Medical Disorders that can Cause Eye Problems

Ocular Symptoms and Conditions: Medical Conditions that can Cause Eye Problems

This page discusses a selection of medical disorders which are known to lead to a variety of eye problems. Links to other pages discussing medical conditions causing eye problems are provided as well. There are many medical disorders where eye complications are found as part of a larger symptom complex. In some cases, several different parts of the eye, orbit, or visual system can be affected by the condition, which is why they are discussed on this page rather than on a specific symptom category page.

One example is thyroid related ocular problems, which is discussed on the Double Vision page. This condition not only causes double vision due to eye muscle involvement, but also can cause dry eye problems, eyelid problems, and potential loss of vision. Since the eye muscle problems are relatively common with thyroid dysfunction, it is discussed on that page.

In some cases, a medical physician may request an eye examination to determine if the eyes are being affected by the medical condition. There are numerous conditions which potentially have eye complications, and only a few are discussed here.

This page is divided into a group of medical disorders which also can affect the eyes. The next section discusses other medical disorders discussed elsewhere that have ocular complications.

Conditions Discussed on this Page:

Cicatricial Pemphigoid
Myasthenia Gravis
Sarcoidosis
Lyme Disease
Eye Problems during Pregnancy
Eye and Orbital Cancer
Other medical conditions causing eye problems found on other pages

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Cicatricial Pemphigoid

Cicatricial Pemphigoid (also known as ocular cicatricial pemphigoid, and benign mucous membrane pemphigoid) is a relatively rare chronic inflammatory disease mainly affecting mucous membranes, such as the conjunctiva and inside of the mouth. Sometimes the throat, esophagus, and other areas are affected as well. In 25% of cases, the skin itself is involved. Patients most commonly affected are females under the age of 60.

When the eyes are involved (75% of the time), the condition usually begins as a chronic conjunctivitis, followed by scarring of the conjunctiva. One, or more commonly both, eyes can be affected. Over time, this leads to bands of scar tissue connecting the surface of the eye to the inside of the eyelid (symblepharon), with a loss of the space between the eyelid and the eye (the conjunctival fornix). This can lead to inturning of the eyelid (entropion), and inturning of eyelashes (trichiasis) which can scratch the eye. The scarring of the conjunctiva can lead to a loss of mucous secreting cells which help to lubricate the eye, as well as closure of tear glands (lacrimal ducts). This leads to drying of the corneal and ocular surface, which potentially can cause symptoms of dry eye (gritty sensation, burning, light sensitivity, and loss of vision), as well as more severe corneal ulceration, scarring, and neovascularization (growth of blood vessels on the corneal surface). Blindness from these problems occurs in 25% to 33% of patients with the disorder. Other areas of the body can be involved as well, requiring care from dermatologists, gastroenterologists, and ENT specialists. A rheumatologist or internist may coordinate treatment of the patient.

The diagnosis of the disorder is usually based on clinical findings. However, biopsy of the conjunctiva, or other involved mucous membranes or skin, can give a definitive diagnosis 80% of the time. Immunopathologic techniques, such as direct immunofluorescence or direct immunoelectron microscopy can identify linear immune deposits at the level of the epithelial basement membrane of the examined tissue. Other disorders which can simulate ocular cicatricial pemphigoid include:

Acne rosacea
Drug induced pseudo-pemphigoid
Infectious disorders, such as fungal infections
Chemical burns
Sarcoidosis
Squamous cell carcinoma of the conjunctiva
Stevens-Johnson syndrome
Trachoma
Epidermal bullosa
Atopic keratoconjunctivitis

The disorder requires systemic treatment (oral medication) rather than simply local treatment to the eye. Immunosuppressive agents, such as steroids and dapsone (a sulfa derivative), are used, but can have side effects. Dapsone has showed improvement in the ocular and oral condition in up to 88% of cases. Laboratory testing is required while dapsone is used to rule out hemolytic anemia. In more severe cases, cyclophosphamide, steroids, and azathioprine in combination can be used.

Supportive ocular care involves dealing with complications of the conjunctival scarring, and restoring the ocular surface lubrication. Preservative free lubricating ointments and drops need to be used frequently. Treatment of eyelid malpositions and inturning eyelashes can prevent corneal scarring. In some cases, corneal transplant may be necessary to restore corneal clarity, but the results are often disappointing even when the underlying disease can be controlled.

