Chronic Closed Angle Glaucoma

Etiology

Peripheral anterior synechiae (PAS) formation between the peripheral iris and trabecular meshwork of the iridocorneal angle is the main etiologic factor in chronic angle closure. 

Risk factors for angle-closure include:[2]

• Race: Asian ethnicity
• Age: above 40 years
• Sex: 2-3 times more common in females 
• Ocular biometry: shallow anterior chamber depth, short axial length, increased lens thickness, increased anterior curvature of the lens, small corneal radius of curvature. 
• Family history of angle-closure
• Refractive error: hyperopia. 
• Recurrent intraocular inflammation. 
• Cataract with an intumescent lens. 
• Plateau iris

In susceptible individuals, some systemic drugs can induce angle-closure:[3]

• Nebulized bronchodilator (such as salbutamol, ipratropium bromide)
• Selective serotonin reuptake inhibitors (SSRIs)
• Tricyclic antidepressant
• Some cold and flu medications
• Muscle relaxant
• Anti-epileptic
• Parasympatholytic
• Sympathomimetics

Epidemiology

Glaucoma is the leading cause of irreversible blindness worldwide. Primary open-angle glaucoma is three times more common than angle-closure glaucoma, although angle closure is responsible for 50% of blindness caused by glaucoma. The primary risk factors for angle-closure include older age, female gender, and Asian or Eskimoan race.[1]

Pathophysiology

Angle-closure impairs aqueous outflow by obstructing, damaging, or degenerating trabecular meshwork, leading to an increase in intraocular pressure and subsequent glaucomatous optic nerve damage. Angle-closure is characterized by the presence of irido-trabecular contact. This contact may lead to chronic closure of the angle due to peripheral anterior synechiae formation. If a glaucomatous optic neuropathy is also present, this is termed chronic angle-closure glaucoma.

The major mechanisms leading to angle closure include:[1]

• Pupillary block
• Anomalies at the level of the iris and/or ciliary body. These anomalies may result in a plateau iris configuration.
  • Thicker iris 
  • Anterior iris insertion
  • Anterior ciliary body position
  • Anteriorly positioned ciliary processes 
• Anomalies at the level of the lens
  • Cataract or lens intumescence
  • Lens subluxation
  • Microspherophakia
• Anomalies posterior to the lens
  • Aqueous misdirection
• Other secondary causes
  • Uveitis
  • Trauma
  • Iris neovascularization
  • Surgery
  • Iridociliary cysts or tumors
  • Retinal gas or silicone oil tamponade
  • Massive vitreous hemorrhage
  • Iridocorneal endothelial syndrome
  • Epithelial and/or fibrous ingrowth after surgery or trauma
  • Uveal effusion
  • Retinopathy of prematurity
  • Congenital anomalies

History and Physical

Chronic angle-closure does not cause symptoms in the majority of patients. Some individuals may present with the following symptoms:[1]

• Visual disturbances such as "halos" and/or a reduction in vision
• Ocular discomfort 

Medical History

• Ophthalmic history of surgery, trauma, recurrent inflammation, acute angle-closure glaucoma, hyperopia, or long-standing cataract. 
• Systemic medical history of diabetes mellitus, connective tissue disease leading to uveitis (such as rheumatoid arthritis, spondylitis).
• Use of medications (see above) that may precipitate angle closure in susceptible patients. 
• Family history of angle-closure glaucoma. 

Clinical Signs

• Visual acuity may be normal.
• Elevated intraocular pressure, usually above 21 mmHg. 
• Peripheral anterior synechiae of various degrees on gonioscopy.
• Optic nerve head damage.
• Visual field loss is typical of glaucoma.

Evaluation

The investigations for angle-closure glaucoma are as under:

Gonioscopy: Indentation gonioscopy is the standard technique used to visualize the angle dynamically to determine the extent of angle-closure due to peripheral anterior synechiae. 

Tonometry: Measurement of intraocular pressure. The gold standard is Goldmann applanation.[1]

Pachymetry: Central corneal thickness to adjust intraocular pressure according to corneal thickness.

Slit-lamp examination: Anterior segment examination.

Indirect ophthalmoscopy: Optic nerve head clinical examination.

Perimetry: Visual field analysis. 

