Ocular Toxoplasmosis Masquerading as Acute Retinal Necrosis and Cytomegalovirus Retinitis: A Systematic Review

This systematic review synthesizes clinical features, diagnostic pathways, interventions, and visual outcomes of atypical ocular toxoplasmosis initially masquerading as acute retinal necrosis (ARN) or cytomegalovirus (CMV) retinitis.

Ocular toxoplasmosis occasionally presents atypically, mimicking viral retinitides. This masquerade poses a challenge, as misdiagnosis and empiric corticosteroids for presumed viral inflammation delay anti-toxoplasma therapy and can precipitate fulminant, vision-threatening infection.

Following PRISMA guidelines, MEDLINE and Embase were searched from database inception to February 2, 2026, for peer-reviewed studies reporting ocular toxoplasmosis initially misdiagnosed as ARN or CMV retinitis. Risk of bias was assessed using the Joanna Briggs Institute (JBI) Critical Appraisal Checklists for case reports and case series, and certainty of evidence was rated using GRADE. This study is registered with PROSPERO (CRD420261453307). Data on patient demographics, immune status, clinical presentation, diagnostic delay, and visual outcomes were analyzed.

The review included 14 studies comprising 43 patients (50 eyes) with a mean age of 52.9 years. Most (79.1%, n=34) were immunocompromised, and 65.1% (n=28) had prior corticosteroid use. The most frequent initial misdiagnoses were ARN (74.4%, n=32) and CMV retinitis (23.3%, n=10). The clinical masquerade led to a mean diagnostic delay of 26.4 days while patients received ineffective empiric antiviral therapies. Diagnosis was ultimately confirmed through serum serology (48.8%) or intraocular fluid polymerase chain reaction (34.9%). Upon correct diagnosis, patients were transitioned to anti-toxoplasma regimens, most commonly pyrimethamine-based (67.4%). Despite eventual anatomical consolidation of the active lesions, final visual outcomes were poor. Over half of the affected eyes (55.8%, n=24) retained a final visual acuity worse than 20/200, with 18.6% (n=8) progressing to light perception, no light perception, phthisis bulbi, or requiring enucleation.

Very low certainty evidence suggests that typical ocular toxoplasmosis frequently masquerades as viral necrotizing retinitis, primarily in immunocompromised and corticosteroid-exposed individuals. As this evidence derives entirely from case reports and series subject to selection and publication bias, these findings should not be considered definitive. The resulting diagnostic delay leads to largely irreversible visual impairment. Early multimodal testing, specifically intraocular fluid PCR, and avoidance of empiric corticosteroids without concurrent anti-toxoplasma coverage may contribute to vision preservation.