Infectious Uveitis: Toxoplasmosis & CMV Retinitis

The retina and choroid, richly vascularized and immunologically distinct from the rest of the body (the "immune privilege" of the eye), are vulnerable to both opportunistic and reactivation infections. Ocular toxoplasmosis and cytomegalovirus (CMV) retinitis are the two most important infectious causes of posterior segment inflammation encountered in ophthalmology, with toxoplasmosis being the most common infectious cause of posterior uveitis worldwide.¹

Toxoplasmosis causes focal necrotizing retinochoroiditis through direct parasitic invasion, typically adjacent to a pre-existing scar (reactivation of dormant tissue cysts), with overlying vitritis.¹ CMV retinitis causes slowly progressive, full-thickness retinal necrosis with a granular, hemorrhagic appearance from direct viral cytopathic effect in an inadequately immune-surveilled retina — one of two major herpesvirus retinitis phenotypes, alongside acute retinal necrosis (typically VZV/HSV), which differ substantially by host immune status and clinical course.²

Toxoplasmosis presents with unilateral blurred vision, floaters, and sometimes pain/photophobia in an otherwise healthy patient. CMV retinitis presents with painless, gradually progressive blurred vision or field loss in an immunocompromised patient, sometimes subtly at first.

Key differentials: acute retinal necrosis (more fulminant, broader involvement, earlier detachment)², other causes of focal necrotizing chorioretinitis (toxocariasis, syphilis, tuberculosis), non-infectious posterior uveitis (sarcoidosis, VKH), and immune recovery uveitis as immune function improves during CMV retinitis treatment.³

Toxoplasmosis diagnosis is mainly clinical, supported by serology (IgG/IgM) and, when needed, PCR of intraocular fluid or the Goldmann-Witmer coefficient.¹ CMV retinitis is diagnosed by classic fundus appearance in an at-risk host, supported where needed by PCR of intraocular fluid; the Standardization of Uveitis Nomenclature classification criteria can be applied regardless of PCR status.²

Standard toxoplasmosis treatment is systemic antiparasitic therapy (pyrimethamine with sulfadiazine, or trimethoprim-sulfamethoxazole) with corticosteroids. In sulfonamide-allergic patients, alternatives — pyrimethamine with clindamycin or azithromycin, or intravitreal clindamycin with dexamethasone — are effective and safe.¹ CMV retinitis requires systemic and/or intravitreal antiviral therapy (ganciclovir, valganciclovir, or foscarnet) alongside correcting the underlying immunocompromise where possible. Retinal detachment developed earlier and more often in ARN than CMV retinitis; ARN and worse baseline visual acuity independently predicted detachment risk, while surgical intervention was associated with lower odds of severe visual impairment when detachment occurred.² Close monitoring for immune recovery uveitis is warranted as immune status improves.³

• Toxoplasmosis is the most common infectious cause of posterior uveitis worldwide, classically a focal necrotizing lesion near an old scar with overlying vitritis¹
• Sulfonamide-allergic toxoplasmosis patients have effective alternative regimens rather than being denied treatment¹
• Consider CMV retinitis in any significantly immunocompromised patient with new visual symptoms, even if HIV-negative³
• Distinguish CMV retinitis (more indolent) from ARN (more fulminant, earlier detachment) as the two major herpesvirus retinitis phenotypes²
• Common pitfall: withholding treatment in sulfonamide-allergic patients instead of using an established alternative
• Common pitfall: missing immune recovery uveitis during CMV retinitis treatment