6-year-old girl presents with decreased vision, macular lesion

The left eye had chorioretinal scarring with pigmentation in the macula, and the right eye had a scar with pigmentary changes along the superior arcade.

Issue: June 1, 2006

ByJay S. Duker, MD

ByShazia Ahmed, MD

Jane
Loman

Zinaria Williams

A 6-year-old white girl was referred from an outside ophthalmologist for a retinal evaluation. The patient experienced a recent decrease in visual acuity of the left eye. She reported no eye pain, photophobia or redness. The patient was currently not on any medications, and her family history was unremarkable for any eye disease.

Examination

On exam, the patient’s visual acuity was noted to be 20/25 in the right eye and 20/40 in the left eye. IOP was within normal limits, and pupils were equal and reactive to light. Anterior slit-lamp exam revealed a white, quiet eye with no cells in the anterior chamber or vitreous. Dilated fundus exam of the left eye revealed chorioretinal scarring with pigmentation in the macula. There was subretinal hemorrhage noted contiguous to the scarring. Examination of the right eye revealed a scar with pigmentary changes along the superior arcade (Figures 1a-1c). Fluorescein angiogram demonstrated staining of the lesion in the right eye (Figures 2a-2b) and increasing hyperfluorescence consistent with leakage in the left eye (Figures 3a-3c).


Color fundus photos of both eyes. The right eye demonstrates a scar with hyperpigmentation along the superior arcade. The left eye demonstrates a macular scar with pigment hyperplasia and subretinal hemorrhage.


Fluorescein angiogram of the right eye demonstrates staining of the lesion along the superior arcade. Figure 2a is a red-free image. Figure 2b was taken at 7:37.7.


Fluorescein angiogram of the left eye demonstrates increasing hyperfluorescence consistent with leakage. Figure 3a is a red-free image. Figure 3b was taken at 6:59.9 and 3c at 20:22.3. Images: Ahmed S, Duker J

What is your diagnosis?

Macular lesion

The differential diagnosis of a macular scar associated with pigmentary changes in a young child includes infectious etiologies. TORCH infections, such as toxoplasmosis, rubella, cytomegalovirus and the herpes simplex virus, are at the top of the list. Other infections to consider would include Treponema pallidum, Toxocara canis and Mycobacterium tuberculosis. The subretinal hemorrhage in the left eye suggests formation of a choroidal neovascular membrane. This is confirmed on fluorescein angiography.

Treatment and clinical course

The patient was known to have congenital toxoplasmosis diagnosed by a screening test. Her retinal findings were consistent with a choroidal neovascular membrane secondary to toxoplasmosis. The patient was started on leucovorin, pyrimethamine, sulfadiazine and prednisone. The medications were aimed at treating a potential reactivation of infection, although no signs of an active infection were apparent.

During a 1.5 month course of antibiotic treatment, the patient’s visual acuity declined from 20/40 to 20/100. On exam, her choroidal neovascular membrane appeared fibrotic with associated subretinal fluid. She underwent photodynamic therapy treatment to the subfoveal choroidal neovascular membrane. Four months later the patient presented with another precipitous drop in vision in the left eye to counting fingers at 4 feet. A new choroidal neovascular membrane was noted, and the patient underwent a repeat treatment with photodynamic therapy. Her visual acuity remains stable at 20/400.

Discussion

Toxoplasmosis is a common cause of severe visual loss in young people. The infection can be acquired congenitally or postnatally. Congenital exposure is secondary to maternal exposure during or slightly before pregnancy. Acquired infection can be due to multiple sources, including ingestion of tissue cysts in raw or undercooked meat, ingestion of oocysts on unwashed vegetables and drinking contaminated water. Cats are known to be the definitive host of this obligate intracellular parasite. The prevalence of infection increases with age. Epidemiologic evidence shows that 22.5% of the United States population has serologic evidence of previous exposure to Toxoplasma gondii, while only two to six out of every 1,000 pregnant women acquire the infection during pregnancy. This implies that postnatally acquired infections are far more prevalent than congenitally acquired infections.

