Angle-closure glaucoma

Angle-closure glaucoma, also called closed-angle glaucoma or narrow-angle glaucoma, is where the drain of your eye is partially or fully obstructed or “closed” by the bulging iris ¹, ², ³, ⁴, ⁵, ⁶, ⁷, ⁸, ⁹, ¹⁰, ¹¹. The bulging iris partially or completely blocks the drainage angle. You can think of it like a piece of paper sliding over a sink drain. As a result, the fluid (aqueous humor) cannot exit the eye and eye pressure or intraocular pressure (IOP) increases. The angle also called the drainage angle is the space between the clear part of your eye (cornea) and the colored part (iris), close to their meeting point near the white eye wall (sclera). The angle or drainage angle contains the trabecular meshwork (TM), which is the main structure that drains fluid out of your eye. The angle can be viewed by eye doctors with a simple office test called gonioscopy. In angle-closure glaucoma or closed angle glaucoma, the angle is closed in many or most areas, causing increased eye pressure (raised intraocular pressure [IOP]), which leads to optic nerve damage, and possible vision loss. When the aqueous humor outflow through the trabecular meshwork becomes suddenly blocked by the iris due to a narrow angle, this sudden increase in eye pressure (IOP) is called an acute attack of angle closure. The abrupt blockage is an eye emergency because it can acutely damage the optic nerve and result in blindness ¹², ¹³, ¹⁴, ³. This blockage can also occur gradually called chronic closed angle glaucoma, such as from the deposition of infiltrates or neovascularization in the anterior chamber ⁴. There is also precursor form of the angle-closure glaucoma called ‘angle closure suspect’ in which the angle is closed but the eye pressure is not high and the optic nerve is not affected yet.

Angle-closure glaucoma is a uncommon type of glaucoma and usually affects one eye at a time. Glaucoma is an umbrella term for a group of serious eye conditions that is caused by increased pressure inside your eye (raised intraocular pressure [IOP]) that damages your eye’s optic nerve (cranial nerve number 2 [CN II]), potentially leading to irreversible vision loss and blindness, and early detection and treatment are essential for preserving your eyesight ¹⁵, ¹⁶, ¹⁷, ¹⁸, ¹⁹.

There are 2 main types of closed-angle glaucoma:

• Acute closed-angle glaucoma is a medical emergency. No fluid can drain out of your eye, so eye pressure increases suddenly. This causes eye pain, blurry vision, and other symptoms. Without prompt treatment, acute angle-closure glaucoma can cause blindness in a few days ³.
  • Symptoms of an acute angle-closure glaucoma attack:
    • Your vision is suddenly blurry
    • You have severe eye pain
    • You have a headache
    • You feel sick to your stomach (nausea)
    • You throw up (vomit)
    • You see rainbow-colored rings or halos around lights
  • Signs of acute angle closure glaucoma (findings of acute angle closure glaucoma are seen in an examination by an eye doctor):
    • Cloudy cornea
    • Red eyes
    • Forward bowing iris (narrow drainage angle)
    • Mid-dilation of the pupil
    • High intraocular pressure (several times higher than normal pressure)
• Chronic closed-angle glaucoma develops slowly over time. You may not have any symptoms at first. Or you may have symptoms such as eye discomfort, blurry vision, redness, or headaches. The symptoms often get better with sleep. Without treatment, vision loss develops slowly ⁴.

There are also different forms of angle-closure glaucoma labeled according to the underlying cause:

• Primary angle-closure glaucoma: In primary angle closure glaucoma the mechanism causing the glaucoma is primarily pupillary block (iridotrabecular contact is present in three or more quadrants of the drainage angle), being either functional or absolute, resulting in elevated intraocular pressure (IOP) that causes optic nerve damage and visual field loss. The American Academy of Ophthalmology guidelines classify primary angle closure glaucoma based on specific criteria, including the presence of a narrow angle of more than 180° of iridotrabecular contact (ITC), presence of peripheral anterior synechiae (PAS), elevated intraocular pressure (IOP), and signs of optic nerve damage ²⁰. Doctors don’t clearly understand why primary angle closure glaucoma happens.
  
  • Acute angle-closure glaucoma comes on quickly and is a medical emergency because permanent vision damage can happen very quickly. Symptoms include severe eye pain, blurred vision, halos, nausea, vomiting and red eye.
  • Intermittent angle-closure glaucoma refers to cases where the drainage system changes from open to closed. You may or may not have symptoms.
  • Chronic angle-closure glaucoma may not cause symptoms at the beginning. But gradually, symptoms develop over time. Later, it might result in an episode of acute angle-closure glaucoma or a gradual increase of pressure with possible damage to your optic nerve.
  • Primary angle closure suspect refers to an eye with a narrow angle between the iris and the trabecular meshwork (TM), but without signs of elevated intraocular pressure (IOP) or other damage associated with angle-closure glaucoma.
• Secondary angle-closure glaucoma: Secondary angle-closure glaucoma happens along with another eye or health condition you have. These include:
  • Poorly managed diabetes, which can cause a condition called proliferative diabetes-related retinopathy.
  • Poorly managed blood pressure or other vascular diseases that can lead to conditions like ischemic central retinal vein occlusion.
  • Uveitis a form of eye inflammation that affects the middle layer of tissue in the eye wall called the uvea. Uveitis warning signs often come on suddenly and get worse quickly. They include eye redness, pain and blurred vision.
  • Membranes and scars from injury or inflammation.
• Both primary and secondary angle closure glaucoma can result in dramatic acute angle closure attacks and chronic asymptomatic angle closure disease leading to glaucoma.

Angle-closure glaucoma happen to about 1 in 1,000 people. It’s most likely to happen after the age of 40. One estimate is that 17.14 million people throughout the world who are over 40 have primary angle-closure glaucoma, with a majority (12.3 million people) in Asia. People living in Asia are estimated to represent more than 75% of acute and chronic angle-closure glaucoma cases worldwide ²¹, ¹⁵, ⁴.

Acute angle-closure glaucoma is an eye emergency that typically presents with sudden blurring of vision, unilateral painful red eye, headache (often unilateral), and nausea, and vomiting ²², ¹², ¹³. The patient’s history may identify a precipitating condition, such as activity in low light that results in marked pupillary dilation or the recent use of common medications causing pupillary dilation ¹. There may also be a history of similar episodes of haloes and transient blurred vision that resolved spontaneously ¹. Physical examination of patients with acute angle-closure glaucoma demonstrates reduced visual acuity and may show conjunctival injection surrounding the iris, hazy cornea, or fixed mid-dilated pupils ¹. The diagnosis is confirmed by tonometry that detects elevated intraocular pressure (IOP), corneal edema, shallow anterior chamber, and a closed angle on gonioscopy ³. Medical or surgical therapy is directed at widening the angle and preventing further angle closure. If glaucoma has developed, it is treated with therapies to lower intraocular pressure.

In the chronic form of angle-closure glaucoma, the increase in intraocular pressure (IOP) is gradual, and there are minimal symptoms ¹³, ³. Chronic angle-closure glaucoma is diagnosed by noting peripheral anterior synechiae on gonioscopy, as well as progressive damage to the optic nerve and characteristic visual field loss. Chronic angle-closure glaucoma is treated with therapies to lower intraocular pressure. However, 30% of individuals with chronic angle-closure glaucoma experience an acute episode ²³.

A thorough history and eye examination are essential in differentiating between primary and secondary angle closure glaucoma. This distinction is crucial as the treatment of each form can vary greatly.

The mainstays of therapy are medications that lower intraocular pressure and laser peripheral iridotomy for any component of pupillary block. The same procedure (iridotomy) should eventually be performed in the unaffected fellow eye to prevent an occurrence in that eye. Once the procedure is performed in both eyes, pharmacologic pupil dilation or medications are no longer contra-indicated. Patients may be dilated or take these medications without fear of future acute angle closure glaucoma. Although angle closure glaucoma in all its forms is vision threatening, early diagnosis and appropriate management can stabilize the angle closure glaucoma and minimize vision loss.

Figure 1. Eye anatomy

Figure 2. Retinal layers showing retinal ganglion cell

Footnotes: Schematic representation of the retina and the retinal cell layers. (A) Blood supply and (B) structure of the retina. The retina is a layered structure lining the back of the eye consisting of a pigmented layer called retinal pigment epithelium (RPE), and a multilayered neuroretina. The retinal pigment epithelium (RPE) is in close contact with the outer segments of the photosensitive rod and cone cells of the neuroretina. The connecting cilium connects the photoreceptor outer segments with the cell bodies, which constitute a layer known as the outer nuclear layer (ONL). The axons of the photoreceptors synapse with the neuronal (bipolar, amacrine, and horizontal) cells of the inner nuclear layer (INL) via the outer plexiform layer (OPL). The axons of the inner nuclear layer (INL) cells in turn synapse with the ganglion cell layer (GCL) via the inner plexiform layer (IPL). The axons of the ganglion cells converge to form the optic nerve. Approximately 1.2 million nerve fibers, or axons, make up each human optic nerve. A retinal ganglion cell (RGC) is a type of neuron located near the inner surface (ganglion cell layer [GCL]) of the retina of the eye. A retinal ganglion cell (RGC) receives visual information from photoreceptors via two intermediate neuron types: bipolar cells and retina amacrine cells. Retina amacrine cells, particularly narrow field cells, are important for creating functional subunits within the ganglion cell layer and making it so that ganglion cells can observe a small dot moving a small distance. Retinal ganglion cells collectively transmit image-forming and non-image forming visual information from the retina in the form of action potential to several regions in the thalamus, hypothalamus, and mesencephalon, or midbrain. Visual images from the retina travel through the optic nerve, optic tract, and eventually to the visual part of the brain (the occipital lobe). There the images are processed and interpreted by the brain. Any disease process which affects the optic nerve could disrupt this input, leading to visual loss.

Abbreviations: ILM: internal limiting membrane, NFL: nerve fiber layer, GCL: ganglion cell layer, IPL: inner plexiform layer, INL: inner nuclear layer, OPL: outer plexiform layer, ONL: outer nuclear layer, ELM: external limiting membrane, OS: photoreceptor outer segment, RPE: retinal pigment epithelium

[Source ²⁴ ]

Figure 3. Angle closure glaucoma (blocked aqueous outflow increases intraocular pressure causing glaucoma)

Footnotes: (Left) In an eye with a normal configuration of the anterior segment, the angle between the iris and cornea is wide open (approximately 40˚). Aqueous fluid has free access to the trabecular meshwork and exits the eye unimpeded. (Right) In an eye with acute angle closure, the angle between the iris and the cornea is obstructed and closed. Aqueous fluid is trapped within the eye and causes the intraocular pressure to rise rapidly.

Figure 4. Acute angle-closure glaucoma

Footnotes: Blockage of the drainage angle causes intraocular pressure (IOP) to rise. Rapid elevation of intraocular pressure (IOP) is a key feature of acute angle closure glaucoma. High pressure results in a constellation of signs seen in acute angle closure glaucoma including redness of conjunctiva (red arrow) especially at corneal edge (“ciliary flush”), haziness of the cornea, and a mid-dilated pupil (white arrow).

[Source ²⁵ ]

Figure 5. Glaukomflecken

Footnotes: Glaukomflecken under the anterior lens capsule after an attack of acute angle closure. These lens changes are caused by necrosis of the lens epithelium.

[Source ²⁶ ]

Figure  6. Iris atrophy after acute angle closure glaucoma

[Source ²⁶ ]

What is the angle and what is angle closure?