Myasthenia Gravis

Myasthenia Gravis is an autoimmune disease of the muscles leading to weakness and easy fatigability. Commonly (80% to 90% of cases), the disorder presents itself with drooping upper eyelids (ptosis) and double vision. The symptoms are typically highly variable, intermittent, and may be asymmetrical between the two eyes. There may also be speech and swallowing difficulties, problems with facial expression, and weakness of the muscles of the arms and legs. The symptoms tend to improve after rest and in the morning, and tend to be worse later in the day and after exercise. The underlying problem is the development of antibodies to neuromuscular receptors present in all muscles (acetylcholine receptors). There is some relationship with the thymus gland, and there is a positive family history in about 5% of cases. Symptoms tend to appear in the middle age years for men and women. Some cases have occurred after bone marrow transplantation.

Patients with prominent ocular symptoms often develop a fairly severe drooping of one or both upper eyelids, worse when tired, that may interfere with vision. The double vision associated with myasthenia can be variable, and does not usually fit into a typical pattern of any one specific eye muscle being involved. Two recent tests that can be suggestive of myasthenia are the sleep test, and the ice pack test. In the sleep test, the degree of eyelid drooping and double vision lessens after the patient sleeps, or rests in a quiet, darkened room, for 30 minutes. In the ice pack test, the ice is placed over the droopy eyelid for 2 minutes. If the drooping lessens by 2 millimeters or more, myasthenia may be a cause. There are other office tests that can be performed to aid in diagnosis (Tensilon test).

Treatment of the disorder has typically been with drugs that block the enzyme that degrades the neurotransmitter acetylcholine at the neuromuscular junction. Thus, the neurotransmitter will stay in the junction longer, and is better able to stimulate the muscle to contract. However, these drugs seem to be less effective in reducing the ocular symptoms than those related to other parts of the body. Steroids and other immunosuppressants such as azathioprine have been successful in reducing ocular symptoms, and in slowing the worsening of the disease over time. These medications are not without side effects, and need to be closely monitored by the treating physician. In some cases, removal of the thymus gland may help the disorder.

Sarcoidosis

Sarcoidosis is an inflammatory disease of the body which commonly affects the eyes (25% to 50% of patients). It is more frequently seen in African-Americans at a rate of 10:1 compared to Caucasians. Females tend to be more commonly affected. Multiple systems throughout the body can show symptoms. Granulomas, or inflammatory nodules, develop in organs and throughout the body. They lungs are commonly affected (90% of cases), and pulmonary function may be reduced. Chest X-rays are commonly monitored in sarcoidosis, since nodules in and around the lungs can be visualized. Skin nodules can occur, as well as muscle aches, generalized fatigue, and low grade fever.

Less commonly, neurological and central nervous system involvement can occur, potentially affecting the visual system. An inflammatory neuropathy of the optic nerve of one or both eyes can lead to a loss of vision, or blind spots in the vision. Involvement of the brain itself can cause visual loss. Paralysis of the third cranial nerve has been reported, leading to double vision, as well as the facial nerve (seventh cranial nerve), leading to a paralysis of the facial muscles.

The most common ocular complication of sarcoid is inflammation within the eye, known as iritis or uveitis. In fact, sarcoidosis is one of the most common identifiable causes of uveitis in adults. Symptoms of uveitis can range from ocular redness, aching, and sensitivity to light, to blurred vision and floaters in the vision.

Eyelid nodules and orbital nodules can affect ocular movement, and in some cases, cause protrusion of the eye itself. If the tear gland (lacrimal gland) is involved, tear production may stop, and a significant dry eye problem can ensue. In some cases, nodules of the conjunctiva can occur. Biopsy of conjunctival or lacrimal gland nodules can be useful for diagnosis.

The cause of sarcoidosis is unknown. Diagnosis is by clinical findings as well as laboratory testing (elevation of the ACE level, or angiotensin converting enzyme level), chest X-ray, biopsy of nodules, and in some cases, Gallium scan of the head and neck. Treatment is by anti-inflammatory agents, most commonly steroids by mouth. Since the disorder tends to be chronically recurrent, the amount of steroid is titrated to the level of disease activity. In some cases, sarcoid has only a mild, self-limited course. In more severe cases, or in those affecting the central nervous system, stronger anti-inflammatory agents such as cyclophosphamide may be needed. Ocular steroids, usually in the form of eyedrops, can control inflammation, but may lead to complications of cataract and glaucoma.

