Glaucoma

Overview

Definition

• Glaucoma is an optic neuropathy that results in a characteristic atrophy of the optic nerve head with corresponding progressive visual field defects.
• Often associated with elevated intraocular pressure (IOP), but can occur in normal IOP (normal: 8–21 mm Hg)

Epidemiology

• Glaucoma: 2nd-leading cause of permanent blindness worldwide (after cataract) 
• Typically occurs after age 40
• Primary open-angle glaucoma: most common type in the United States
• Angle-closure glaucoma: more common in Asian population

Physiology

• Aqueous humor
  • Clear fluid produced by the ciliary body
  • Functions:
    • Preserves intraocular pressure
    • Supplies nutrients and oxygen to cornea and lens
    • Removes waste products from the same structures
  • Drainage: fluid from ciliary body → posterior chamber → through the pupil → anterior chamber (angle of cornea and iris) → 90% to trabecular meshwork → canal of Schlemm → episcleral veins (venous circulation)
• Intraocular pressure
  • Determined by the aqueous humor formation and outflow
  • Autonomic nervous system effects on IOP:
    • Parasympathetic system: ↓ IOP
      • Ciliary muscle contraction → increased pore size of trabecular meshwork → promotes fluid drainage and decreased pressure
      • Pupillary sphincter muscle contraction (miosis) → opens trabecular meshwork → promotes fluid drainage and decreased pressure
    • Sympathetic system: ↑ IOP
      • Ciliary muscles relaxation → decreased pore size of meshwork → increased intraocular pressure
      • Pupillary dilator muscle contraction (mydriasis) → blocks trabecular meshwork → increased pressure

Types of glaucoma

• Primary open-angle glaucoma (POAG): 
  • Overproduction or decreased outflow of aqueous humor
  • More common than angle-closure glaucoma
• Primary angle-closure glaucoma (PACG): 
  • Physical blockage of aqueous humor outflow due to anatomic predisposition 
• Both types have secondary forms (caused by other eye conditions, trauma, medications).
• Subsets:
  • Juvenile open-angle glaucoma: 
    • Affects younger population
    • Less common and presents as gradual increase in IOP
  • Normal-tension or low-tension glaucoma:
    • Characteristic optic disc cupping and peripheral visual field defect
    • IOP is normal.

Open-angle Glaucoma

Risk factors

• Advanced age
• Family history of glaucoma
• African American race
• Other conditions: hypertension, diabetes, elevated IOP

Etiology

• Primary open-angle glaucoma due to idiopathic overproduction or decreased drainage of aqueous humor
• Secondary causes: uveitis, trauma, steroids, and retinopathy

Clinical presentation

• Initially, asymptomatic (even with elevated IOP)
• Incidental finding on comprehensive eye examination
• As chronic disease progresses: gradual loss of bilateral peripheral vision → loss of central vision (late manifestation)
• Blindness, if left untreated

Diagnosis

• Diagnostic triad:
  1. Optic disc changes
  2. Visual field changes 
  3. Elevated IOP
• Fundus examination:
  • “Cupping”: hollowed-out appearance of optic nerve
  • Increased cup-to-disc ratio (cup diameter > 50% of vertical disc diameter)
• Visual field testing: automated perimetry
• Intraocular pressure:
  • Elevated IOP (> 21 mm Hg): glaucoma suspect; refer to ophthalmology
  • IOP > 40 mm Hg: emergency referral
  • Affected by corneal thickness and diurnal variation
  • Goldmann applanation tonometry: measures IOP but affected by corneal thickness (↑ thickness, false ↑ in pressure) 
  • Pachymetry: measures corneal thickness; helps in accuracy of IOP reading
  • Pneumotonometry/air-puff tonometry: 
    • Non-contact
    • Uses air to flatten cornea
• Gonioscopy: 
  • Allows ophthalmologist to visualize angle between cornea and iris
  • “Open” angle: 20–45 degrees
• Optical coherence tomography:
  • Non-contact
  • Provides digital cross-sectional imaging of optic nerve, retina, and anterior chamber

Management

• Goals:
  • Prevent progression of optic nerve changes
  • Prevent visual field deterioration
• Pharmacologic therapy (topical agents):
  • Prostaglandin F2α agonists (preferred initial therapy)
    • Increase drainage of aqueous humor
    • Once- to twice-daily dosing
    • No systemic side effects
    • Side effects: eye irritation, hyperemia, lengthened lashes
    • Latanoprost, bimatoprost, tafluprost
  • β-blockers 
    • Decrease aqueous humor production 
    • Once–twice daily dosing
    • More affordable than prostaglandin agonists
    • Contraindicated in pulmonary disease (can ↑ airway obstruction) or heart disease (worsens bradycardia, heart failure; ↑ heart block, hypotension)
    • Timolol (non-selective), betaxolol
  • α-adrenergic agonists
    • Dual effect: increase outflow and decrease production of aqueous humor
    • Side effects: allergic conjunctivitis, hyperemia
    • Also with systemic effects: hypertension; caution in cardiovascular disease
    • Brimonidine, apraclonidine
  • Carbonic anhydrase inhibitors
    • Decrease in aqueous humor production
    • Not as effective in reducing IOP
    • Dorzolamide
  • Cholinergic agonists
    • Increase aqueous outflow
    • Rarely used
    • Side effects: fixed, small pupils
    • Pilocarpine
  • Rho-kinase inhibitor
    • Increase aqueous outflow
    • New medication: netarsudil
• Laser therapy:
  • Laser trabeculoplasty
    • Increases outflow of aqueous humor through trabecular network
    • Can be first-line therapy or an option in failed medical therapy or medication intolerance
  • Diode laser cyclophotocoagulation (DLCP)
    • Ablation of ciliary process
    • For refractory glaucoma
• Surgical treatment (trabeculectomy):
  • Trabeculectomy
    • Creates a bleb in sclera to allow drainage of the aqueous humor
    • Primary treatment for advanced glaucoma (severe visual field loss)
    • Risks of cataracts, scarring, hypotony
  • Minimally invasive glaucoma surgery (MIGS)
    • Conjunctiva-sparing surgery