The angle also called the drainage angle is the space between the clear part of your eye (cornea) and the colored part (iris), close to their meeting point near the white eye wall (sclera). The angle or drainage angle contains the trabecular meshwork (TM), which is the main structure that drains fluid out of the eye. The angle can be viewed by doctors with a simple office test called gonioscopy.

What is angle closure suspect?

“Angle closure suspect” refers to an eye with a narrow angle between the iris and the trabecular meshwork (TM), but without signs of elevated intraocular pressure (IOP) or other damage associated with angle-closure glaucoma. ‘Angle closure suspect’ is essentially an eye with a high risk of developing angle-closure glaucoma later in life. In ‘angle closure suspect’ persons, the iris blocks the view of the trabecular meshwork (TM) during gonioscopy for at least half of the angle, but the eye pressure (IOP) is normal and the optic nerve is healthy. In the next stage called the ‘angle closure’, there are signs of damage to the trabecular meshwork (TM) such as elevated intraocular pressure (IOP) or scar tissue in the angle or drainage angle, but the optic nerve is still healthy. Elevated intraocular pressure (IOP) in angle closure can happen either suddenly and painfully in an acute angle-closure attack, or more commonly, it develops gradually and silently. When elevated intraocular pressure (IOP) causes optic nerve damage, the disease stage is called “angle-closure glaucoma”. There are many more ‘angle-closure suspects’ than persons with ‘angle closure’ or ‘angle-closure glaucoma’ ²⁷.

Aqueous Humor Production and Physiology

The aqueous humor is a water-like fluid that is produced by the ciliary body that sits directly behind the iris (the colored part of your eye). Aqueous humor is produced at a rate of 2-3 microliters per minute (2-3 μL/minute) ²⁸, ²⁹. The aqueous humor is composed of organic and inorganic ions, carbon dioxide, amino acids, carbohydrates, glutathione, and water ²⁸, ³⁰. The aqueous humor fills the anterior chamber of your eye with continual production, secretion, and reabsorption ²⁸. The cornea and the lens of your eye have no blood supply. They receive nourishment from nutrients in the aqueous fluid that fills your eye. The aqueous fluid flows between the iris and lens through the pupil and to the drainage angle at the junction of the iris and the cornea. Aqueous fluid exits the eye through a tissue called the trabecular meshwork in the drainage angle. As the aqueous fluid passes through the eye, it supplies the lens and cornea with nutrients and carries away waste products. The production, circulation and reabsorption of aqueous humor are vital processes maintaining homeostasis of the eye. The pressure of the fluid in your eye called the intraocular pressure (IOP) is determined by the amount of aqueous humor fluid entering the eye through the ciliary body and exiting the eye through the trabecular meshwork. In most people, the balance between the aqueous humor fluid coming in and going out of the eye results in an eye pressure between 10 and 21 mm of Hg. In patients with glaucoma, aqueous humor fluid drains from the eye through the trabecular meshwork at a slower rate causing the pressure in your eye to rise or increased intraocular pressure (ocular hypertension) resulting in optic nerve damage and glaucoma.

Aqueous humor functions as a physical component allowing clear optics and filling the anterior chamber of the eye ²⁸, ²⁹. The aqueous humor is responsible for providing nourishment to the avascular components of the anterior chamber including the cornea and lens ²⁸, ²⁹. In addition, aqueous humor is responsible for removing waste products, blood, macrophages and other debris from the anterior chamber, including the trabecular meshwork ²⁸, ²⁹. The structure and function of the trabecular meshwork may become compromised by chronic oxidative stress from reactive oxygen species and insufficient antioxidant defense in the aqueous humor ²⁸, ²⁹, ³¹, ³². Decreased levels of antioxidants in aqueous humor are present in glaucomatous eyes versus normal eyes, consistent with the presence of increased oxidative stress and low-grade inflammation ³¹, ³².

The primary anatomic structures vital to the homeostasis of aqueous humor include the ciliary body as the site of principle production, and the trabecular meshwork and uveoscleral pathway as the sites of primary outflow ²⁸, ³³. Aqueous humor is produced by the ciliary body via a multistep process closely correlating with systemic vascular blood flow ²⁸, ³⁴, ³⁵. Initially, blood enters the ciliary processes, which propels ultrafiltrate from the blood into the ciliary interstitial space via a pressure gradient ²⁸, ³⁴, ³⁵. Next, the ciliary epithelium transports plasma components from the basal to the apical surface in order to synthesize aqueous humor and transport it into the posterior chamber ²⁸, ³⁴, ³⁵. Passive diffusion and ultrafiltration are key in initial synthesis, and active secretion across a blood-aqueous barrier via aquaporins, Na-K-ATPase and carbonic anhydrase enzymes are necessary for final synthesis ²⁸, ³⁴, ³⁵, ³⁶. These active transport enzymes necessary for final synthesis are common pharmacologic targets in decreasing aqueous humor production. Although systemic blood flow via the ciliary artery is required for the initial production of ultrafiltrate, the production of aqueous humor is independent from systemic blood pressure due to a fixed rate of 4% filtration of plasma ³⁵. Therefore, there is minimal association between systemic high blood pressure (hypertension) and elevated intraocular pressure (IOP). The estimated rate of aqueous humor production is approximately 2.4 microliters per minute (2.4 μL/minute), with diurnal variations leading to higher aqueous humor flow in the morning and lower flow in the evening ²⁸, ³⁴.

While aqueous humor production is well documented, the mechanism of drainage is still poorly understood.

There are 2 main drainage pathways for aqueous humor ²⁸, ³⁷, ³⁴:

1. The conventional pathway via trabecular meshwork, Schlemm’s canal, collector channels, and the episcleral venous system), and
2. The unconventional pathway via uveoscleral, uveovortex, uveolymphatic.

The conventional pathway drainage pathways for aqueous humor involves passive drainage throughout the trabecular meshwork although the Schlemm’s canal has been documented with paracellular and intracellular pores ²⁸, ³⁷, ³⁴. The trabecular meshwork is a triangular porous structure composed of a layer of connective tissue and endothelium with sympathetic innervation from superior sympathetic ganglion, and parasympathetic innervation from the ciliary ganglion ²⁸, ³⁷, ³⁴. The trabecular meshwork may be divided into the uveal meshwork (iris root, ciliary body, peripheral cornea), corneoscleral meshwork (scleral spur), and juxtacanalicular meshwork (transition into Schlemm’s canal) ²⁸, ³⁷, ³⁴. Schlemm’s canal is a structure with composition similar to venous vasculature, with fenestrated thin endothelium surrounded by connective tissue ²⁸, ³⁷, ³⁴. After drainage through the trabecular meshwork and the Schlemm’s canal, aqueous humor continues through collector channels into the episcleral venous system which deposits into the main venous system ²⁸, ³⁷, ³⁴.

Resistance to outflow through the trabecular meshwork and Schlemm’s canal has been documented although it is poorly understood, yet resistance remains an important factor in regulating intraocular pressure and the pathogenesis of glaucomatous processes. In humans, up to 75% of aqueous outflow resistance is contributed by the trabecular meshwork while the remaining 25% is due to resistance beyond Schlemm’s canal ²⁸. The rate of outflow is directly influenced by iris and ciliary muscles which contract and relax based on cholinergic innervation and pharmacodynamics ²⁸, ³⁷, ³⁴, ³³, ³⁸. In ciliary contraction, the trabecular meshwork and Schlemm’s canal dilate, decreasing resistance and increasing outflow ²⁸, ³⁷, ³⁴, ³³, ³⁸. The rate of outflow is also influenced by intraocular pressure, with higher intraocular pressure altering the structure of endothelial lining in Schlemm’s canal to increase the number of porous vacuoles allowing increased outflow ²⁸, ³⁷, ³⁴, ³³, ³⁸. However, it is still debated if this finding substantially contributes to increasing outflow in glaucomatous eyes ²⁸, ³⁷, ³⁴, ³³, ³⁸.

The unconventional pathway involves drainage into the orbital vasculature, vortex veins and ciliary lymphatics, contributing up to 25-40% of total aqueous outflow in cynomolgus and vervet monkey models. The uveoscleral pathway involves diffusion into the sclera and episcleral through the orbital vasculature. The uveovortex pathway involves osmotic absorption of fluid through the choroid, passing into the vortex veins ³⁷. Lastly, the uveolymphatic pathway involves drainage into lymphatic vessels within the ciliary body, although the extent of drainage under normal physiological conditions remains controversial ³⁷. In addition, the unconventional pathway also includes corneal, iridial and retinal routes, albeit less clinically significant ³⁹. Regardless of downflow pathway, all unconventional paths require drainage through the interstitial spaces of the ciliary muscle ³⁷, ³⁹. Resistance also exists within the unconventional pathway likely due to ciliary muscle tone, as seen with changes in outflow in the setting of pilocarpine, increasing ciliary tone and decreasing flow, and atropine, decreasing ciliary tone and increasing flow ³⁷, ³⁹. Therefore, the unconventional pathways are also clinically important in moderating intraocular pressure, and serve as a potential target in glaucoma therapy.

Figure 7. Normal aqueous outflow

Footnotes: The ciliary body is a structure that sits directly behind the iris (the colored part of your eye). One of ciliary body’s jobs is to create an important fluid called aqueous humor, a fluid that nourishes the cornea and lens. Aqueous humor flows through a specific route into the front of the eye (the anterior chamber). This route allows aqueous humor to send important nutrients and oxygen to other parts of the eye, such as the lens and cornea. The aqueous humor is produced behind the iris, flows into the anterior chamber through the pupil, and exits the eye between the iris and cornea via the trabecular meshwork, a specialized eye tissue located at the chamber angle of the eye next to the cornea ⁴⁰. In a healthy eye, this is a constant process. The ciliary body is always producing aqueous humor, and 80%-90% aqueous humor is always draining through the trabecular meshwork. The trabecular meshwork is a specialized spongy tissue in the anterior chamber of the eye that regulates the outflow of aqueous humor ⁴⁰. The trabecular meshwork acts as a filter, controlling how quickly aqueous humor drains out of the eye through a structure called Schlemm’s canal, ultimately maintaining intraocular pressure (IOP). The canal of Schlemm, also known as Schlemm’s canal or the scleral venous sinus, is a circular, lymphatic-like vessel in the eye that drains aqueous humor from the anterior chamber into the episcleral blood vessels. The canal of Schlemm and the trabecular meshwork (TM) play a crucial role in maintaining intraocular pressure (IOP) by facilitating the outflow of aqueous humor. Too much aqueous humor production or obstruction of its outflow causes a rise in intraocular pressure (IOP) that can lead to glaucoma.

[Source ⁴¹ ]

Angle-closure glaucoma causes

Primary angle-closure glaucoma

Primary angle closure glaucoma is caused by relative pupillary block (angle closure) in the majority of cases ³. In pupillary block (angle closure), aqueous humor encounters increased resistance as it flows from the posterior to anterior chamber through the iris-lens channel. Some degree of relative pupillary block is present in most phakic eyes. The risk of pupillary block is highest with a mid-dilated pupil where there appears to be maximum contact between the iris and the lens. In eyes with angle closure, other factors exacerbate the block, such as the front lens surface being anterior to the plane of iris insertion into the ciliary body base. The increased pressure gradient across the pupil causes the peripheral iris to bow forward and cover some or all of the filtering portion of the trabecular meshwork, resulting in appositional angle closure. Peripheral anterior synechiae form after prolonged or repeated contacts of the peripheral iris with trabecular meshwork. Another mechanism thought to be important in primary angle closure is iris angle crowding, which is caused by a thickened peripheral iris filling the space between the trabecular meshwork and angle recess under dark conditions ⁴².

