What is the physiological basis behind visual field defects in glaucoma?

Physiological Basis of Visual Field Defects in Glaucoma

Visual field defects in glaucoma result from the progressive death of retinal ganglion cells (RGCs) and degeneration of their axons, which form the optic nerve, leading to characteristic patterns of vision loss that correspond anatomically to the specific nerve fiber bundles damaged. 1

Primary Pathophysiological Mechanism

Glaucoma is fundamentally a chronic, progressive optic neuropathy characterized by acquired atrophy of the optic nerve and loss of RGCs and their axons. 1 The disease causes:

• Progressive RGC death that begins at the optic nerve head and extends to involve the entire retinal ganglion cell layer 2, 3
• Axonal degeneration of RGC fibers as they pass through the lamina cribrosa and form the optic nerve 1, 2
• Structural changes in the optic nerve head, including extracellular matrix remodeling and astrocyte responses that alter susceptibility of remaining nerve fibers to damage 4

Anatomical Correlation: Structure to Function

The characteristic visual field defects in glaucoma directly reflect the anatomical organization of retinal nerve fiber bundles:

• Arcuate nerve fiber bundles from the superior and inferior retina are preferentially damaged, especially at the superior and inferior poles of the optic disc 1
• This anatomical vulnerability produces the classic arcuate scotomas (arcuate field defects) that respect the horizontal midline 1
• Nasal step defects occur when damage affects the arcuate bundles asymmetrically 1
• Paracentral depressions in clusters of test sites represent focal areas of RGC loss 1

Visual field loss characteristically shows greater defects in one hemifield compared to the opposite hemifield across the horizontal midline in early to moderate disease. 1

Progressive Nature of Damage

The damage follows a predictable progression pattern:

• Early stage: Diffuse or localized RNFL thinning, particularly at inferior or superior poles, often precedes detectable visual field defects 1, 5
• Moderate stage: Visual field abnormalities appear in one hemifield but remain outside 5 degrees of fixation 1
• Severe stage: Visual field abnormalities affect both hemifields and/or involve loss within 5 degrees of fixation in at least one hemifield 1

Pressure-Related and Pressure-Independent Mechanisms

Elevated intraocular pressure (IOP) is the major modifiable risk factor that triggers RGC death and optic nerve damage, though nearly 40% of patients with characteristic glaucomatous damage may not have elevated IOP measurements during office hours. 1

The mechanisms of damage include:

• Direct mechanical stress on RGC axons as they pass through the lamina cribrosa at the optic nerve head 4
• Chronic IOP elevation produces progressive changes in the optic nerve head and retina that alter susceptibility of remaining nerve fibers to pressure 4
• Vascular compromise and ischemic injury to the optic nerve head 4
• Neurotrophin deprivation as RGCs undergo changes in neurotrophin response prior to cell death 4

Clinical Implications

The higher the level of IOP, the greater the likelihood of glaucomatous field loss and optic nerve damage. 6, 7 This explains why:

• Lowering IOP reduces the risk of developing glaucoma and slows disease progression 1
• A reasonable initial treatment goal is to reduce IOP 20-30% below baseline 1
• Some patients continue to lose vision despite well-controlled IOP, suggesting pressure-independent mechanisms of ongoing RGC death 3, 4

Common Pitfall

Structural optic nerve damage often precedes detectable visual field defects on standard automated perimetry. 1, 5 This means that by the time visual field loss is detected, significant RGC loss has already occurred—emphasizing the critical importance of careful optic nerve head and RNFL examination for early detection. 1, 5