What are the risks of long‑term ocular topical corticosteroid use on intra‑ocular pressure and retinal nerve‑fiber‑layer thickness, and how should these be monitored and managed?

Long-Term Topical Steroid Use and RNFL Thinning

Long-term topical corticosteroid use can cause retinal nerve fiber layer (RNFL) thinning, with the risk increasing proportionally to duration of therapy, and this occurs even when intraocular pressure remains normal. 1

Evidence for RNFL Thinning

The most direct evidence comes from a study of vernal keratoconjunctivitis (VKC) patients on long-term topical corticosteroids (mean duration 23.8 months), which demonstrated significantly thinner mean global, superior, and inferior RNFL thickness compared to controls, despite normal IOP measurements. 1 Critically, there were significant negative correlations between duration of topical corticosteroid use and mean global, superior, and temporal RNFL thickness, indicating a dose-duration relationship. 1

This finding is particularly concerning because RNFL thinning occurred independently of IOP elevation, suggesting a direct toxic or metabolic effect of corticosteroids on retinal ganglion cells or their axons beyond the traditional glaucoma mechanism. 1

Intraocular Pressure Risks

Incidence and Risk Factors

• Clinically significant IOP elevation (≥10 mmHg from baseline) occurs in 0.8-1.5% of patients on topical corticosteroids, with higher rates in long-term use (≥28 days). 2
• Risk factors include prolonged use, high frequency of administration, young age, higher ocular penetrance, and higher anti-inflammatory potency. 3
• Early generation corticosteroids (dexamethasone, prednisolone) carry higher risk of IOP elevation compared to newer agents like loteprednol etabonate. 4

Steroid-Induced Glaucoma

• Prolonged steroid therapy produces secondary open-angle glaucoma similar to chronic simple glaucoma, with the IOP elevation being reversible but the optic nerve damage being irreversible. 5
• Systemic steroids used for more than 8 weeks can also induce raised IOP and cataract formation. 5

Monitoring Protocol

For any patient on topical corticosteroids beyond 2 weeks, implement the following surveillance:

Baseline Assessment

• Measure baseline IOP before initiating therapy 3, 4
• Obtain baseline RNFL thickness via optical coherence tomography (OCT) for patients anticipated to require therapy beyond 4 weeks 1
• Document baseline visual acuity and perform dilated fundus examination 1

Ongoing Monitoring Schedule

• IOP checks at 2 weeks, then every 4-6 weeks during continued therapy 3, 4
• RNFL thickness measurements every 3-6 months for patients on therapy beyond 3 months, as RNFL thinning correlates with duration of use 1
• More frequent monitoring in known steroid responders, children, and patients with family history of glaucoma 3, 4

Critical Thresholds

• IOP elevation ≥10 mmHg from baseline requires immediate intervention 2, 3, 4
• Progressive RNFL thinning on serial OCT measurements warrants discontinuation or transition to lower-potency agents 1

Management Strategies

Agent Selection

Preferentially use loteprednol etabonate for conditions requiring long-term therapy, as it demonstrates minimal IOP impact (0.8% incidence of ≥10 mmHg elevation in short-term use, 1.5% in long-term use) regardless of formulation, dosage, or duration, including in known steroid responders. 2

• Loteprednol etabonate shows significantly lower rates of IOP elevation compared to prednisolone acetate or dexamethasone. 2
• Lower anti-inflammatory potency steroids with reduced intraocular penetration are associated with reduced incidence of both IOP elevation and potentially RNFL damage. 3

When IOP Elevation or RNFL Thinning Occurs

• Discontinue or taper topical corticosteroid immediately 5
• Transition to lower-potency agent if continued anti-inflammatory therapy is essential 3, 4
• Initiate IOP-lowering therapy if discontinuation is not feasible and IOP remains elevated 5
• Consider non-steroidal anti-inflammatory alternatives when appropriate 3

Critical Pitfalls

The most dangerous pitfall is assuming normal IOP excludes steroid-related ocular damage. RNFL thinning can occur with normal IOP measurements, making visual field analysis and RNFL thickness monitoring essential adjuncts to routine IOP checks in long-term users. 1 Because visual field testing is difficult in pediatric patients and IOP may be misleading, RNFL thickness measurements become even more critical in children on chronic topical corticosteroids. 1