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Morning Rounds

When the Old News Held the Clue

By John W. Kitchens, MD, Thomas A. Weingeist, PhD, MD,
and Andrew J. Lotery, MD
Edited by Thomas A. Oetting, MD

George Stringer,* a tall, thin gentleman, was referred to the Iowa City Veterans Administration Hospital with a diagnosis of uveitis of unknown origin. He was initially treated with artificial tears and new glasses, which did not relieve all of his symptoms.

Mr. Stringer was 59 but appeared older. When we first saw him, he complained of decreased vision, persistent floaters and light flashes that had gradually worsened over the past year. Other than these complaints, he did not report any significant previous ocular problems. He did report generalized fatigue, a 20-pound weight loss and a chronic cough. The weight loss had occurred over the past six months. As for the cough, he was a chronic smoker, at the rate of two packs per day for the past 35 years.

Mr. Stringer’s BCVA was 20/25 on the right and 20/50 on the left. His IOPs, motility and visual fields were all normal. The slit-lamp exam revealed moderate cell and flare bilaterally and a prominent posterior synechia in the left eye. The dilated fundus exam revealed significant vitreous cells limiting visualization of the macula. In both eyes, he had 10 to 20 small, superficial, white retinal lesions. The lesions were less than 50 microns in size and were scattered along the inferior half of the midperipheral retina. His optic nerves appeared normal.

Systemic Suspects
Our differential diagnosis for Mr. Stringer’s vitritis and chorioretinitis included several serious systemic diseases—sarcoidosis, syphilis, lymphoma and tuberculosis. He underwent an extensive evaluation, which included a complete blood count, blood chemistries, angiotensin-converting enzyme, HLA-B27, syphilis serology and TB skin testing, all of which were negative. His chest X-ray was unremarkable. We started him on frequent topical corticosteroids and a cycloplegic agent.

When he returned two weeks later with little improvement in vision or inflammation, we gave him a sub-Tenon’s injection of 4 milligrams of triamcinolone acetonide (Kenalog) to his left eye. His symptoms, visual acuity and inflammation improved moderately with this injection.

Was This Ocular Lymphoma?
Given Mr. Stringer’s age and recent weight loss, our primary concern was intraocular lymphoma. He was referred to the neurology department for evaluation, an MRI and a lumbar puncture with cytologic analysis of the cerebrospinal fluid. However, the results from these tests were all normal.

Mr. Stringer returned three weeks later. This time, he reported a sudden loss of vision in his right eye, to the counting fingers level. His examination revealed 2 to 3+ vitreous cell bilaterally. The loss of vision appeared to be due to a branch retinal arteriolar occlusion in the macula area. Additionally, the multiple small, white midperipheral retinal opacities had increased in size and number.

We decided to dig a little deeper into his medical history. Upon further questioning, Mr. Stringer noted that he had a long history of “loose stools.” (Interestingly, when we first asked him if he had had a change in his bowel movements, he said no. Our question was faulty, as he eventually told us that he “had not had a solid bowel movement in over three years”—thus, no recent change.) He also noted recent blood in his stool. We quickly referred him to the gastroenterology service for evaluation of his chronic diarrhea for a possible diagnosis of Whipple’s disease, and he underwent colonoscopy with jejunal biopsy. The biopsy revealed the telltale periodic acid Schiff’s reagent (PAS) staining of foamy macrophages in the lamina propria.

Whipple’s Disease
Whipple’s disease is a rare disorder (18 to 30 cases per year per 100,000 people) that commonly affects middle-aged men. It is caused by the bacterium Tropheryma whippelii and is characterized by malabsorption, diarrhea, progressive weight loss and migratory polyarthritis.

Ocular manifestations often occur late in the disease. Ophthalmic findings may be secondary to central nervous system involvement (gaze palsies, nystagmus and ophthalmoplegia) or direct intraocular involvement (uveitis, vitritis, retinitis and optic neuritis). The latter is uncommon. In a study of 34 patients with ocular Whipple’s disease, 22 of the patients had ocular manifestations secondary to CNS involvement, while eight presented with CNS and intraocular signs. Only four patients presented with intraocular signs alone.¹

Diagnosis can be made early by jejunal biopsy demonstrating characteristic PAS-positive staining of foamy macrophages in the lamina propria of the small bowel mucosa. Electron microscopic evaluation of vitreous biopsies demonstrates bacillary bodies. PCR detection of the 16S rRNA gene of the organism is also diagnostic.² Late diagnosis may be made with pathognomonic neurologic findings of oculomasticatory myorhythmia.³

Recommended treatment consists of intravenous induction therapy followed by long-term maintenance therapy. Current recommendations are IV induction therapy with either ceftriaxone (Rocephin; 2 grams twice daily) plus streptomycin (1 g daily) for 14 days or penicillin (1.2 million units) plus streptomycin (1 g daily) for 10 to 14 days. Maintenance therapy consists of one year of double-strength trimethoprim-sulfamethoxazole (Septra; 960 milligrams).^4,5 Recurrences are common.

Patient Update
Mr. Stringer was started on IV ceftriaxone for two weeks, followed by oral antibiotics therapy. He responded well: He regained some weight, his chronic diarrhea and fatigue resolved, and his intraocular inflammation and visual acuity improved.


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1 Avila, M. P. et al. Arch Ophthalmol 1984; 102:384–390.
2 Relman, D. A. et al. N Engl J Med 1992;327: 293–301.
3 Schwartz, M. A. et al. Ann Neurol 1986; 20:677–683.
4 Keinath, R. D. et al. Gastroenterology 1985; 88:1867–1873.
5 Schnider, P. J. et al. Ann Neurol 1997;41: 561–562.

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Dr. Kitchens is a retina fellow at the University of Miami; Dr. Weingeist is professor and head of ophthalmology at the University of Iowa; and Dr. Lotery is professor and head of ophthalmology at the University of Southampton, England.

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* Patient name is fictitious.