Korioretinitis

01Pathophysiology

Chorioretinitis refers to inflammation that involves both the choroid (the vascular layer of the eye) and the overlying retina. Because the choroid supplies blood to the outer retina, any inflammatory or infectious process seeding through the bloodstream can lodge in this highly vascular tissue and extend into the retina. This is why hematogenous spread is the dominant route for most causes.

In toxoplasmic chorioretinitis, the parasite Toxoplasma gondii reaches the eye via the bloodstream, either during acute primary maternal infection (congenital) or during reactivation of latent tissue cysts in immunosuppressed individuals. The organism has a strong tropism for neural and retinal tissue. In congenital disease, the parasite crosses the placenta during maternal parasitemia and disseminates to the fetal brain and retina. This is why congenital toxoplasmosis classically presents with the triad of chorioretinitis, hydrocephalus, and diffuse intracranial calcifications. The retinal lesions in toxoplasmosis are characterized by focal necrotizing retinitis surrounded by intense vitreal inflammation, producing the classic "headlight in the fog" appearance on fundoscopy: a bright yellow-white active lesion (the headlight) obscured by surrounding vitreous haze (the fog).

In CMV retinitis, the mechanism differs. CMV is an opportunistic pathogen that reactivates from latency when CD4 counts fall below 50 cells/microL in HIV/AIDS patients. The virus causes a full-thickness necrotizing retinitis that spreads centrifugally from initial foci. The necrotic retina appears white and opaque ("cottage cheese"), while associated hemorrhage creates the red component ("ketchup"), yielding the "pizza pie" or "cottage cheese and ketchup" retinal appearance. Importantly, CMV retinitis produces relatively little vitritis compared to toxoplasmosis, which is a key distinguishing feature. The lack of vitreous inflammation is explained by the profound immunosuppression required for CMV reactivation: the patient simply lacks the immune cells to mount a vigorous inflammatory response.

For syphilitic chorioretinitis, Treponema pallidum reaches the eye during secondary or tertiary syphilis. Ocular syphilis is now classified as a form of neurosyphilis regardless of stage, and this has direct implications for treatment (IV penicillin rather than IM benzathine penicillin). The lesions can be varied and may mimic nearly any other uveitis, earning syphilis the title "the great imitator" in ophthalmology as well.

02Classification and Clinical Manifestation

03Diagnostic Workup

Dilated fundoscopic examination is the best initial test and often the only test needed to make a clinical diagnosis when the presentation is classic. In immunocompetent patients with a unilateral focal necrotizing retinal lesion adjacent to an old pigmented scar, a clinical diagnosis of toxoplasmic reactivation can be made without further laboratory testing, and empiric treatment is started.

When the diagnosis is uncertain or atypical, PCR of aqueous or vitreous humor obtained via anterior chamber paracentesis (aqueous tap) is the most accurate test. This is reserved for atypical presentations, immunocompromised patients with multiple potential pathogens, or cases unresponsive to empiric therapy. PCR can simultaneously test for Toxoplasma, CMV, HSV, VZV, and other pathogens from a single sample.

For CMV retinitis, diagnosis is largely clinical in the right setting: an AIDS patient with CD4 < 50 presenting with characteristic fundoscopic findings does not routinely require vitreous biopsy. However, CMV blood PCR supports the diagnosis and is useful for monitoring treatment response.

Every patient presenting with unexplained chorioretinitis or any form of posterior uveitis should have syphilis serologies drawn. This is a frequently tested concept. If RPR/VDRL is positive and confirmed with FTA-ABS, a lumbar puncture must follow because ocular syphilis is managed as neurosyphilis.

04Management and Treatment

Acute management of toxoplasmic chorioretinitis begins with the classic "triple therapy" of pyrimethamine, sulfadiazine, and leucovorin. Leucovorin (folinic acid, not folic acid) is critical because pyrimethamine inhibits dihydrofolate reductase, causing dose-dependent bone marrow suppression. Folinic acid rescues human cells without rescuing the parasite. A common exam trap tests whether you know the difference between folinic acid and folic acid: folic acid would be converted by the same enzyme that pyrimethamine inhibits, making it ineffective.

For patients who cannot tolerate sulfadiazine (e.g., sulfa allergy), clindamycin can substitute. Alternative regimens include trimethoprim-sulfamethoxazole (TMP-SMX), which has reasonable efficacy and better tolerability.

Systemic corticosteroids are added 24 to 48 hours after initiating antimicrobial therapy in cases with significant vitreal or perilesional inflammation. Steroids should never be given alone or before antimicrobials, as this can lead to fulminant parasitic proliferation.

For CMV retinitis, the foundational principle is that antiretroviral therapy (ART) must be initiated or optimized concurrently. Antiviral treatment alone is suppressive, not curative. Maintenance therapy can be discontinued once immune reconstitution is achieved (CD4 sustained above 100 for 3 to 6 months). A critical complication to recognize is immune reconstitution inflammatory syndrome (IRIS), which can cause paradoxical worsening of ocular inflammation after ART initiation even as CD4 counts rise.

Sight-threatening CMV lesions (within 1500 micrometers of the fovea or optic disc) warrant intravitreal antiviral injection (ganciclovir or foscarnet) in addition to systemic therapy for rapid local drug delivery.

For syphilitic chorioretinitis, the key teaching point is that it requires the same IV penicillin regimen used for neurosyphilis. IM benzathine penicillin does not achieve adequate intraocular or CSF levels. Penicillin allergy necessitates desensitization, not substitution, because no alternative regimen has proven reliability for neurosyphilis.

05Differential Diagnosis and Distractors

06Traps and High-Yield Pearls

The most common way students miss chorioretinitis questions is by failing to match the retinal lesion morphology to the correct pathogen in an immunocompromised patient. When a vignette describes an HIV-positive patient with visual complaints, students must immediately look at the CD4 count. A CD4 below 50 with painless vision loss and hemorrhagic retinal necrosis with minimal vitritis points to CMV, not toxoplasma. Conversely, a CD4 of 80 with a focal "headlight in the fog" lesion and dense vitreous haze points to toxoplasma. The presence or absence of vitritis is the single most reliable discriminator between these two diagnoses.

Another common trap involves congenital toxoplasmosis: students confuse the intracranial calcification patterns. Toxoplasma produces diffuse, scattered calcifications throughout the brain parenchyma, while CMV produces periventricular calcifications. This distinction frequently appears alongside chorioretinitis in neonatal TORCH vignettes.

Students also lose points by not recognizing that any unexplained uveitis requires syphilis testing. A vignette describing a young adult with bilateral posterior uveitis that does not respond to topical steroids should trigger syphilis serologies before further workup.

Finally, the leucovorin pearl is tested repeatedly: pyrimethamine therapy requires folinic acid (leucovorin), not folic acid. Picking folic acid as the bone marrow rescue agent is a classic distractor designed to catch students who do not understand the enzyme pharmacology.

The core competency being tested is the ability to synthesize fundoscopic findings, immune status, and serologic data to arrive at the correct infectious etiology and initiate pathogen-directed therapy while managing the underlying immunodeficiency.