The protozoa can exist in multiple forms, such as an oocyst, a bradyzoite and a tachyzoite. The oocyst and bradyzoite represent the latent, nonproliferative phase of the protozoa lifecycle while the tachyzoite represents the proliferative phase. Initially, oocysts or bradyzoites are ingested and infect cells in the mucosa of the small intestine. The protozoa then are converted over to the tachyzoite phase in which they undergo rapid asexual reproduction and induce subsequent cell death. The tachyzoites are distributed throughout the host body. As the body mounts a response to the infection, over the course of several weeks, the tachyzoite form reverts back to its encysted bradyzoite form, thus allowing for recurrence of infection.

Symptoms of active ocular toxoplasmosis include blurred vision, floaters, pain, metamorphopsia and photophobia. General ocular findings on exam include a necrotizing retinochoroiditis, papillitis, neuroretinitis, vitritis, and a granulomatous or nongranulomatous anterior uveitis. The retinal lesions are cream-colored, elevated and, when reactivated, tend to occur near old pigmented scars. The lesions can be focal or multifocal, and there is most often evidence of bilateral involvement. The macula is frequently involved in cases of congenital toxoplasmosis. Lesions larger than one disc diameter tend to persist longer and are associated with greater visual loss. Patients with retinochoroiditis may present with complications such as choroidal neovascularization, retinal detachment, vascular occlusion and epiretinal membrane formation.

Friedman and Knox noted that recurrences occurred in clusters separated by long intervals of time. Toxoplasmosis is known to recur at the border of old scars. The risk of disease recurrence is greatest during the first year after an active episode. Two competing theories regarding the pathogenesis of toxoplasmosis-related retinochoroiditis exist. Some believe the retinal necrosis occurs secondary to proliferation of live parasites while others believe it represents a hypersensitivity response to toxoplasmic antigens.

Diagnosis is made by clinical exam in conjunction with antibody titers. It is important to remember that the presence of titers does not necessarily correlate with disease. Treatment consists of a triple therapy: pyrimethamine, sulfadiazine and prednisone. Folinic acid is administered concurrently since pyrimethamine can inhibit folic acid metabolism. Physicians may also choose to treat with a quadruple therapy, which is clindamycin combined with the triple therapy, or a host of newer agents such as atovaquone, spiramycin, azithromycin or minocycline. No formal guidelines or studies exist regarding treatment of CNV secondary to toxoplasma. In a report by Oliveira, an 11 year old with an extrafoveal CNV secondary to toxoplasma retinochoroiditis experienced an improvement in visual acuity from 10/160 to 20/25 6 weeks after PDT treatment.

For more information:

Shazia Ahmed, MD, and Jay Duker, 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; Web site: www.neec.com.

Edited by Jane Loman, MD, and Zinaria Williams, MD. Drs. Loman and Williams 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; Web site: www.neec.com. Drs. Loman and Williams have no direct financial interest in the products mentioned in this article, nor are they paid consultants for any companies mentioned.

References:

Holland GN. Ocular toxoplasmosis: a global reassessment. Part I: epidemiology and course of disease. Am J Ophthalmol. 2003;136(6):973-988.

Holland GN. Ocular toxoplasmosis: a global reassessment. Part II: disease manifestations and management. Am J Ophthalmol. 2004;137(1):1-17.

Stanford MR, See SE, Jones LV, Gilbert RE.Antibiotics for toxoplasmic retinochoroiditis: an evidence-based systematic review. Ophthalmology. 2003;110(5):926-931.

Bosch-Driessen LE, Berendschot TT, Ongkosuwito JV, Rothova A. Ocular toxoplasmosis: clinical features and prognosis of 154 patients. Ophthalmology. 2002;109(5):869-878.

Wallon M, Kodjikian L, et al. Long-term ocular prognosis in 327 children with congenital toxoplasmosis. Pediatrics. 2004;113(6):1567-1572.

Oliveira LB, Reis PA. Photodynamic therapy-treated choroidal neovascular membrane secondary to toxoplasmic retinochoroiditis. Graefes Arch Clin Exp Ophthalmol. 2004;242(12):1028-1030.

Friedman CT, Knox DL. Variations in recurrent active toxoplasmic retinochoroiditis. Arch Ophthalmol. 1969;81(4):481-493.