With our patient’s medical history of multiple myeloma and SCC, the finding of a retinal lesion was concerning for possible neoplastic etiologies including plasmacytoma, metastatic SCC or lymphoma. Plasmacytomas can be found as solitary tumors or in association with multiple myeloma as either a first manifestation of systemic disease or insufficient treatment. They can rarely present in the eye and have appeared in the eyelid, conjunctiva and orbit and as uveal lesions affecting the iris, ciliary body or choroid.1-3 However, the presence of anterior and posterior inflammation focused our differential on more infectious processes including toxoplasmosis, syphilis, tuberculosis, toxocariasis, cytomegalovirus or candidiasis.Acute retinal necrosis (ARN) was also high on the differential. While ARN is more typically seen with VZV, it can also be caused by HSV, EBV or CMV.4 Additionally, breakthrough ARN can occur despite prophylactic use of acyclovir, which our patient was taking.5 Inflammatory lesions including sarcoid, lupus and Wegener’s were also considered.
A B-scan revealed cells in the vitreous as well as choroidal thickening. Optical coherence tomography demonstrated hyperreflective lesions on the retinal surface consistent with inflammatory precipitates along with choroidal thickening (See Figure 2).
Laboratory studies on presentation were significant for a white blood cell count of 64,600 per mm3 with 45 percent monocytes and only 5 percent segmented neutrophils. This unusual blood count was consistent with her current use of plerixafor, an immunostimulant that mobilizes hematopoietic stem cells and is used prior to autologous transplant in cancer patients. This clinical picture and diagnostic results were consistent with a diagnosis of ocular toxoplasmosis. The patient was treated with trimethoprim/sulfamethoxazole for six weeks and her vision slowly improved. By seven weeks, all of the inflammation in her left eye had resolved and her vision in the left eye had improved to 20/40.
Ocular toxoplasmosis, a disease caused by the parasite Toxoplasma gondii, accounts for 25 percent of posterior uveitis cases in the United States today. While cats are the definitive hosts, humans serve as intermediate hosts to T. gondii and approximately one-third of the human population worldwide is infected by the parasite. Ocular manifestations are generally found in only 2 percent of those infected.6,7
While it was traditionally thought that the majority of human infection by T. gondii occurred most commonly by congenital transplacental transmission, it is now known that acquired infections are the most common causes of ocular toxoplasmosis and ocular lesions may first develop years after initial infection.7 Acquired transmission can occur through ingestion of undercooked, infected meat; contaminated water, fruit or vegetables; unpasteurized goat milk from a chronically infected animal; or contact with cat feces or cat litter.
The diagnosis is most often made clinically, based on characteristic fundus lesions. In patients with atypical presentations or in whom there is inadequate response to initial therapy, anterior chamber or vitreous PCR or diagnostic vitrectomy can be useful tools to rule out toxoplasmosis infection.9 IgM antibodies will rise early after infection and remain detectable for less than one year while IgG antibodies will appear within the first two weeks after infection and remain detectable for life. Because these antibodies are highly sensitive markers of the disease state, antibody testing is helpful in ruling out toxoplasmosis when the result is negative.
When treating ocular toxoplasmosis, the goal is to stop parasitic replication and reduce intraocular damage due to the associated inflammatory response. The infection is most often self-limited in immunocompetent patients and small extramacular lesions can be observed untreated with resolution to pigmented scars over the course of one to two months. However, in immunocompromised patients, the disease can be much more severe and progressive. Antibiotic treatment should be offered for sight-threatening lesions, such as those with zone 1 or zone 2 involvement, infants up to 1 year old, patients with severe inflammation or in patients with persistent symptoms or significant loss of vision.
Traditional therapy consists of 75 to 100 mg of pyrimethamine daily for two days followed by a 25- to 50-mg daily dose and 2 to 4 g of sulfadiazine daily for two days followed by a 0.5- to 1-g dose four times a day.10 Folinic acid is also used at 5 mg daily three times a week during pyrimethamine therapy to protect against leukopenia and thrombocytopenia. Concomitant prednisone therapy of 0.5 to 1 mg/kg daily is also often used to reduce inflammation, however this should not be used without antibiotics or in the immunocompromised patient. Trimethoprim/sulfamethoxazole 160/800 mg twice daily has been shown to be equivalent to the traditional triple-therapy regimen.10 Other oral treatment regimens have been used including azithromycin, clindamycin and atovaquone alone or combined with the aforementioned treatments. Intravitreal clindamycin plus dexamethasone is perhaps safer and more convenient than conventional oral therapy and has also been shown to be equally as effective.11 There is little evidence to support one antibiotic regimen over another, and treatment regimens should be based on the clinical presentation and safety profile of the intended treatment.12
Patients who are immunocompromised, especially those with HIV/AIDS, should have brain imaging performed, as there is a high frequency of cerebral involvement associated with ocular disease. These patients also often need long-term antitoxoplasmic medication, as they are at greater risk of disease recurrence. A prospective, randomized clinical trial conducted in Brazil, where the incidence of toxoplasmosis infection is as high as 85 percent, demonstrated that maintenance trimethoprim/sulfamethoxazole therapy reduced the incidence of recurrent toxoplasmosis retinochoroiditis from 13 percent on placebo to 0 percent on treatment over a one-year period.13
Ocular toxoplasmosis is a common cause of posterior uveitis worldwide. A bright yellow or gray-white retinal lesion through dense vitritis with adjacent pigmented scar is considered pathognomonic for the diagnosis. While most cases are self-limited, better-tolerated and possibly safer treatment options such as trimethoprim/sulfamethoxazole or intravitreal clindamycin offer the ophthalmologist greater flexibility in tailoring treatment to each patient. REVIEW
The author thanks Marc Spirn, MD, of the Wills Retina Service for his time and assistance in preparing this report.
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