Angle-closure Glaucoma

Risk factors

• Female
• Age > 60 years
• Hyperopia
• Family history of angle-closure glaucoma
• Pseudoexfoliation
• Asians (Southeast Asians, Chinese) and Inuit

Etiology

• Results from blockage of aqueous humor outflow from posterior chamber to the anterior chamber
• Anatomic predisposition:
  • Shallow anterior chamber
  • Lens size
  • Anterior location of the iris-lens diaphragm
  • Narrow entrance to the anterior chamber angle
• Lens is located forward, in contact with the iris, slowing aqueous drainage → pupillary block (fluid no longer flows normally through the pupil)
• Aqueous fluid accumulates → ↑ IOP → compression of optic disc
• Secondary causes: medication (topiramate), trauma or surgery, tumor, lens subluxation in Marfan’s syndrome

Clinical presentation

• Acute angle-closure glaucoma:
  • Medical emergency!
  • More rapid ↑ in IOP: more symptoms
  • Often occurs in evening; lower light levels cause pupillary dilation (mydriasis)
  • Symptoms:
    • Severe eye pain, headache
    • Photophobia
    • Blurred vision
    • Halos around bright lights
    • Nausea and vomiting
  • Signs:
    • Red-eye with a “steamy cornea”
    • Pupil mid-dilated and non-reactive to light
    • Absence of accommodation and light reflex
• Chronic closed angle-closure glaucoma:
  • Less severe and may be asymptomatic
  • Due to partial angle blockage or gradual angle closure: slow ↑ in IOP
  • Symptom: gradual loss of peripheral vision then decrease in central vision

Diagnosis

• IOP: 
  • Diagnostic in acute angle-closure glaucoma (no imaging needed) 
  • Tonometry can show 60–80 mm Hg pressure in an acute attack.
• Undilated fundus examination:
  • Pupillary dilation will exacerbate condition.
  • Cupping of optic disc
  • Scattered opacities on anterior lens
• Gonioscopy:
  • Ophthalmologist able to view the angle
  • Use of special lens with slit lamp
• Anterior segment optical coherence tomography:
  • High-definition imaging showing details of anterior chamber
  • Non-contact
  • Mechanism of angle closure can be discerned from findings.
• Ultrasound biomicroscopy
  • Ultrasound of anterior chamber, showing angle
  • Not widely available

Management

• Acute angle-closure glaucoma
  • Refer immediately to ophthalmology
  • Empiric treatment can be started when IOP significantly elevated (> 40 mm Hg) with:
    • 0.5% timolol (1 drop)
    • 1% apraclonidine (1 drop)
    • 2% pilocarpine (1 drop)
    • Systemic medications: (carbonic anhydrase inhibitor: acetazolamide 500 mg PO or IV; alternative: mannitol IV once angle-closure confirmed; not in diabetics)
    • Same eye drops after ½–1 hour (if IOP still elevated)
  • Laser peripheral iridotomy 
    • Definitive management after acute episode subsides
    • Relieves pupillary block by allowing aqueous flow in a different route
    • Surgical iridotomy: option if laser iridotomy not possible 
• Chronic angle-closure glaucoma
  • Laser peripheral iridotomy
  • Avoid anticholinergic agents and decongestants while awaiting surgery

Differential Diagnosis

The differential diagnoses of glaucoma include the following conditions:

• Cataracts: a decrease in vision due to clouding of the lens, which presents as painless, often bilateral blurry vision and glare problems. Cataracts are the leading cause of blindness worldwide. Although the condition can occur at any age, most cases affect those > 60 years.
• Ischemic optic neuropathy (ION): loss of vision secondary to reduced blood flow causing optic nerve damage. The condition commonly occurs after age 50 and can be arteritic (due to giant cell arteritis) or nonarteritic (other causes). Nonarteritic ION is more frequent and presents as an acute, painless visual loss (monocular) associated with altitudinal visual field defect. Patients often have vascular risk factors such as diabetes and hypertension.
• Conjunctivitis: inflammation of the conjunctiva, the outer lining of the eye. Etiology can be infectious or non-infectious. Patients present with redness and discharge on 1 or both eyes. Bacterial conjunctivitis often has purulent discharge, whereas viral causes have watery discharge.
• Uveitis: inflammation of the uvea or the middle layer of the eye. Uveitis can be caused by infections (herpes, syphilis) or can be related to systemic inflammatory disease (inflammatory bowel disease, rheumatoid arthritis). The condition can present with red-eye with pain (anterior uveitis) or without pain (intermediate and posterior uveitis). Symptoms can include visual floaters.