What eye conditions are 5-Fluorouracil (5-FU) eye drops used for?

5-Fluorouracil Eye Drops for Ocular Surface Squamous Neoplasia

Topical 5-Fluorouracil (5-FU) eye drops are primarily used for the treatment of ocular surface squamous neoplasia (OSSN). 1

Primary Indication

• Ocular surface squamous neoplasia (OSSN) is the main indication for 5-FU eye drops, as confirmed by multiple ophthalmology guidelines 1
• 5-FU is one of several topical chemotherapeutic agents (along with interferon and mitomycin-C) that can be used either as primary therapy or as adjunctive treatment following surgical excision of OSSN 1
• Treatment with topical 5-FU has shown complete response rates of 70-96% in patients with OSSN 2, 3

Treatment Protocol

• Standard concentration is typically 1% 5-FU applied topically 4 times daily 4, 3
• Lower concentrations (0.5%) have also shown efficacy with potentially fewer side effects 2
• Treatment regimens usually involve:
  • 1-2 weeks of active treatment followed by 2-3 weeks of drug holiday 2, 3
  • Multiple cycles are often required (median 2-4 cycles) 2, 3
  • Treatment continues until complete clinical resolution 4

Efficacy Factors

• Tumor characteristics that predict better response to 5-FU include:
  • Tumor thickness <1.5 mm 4
  • Absence of fornix or tarsal involvement 4
  • Non-multifocal lesions 4
  • Earlier AJCC classification (T1 vs T2/T3) 4
• Location may affect response rates, with nasally located tumors showing lower response rates 3

Side Effects and Safety

• Common side effects include:
  • Eyelid erythema and edema 2, 5
  • Conjunctival hyperemia 2
  • Pain and discomfort 3
  • Tearing 3, 5
  • Photophobia 3
• Punctal stenosis can occur as a long-term complication 2
• Despite side effects, treatment discontinuation rates are low (approximately 2%) 3
• Long-term safety studies show no significant corneal toxicity, with no differences in:
  • Endothelial cell count and morphology 6
  • Stromal keratocyte density 6
  • Sub-basal nerve plexus parameters 6
  • Central corneal epithelium thickness 6

Comparative Efficacy

• When compared to interferon alfa-2b (another common treatment for OSSN):
  • 5-FU shows higher initial resolution rates (96.3% vs 81.3%) 5
  • Time to resolution is similar between agents (5-6 months) 5
  • Recurrence rates are comparable (11.5% with 5-FU vs 5.1% with interferon) 5
  • 5-FU is associated with more eyelid edema and tearing 5

Treatment Considerations

• 5-FU is particularly useful for:
  • Patients who cannot undergo surgery 3
  • Large or multifocal lesions 4
  • Cases where tissue preservation is important 1
• Patients should be monitored for:
  • Clinical response (typically evaluated every 4-6 weeks) 3
  • Development of side effects 2
  • Recurrence after treatment completion (follow-up for at least 12 months recommended) 3, 5

Clinical Pearls

• DPD (dihydropyrimidine dehydrogenase) testing should be considered before initiating 5-FU treatment to identify patients at risk for systemic toxicity 7
• For patients with partial DPD deficiency, alternative treatments should be considered, or if 5-FU must be used, smaller areas should be treated with close monitoring 7
• Recurrences can often be successfully treated with additional courses of 5-FU 6