A 66‐year‐old man with acute retinal necrosis

Access at https://isn-slidearchive.org/?col=ISN&fol=Archive&file=ID-9336200.svs. A 66-year-old male with a history of hypertension presented with acute vision loss in his left eye for a few weeks. He had a history of blurred vision in the left eye, which had been treated for suspected acute retinal necrosis/herpetic retinitis with intravitreal valacyclovir and ganciclovir and topical corticosteroids at an outside institution, but he had been lost to follow up for several months. Outside laboratory work-up on serum was positive for CMV IgG, Toxoplasma IgG, HSV1 IgG, and VZV IgG. Negative results were reported for CMV IgM, Toxoplasma IgM, HSV2 IgG, and CMV, HSV, and Toxoplasma DNA on PCR, HIV1/2, RPR, quantiFERON, hepatitis B surface antigen, and HLA-B27. Anterior chamber paracentesis was positive for HSV IgG and negative for CMV, VZV, and Toxoplasma DNA on PCR. Chest X-ray was normal. Visual acuity on right was 20/30 and left bare light perception. Slit lamp exam revealed vitritis with a hazy view on fundus exam (Figure 1A), and B scan showed open funnel retinal detachment (Figure 1B). He underwent pars plana vitrectomy and retinal biopsy (Box 1). Microscopic examination of H&E stained sections demonstrated fragments of retina with patchy areas of necrosis that were relatively well demarcated from adjacent uninvolved retina (Figure 2A). Mostly within the necrotic areas were Toxoplasma bradyzoites (Figure 2B,C) and tachyzoites (Figure 2D,E) highlighted on T. gondii immunohistochemistry (Figure 2F). Immunohistochemistry for HSV types 1 and 2, VZV, CMV, and adenovirus, and in-situ hybridization for EBV EBER were negative. Concurrent PCR performed on the vitreous biopsy was positive for Toxoplasma DNA. Toxoplasma retinitis. Ocular toxoplasmosis, a retinitis usually with choroiditis and vitritis, is caused by the obligate intracellular protozoan parasite Toxoplasma gondii, a member of the phylum Apicomplexa [1, 2]. Toxoplasma retinochoroiditis is one of the most common causes of posterior uveitis worldwide [1]. Approximately one third of the world's population is infected with T. gondii, which has three primary forms during its lifecycle [1, 2]. Tachyzoites are the replicating form and indicate active infection while bradyzoites are the latent encysted form that exists in tissue (tissue cysts). Sporozoites, four sporozoites comprising a sporocyst and two sporocysts comprising an oocyst, are the dormant form in the environment and highly infectious [2]. Humans become infected by ingesting encysted bradyzoites in undercooked meat of infected animals or oocysts on produce or water contaminated with the feces of Felidae family members (such as domestic cats), which are the definitive hosts [2]. Ingested oocysts or tissue cysts then release sporozoites or bradyzoites, respectively, in the small intestine which infect enterocytes and disseminate to other organs through blood and lymphatics [2]. If a primary infection occurs during pregnancy, tachyzoites can be transmitted to the fetus transplacentally causing a serious congenital infection [1]. In immunocompetent individuals, most primary infections are asymptomatic or associated with lymphadenopathy and fever [1]. Retinitis is nearly always self-limited in immunocompetent individuals who comprise the majority of patients [2]. In a typical presentation, comprising >90% of cases, the diagnosis can be made clinically on ophthalmic examination, which characteristically shows focal active retinitis/retinochoroiditis adjacent to a variably pigmented retinochoroidal scar [1]. In most cases, ocular toxoplasmosis is unilateral and presents with a single lesion, whether occurring as a primary or reactivated disease, with absence of a scar suggesting primary infection [1, 2]. Patients commonly complain of changes in vision and floaters, although the disease can be asymptomatic [2]. Variable degrees of vitritis are nearly always present, and retinal vasculitis is occasionally seen [1]. Complications include raised intraocular pressure, retinal tear/detachment, retinal vascular occlusion, macular edema, preretinal membrane, vitreous hemorrhage, cataracts, optic atrophy, and choroidal neovascularization [1]. In immunocompromised patients such as those with AIDS, ocular toxoplasmosis can cause fulminant disease with progression to panophthalmitis and orbital cellulitis even with treatment [1]. Furthermore, it may mimic acute retinal necrosis from viral infection or intraocular lymphoma [1, 3]. As ocular toxoplasmosis is usually diagnosed clinically, most histopathologic descriptions are from enucleations and autopsies performed on immunocompromised patients and infants/fetuses with congenital toxoplasmosis [2]. Biopsies are rare, typically reserved for atypical presentations when clinical differential diagnoses include other infections and lymphoma [1, 3]. Characteristic histopathologic findings include well-demarcated areas of coagulative necrosis in the retina with Toxoplasma organisms in the forms of encysted bradyzoites and tachyzoites, most frequently in foci of necrosis or areas adjacent to the necrosis [1]. The parasites can be identified on routine H&E stain, but immunohistochemistry for T. gondii is helpful in highlighting the organisms [1]. There may be disruption of the underlying retinal pigment epithelium which can show necrosis with granulomatous or non-granulomatous inflammation of the adjacent choroid [1]. The inflammatory infiltrate is typically comprised predominantly of T-cells but also B-cells, as well as plasma cells and macrophages [1]. The iris and ciliary body may also show chronic inflammation, and optic neuritis with presence of parasites has been reported [1]. Laboratory testing for Toxoplasma DNA using PCR and/or Toxoplasma antibodies in ocular fluid is useful in atypical presentations. Treatment of patients with active retinochoroiditis generally consists of oral therapy with trimethoprim/sulfamethoxazole or pyrimethamine/sulfadiazine, often with a corticosteroid [1]. In patients intolerant of sulfonamides, clindamycin or azithromycin has been used [1]. In different cohorts, 17%–24% of patients have shown severe visual impairment after ocular toxoplasmosis [2]. Colin A. McCannel performed acquisition and analysis of clinical data. Shino Magaki, Fausto J. Rodriguez, and Matthew Koo performed acquisition and analysis of histopathologic data. All authors have reviewed and approved the final manuscript. The authors declare no conflicts of interest. The data that support the findings of this study are available from the corresponding author upon reasonable request.