Low-Dose Naltrexone Therapy Is an Option for Neuropathic Corneal Pain

Dupont-Merk’s Revia pill, used to fight alcohol dependency. (Photo by James Leynse/Corbis via Getty Images)
A chart review examines the effectiveness and tolerability of low-dose naltrexone to relieve symptoms of neuropathic corneal pain.

A study published in The Ocular Surface shows the off-label applicability of low-dose naltrexone (LDN) for ocular pain. Because neuropathic corneal symptoms can be severe and refractory to topical anesthetics, a first-of-its-kind study was launched to explore the effectiveness and tolerability of LDN to relieve symptoms of neuropathic corneal pain (NCP).

The chart review, conducted at the Cornea Service at Tufts University Medical School in Boston, represents a patient cohort treated from July 2015 to March 2019. The 30 patients (mean age, 45.60 ± 19.30) at baseline exhibited a centralized component of pain at the level of 4 or greater on a scale of 0 to 10 and discomfort that persisted after the administration of anesthetic drops. Participants underwent LDN therapy for 4 weeks or more, and completed ocular pain assessment surveys before and after treatment.

LDN treatment produced meaningful results: 16 patients experienced a 50% or greater reduction in pain, 9 expressed a 1% to 49% improvement in symptoms, 2 showed no improvement, and 3 felt more discomfort. The highest intensity of pain reported in the previous 24 hours reached a mean standard deviation (SD) of 7.00 (± 1.59) at the first visit, decreasing to 4.56 (± 3.10) at the last appointment (P =.003), and the highest level of pain in the prior 2 weeks lessened from 6.87 (± 2.07) to 2.42 (± 2.41; P =.008).

In addition to pain, other symptoms included photoallodynia, burning, and a foreign body sensation. Surveys affirmed that patients spent less time thinking about discomfort, with 35.56% improvement from the initial appointment to last visit (P =.021), and had their enjoyment of life rise by 43.58% from first to final appointment (P =.043). 

Further, side effects were relatively minor. Of 30 in the test group, 3 had vivid dreams, 2 experienced headaches, 1 participant had a stomachache that eased with dose adjustment from 4.5 mg to 3.0 mg, and 1 in the cohort stopped therapy after reporting headache pain.

Naltrexone is approved by the US Food and Drug Administration at a dosage of at least 50 mg for treatment of alcohol or opioid use disorders, and off-label therapy with 1.5 mg to 5 mg doses has been specified in the scientific literature as early as the mid-1980s. 

Naltrexone given in a low dose temporarily blocks opioid receptors and increases endogenous endorphins. It also reduces inflammation of neural tissue when binding to the toll-like receptor 4 proteins on glia cells in the central and peripheral nervous system. In prior trials, LDN surpassed placebo in reducing chronic pain for individuals with fibromyalgia and improved quality of life for patients with multiple sclerosis, the researchers explained.

They acknowledge that this study is retrospective and the cohort is small, but note that NCP is rare. Their analysis is the largest yet to show effectiveness of a possible therapy. 

“Taking into account the limited number of therapeutic options and the positive efficacy and tolerability profile of LDN, this medication could be considered as an alternative therapeutic modality for the treatment of patients with refractory NCP,” the investigation concludes.

Disclosure: One study author declared multiple affiliations with industry. Please see the original reference for a full list of authors’ disclosures.


Dieckmann G, Ozmen MC, Cox SM, Engert RC, Hamrah P. Low-dose naltrexone is effective and well-tolerated for modulating symptoms in patients with neuropathic corneal pain. Ocul Surf. Published online January 12, 2021. doi:10.1016/j.jtos.2020