Systemic and Autoimmune Diseases That Lead to Dry Eye

By James McCulley, MD

There exists a host of systemic diseases that can lead to dry eye. Systemic disease can affect any one of the three principal layers of the tear film—the lipid, aqueous mucin or mucin/glycocalyx. Here, I will discuss the more common major systemic diseases that contribute to dry eye and which specific layer of the tear film they influence.

The Lipid Layer

A compromised lipid layer is a frequent cause of dry eye. The most common systemic disease that affects this layer is acne rosacea. Rosacea affects the meibomian gland, which in turn affects the lipid layer, causing dry eye. The dry eye can have one of two major components; it can be hyperevaporative because of the abnormality in the lipid layer or it can be associated with hyposecretory dry eye due to deficient aqueous tear production by the main and accessory lacrimal glands.

There are other skin diseases associated with abnormalities in the lipid layer, which are now being categorized as meibomian gland dysfunction (MGD). This includes seborrheic dermatitis, which is associated with a presumed hyperevaporative dry eye. With the hyperevaporative dry eye and the association with MGD, there is a qualitative or a quantitative change in the meibomian secretions and therefore the lipid layer of the tear film. So, rosacea, seborrheic dermatitis and the associated MGD can affect the lipid layer and result in either a hyperevaporative or a hypoevaporative secretory form of dry eye.

The Aqueous Mucin Layer

The most common diseases in the aqueous mucin layer are autoimmune diseases including Sjogren's syndrome, lupus and rheumatoid arthritis. These diseases result from an autoimmune attack on the lacrimal and accessory lacrimal glands—causing damage to the glands, reducing the aqueous layer and resulting in a hyposecretory aqueous deficient dry eye. Virtually any of the autoimmune diseases can be associated with an immune attack on the lacrimal glands and therefore can contribute to dry eye.

Another inflammatory disease that can result in severe dry eye is graph-versus-host disease. For example, if a person has a bone marrow transplant, the cells that have immune capability recognize as foreign the body they've been transplanted into and attack it. They may attack the lacrimal gland, the accessory lacrimal gland and the ocular surface directly, which can produce severe dry eye.

With autoimmune diseases, I typically work with an internist or rheumatologist to control the systemic inflammatory process, which will have a positive impact on the eye.

Mucin Glycocalyx Layer

Dry eye from an abnormality of the mucin glycocalyx layer is commonly associated with skin diseases that involve mucus membranes, such as Stevens Johnson syndrome or ocular ciccatricial phemphigoid, which are immune-mediated diseases, and also vitamin A deficiency. All of these are associated with a mucin glycocalyx deficiency, which results in a “wet” dry eye. A wet dry eye occurs when mucin deficiency prevents conversion of the epithelial cell hydrophobic environment into a hydrophilic environment and thus the inability to support an overlying aqueous mucin layer. There is a sufficient amount of aqueous, but it can't coat the ocular surface because it's a hydrophilic layer trying to coat a cellular membrane, which is a hydrophobic layer.

Other Conditions Which Create a Dry Eye

Any disease requiring antimetabolite therapy can exacerbate dry eye because antimetabolites attack cells that are turning over rapidly—and lacrimal cells typically turn over rapidly. So, the antimetabolites may decrease the inflammation, which is a plus, but they also decrease the aqueous tear production because they adversely affect the lacrimal and accessory lacrimal glands.

Systemic therapy that has nothing to do with the eye can still have a negative effect on the eye. Any systemic medication that dries the mucosal surface or slows down the activity of the mucosal surface may produce dry eye. Additionally, if a medication causes dry mouth, it will cause dry eye, too.

Antihistamines, antidiarrhea drugs, some of the psychotropic drugs, and antihypertensives that have a diuretic effect have an unintended drying effect on the eye.

Topical Medications

Any topical medications that may result in a dry eye are a concern because they prevent epithelial cells from supporting the overlying tear film. The generally held view is that any topical drop that has a preservative in it may have a negative effect on the integrity of the tear film and may contribute to dry eye. Most of the preservatives are mild and most of the drops are used infrequently enough that the preservative effect in the majority of patients is not a major one, in my view. However, there are ophthalmologists who believe that preservatives have a much greater primary role in dry eye.

Treatment

Some patients with a genetic, systemic disease come to an ophthalmologist because they're having difficulty with their eyes. I try to address the underlying disease, generally with the help of a rheumatologist or a dermatologist because the diseases typically involve skin and mucosal membranes. As my co-physician begins treatment of the underlying cause, I begin my therapy at the same time by addressing the ocular manifestations of the disease.

A specialist treating the systemic disease makes it easier for me to deal with the dry eye for two reasons; one, the underlying disease is controlled, so it will be easier for me and the patient to control the ocular disease and two, once I get the ocular surface healthy, it is easier to keep it healthy.

Systemic steroids have strong anti-inflammatory capabilities and while they don't have the adverse effects of anti metabolites, they do have their own set of side effects. If NSAIDs work, they are a great option because they have a more acceptable side effect profile than steroids and anti-metabolites. Antimetabolites are cancer drugs, which means they attack all rapidly dividing cells. Unfortunately, this puts lacrimal gland and accessory lacrimal gland cells at risk because they are rapidly dividing cells as well.

If the underlying disease is not chronic, then the patient will not need to be treated chronically for sake of the eye. Several of the autoimmune diseases affect goblet cells, and therefore affect the mucin. If the immune process is attacking the eyes, then systemic therapy will come into play, so I may also supplement with local anti-inflammatory therapy. First, I would try steroids or NSAIDs. Restasis can also be considered but it takes several months before therapeutic effects become clear. So, it is used more often in chronic therapy than in acute therapy.

If there is a deficiency in the tear film, I typically try to supplement the deficiency. We now have drops on the market that have a lipid component. If the aqueous layer is involved, I try to decrease evaporation and supplement the aqueous component.

If the dry eye is related to medications for a systemic disease, I would make the patient and whomever is treating the systemic issue aware that the drugs are causing dry eye and attempt to get the medications switched if possible. ■

James McCulley, MD, is Professor and Chairman of the Department of Ophthalmology at UT Southwestern and is currently entering his 30th year of chairmanship. He is a recognized expert in cornea, external disease, keratorefractive and cataract surgery. He has published more than 260 peer-reviewed articles.