Case Report
Irritated Eyes, Other Symptoms Reveal Rare Thyroid Dysfunction

This patient's superior limbic keratoconjunctivitis was caused by hyperthyroidism. Here's a look at your role in treating the whole patient.

Andrew M. Archila, O.D., San Diego and Todd Sheldon, O.D.,Beaufort, S.C.

A 21-year-old white female was referred to our clinic by the physician on call. She initially presented to the physician complaining of worsening irritation in both eyes for three days. She described it as a constant burning sensation and said she felt like "grain was in her eyes." She had been irrigating her eyes with water, but reported no relief.

Table 1. Symptoms of Hyperthyroidism • Nervousness • Heat intolerance • Perspiration • Fatigue • Palpitation • Insomnia • Early waking • Brittle nails

The physician noted thyromegaly, watery eyes and a possible ocular foreign body. The patient also said that she felt "miserable." Upon further questioning, she reported increased fatigue, nervousness, difficulty breathing, weight loss and decreased appetite. Small tremors in her hands were evident, and her pulse rate was elevated. The physician ordered blood work, including a complete blood count (CBC) and thyroid function tests, and then referred the patient to us to treat her ocular condition.

At the optometry clinic, the patient reiterated her chief complaint and other symptoms. Her ocular history was non-contributory and revealed no past trauma or foreign bodies. Her past medical history and family history were unremarkable. She had no allergies and was not taking any medications.

Diagnostic Data
Best-corrected visual acuity was 20/20 O.U. Extraocular muscles were unrestricted in both eyes, and pupil exam was normal. Intraocular pressures were 18mm Hg O.D., 19mm Hg O.S.

Superior limbic keratoconjunctivitis of Theodore appears at the limbal margin, specifically in the 10-2 o'clock position.

Biomicroscopy revealed 2-3+ injection of the superior bulbar conjunctiva O.D.; this was most intense at the limbus.

Also evident were 3+ papillae on the superior tarsal conjunctiva upon lid eversion, corneal filaments with early micropannus of the superior corneas, and punctate staining on the upper third of both corneas. The anterior chamber angles were open, and no cells or flare were evident in either eye.

Exophthalmometry results were 20 O.D., 19 O.S. This was less than E. Hertel's standards of greater than 21 for a proptotic eye.1 A phenol red thread test revealed mild dry eye in both eyes. Direct ophthalmoscopy was unremarkable.

Diagnosis
We diagnosed superior limbic keratoconjunctivitis of Theodore with an associated filamentary keratitis and mild dry eye in both eyes.

Treatment and Follow-up
Treatment included removal of the corneal filaments in the office, erythromycin ointment QID and artificial tears as needed. We told the patient to return in two weeks, sooner if her condition worsened.

Rose Bengal staining reveals a punctate stain in the superior bulbar conjunctiva. Also note the corneal filaments.

Two weeks later her condition remained stable. She reported feeling "a little less irritated." However, the slit lamp exam showed no improvement in objective findings. Corneal filaments were still evident, so we debrided them as before. We added Mucomyst (acetylcystiene) 10 percent every three hours while awake and Lacri-Lube at night to the treatment regimen. At the next follow-up her exam revealed fewer filaments, and some subjective improvement. We told her to return as needed.

We also explained to the patient that her condition might be related to hyperthyroidism and referred her back to the physician.

Her blood work revealed decreased serum TSH (thyroid-stimulating hormone) levels of 0.02 uIU/ml and increased serum free T4 (thyroxine) levels of 6.0 ug/dl. These were definitive for a diagnosis of hyperthyroidism.2 Normal serum levels are 2.0-5.4 uIU/ml of TSH and 1.0-2.3 ug/dl of free T4.2

The physician prescribed Inderal (propanolol) 20mg TID to relieve the hand tremors and counseled the patient on available treatments. However, the patient was released from the military because of her condition and lost to follow-up.

Discussion
Superior limbic keratoconjunctivitis of Theodore, commonly referred to as SLK, is a chronic inflammatory disorder of the ocular surface that may be associated with hyperthyroidism.3,4 Frederick H. Theodore, M.D., first described the condition in 1963.

Table 2. Differential Diagnosis of SLK 5,15 Contact lens SLK • Universally responds to discontinuation of contact lens wear and aggressive artificial tear therapy. Giant Papillary Conjunctivitis • SLK patients have fine papillae. • GPC is more likely related to contact lens wear. 'Floppy Lid' Syndrome • Typically occurs in obese individuals. • Upper lid everts with minimal force. Vernal Conjunctivitis • May be seasonal in nature. • Commonly occurs in young males. • Giant papillae are present. • More dramatic presentation than SLK.

