowest among Africans and people of Middle Eastern ancestry (0.16%). [42]

Among the subtypes of angle closure, creeping angle closure is uncommon in whites, but it is much more prevalent in Asians, in whom it ranks high as a cause of blindness. Black patients with angle closure also tend to have this form.

Sex

Patients with PACG and plateau iris tend to be female.

Age

Patients with PACG tend to be elderly, often with coexisting cataract or at least lens thickening.

Patients with plateau iris tend to be in their fourth to sixth decade of age.

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Prognosis

The prognosis is favorable with control of the IOP. [8]

Factors associated with disease progression in PACG eyes include large IOP fluctuations [9]  and a thin central corneal thickness. [10]

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Patient Education

For excellent patient education resources, visit eMedicineHealth's Eye and Vision Center. Also, see eMedicineHealth's patient education articles Glaucoma OverviewGlaucoma FAQsGlaucoma Medications, and How to Instill Your Eyedrops.

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