Eyes that experience angle closure glaucoma are anatomically different than normal eyes — they have shorter axial lengths, shallower anterior chambers, thicker and relatively anteriorly positioned lenses, and flatter corneas ⁴³ and they are also physiologically different. Thicker irides may increase the posterior to anterior pressure differential ⁴⁴. Dynamic factors in angle closure eyes that can contribute to increased pupillary block (angle closure) are the tendency to retain more iris volume after dilation and choroidal expansion causing forward lens movement ⁴⁵. As imaging modalities, such as ultrasound biomicroscopy and anterior segment optical coherence tomography improve, these dynamic factors will be better studied and understood.

A less common cause of primary angle closure glaucoma is anterior non-pupillary block. This is observed in eyes in which angle closure progresses despite a patent iridotomy, for example, as seen in plateau iris. Plateau iris configuration is characterized by a normal central anterior chamber depth, flat iris profile, and crowding of the angle by the iris base. There is a forward displacement of the iris base by anteriorly located ciliary processes that can lead to subsequent angle closure. Plateau iris syndrome occurs when an eye with plateau iris configuration develops a closed angle ⁴⁶. Prominent last iris roll is another mechanism of anterior nonpupillary block in which a very thick iris with prominent peripheral circumferential folds becomes more pronounced and contacts trabecular meshwork with dilation ⁴⁷.

Secondary angle-closure glaucoma

Secondary angle closure glaucoma is caused by a myriad of other eye diseases. There are several secondary causes of angle closure that involve relative and absolute pupillary block. In phacomorphic glaucoma, the mass effect of a thickened or intumescent cataract pushes the iris forward and causes pathological angle narrowing. Forward displacement of the lens in ectopia lentis or microspherophakia can also push the iris forward and shallow the angle. Absolute pupillary block occurs when there is no movement of aqueous through the pupil because of 360 degrees posterior synechiae between the iris and a crystalline lens, an intraocular lens, capsular remnants, or the vitreous face. In secondary angle closure glaucoma without pupillary block, angle closure is due to either a.) contraction of an inflammatory, hemorrhagic, or vascular membrane in the angle leading to peripheral anterior synechiae, or b.) forward displacement of the lens-iris diaphragm, often associated with ciliary body swelling and anterior rotation ³, ⁴.

Mechanisms that push the iris forward from behind:

• Relative pupillary block (primary angle closure)
• Plateau iris configuration (primary angle closure)
• Absolute pupillary block – 360o posterior synechiae secluding pupil
• Aqueous misdirection or malignant glaucoma
• Ciliary body swelling, inflammation or cysts
• Choroidal swelling, effusions, or detachments
• Posterior segment tumors or space-occupying substances (silicone oil or gas bubble)
• Contracting retrolental tissue as seen in retinopathy of prematurity
• Anteriorly displaced lens
• Encircling retinal bands/buckles

Mechanisms that pull the iris forward into contact with the trabecular meshwork:

• Contraction of inflammatory membrane or fibrovascular tissue
• Iridocorneal endothelial (ICE) syndrome with migration of corneal endothelium
• Fibrous ingrowth
• Epithelial downgrowth
• Iris incarceration in traumatic or surgical wound

Clinical findings in various types of secondary angle closure glaucoma:

• Neovascularization of the angle – blood vessels from iris that cross scleral spur to arborize along trabecular meshwork, peripheral anterior synechiae
• Anterior chamber inflammation – keratic precipitates, posterior synechiae, iris bombé, inferior PAS (as opposed to primary angle closure where PAS tend to develop superiorly)
• Iridocorneal endothelial (ICE) syndrome – beaten-bronze corneal endothelium, corneal edema, high PAS that can extend anterior to the Schwalbe line, iris atrophy, corectopia
• Drug induced (e.g. systemic topiramate) – acute bilateral disease, acute myopic shift, uniformly shallow chamber with anterior iris and lens displacement, ciliochoroidal effusion or detachment
• Aqueous misdirection (malignant glaucoma) – flattening of central and periperhal anterior chamber, anterior displacement of lens (cystralline or intraocular lens) or vitreous face, clear “aqueous” zones in vitreous
• Lens-induced angle closure – thick cataract, unstable or subluxed lens
• Nanophthalmos – small but normal eye with short axial length, microcornea, large lens, and thickened sclera; choroidal effusion
• Retinopathy of prematurity or persistent hyperplastic primary vitreous – contracting retrolental tissue
• Iris or ciliary body mass lesions or cysts – irregular contour of iris or neovascularization, hyphema or vitreous hemorrhage, episcleral sentinel vessel, ciliary body mass through dilated pupil or on ultrasound biomicroscopy
• Posterior segment mass or large serous retinal detachment – signs of each on funduscopic exam
• Epithelial and/or fibrous downgrowth – wound dehiscence or gape, epithelial cysts in anterior chamber adjacent to wound, gray sheetlike membrane covering anterior segment structures that whitens with argon laser
• Pseudophakic or aphakic pupillary block – pupilary obstruction or synechiae to anterior hyaloid surface, the intraocular lens, or posterior capsule
• Ciliary body engorgement associated with retinal vascular occlusion or panretinal photocoagulation – anterior rotation of iris and lens; retinal signs of each underlying etiology, e.g. retinal hemorrhages for vein occlusion and extensive retinal laser scars from photocoagulation.
• Retinal surgery
  • Encircling scleral buckle – relatively deep central anterior chamber with peripheral iris flattening, choroidal effusion
  • Pars plana vitrectomy – pupillary block from expansile gases pushing iris and lens forward, silicone oil in the anterior chamber, non-patent iridotomy

Angle-closure glaucoma risk factors

A large number of angle closure glaucoma risk factors have been identified:

• Hyperopia (farsightedness or hypermetropia) ⁴⁸
• Family history of angle closure ⁴⁹, ⁵⁰, ⁵¹
• Advancing age ⁵², ⁵³
• Female gender ⁵⁴, ⁵⁵
• Asian (predominantly Southeast Asian and Chinese) or Inuit descent (Alaska Native) ⁵⁶. In white people, angle-closure glaucoma accounts for 6% of all glaucoma diagnoses ⁵⁷. The variability in ethnicities could be due to anatomical differences in the ciliary body and iris ⁵⁸.
• Shallow anterior chamber depth ⁵⁹
• Shorter axial length ⁶⁰
• Thicker lens ⁶¹
• Medications: Over 60 drugs have been reported to be associated with angle closure glaucoma and are considered risk factors, particularly for individuals with ocular predispositions ¹², ¹³, ³. These drugs include topical anticholinergic pupil dilators, such as atropine and cyclopentolate, and systemic medication, including topiramate, sulfonamides, duloxetine, and phenothiazines ⁶². Patients using these medications should undergo regular eye examinations, especially if they have risk factors for angle closure glaucoma ⁶³. Sulfonamide antibiotics, diuretics, and topiramate are thought to precipitate angle closure via ciliary body edema ¹.

Risk factors for secondary angle closure glaucoma are related to the underlying diseases that cause it.

Table 1. Medications associated with angle-closure glaucoma

[Source ¹ ]

Angle-closure glaucoma prevention

You can’t prevent angle-closure glaucoma, but early detection and treatment can manage pressure inside your eye and help prevent or delay vision loss. Screening eye exams with an eye care specialist will help you know if you have risks for angle closure glaucoma. Your eye care specialist can then suggest treatment and medications to avoid angle-closure glaucoma if you’re at risk. It’s also very important to manage or prevent risk factors such as high blood pressure and blood sugar if you have diabetes. Using protective items like safety glasses and goggles can help prevent eye injuries.

Screening

Given the high prevalence and morbidity of angle closure glaucoma in many countries, there is a need for quick, inexpensive screening methods that do not require highly skilled operators.

Oblique flashlight test uses a penlight that is held next to the temporal side of an eye with the beam of light parallel to the iris and shining across the anterior chamber. If there is a shadow projected onto the nasal iris, the angle is narrow because the iris is bowed forward and blocking the path of light. If there is no shadow, the anterior chamber angle is considered open. Because of variability in flashlight illumination and subjectivity in assessment of the test result, however, this test has a relatively low specificity ⁶⁴.

The Van Herick method uses a narrow slit beam at 60 degrees onto the cornea just anterior to the limbus to evaluate the anterior chamber depth. If the distance from the anterior iris surface to the posterior corneal surface is less than one-fourth the corneal thickness, the angle may be narrow and should undergo gonioscopy. Modification of this method by creating additional grades, called the limbal chamber depth test, outperformed central anterior chamber depth (as measured by optical pachymetry and ultrasound) and autorefraction as a screening tool for the detection of occludable drainage angles identified by gonioscopy ⁶⁵.

Laser peripheral iridotomy for narrow angles

The goal of screening for narrow angles is to identify patients at risk of developing angle closure and to treat prophylactically with a laser peripheral iridotomy. Patients with narrow but open angles should be followed for intraocular pressure elevation, progressive angle narrowing, and development of PAS. There is no evidence that iridotomy is indicated for narrow but open angles with normal intraocular pressure; however, laser peripheral iridotomy is fairly safe and can prevent a potentially vision-threatening outcome so the risks and benefits must be carefully considered in each case and discussed with the patient in details.

Indications for laser peripheral ridotomy ²:

• Elevation of previously normal intraocular pressure
• Presence of potentially occludable angle
• Peripheral anterior synechiae attributable to episodes of angle closure
• Progressive narrowing of the angle
• Requirement for medication that may provoke pupillary block (i.e. — antidepressants, anticholinergics, etc.)
• Symptoms that suggest prior or intermittent subacute angle closure
• Situation limiting a patient’s ability to immediately receive ophthalmic care (e.g.,frequent travel to less developed countries where treatment may not be readily available, lack of insurance, and poor access to transportation)
• Having another eye disorder that requires frequent dilated eye exams (e.g. diabetic retinopathy)
• History of acute primary angle closure glaucoma in other eye

Angle-closure glaucoma signs and symptoms

Acute angle-closure glaucoma symptoms may include:

• Severe eye pain.
• Eye redness.
• Vision loss.
• Sudden blurry vision.
• Seeing rainbow-colored rings around lights or halos.
• Headache.
• Nausea and vomiting.

Symptoms of chronic angle-closure glaucoma and other forms of non-acute angle-closure glaucoma when they’re present, which doesn’t always happen, may include:

• Eye redness.
• Blurred vision.
• Eye discomfort.
• Headache or brow ache.

Angle-closure glaucoma symptoms

Patients with anatomic narrow angles without acute angle closure are typically asymptomatic in both the primary and secondary angle closure glaucoma. Similarly, primary and secondary chronic angle closure  glaucoma patients often experience no symptoms unless they develop end-stage glaucoma, in which case they may complain of decreased vision or reduced peripheral vision.

Acute angle closure glaucoma, on the other hand, usually presents with dramatic symptoms from the quick rise in intraocular pressure. Patients complain of blurred vision, rainbows, halos around lights, or even transient loss of vision. They often have intense pain that may be localized to the eye, may follow the trigeminal distribution, or may be described as diffuse discomfort. Nausea and vomiting are common.

Subacute or intermittent angle closure attacks are brief episodes of angle closure that resolve spontaneously. Patients experience the above symptoms of acute angle closure, but on a milder scale. They will typically experience some blurring of the vision or halos with mild to moderate eye pain, brow ache, or headache. These attacks are often resolved by entering a well lit room which may cause miosis or sleep as sleep-induced miosis ameliorates the lesser degree of pupillary block (angle closure) in these patients.

Angle-closure glaucoma signs

Signs of a primary anatomic narrow angle on slit lamp exam can be subtle and include a shallow anterior chamber and an anteriorly bowed iris.

