Chorioretinitis

Overview

Definition

• Also called retinochoroiditis
• Inflammation of the choroid, a part of the posterior uvea, and the retina
• A type of posterior uveitis

Anatomy

• Choroid:
  • Vascular structure that provides support and nutrition to the retina
  • Continuous anteriorly with the ciliary body
• Retina:
  • Innermost layer
  • Contains photoreceptors that convert light stimuli into nervous impulses

Epidemiology and Etiology

Epidemiology

• Among the types of uveitis, posterior uveitis is the least common form.
• Chorioretinitis: often from infectious etiology
• Toxoplasmosis: most common cause of chorioretinitis worldwide

Etiology

• Infectious causes:
  • Toxoplasmosis (Toxoplasma gondii) 
  • Syphilis (Treponema pallidum)
  • Tuberculosis (TB) (Mycobacterium tuberculosis) 
  • Herpes simplex virus
  • Lymphocytic choriomeningitis virus
  • Rubella virus
  • Varicella virus
  • Cytomegalovirus (CMV) 
  • Histoplasmosis (Histoplasma capsulatum)
  • Candidiasis (Candida albicans)
  • Coccidioidomycosis (Coccidioides)
  • Toxocariasis (Toxocara canis, Toxocara cati)
• Non-infectious causes:
  • Autoimmune diseases:
    • Sarcoidosis
    • Behcet’s disease
    • Systemic lupus erythematosus
    • Polyarteritis nodosa
    • Granulomatosis with polyangiitis 
  • No systemic association:
    • Birdshot choroidopathy
    • Multifocal choroiditis and panuveitis
    • Serpiginous choroidopathy
    • Multiple evanescent white dot syndrome (MEWDS)

Clinical Presentation

• Usually painless, but pain occurs with panuveitis
• Floaters 
• Flashes of light (photopsia)
• Vision impairment or loss
• Scotomas (blind spots)
• In neonates: usually asymptomatic at birth with manifestations observed later
• Extraocular symptoms are dependent on the associated disease.

Infectious Chorioretinitis

Congenital toxoplasmosis

• Only 10%–30% of patients have manifestations at birth and in early infancy.
• Fetuses infected in early pregnancy are more likely to show signs of infection.
• In utero findings: intracranial calcifications/densities and hydrocephalus (most common findings)
• Classic triad: 
  1. Intracranial calcifications
  2. Hydrocephalus
  3. Chorioretinitis: a common late manifestation of congenital toxoplasmosis
• Symptoms: often painless blurred vision, scotoma, photophobia

Acquired toxoplasmosis

Active infection

• High-risk patients: 
  • Can occur in all age groups
  • Patients from South and Central America (predominantly genotype I, which causes severe disease)
• Symptoms: unilateral visual loss or floaters

Reactivated infection

• High-risk patients: 
  • Those who acquired infection in utero or postnatally
  • Onset at > 40 years of age: increased risk of recurrence
• Symptoms: bilateral visual loss or floaters with an inflammatory chorioretinal lesion

Congenital CMV retinitis

• 90% asymptomatic at birth
• High-risk patients: 
  • Newborns of mothers with known or suspected CMV infection
  • Immunocompromised newborns (severe combined immunodeficiency disorder)
• In utero findings: growth restriction, periventricular calcifications, ventriculomegaly, microcephaly
• Chorioretinitis: most common ocular finding
• Symptoms: visual impairment, strabismus
• Extraocular symptoms: petechiae, jaundice, hepatosplenomegaly, hearing loss, microcephaly, and ventricular calcifications

Acquired CMV retinitis

• High-risk patients: 
  • Severely immunocompromised patients: AIDS with CD4 count < 50 cells/microL
• Symptoms: 
  • Typically unilateral
  • Blurry or loss of central vision 
  • Scotoma 
  • Floaters, photopsia: symptomatic predictors of CMV retinitis in patients with AIDS
• Associated with necrotizing retinitis, retinal vasculitis, and optic neuropathy

Tuberculosis

• High-risk patients: 
  • Those living in endemic countries
  • Immunocompromised state
• Results from hematogenous spread
• Frequently presents as posterior uveitis with disseminated choroiditis
• Symptoms: 
  • Diminished visual acuity when the macula is affected 
  • Unilateral or bilateral

Toxocariasis

• High-risk patients: young patients with pets
• Symptoms: Unilateral reduced vision, photophobia, floaters
• Signs: leukocoria, ocular injection

