Syphilitic Uveitis

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Article initiated by:

Arjun B. Sood, MD

All contributors:

Ghazala A. D. O'Keefe, MD, Leo A. Kim, MD, PhD, Arjun B. Sood, MD, Koushik Tripathy, MD (AIIMS), Alan Palestine, MD, Aumer Shughoury, MD, Amanda Mohanan Earatt MBBS MS(Ophth) MRCS(Glasgow) MRCSEd FICO, Jennifer I Lim MD, Homaira Ayesha Hossain, MD, Razek Georges Coussa, MDCM, MPhil, MEng

Assigned editor:

Razek Georges Coussa, MDCM, MPhil, MEng, Olena Hurzhii, MD

Review:

Assigned status Up to Date

 by Razek Georges Coussa, MDCM, MPhil, MEng on March 8, 2026.

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Disease Entity

Syphilis is an infectious disease caused by Treponema Pallidum and is most commonly spread through sexual transmission. Syphilitic uveitis is the most common ocular manifestation, is a potentially blinding disease, and is one of the most important infectious causes of uveitis to rule out. Key points to consider:

• “Test for syphilis in all cases of uveitis.”
• Ocular syphilis is called the “great masquerader.”
• Most cases are posterior uveitis or panuveitis.
• Treat as neurosyphilis with IV penicillin.

Modern reviews stress that failure to consider syphilis leads to delayed treatment and worse outcomes

Brief History

Syphilis was first reported in Europe in the 15^th century.  There was rapid spread throughout Europe that was associated with the French invasion of Italy in 1494.  The origin of syphilis has been well debated for over 500 years.  Due to the temporal relation with Christopher Columbus’s voyage in 1492, many theorized the disease was brought to Europe by Columbus and his crew – the “Columbian Hypothesis.”  Others theorized the disease was already present in the Old World before the 1490’s and the emergence of the disease in the 15^th century was attributed to increased virulence and medical recognition – the “Pre-Columbian Hypothesis.”  It is a debate that still continues today but an extensive review published by Harper et al. in 2011 supports the Columbian Hypothesis.

Timeline of Syphilis in the United States

• 1905, Treponema pallidum was first described by Schaudin and Hoffin as the causative bacteria of syphilis.  They demonstrated spirochetes in Giema stained smears from syphilitic lesions. 
• 1943: first reported cure with penicillin
• 1947: incidence of primary and secondary syphilis was 66.4 cases/100,000
• 1956: rates decline to 3.9 cases/100,000
• 1999: introduction of the National Plan to Eliminate Syphilis from the United States announced by the United States Surgeon General
• 2000: lowest ever recorded rate of 2.1 cases/100,000 (approximately 5,979 cases in year 2000)
• 2000-2012: steady increase with incidence exceeding 55,000 new cases a year

Risk Factors and At-Risk Populations

• Men who have sex with men (MSM)
• HIV co-infection
• Unprotected sex

Diagnosis

Syphilis is known as the Great Imitator as systemic manifestations vary. Ocular manifestations can affect any part of the eye, with syphilitic uveitis being the most common.

History

Any patient with intraocular inflammation (uveitis) should have a thorough history and review of systems. Information or risk factors that may suggest syphilis include a history of unprotected sex, recent STDs or HIV infection, MSM and substance abuse.

Physical Examination

Systemic features of Syphilis

Syphilis can affect many parts of the body. Most common physical exam findings include:

• Skin Rash
• Palms and Sole maculopapular rash
• Genital and Perianal chancres
• Lymph Node Swelling
• Oral Cavity gummas

Ocular Symptoms

Due to the varying degrees of presentation patients may complain of blurry vision, floaters, light sensitivity, double vision, eye pain, and foreign body sensation

Clinical Diagnosis and Ocular Findings

Syphilis can affect any ocular structure, including retina, choroid, optic nerve, and anterior segment.

