Infectious Uveitis: Toxoplasmosis & CMV Retinitis

Overview

Ocular toxoplasmosis and cytomegalovirus (CMV) retinitis are the two most important infectious causes of posterior segment inflammation encountered in ophthalmology. Ocular toxoplasmosis is the most common infectious form of posterior uveitis worldwide, typically presenting as necrotizing retinochoroiditis in an immunocompetent host, while CMV retinitis is a manifestation of severe immunosuppression, most classically seen in advanced HIV/AIDS but increasingly recognized in other immunocompromised states.¹

Epidemiology & Risk Factors

Ocular toxoplasmosis results from infection with Toxoplasma gondii and can be congenital (reactivation of a prior in-utero infection) or acquired, occurring in both immunocompetent and immunocompromised hosts. CMV retinitis, by contrast, occurs almost exclusively in significantly immunocompromised patients — classically those with advanced HIV/AIDS and low CD4 counts, but also solid organ or bone marrow transplant recipients, and patients on prolonged immunosuppressive therapy for hematologic or rheumatologic disease.² CMV retinitis has been reported even in HIV-negative patients with other causes of significant immune compromise, such as chronic lymphoproliferative disease under treatment — a presentation that can be diagnostically challenging given the atypical host.³

Pathophysiology

Ocular toxoplasmosis causes focal necrotizing retinochoroiditis through direct parasitic invasion and destruction of retinal tissue, typically adjacent to a pre-existing chorioretinal scar (representing reactivation of dormant tissue cysts), accompanied by vitritis and vitreomacular adhesion from the overlying inflammatory response.¹ CMV retinitis, in contrast, causes a slowly progressive, full-thickness retinal necrosis with a granular or "cottage-cheese"-like appearance and associated hemorrhage, reflecting direct cytopathic viral effect within an inadequately immune-surveilled retina; it is one of two major herpesvirus retinitis phenotypes (along with acute retinal necrosis, ARN, typically caused by varicella-zoster or herpes simplex virus), which differ substantially by host immune status, with CMV retinitis specifically occurring in immunocompromised patients and following a comparatively more indolent course than ARN.²

Clinical Presentation

Ocular toxoplasmosis typically presents with unilateral blurred vision, floaters, and sometimes pain or photophobia if there is significant anterior segment inflammatory spillover, in an otherwise healthy patient. CMV retinitis typically presents with painless, gradually progressive blurred vision, floaters, or visual field loss in a patient with a known or unrecognized immunocompromising condition — the diagnosis should be actively considered in any significantly immunosuppressed patient with new visual symptoms, since early presentations can be subtle.

Exam Findings

• Toxoplasmosis: a focal, white-yellow necrotizing retinochoroiditis lesion (a "headlight in the fog" appearance from overlying vitritis), often adjacent to a pigmented chorioretinal scar from prior infection
• Toxoplasmosis: significant vitritis is characteristic and helps distinguish active from purely scarred, inactive disease
• CMV retinitis: granular, indolent peripheral retinal whitening with scattered hemorrhage (classically described as a "pizza pie" or "cottage cheese and ketchup" fundus appearance), typically without the dense vitritis seen in toxoplasmosis
• CMV retinitis: can be associated with occlusive retinal vasculopathy and, later, macular edema³
• Acute retinal necrosis (the other major herpesvirus retinitis phenotype) more commonly shows unilateral involvement, peripheral necrosis, and a more fulminant course with earlier, more frequent retinal detachment than CMV retinitis²

Differential Diagnosis

• Acute retinal necrosis (VZV/HSV), distinguished from CMV retinitis by immune status, more fulminant course, and higher, earlier retinal detachment risk²
• Other causes of focal necrotizing chorioretinitis (toxocariasis, syphilis, tuberculosis)
• Non-infectious posterior uveitis (sarcoidosis, VKH disease), distinguished by the absence of a discrete infectious focus and different systemic associations
• Immune recovery uveitis, a distinct inflammatory syndrome that can develop in CMV retinitis patients as immune function improves (e.g., after starting antiretroviral therapy), requiring separate recognition and management³

Management

Diagnosis of ocular toxoplasmosis is mainly clinical, supported by serology (IgG/IgM) and, when needed, PCR of intraocular fluid or the Goldmann-Witmer coefficient. Standard treatment includes systemic antiparasitic therapy (classically pyrimethamine with sulfadiazine, or trimethoprim-sulfamethoxazole) combined with corticosteroids to control the inflammatory response. In patients with sulfonamide allergy, alternative regimens — pyrimethamine with clindamycin or azithromycin, or intravitreal clindamycin with dexamethasone — have shown comparable efficacy and are effective, safe options.¹ Prompt treatment of active disease helps reduce retinal damage and recurrence risk.¹

CMV retinitis is diagnosed based on the 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 Treatment requires systemic and/or intravitreal antiviral therapy (e.g., ganciclovir, valganciclovir, or foscarnet), alongside correction of the underlying immunocompromised state where possible (e.g., antiretroviral therapy in HIV, reducing immunosuppression in transplant recipients). Retinal detachment developed earlier and more frequently in acute retinal necrosis than in CMV retinitis in a large cohort, and both worse baseline visual acuity and ARN itself were independently associated with increased retinal 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 an immunocompromised patient's immune status improves during treatment.³

Complications

• Toxoplasmosis: recurrent retinochoroiditis, chorioretinal scarring with permanent visual field or acuity loss if the macula or optic nerve is involved
• Toxoplasmosis: rarely, choroidal neovascularization adjacent to a scar
• CMV retinitis: retinal detachment, though less frequent and later-occurring than in acute retinal necrosis²
• CMV retinitis: occlusive retinopathy and macular edema, sometimes requiring adjunctive laser or anti-VEGF therapy³
• Immune recovery uveitis as a distinct, potentially vision-threatening complication during immune reconstitution³

Clinical Pearls

• Toxoplasmosis is the most common infectious cause of posterior uveitis worldwide and classically presents as a focal necrotizing lesion adjacent to an old scar with a "headlight in the fog" appearance from vitritis¹
• Sulfonamide-allergic patients with ocular toxoplasmosis have effective alternative options (clindamycin- or azithromycin-based regimens, or intravitreal clindamycin/dexamethasone) rather than being denied appropriate treatment¹
• CMV retinitis should be considered in any significantly immunocompromised patient with new visual symptoms, even in HIV-negative patients with other causes of immune compromise³
• Compare CMV retinitis (immunocompromised, more indolent course) against acute retinal necrosis (broader retinal involvement, earlier detachment, more fulminant course) as the two major herpesvirus retinitis phenotypes²
• Watch for immune recovery uveitis as a patient's immune status improves during CMV retinitis treatment, since it can itself threaten vision if not recognized³

Common Pitfalls

• Withholding appropriate antiparasitic treatment in a sulfonamide-allergic toxoplasmosis patient rather than using an established alternative regimen
• Failing to consider CMV retinitis in an atypical or HIV-negative immunocompromised host, delaying diagnosis
• Confusing CMV retinitis with acute retinal necrosis, leading to a mismatched urgency of treatment and detachment surveillance
• Missing immune recovery uveitis as a cause of new inflammation or vision decline during the recovery phase of CMV retinitis treatment
• Assuming all focal chorioretinal lesions are toxoplasmosis without considering other infectious or non-infectious causes