Why do steroids increase intraocular pressure?

Mechanism of Steroid-Induced Intraocular Pressure Elevation

Steroids increase intraocular pressure primarily by decreasing aqueous humor outflow through the trabecular meshwork, causing fluid buildup that raises pressure within the eye. 1

Pathophysiological Mechanisms

Primary Mechanism: Trabecular Meshwork Changes

• Morphological changes: Steroids induce structural alterations in the trabecular meshwork cells, including:

  • Endoreplication of nuclei
  • Increase in cell size
  • Excessive production of extracellular matrix proteins 2

• Molecular changes:

  • Increased production of a 56kD glycoprotein identified as myocilin, transcribed by the GLC1A gene 2
  • Accumulation of glycosaminoglycans and fibronectin in the extracellular matrix
  • Decreased phagocytic activity of trabecular meshwork cells

Secondary Mechanisms

• Decreased proteolytic activity: Steroids inhibit the breakdown of extracellular matrix components
• Cytoskeletal changes: Reorganization of microfilaments and microtubules in trabecular cells
• Increased expression of glucocorticoid receptors: Enhanced steroid sensitivity in the trabecular meshwork

Risk Factors for Steroid-Induced IOP Elevation

Patient-Related Factors

• Pre-existing glaucoma: 46-92% of patients with primary open-angle glaucoma are steroid responders 2
• Family history of glaucoma: First-degree relatives have increased susceptibility
• Age: Patients over 40 years have higher risk 2
• Comorbidities: Diabetes mellitus and high myopia increase vulnerability 2
• Genetic predisposition: Approximately 18-36% of the general population are steroid responders 2

Steroid-Related Factors

• Potency: Higher anti-inflammatory potency correlates with greater IOP elevation risk 3
• Penetration: Steroids with greater ocular penetration cause more significant IOP increases 3
• Duration: Prolonged use increases risk of IOP elevation 3
• Frequency: Higher frequency of administration increases risk 3
• Administration route: Risk varies by route (highest with intraocular > topical > periocular > inhaled > nasal > systemic)

Clinical Implications

Timing of IOP Elevation

• May occur as early as 1 day or as late as 12 weeks after steroid initiation 4
• With intravitreal triamcinolone, 20-65% of patients experience IOP elevation 4
• With steroid implants, approximately 75% of patients require IOP-lowering therapy within 3 years 4

Monitoring Recommendations

• Baseline IOP measurement before initiating steroid therapy, especially in high-risk patients 5
• Regular IOP monitoring during steroid therapy
• For patients with glaucoma using nasal steroids, consider the potential impact on IOP management 6

Management of Steroid-Induced IOP Elevation

• IOP typically returns to normal within 2-4 weeks after discontinuing steroids 4
• For patients requiring continued steroid therapy:
  • Consider lower potency steroids
  • Use steroid-sparing agents when possible
  • Approximately 1-5% of patients may require surgical intervention if medical therapy fails 4

Special Considerations

Nasal Steroids and IOP

• Evidence suggests nasal steroids may increase IOP in patients with glaucoma 6
• Discontinuation of nasal steroids in glaucoma patients has been shown to significantly reduce IOP 6
• The European Position Paper on Rhinosinusitis and Nasal Polyps (2020) states that nasal corticosteroids do not affect intraocular pressure in the general population 1

Inhaled Steroids and IOP

• Studies suggest a probable association between inhaled corticosteroids and IOP elevation 5
• Mean IOP in patients using inhaled steroids (15.31 ± 3.27 mm Hg) was significantly higher than in controls (13.39 ± 1.95 mm Hg) 5

Topical Steroids and IOP

• Risk increases with higher potency, greater penetration, and prolonged use 3
• Children may be more susceptible to IOP elevation with topical steroids 3

Understanding these mechanisms is crucial for clinical decision-making when prescribing steroids, especially in patients with risk factors for glaucoma or those requiring long-term steroid therapy.