Infectious Uveitis

Infectious uveitis belongs to the broader category of intraocular inflammatory disease—conditions characterized by inflammation inside the eye. Uveitis as a whole encompasses more than 25 recognized disorders involving the uvea, the middle vascular layer of the eye. The uvea is made up of the iris (the colored ring that controls how much light enters), the ciliary body (the structure behind the iris that produces the fluid filling the eye), and the choroid (the layer of blood vessels between the retina and the outer wall of the eye). Uveitis is the fourth leading cause of blindness in the working-age population worldwide, accounting for approximately 10% of blindness among working-age adults in the Western world. The two main categories are infectious uveitis (caused by a live germ actively damaging eye tissue) and autoimmune or noninfectious uveitis (caused by the immune system mistakenly attacking the eye). This page covers infectious uveitis specifically.

Infectious uveitis is inflammation of the uvea and surrounding ocular structures caused by the direct, damaging effect of a replicating infectious organism—whether a virus, bacterium, fungus, or parasite. The critical distinction from autoimmune uveitis is that the pathogen itself—not an errant immune response—is the primary driver of damage. This distinction matters enormously for treatment: immune-suppressing medications that control autoimmune uveitis can be catastrophically dangerous if given to a patient whose eye is actively infected. Ruling out infectious causes is always the first priority in any uveitis evaluation. Infectious uveitis is not a single condition but an umbrella term for a disease spectrum caused by more than 60 identified organisms, each with its own presentation, diagnostic test, treatment, and prognosis.

Infectious uveitis affects an estimated 60.6 per 100,000 persons in the United States, with a mean annual incidence of 18.9 per 100,000 persons per year. In the United States, infectious causes account for less than 20% of all uveitis cases. Globally, however, the proportion is dramatically higher in many parts of the developing world—from approximately 21% in China to 37% in India, 49% in Pakistan, 63% in Angola, 73% in Tanzania, and 81% in Brazil—reflecting the burden of endemic infections such as tuberculosis, toxoplasmosis, and parasitic diseases in these regions. Infectious uveitis accounts for up to 25% of visual impairment in developing countries. Most cases affect adults between the ages of 20 and 50, with the mean onset age approximately 40 years. The odds of having infectious uveitis increase by more than threefold with each decade of life over age 18.

Infectious uveitis is classified along two intersecting axes: the pathogen class causing it (viral, bacterial, fungal, or parasitic) and the anatomic location of the inflammation inside the eye (anterior, intermediate, posterior, or panuveitis). Etiological classification guides which drug is used; anatomic classification guides prognosis and monitoring. Globally, anterior uveitis accounts for 53% of cases, posterior uveitis for 39%, and intermediate uveitis for 8%. The following are the major clinical categories and the most important named syndromes within each.

• Herpes simplex virus (HSV-1 and HSV-2) uveitis: HSV is one of the most common causes of viral anterior uveitis and also one of the causes of acute retinal necrosis (ARN), a rapidly progressive, retinal-destroying emergency. A characteristic sign of HSV anterior uveitis is sector iris atrophy—a wedge-shaped loss of iris pigment from viral necrosis of the iris sphincter muscle, visible on examination with a light shone from the side. HSV-2 is the dominant cause of ARN in patients younger than age 25.
• Varicella-zoster virus (VZV) uveitis and herpes zoster ophthalmicus (HZO): Reactivation of the chickenpox virus along the trigeminal nerve (the nerve serving the forehead and eye) causes shingles of the eye. This produces anterior uveitis with elevated eye pressure, corneal involvement, and sector iris atrophy alongside a characteristic shingles rash on the forehead. VZV is the most common cause of ARN in adults over age 50.
• Cytomegalovirus (CMV) uveitis: In people with healthy immune systems, CMV causes a chronic, recurring anterior uveitis with trabeculitis (inflammation of the eye’s drainage system), leading to elevated eye pressure. In people with human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) whose CD4 T-cell count has fallen below 50 cells per microliter, CMV causes CMV retinitis—an AIDS-defining illness in which the virus destroys full-thickness sections of the retina through hemorrhagic, necrotizing lesions, producing the characteristic “pizza pie” retinal appearance on examination.
• Rubella virus (Fuchs uveitis syndrome): The rubella virus can persist chronically inside the eye, causing a quiet, unilateral, low-grade anterior uveitis with characteristic stellate (star-shaped) deposits on the cornea and gradual iris color change (heterochromia). There is usually no redness or pain. Rubella virus ribonucleic acid (RNA) is detectable in aqueous humor by polymerase chain reaction (PCR), and the diagnosis is increasingly confirmed through metagenomic sequencing.
• Acute retinal necrosis (ARN): a named syndrome caused by HSV or VZV in people with functioning immune systems. It is defined by four criteria occurring together: peripheral white necrotizing retinitis, occlusive vasculitis of retinal blood vessels, significant anterior uveitis, and rapid circumferential spreading of the retinal destruction without treatment. Retinal detachment occurs in approximately 50% of ARN cases even with treatment, and nearly half of patients are left with visual acuity of 20/200 or worse within six months.
• Progressive outer retinal necrosis (PORN): a rapidly destructive form of VZV retinitis that occurs in severely immunocompromised patients (HIV with CD4 below 50). Unlike ARN, PORN causes rapid painless peripheral retinal destruction with essentially no vitreal inflammation and minimal anterior uveitis—the eye can look almost normal while the retina is being destroyed. Prognosis is extremely poor without immediate antiviral treatment.
• Dengue, Chikungunya, Zika, and West Nile virus uveitis: Arboviral infections (transmitted by mosquitoes) can cause posterior uveitis—including macular edema, disc edema, and multifocal chorioretinal lesions—typically appearing two to eight weeks after the acute febrile illness. West Nile virus produces a distinctive pattern of clustered “creamy white” chorioretinal lesions.
• HIV-related ocular disease, including immune recovery uveitis (IRU): a paradoxical inflammatory response that occurs when the immune system rebounds after antiretroviral therapy in patients who had previously undetected CMV retinitis. IRU is treated with anti-inflammatory therapy, not additional antivirals.

