Dry Eye Syndrome and Corneal Sensitivity

Guest author, Seth Biser, MD

A continuing education lecture with Dr. Biser sparked some lively discussion and follow-up. Dr. Biser was kind enough to share the results of his research:

Question: Are patients with chronic dry eye syndrome at an elevated risk for long term damage?

Answers:

A. Chronic dry eye definitely damages the corneal nerves (as do other forms of damage such as chemical burns, LASIK, and other injuries).  Chronic damage from dryness makes the nerves shorter, stubbier, and more tortuous than they were before. (Ref 1) It also makes them less accurate in their reporting of the true condition of the eye surface. (Ref 2) 

B. Among patients who have dry eye, those whose corneal nerves are more normal (have longer axons) are more likely to feel better after therapy than those with less-normal anatomy.  (Ref 3).  This likely means that this subset of dry eye patients–especially those with “early” dry eye–are actually feeling real improvements that occur on their ocular surface.     So, these patients with early dry eye and normal nerves are the “happy campers:” Treat them, and they feel better, and they are grateful to their eye care provider.     
Unfortunately, this also means that patients with longstanding dry eye will be less likely to feel any improvement, even if their ocular surface improves. These are the “moderately unhappy campers.”  I think of these as the older patients who sit there, often without blinking, wondering why I am concerned about their eye surface. They have diffuse staining and some of them have Salzmann’s nodules, but they feel nothing is wrong. It is all the more important to treat their underlying condition.  I often tell these patients about diabetic patients who can no longer feel their own feet: Although this may seem like a small problem, because the patient feels no pain, it can lead to amputation. 

C. Neuropathic pain (or neuropathic ocular pain, etc.–there are a number of different terms) affects a variety of patients, especially those with dry eye.  In neuropathic pain, small disturbances on the eye surface create intensely elevated nerve signaling, so the patients may react with dramatic discomfort even to mild air currents. Some patients even feel persistence of pain after topical proparacaine (common anesthetic used by eye care providers), indicating that the nerve signaling is coming from the brain, not from the eye surface.  Patients with this type of pain often have associated mood disorders such as depression. (Refs. 4, 5, 6, and 7)       
So this last group are the “incessantly tortured campers.” They are not as common as the other campers, but they are more problematic.  They may have signs of dry eye; they may have normal or abnormal-appearing nerves; but their pain persists even when their ocular surface is improved. 

So my interpretation is that we have two tasks in dry eye:

1. healing the ocular surface, and
2. providing some settling-down of discomfort.  That’s part of what makes it an incessant challenge.

Ref 1:  https://iovs.arvojournals.org/article.aspx?articleid=2127686
Patients with non-Sjogren’s dry eye had corneal sensory nerves that were “stubbier” (shorter, wider, and more twisted) than normal patients, as seen in nerves that have responded to tissue damage.  

Ref 2:  https://iovs.arvojournals.org/article.aspx?articleid=2182826
Patients with dry eye (and increased age) were less likely to sense mechanical, chemical, and thermal stimuli, and to have greater corneal staining. 

Ref 3:  https://www.aaojournal.org/article/S0161-6420(14)01052-5/fulltext
When a group of patients with dry eye are treated, the sub-group with more normal nerves responded with greater symptomatic improvement, while the sub-group with more abnormal nerves did not feel much improvement.  

Refs 4, 5, 6, and 7: 

https://www.ncbi.nlm.nih.gov/pubmed/25376119

https://www.ncbi.nlm.nih.gov/pubmed/25943558

https://www.ncbi.nlm.nih.gov/pubmed/28100479

https://www.ncbi.nlm.nih.gov/pubmed/27130915

MISCELLANEOUS ADDENDA

Among patients with diabetes, those with dry eye showed no change in corneal nerve anatomy compared to those without dry eye. Why? Most likely, it’s because diabetes damages the nerves so much that any additional damage from dry eye is too minimal to be detected. After all, diabetics in general have been found to have abnormal corneal nerves. https://iovs.arvojournals.org/article.aspx?articleid=2716390
https://www.ncbi.nlm.nih.gov/pubmed/30309785

The cat cornea has a maximum density of 1011 ± 260 nerve terminals / mm² (centrally) and a minimum (peripherally) of 441 ± 116.
https://www.ncbi.nlm.nih.gov/pubmed/30701644

“I greatly appreciate your bringing up a very good question and helping both of us learn a little more about this perplexing topic! ”
—Dr. Seth Biser

Seth A. Biser, M.D., is a Board-Certified ophthalmologist and eye surgeon, and a Clinical Assistant Professor of Ophthalmology at N.Y.U. with a private office in Fleetwood, NY.

He specializes in comprehensive ophthalmic evaluations and treatments, and performs several types of eye surgery including routine and advanced cataract surgery as well as laser treatments for glaucoma. He regularly receives referrals from other eye doctors in Westchester.