Why do my eyes hurt - even though my eye doctor says they look fine?
This is a fairly common question I hear in my dry eye center, and the answer can be complex. No one answer fits all eyes or all eye pain, but the usual name given to this group of complaints is “pain without stain,” implying the eye looks normal, so there is no obvious cause to the pain described by the patient.
A few weeks ago I posted about “pain without stain” here: https://www.eyethera.com/blog/testing-part-8-miscellaneous-testing-the-good-the-bad-and-the-ugly-side-of-testing As I mentioned, this opens the door to a portion of dry eye patients with complex problems that are often overlooked or passed over, as our ability to effectively detect, diagnose, and treat this problem remain limited. Treating pain is an important part of a doctor’s duty and dry eye doctors are constantly looking for better tools to fill this toolbox.
One increasingly off-label utilized medication is Naltrexone – in the news as an emergency rescue drug for those who overdose on opioids like Fentanyl. Due to the complex nature of how our bodies deal with pain, we have our own versions of opioids - and the receptors for these innate chemicals exist in nerves and tissues occurring throughout our body.
In numerous prior posts, I’ve covered the role of irritation from dryness activating our natural defense (immune) system, leading to inflammation and initiating the “viscous cycle of dry eye disease.” Corneal nerves become damaged and abnormal – which can lead to chronic pain. Treating the dry eye can reduce irritation, but in some cases the damage to the nerves appears to be too great and the pain lingers. Low Dose Naltrexone (LDN) has been shown to reduce inflammation and has been helpful in curbing pain in a number of chronic, painful conditions such as fibromyalgia and MS. Recent research has shown that LDN eye drops appeared to improve tear production in rats who were made diabetic, with related diabetic dry eye disease, so there may be a number of benefits to the way this drug can reduce inflammation. Zagon IS, Klocek MS, Sassani JW, McLaughlin PJ. Dry eye reversal and corneal sensation restoration with topical naltrexone in diabetes mellitus. Arch Ophthalmol. 2009 Nov;127(11):1468-73. doi: 10.1001/archophthalmol.2009.270. PMID: 19901212; PMCID: PMC2840396.
In a recent post from Glance By Eyes On Eyecare https://glance.eyesoneyecare.com/ a new product for neuropathic corneal pain was announced as under investigation. The following is an excerpt from a physician-level communication I received from them:
“Are there any new treatments for neuropathic pain?
OKYO Pharma Limited announced it has submitted an investigational new drug (IND) application for the development of OK-101 to treat neuropathic corneal pain (NCP).
What is OK-101?
OK-101 is a lipid-conjugated chemerin peptide antagonist of the ChemR23 G-protein coupled receptor, which is typically found on immune cells of the eye and is responsible for the inflammatory response.
How does it work?
OK-101 was developed using a membrane-anchored-peptide (MAP) technology and has been shown to produce anti-inflammatory and pain-reducing activities in mouse models of DED and NCP.
Didn’t OKYO already file an IND for OK-101?
Good memory! And yes—back in November 2022. However, this IND was for DED, not NCP.
As for updates on that application… in April 2023, the company activated the first U.S. clinical trial site for its first-in-human (FIH) phase 2 multi-center, placebo-controlled trial of OK-101 for DED, which was followed by randomized dosing of participants in June 2023.
How about for NCP?
According to the company, preclinical data from a ciliary nerve ligation model on mice found that OK-101 reduced NCP response similar to that of gabapentin (a common oral drug used for such pain), administered via intraperitoneal injection.
The model supported the topical administration of OK-101 as a potential non-opioid analgesic for NCP.
Gotcha. So what’s next?
Pending FDA acceptance, the company—in partnership with Boston-based Tufts Medical Center—is planning to launch an open-label phase 2 study in Q1 2024, with an anticipated 40 patients to be enrolled.
And the significance of this?
With no current FDA-approved drug on the market to treat NCP, this second indication for OK-101 could become the first, proving to be a game changer for patients suffering from this chronic condition.”
I should add that I don’t have any “insider knowledge” about OK-101, but I’d guess that it comes out of the research-information obtained from studying the natural opioids in humans (also known as endorphins, enkephalins and dynorphin-related “natural painkillers”). I welcome any additional tools to this important toolbox as current approaches remain all to limited!
To schedule an appointment with Dr. Jaccoma, call Excellent Vision at either of these two dry eye offices:
(1) 155 Griffin Rd, Portsmouth, NH 03801 (603) 574-2020
(2) 3 Woodland Rd, STE 112 Stoneham, MA 02180 (near Boston) (781) 321-6463