Anatomic Location	Ocular Findings
Conjunctiva	Mucous Patches, Papillary Conjunctivitis, Graulomatous Conjunctivitis
Sclera	Episcleritis and Scleritis
Cornea	Stromal Keratitis, marginal corneal infiltrates, Keratic precipitates
Lens	Congenital Cataract, Uveitic cataract
Uveal Tract	Iritis, iridocyclitis, iris nodules, multifocal choroiditis, Posterior Placoid chorioretintis (typical), round viteous floaters just in front of the retina
Retina/RPE	Retinal vasculitis, RPE mottling, necrotizing retinitis, macular edema, retinochoroiditis, serous retinal detachment, rhegmatogenous retinal detachment, tractional retinal detachment
Optic Nerve	Disc edema and atrophy
Pupils	Argyll Robertson Pupil
Cranial Nerve and Brainstem	Extraocular motility deficit

Images of posterior placoid chorioretinitis are available at https://imagebank.asrs.org/discover-new/files/1/25?q=Posterior%20Placoid%20Chorioretinitis

The most common manifestations are: posterior uveitis, panuveitis, placoid chorioretinitis, retinal vasculitis, optic neuritis/papillitis, and neuroretinitis. Posterior uveitis and panuveitis are the most frequent ocular presentations.

Multimodal Imaging

Multimodal retinal imaging plays an important role in the evaluation and follow-up of patients with syphilitic uveitis. Because ocular syphilis can present with a wide spectrum of posterior segment findings—including acute syphilitic posterior placoid chorioretinitis (ASPPC), multifocal retinitis, retinal vasculitis, and optic nerve involvement—imaging modalities such as optical coherence tomography (OCT), fluorescein angiography (FA), and optical coherence tomography angiography (OCTA) are frequently used to support diagnosis, characterize disease activity, and monitor response to therapy.

Optical coherence tomography (OCT) is particularly useful for identifying structural retinal changes associated with syphilitic inflammation. In cases of ASPPC, OCT often demonstrates disruption of the outer retinal layers, including the ellipsoid zone and interdigitation zone, with associated hyperreflective material at the level of the retinal pigment epithelium (RPE) and outer retina. Subretinal fluid and focal RPE irregularities may also be present. Inflammatory retinitis associated with syphilis can appear as hyperreflective lesions involving the inner or outer retina, sometimes accompanied by cystoid macular edema or serous retinal detachment. OCT is also valuable for documenting the gradual restoration of outer retinal architecture after successful antimicrobial therapy.

Fluorescein angiography (FA) can help identify retinal vascular and chorioretinal abnormalities associated with syphilitic uveitis. FA frequently demonstrates retinal vasculitis, which may involve both arteries and veins, and may show areas of vascular leakage, capillary nonperfusion, or optic disc leakage. In ASPPC, placoid lesions often appear hypofluorescent in the early phases of angiography due to blockage or choriocapillaris hypoperfusion, followed by late staining as dye accumulates within the inflamed outer retina and RPE. FA can also be helpful in distinguishing syphilitic lesions from other infectious or inflammatory retinopathies by demonstrating characteristic leakage patterns and the extent of vascular involvement.

Optical coherence tomography angiography (OCTA) is an increasingly used adjunctive imaging modality that allows noninvasive visualization of retinal and choroidal microvasculature. In syphilitic uveitis, OCTA may demonstrate alterations in the choriocapillaris or deep retinal capillary plexus corresponding to areas of placoid inflammation or retinal ischemia. In atypical presentations, OCTA may also aid in detecting secondary complications such as inflammatory choroidal neovascularization (CNV). Although OCTA findings in syphilitic uveitis are still being characterized, the modality can provide additional insight into vascular changes and may be useful for longitudinal monitoring.

Taken together, multimodal imaging can provide complementary structural and vascular information that helps differentiate syphilitic uveitis from other infectious or inflammatory entities such as acute retinal necrosis, viral retinitis, or inflammatory white-dot syndromes. Imaging findings often improve with appropriate antimicrobial therapy and can be used to document disease resolution and retinal recovery over time.

