Woman has decreased vision, pain and photophobia in left eye

There was active uveitis, increased pressure, dense vitritis and peripheral yellow chorioretinal lesions.

Catherine A. Cox

Jordana F. Goren

A 58-year-old woman was referred by her primary care doctor for a 4-day history of decreased vision, periocular pain and light sensitivity in her left eye to the New England Eye Center for evaluation.

Medical history was significant for insulin-dependent diabetes. Ocular history was unremarkable. Social history was notable for travel to her native Uruguay 5 months before presentation, where she had experienced a gastrointestinal illness that lasted several weeks. Review of systems was positive for headaches, night sweats and a swollen tender node on the back of her left neck.

Examination

Best corrected visual acuity was 20/30 in the right eye and 20/60 in the left. Pupils were equal, round and reactive to light without relative afferent pupillary defect. Extraocular motility was full. IOP was 14 mm Hg in the right eye and 28 mm Hg in the left.

On slit lamp examination, the right eye was unremarkable, and the left eye demonstrated diffuse corneal edema with Descemet folds, mutton fat keratic precipitates and 2+ cell in the anterior chamber. On dilated fundus examination, there was mild background diabetic retinopathy in the right eye. The left eye had dense vitritis, multiple blot/flame hemorrhages, and two peripheral yellow chorioretinal lesions with overlying vitritis in the inferotemporal quadrant (Figures 1a and 1b). Fluorescein angiography demonstrated central and peripheral staining of the chorioretinal lesions, without evidence of vasculitis (Figure 2). There was also a tender posterior cervical lymph node noted on neck palpation.

Figure 1a. Color fundus photograph of the left eye demonstrates vitritis as well as flame hemorrhages. Images: Sitko K, Duker JS

Figure 1b. Color photo of two peripheral chorioretinal lesions with overlying vitritis inferotemporally.

Figure 2. Left eye — fluorescein angiogram of two peripheral chorioretinal lesions 7 minutes after injection demonstrating late staining centrally and peripherally within the lesion.

What is your diagnosis?

Localized chorioretinitis

The patient presented with localized chorioretinitis, with overlying vitritis and associated granulomatous uveitis. Toxoplasmosis and acute retinal necrosis secondary to herpes simplex or varicella zoster virus were highest on the differential diagnosis. Other possible etiologies included syphilis, tuberculosis, Behçet’s disease, endogenous bacterial or fungal endophthalmitis, or masquerade syndromes such as lymphoma. An atypical presentation of a white dot syndrome with vitritis (ie, birdshot chorioretinitis) should be considered but is much less likely given the clinical presentation.

Follow-up

The patient was admitted and started on empiric treatment with IV acyclovir, pyrimethamine, sulfadiazine, prednisone and folinic acid to prevent bone marrow suppression. She underwent an anterior chamber tap for diagnostic purposes. She was also treated with topical brimonidine and timolol/dorzolamide to control IOP. Labs sent on presentation were significant for negative HIV, VZV, RPR, FTA-ABS antibodies and PPD. ACE levels were normal, and chest X-ray was without infiltrate or lymphadenopathy. Toxoplasma gondii IgG and IgM were positive. Anterior chamber PCR was positive for toxoplasma and negative for HSV; however, there was not adequate sample to test for VZV.

The acyclovir was discontinued when the toxoplasma titers returned positive and the HIV serology was negative. Once acute retinal necrosis was ruled out, the patient was discharged from the hospital because she no longer required treatment with IV acyclovir, and at that time, she had already noted subjective improvement in her vision with a decrease in the vitritis. Her lymphadenopathy, headaches and night sweats had resolved. She was discharged on oral pyrimethamine, sulfadiazine, folinic acid and oral prednisone to the care of her community ophthalmologist with plans to follow her CBC weekly while on treatment.

Discussion

Active ocular infection with toxoplasmosis typically manifests as a localized necrotizing retinitis. The classic lesion is a gray-white focus of retinal necrosis at the edge of a pre-existing pigmented chorioretinal scar, which is generally thought to be secondary to reactivation of congenital disease. An associated chorioretinal scar may not be present, in particular, with recently acquired disease. Ocular toxoplasmosis is typically a self-limited process in immunocompetent patients, and most episodes will resolve over a period of 1 to 2 months. Historically, toxoplasmosis has been thought to be almost entirely secondary to reactivation of a congenital infection; however, it is now recognized that acute infection makes up a significant proportion of ocular toxoplasmosis cases, as may be the case in this patient, who had recently traveled to Uruguay and experienced a gastrointestinal illness. In southern Brazil, it has been shown that the majority of infected individuals were infected after birth and not prenatally. In one study that followed a group of 100 seronegative subjects, 21% seroconverted after a period of 7 years.

Eighty percent to 90% of acute toxoplasmosis cases are completely asymptomatic, and when there are symptoms, they are typically non-specific and include lymphadenopathy, fever and headache. Ocular manifestations occur in only about 1% of acutely infected patients. One study of the epidemic in Atlanta in 1977 followed 29 acutely infected subjects over time, and only one of these patients developed ocular toxoplasmosis over 4 years. A larger outbreak in British Columbia in 1994 estimated the incidence of ocular toxoplasmosis to be between 0.26% and 0.69% during the acute initial infection.

The clinical features often make the diagnosis of ocular toxoplasmosis. Serologic studies may be helpful in selected cases, but a positive systemic serology itself does not confirm the diagnosis, given the high rate of seropositive individuals found in many populations. A negative serology, however, can assist in eliminating the disease from the differential diagnosis. If there is an atypical presentation or diagnostic confusion, aqueous humor sampling can be a useful method in diagnosing infection in cases of posterior uveitis, particularly when utilizing PCR. In a study of 152 cases of posterior uveitis, anterior chamber sampling led to a change in treatment regimen in 24% of cases and a focusing of treatment in an additional 12% of cases.

References:

• Akstein RB, Wilson LA, Teutsch SM. Acquired toxoplasmosis. Ophthalmology. 1982;89(12):1299-1302.
• Burnett AJ, Shortt SG, Isaac-Renton J, King A, Werker D, Bowie WR. Multiple cases of acquired toxoplasmosis retinitis presenting in an outbreak. Ophthalmology. 1998;105(6):1032-1037.
• Rothova A, de Boer JH, Ten Dam-van Loon NH, et al. Usefulness of aqueous humor analysis for the diagnosis of posterior uveitis. Ophthalmology. 2008;115(2):306-311.
• Silveira C, Belfort R, Muccioli C, et al. A follow-up study of Toxoplasma gondii infection in southern Brazil. Am J Ophthalmol. 2001;131(3):351-354.
• Weiss LM, Dubey JP. Toxoplasmosis: A history of clinical observations. Int J Parasitol. 2009;39(8):895-901.

• Kevin Sitko, MD, and Jay S. Duker, MD, can be reached at New England Eye Center, Tufts University School of Medicine, 800 Washington St., Box 450, Boston, MA 02111; 617-636-4219; fax: 617-636-4866; website: www.neec.com.

• Edited by Catherine A. Cox, MD, and Jordana F. Goren, MD, MS. Drs. Cox and Goren can be reached at New England Eye Center, Tufts University School of Medicine, 800 Washington St., Box 450, Boston, MA 02111; 617-636-4219; fax: 617-636-4866; website: www.neec.com.