SLK of Theodore is somewhat uncommon. When it occurs, it's usually in women ages 20-50.5 Studies show that 20-65 percent of patients with SLK have associated hyperthyroid-ism.1,3,5,6 Hyperthyroidism has a pre-valence of 0.4 percent of the general population, with women six times more likely to have it than men.7

SLK often foretells severe Graves' ophthalmopathy as well. Patients who have SLK and thyroid disease have a 90 percent chance of manifesting some level of ophthalmopathy; about half of those cases will be classified as severe.1

The exact cause of SLK of Theodore is unknown, but researchers have suggested several possibilities. One study suggests that SLK is associated with environmental agents.8 Others suggest immunological, infectious or mechanical origins. An immunological origin seems unlikely because there are minimal inflammatory changes apparent with light microscopy, immunofluorescence reveals no immunoglobulin deposition and eosinophils are not apparent.6 Also, SLK patients often respond poorly to topical corticosteroids.6 No causative virus or other infectious agent has been isolated to date, so an infectious origin is also unlikely.8

Most authors agree that the cause is likely mechanical.6,9,10 One theory suggests SLK is caused by the movement of the upper eyelid. Specifically, the eyelid is in tight apposition to the superior bulbar conjunctiva due to a thyroid abnormality, exophthalmos or chronic inflammation. The superior bulbar conjunctiva, which may be lax due to a congenital or aging process, is subject to constant abnormal movement as the eyelid opens and closes, resulting in chronic irritation.6

A papillary reaction occurred in this patient with superior limbic keratoconjunctivitis of Theodore.

Other researchers believe SLK may be caused, at least in part, by a tear deficiency. Tear deficiency in the upper conjunctiva may result in abnormal friction between the upper lid and the superior limbal region. This causes irritation and interferes with the supply of essential chemicals such as growth factors and vitamin A to the upper conjunctiva.10

Patients with SLK typically present with non-specific symptoms of foreign body sensation and associated burning, photophobia and mucoid discharge.3 They may report feeling worse than the examination indicates, and they may report that one eye feels worse than the other.3,11 Subjective complaints of dry eye are not uncommon; 25 percent of SLK patients have keratoconjunctivitis sicca.3,6 Patients may also experience associated systemic symptoms related to underlying hyperthyroidism (table 1).7

SLK appears at the limbal margin, specifically in the 10-2 o'clock position. Slit lamp exam reveals mild to moderate injection and, in more advanced cases, thickening of the limbal conjunctiva due to keratinization. A classic clinical feature of SLK: a relatively intense punctate stain in the superior bulbar conjunctiva, as observed with rose Bengal or lissamine green dye.11

Papillae are also evident on the superior palpebral conjunctiva and give it a velvety appearance. The inferior palpebral conjunctiva remains uninvolved. Corneal filaments have been reported in one-third of SLK patients.3,9

Your work-up starts with a thorough case history. SLK can last up to 10 years with various flare-ups, so ask about any past exacerbations and remissions.5 Perform a thorough slit lamp exam, complete with lid eversion, to rule out other ocular conditions (table 2). If you suspect SLK, refer the patient for evaluation of serum T3 (triiodothyronine), T4 and TSH levels.2 A quantitative tear test such as phenol red thread or Schirmer's is also important to determine if dry eye exists.10

Currently, there is no definitive treatment for SLK other than to relieve the patient's symptoms. Options for doing so include:

• Topical medications. These are usually the first line of treatment. Lubricants, topical vitamin A and acetylcysteine are all reasonable initial choices.6 Mast cell stabilizers have been investigated as viable options, although their mechanisms remain unclear.12,13

• A soft bandage contact lens or pressure patching. Although a viable option, this provides only temporary relief of symptoms.6,9

• Lacrimal punctal occlusion. A study suggested this may help relieve dry eye symptoms in SLK patients.10

• Chemocauterization of the superior conjunctiva. Silver nitrate 0.25 percent is applied to the upper tarsal and bulbar conjunctiva with a cotton-tipped applicator. In moderate cases, this may relieve symptoms for several months or longer.

• Resection of the involved conjunctiva. This may be warranted in severe recalcitrant cases.14 A limbal-based flap is turned down and then dissected out. The remaining conjunctiva is not sutured. Antibiotic drops are then prescribed.14

In cases of hyperthyroidism and SLK, correction of the thyroid dysfunction can also be beneficial.6 Options include:

• Beta-blockers. These are acceptable for temporary relief of symptoms, but these are only palliative. Beta-blockers prevent tremors and palpitations but have no direct effect on the thyroid hormones.

• Anti-thyroid medications. Propylthiouracil and Tapazole (methimazole) prevent the thyroid from producing T hormones, but these medications may take a few weeks to produce noticeable results. Another drawback: The underlying hyperthyroidism may recur if the patient discontinues these medications.

• Radioactive iodine. This is an available permanent treatment. The radiation, which can be taken orally, kills thyroid cells selectively. It takes one to two months, but it can cure the hyperthyroidism by a single dose.

• Surgical removal of the thyroid gland. This is utilized infrequently and is a last resort.7

This case is another example of how we can treat the patient's eye condition, help diagnose underlying systemic disease and comanage patients with primary-care physicians. A complete history, thorough slit lamp exam, patient education and timely referral enable us to treat the whole patient and not just his or her ocular disorder.

Drs. Archila and Sheldon both now practice in the U.S. Navy.

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