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Man presents with unilateral loss of vision after fever
Moderate vitritis, prominent retinal whitening and arterial sheathing along the superotemporal arcade were seen on exam.
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A 66-year-old man was referred to the New England Eye Center for loss of vision in his right eye.
Three months prior, the patient had been admitted to an outside hospital for a fever of unknown origin. An extensive workup for the fever was performed, but no cause was discovered. The patient was discharged 1 month later after resolution of the fever. However, a few days after discharge, he noticed a gradual loss of vision in the inferior field of his right eye associated with new floaters and flashing lights. He went to see a local ophthalmologist who started him on Valtrex (valacyclovir hydrochloride, GlaxoSmithKline) for a possible viral etiology and pressure-lowering drops to treat his elevated IOP. By the time the patient was examined at the New England Eye Center at Tufts Medical Center, his visual symptoms had been present for approximately 6 weeks.
The patient’s ocular history was otherwise unremarkable. Other than the recent fever of unknown origin, his only medical problems were hypercholesterolemia and hearing loss. His medications included Zetia (ezetimibe, Merck/Schering-Plough Pharmaceuticals), niacin and aspirin. His family history was significant for heart disease and diabetes. He did not smoke, drink or use illicit substances. He had not traveled recently.
Examination
On examination, the patient’s best corrected visual acuity was 20/100-2 in the right eye and 20/25 in the left eye. Pupils were equal, round and reactive to light with no afferent pupillary defect. Extraocular movements were full. IOP was 20 mm Hg in the right eye and 19 mm Hg in the left eye.
Confrontation visual fields showed an inferior hemi-field defect in the right eye. Anterior segment exam was remarkable for a few fine keratic precipitates, 2+ anterior chamber cells, 2+ vitreous cells and a mild nuclear sclerosis cataract in the right eye. The anterior segment exam of the left eye was unremarkable except for a mild nuclear sclerosis cataract. Dilated fundus exam demonstrated moderate vitritis and an area of superficial retinal whitening and arterial sheathing along the superotemporal arcade in the right eye. The fundus was normal in the left eye (Figures 1a and 1b). Fluorescein angiography showed vasculitis along the superotemporal arcade in the right eye in the area of the arterial sheathing visible on exam (Figure 2). Spectral domain optical coherence tomography revealed an epiretinal membrane with perifoveal thickening in the right eye (Figure 3). The left macula was normal.
Figure 1a. Fundus photography showed retinal whitening and arterial sheathing along the superotemporal arcade in the right eye. Moderate vitritis was present over the lesion. The left eye was unremarkable.
Images: Bartolini CE, Duker JS
Figure 1b. A mosaic of the right eye showed the extent of the lesion.
Images: Bartolini CE, Duker JS
Figure 2. Fluorescein angiography demonstrated vasculitis along the superotemporal arcade in the right eye.
Images: Bartolini CE, Duker JS
Figure 3. Spectral domain OCT revealed an epiretinal membrane with perifoveal thickening in the right eye.
Images: Bartolini CE, Duker JS
What is your diagnosis?
Retinitis
The differential diagnosis for a 66-year-old man with unilateral retinitis includes infectious etiologies such as acute retinal necrosis, progressive outer retinal necrosis, diffuse unilateral subacute neuroretinitis, toxoplasmosis, cytomegalovirus, endogenous bacterial or fungal infections, tuberculosis, syphilis, and Lyme disease. Sarcoidosis, Behçet’s disease and lymphoma might also mimic this clinical picture.
Because the retinitis was not progressing rapidly and appeared focal, acute retinal necrosis, progressive outer retinal necrosis and endophthalmitis seemed less likely. The patient was not immunocompromised, and the retinitis did not have the “brushfire” pattern typical of cytomegalovirus.
Based on the clinical appearance, the presumptive diagnosis of toxoplasmosis was made. Given that the patient had a recent fever of unknown origin, additional blood work and imaging were necessary to rule out another systemic process such as infection, inflammatory disease or neoplasm.
Follow-up
The patient had undergone an extensive workup during his initial hospitalization for fever. The results pertinent to his ophthalmic manifestations included a negative RPR, FTA-ABS, Lyme antibody, HIV, ANA, c-ANCA and p-ANCA. CBC, ESR and CRP were also within normal limits. A temporal artery biopsy was performed and was unremarkable. PPD was negative. A CT scan of the chest showed nonspecific hilar adenopathy, but subsequent bronchial lymph node biopsy was negative, ruling out sarcoidosis or lymphoma. Cardiac echo and blood cultures were similarly unrevealing.
