Man presents with blind spot in right eye

On examination, bilateral acute chorioretinitis was found.

Priti Batta

Namrata Nandakumar

A 60-year-old man presented to the retina clinic complaining of an inferior scotoma in his right eye for 5 days. His medical history was notable for cirrhosis and hepatocellular carcinoma, for which he underwent liver transplantation. He subsequently developed graft-versus-host-disease, which persisted despite immunosuppression and had been complicated by opportunistic infections due to leukopenia. He was most recently admitted to the hospital for treatment of herpes simplex virus esophagitis.

Examination

On ophthalmic examination, the patient’s best corrected visual acuity was 20/25 in both eyes. His extraocular motility was full in both eyes, and his pupils were reactive with no relative afferent pupillary defect. His IOP was 15 mm Hg in the right eye and 17 mm Hg in the left eye. Anterior segment evaluation revealed mild anterior chamber cell and flare in the right eye. Dilated funduscopic examination of the right eye revealed a dense retinal infiltrate, measuring approximately 3 disc diameters, extending from the optic nerve along the superior arcade (Figure 1a). In the left eye, a subtle area of retinal whitening was noted along a vein inferonasal to the optic disc (Figure 1b). No vitreous cells or chorioretinal scars were observed in either eye.

Figure 1a. Funduscopic photograph of the right eye revealed a full-thickness retinal infiltrate, measuring approximately 3 disc diameters. Images: Monson BK, Rizzo JL and Marx JL

Figure 1b. A focal area of retinal whitening adjacent to a retinal vein was noted inferonasal to the optic disc in the left eye.

Figures 2a-2c. Fluorescein angiography of the right eye demonstrating early hypofluorescence (24 sec) (a) and late hyperfluorescence and leakage (11 min 53 sec) (b). Fluorescein angiography of the left eye (2 min 40 sec) demonstrating late hyperfluorescence and leakage of the lesion (c).

Fluorescein angiography in the right eye demonstrated early hypofluorescence of the lesion, followed by late hyperfluorescence and leakage (Figures 2a and 2b). Fluorescein angiography in the left eye showed late hyperfluorescence and leakage from the vein overlying the area of retinal whitening (Figure 2c).

What is your diagnosis?

Bilateral acute chorioretinitis

This patient presented with bilateral acute chorioretinitis. The differential diagnosis in the setting of immunosuppression includes cytomegalovirus retinitis, herpes simplex virus or herpes zoster virus retinitis, and toxoplasmosis chorioretinitis. A systemic workup was initiated, and a diagnostic anterior chamber paracentesis was performed.

Serum titers of anti-toxoplasmosis antibodies were positive at IgG greater than 2,500 IU/mL, while the IgM titer was negative at 0.13 IU/mL. Polymerase chain reaction (PCR) analysis of the aqueous obtained from the anterior chamber tap was performed for toxoplasmosis, cytomegalovirus, herpes simplex and herpes zoster, and it confirmed the diagnosis of toxoplasmosis. The clinical appearance of a focal, creamy necrotic chorioretinitis in an immune-compromised patient is consistent with toxoplasmosis.

Discussion

The necrotizing chorioretinitis in our patient was most likely secondary to immunosuppression after organ transplantation. While Toxoplasma gondii is a common cause of posterior uveitis in adults, it is relatively rare in immunocompromised patients. Active toxoplasmosis is almost always reactivated congenital disease in immune-competent patients and is most likely acquired in immunocompromised patients. Given the patient’s pre-transplant seropositive toxoplasma IgG, it is unlikely our case represents acutely acquired infection. It is more likely the toxoplasma was introduced to our patient by immunocompromised reactivation of congenital infection, as the majority of cases of ocular toxoplasmosis are thought to be acquired in utero. Indolent organisms may reside in the nerve fiber layer, thus circumventing the prerequisite of a chorioretinal scar.