• Syphilitic uveitis: Syphilis caused by Treponema pallidum is called “the great masquerader” because it can present as virtually any form of uveitis—anterior, posterior, panuveitis, retinitis, or inflammation of the optic nerve. It occurs during secondary and tertiary syphilis and is strongly associated with HIV co-infection (29% of one U.K. series was HIV-positive). In the United States, syphilitic uveitis cases rose by 28.6% year-over-year from 2020 to 2021. Syphilis serology is mandatory in every new uveitis evaluation because the disease is completely curable, but can cause permanent vision loss if missed.
• Ocular tuberculosis (OTB): Tuberculosis reaches the eye through the bloodstream, establishing itself most likely in the retinal pigment epithelium. The resulting chronic granulomatous uveitis most commonly presents as serpiginous-like choroiditis (a geographic destructive pattern spreading across the retina), multifocal chorioretinal scars, retinal periphlebitis (inflammation of the veins that supply the retina), or a discrete choroidal granuloma. OTB uveitis accounts for 19–28% of infectious uveitis in India and has increased substantially in developing-world referral series over the past two decades.
• Lyme disease uveitis: The bacterium Borrelia burgdorferi, transmitted by deer tick bites in the northeastern and midwestern United States, can cause intermediate uveitis with vitreous snowball opacities that is easily confused with idiopathic pars planitis or sarcoidosis. A history of tick exposure and two-tier serological testing (enzyme-linked immunosorbent assay—ELISA followed by Western blot) lead to the diagnosis.
• Bartonella neuroretinitis (cat scratch disease): The bacterium Bartonella henselae, associated with cat scratches or bites, seeds the optic nerve head through the bloodstream, causing swelling of the optic disc and a radiating pattern of lipid deposits in the macular retina called a “macular star”—the hallmark sign of neuroretinitis.
• Endogenous bacterial endophthalmitis: A severe panuveitis from bacteria seeding the eye via the bloodstream from a distant site of infection (endocarditis, urinary tract infection, IV drug use). A layered white collection of cells visible at the bottom of the anterior chamber (hypopyon) is the hallmark sign. Organisms include Staphylococcus, Streptococcus, Klebsiella, and E. coli.
• Other named bacterial causes: Brucellosis (panuveitis in patients from the Middle East or Mediterranean), Whipple’s disease (rare; characterized by the pathognomonic finding of oculomasticatory myorhythmia—a rhythmic jerking movement of the jaw and eyes), and leptospirosis (bilateral recurrent anterior or posterior uveitis in tropical regions).

• Presumed ocular histoplasmosis syndrome (POHS): the most common infectious uveitis in the United States per some large cohort studies. Histoplasma capsulatum is endemic in the Ohio and Mississippi River valleys. POHS is characterized by a distinctive triad: scarring around the optic disc (peripapillary atrophy), punched-out peripheral chorioretinal scars, and choroidal neovascularization—abnormal new blood vessel growth that causes vision loss. Crucially, there are no white blood cells in the vitreous (“quiet vitreous”) despite active disease, which distinguishes it from most other forms of posterior uveitis. The fungal infection itself is long past by the time POHS is diagnosed; the vision threat is entirely from the choroidal neovascularization it leaves behind.
• Candida endophthalmitis: endogenous (bloodstream-spread) Candida infection of the eye, typically arising in patients with intravenous (IV) drug use, IV catheters, or immunocompromise. The characteristic appearance is fluffy white vitreal opacities with a “string of pearls” pattern of lesions.
• Aspergillus endophthalmitis: an aggressive fungal infection most commonly seen after bone marrow transplant, prolonged neutropenia, or intraocular surgery. It can cause orbital and retinal necrosis.
• Cryptococcal choroiditis: multifocal choroidal lesions in HIV patients, often accompanying cryptococcal meningitis. Serum cryptococcal antigen testing is positive in most cases.

• Ocular toxoplasmosis: the most common cause of infectious posterior uveitis worldwide. It is caused by reactivation of Toxoplasma gondii tissue cysts in the retina, acquired either congenitally (before birth) or later in life through undercooked meat or cat feces exposure. The hallmark sign is a focal, white or yellow active retinal lesion adjacent to a pigmented old chorioretinal scar—described as a “headlight in fog.” The active lesion represents living parasites bursting out of a dormant cyst site and destroying the surrounding retina. The Goldmann-Witmer coefficient—a test comparing anti-Toxoplasma antibodies in the aqueous humor to those in the blood—is the primary confirmatory test.
• Toxocariasis (ocular larva migrans): most common in children. Larvae of Toxocara canis or Toxocara cati migrate to the retina and form a white elevated granuloma at the posterior pole or retinal periphery. Children with a history of eating dirt (pica) or contact with puppies are at risk. Serum ELISA testing detects exposure.
• Onchocerciasis (river blindness): Microfilariae of Onchocerca volvulus enter the anterior chamber, causing anterior uveitis and punctate keratitis. This is the leading cause of infectious blindness in sub-Saharan Africa.
• Ocular cysticercosis: A cyst of the pork tapeworm Taenia solium develops inside the eye or beneath the retina, causing tractional retinal detachment. B-scan ultrasound identifies the cyst.

