Neural Dysfunction & Altered Sensation

It is easy to think of corneal nerves simply as the structures that allow us to feel the eye. But their role is much broader, as we saw in Your Corneal Nerves.

Sensory nerves detect changes and potential threats at the ocular surface. Information travels through branches of the trigeminal nerve toward the central nervous system. The nervous system can then help generate appropriate responses. Depending on the signal, those responses may include blinking, tear secretion, and protective sensations such as discomfort or pain.

This means sensory nerves are part of the system that helps maintain ocular-surface homeostasis. They do not simply report that something has already gone wrong.

Neural dysfunction means that sensory signaling is no longer operating normally. That does not necessarily mean the nerves are completely damaged or absent.

The problem can occur at different levels of the sensory pathway, and the resulting signal can change in different directions. Broadly, sensation may become:

• •increased
• •decreased
• •altered in quality or processing

This distinction is important because neural dysfunction does not produce one universal dry-eye experience. Two people with abnormalities in the sensory system may experience almost opposite problems.

Sometimes sensory pathways become unusually responsive to stimulation. A stimulus that would normally produce little discomfort may begin to feel unpleasant or painful. This increased responsiveness is often discussed in terms of sensitization.

Sensitization can occur in peripheral sensory nerves and, in some circumstances, within the central nervous system. At the peripheral level, nerve endings at or near the ocular surface may become more responsive after repeated injury, inflammation or other forms of stress. At the central level, changes in the way incoming sensory signals are processed can potentially amplify the experience further.

The result may be symptoms that seem unusually intense compared with the ocular-surface findings visible during a routine examination.

This is one of the most important consequences of altered sensory processing. A person may report severe burning, dryness, irritation, light sensitivity or pain while routine clinical tests show relatively limited tear-film or ocular-surface abnormalities.

Historically, this mismatch could sometimes lead to the assumption that the symptoms were exaggerated or that nothing significant was wrong. We now know that this conclusion is too simplistic.

Symptoms are generated by the nervous system. If sensory signaling or processing has changed, the intensity of the symptoms does not have to correspond directly to the amount of visible tissue damage.

This does not mean that every person whose symptoms exceed their signs has neuropathic pain. It means that neurosensory dysfunction is one possible explanation that needs to be considered.

Neural dysfunction does not always increase sensation. Sometimes corneal sensitivity becomes reduced. This is known as hypoesthesia.

If sensory input from the ocular surface decreases, a person may feel surprisingly little discomfort even when clinically significant abnormalities are present. This creates the opposite mismatch: more signs, fewer symptoms.

And reduced sensation can matter for more than comfort. Because sensory nerves participate in reflex tearing and blinking, reduced sensory input may interfere with some of the protective responses that normally help maintain the ocular surface. In more severe forms of sensory impairment, reduced corneal innervation can also interfere with epithelial health and healing.

This is an important idea to understand. The sensation we call “dryness” is not a direct measurement of how much tear fluid is present. The brain does not contain a simple moisture gauge that reports the volume of tears on the eye.

Instead, sensations arise from sensory signals generated by the ocular surface and interpreted by the nervous system. Those signals can be influenced by many things, including tear-film breakup, evaporation, temperature changes, hyperosmolarity, inflammation, mechanical stress and tissue damage. And the sensory system itself can change.

So feeling very dry does not necessarily mean that tear volume is extremely low. And having little discomfort does not necessarily mean that the ocular surface is healthy. Symptoms and physical findings provide different kinds of information.

The sensory system of the cornea is not made up of one single type of receptor. Different populations of sensory nerve endings respond preferentially to different kinds of stimuli.

Mechanoreceptors respond primarily to mechanical forces. Polymodal nociceptors can respond to mechanical, chemical, thermal and inflammatory stimuli. Cold thermoreceptors respond to reductions in ocular-surface temperature and changes associated with tear-film evaporation.

These different sensory pathways contribute to the continuous information the nervous system receives from the ocular surface. This helps explain why dry-eye sensations can be so varied. One person may describe dryness. Another may describe burning. Another may feel grittiness, aching, stinging or sensitivity to air. And some may experience pain that seems qualitatively different from ordinary dryness.

When pain arises because of a lesion or disease affecting the somatosensory nervous system, it is described as neuropathic pain. In the eye, terms such as neuropathic ocular pain or neuropathic corneal pain are sometimes used when abnormal sensory nerve function appears to be an important contributor to symptoms.

This can involve peripheral mechanisms at the ocular surface, central mechanisms within the nervous system, or a combination of both.

But neuropathic pain should not become a catch-all explanation for difficult dry-eye symptoms. Severe symptoms can occur for many reasons. And a mismatch between symptoms and signs does not by itself establish a neuropathic diagnosis.

The important concept here is simply that pain can sometimes become partly a problem of the sensory system itself rather than a direct reflection of ongoing surface damage alone.

Not all ocular pain is neuropathic. If the ocular surface is unstable, inflamed, damaged or exposed, sensory nerves can respond normally to those harmful or potentially harmful stimuli. This is generally described as nociceptive pain. In this situation, the sensory system is doing what it is designed to do: detecting tissue stress and warning the brain.

The distinction between nociceptive and neuropathic mechanisms is therefore important. And in real patients, they are not always completely separate. A person can have genuine ocular-surface disease producing nociceptive signals while also developing changes in sensory processing. The result can be a mixed pain mechanism.

Because sensory nerves participate in ocular-surface regulation, abnormal nerve function can potentially affect other parts of the system. Reduced sensory input may alter reflex tearing. It may affect blink responses. Changes in innervation can influence epithelial maintenance and healing. Neural and immune pathways also communicate with one another.

So neurosensory dysfunction is not simply a question of “How much pain do I feel?” It can become part of the broader biological system that maintains — or fails to maintain — ocular-surface homeostasis.

We can now see why the relationship between signs and symptoms in dry eye can become complicated.

Imagine two people with similar tear-film instability. One person’s sensory system may respond strongly, producing substantial discomfort. Another person’s corneal sensitivity may be reduced, producing much less sensation. Or imagine someone whose original ocular-surface problem has improved significantly, but whose sensory system remains unusually responsive.

The physical state of the eye and the sensory response to that state are related — but they are not identical measurements of the same thing. This is why neither symptoms nor clinical signs should automatically invalidate the other. Both provide information about different parts of the system.

Corneal Sensitivity & Nerve Testing

There are many possible pathways. Corneal nerves can be affected by ocular-surface inflammation, prolonged tissue stress, injury, surgery, infection and other conditions. Changes can occur at the peripheral nerve level or within central sensory processing. Some systemic neurological or metabolic conditions can also influence corneal innervation or sensation.

But those are questions about why neural dysfunction developed. For now, the important point is that the sensory nervous system itself can become one of the dysfunctional components of dry eye disease.