Lyme Disease

Lyme disease is a multi-system disorder caused by an immune reaction to the spirochete Borrelia burgdorferi transmitted by the Dear tick (Ixodes dammini). There are common ocular complications during all stages of Lyme disease. The disease is most common in the Northeast and upper Midwest United States. It involves joint pain and dermatological and ophthalmic findings, as well as neurologic and cardiac abnormalities. Three stages of Lyme disease have been described, which may overlap:

Stage 1: The earliest stage includes a flu-like illness with a typical expanding "bull's-eye" rash. This may or may not be associated with a known tick bite. Some patients can develop conjunctivitis during this stage.

Stage 2: The second stage of the disease (after weeks to months of the disease) includes cardiac involvement (8%) and neurologic involvement (15%). This can include meningitis and paralysis of cranial nerves. Paralysis of the third or sixth cranial nerves affect eye movement, and lead to double vision. Paralysis of the seventh cranial nerve causes Bell's palsy, or drooping of one side of the face. During this stage inflammatory ocular disorders such as iritis, retinal vasculitis, chorioretinitis, and optic disc edema can occur. These conditions can cause a loss of vision.

Stage 3: The last stage of the disease, starting within 2 weeks to 2 years of the infection, include arthritis and chronic neurologic syndromes. This includes fatigue syndromes and focal central nervous system disorders. Ocular findings in this stage include corneal inflammation (keratitis) and double vision.

Treatment of Lyme disease is by commonly available antibiotics. Longer treatment is required for cases with neurological involvement, and intravenous antibiotics are required for severe neurological involvement and arthritis.

Eye Problems During Pregnancy

There are a number a visual and ocular changes that can occur during pregnancy, and most of these are self limited and resolve at the time of delivery. In some cases, symptoms might persist during nursing after delivery.

