Treatment and prophylaxis of radiation optic neuropathy: A systematic review and meta-analysis

Eur J Ophthalmol. 2022 Nov;32(6):3129-3141. doi: 10.1177/11206721221085409. Epub 2022 Mar 9.


Purpose: Radiation optic neuropathy (RON) generally follows radiation therapy that exceed 50 Gy to the visual axis and occurs within three years of therapy. Currently, there are no universally accepted treatments or prophylaxis for RON. The review aimed to examine the efficacy of all treatments and prophylaxis for RON.

Methods: MEDLINE, Embase, the Cochrane Library, and gray literature were searched to December 2020. Studies on treatment(s) and/or prophylaxis of RON were included. Results were meta-analyzed using a random-effects model. Primary outcomes included the proportions of patients who experienced improvement, no change, or worsening of visual acuity (VA) for each treatment. Secondary outcome was the incidence of RON for studies on prophylaxis.

Results: Overall, 50 studies (n = 5397) were included. Meta-analysis (n = 1752) showed significantly lower incidence of RON in patients who underwent intravitreal anti-VEGF prophylaxis compared to control (RR 0.64, 95%CI [0.48, 0.86]) for uveal melanoma. Intravitreal anti-VEGF injections (n = 68), hyperbaric oxygen therapy alone (n = 14), and pentoxifylline (n = 5) resulted in improved or stable vision ≤1 logMAR in 54.5%, 42.9%, and 40.0% of patients, respectively. Systemic corticosteroids (n = 82), anticoagulants (n = 12), and systemic bevacizumab (n = 7) showed improved or stable vision ≤1 logMAR in 17.1%, 33.3%, and 14.3% of patients, respectively. Overall risk of bias was low, but evidence was limited to retrospective studies.

Conclusion: Intravitreal anti-VEGF injections reduced incidence of RON in irradiated uveal melanoma patients. Systemic corticosteroids, systemic bevacizumab, and warfarin alone are likely ineffective treatments. Early hyperbaric oxygen therapy and intravitreal anti-VEGF injections were most effective among those investigated and require further investigation.

Keywords: Neuro ophthalmology; optic neuropathy; tumors; tumors/neoplasms; uveal tumors.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Adrenal Cortex Hormones
  • Angiogenesis Inhibitors / therapeutic use
  • Anticoagulants / therapeutic use
  • Bevacizumab / therapeutic use
  • Humans
  • Intravitreal Injections
  • Melanoma
  • Optic Nerve Diseases* / drug therapy
  • Pentoxifylline*
  • Ranibizumab / therapeutic use
  • Retrospective Studies
  • Uveal Neoplasms
  • Vascular Endothelial Growth Factor A
  • Warfarin


  • Adrenal Cortex Hormones
  • Angiogenesis Inhibitors
  • Anticoagulants
  • Vascular Endothelial Growth Factor A
  • Bevacizumab
  • Warfarin
  • Pentoxifylline
  • Ranibizumab

Supplementary concepts

  • Uveal melanoma