Infectious uveitis develops when a pathogenic organism enters the eye, either by traveling through the bloodstream from a distant infection, by direct physical entry through trauma or surgery, or by reactivating from a dormant state it has established inside the eye or body. Each route creates distinct clinical scenarios, and identifying which pathway is involved helps direct the workup.

Hematogenous dissemination—spread through the bloodstream—is the most common route. The choroid, with its very high blood flow, is particularly vulnerable to seeding from circulating pathogens. This is how CMV, Toxoplasma, syphilis, tuberculosis, Candida, Histoplasma, Bartonella, dengue virus, and West Nile virus reach the eye from a distant source. Direct inoculation enters the eye through penetrating trauma, intraocular surgery (producing postoperative endophthalmitis), contact lens misuse (Acanthamoeba), or spread from a corneal infection inward. Reactivation of a latent infection is particularly important for herpes viruses (HSV, VZV, CMV), Toxoplasma gondii, and Mycobacterium tuberculosis, all of which establish dormant infections in the eye or body that reactivate when the host’s immune defenses weaken—due to aging, HIV infection, corticosteroids, biologic drugs, or organ transplantation.

Different classes of organisms cause damage through different mechanisms. Herpes viruses (HSV and VZV) directly kill the cells of the retinal pigment epithelium, photoreceptors, and iris through cytolytic (cell-destroying) infection. T-cell-mediated immune responses to the dying infected cells amplify the destruction and are responsible for much of the necrosis in ARN. CMV destroys full-thickness retinal sections through unchecked lytic viral replication in patients whose CD4 T cells—which would normally contain the infection—have been depleted by HIV. Syphilis spreads through the bloodstream as a spirochete (corkscrew-shaped bacterium) and causes immune complex-mediated vasculitis and direct invasion of ocular tissues; ocular syphilis is classified as a form of neurosyphilis under Centers for Disease Control and Prevention (CDC) guidelines. Tuberculosis reaches the eye and establishes granulomas (organized immune cell clusters) through delayed-type hypersensitivity reactions in the choroid; the inflammatory response to heat shock proteins produced by the bacteria is a major driver of the characteristic serpiginous-like retinal destruction pattern. Toxoplasma gondii establishes tissue cysts (containing dormant bradyzoite forms) in the retina; when the cysts rupture, actively replicating tachyzoites spill out and destroy adjacent retinal tissue while triggering a cytokine response that causes additional collateral damage. All of these infections ultimately disrupt the blood-retinal barrier, causing leakage, vascular damage, retinal edema, and—in the most severe cases—neovascularization (growth of fragile new blood vessels) that further damages the retina.

The dominant risk factors for infectious uveitis are immune status, geographic exposures, and specific behavioral risks. Understanding these factors helps identify at-risk patients before vision is threatened.

• HIV/AIDS with CD4 below 50 cells per microliter: the highest-risk immune state. Patients at this level of immune depletion are at risk for CMV retinitis (an AIDS-defining illness), progressive outer retinal necrosis (PORN), Toxoplasma reactivation, and fungal endophthalmitis. Antiretroviral therapy (ART) has reduced CMV retinitis incidence by 80% in treated populations.
• Solid organ and hematopoietic stem cell transplantation: CMV, Aspergillus, Toxoplasma, and donor-derived infections are major post-transplant ocular risks.
• Malignancy and chemotherapy: These are associated with an elevated risk for fungal infections (Candida, Aspergillus) and CMV.
• Chronic systemic corticosteroids and biologic immunosuppressants: reactivate latent tuberculosis, HSV, VZV, and Toxoplasma. Mandatory tuberculosis screening before starting anti-tumor necrosis factor (TNF) biologic agents (adalimumab, infliximab, etanercept) is a standard-of-care requirement.
• Diabetes mellitus with older age: This increases CMV retinitis risk even in persons without classical immunocompromise.

• Travel to or residence in toxoplasma-endemic regions: Brazil, France, Central and South America, and sub-Saharan Africa carry the highest rates of primary Toxoplasma acquisition and reactivation disease. Raw or undercooked meat consumption in these regions significantly elevates risk.
• Ohio and Mississippi River valleys (United States): This is an endemic region for Histoplasma capsulatum; POHS is the most common infectious uveitis in some large U.S. cohort studies.
• Southwest United States (Arizona, California): This is endemic for Coccidioidomycosis; construction and soil disturbance in these areas increase exposure.
• Sub-Saharan Africa, Southeast Asia, South Asia: Tuberculosis uveitis, onchocerciasis, dengue, Rift Valley fever, and other endemic infectious causes are significantly more prevalent.
• Northeastern and midwestern United States: Tick exposure in wooded areas elevates the risk of Lyme disease intermediate uveitis.
• Cat exposure and contaminated soil: The primary acquisition route for Toxoplasma gondii is through cat feces and undercooked meat.
• Tropical mosquito-endemic regions: Dengue, Chikungunya, Zika, and West Nile viruses all spread by mosquito vectors and all cause posterior uveitis as a complication.

• Intravenous drug use: Contaminated needles seed Candida and other organisms directly into the bloodstream, causing endogenous Candida endophthalmitis.
• Men who have sex with men (MSM) and unprotected sex: In one U.K. series, 94% of ocular syphilis cases were male and 75% were MSM. Annual syphilis screening is recommended by the CDC for MSM and HIV-positive individuals.
• Limited access to antiretroviral therapy (ART): CMV retinitis risk persists in resource-limited settings even in 2024 for HIV-positive individuals who cannot access or sustain ART.

