What is the pathophysiology and treatment of open-angle and closed-angle glaucoma?

Pathophysiology and Treatment of Open-Angle and Closed-Angle Glaucoma

Pathophysiology of Glaucoma

Open-Angle Glaucoma

• Primary open-angle glaucoma (POAG) is characterized by progressive optic nerve damage and retinal ganglion cell loss with open anterior chamber angles, resulting in characteristic visual field defects 1.
• The primary mechanism involves elevated intraocular pressure (IOP) causing mechanical stress on the optic nerve head and retinal nerve fiber layer (RNFL), though nearly 40% of POAG patients may not have elevated IOP during office measurements 1.
• Risk factors include older age, African race or Latino/Hispanic ethnicity, elevated IOP, family history of glaucoma, lower ocular perfusion pressure, type 2 diabetes mellitus, myopia, and thin central cornea 1.
• Oxidative stress, mitochondrial dysfunction, and neuroinflammation contribute to retinal ganglion cell damage and death, even in the absence of elevated IOP 2.
• Trabecular meshwork dysfunction in the anterior chamber contributes to impaired aqueous humor outflow and elevated IOP in POAG 2.

Closed-Angle Glaucoma

• Acute angle-closure glaucoma occurs when the peripheral iris blocks the trabecular meshwork, preventing aqueous humor outflow and causing a sudden, dangerous rise in IOP 3.
• Risk factors include Asian descent, hyperopia, older age (typically over 50), female gender, short axial length, thick and anteriorly positioned crystalline lens, shallow anterior chamber, steep corneal curvature, and family history 3.
• Clinical presentation includes blurred vision, halos around lights, severe eye pain, headache, eye redness, corneal edema, mid-dilated pupil, and potentially nausea and vomiting 3.
• Even patients with initially open angles can develop angle closure under certain conditions, such as with specific medications that cause pupillary block 4.

Treatment of Glaucoma

Open-Angle Glaucoma Treatment

• The primary goal of POAG treatment is to lower IOP to a target level that prevents further optic nerve damage and visual field loss 1.
• Initial target IOP should be at least 25% lower than pretreatment levels, with more aggressive targets for severe damage or rapid progression 1.
• Treatment options include:
  1. Medications: First-line therapy typically includes:
     • Topical beta-blockers (e.g., timolol) 5, 6
     • Prostaglandin analogs 6
     • Alpha-2 adrenergic agonists 6
     • Carbonic anhydrase inhibitors (e.g., acetazolamide) 7, 6
  2. Laser therapy: Laser trabeculoplasty is an effective alternative or adjunct to medications 1, 6.
  3. Incisional surgery: Reserved for patients in whom medical and laser treatments have failed 1, 6.

Closed-Angle Glaucoma Treatment

• Acute angle-closure glaucoma is a medical emergency requiring immediate intervention to prevent permanent vision loss 3.
• Initial medical therapy to lower IOP includes topical beta-blockers, alpha2-adrenergic agonists, carbonic anhydrase inhibitors, parasympathomimetics, and oral or intravenous hyperosmotic agents 3.
• Definitive treatment once IOP is controlled includes:
  1. Laser peripheral iridotomy (LPI): Creates an opening in the iris to allow aqueous flow 3.
  2. Surgical iridectomy: If LPI is not possible 3.
  3. Prophylactic laser iridotomy in the fellow eye: To prevent angle closure in the unaffected eye 3.
  4. Lens extraction: Growing evidence shows cataract extraction alone may substantially lower IOP in primary angle closure and primary angle-closure glaucoma patients 3.

Monitoring and Follow-up

• Regular assessment of optic nerve structure and function through clinical examination, imaging, and visual field testing 1.
• Severity of glaucoma can be classified as:
  • Mild: Optic disc/RNFL abnormalities with normal visual field 1
  • Moderate: Optic disc/RNFL abnormalities with visual field abnormalities in one hemifield not within 5 degrees of fixation 1
  • Severe: Optic disc/RNFL abnormalities with visual field abnormalities in both hemifields and/or loss within 5 degrees of fixation 1
• For angle-closure patients after treatment, follow-up should include confirmation of iridotomy patency, IOP measurement, dark-room gonioscopy, and fundus examination 3.

Important Considerations and Pitfalls

• Delayed diagnosis of angle-closure glaucoma can lead to permanent vision loss, with 18% of eyes becoming blind and 48% developing glaucomatous optic neuropathy within 4-10 years following untreated acute angle closure 3.
• In angle-closure glaucoma, recognize plateau iris configuration that may persist after iridotomy 3.
• Patients with asthma require careful consideration when selecting glaucoma medications, as some may exacerbate respiratory symptoms 8, 5.
• Ocular surface disease due to topical glaucoma treatments can negatively impact treatment efficacy and surgical outcomes 2.