Syphilis

• High-risk patients: history of sexually transmitted diseases
• Commonly manifests as iritis or iridocyclitis but also causes chorioretinitis
• In HIV, placoid lesions develop: placoid chorioretinitis
• Symptoms: blurry vision, floaters, light sensitivity

Ocular histoplasmosis syndrome

• High-risk patients: in regions endemic for Histoplasma 
• Often asymptomatic until choroidal neovascularization (CNV) occurs
• Symptoms: central vision loss, metamorphopsia (distorted straight lines), scotomas

Non-infectious Chorioretinitis

Sarcoidosis

• High-risk patients: African American women
• Pulmonary and extrapulmonary symptoms
• Affects posterior uvea in ⅓ of cases
• Symptoms: blurry vision, floaters, photophobia; pain if with anterior uveitis

Behcet’s disease

• Characterized by recurrent oral and genital ulcers, polyarthritis
• Symptoms: 
  • Often bilateral, episodic
  • Can present as panuveitis (redness, tearing, pain, photophobia, blurry vision)
  • Severe visual loss from retinal vasculitis and optic neuritis

Birdshot retinochoroidopathy

• High-risk patients: associated with HLA-A29
• Symptoms: blurry vision, floaters, and glare

MEWDS

• Rare but affects healthy young women
• Symptoms: 
  • Acute unilateral painless loss of vision
  • Self-limited and resolves by 9 weeks

Diagnosis

Prenatal diagnosis

• Screening includes syphilis
• Sonogram can detect fetal changes that are suggestive of CMV and toxoplasmosis

Laboratory tests and imaging

Guided by:

• High level of suspicion in patients with known or suspected perinatal infections
• Presenting manifestations at birth and subsequent symptoms
• Medical history
• Predisposing high-risk factors (e.g., sexual behavior, pet ownership, residence in or travel to endemic areas)

Dilated fundus examination and slit-lamp biomicroscopy

• Choroiditis: yellow patches, regular borders
• Retinitis: whitish patch with ill-defined borders
• Vitreous inflammation (leukocytes in the vitreous humor)
• Vitreous opacities

Ophthalmologic findings in infectious chorioretinitis

Ophthalmologic findings in non-infectious chorioretinitis

Management

Goals

• Preserve visual function.
• Suppress host inflammatory response.
• Eliminate infection (for infectious causes).

Infectious chorioretinitis

• Toxoplasmosis:
  • Inactive disease: no treatment if asymptomatic
  • Active disease: trimethoprim-sulfamethoxazole or pyrimethamine + sulfadiazine + leucovorin
  • < 14 weeks’ pregnant with active disease: spiramycin
  • > 14 weeks’ pregnant with active disease: pyrimethamine-sulfadiazine
  • Infants with confirmed diagnosis: pyrimethamine + sulfadiazine + leucovorin
• CMV retinitis: severity determines medication and route
  • Ganciclovir
  • Valganciclovir
  • Foscarnet
  • Cidofovir
• Tuberculosis: antitubercular therapy
  • Isoniazid
  • Rifampicin
  • Pyrazinamide
  • Ethambutol
• Toxocariasis: prednisone and albendazole (for sight-threatening inflammation)
• Syphilis: IV penicillin G 24 million units/day for 10–14 days (similar to neurosyphilis)
• Histoplasmosis: 
  • Observation and monitoring for CNV
  • Anti-vascular endothelial growth factor (VEGF) for CNV

Non-infectious chorioretinitis

Non-infectious chorioretinitis is treated with corticosteroids and immunosuppressants.

Non-resolving chorioretinitis

For non-resolving chorioretinitis, rule out malignancies (masquerade syndromes).

Differential Diagnosis

The differential diagnoses of chorioretinitis include the following conditions:

• Vitreoretinal lymphoma: most common intraocular lymphoproliferative disorder. The disorder is one of the masquerade syndromes that presents a diagnostic dilemma. Patients have gradual visual impairment with floaters. Gold standard of diagnosis is cytopathologic examination of ocular fluid or chorioretinal biopsy.
• Choroidal melanoma: a malignancy that presents with uveitis (masquerade syndrome). Patients can be asymptomatic or can present with floaters, visual field defects, and flashes. Diagnosis is by funduscopic examination showing pigmented dome-shaped tumor. Fine needle biopsy is performed for molecular prognostic testing.
• Retinoblastoma: the most common intraocular malignancy in childhood, usually diagnosed before the age of 5. Retinoblastoma frequently presents as abnormal white reflection from the retina, called leukocoria. Other features include red-eye, strabismus, and nystagmus. Ophthalmoscopic examination reveals a retinal mass. Additional imaging studies, including ocular ultrasound, can be used for diagnosis.