Infectious uveitis has no population-wide screening program. Screening is targeted to at-risk populations and is urgency-based when symptoms appear. Two laboratory tests are considered mandatory for every new uveitis patient, regardless of the presumed cause, because both syphilis and tuberculosis can mimic virtually any form of uveitis and are completely treatable:

• Syphilis serology: A nontreponemal test (rapid plasma reagin—RPR or venereal disease research laboratory—VDRL) to detect active syphilis, followed by a confirmatory treponemal test (fluorescent treponemal antibody absorption—FTA-ABS, Treponema pallidum particle agglutination assay—TP-PA, or equivalent) to confirm infection. Nontreponemal titers are also used to track treatment response over time.
• Tuberculosis screening: QuantiFERON-TB Gold (an interferon gamma release assay blood test) is preferred over the traditional skin test in immunocompromised patients; a chest X-ray or high-resolution computed tomography (CT) of the chest is added when clinical suspicion is high.

Additional targeted screening depends on the clinical scenario. In any HIV-positive patient whose CD4 count falls below 100 cells per microliter, dilated fundus examination to screen for early CMV retinitis is recommended before symptoms develop. Patients with posterior uveitis of unclear cause should have aqueous humor sampled for PCR testing for HSV, VZV, CMV, and Toxoplasma; the Goldmann-Witmer coefficient for Toxoplasma (comparing antibody concentrations in the aqueous fluid versus the blood) is the primary confirmatory test for active ocular toxoplasmosis. Patients planning to start immunosuppressive therapy—corticosteroids, anti-TNF biologics, or transplant immunosuppression—should have TB and toxoplasma serology, CMV PCR, and syphilis screening before treatment begins, because the upcoming immune suppression can reactivate latent infections. After highly active antiretroviral therapy (HAART) initiation in HIV patients with prior CMV, ophthalmic monitoring every three to six months is recommended to watch for immune recovery uveitis as CD4 cells recover.

Infectious uveitis is not uniformly preventable because the majority of cases arise from systemic infections, latent reactivation, or unavoidable exposures. Prevention is organized by achievable strategy:

• Antiretroviral therapy (ART/HAART): the single most impactful preventative measure globally. Consistent ART adherence reduces CMV retinitis incidence by 80% by preventing the CD4 depletion that enables opportunistic infections. Maintaining viral suppression in HIV directly prevents the immune vulnerability that makes CMV retinitis possible.
• CMV prophylaxis in transplant recipients: Valganciclovir prophylaxis is the standard of care after solid organ and stem cell transplantation to prevent CMV from reactivating during the period of maximum immunosuppression.
• Toxoplasma prophylaxis in HIV: Trimethoprim-sulfamethoxazole (TMP-SMX) taken when CD4 falls below 100 cells per microliter prevents Toxoplasma reactivation in HIV-positive patients who are seropositive.
• Safe sex practices and regular sexually transmitted infection (STI) screening: Condom use and annual syphilis testing (CDC-recommended for MSM and HIV-positive individuals) reduce syphilitic uveitis, which is increasingly prevalent.
• Tuberculosis testing before immunosuppression: An interferon-gamma release assay (IGRA) or tuberculin skin test is recommended before starting any biologic or transplant immunosuppressive regimen, with treatment for latent TB before immunosuppression begins.
• Food safety measures for Toxoplasma: Avoid raw or undercooked meat; avoid handling cat litter during pregnancy; wash hands after gardening or soil contact.
• Mosquito protection in endemic regions: DEET-containing repellents, permethrin-treated clothing, and bed nets to prevent arboviral infections (dengue, Zika, Chikungunya, West Nile) in endemic areas should be used.
• Harm reduction for IV drug use: Clean needle programs reduce endogenous Candida endophthalmitis from contaminated needles.
• Long-term antiviral prophylaxis after herpetic uveitis: Valacyclovir (500 mg to 1 g daily) reduces the frequency of recurrent HSV and VZV uveitis in patients who have had an episode.
• Prophylactic laser in ARN: Barrage laser photocoagulation placed in the unaffected retina adjacent to necrotic areas reduces the risk of retinal detachment from ARN spreading posterior to the laser marks.

The hallmark presentation of infectious uveitis depends entirely on the anatomic location of the infection. Anterior infections typically cause a dramatically painful red eye that is hard to miss. Posterior infections are often painless but cause progressive retinal destruction that can permanently destroy vision while the eye looks completely normal from the outside. The most critical clinical rule: a painless floater combined with a white retinal lesion in an immunocompromised patient is a medical emergency until infectious uveitis is excluded.

• Painful red eye: Perilimbal injection (a ring of redness around the cornea rather than diffuse conjunctival redness) is the hallmark of anterior chamber inflammation.
• Photophobia (intense light sensitivity): This is caused by inflammation of the iris and ciliary muscle, which contract painfully in bright light.
• Blurred vision: This arises from inflammatory cells floating in the anterior chamber, protein leakage, and corneal changes.
• Keratic precipitates (KPs): clusters of inflammatory cells visible on the back surface of the cornea under slit-lamp examination. The morphology varies by pathogen and is a key diagnostic clue: stellate (star-shaped) KPs suggest rubella/Fuchs uveitis syndrome; large, greasy “mutton-fat” KPs indicate granulomatous infection (tuberculosis, syphilis); irregular dendritiform (branch-shaped) KPs suggest herpetic uveitis; small, round diffuse KPs are characteristic of CMV anterior uveitis.
• Sector iris atrophy: a wedge-shaped area of iris pigment loss, pathognomonic (uniquely characteristic) of HSV and VZV anterior uveitis, caused by viral necrosis of the iris sphincter muscle. Best seen when a light is shone from the side through the pupil.
• Elevated intraocular pressure: Trabeculitis (inflammation of the eye’s drainage meshwork) from CMV or herpetic infection impairs aqueous drainage and raises eye pressure, sometimes to dangerous levels.
• Hypopyon: a visible horizontal layer of white cells settling at the bottom of the anterior chamber, indicating severe anterior inflammation or endophthalmitis. The hallmark of severe Behcet’s disease-associated uveitis and endogenous bacterial endophthalmitis.