Optical Coherence Tomography[4]

• Optic nerve head evaluation: Retinal nerve fiber layer thickness and the structure of the optic nerve head.
• Macula evaluation: Macular structural parameters such as macular retinal nerve fiber layer, ganglion cell layer with inner plexiform layer, and ganglion cell complex.
• Anterior segment: Examine the extent of peripheral anterior synechiae and iridocorneal angle.

Ultrasound biomicroscopy: This can assist in evaluating the position of the ciliary body, lens position, and presence of an iridociliary cyst or mass.[2]

A darkroom-prone provocation test has been described but is not useful in discriminating primary angle-closure suspects from those with open angles.[5]

Treatment / Management

Treatment includes the release of pupil block, if present, by means of iridotomy, iridectomy, or lens extraction. If the intraocular pressure cannot be controlled medically after releasing any pupil block, surgery may be required. Because these eyes may be more likely to develop aqueous misdirection, precautions must be considered when undertaking surgery.

Medical Treatment

• Aqueous suppressants: Carbonic anhydrase inhibitor topical/oral (dorzolamide, brinzolamide acetazolamide, methazolamide), beta-blocker (timolol, levobunolol), alpha-agonist (brimonidine tartrate, apraclonidine). 
• Increase trabecular outflow: The effectiveness of medications with this mechanism of action (rho kinase inhibitors, pilocarpine) may be reduced as the trabecular meshwork is obstructed due to peripheral anterior synechiae. 
• Increase uveo-scleral outflow: Prostaglandin analogs (latanoprost, bimatoprost, travoprost, tafluprost); however, these may increase inflammation so if there is any chronic inflammatory etiology leading to the chronic closed-angle it may be avoided.

Laser Treatment

• Iridotomy: This can be performed using an Nd-Yag laser with or without argon laser pre-treatment[6]
• Argon Laser Peripheral Iridoplasty: This may be beneficial in reducing appositional angle closure caused by non-pupillary block mechanisms, such as plateau iris syndrome.[7]
• Micropulse trans-scleral cyclophotocoagulation[8]
• Continuous transscleral cyclophotocoagulation. This has traditionally been reserved for refractory glaucoma with poor visual potential.
• Endocyclophotocoagulation.
(B2)

Surgical Treatment 

• Phacoemulsification/lens extraction[9]
• Surgical iridectomy
• Trabeculectomy
• Phacoemulsification in a patient with less than 180 degrees of angle-closure[10]
• Phacoemulsification with trabeculectomy in more than 180 degrees of angle-closure
• Phacoemulsification with endocyclophotocoagulation[11]
• Phacoemulsification with viscogoniosynechiolysis with endocyclophotocoagulation[12]
• Glaucoma drainage device
(A1)

Differential Diagnosis

Chronic angle-closure glaucoma must also be differentiated from open-angle glaucoma (primary and secondary) as well as causes of nonglaucomatous optic neuropathy such as ischemic, compressive, and hereditary optic neuropathies.[13] Many different etiologies may lead to chronic angle-closure glaucoma (see pathophysiology section above). Determining the mechanism of angle closure is important as treatments may vary depending on the cause of the angle closure.

Primary angle-closure consists of other subtypes which must also be considered in the differential diagnosis:[1]

• Primary angle-closure suspect
• Acute angle-closure
• Intermittent angle closure
• Status post-acute angle-closure attack

Prognosis

The prognosis of chronic angle-closure glaucoma is variable and likely depends on many factors such as the stage of disease at detection. A prophylactic peripheral iridotomy does not guarantee the prevention of angle-closure glaucoma as over 50% of the fellow eyes may still develop chronic angle-closure glaucoma over time despite receiving a peripheral iridotomy at the time of an attack of angle-closure in the contralateral eye.[14] 

More extensive peripheral anterior synechiae and narrower width of the drainage angle are associated with higher intraocular pressure and a larger vertical cup-to-disc ratio.[15] Higher mean intraocular pressure and history of acute angle-closure are associated with poorer visual field and acuity outcomes with 7% progressing to blindness while on treatment over a ten-year period in a Chinese population.[16]

Complications

Glaucomatous damage to the optic nerve may lead to visual field loss, decreased visual acuity, and complete blindness. Damage to the corneal endothelium may occur, leading to corneal decompensation. Blind eyes with end-stage glaucoma may also become phthisical. Aqueous misdirection syndrome may develop more frequently in eyes with chronic angle-closure glaucoma following surgery.