Both primary and secondary forms of angle closure can cause acute angle closure attacks. The intraocular pressure usually exceeds 40 mmHg and may rise to as high as 80 mmHg. The conjunctiva is significantly injected. The cornea develops stromal and microcystic edema in response to the acute rise in eye pressure and decompensation of the endothelial pump mechanism. Iris sphincter ischemia leads to a fixed, mid-dilated pupil. Sectoral iris atrophy may occur, releasing pigment into the anterior chamber that dusts the corneal endothelium and anterior lens capsule. The overall anterior chamber is shallow. The center is usually formed, but the mid-peripheral iris bows forward and may touch the peripheral cornea. Often there is anterior chamber inflammation. The fundus is typically difficult to examine because of corneal edema. If visualized, the optic nerve head may be hyperemic and edematous. The angle is often difficult to examine with gonioscopy because of corneal edema, but if visualized, reveals contact of the peripheral iris with cornea.

In the aftermath of an acute attack, pupillary distortion may result if there is permanent sphincter damage and/or iris atrophy. Anterior lens capsule opacities, known as glaukomflecken, may result from damage to the anterior lens epithelium from high intraocular pressure. The angle may have permanent synechiae formation. Intraocular pressure may be low if the ciliary body is so ischemic that aqueous humor production is compromised. As the ciliary body recovers, normal aqueous humor production resumes and the intraocular pressure rises.

Angle closure glaucoma exhibits signs of optic neuropathy in the typical glaucomatous pattern with increased cupping of the optic nerve and retinal nerve fiber layer dropout.

Angle-closure glaucoma complications

Complications of acute angle-closure glaucoma attacks are the result of a rapid, extreme rise in intraocular pressure (IOP). Possible complications include corneal decompensation, cataractous lens changes, iris ischemia resulting in atrophy and distortion, ciliary body shutdown with resultant hypotony, central retinal vein occlusion, optic nerve ischemia, and acute permanent vision loss.

Complications of chronic angle-closure glaucoma include all the same ones that can be seen in acute disease. The difference in chronic angle-closure glaucoma is that these conditions develop in a more insidious fashion over a longer period of time. These patients typically have asymptomatic progression of glaucomatous optic neuropathy with corresponding visual field defects developing over time and eventually permanent loss of vision.

Angle-closure glaucoma diagnosis

Diagnosis of both primary and secondary angle closure glaucoma is based on history and eye exam. Gonioscopy is a noninvasive diagnostic test that assesses the drainage angle in your eye that your eye care specialists use to check for glaucoma is the gold standard for evaluating the anterior chamber angle, but imaging modalities assist in quantifying and objectifying angle characteristics. To distinguish between primary and secondary angle closure glaucoma causes, your eye specialist (ophthalmologist) must actively look for signs and symptoms of possible secondary causes and rule each out before your can be diagnosed with primary angle closure glaucoma.

History

• History of present illness – typical signs and symptoms of acute or subacute angle closure attacks and if patient was upset or in the dark when symptoms started
• Past ocular history
  • Trauma – can cause zonular weakness or dehiscence allowing lens to displace anteriorly
  • Incisional or laser surgery – can cause anterior chamber inflammation or predispose to epithelial/fibrous ingrowth; may also lead to aqueous misdirection (e.g. after laser peripheral iridotomy) or ciliary body engorgement (e.g. after extensive panretinal photocoagulation).
  • History of prior retinal vein occlusion – can cause angle neovascularization or ciliary body engorgement rotating lens forward
• Past medical history – history of diabetes or carotid stenosis disease that can cause angle neovascularization
• Medications – use of systemic medications, such as sulfonamide, topiramate, and phenothizaines, that may cause ciliary body engorgement or suprachoroidal effusion; use of medications to treat allergy, bladder dysfunction, or depression; use of anticholinergics or sympathomimetics that can dilate pupil
• Family history of acute angle glaucoma

Physical examination

• Refractive status – hyperopic eyes tend to have shallower anterior chamber angles which places them at risk for angle closure
• Pupil size and reactivity
• Slit lamp exam – a detailed examination of your eye using a special microscope called a slit lamp. It allows for a magnified, three-dimensional (3D) view of your eye’s structures
  • Conjunctiva – injection
  • Cornea – clarity, presence of edema, evidence of surgical or traumatic wounds
  • Anterior chamber – central and peripheral depth, inflammation
  • Iris – areas of atrophy, mass, neovascularization, or posterior synechiae
  • Lens – thickness, phacodonesis, subluxation, glaucomflecken (necrosis of anterior lens capsule; may indicate previous attacks). Glaukomflecken are small anterior subcapsular opacities secondary to lens epithelial necrosis resulting from acute angle closure glaucoma. 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 ⁶⁶.
• Intraocular pressure (IOP) measurement, preferably with applanation prior to gonioscopy
• Tonometry. This measures the pressure inside your eye. Increased eye pressure is the most important risk factor for glaucoma. There are several methods of measuring eye pressure. The most common method is known as applanation, in which a tiny instrument contacts the eye’s surface after it is numbed with an eye drop.
  • Air-puff test. You’ll rest your chin on a machine and your eye specialist will blow a puff of air into your eye. This quick and painless test is used as part of a routine glaucoma screening. If the results show that your eye pressure is high, your eye specialist will do other eye-pressure tests to get a more accurate measurement.
  • Applanation tonometry. Your eye specialist will numb your eyes with drops before measuring your eye pressure using one of these methods:
    • You’ll rest your chin on a special magnifying device called a slit lamp. Your eye care specialist will examine your eye through the slit lamp while gently pressing a special tool on your eye to test the pressure.
    • Your eye care specialist will gently press a handheld device against your eye. The device measures your eye pressure.
• Pachymetry. Pachymetry is a simple, painless test that measures the thickness of the cornea, the clear front part of the eye. The eye doctor uses an ultrasonic wave instrument to help determine the thickness of the cornea and better evaluate eye pressure.
• Ophthalmoscopy. Your eye care specialist will examine the fundus and optic nerve of your eyes – dilation is often not advisable in primary angle closure attack until an iridotomy has been performed and/or the acute attack has resolved as pupil dilation can exacerbate the condition because the eye drops to dilate your pupil could make drainage worse. In contrast, pupil dilation may be permissible as the appropriate treatment in certain forms of secondary angle closure. The fundus should be examined for underlying causes leading to the angle closure. You’ll look straight ahead while your eye care specialist looks into your eye using a device with a light and magnifying lens.
• Gonioscopy of both eyes with indentation to evaluate for appositional versus synechial angle closure. Gonioscopy is a specialized eye examination that allows an ophthalmologist to visualize the anterior chamber drainage angle, the space between the iris and the cornea where fluid drains out of the eye. Gonioscopy is a crucial part of diagnosing and monitoring glaucoma and other eye conditions. Eye doctors regularly examine the drainage angle to see if there is any visible obstruction to fluid leaving the eye through the trabecular meshwork. A special lens (gonioscopy lens) is needed to examine the trabecular meshwork. The gonioscopy lens is gently placed against the surface of the cornea and allows eye doctors to see the trabecular meshwork in the drainage angle.

If your eye specialist (ophthalmologist) has a reason to suspect damage to your retina and/or optic nerve, they may also use additional types of eye imaging. These include:

• Optical coherence tomography (OCT). Optical Coherence Tomography (OCT) measures the reflection of laser light similar to the way that ultrasound measures the reflection of sound. Using this device, a 3D reconstruction of the optic nerve can be created. Optical coherence tomography (OCT) is valuable for monitoring morphological changes in the optic nerve and retinal nerve fiber layer, especially in patients with ocular hypertension and early-to-moderate glaucoma ⁶⁷. The most recent advances of OCT include OCT-A, or OCT-Angiography, whereby the blood flow to vessels surrounding the optic nerve and in the macula can be measured. This is still an active area of research, but scientists do know that some patients’ optic nerves are very vulnerable to changes in optic nerve blood flow, and this new measurement may be useful in evaluating these patients.
• Heidelberg Retina Tomograph (HRT): Heidelberg Retina Tomograph (HRT) is also a laser that can produce a 3D representation of the optic nerve.
• Nerve Fiber Analyzer (GDx): Nerve Fiber Analyzer (GDx) uses laser light to measure the thickness of the nerve fiber layer.
• Fluorescein angiography. Fluorescein angiography is a diagnostic test used to examine the blood vessels in the retina and choroid of the eye. Fluorescein angiography involves injecting a fluorescent dye into the bloodstream and taking photographs of your retina and its blood vessels as the dye circulates, revealing potential blockages, leaks, or other abnormalities in the blood vessels. Fluorescein angiography is often recommended to find and diagnose eye disease including ⁶⁸:
  • macular edema (swelling in the retina that distorts vision)
  • diabetic retinopathy (damaged or abnormal blood vessels in the eye caused by diabetes)
  • macular degeneration
  • blockage of veins inside the eye, called branch retinal vein occlusion (BRVO) or central retinal vein occlusion (CRVO)
  • macular pucker (a wrinkle in the retina caused by a buildup of fluid behind it)
  • ocular melanoma (a type of cancer affecting the eye)
  • rack changes in eye disease over time
  • target treatment areas
• Less commonly, ultrasound, computed tomography (CT) or magnetic resonance imaging (MRI).

Gonioscopy

The key to diagnosis of anatomic narrow angle or angle closure is gonioscopy, which is still the gold standard method of angle evaluation. The ideal way to perform gonioscopy is in a dark room using a small rectangle of light only as bright as necessary to view the angle structures, as light can open an appositionally closed angle in about one-third of cases ⁶⁹. Dynamic or compression or indentation gonioscopy is essential to differentiate appositional closure from synechial closure. Gentle pressure on the cornea with the goniolens pushes back the iris and reveals whether the angle can be opened any further; if not, synechial closure is present. This maneuver can also help break acute attacks by forcing fluid into the periphery and opening areas of appositional closure.

Occludable angles are typically described as eyes in which the posterior, usually pigmented, trabecular meshwork is seen for less than 90° of the angle circumference or if the angle width is less than 20° ⁷⁰.

Angle Grading and Classification Systems

A. Scheie system (R)

• 0 – entire angle visible with wide ciliary body band
• I – last roll of iris obscuring part of the ciliary body
• II – nothing posterior to trabecular meshwork visible
• III – posterior portion of trabecular meshwork not visible
• IV – no structures posterior to Schwalbe’s line visible

Pigmentation graded 0 (no pigmentation) to 4 (heavily pigmented)

B. Shaffer system (R)

• 0 – closed or slit
• 1 – extremely narrow, ≤10 degrees
• 2 – narrow, 20 degrees
• 3 – open, 20-35 degrees
• 4 – wide open, 35-45 degrees

C. Spaeth system (R)

Level of iris insertion:

• A – anterior to trabecular meshwork
• B – anterior to posterior limit of trabecular meshwork
• C – posterior to scleral spur
• D – into the mid-ciliary body face (anterior ciliary body band visible)
• E – posterior ciliary body (wide band of ciliary body band visible)

Angle width – estimated in degrees from line tangential to the trabecular meshwork to line tangential to the iris surface one third of the way from the periphery (ranges from 0 – 40 degrees)

Curvature of iris:

• r – regular configuration, no significant forward or backward arching of iris
• s – steep or forward bowing (convex) curve
• q – queer or posterior bowing (concave) curve

Pigmentation: 0 (no pigment) to 4 (heavy pigmentation)

Change in angle configuration after indentation performed described by putting the original insertion in parenthesis, followed by the insertion after indentation. For example, if indentation shows that the insertion is actually a D when it originally appeared to be a C, it is indicated as a (C)D ².