Approximately 10% of infants born with congenital toxoplasmosis manifest with ocular involvement without clinical evidence of the disease in other organ systems. About 60% to 70% are asymptomatic at birth. However, a substantial proportion of asymptomatic infants develop delayed adverse sequelae of the congenital infection months to years later, with chorioretinitis being the most common finding, occurring in about 80% of cases.

Active, bilateral or multifocal lesions and absence of vitritis may be seen in the immunosuppressed host, as was the case with our patient. In addition, immunocompromised patients may present with more relentlessly progressive, severely necrotic and hemorrhagic lesions.

Toxoplasmosis chorioretinitis is generally diagnosed based on clinical examination. In ambiguous cases, PCR has been shown to have high sensitivity and specificity in the identification of toxoplasmosis and is minimally invasive. IgG serology is unreliable in diagnosing toxoplasmosis, given that between 20% and 70% of the U.S. population is IgG positive for toxoplasmosis. Also, particularly in the leukopenic or immunosuppressed patient, some authors suggest serologic studies may have unreliable sensitivity and specificity.

Management

Treatment of ocular toxoplasmosis infection should be promptly initiated in visually symptomatic patients or when the macula or the optic nerve is threatened. Classic therapy includes oral pyrimethamine, sulfadiazine and folinic acid. Alternatively, monotherapy with clindamycin or double-strength Bactrim (sulfamethoxazole and trimethoprim, Roche) or in combination with classic therapy has been shown to be effective. To date, no randomized clinically controlled study has established superiority of any of the proposed regimens, but these alternatives may be useful in consideration of drug allergy or compliance. Additionally, topical anti-inflammatory and cycloplegic agents may be initiated, followed by oral prednisone at least 24 to 48 hours later. Non-sight-threatening lesions may be closely observed, particularly in pregnant patients, to reduce risks of systemic antibiotic therapy to the fetus.

Our patient began treatment for acute toxoplasmosis chorioretinitis with oral pyrimethamine, sulfadiazine and leucovorin. Two weeks after the initiation of therapy, the lesions were markedly diminished bilaterally, with resolution of the scotoma.

References:

• Chiquet C, Fleury J, Blanc-Jouvan M, et al. Acquired ocular toxoplasmosis (panuveitis) after liver transplantation. J Fr Ophtalmol. 2000;23(4):375-379.
• Cohen SN. Toxoplasmosis in patients receiving immunosuppressive therapy. JAMA. 1970;211(4):657-660.
• Engstrom RE Jr., Holland GN, Nussenblatt RB, Jabs DA. Current practices in the management of ocular toxoplasmosis. Am J Ophthalmol. 1991;111(5):601-610.
• Perry DD, Merritt JC. Congenital ocular toxoplasmosis. J Natl Med Assoc. 1983;75(2):169-174.
• Ruskin J, Remington JS. Toxoplasmosis in the compromised host. Ann Intern Med. 1976;84(2):193-199.
• Singer MA, Hagler WS, Grossniklaus HE. Toxoplasma gondii retinochoroiditis after liver transplantation. Retina. 1993;13(1):40-45.
• Soheilian M, Sadoughi MM, Ghajarnia M, et al. Prospective randomized trial of trimethoprim/sulfamethoxazole versus pyrimethamine and sulfadiazine in the treatment of ocular toxoplasmosis. Ophthalmology. 2005;112(11): 1876-1882.

• Bryan K. Monson, MD, Jennifer L. Rizzo, MD, and Jeffrey L. Marx, MD, can be reached at New England Eye Center, Tufts University School of Medicine, 750 Washington St., Box 450, Boston, MA 02111; 617-636-4219; fax: 617-636-4866; website: www.neec.com.

• Edited by Priti Batta, MD, and Namrata Nandakumar, MD. Drs. Batta and Nandakumar can be reached at New England Eye Center, Tufts University School of Medicine, 750 Washington St., Box 450, Boston, MA 02111; 617-636-4219; fax: 617-636-4866; website: www.neec.com.
• Disclosures: No products or companies are mentioned that would require financial disclosure.