• Floaters: “cloud-like” or “cobweb” visual disturbances in the vitreous, caused by inflammatory cells in the gel
• Snowball opacities: discrete white round opacities in the inferior vitreous, seen in Lyme disease, tuberculosis, and sarcoidosis-associated intermediate uveitis
• Minimal pain and redness: the “quiet eye” with significant internal disease, distinguishing intermediate from anterior uveitis

• Floaters with sudden onset alongside a retinal lesion: requires urgent evaluation. New floaters in the context of visible retinal whitening must be assessed the same day to exclude a spreading infectious process.
• Visual field defects (scotomas): These are blind spots corresponding to areas of retinal involvement or necrosis.
• Decreased central vision: This is when the macular region is involved.
• “Headlight in fog” sign: a focal white active retinal lesion with surrounding vitreous haze adjacent to a pigmented old chorioretinal scar. This sign is pathognomonic (uniquely diagnostic) for active toxoplasmic retinochoroiditis and should prompt immediate treatment.
• “Pizza pie” retinopathy: full-thickness hemorrhagic retinal necrosis with yellow-white patches in the distribution of retinal vessels. It is the characteristic appearance of CMV retinitis in AIDS. The name reflects the visual resemblance to a pizza slice on fundus examination.
• Circumferential peripheral necrotizing retinitis: white confluent peripheral lesions spreading rapidly toward the posterior pole in all directions. The hallmark of ARN.
• “Macular star” sign: stellate (star-shaped) lipid exudates radiating from the fovea combined with optic disc swelling (neuroretinitis). Characteristic of Bartonella cat scratch disease, and also seen in Lyme disease and leptospirosis.
• No redness or pain with severe progressive visual loss: PORN (progressive outer retinal necrosis) in immunocompromised patients destroys the retina rapidly, while the eye appears externally calm. The absence of typical pain or redness is itself a warning sign in an immunocompromised patient.

• Maculopapular rash on the trunk, extremities, palms, and soles: secondary syphilis; present concurrently with 41% of syphilitic uveitis cases. Any patient with uveitis and a rash should have immediate syphilis testing.
• Fever, malaise, and lymphadenopathy: viral prodrome from dengue, Chikungunya, West Nile, or Epstein–Barr viruses preceding the ocular symptoms
• Regional lymphadenopathy with a scratch or bite mark: Bartonella/cat scratch disease
• Night sweats, weight loss, and cough: systemic tuberculosis
• Herpetic skin blisters (labial or genital herpes, or a shingles rash): accompanying HSV or VZV uveitis

• In children: Toxocariasis presents as a single white retinal granuloma in a child with a history of eating dirt or contact with puppies. Congenital toxoplasmosis produces bilateral chorioretinal scars visible at or shortly after birth, often with intracranial calcifications. ARN in children is disproportionately caused by HSV-2 and carries a high risk of bilateral involvement.
• In young adults (ages 20 to 50): This is the primary risk group, accounting for 60–80% of all infectious uveitis cases. The most common presentations are herpetic anterior uveitis, toxoplasmic retinochoroiditis, and syphilitic uveitis. The MSM demographic is at particular risk for syphilis and HIV co-infection.
• In HIV-positive adults: CMV retinitis in those with CD4 below 50—initially painless and unilateral, becoming bilateral if untreated. PORN from VZV in severely immunocompromised patients causing rapid, painless peripheral visual loss.
• In older or immunocompromised adults: ARN is more severe with worse visual outcomes than in younger patients. VZV becomes the dominant ARN pathogen after age 50. Aspergillus endophthalmitis after surgery or systemic bacteremia. Fungal endophthalmitis after transplantation or prolonged hospital stays.

• Retinal detachment: approximately 50% in ARN; the most feared complication, driven by necrosis, creating multiple retinal breaks through which fluid passes and detaches the retina
• Cataract: 36% of patients requiring vitrectomy; from chronic inflammation and corticosteroid use
• Elevated intraocular pressure and glaucoma: 17% early after vitrectomy; trabeculitis from herpetic or CMV infection impairs aqueous drainage
• Cystoid macular edema (CME): fluid accumulation in the macular retina; 18% in ARN series; the leading cause of vision loss in posterior uveitis
• Optic nerve atrophy: 18% in ARN series; permanent damage to the optic nerve from vasculitis or direct viral involvement

Infectious uveitis is diagnosed by a uveitis subspecialist ophthalmologist, ideally in collaboration with an infectious disease specialist. The diagnostic approach is tiered: clinical examination and universal serology first, then pathogen-specific targeted tests, then invasive intraocular fluid sampling for unresolved diagnostic dilemmas. Crucially, infectious causes must be excluded before any corticosteroid or immunosuppressive treatment is initiated. Giving immune-suppressing medications to a patient with an undiagnosed active eye infection can be blinding or life-threatening—steroids allow the infection to spread unchecked while removing the body’s last defenses. Approximately 30–50% of presumed infectious uveitis cases cannot have a causative organism confirmed, even with PCR testing.