Figure 8. Gonioscopy (the drainage angle is examined using a special lens)

Footnotes: Gonioscopy. (A) and (B) Gonioscopy lens. (C) The gonioscopy lens is gently held against the cornea. Eye doctors look through the gonioscopy lens to see the drainage angle.

[Source ⁷¹ ]

Provocative tests

Various provocative tests have been developed in an attempt to separate out patients who may be at higher risk of angle closure. In these tests, different maneuvers are used in an attempt to induce pupillary block, and then the pressure is rechecked and the angle is examined for narrowing. A test is considered positive if the IOP increases by 8 or more mmHg. In the dark room test, patients are placed in a dark room for 1-2 hours to dilate the pupil and increase resistance at the lens-iris channel.

The prone test involves placing the patient in the prone position for 1-2 hours without sleeping to anteriorly displace the lens and increase pupillary block. These tests have not been found to be very predictive of angle closure ⁷². Combining anterior chamber imaging (e.g. ultrasound biomicroscopy) with provocative testing assists in detecting apposition and allows measurement of various parameters of the angle ⁷³, but their ability to predict future angle closure is not well established.

Pharmacologic provocative tests using mydriatic eye drops to increase pupillary block via pupil dilation have fallen out of favor as they carry a significant risk of angle closure in and of themselves.

Imaging modalities

To supplement information obtained through gonioscopy, there are several anterior segment imaging devices available that provide detailed images of structures and quantitative measurements. They are useful in primary angle closure but can also help detect secondary cases of angle closure, such as ciliary body masses or anterior rotation. At this time, there are no widely agreed upon quantitative measurement cutoffs obtained from these devices that distinguish a narrow angle from an open one.

Ultrasound biomicroscopy

This high-frequency B scan ultrasound provides high-resolution cross-sectional images of the anterior segment of the eye to the anterior vitreous. Because it uses sound, it can pass through opaque structures to visualize structures hidden from direct clinical examination, such as the ciliary body ⁷⁴. It is particularly helpful for evaluating plateau iris and other ciliary body pathology. The disadvantages of ultrasound biomicroscopy include: requirement of a water bath immersion, specialized equipment, and a skilled technician to operate; it is also relatively costly and time consuming.

Anterior segment optical coherence tomography

This modality uses a diode light source instead of sound to produce highly detailed images of the cornea, angle region, and anterior ciliary body similar to those seen with ultrasound biomicroscopy. Compared to ultrasound biomicroscopy, anterior segment optical coherence tomography (OCT) is unable to image structures posterior to the iris plane well because of posterior pigmented iris shadowing and scleral light scattering ⁷⁴. The advantages of anterior segment optical coherence tomography are that it is a noncontact exam: the patient can be imaged in an upright position avoiding positional lens changes, and all four quadrants can be scanned at once.

Scheimpflug photography

Digital images of the anterior chamber angle can be obtained using a Scheimpflug camera. Rotating versions of the camera provide three-dimensional photos that can be analyzed by computer software to measure specific parameters of the angle. The camera has an easy-to-use slit lamp type configuration but is expensive and requires special equipment. It cannot image the ciliary processes or body behind the iris.

Optic nerve assessment and imaging, retinal nerve fiber layer analysis, and visual field testing should be preformed to assess for signs of glaucomatous optic neuropathy in any patient with angle narrowing or angle closure glaucoma.

Angle-closure glaucoma differential diagnosis

Numerous eye conditions can lead to elevated intraocular pressure (IOP), corneal haze, inflammation of the conjunctiva and the anterior segment, and similar signs and symptoms seen in patients with acute angle-closure glaucoma. When evaluating a patient presenting with these signs and symptoms, the following differential diagnosis should be considered ³:

• Allergic conjunctivitis
• Bacterial conjunctivitis (pink eye)
• Viral conjunctivitis
• Keratitis
• Episcleritis or scleritis
• Eye trauma
• Chemical eye injury
• Corneal ulcer
• Open-angle glaucoma
• Drug-induced glaucoma
• Malignant glaucoma
• Neovascular glaucoma
• Phacomorphic glaucoma
• Senile cataract (age-related cataract)
• Lens subluxation ⁷⁵
• Migraine headache ⁷⁶
• Cluster headache
• Suprachoroidal hemorrhage

Angle-closure glaucoma treatment

There’s no cure for angle-closure glaucoma, but there are treatments. The overall goals for angle-closure glaucoma management are to reverse or prevent the angle closure process, control intraocular pressure (IOP) elevation, and prevent damage to the optic nerve. Some primary and secondary forms of angle-closure glaucoma may be treated similarly, while others require very different treatment approaches based on their underlying pathophysiology. Intraocular pressure (IOP) is lowered with glaucoma medications. Iridotomy (a laser procedure used to create a small hole in the iris, the colored part of the eye, to open up the drainage angle and prevent or treat angle-closure glaucoma) is an essential part of treatment in primary angle closure glaucoma, but may not be indicated in some forms of secondary angle closure glaucoma. Trabeculectomy (a surgical procedure to create a new drainage channel in the eye, typically by making a small incision in the sclera [the white part of the eye] and creating a “trapdoor” or “flap” to allow fluid to escape and relieve eye pressure to treat glaucoma) and tube shunts may also not be indicated for certain secondary forms of angle closure glaucoma.

Acute angle-closure glaucoma treatment

Treatment for acute angle-closure glaucoma must happen quickly to avoid vision loss.

Your eye specialist (ophthalmologist) will offer treatments that may include:

Medications

The role of medications in acute angle closure attacks is to rapidly lower intraocular pressure (IOP), reduce eye pain, and clear corneal edema in preparation for iridotomy. 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 intraocular pressure (IOP) by blocking the enzyme responsible for forming bicarbonate ions, reducing the aqueous humor secretion ⁷⁷. 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 intraocular pressure (IOP) rapidly. It draws fluid out of the eye, thereby reducing intraocular pressure ⁷⁸. 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 intraocular pressure (IOP) by inhibiting the beta-adrenergic receptors in the ciliary body, thereby decreasing aqueous humor production ⁷⁹. 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 ⁸⁰. 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 intraocular pressure (IOP) is below 40 mm Hg ⁸¹.

In acute angle-closure glaucoma, rapid reduction of intraocular pressure (IOP) is essential to preventing further damage to the optic nerve. Although your ophthalmologist may attempt the use of topical, oral, and intravenous medications to lower the pressure acutely, definitive therapy typically involves a surgical intervention to clear the obstruction and promote aqueous drainage. These procedures include laser peripheral iridotomy, lens extraction, or anterior chamber paracentesis as appropriate to decrease intraocular pressure (IOP) and prevent the loss of vision ¹², ¹³, ¹⁴, ³, ⁸², ⁸³.

During the acute phase of angle-closure glaucoma, it is crucial to closely monitor intraocular pressure (IOP) to assess the effectiveness of treatment and ensure that it returns to normal values ³. Frequent intraocular pressure (IOP) measurements are necessary to evaluate the response to therapy and make any necessary adjustments. The recommended frequency of intraocular pressure (IOP) checks may vary depending on the specific situation and the response to treatment. Still, generally, it is advised to measure intraocular pressure (IOP) at least every hour after the initial onset of symptoms until the intraocular pressure (IOP) stabilizes ³.

After the acute episode of angle-closure glaucoma subsides, definitive treatment focuses on preventing future angle-closure attacks and managing the underlying anatomical risk factors ³.

After the acute episode of angle-closure glaucoma subsides, laser peripheral iridotomy is the treatment of choice ⁸³ and surgical iridectomy is indicated when laser iridectomy cannot be performed or is insufficient ⁸⁴. 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 ⁸⁵.

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 ⁸⁶. 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 angle-closure glaucoma ³.

If elevated IOP persists after the acute phase of angle-closure glaucoma, 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.

Table 2. Medications for initial management of acute angle-closure glaucoma

[Source ¹ ]

Laser peripheral iridotomy

After the acute episode of angle-closure glaucoma subsides, laser peripheral iridotomy is the treatment of choice ⁸³. Laser peripheral iridotomy is considered an effective and safe treatment. Laser peripheral iridotomy 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. Laser peripheral iridotomy helps to relieve pupillary block and prevent future angle-closure attacks. Laser peripheral iridotomy is a minimally invasive procedure performed on an outpatient basis. If you have an episode of acute angle-closure glaucoma in one eye, your eye specialist (ophthalmologist) will do a laser peripheral iridotomy on both eyes. Otherwise, you’re at risk of having an acute episode of angle-closure glaucoma in your other eye. If a patient cannot sit for a laser procedure, such as in children, a surgical iridectomy may be performed in the operating room.

The fellow eyes of patients that have undergone primary acute angle-closure are generally at significant risk for an acute attack and should receive an iridotomy ⁸⁷. An untreated fellow eye has a 40% to 50% chance of developing an acute primary angle-closure attack over the next 5 to 10 years ⁸⁷. Chronic miotic therapy is not an acceptable alternative, as 50% of contralateral eyes of individuals suffering acute primary angle-closure developed acute attaks when treated with pilocarpine alone. This is in contrast to the 1.8% of patients treated with prophylactic incisional iridectomy who developed an attack during this same time period ⁸⁸.

Surgical iridectomy

Surgical iridectomy is indicated when laser iridectomy cannot be performed or is insufficient ⁸⁴. Surgical iridectomy may be necessary in cases of cloudy corneas, flat anterior chamber, poor patient cooperation at the laser, or inability to substantially lower the IOP with medications after a failed laser peripheral iridotomy attempt. Surgical iridectomy involves surgically removing a portion of the iris to create a permanent opening and relieve the pupillary block ³. Surgical iridectomy is typically reserved for situations where laser treatment is not feasible or unsuccessful ³.

Paracentesis

Paracentesis can be perfomed in an acute setting. Technically, it can be difficult to perform on a phakic eye (an eye that still retains its natural lens) in pain with a shallow chamber, and there is a risk of permanent damage to the cornea, lens, and iris ². Devastating complications such as endophthalmitis and choroidal hemorrhage from a rapid pressure drop may occur ². Also the effects are typically short-term, because, as the ciliary body begins to form aqueous again, the intraocular pressure (IOP) will inevitably rise. This procedure can be used in cases of extreme intraocular pressure (IOP) elevation to “buy time” until medications take effect or iridotomy can be performed.

Lens extraction

Although lens extraction is effective in radically resolving pupillary block ⁸⁹, it carries a higher risk of intraoperative complications compared to cataract surgery on eyes without an acute attack of primary angle closure glaucoma. Lens extraction for primary angle closure glaucoma, particularly in the acute phase, is prone to complications and should be performed by a skilled surgeon ⁹⁰.

Chronic angle closure glaucoma treatment

Your eye specialist (ophthalmologist) is likely to treat chronic angle-closure glaucoma with laser iridotomy. Your eye specialist may also suggest cataract removal, which should make the progression of chronic angle-closure glaucoma go more slowly.

Medications

The role of medical therapy in acute angle closure attacks is to lower intraocular pressure (IOP), reduce pain, and clear corneal edema in preparation for iridotomy. Very few studies exist to address medical therapy in chronic angle closure glaucoma after laser iridotomy. In cases where elevated IOP becomes an issue, aqueous suppressants are helpful in reducing IOP ⁹¹. Prostaglandin analogues have been shown to be effective in lowering IOP, even in angles that are partially closed ⁹¹, ⁹². Evidence is not conclusive regarding their effectiveness in cases of 360° degrees of synechial closure ⁹³.

The medications below can be used, provided the patient has no condition contraindicating them.

