Low-dose naltrexone is effective and well-tolerated for modulating symptoms in patients with neuropathic corneal pain

Ocul Surf. 2021 Apr;20:33-38. doi: 10.1016/j.jtos.2020.12.003. Epub 2021 Jan 12.


Purpose: Neuropathic corneal pain (NCP) is caused by damage or disease of the somatosensory nervous system that innervates the cornea and presents with symptoms of pain or persistent unpleasant sensations, such as burning, dryness, or light sensitivity. This retrospective study aims to assess the efficacy and tolerability of low-dose naltrexone (LDN) in refractory NCP patients.

Methods: Fifty-nine NCP patients with a centralized component treated with oral LDN 4.5 mg at bedtime for at least four weeks were identified. Thirty out of 59 patients who had a baseline pain score ≥4 on the visual analogue scale had completed the ocular pain assessment survey (OPAS) and presented persistent pain, despite instillation of topical anesthetic drops, were included. Changes in pain scores, comorbidities, side effects, among others, were analyzed. Change in ocular pain scores (scale 0-10) and quality of life (QoL) scores (scale 0-100%) were the main endpoints.

Results: Mean age (years ± SD) was 45.60 ± 19.30 with a white (80.00%) female (73.33%) predominance. Duration of LDN use was 14.87 ± 11.25 months, and the duration of NCP before treatment was 17.53 ± 17.29 months. Eight patients used LDN as a monotherapy, whereas the remaining used it as an adjunct therapy. LDN resulted in a 49.22% decrease in mean pain score from 6.13 ± 1.93 to 3.23 ± 2.60 (p < 0.001). Mean QoL scores by the OPAS were 5.84 ± 2.57 at the first visit and improved to 3.77 ± 2.91 at the last visit (p = 0.023). Common side effects were vivid dreams, headaches, and stomachache.

Conclusion: LDN was effective and well-tolerated for NCP treatment.

Keywords: Corneal neuralgia; Low-dose naltrexone; Neuropathic corneal pain.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cornea
  • Female
  • Humans
  • Naltrexone*
  • Neuralgia*
  • Quality of Life
  • Retrospective Studies


  • Naltrexone