• Slit-lamp biomicroscopy: the gold standard. The ophthalmologist examines the anterior chamber, grading inflammatory cells (0 to 4+ per Standardization of Uveitis Nomenclature—SUN criteria) and protein leakage (flare), characterizing the morphology and distribution of keratic precipitates on the corneal surface, and identifying posterior synechiae, sector iris atrophy, hypopyon, and iris nodules. Dilated fundus examination at the same visit assesses the vitreous, retina, choroid, and optic nerve for posterior segment findings.
• Intraocular pressure measurement: Elevated pressure suggests trabeculitis from CMV or herpetic infection. The pressure trajectory during treatment provides diagnostic and therapeutic feedback.
• Dilated fundus examination with indirect ophthalmoscopy: This is essential for detecting retinal whitening, chorioretinal lesions, retinal vasculitis, vitreous haze, retinal detachment, and the pathognomonic patterns of specific infections (headlight in fog, pizza pie retinopathy, circumferential necrosis, macular star).

• Fundus fluorescein angiography (FFA): intravenous fluorescein dye injected and retinal vascular images captured. Reveals vascular leakage, retinal ischemia, disc hyperfluorescence, active versus scarred lesions, and retinal neovascularization. Essential for toxoplasmosis, syphilis, ARN, dengue, TB periphlebitis, and West Nile chorioretinitis.
• Optical coherence tomography (OCT): high-resolution cross-sectional retinal imaging. Detects and quantifies cystoid macular edema, outer retinal destruction, choroidal changes, and subretinal fluid. Used across all forms of posterior infectious uveitis to monitor structural damage and treatment response.
• Indocyanine green angiography (ICGA): evaluates choroidal vessel filling. Reveals hidden choroidal granulomas appearing as dark lesions on ICGA even when the overlying fundus looks normal. Particularly useful for tuberculosis choroiditis, histoplasmosis, and fungal choroidal lesions.
• B-scan ultrasonography: provides cross-sectional imaging when dense vitreous hemorrhage or cataract obscures the view. Essential for detecting retinal detachment in ARN and for identifying the cystic structure of intraocular cysticercosis.
• Chest X-ray and high-resolution CT: These are for tuberculosis workup (miliary TB, hilar lymphadenopathy, pulmonary consolidation).

Universal tests for all new uveitis patients: syphilis non-treponemal serology (RPR or VDRL) with confirmatory treponemal testing (FTA-ABS or TP-PA); tuberculosis screening with QuantiFERON-TB Gold (preferred over skin test in immunocompromised); HIV antibody/antigen testing; and CD4 count in confirmed HIV-positive patients. Pathogen-specific tests are then added based on clinical presentation. For herpetic anterior uveitis or suspected ARN: PCR of aqueous humor (greater than 95% sensitivity for herpesviruses). For suspected toxoplasmosis: Goldmann-Witmer coefficient of aqueous humor IgG (ratio of aqueous to serum antibody; a ratio of 3 or higher is diagnostic) and serum IgG. For syphilis: lumbar puncture (LP) for CSF-VDRL if neurosyphilis is suspected; ocular syphilis is treated as neurosyphilis regardless of CSF result. For suspected fungal endophthalmitis: intraocular fluid culture, serum (1,3)-beta-D-glucan, and blood cultures. For dengue, Chikungunya, or other arboviruses: specific IgM antibodies and RT-PCR based on travel history.

When clinical examination and serology leave the diagnosis uncertain, direct sampling of the eye’s fluids provides the most specific diagnostic information. Anterior chamber paracentesis (aqueous tap) is a low-risk slit-lamp procedure under topical anesthesia in which approximately 0.1 to 0.2 mL of aqueous humor is withdrawn with a fine needle for PCR, Goldmann-Witmer coefficient testing, and cultures. Results typically return within 24 to 48 hours. Diagnostic pars plana vitrectomy—in which a small volume of vitreous is aspirated through microincisions in the sclera—provides a larger volume sample and has an overall diagnostic yield of approximately 42% in uveitis broadly, rising to 76% when active disease is present. Vitreous samples are tested by PCR, culture, cytology, and flow cytometry. Chorioretinal biopsy is reserved for the most challenging diagnostic dilemmas—particularly when intraocular lymphoma (a cancer that can mimic infectious uveitis in adults over 50) must be distinguished from infection. An IL-10 to IL-6 cytokine ratio above a threshold in vitreous fluid supports lymphoma over infectious uveitis. Emerging technologies including metagenomic next-generation sequencing—which can detect any known or unknown pathogen in a single intraocular fluid sample—are rapidly entering clinical practice and may soon substantially increase the diagnostic yield in previously unresolvable cases.

Many forms of infectious uveitis are curable—syphilis, tuberculosis, Lyme disease, and most bacterial endophthalmitis cases can achieve full visual recovery with appropriate targeted antimicrobial therapy. The central treatment principle is: target the organism first, control inflammation second. Antimicrobial therapy is always initiated before anti-inflammatory treatment. Corticosteroids are introduced only 24 to 72 hours after antimicrobials, once therapeutic drug concentrations have built up and the infection is being controlled. Using steroids without this delay—or without antimicrobials at all—removes the immune response that is partially containing the infection and allows it to spread without restraint. Multidisciplinary care involving ophthalmology and infectious disease—and in HIV patients, the HIV specialist—is essential for complex cases. Your treating team will tailor the antimicrobial regimen precisely to the identified or strongly suspected pathogen, your immune status, and the severity of your eye involvement.

