How does chronic inflammation affect the retinal nerve fiber layer (RNFL)?

Mechanisms of Retinal Nerve Fiber Layer Changes in Chronic Inflammation

Chronic inflammation causes retinal nerve fiber layer (RNFL) thinning through inflammatory mediators, particularly IL-17, which leads to progressive neurodegeneration and structural damage over time. 1

Acute vs. Chronic Inflammatory Effects on RNFL

Inflammation affects the RNFL differently depending on whether it is acute or chronic:

Acute Phase

• RNFL initially thickens during acute inflammatory episodes
  • In acute uveitis flares, RNFL thickness increases significantly (132.17±35.54μm during flares vs. 107.66±17.10μm after resolution) 2
  • This thickening represents edema and inflammatory cell infiltration
• In acute primary angle closure glaucoma (PACG), RNFL shows significant swelling immediately after acute attacks (121.49±23.84μm) 3

Chronic Phase

• RNFL progressively thins over time with chronic inflammation
  • In eyes with acute PACG, initial RNFL thickening resolves and transitions to thinning over 6 months (78.98±19.17μm) 3
  • Chronic PACG shows diffuse RNFL thinness without the initial swelling phase 3
• Multiple sclerosis patients without history of optic neuritis show reduced RNFL thickness (89.1μm vs. 98.0μm in controls), indicating subclinical neurodegeneration 4

Inflammatory Mediators and Mechanisms

Key Inflammatory Mediators

• IL-17 plays a central role in inflammatory damage to the optic nerve:
  • IL-17 mRNA is highly abundant in optic nerve during inflammation 1
  • Neutralizing IL-17 prevents RNFL atrophy in experimental autoimmune encephalomyelitis 1
  • IL-17 is produced by both CD4+ T cells and γδ T cells in the optic nerve 1

Cellular Mechanisms

• Inflammatory cell infiltration varies by location:
  • Optic nerve inflammation is characterized by high fractions of Ly6G+ granulocytes 1
  • T-cell differentiation toward Th17 phenotype is more pronounced in optic nerve than spinal cord 1

Systemic and Local Factors Affecting RNFL in Inflammation

Intraocular Pressure (IOP)

• Elevated IOP is a significant risk factor for RNFL damage in inflammatory conditions:
  • In uveitic eyes with elevated IOP, RNFL thinning occurs even before optic disc or visual field changes 5
  • Inferior quadrant RNFL thinning is an early sign of glaucomatous damage in uveitic eyes with ocular hypertension 5
  • Risk factors for RNFL defects include higher peak IOP and longer duration of follow-up 5

Disease-Specific Factors

• In multiple sclerosis, RNFL thinning occurs predominantly in:
  • Temporal quadrant (56.6μm vs. 67.8μm in controls) 4
  • Inferior quadrant (117.9μm vs. 132.1μm in controls) 4
• Macular thickness also decreases in chronic inflammation (280μm vs. 287μm in controls) 4

Gender and Anatomical Factors

• Male sex is a risk factor for elevated IOP in uveitis 5
• Anterior uveitis carries higher risk for IOP elevation than other forms 5

Clinical Implications and Monitoring

• RNFL thickness measurement should be performed during quiescent periods of inflammation to accurately assess for glaucomatous damage 5
• OCT provides a non-invasive method to monitor RNFL changes as a biomarker of inflammation 2
• Early detection of RNFL thinning, particularly in the inferior quadrant, may identify patients requiring more aggressive treatment before irreversible damage occurs 5

Common Pitfalls and Caveats

• RNFL measurements during active inflammation may be misleading due to inflammatory thickening masking underlying damage
• Failure to account for the biphasic nature of RNFL changes (initial thickening followed by thinning) may lead to misinterpretation of disease progression
• Different patterns of RNFL damage occur in different inflammatory conditions, requiring disease-specific monitoring approaches
• Macular edema does not significantly affect RNFL thickness measurements, allowing for reliable assessment even in its presence 2