To confirm the clinical impression, during the patient’s examination at the New England Eye Center, an anterior chamber tap was performed and polymerase chain reaction (PCR) of the aqueous fluid confirmed the diagnosis of toxoplasmosis. Intravitreal injections of clindamycin and dexamethasone were given, and the patient was started on oral Bactrim (sulfamethoxazole trimethoprim, Roche) and clindamycin.
Discussion
Toxoplasma gondii is a ubiquitous obligate intracellular protozoan parasite considered to be the most common cause of infectious uveitis. It is estimated to infect 13% to 50% of people worldwide. In humans, it is most commonly acquired congenitally or by eating the meat of infected animals. Other sources of infection include contaminated garden vegetables, water or cat litter boxes. It is unclear what causes primary ocular toxoplasmosis or triggers its recurrences. Many individuals infected with T. gondii do not develop ocular disease. Although it is a relatively uncommon condition in early childhood and after age 50 years, it is important for the ophthalmologist to remember ocular toxoplasmosis in the differential diagnosis of an older patient who presents with posterior uveitis.
Patients with ocular toxoplasmosis usually present with decreased vision, floaters, pain, photophobia and a red eye. Toxoplasmosis retinochoroiditis is seen as a result of primary infection or recurrence. On examination, there is a gray-white focus of retinal necrosis that may or may not occur at the edge of a pre-existing chorioretinal scar. Associated features include choroiditis, retinal vasculitis, vitritis, iritis or papillitis. Even though a satellite lesion adjacent to a chorioretinal scar is classic for recurrence of toxoplasmosis chorioretinitis, it does not distinguish between congenital and postnatally acquired infection. Likewise, the absence of a pre-existent scar may not definitively indicate primary retinal disease unless the patient shows evidence of recent seroconversion.
A definitive diagnosis of ocular toxoplasmosis is not always possible. Many cases are presumed based on the clinical appearance alone. Supportive evidence can be found in serologic results, exclusion of other entities and response to antiparasitic treatment. Antibody detection may help in differentiating between recently acquired and chronic infection, but serology is generally more helpful for ruling out disease. IgM antibodies appear within the first week and generally decline after a few months. In contrast, IgG antibodies are produced within 2 weeks of infection and remain positive for life. In cases in which the diagnosis is unclear and confirmation is needed, intraocular fluid can be examined for T. gondii DNA using PCR.
In the immunocompetent individual, ocular toxoplasmosis may be mild and does not require treatment. Indications for treatment include a two-line decrease in visual acuity, lesions located within the macula or affecting the optic nerve, moderate to severe vitritis, newly acquired infections, and immunodeficiency. Relative criteria for treatment include multiple active lesions or an active lesion lasting longer than 1 month.
Many medications are effective in the treatment of ocular toxoplasmosis. Triple therapy, a combination of pyrimethamine, sulfadiazine and oral corticosteroids, is most commonly used. Successful alternatives include quadruple therapy (triple therapy plus clindamycin), atovaquone, spiramycin, azithromycin, minocycline and Bactrim double strength. Interestingly, there are no randomized controlled trials showing superiority of any one systemic regimen. Typically, antiparasitics are started at least 24 hours before giving steroids. Treatment should be continued until the retinochoroiditis is no longer active, which usually takes 4 to 6 weeks.
Unfortunately, the systemic regimens are costly and associated with side effects. Intravitreal therapy with clindamycin and dexamethasone provides greater drug bioavailability, has a better safety profile and requires fewer follow-up visits. It is a great option for patients who cannot tolerate systemic medications. Regardless, newly acquired toxoplasmosis may be better treated with systemic therapy, as shown by a greater reduction in lesion size with triple therapy when compared with intravitreal therapy.
In general, patients with ocular toxoplasmosis have good visual outcomes. Permanent vision loss is unlikely unless the lesions involve the macula or optic nerve, or the clinical course is complicated by choroidal neovascularization or retinal detachment. Recurrences occur at a reported rate of 57% to 79% and are not prevented by treatment with current regimens. However, immunocompromised and elderly patients may have a more prolonged and severe clinical course. Ocular lesions appear to respond to standard antiparasitic drug therapies, but maintenance therapy with Bactrim or clindamycin is probably necessary to prevent reactivation of disease in immunocompromised patients.
Conclusion
In summary, a 66-year-old man presented with fever and gradual onset right-sided inferior visual field loss and was found to have chorioretinitis, vasculitis and vitritis in the right eye on clinical exam. Primary toxoplasmosis was presumed based on the clinical appearance and the exclusion of other entities. This was confirmed with PCR of the aqueous fluid.