Dry Eye Is Often a Mixed Problem

For many years, dry eye was commonly divided into two major categories:

• •aqueous-deficient dry eye — not enough aqueous tears
• •evaporative dry eye — excessive loss of tears through evaporation

This distinction is still useful. It describes two important ways in which tear-film homeostasis can be disturbed. But it can also create the impression that every person belongs neatly in one category or the other.

In reality, many people have features of both. And even that does not describe the entire picture.

Modern understanding of dry eye increasingly looks beyond a simple aqueous-versus-evaporative division and asks which etiological drivers are contributing to loss of tear-film and/or ocular-surface homeostasis in an individual patient. These may involve the tear film, eyelids, ocular surface, inflammation, nerves or anatomy.

Imagine that the original problem begins in the meibomian glands. If meibum delivery becomes abnormal, the lipid component of the tear film may become less effective. The tear film may then become unstable. Areas of the ocular surface may experience greater evaporation and hyperosmotic stress. Epithelial cells may become stressed. Inflammatory pathways may become activated. The ocular surface may become damaged. Sensory nerve activity may change.

What began as a gland problem has now become a much broader ocular-surface problem. A simplified pathway might look like this:

meibomian gland dysfunction→abnormal tear-film lipids→tear-film instability→ocular-surface stress→inflammation and surface disruption→altered sensory signaling

But this is only one possible pathway.

Imagine someone whose initial problem is insufficient aqueous tear fluid. Lower tear volume can make the tear film more vulnerable to instability and hyperosmolarity. That can place stress on the ocular surface. Inflammation may become involved. Surface damage may then further destabilize the tear film.

Another person may begin with incomplete blinking. Another with an ocular-surface disorder. Another with abnormal eyelid anatomy. Another with an immune-mediated disease. And another may have several contributing factors from the beginning.

The important point is that there is no single universal starting point for dry eye.

Two people can both be told: “You have dry eye.” But what is happening underneath that label may be very different.

One may primarily have a problem with meibomian gland function and tear-film lipids. Another may have significantly reduced aqueous tear production. Another may have relatively normal tear quantity but incomplete blinking and increased exposure. Another may have prominent ocular-surface inflammation. Another may have substantial sensory dysfunction. And many people will have some combination of these.

This is why the diagnosis dry eye disease is only the beginning of the explanation. The next question is: what is driving it?

This distinction is especially important.

Suppose someone has meibomian gland dysfunction. The condition may be MGD. The resulting tear-film problem may involve abnormal lipid delivery. A downstream mechanism may be increased tear-film instability and evaporation. A later consequence may be ocular-surface stress and inflammation.

These are connected, but they are not interchangeable.

Similarly, inflammation may be a major driver in one person but develop downstream of another problem in someone else. Ocular-surface damage may result from tear-film instability — and then begin contributing to further instability itself.

Something that starts as a consequence can therefore become part of the mechanism maintaining the disease. This is one reason dry eye can become difficult to describe with a single label.

Many of the mechanisms we have discussed can form feedback loops. For example:

tear-film instability→hyperosmolarity and surface stress→inflammation and epithelial disruption→poorer tear-film stability

Or:

incomplete blinking→poor tear redistribution and greater exposure→tear-film instability→surface discomfort and stress→altered blinking

Or:

surface disruption→abnormal tear–surface interaction→localized tear-film breakup→further surface stress

Once several parts of the system become involved, they may begin reinforcing one another. This is sometimes described as the vicious circle of dry eye. But it is important not to imagine one identical circle occurring in everyone. Different people can have different entry points, different dominant mechanisms and different feedback loops.

Dry eye is not necessarily static. The mechanism that was most important at the beginning may not remain the most important mechanism later.

For example, an initial tear-film problem may lead to persistent ocular-surface inflammation. Or an ocular-surface injury may improve while abnormal sensory processing remains. A person may also develop additional contributing factors over time.

This means the dry-eye picture can evolve. Understanding what started the problem can be useful. But understanding what is maintaining it now can be equally important.

There is another important distinction. Saying that dry eye is often mixed does not mean that every person has every possible abnormality. It means that more than one mechanism can contribute at the same time.

Someone may have two important drivers. Someone else may have four. Another person may have one clearly dominant problem with several smaller secondary effects.

The goal is not to assume that everything is abnormal. The goal is to identify which parts of the system actually appear relevant in the individual patient.

Unfortunately, the way dry eye feels does not reliably identify which mechanism is responsible.

Burning can occur with several different ocular-surface problems. A sensation of dryness does not automatically mean aqueous tear production is low. Watery eyes do not automatically mean tear function is normal. Severe pain does not necessarily mean severe visible surface damage. And relatively mild symptoms do not necessarily mean the ocular surface is healthy.

Symptoms are extremely important — but they are only one part of the picture.

The same principle applies to testing.

A short tear-breakup time tells us something about tear-film stability. It does not automatically tell us why the tear film is unstable. A Schirmer test provides information about tear production under particular test conditions. It does not describe the entire tear-film system. Meibography shows the structure of the meibomian glands. It does not directly tell us how well the current tear film is functioning. Ocular-surface staining can reveal areas of epithelial disruption. It does not by itself identify the original cause. Corneal sensitivity testing provides information about sensory function. It does not replace assessment of the tear film.

Each test looks at a different part of the system. That is why no single dry-eye test can tell the whole story.

It is understandable to want one clear label. Do I have aqueous dry eye? Evaporative dry eye? MGD? Inflammatory dry eye? Neuropathic pain?

Sometimes these labels are clinically useful. But they can also make a complex system look simpler than it really is. A more useful set of questions may be:

• •Which parts of my tear-film and ocular-surface system are abnormal?
• •Which abnormalities appear to be driving the problem?
• •Which may be consequences?
• •Which are actually important enough to treat?
• •And how do we know?

Those questions lead directly to the next stage of understanding dry eye.

How Is Dry Eye Diagnosed?