For herpetic anterior uveitis caused by HSV or VZV, the first-line treatment is oral valacyclovir (500 mg to 1 g three times daily for active episodes), preferred over acyclovir because of its better absorption and simpler dosing. The Infectious Uveitis Treatment Algorithm Network (TITAN) working group recommends valacyclovir as the standard of care. After the acute episode, long-term maintenance valacyclovir at 500 mg once daily reduces recurrence rates and is recommended for patients with frequent episodes. For acute retinal necrosis, treatment begins with intravenous acyclovir (10 mg/kg every 8 hours) for 10 to 14 days to rapidly suppress viral replication, then transitions to oral valacyclovir (1 g three times daily) for 6 to 12 weeks. Intravitreal antiviral injections—foscarnet (2.4 mg) or ganciclovir (400 mcg)—are added alongside systemic therapy to provide immediate intraocular viral suppression in severe or rapidly progressing ARN; combining systemic and intravitreal antivirals significantly improves visual outcomes and reduces retinal detachment rates compared to systemic therapy alone. For CMV retinitis in HIV/AIDS, the standard treatment is oral valganciclovir (900 mg twice daily as an induction dose for 14 to 21 days, then 900 mg once daily as maintenance), which has replaced intravenous ganciclovir for most patients. Intravenous ganciclovir remains the option when rapid blood concentration is needed (Zone 1 retinitis near the fovea, inability to tolerate oral medication). For ganciclovir-resistant CMV, intravenous foscarnet (60 mg/kg every 8 hours, with mandatory intravenous hydration to protect the kidneys) or intravenous cidofovir (with probenecid premedication to prevent nephrotoxicity) are second-line options. Maribavir (Livtencity®), a novel oral antiviral approved by the FDA in 2021 for refractory or resistant CMV in transplant recipients, offers a lower side-effect profile than foscarnet or cidofovir. Antiretroviral therapy (ART/HAART) is the cornerstone of CMV retinitis management—not just supplementary—because immune recovery from ART directly prevents the CD4 depletion that enables CMV to replicate unchecked.

Syphilitic uveitis is treated as neurosyphilis regardless of cerebrospinal fluid results, per the 2021 CDC STI Treatment Guidelines. The gold standard is intravenous aqueous crystalline penicillin G (3 to 4 million units every 4 hours) for 10 to 14 days. For patients with penicillin allergy, intravenous ceftriaxone (2 g once daily for 10 to 14 days) is a non-inferior alternative. Benzathine penicillin given by intramuscular injection—the standard treatment for non-ocular syphilis—is specifically insufficient for ocular or neurological syphilis because it does not achieve adequate concentrations in the eye or cerebrospinal fluid. After treatment, serial RPR titers at 3, 6, and 12 months confirm a four-fold titer reduction, indicating successful treatment. For ocular tuberculosis, the standard four-drug RIPE regimen (rifampicin + isoniazid + pyrazinamide + ethambutol) is given for 6 to 12 months—two months of all four drugs, then four to seven months of continuation therapy. Approximately 15% of eyes experience uveitis recurrence over long-term follow-up even after successful antibacterial treatment, reflecting the possibility of a persisting immune-mediated component. For Lyme uveitis, oral doxycycline (100 mg twice daily for 14 to 28 days) is first-line for mild disease; intravenous ceftriaxone is used for central nervous system or severe ocular involvement. For Bartonella neuroretinitis, azithromycin combined with doxycycline for four to six weeks is the recommended regimen. Endogenous bacterial endophthalmitis requires intravenous vancomycin (gram-positive coverage) combined with ceftazidime (gram-negative coverage), with intravitreal antibiotic injections directly into the eye cavity alongside systemic therapy.

For ocular toxoplasmosis, the classic treatment regimen combines pyrimethamine (an antiparasitic drug that blocks folic acid synthesis in the parasite) with sulfadiazine (an antibiotic with anti-Toxoplasma activity), plus leucovorin (folinic acid supplementation, which is mandatory to prevent the myelosuppression that pyrimethamine causes in the patient’s own bone marrow). An oral corticosteroid taper is added 24 to 48 hours after the antimicrobials begin to reduce collateral inflammatory damage. An increasingly used alternative that avoids the complexity and toxicity of the classic regimen is trimethoprim-sulfamethoxazole (TMP-SMX, two-tablet dose twice daily), which has demonstrated comparable efficacy in clinical trials with a simpler dosing schedule. Intravitreal clindamycin injection (1 mg per 0.1 mL) is a highly effective local approach that uses less than 10 mg of drug total versus approximately 50 grams for a full systemic course, dramatically reducing systemic toxicity. For patients with toxoplasma-associated choroidal neovascularization (abnormal new blood vessel growth threatening vision), intravitreal anti-vascular endothelial growth factor (VEGF) injections (bevacizumab or ranibizumab) are given alongside the antiparasitic regimen. For toxocariasis, oral albendazole combined with anti-inflammatory therapy addresses the larval infection and its inflammatory consequences. For onchocerciasis (river blindness), annual oral ivermectin (150 mcg/kg single dose) kills the circulating microfilariae that enter the eye and cause anterior uveitis, though the adult worm in the skin is not killed by this regimen.

Candida endophthalmitis is treated with oral or intravenous fluconazole (400 to 800 mg daily) for susceptible Candida albicans strains because fluconazole achieves good penetration into ocular tissues. For non-albicans Candida species or Aspergillus, voriconazole (oral or intravenous) provides better vitreous penetration and a broader antifungal spectrum. When vitreous infection is established, intravitreal amphotericin B (5 mcg per 0.1 mL) is injected directly into the eye to achieve local antifungal concentrations. For POHS, the historical Histoplasma infection is long past and inactive at the time the patient presents with visual symptoms—antifungal therapy is not indicated for stable POHS. The vision threat is entirely from choroidal neovascularization, which is treated with intravitreal anti-VEGF injections (bevacizumab, ranibizumab, or aflibercept) exactly as it is for neovascular age-related macular degeneration.