Table 3. Glaucoma medications

Intraocular pressure lowering agents
Drug Class	Example	Mechanism	IOP Lowering	Dosing	Side Effects	Notes
Prostaglandin F2a analogues	Latanoprost (Xalatan) Travoprost (Travatan) Bimatoprost (Lumigan) Tafluprost (Zioptan; preservative free) Latanoprostene bunod (Vyzulta)	Increase outflow via uveoscleral pathway; decrease outflow resistance; mechanism unclear	Latanaprost and Travoprost: 25-32% Bimatoprost: 27-33% Tafluprost: 27-31% Latanoprostene: 29-32%1 As a class, most potent	Once daily, usually in evening	Ocular: Irritation, increased pigmentation of iris, lashes, and skin, hypertrichosis, prostaglandin associated periorbitopathy, loss of orbital fat over time	Often preferred as first line; highly effective at IOP lowering, with minimal systemic side effects. Among preservative containing drops, side effects tend to be greatest with bimatoprost, and least with latanoprost. Preservative free tafluprost may reduce irritation and ocular side effects and improve compliance in some patients.2
					Systemic:  flu-like symptoms, myalgias and arthralgias, nasal congestion; generally very well tolerated
Beta blockers (beta-adrenergic antagonists)	Non-Selective: Timolol maleate (Timoptic; Timoptic occudose = preservative free)Timolol hemihydrate (Betimol)Levobunolol (Betagan)MetipranololCarteolol HCl (partial alpha agonist)	Decrease aqueous production	20-30%	1-2 times daily OR Once daily in morning; more effective in AM	Ocular: Blurring, irritation, punctate keratitis; metipranolol associated with uveitis	Generally well tolerated from the perspective of ocular side effects. History of asthma or other airway disease is a strong contraindication. Suspect side effects of therapy in a patient with new onset depression, lethargy, or sexual dysfunction. Carteolol may have less detrimental effect on lipid profile in some patients.3 Betaxolol may be slightly less likely to cause asthma or lung disease exacerbation, but still carries significant risk.4
					Systemic: symptoms of b-blockade: heart block and bradycardia, decreased exercise tolerance, asthma and lung disease exacerbation, decreased symptoms of hypoglycemia in diabetes, depression, sexual dysfunction, lipid profile changes
	Selective b 1: Betaxalol	Same	15-20%	2 times daily
Alpha agonists (Alpha2-adrenergic agonists)	Apraclonidine HCl (Iopidine) Brimonidine tartrate (Alphagan)	Decreases aqueous production, increases uveoscleral outflow to lesser extent	20-30%	2-3 times daily	Ocular: Irritation, allergy, pruritis, dry eye	As a class, most likely to cause ocular irritation. High risk of apnea and CNS depression in infants with brimonidine. If CNS depression is a particular concern in any patient, apraclonidine does not cross blood-brain barrier and may be better choice.5,6
					Systemic: Lethargy, hypotension, vasovagal attack, headache, dry mouth and nose, insomnia, anxiety; risk of apnea and CNS depression in infants with brimonidine, apraclonidine will not cross blood-brain barrier
Carbonic anhydrase inhibitors	Oral: Acetazolamide (Diamox)Methazolamide (Neptazane)	Decreases aqueous production	15-20%	Acetazolamide: 500-1000mg per day in 2-4 doses Methazolamide: 25-50mg 2-3 times per day IV Acetazolamide: 5-10mg/kg q6-8 hours	Ocular: None	Sulfa allergies are often cited as a contraindication to use of these drugs, but there is little structural overlap with antibiotic sulfa drugs, and thus most patients allergic to sulfa drugs will not be affected by carbonic anhydrase inhibitors. 7
					Systemic: hypokalemia, poor tolerance of carbonated beverages, acidosis, paresthesias, blood dyscrasias, lethargy, nephrolithiasis, others
	Topical: Dorzolamide (Trusopt)Brinzolamide (Azopt)	Same	Generally not as effective as oral acetazolamide	2 times daily (only FDA approved for 3 times daily)	Ocular:  Induced myopia, blurred vision, stinging (less with Brinzolamide), allergic conjunctivitis, keratopathy	Generally very safe, often used in infants and pregnant women.
					Systemic: Less than with oral agents; bad taste in mouth
Parasympathomimetic agents	Pilocarpine HCl Echothiophate iodide (Phospholine iodide)	Miotics; increase trabecular outflow; ciliary muscles contract, put traction on scleral spur, open trabecular meshwork	15-25%	Pilocarpine: 2-4 times daily, usually 4 times daily Echothiopentate: 1-2 times daily, usually 2 times daily	Ocular: Posterior synechiae, intense miosis, keratitis, cataract, retinal detachment, angle closure, epiphora, induced myopia	Consider echothiophate in patients with a complicated anterior segment, e.g. aphakia, PK, ACIOL, etc., with inadequate pressure control. In certain patients it can be the sole effective drug.8
					Systemic: increased salivation, increased gastric secretion, abdominal cramps
Rho kinase inhibitors	Netarsudil (Rhopressa)	Increases trabecular outflow, decreases episcleral venous pressure9	Reduces IOP by ~5.5-6 mmHg regardless of baseline IOP10	FDA approved for once daily, more efficacious when used twice daily in studies	Ocular: conjunctival hyperemia and hemorrhage, corneal deposits (verticillata), blurry vision, epiphora, pruritis, punctate keratitis, eyelid erythema, conjunctival edema, foreign body sensation	Though not as effective at IOP reduction as other classes, may have benefit in patients with lower baseline IOP (IOP reduction less dependent on baseline IOP than other classes), and as an adjunct to other drugs, as mechanism of action (increases trabecular outflow rather than uveoscleral) is different from the most commonly used classes.10
					Systemic: None achieving statistical significance in recent studies10
Hyperosmotic agents	Mannitol 20% (parenteral) Glycerol 50% (oral)	Creates osmotic gradient, dehydrates vitreous		Mannitol: 0.5-2.0 g/kg Glycerol: 1-1.5 g/kg	Ocular: IOP rebound, aqueous flare
					Systemic: urinary retention, headache, nausea, vomiting, diarrhea, electrolyte disturbances, cardiac complications, contraindicated in renal failure

[Source ⁹⁴ ]

Eye drops

Glaucoma treatment often starts with prescription eye drops. Some may decrease eye pressure by improving how fluid drains from your eye. Others decrease the amount of fluid your eye makes. Depending on how low your eye pressure needs to be, more than one eye drop may be prescribed.

Prescription eye drop medicines include:

• Prostaglandins. These increase the outflow of the fluid in your eye, helping to reduce eye pressure (IOP). Medicines in this category include latanoprost (Xalatan), travoprost (Travatan Z), tafluprost (Zioptan), bimatoprost (Lumigan) and latanoprostene bunod (Vyzulta). Possible side effects include mild reddening and stinging of the eyes, darkening of the iris, darkening of the pigment of the eyelashes or eyelid skin, and blurred vision. This class of medicine is prescribed for once-a-day use.
• Beta blockers. These reduce the production of fluid in your eye, helping to lower eye pressure. Examples include timolol (Betimol, Istalol, Timoptic) and betaxolol (Betoptic S). Possible side effects include difficulty breathing, slowed heart rate, lower blood pressure, impotence and fatigue. This class of medicine can be prescribed for once- or twice-daily use depending on your condition.
• Alpha-adrenergic agonists. These reduce the production of the fluid that flows throughout the inside of your eye. They also increase the outflow of fluid in the eye. Examples include apraclonidine (Iopidine) and brimonidine (Alphagan P, Qoliana). Possible side effects include irregular heart rate; high blood pressure; fatigue; red, itchy or swollen eyes; and dry mouth. This class of medicine is usually prescribed for twice-daily use but sometimes can be prescribed for use three times a day.
• Carbonic anhydrase inhibitors. These medicines reduce the production of fluid in your eye. Examples include dorzolamide and brinzolamide (Azopt). Possible side effects include a metallic taste, frequent urination, and tingling in the fingers and toes. This class of medicine is usually prescribed for twice-daily use but sometimes can be prescribed for use three times a day.
• Rho kinase inhibitor. This medicine lowers eye pressure by suppressing the rho kinase enzymes responsible for fluid increase. It is available as netarsudil (Rhopressa) and is prescribed for once-a-day use. Possible side effects include eye redness and eye discomfort.
• Miotic or cholinergic agents. These increase the outflow of fluid from your eye. An example is pilocarpine (Isopto Carpine). Side effects include headache, eye pain, smaller pupils, possible blurred or dim vision, and nearsightedness. This class of medicine is usually prescribed to be used up to four times a day. Because of potential side effects and the need for frequent daily use, these medicines are not prescribed very often anymore.

Combination drugs:

• Timolol/Brinzolamide (Azarga-not available in the US)
• Timolol/Dorzolamide (Cosopt)
• Timolol/Latanoprost (Xalacom-not available in the US)
• Timolol/Bimatoprost (Ganfort-not available in the US)
• Timolol/Brimonidine (Combigan)
• Brinzolamide/Brimonidine (Simbrinza)

Because some of the eye drop medicine is absorbed into the bloodstream, you may experience some systemic side effects unrelated to your eyes. To minimize this absorption, close your eyes for 1 to 2 minutes after putting the drops in. You also may press lightly at the corner of your eyes near your nose to close the tear duct for 1 to 2 minutes. Wipe off any unused drops from your eyelid.

You may be prescribed multiple eye drops or need to use artificial tears. Make sure you wait at least five minutes in between using different drops.

Never change or stop taking your glaucoma medications without talking to your ophthalmologist. If you are about to run out of your medication, ask your ophthalmologist if you should have your prescription refilled.

Alpha agonists for glaucoma

Alpha agonists also called alpha2-adrenergic agonists work by reducing the amount of fluid your eye produces. Alpha agonists also increase the amount of fluid that drains out of the eyes. This helps lower eye pressure and, hopefully, saves your vision.

Possible side effects of alpha agonists include:

• red, stinging or painful eyes after using drops
• blurry vision
• allergy (redness, itching, tearing and swelling of the eye)
• a large (dilated) pupil
• headaches
• dry mouth
• feeling tired, weak or dizzy
• decreased blood pressure
• a fast or irregular heartbeat
• feeling nervous

Blurry vision, stinging, and redness may improve with time. But if the side effects still bother you, call your ophthalmologist. They may be able to lower your dose or change your medicine. Most side effects go away when the medicine is stopped. If you feel you need to stop taking this medication due to side effects or other concerns, please discuss with your doctor.

Beta-blockers for glaucoma

Beta-blockers also called beta-adrenergic antagonists work by reducing the amount of fluid your eye produces. This helps lower pressure in your eye and, hopefully, saves your vision.

Possible side effects of beta-blockers include:

• red, stinging or painful eyes after using drops.
• blurry vision
• breathing problems in people with asthma, emphysema, or chronic obstructive pulmonary disease (COPD)
• a slow or irregular heartbeat
• feeling tired
• depression
• dizziness
• a change in sex drive or sexual function
• getting overly tired during exercise
• in people with diabetes, low blood sugar symptoms becoming difficult to notice

Blurry vision, stinging, and redness may improve with time. But if the side effects still bother you, call your ophthalmologist. They may be able to lower your dose or change your medicine. Most side effects go away when the medication is stopped. Never suddenly quit taking your medicine unless your doctor tells you to.

Carbonic anhydrase inhibitors for glaucoma

Carbonic anhydrase inhibitors work by reducing the amount of fluid your eye produces. This helps lower eye pressure and, hopefully, saves your vision. Your ophthalmologist may have you take this medicine as an eye drop or by mouth as a pill.

