What is the approach to studying and managing glaucoma?

Approach to Studying and Managing Glaucoma

The most effective approach to studying and managing glaucoma involves understanding its pathophysiology as a chronic, progressive optic neuropathy characterized by optic nerve damage, retinal ganglion cell death, and retinal nerve fiber layer loss, with the goal of controlling intraocular pressure (IOP) to prevent vision loss. 1

Definition and Pathophysiology

• Glaucoma is the second leading cause of blindness worldwide after cataracts, affecting approximately 76 million people globally in 2020 1
• Primary open-angle glaucoma (POAG) is the most common form, characterized by open anterior chamber angles and optic nerve damage with or without elevated IOP 1
• Glaucoma damages the optic nerve and retinal nerve fiber layer, leading to progressive visual field loss 2

Risk Factors

• Elevated intraocular pressure (IOP) - the only modifiable risk factor for glaucoma progression 1
• Older age and family history of glaucoma 1
• African race or Latino/Hispanic ethnicity 1
• Thin central corneal thickness 1
• Low ocular perfusion pressure 1

Diagnostic Approach

Essential Clinical Assessment

• Complete ocular history (refractive error, trauma, prior surgery) 1
• Family history of glaucoma, including severity and outcomes 1
• Systemic history (asthma/COPD, migraine, Raynaud's syndrome, diabetes, cardiovascular disease) 1
• Race/ethnicity assessment 1

Key Diagnostic Tests

• Intraocular pressure (IOP) measurement with multiple readings at different times of day 1, 3
• Gonioscopy to assess anterior chamber angle and exclude angle closure or secondary causes 1, 3
• Central corneal thickness (CCT) measurement (thinner corneas increase progression risk) 1, 3
• Optic nerve head (ONH) examination to identify structural changes 1
• Retinal nerve fiber layer (RNFL) assessment 1
• Visual field testing using standard automated perimetry (SAP) 1
• Structural imaging:
  • Stereoscopic optic disc photography 1, 3
  • Optical coherence tomography (OCT) of ONH, RNFL, and macular ganglion cell complex 1, 3

Classification of Glaucoma Severity

• Mild: Definite optic disc, RNFL, or macular imaging abnormalities with normal visual field on standard automated perimetry 1
• Moderate: Definite optic disc, RNFL, or macular imaging abnormalities with visual field abnormalities in one hemifield not within 5 degrees of fixation 1
• Severe: Definite optic disc, RNFL, or macular imaging abnormalities with visual field abnormalities in both hemifields and/or loss within 5 degrees of fixation in at least one hemifield 1

Management Approach

Treatment Goals

• Control IOP in the target range 1
• Maintain stable optic nerve/RNFL status 1
• Preserve stable visual fields 1
• Maintain quality of vision and preserve quality of life 1

Target IOP

• Target IOP should be based on stage of glaucoma damage, baseline IOP, age, and additional risk factors 1
• Lowering pretreatment IOP by 25% or more has been shown to slow progression of POAG 1

Treatment Options

Pharmacotherapy (First-line)

• Prostaglandin analogs (PGAs) like latanoprost 0.005% once daily:

  • Reduce IOP by 6-8 mmHg (equivalent to timolol 0.5% twice daily) 4
  • Mechanism: Increase uveoscleral outflow of aqueous humor 4
  • Side effects: Increased iris pigmentation (may be permanent), eyelid skin darkening, eyelash changes 4

• Other medication classes include:

  • Beta-adrenoceptor antagonists 5
  • Alpha-adrenoceptor agonists 5
  • Carbonic anhydrase inhibitors 5
  • Cholinergics 5

Laser Therapy

• Options include argon laser trabeculoplasty and selective laser trabeculoplasty 5
• Both techniques increase aqueous humor outflow through the trabecular meshwork 5
• May be considered when medications are ineffective or not tolerated 2

Surgical Options

• Trabeculectomy, glaucoma drainage tube implantation, and ciliary body cyclodestruction 5
• Minimally invasive glaucoma surgeries (MIGS) have improved safety profiles with slightly less efficacy than traditional surgeries 2
• Consider when medication and laser therapy fail to control IOP 2

Monitoring and Follow-up

• Untreated low-risk patients: Follow-up every 12-24 months 1
• Treated or high-risk patients: More frequent follow-up (every 3-6 months) until stable 1
• Each follow-up visit should include:
  • Visual acuity measurement 1
  • Slit-lamp biomicroscopy 1
  • IOP measurement 1
  • Periodic ONH and RNFL evaluation 1

Special Considerations

Preperimetric Glaucoma

• Defined as glaucomatous optic nerve or RNFL damage without detectable visual field defects on SAP 3
• Treatment decisions based on risk assessment, with high-risk patients considered for IOP-lowering therapy 3
• More frequent monitoring may be necessary for high-risk patients 3

Quality of Life Impact

• Glaucoma significantly impacts quality of life, affecting daily activities like reading, walking, and driving 1
• Performance deteriorates with worsening glaucoma severity or when both eyes are affected 1
• People with glaucoma are more likely to experience falls and motor vehicle collisions 1
• Direct medical costs for glaucoma in the US are estimated at nearly $3 billion annually 1

Future Directions

• Neuroprotection strategies targeting retinal ganglion cell survival 6, 7
• Advanced gene therapy to elevate intraocular levels of neurotrophic factors 6
• Development of selective agonists of neurotrophin receptors 6