Dry eye - Dry eye symptoms can develop or worsen during pregnancy. This is due to changes in hormone levels during pregnancy. Symptoms of grittiness, foreign body sensation, itching, and ocular redness are common. Spontaneous tearing can also be a symptom of dryness, and this is referred to as reflex tearing. Dry eye can lead to fluctuations in vision and difficulty with contact lens wear. Artificial tears can help alleviate these symptoms.
Contact lens intolerance - Subtle changes in the shape of the eye during pregnancy may make contact lenses uncomfortable. This, in combination with ocular dryness, may greatly shorten the time that contact lenses can be worn during the day. Glasses might have to be worn instead of contact lenses.
Visual fluctuations - Changes in the shape of the eye during pregnancy can also lead to fluctuations in a glasses prescription, and may lead to intermittent blurred vision. It has been found that the cornea can become steeper and thicker during pregnancy, and there may be a decrease in corneal sensation. It is usually best to wait until after delivery to be fit for new glasses or contact lenses when the prescription stabilizes. Lasik and refractive surgery should also be done after delivery in order to insure that the correct prescription is treated.
Diabetes - Diabetic retinopathy can rapidly deteriorate during pregnancy, especially in cases of hypertension. Several dilated eye examinations during pregnancy might be necessary to monitor for this complication. Fortunately, the retinopathy can be safely treated during pregnancy if necessary.
Retinopathy related to Pregnancy Induced Hypertension (preeclampsia, PIH) - Hypertensive retinopathy from PIH can cause numerous retinal hemorrhages and in some cases floaters or blind spots in the vision. Symptoms can also include a temporary loss of vision, light sensitivity, blurry vision, auras, and the appearance of flashing lights, and dimming of the vision. These symptoms might indicate that PIH is developing, which may need to be emergently treated. The ob/gyn doctor should be contacted immediately if these symptoms occur.
Occlusive vascular disorders - It is well known that pregnancy represents a hypercoagulable state, through various changes that occur with platelets, clotting factors, and arteriovenous flow dynamics. Such changes may be related to the development of retinal artery and vein occlusions, disseminated intravascular coagulopathy (DIC), thrombotic thrombocytopenic purpura (TTP), amniotic fluid embolism, and cerebral venous thrombosis. Both branch and central retinal artery occlusions have been reported to occur in pregnancy. Although a hypercoagulable workup may detect an abnormality, routine hematological workup may be unremarkable. Retinal vein occlusions are less common than arterial occlusions.
Eye Drop Medication use - As described below, patients who are pregnant may require the use of medication to supplement their treatment. However, to ensure a decreased incidence of systemic absorption and toxicity two simple measures have been used. First, prescribing the patient the lowest recommended dose reduces the total amount of available drug. Secondly, patients are instructed when using topical medications to provide nasolacrimal duct and punctual occlusion thus reducing the amount of medication absorbed by the nasal mucosa.
Ophthalmic Medications During Pregnancy - There is very little knowledge about effect of ophthalmic medications on pregnancy, fetal well-being, and breast milk contamination. The National Registry of Drug-Induced Ocular Side Effects published a comprehensive review of their findings which are summarized below:
- Glaucoma medications (listed from safest to least safe, although most have some considerations):
  - Miotics (e.g., pilocarpine, echothiophate, carbachol) appear to be safe during pregnancy. The toxicity during lactation is unknown.
  - In animal studies, adrenergic agonists (e.g., brimonidine, Alphagan-P, Simbrinza, Combigan, Iopidine) have not demonstrated any fetal risk. Although no studies were conducted in pregnant patients, it may be used if necessary. Whether brimonidine is excreted in human milk is not known. Therefore, caution should be exercised since topical brimonidine given to human infants aged younger than 2 months has been reported to cause bradycardia, hypertension, hypothermia, and apnea.
  - Prostaglandin analogs (e.g., latanoprost, Lumigan, Xalatan, Travatan-Z, Zioptan) are not well studied, and the reports that do exist are conflicting. Prostaglandins are used systemically for labor induction and termination, and as such, the topical use for glaucoma during pregnancy raises natural concern. Therefore, caution should be exercised when latanoprost is administered in women who are pregnant or breastfeeding.
  - Beta-blockers (e.g., timolol, levobunolol, betaxolol, carteolol) should be avoided or used in the lowest possible dose in the first trimester of pregnancy and be discontinued 2-3 days prior to delivery to avoid beta-blockade in the infant. Due to case reports of beta-blockers being concentrated in breast milk, they should be avoided in mothers who are breastfeeding. However, timolol has been reported to be compatible with lactation according to the American Academy of Pediatrics.
  - Topical and systemic carbonic anhydrase inhibitors (e.g., acetazolamide, dorzolamide, brinzolamide, Azopt, Trusopt, Simbrinza, Cosopt, Diamox, Neptazane) are contraindicated during pregnancy because of potential teratogenic effects. They should be avoided in mothers who are breastfeeding because of the potential hepatic and renal effects to the infant. However, acetazolamide has been reported to be compatible with lactation according to the American Academy of Pediatrics.
- Mydriatics (dilating eye drops) - Use of occasional dilating drops during pregnancy for the purposes of ocular examination is safe. However, repeated use is contraindicated because of potential teratogenic effects of both parasympatholytics (eg, atropine) and sympathomimetics (eg, epinephrine). Due to either the anticholinergic or hypertensive effects on the fetus, use of mydriatics is contraindicated in mothers who are breastfeeding.
- Corticosteroids - Although systemic corticosteroids are contraindicated in pregnancy, there are no known teratogenic effects of topical steroids. Because little is known about the risk of topical corticosteroids during lactation, it should be avoided in mothers who are breastfeeding.
- Antibiotics - Antibiotics that are known to be safe during pregnancy include erythromycin, ophthalmic tobramycin, ophthalmic gentamicin, polymyxin B, and the quinolones. During lactation, polymyxin B and sulfonamides have been shown to be safe. Known antibiotics that should be avoided during pregnancy include the following: Chloramphenicol, Systemic gentamicin, Neomycin, Rifampin, Tetracycline, Systemic tobramycin.
- Antivirals - All antivirals should be avoided during pregnancy because of teratogenic effects. Moreover, they should be avoided in mothers who are breastfeeding because of tumorigenicity. However, acyclovir has been reported to be compatible with lactation according to the American Academy of Pediatrics.
- Fluorescein - No known teratogenic effects of fluorescein during pregnancy exist. However, the effect of fluorescein in mothers who are breastfeeding is unknown.
- Topical anesthetic - No known contraindications exist to the use of topical anesthetic drops in pregnancy or in mothers who are breastfeeding.

Eye and Orbital Cancer

There are numerous malignancies that can affect virtually any part of the eye, eyelids, orbit, and optic nerve. Fortunately, these conditions are very rare. Due to the wide scope of information concerning ocular and orbital malignancies, I recommend the following site for further information on this subject: Eye Cancer.com. This site contains an excellent review of ocular, orbital, and eyelid malignancies, including photographs, case histories, and treatment options. The site is written by a prominent specialist in the field of ocular cancer.