Possible side effects of carbonic anhydrase inhibitors include:

• stinging eyes after putting drops in.
• red eyes
• blurry vision
• a skin rash (especially in people who are allergic to sulfa drugs)
• changes in how things taste to you (especially with carbonated drinks)
• bad taste or upset stomach (nausea)
• feeling tired
• decreased energy
• increase in urination (with the pills)
• tingling around the mouth and fingertips (with the pills)
• lower potassium (with the pills)

Blurry vision, stinging, and redness may improve with time. But if the side effects still bother you, call your ophthalmologist. They may be able to lower your dose or change your medicine. Most side effects go away when the medication is stopped. Never suddenly quit taking your medicine unless your doctor tells you to.

Miotics for glaucoma

Miotics also called cholinergic agents make your pupil constrict (get smaller or miosis), increasing the amount of fluid that drains out of the eye. This helps lower eye pressure and, hopefully, helps protect your vision.

Possible side effects of miotics include:

• blurred vision
• nearsightedness (trouble focusing on distant objects)
• dim vision with difficulty seeing in the dark or at night
• headache or brow ache (aching around eye)

While very rare, there is the possibility that your retina could detach. This is when the light-sensitive tissue lining the back of the eye pulls away. You would suddenly notice dark specks or spots (floaters) or flashing lights in your vision. If you have these symptoms, see your ophthalmologist immediately.

Side effects may go away after you take the medicine for a while. But if the side effects still bother you, call your ophthalmologist. They may be able to lower your dose or change your medicine. If you feel you need to stop taking this medication due to side effects or other concerns, please discuss with your doctor.

Prostaglandin analogs for glaucoma

Prostaglandin analogs also called prostaglandin F2a analogues work by increasing the drainage of fluid out of your eye. This helps lower eye pressure and, hopefully, saves your vision.

Possible side effects of prostaglandin analogs include:

• red, stinging or painful eyes after using drops.
• feeling like something is in your eye
• blurry vision
• a permanent change in your eye color (occurs mostly in hazel eyes)
• an increase in thickness, number and length of eyelashes
• darkening of the eyelid
• worsening of existing angina and asthma
• joint aches
• light sensitivity
• eyes gradually sinking deeper into their sockets, keeping eyelids from working properly

Blurry vision, stinging, and redness may improve with time. But if the side effects still bother you, call your ophthalmologist. They may be able to lower your dose or change your medicine. Most side effects go away when the medication is stopped. Never suddenly quit taking your medicine unless your doctor tells you to.

Oral medicines

Eye drops alone may not bring eye pressure down to the desired level. So an eye doctor also may prescribe oral medicine. This medicine is usually a carbonic anhydrase inhibitor. Possible side effects include frequent urination, tingling in the fingers and toes, depression, stomach upset, and kidney stones.

• Carbonic anhydrase inhibitors – oral acetazolamide’s maximum intraocular pressure reduction is reached in 2-4 hours and lasts for 6-8 hours. Intravenous acetazolamide drops the intraocular pressure (IOP) within 2 minutes with a peak effect noted by 10-15 minutes. In acute situations, a single dose of 500 mg acetazolamide should be given orally if the patient is not vomiting. Regular acetazolamide is preferred over the sustained-release sequel form because of quicker onset of action. If the patient is vomiting, acetazolamide can be given intravenously.
• Osmotic agents
  1. Mannitol can decrease the intraocular pressure (IOP) 30 mm Hg or more within 30 minutes of administration. The recommended intravenous dose is 0.5-1.5 g/kg body weight as a 15% or 20% solution, delivered at 3 to 5 mL/minute. Frail patients with cardiac or conditions may develop circulatory overload, pulmonary edema, congestive heart failure, and electrolyte imbalance. A rapid reduction in cerebral volume may result in subdural hematomas from vein rupture between the sagittal sinus and cortical surface. Therefore, patients receiving IV mannitol should be monitored in a hospital setting.
  2. Oral osmotic agents:
     • Glycerin: 1 to 1.5 g/kg body weight of a 50% solution. Onset of pressure reduction is typically 10 to 30 minutes. Avoid in diabetics because the increased caloric load can cause ketoacidosis.
     • Isosorbide is commercially available as a 45% (45 g/100 mL) solution (Ismotic; Alcon Surgical). The recommended dose is 1 to 1.5 g/kg body weight. Its effect is similar to glycerin’s but is safe for use in diabetics because it is not metabolized.
     • Although less common, oral agents can also cause subdural hematomas. Headache and gastrointestinal upset are common adverse reactions.

Surgery

These mainly focus on improving the drainage of aqueous humor fluid to lower pressure inside your eye. Surgery options include trabeculectomy, tube shunts, laser iridotomy and minimally invasive glaucoma surgeries (MIGS).

Laser peripheral iridotomy

Laser peripheral iridotomy creates a hole in the outer edge of the iris, leading to an opening of the angle in the majority of cases. After the angle is widened from the procedure, the trabecular meshwork is exposed and fluid outflow is enhanced. Laser peripheral iridotomy should be performed as soon as possible in the affected eye and in the contralteral eye to avoid an attack of acute angle closure glaucoma in the future ⁹⁵. Laser peripheral iridotomy ability to control IOP, however, may not be long-lasting, especially in eyes where glaucomatous optic neuropathy has already developed. Additional medications or surgical treatment is often necessary ⁹⁶. In cases where laser peripheral iridotomy does successfully lower IOP, eyes still need to be monitored routinely as IOP can increase months or years after the procedure ⁹⁷.

Persistent or progressive rise in IOP after laser peripheral iridotomy

• Damage to trabecular meshwork and/or formation of PAS has occurred when iridocorneal apposition present
• Pupillary block may recur if iridotomy becomes occluded
• Factors other than pupillary block causing angle closure may have gone unrecognized until after the LPI (e.g. plateau iris syndrome)
• Angle closure may have been superimposed on pre-exisitng open angle glaucoma or another eye condition causing IOP elevation, such as pseudoexfolation
• There may be co-existing chronic open angle glaucoma

What should I expect during laser iridotomy ?

Your eye is usually pretreated about half an hour before the procedure with drops that make the pupil small. Just before the laser iridotomy, anesthetic drops are placed to numb the surface of your eye, a lens is then placed on the eye to perform the laser. Laser iridotomy procedure usually takes 5-10 minutes and some patients may experience minor pain.

There is temporary blurriness of vision. Your eye may be a little red, light sensitive, and/or uncomfortable, and there may also be a mild headache due to the eyedrops given before the laser. The eye pressure is usually assessed within 30 minutes to 2 hours after the laser and anti-inflammatory eyedrops are usually prescribed for a few days.

Complications of laser peripheral iridotomy

The most common complications of laser peripheral iridotomy are transient bleeding at site of treatment, hyphema, postoperative pressure spike, and anterior chamber inflammation. Occasionally, patients may complain of a seeing a double image if the lid does not cover the iridotomy site. Extra visual images including bright lights or flashes, or double vision in the treated eye, may rarely occur. More severe but rare complications include aqueous misdirection and injury to the cornea, lens, or retina. There’s also a small chance of closure of the iridotomy may occur, requiring retreatment.

In about 25% of cases, the angle may not open. Depending on the situation, some patients might need further laser procedures, medical treatment, or surgery. It may be possible that your ophthalmologist suggests close follow up.

Who is a candidate for laser iridotomy?

Laser iridotomy is recommended in eyes which have the angle closed for at least half the eye and have high eye pressure or glaucoma. In eyes which have a closed angle but normal eye pressure and no optic nerve damage, laser iridotomy may be recommended as a preventive treatment. In a recent large prospective study of such eyes, it was shown that there was overall a low risk of developing high eye pressure but the risk was lower among eyes that received laser iridotomy compared to those that did not.

Will the laser iridotomy improve my vision?

No. Laser iridotomy is intended to preserve the vision and prevent glaucoma from appearing or progressing.

After laser iridotomy, will I still need to use my glaucoma medications?

Yes. Laser iridotomy is not a substitute for glaucoma eye drops in most cases if you’re already on medication prior to the procedure.

How long does the effect of my laser iridotomy last?

Although the angle widens in most cases after laser iridotomy, normal age-related changes may subsequently alter the angle region. Cataract formation could close the angle again and cataract extraction may be required.

Laser iridoplasty

Laser iridoplasty is a procedure that uses a laser to create controlled burns on the iris, shrinking and retracting the tissue to widen the angle between the iris and the cornea ⁹⁸. This widening helps improve fluid drainage in the eye, reducing pressure and preventing or treating angle-closure glaucoma. The procedure is typically performed under topical anesthesia and takes about 5 minutes.

Laser iridoplasty can be used in cases that are medically unresponsive, in which systemic carbonic anhydrase inhibitors must be avoided, when immediate iridotomy is not possible, or rarely when the attack continues despite a successful laser peripheral iridotomy. It is the procedure of choice for plateau iris syndrome when the angle fails to open and IOP remains elevated despite a patent peripheral iridotomy. In chronic cases of angle closure, iridoplasty may slightly decrease the formation of peripheral anterior synechiae ⁹⁹.

The laser creates controlled burns on the peripheral (outer edge) of the iris, causing the tissue to shrink and pull away from the trabecular meshwork, the drainage network in the eye. This retraction widens the angle between the iris and cornea, allowing fluid to flow more freely.

In acute angle closure, laser iridoplasty has been found effective and safe in short-term lowering of IOP, potential complications of laser iridoplasty include temporary eye pressure increase, iris atrophy from destruction of iris vessels, corneal burns, marked anterior chamber inflammation, and corneal endothelial damage ⁹³.

It is important to note that laser iridoplasty does not eliminate pupillary block, so iridotomy remains necessary if pupillary block is the mechanism of angle closure ¹⁰⁰.

Surgical peripheral iridectomy

Surgical peripheral iridectomy can be performed even when the eye has corneal opacity that makes laser irradiation difficult; however, it also carries risks associated with end ophthalmic surgery. Peripheral iridectomy is a surgical procedure that involves removing a small portion of the iris, the colored part of the eye, near its base. This procedure is primarily used to treat or prevent angle-closure glaucoma.

Goniosynechialysis

If the iris has been blocking the drainage angle for a long time, the iris may permanently stick to the drainage angle. This connection is called peripheral anterior synechiae (PAS). It blocks the flow of fluid out of the eye. Goniosynechialysis is a surgical procedure where peripheral anterior synechiae (PAS), which are adhesions between the iris and the trabecular meshwork, are separated. The goal is to improve drainage of aqueous humor (the fluid in the eye) and reduce intraocular pressure, particularly in cases of angle-closure glaucoma. Goniosynechialysis is preferred over trabeculectomy in eyes with minimal to moderate neuronal damage. Goniosynechialysis is often performed with a peripheral iridotomy, laser peripheral iridoplasty, or lens extraction to help prevent recurrent angle closure ¹⁰¹.

Trabeculectomy

Trabeculectomy a type of glaucoma surgery performed on the eye that creates a new pathway for fluid inside the eye to be drained. In trabeculectomy your eye surgeon creates a tiny flap in the sclera (white of your eye). He or she will also create a bubble (like a pocket) in the conjunctiva (the thin membrane that covers the inside of your eyelids and white part of your eye) called a filtration bleb. It is usually hidden under the upper eyelid and cannot be seen. Fluid will be able to drain out of the eye through the flap and into the bleb, lowering eye pressure. In the bleb, the fluid is absorbed by tissue around your eye. This procedure is often considered when other treatments like eye drops or laser surgery haven’t been effective

Glaucoma drainage devices

Your ophthalmologist may implant a tiny drainage tube in your eye. It sends the fluid to a collection area called a reservoir. Your eye surgeon creates this reservoir beneath the conjunctiva, lowering eye pressure. The fluid is then absorbed into nearby blood vessels.

