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Naltrexone Therapy for Diabetic Corneal Complications

December 6, 2024

Although we’ve previously focused on low-dose naltrexone (LDN) eye drops for ocular conditions, this month, we’re focusing exclusively on their use to treat corneal complications from diabetes. Diabetes mellitus affects millions of patients worldwide, about half of which will have an ocular complication such as diabetic keratopathy, dry eye disease, or retinopathy.

Despite the prevalence of these conditions, there are few inexpensive treatments. Current therapies focus on symptomatic relief without addressing the underlying cause, such as OTC lubricating eye drops, or antibiotics to treat secondary infections. Emerging research on naltrexone, a drug traditionally used in addiction treatment, has shown potential as a novel therapeutic for diabetic corneal complications.

Naltrexone Eye Drops

Naltrexone has been FDA-approved for almost two decades for managing alcohol use disorder and almost fifteen years for treating opioid use disorder. When used to treat these conditions, it is typically administered at a dosage of 50 mg, but when used at lower doses, naltrexone can be used to treat a variety of other conditions, including several ocular conditions associated with diabetes.

Although there have been numerous studies showing the efficacy of naltrexone given orally, a minimal amount is actually delivered to the eye when taken via this administration route. Therefore, topical (ocular) administration is recommended to ensure that the maximum dose of naltrexone reaches the area where it is needed.

What the Research Says

In diabetic patients, the opioid growth factor (OGF), which regulates homeostasis during corneal epithelialization and tear secretion is dysregulated. When administered as eye drops, LDN blocks the OGF-OGFr axis and can restore corneal sensitivity and corneal re-epithelialization, helping treat dry eye disease.

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Early murine studies showed that rats with type-1 diabetes showed slower corneal surface healing. Researchers at Penn State applied low-dose naltrexone to the corneal surface, which led to about 20 to 40 percent faster corneal wound closure times. Since initial results with rat models, there have been several clinical studies in humans that have investigated naltrexone for diabetic corneal complications.¹

Dry Eye Disease

Building off mouse model studies, Dr. Joseph S. Sassani at Penn State conducted a small trial of 60 patients to investigate naltrexone eye drops for treating dry eye disease in humans with diabetes. Although the results have not been peer-reviewed, the investigators reported no serious adverse events in either the treatment or placebo groups after 29 days of treatment. LDN eye drops have also been reported to work for many patients in helping reverse dry eye disease.

Although these are off-label indications, studies have shown that LDN is generally well-tolerated with no major side effects. Despite the lack of large randomized controlled trials, some small clinical studies have investigated it for corneal complications associated with diabetes.

Tolerability and Safety

A small clinical study in healthy human volunteers in 2016 showed that topical naltrexone was well tolerated when applied at low doses and none of the volunteers reported any major adverse events.² At doses up to 50 µM over a 24-hour period, the study showed no major differences between the treatment and control groups during the one-week observation period, further confirming the already-established safety record for LDN via this administration route. Because this trial was exploratory in nature, it was not meant to demonstrate efficacy, but all participants that enrolled in the trial completed the entire 30 days.

Ongoing Research

Murine studies play a critical role in advancing clinical trials in humans. Although no randomized controlled trials have confirmed that LDN is useful, murine models are showing promise, with LDN eye drops helping reverse dry eye disease in rats within hours. Upon longer treatment, the corneal sensitivity was restored in diabetic rats.

Why Choose VLS Pharmacy and New Drug Loft?

Despite this well-established safety profile, LDN eye drops need to be compounded by a licensed pharmacy that specializes in ophthalmic compounding – a niche area of compounding that requires additional protocols and facilities to perform correctly to ensure the purity of the preparations.

As part of our efforts to ensure patient safety, we compound all of our formulations using high-quality pharmaceutical-grade APIs sourced directly from PCCA, the leader of superior-quality APIs. Our pharmacists and technicians tailor each formulation to meet a patient’s specific needs, including the dose and administration route. As a 503A pharmacy specializing in sterile and non-sterile compounding, we will support you and your patients by creating individualized pharmaceutical therapies.

Please comment below with any thoughts or questions.

Reach out to our team to learn about best practices and to partner with our experts on custom compounded medications for your patients. All medications from VLS Pharmacy and New Drug Loft are prepared in a lab that follows safety and quality standards per our status as a 503A pharmacy.

References

McLaughlin PJ, Sassani JW, Zagon IS. Naltrexone as a Novel Therapeutic for Diabetic Corneal Complications. J Cell Immunol. 2020;2(2):42-46. doi:10.33696/immunology.1.018
Liang D, Sassani JW, McLaughlin PJ, Zagon IS. Topical Application of Naltrexone to the Ocular Surface of Healthy Volunteers: A Tolerability Study. J Ocul Pharmacol Ther. 2016;32(2):127-132. doi:10.1089/jop.2015.0070