Neurotrophic Keratopathy (NK) Is When the Eye Can’t See What’s Happening

Eye Health
Neurotrophic Keratopathy (NK) Is When the Eye Can’t See What’s Happening

People say the eyes are the windows to the soul, but eyes are more like the aquariums to the soul. They are specialized, fragile, require continuous maintenance, and are full of living things in a perfect, yet fickle state of balance. Proper aquarium maintenance includes monitoring, testing, and correcting for changes in water cleanliness, salinity, temperature, acidity, chemicals, pests, and as many other variables as your budget allows. Just as we need to keep a close watch on our fish tanks, our eyes must continually sense and respond to changes in their environment, or we risk seeing big problems.

 

Neurotrophic Keratopathy (NK) is a condition associated with several diseases.[1] Neuro- refers to neurons, -trophic describes nourishing or supporting, kerato- refers to the cornea, and -pathy indicates a disease. Together, neurotrophic keratopathy is a disease involving impaired nerves that affect the cornea.[1] This condition has been referred to by several other names - including any combination of neurotropic, neuroparalytic, and neuropathic with keratitis or keratopathy - so the abbreviation NK seems suitable.[1]

 

To understand NK, we first have to be schooled in what the cornea is. The cornea is the outermost layer of the eye and forms a clear, curved, wet surface for light to focus through.[2] We think of the eye as a separate structure in the body - and it is - but the skin of our eyelids (made up of epithelial cells) is strikingly similar to the skin of our corneas (also made up of epithelial cells) and together these form a solid, unbroken, water-tight barrier between the inside of the eye and the outer world.[2] This barrier is vital for acting as the interface between the delicate inner eye and the hostile, dangerous world.[2] To do this, the cornea needs to sense, react, and adapt to changing conditions in the environment, and that requires nerves.[1] The cornea has the densest collection of nerves in the body and quickly responds to changing conditions by blinking, making tears, changing the type of tears, moving the eye, and producing trophic factors, which keep the cornea “fed” and in a healthy state.[3] These nerves also kick the brain into an absolute panic state when we get something painful in the eye. NK can occur when the nerves fail to detect, communicate, or enact changes in the cornea.[1,2]

 

The hallmark of NK is nerve dysfunction. Back to our fish tank analogy, it’s like being unable to test the water. Not testing doesn’t make the problems go away, instead they compound until your beautiful underwater scene of guppies swimming through a sunken pirate ship slowly becomes an algae-filled cesspool full of dead fish. When the nerves don’t work properly, the eye can’t sense or respond to the changes in the environment. This makes it harder for the cornea to stay healthy, leading to damage to corneal cells, problems with the tear film on the eye, and opens the cornea up for infection and NK.[1,3] On top of this, corneal cells are replaced, on average, every 7-10 days.[3] Without the trophic factors, cells fail to regenerate and recover from wounds, leading to a cycle of inflammation, damage, infection, ulcers on the eye, and other problems that will leave you reeling.[1]

 

NK is rare, with between one and five confirmed cases for every ten thousand people globally.[3] This number is considered to be greatly underdiagnosed; the true number is watered down and likely significantly higher.[3,4] Symptoms of NK usually affect only one eye and include:[3]

  • Dry eye
  • Sensitivity to light
  • Excess tears
  • Changes or deficiencies in sight
  • Pain in advanced cases

Diagnosis requires a doctor who can evaluate the eye for signs such as corneal thinning, ulcers, and other related abnormalities.[3] Neurotrophic keratopathy (NK) comes in different severities, ranging from mild surface changes in the outer layer of cells and tear film, to severe, sight-threatening permanent damage to the eye.[3] The risk of developing NK increases with events, diseases, or conditions that affect the trigeminal nerve in the face, which connects the brain to the face.[3,4] Some risks include:[1,3,4]

  • Surgery or trauma of the cornea, jaw, skull, or other trigeminal region, including from stroke and tumors
  • Chemical burns
  • Prolonged contact lens use
  • Certain medications, including antihistamines, neuroleptics, and antipsychotics
  • Infectious diseases of the eye, like herpetic keratitis
  • Systemic diseases, including diabetes, multiple sclerosis, and leprosy

Remember that NK is a RARE disease; talk to your physician before altering your medication regimen.

 

So what can be done? A number of nonspecific treatments may be prescribed by a physician, including:[1,3]

  • Preservative-free fake tears
  • Anti-inflammatory medications
  • Antibiotics
  • Antiproteases, as a supporting medication

Specific treatments for NK include therapeutic contact lenses and surgeries to help with dry eye and lid closure.[1,3] These may prevent further damage, but come at a cost of possible interruption of sight.[1] There are multiple experimental treatments for NK, though the rarity of the disease makes clinical research a challenge. One of the most exciting treatments in development is the investigation of thymosin β4.[3] This protein, found naturally throughout the body, is concentrated in immune cells, blood plasma, and the fluid around wounds.[3] The fact that thymosin β4 is found where the body needs to be repaired gives a clue to its medical use: wound healing. In the body, thymosin β4 helps tissues regenerate from wounds, and researchers hope that using this as a medication will help promote wound healing in the cornea and raise the prognosis of NK.[3] If those suffering from this rare condition can help with the research process, we may be able to turn the tide on NK.

 

Creative Director Benton Lowey-Ball, MWC, BS, BFA

 

 

References:

[1] Dua HS, Said DG, Messmer EM, Rolando M, Benitez-del-Castillo JM, Hossain PN, Shortt AJ, Geerling G, Nubile M, Figueiredo FC, Rauz S. Neurotrophic keratopathy. Progress in retinal and eye research. 2018 Sep 1;66:107-31. https://doi.org/10.1016/j.preteyeres.2018.04.003

[2] Gipson IK. The ocular surface: the challenge to enable and protect vision: the Friedenwald lecture. Investigative ophthalmology & visual science. 2007 Oct 1;48(10):4391-8. https://doi.org/10.1167/iovs.07-0770

[3] Vera-Duarte GR, Jimenez-Collado D, Kahuam-López N, Ramirez-Miranda A, Graue-Hernandez EO, Navas A, Rosenblatt MI. Neurotrophic keratopathy: General features and new therapies. Survey of Ophthalmology. 2024 Sep 1;69(5):789-804. https://www.sciencedirect.com/science/article/pii/S0039625724000420

[4] Gurnani B, Feroze KB, Patel BC. Neurotrophic keratitis. InStatPearls [Internet] 2025 Mar 27. StatPearls Publishing. https://www.ncbi.nlm.nih.gov/books/NBK431106/

 

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