Cyclodestructive procedure

Cyclodestructive procedures are surgical treatments for glaucoma that aim to reduce intraocular pressure (IOP) by reducing the production of aqueous humor, the fluid that fills the eye. This is achieved by destroying or damaging the ciliary body, the structure responsible for producing aqueous humor.

Cyclodestructive procedures are typically considered for patients with glaucoma who have not responded well to other treatments, such as medication or filtration surgery. They may also be used in cases where the risks of filtration surgery outweigh the benefits, especially in eyes with poor visual potential. In recent years, advances in cyclodestructive technology have led to their use in less severe cases of glaucoma as well

How it works:

• The ciliary body is selectively destroyed or damaged using various methods, such as lasers (cyclophotocoagulation), cryotherapy (freezing), or ultrasound.
• This destruction or damage reduces the ciliary body’s ability to produce aqueous humor.
• By decreasing aqueous humor production, the intraocular pressure (IOP) within the eye is lowered.

Types of cyclodestructive procedures:

• Transscleral cyclophotocoagulation (TS-CPC): This is a common procedure that uses a laser to deliver energy through the sclera (the white part of the eye) to the ciliary body.
• Endoscopic cyclophotocoagulation (ECP): This procedure uses an endoscope to access the ciliary body and deliver laser energy, offering a more targeted approach.
• High-intensity focused ultrasound (HIFU): This method uses focused ultrasound waves to damage the ciliary body.
  Cyclocryotherapy: This involves freezing the ciliary body to reduce aqueous humor production.

Cataract extraction

In primary angle closure glaucoma, since the lens is a key player in development of relative pupillary block, it makes sense that cataract extraction can lower IOP in both acute and chronic angle closure. Removal of the lens from an eye with a crowded anterior chamber opens the angle and may prevent or reduce peripheral anterior synechiae formation. In one study, early phacoemulsification was found to be better than laser peripheral iridotomy at preventing IOP rise after an acute angle closure event was controlled medically ¹⁰². Cataract extraction in the setting of an acute angle-closure attack, however, is technically difficult. The eye is inflamed with significant corneal edema, a shallow anterior chamber, an atrophic and atonic iris that is difficult to dilate, and possible zonular weakness. It may be more prudent to control the acute attack with medications and laser peripheral iridotomy first and then wait to perform surgery when the eye has recovered and is less inflamed.

In the chronic phase when patent laser iridotomy and medical treatment have failed to adequately control IOP, lens extraction many months after the initial attack has been found to reduce IOP and reduce the need for IOP medications ¹⁰³. Cataract extraction can be combined with goniosynechialysis to further improve IOP control in the short term ¹⁰⁴. Methods of goniosynechialysis include breaking synechiae with a heavy viscoelastic (viscogonioplasty), forceps, or a cyclodialysis spatula.

In lens-induced angle closure glaucoma, which includes phacomorphic glaucoma and angle closure due to forward subluxation of the lens, the definitive treatment is lensectomy. Acute attacks can be first controlled with medical therapy and/or laser peripheral iridotomy with lens extraction performed when the eye is quiet.

Filtration surgery

Filtration surgery has been performed for both acute and chronic angle closure glaucoma ¹⁰⁵. The indications to perform filtration surgery in primary angle closure glaucoma are similar to those for surgery in POAG. In chronic cases, surgery is considered if the optic neuropathy is progressing and IOP is at a level believed to be contributing to the progression. Reasons for performing filtration surgery in the setting of an acute closure attack include medical unresponsiveness, lack of laser availability, or signs of glaucomatous optic neuropathy already present ¹⁰⁶. The same techniques of filtration surgery are used as in primary open angle glaucoma, although some surgeons advocate tighter suturing of the trabeculectomy flap to avoid low IOP in the immediate postoperative period. A low IOP may contribute to further anterior chamber shallowing, which may lead to a higher rate of malignant glaucoma postoperatively ¹⁰⁷.

Whether to perform filtration surgery versus a tube shunt procedure for secondary angle closure glaucoma depends on the underlying etiology. In most cases, dealing with the underlying pathology (e.g. stopping topiramate in drug-induced glaucoma, removing the lens in lens-induced glaucoma) will slow or stop the progression of disease. If medical therapy is not sufficient to control IOP, even when the primary pathology has been addressed, glaucoma surgery may be necessary and filtration surgery may be appropriate. Conditions such as neovascular glaucoma and ICE, however, tend to do better with glaucoma drainage implants. (see below). It has been proposed that combined phacotrabeculectomy may be more effective at controlling IOP than cataract extraction alone. Recent study results have been mixed, with some showing phacoemulsification as being superior for deepening the chamber ¹⁰⁸, the two procedures being equal in terms of IOP control ¹⁰⁹ and combined procedures being superior for IOP control ¹¹⁰. Of note, one randomized control trial found that patients who undergo combined procedures have more postoperative complications and progression of their optic neuropathy compared to the phacoemulsification alone group ¹¹¹, so the risks and benefits of each procedure need to be carefully considered in each case until more definitive evidence is available.

Glaucoma drainage implants

A limited number of studies look at the use of tube shunt devices in primary angle closure glaucoma. Primary angle closure glaucoma eyes are often placed into the category of refractory glaucoma along with other types of glaucoma and thus are not separately evaluated. Based on the limited data available in these studies, tube implants appear effective in controlling IOP in primary angle closure glaucoma ¹¹². Drainage implants are considered more effective than filtering procedures in neovascular glaucoma and ICE syndrome because, in these diseases, a fibrovascular membrane often grows over the sclerostomy site causing bleb failure.

Other surgical procedures

• May be required depending on the etiology of the underlying disease.
• Aqueous misdirection: Nd:YAG laser can be used to disrupt the anterior vitreous in aphakic and pseudophakic eyes. If that is not successful, definitive surgical treatment in the form of vitrectromy with anterior hyaloid disruption combined with an anterior chamber deepening procedure may be indicated.
• Epithelial and/or fibrous downgrowth: radical surgery to remove the intraocular membrane and affected tissues may be necessary.
• Angle closure that develops after retina surgery may require removing or loosening encircling bands, opening up iridectomy sites, or removing silicone oil.

Surgical follow up

Patients typically need to be watched closely in the immediate postoperative period, sometimes weekly for several months. Once IOP control is achieved and the eye is stabilized, follow up can follow the schedule of routine primary angle closure glaucoma patients.

Secondary glaucoma treatment

The priority in the treatment of secondary glaucoma is to treat the causative disease whenever possible. A treatment method should be planned based on underlying mechanisms of IOP elevation.

Angle closure glaucoma prognosis

If you have treatment for angle-closure glaucoma, your outlook should be good. If you have acute angle-closure glaucoma, you need immediate treatment to preserve your vision. Without treatment, angle-closure glaucoma inevitably causes permanent vision loss and blindness. A study involving 116 cases of acute angle-closure glaucoma found that the timing of presentation and the duration of the acute episode were crucial factors in determining these patients’ outcomes ¹¹³. High IOP was found to have less impact on the long-term prognosis of this condition ¹¹³.

Primary angle closure suspects

Primary angle-closure suspect or anatomic narrow angle – an eye in which the anterior chamber angle recess has an abnormally narrow angular width. The peripheral iris is located close to, but not touching, the posterior pigmented trabecular meshwork. No peripheral anterior synechiae are present. IOP, optic nerve, and visual field are normal.

The overall likelihood of an individual with a anatomic narrow angle developing acute angle closure glaucoma in the United States is less than 10% ¹¹⁴. A prospective multicenter study, however, found that patients judged to be at risk for developing angle closure glaucoma by experienced ophthalmologists through careful slit lamp exam and gonioscopy had a 30% risk of developing angle closure within 5 years when no prophylactic intervention was performed ⁷².

In contrast, fellow eyes in which the other eye has already suffered an acute angle closure attack have a much worse prognosis without prophylactic treatment. An untreated fellow eye has a 40% to 50% chance of developing an acute primary angle closure attack over the next 5 to 10 years ¹¹⁵. An iridectomy or iridotomy virtually eliminates the risk ¹¹⁶. The long-term fate (4–6 years) in terms of IOP and glaucomatous optic neuropathy is good for most fellow eyes after laser peripheral iridotomy with the majority not requiring any additional glaucoma treatment and retaining good vision ¹¹⁷.

Acute angle closure glaucoma

In an eye suffering an acute angle-closure attack, the long-term outcomes vary depending on ethnicity (which may be a reflection of mechanism of angle closure), duration of attack, and severity of attack in terms of whether or not it can be aborted by medical treatment alone. If promptly treated, most (60%–75%) symptomatic episodes of angle closure recover without visual field or optic disc damage in the short term ¹¹⁸. Six months post-attack, one study reported 38% of eyes to have visual field loss secondary to nerve fiber bundle loss ¹¹⁸. In another study, 2 – 16 weeks after an attack, changes were noted in optic disk morphology, with preferential loss in the superotemporal and inferotemporal areas ¹¹⁹.

The longer the duration of an attack and the more difficult to manage, the worse the outcome for the eye, regardless of the initial IOP measurement ¹²⁰. Patients with a 24 to 72 hour delay in presentation had a relative risk of 2.78 for developing chronic glaucoma, whereas those requiring laser iridotomy to control IOP or a trabeculectomy had relative risks of 3.63 and 4.83, respectively ¹²⁰. In Singapore, risk of visual field loss was significant if the duration of symptoms was longer than 7 days ¹¹⁸.

Even despite successful termination of an acute attack by surgical iridectomy, late IOP increase is reported in 19% to 24% of cases ¹²¹. There may be ethnic differences in the rate of IOP control by laser peripheral iridotomy alone ⁵³. A greater extent of peripheral anterior synechiae, a high presenting IOP, and a larger cup to disc ratio have been reported as predictors of poor pressure control following iridotomy in Asian and African eyes ¹²². A significant portion of patients go on to develop primary angle closure glaucoma and require further medical or surgical intervention in an attempt to control their disease. Unfortunately, up to 20% these patients deteriorate to lose significant vision and are classified as blind in that eye ¹²³.

Chronic angle closure glaucoma

Asymptomatic angle-closure patients present with more severe visual field defects than symptomatic patients ¹²⁴. In one study which examined visual field loss on presentation, 52.8% of asymptomatic primary angle-closure glaucoma had end stage visual field loss by Advanced Glaucoma Intervention Study criteria compared to only 17.5% of symptomatic primary angle-closure glaucoma cases. Although presenting IOP was considerably higher in the symptomatic group, the level of IOP was not found to be a significant predictor for visual field outcome ¹²⁵. It is likely that the duration of elevated IOP has a major influence in causing optic nerve damage in primary angle-closure glaucoma, possibly more so than the level of IOP. Once glaucomatous optic neuropathy has developed, almost all cases will require further treatment to control IOP (94%–100%) ¹²⁶. Closer monitoring of IOP is recommended in chronic angle closure glaucoma compared to primary open angle glaucoma, despite the efficacy of medical therapy. Chronic angle-closure glaucoma tends to progress more quickly and fail medical therapy sooner than primary open angle glaucoma ¹²⁷. With aggressive management, however, chronic angle-closure glaucoma patients can maintain stable fields and long-term IOP control ⁶⁰.

Secondary angle closure glaucoma

The prognosis for secondary angle closure patients depends on the underlying cause. Early recognition of the underlying pathology and timely directed treatment helps to improve outcomes.

1. Michels TC, Ivan O. Glaucoma: Diagnosis and Management. Am Fam Physician. 2023 Mar;107(3):253-262. https://www.aafp.org/pubs/afp/issues/2023/0300/glaucoma.html[↩][↩][↩][↩][↩][↩][↩]
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