After antimicrobials have been given 24 to 72 hours to establish therapeutic concentrations, topical corticosteroids (prednisolone acetate 1% eye drops) are added to control the anterior chamber inflammatory response in all anterior infectious uveitides. Cycloplegic drops (atropine or homatropine) are mandatory in acute anterior uveitis to prevent the iris from adhering to the lens (posterior synechiae) and to relieve the painful ciliary muscle spasm that causes photophobia. For posterior segment inflammation, oral prednisone (begun 48 to 72 hours after antimicrobials), periocular triamcinolone acetonide (injected around the eye for macular edema), and intravitreal dexamethasone can reduce inflammatory damage alongside the antimicrobial treatment. Intravitreal anti-VEGF agents are used for cystoid macular edema that does not respond to corticosteroids and for choroidal neovascularization from any infectious cause. Immune recovery uveitis (IRU)—the paradoxical inflammatory response that follows CD4 recovery on HAART in patients with prior CMV retinitis—requires anti-inflammatory treatment (topical or periocular corticosteroids, sometimes systemic steroids for severe cases) and specifically does NOT require additional antivirals, because it is an immune-mediated response to dead CMV antigens rather than active viral replication.

Pars plana vitrectomy (PPV)—performed through tiny microincisions in the sclera using 23, 25, or 27-gauge instruments—serves both diagnostic and therapeutic roles in infectious uveitis. Diagnostically, it provides larger vitreous samples than aqueous tap and achieves a diagnostic yield of 42–76%; it is the highest-yield sampling technique for unresolved diagnostic dilemmas. Therapeutically, it debulks the vitreous (removing inflammatory cells, pathogens, and toxic mediators from the eye’s interior), peels epiretinal membranes, and surgically repairs retinal detachments—the most feared and vision-limiting complication of ARN and other necrotizing posterior infections. Prophylactic barrage laser photocoagulation—placing confluent laser burns around the advancing edge of necrotic retina in ARN—creates a permanent scar barrier that prevents the retinal detachment from spreading posterior to the laser marks, reducing but not eliminating the retinal detachment risk. Scleral buckling (placing a silicone band around the outside of the eye) and silicone oil tamponade (filling the vitreous cavity with silicone oil after vitrectomy to mechanically hold the retina flat) are used for complex retinal detachments associated with ARN, PORN, or proliferative vitreoretinopathy. Anterior chamber paracentesis—withdrawing 0.1 to 0.2 mL of aqueous fluid at the slit lamp under topical anesthesia—provides rapid diagnostic samples and can also immediately lower dangerously elevated intraocular pressure. Cataract surgery, when needed, should be performed under antiviral cover in herpetic uveitis patients and only after uveitis has been controlled for at least three months. For intraocular pressure that cannot be controlled medically, trabeculectomy or glaucoma drainage tube implants (Ahmed® or Baerveldt® devices) are used; the high surgical failure rate in uveitic eyes from inflammation-driven scarring is partially mitigated by intraoperative mitomycin C application.

For many patients with infectious uveitis, the prognosis depends heavily on the specific pathogen, the immune status of the patient at the time of diagnosis, and how quickly treatment begins. Some forms are entirely curable: syphilitic uveitis, when treated with intravenous penicillin, can achieve complete recovery of vision. Tuberculosis uveitis has a recurrence rate of approximately 15% over long-term follow-up but is highly responsive to the standard RIPE regimen. Lyme uveitis typically resolves with antibiotics. For these bacterial infections, the key to a good outcome is simply early diagnosis and prompt treatment—which is why universal syphilis and TB testing in every new uveitis patient is so important.

For viral infections—including herpetic uveitis and CMV retinitis—the virus cannot be fully eradicated with current therapy, and the risk of recurrence is lifelong. Long-term antiviral prophylaxis (valacyclovir for HSV/VZV, valganciclovir for CMV in the right context) substantially reduces recurrence frequency, and most patients on appropriate prophylaxis have infrequent flares. Toxoplasma gondii similarly cannot be eliminated; the parasite establishes permanent tissue cysts in the retina that can reactivate at any time, particularly during periods of immune weakness. Long-term antiparasitic prophylaxis after recurrent episodes is an option, and the risk of reactivation decreases over time. ARN syndrome carries the most severe prognosis of any infectious uveitis form—approximately half of patients are left with visual acuity of 20/200 or worse within six months despite treatment—and retinal detachment remains the dominant complication even with prophylactic laser. CMV retinitis has been transformed by antiretroviral therapy from a nearly universal cause of blindness in AIDS to a manageable condition: HIV-positive patients who maintain viral suppression and immune recovery rarely develop CMV retinitis, and those who do can recover useful vision with treatment. Ongoing ophthalmic monitoring—the frequency determined by the specific pathogen and treatment response—is a permanent feature of life after infectious uveitis, and any new floater, reduction in vision, or return of a red eye should prompt the same-day call to your ophthalmologist that was described when symptoms first began.

To further your understanding of your diagnosis and to contribute to leading-edge research, consider participating in a clinical trial so clinicians and scientists can learn more about causes, symptoms, treatment, and prevention of infectious uveitis and related disorders. Clinical research uses human volunteers to help researchers learn more about a disorder and perhaps find better ways to safely detect, treat, or prevent disease.

All types of volunteers are needed—those who are healthy or may have an illness or disease—of all different ages, sexes, races, and ethnicities to ensure that study results apply to as many people as possible, and that treatments will be safe and effective for everyone who will use them.