Testing for Suspected Syphilis

Serologic Tests

Serologic testing is the mainstay for diagnosis of ocular syphilis

Nontreponemal Tests (NTT)

• Measures antibodies against lipoidal antigens released by damaged host cells and possibly spirochetes
• Examples: RPR (rapid plasma reagin), VDRL (venereal disease research laboratory)
• Most useful test to track active disease and treatment efficacy

Treponemal Tests (TT)

• Measures antibodies against Treponema pallidum proteins
• Examples: EIA (enzyme immunoassay), FTA-ABS (Fluorescent treponemal antibody absorption), TPPA (T pallidum particle agglutination), TPHA (Treponema pallidum hemagglutination), CIA (chemiluminescence immunoassay)
• Stays positive for life

CDC recommendations for Syphilis Testing and Management

Laboratory diagnosis of syphilis

Reverse Sequence Testing

The CDC recommended testing algorithm for syphilis is shown. The algorithm starts with a highly sensitive but non specific immunoassay for treponemal antibodies. If the test is negative, syphilis is ruled out. If the test is positive then a non-treponemal test is performed. A positive non-treponemal test (RPR) is diagnostic of syphilis. A negative RPR following a positive EIA is a discordant test result. The negative RPR must be confirmed by a different treponemal test, the TP-PA, which is both sensitive and specific.

Other Tests

Other tests like Polymerase Chain Reaction and Immunoblot are being investigated for application in the diagnosis of ocular syphilis.

Molecular diagnostics involving the assessment of levels of cytokines and biomarkers for diagnostic purposes are being studied.

Management and other considerations

• Treatment is the same as neurosyphilis: 10-14 day course of systemic antibiotics.
• All patients testing positive for syphilis should be tested for HIV due to the high rate of co-infection.
• All patients should undergo lumbar puncture and CSF analysis.
• Treatment should not be delayed while waiting for lumbar puncture.

Medical therapy

• IV Penicillin G 24 million units daily 10-14 day course or IM Procaine Penicillin 2.4 million units daily and Probenicid 2 grams daily
• Alternative therapeutic regimens including Ceftriaxone or Doxycycline have been attempted in patients who cannot be given Penicillin, albeit with varying success rates.
• Adjunctive Therapy:
  • Topical steroids
  • Oral steroids: useful to decrease inflammatory reaction (Jarisch–Herxheimer reaction) but there is no agreement on if and when to initiate. Those who utilize systemic steroids suggest starting with 40mg daily 2-3 days after initiation of systemic antibiotics. Oral steroid should not be started without proper antimicrobial coverage as it may worsen the disease (https://link.springer.com/article/10.1186/s12348-018-0164-5).

Medical follow up

• Repeat lumbar puncture indicated at 6 months post-treatment if initial CSF VDRL is positive.
• Persistent ocular inflammation despite full treatment course of antibiotics and oral corticosteroids may indicate treatment failure though this is rare. Consultation with infectious disease specialist is recommended to determine need for re-hospitalization and repeat systemic antibiotics.
• Titers are expected to decrease 4 fold after successful treatment.

Prognosis

Visual outcomes are often favorable with prompt diagnosis and treatment, but delayed recognition can lead to permanent visual loss from retinal or optic nerve injury. Clinical follow-up should include monitoring of ocular inflammation, structural recovery, and declining non-treponemal titers after therapy.

References

2. Aldave, A.J., J.A. King, and E.T. Cunningham, Jr., Ocular syphilis. Curr Opin Ophthalmol, 2001. 12(6): p. 433-41.
3. Amaratunge, B.C., J.E. Camuglia, and A.J. Hall, Syphilitic uveitis: a review of clinical manifestations and treatment outcomes of syphilitic uveitis in human immunodeficiency virus-positive and negative patients. Clin Experiment Ophthalmol, 2010. 38(1): p. 68-74.
4. Butler, N.J. and J.E. Thorne, Current status of HIV infection and ocular disease. Curr Opin Ophthalmol, 2012. 23(6): p. 517-22.
5. Chao, J.R., et al., Syphilis: reemergence of an old adversary. Ophthalmology, 2006. 113(11): p. 2074-9.
6. Davis, J.L., Ocular syphilis. Curr Opin Ophthalmol, 2014. 25(6): p. 513-8.
7. Gaudio, P.A., Update on ocular syphilis. Curr Opin Ophthalmol, 2006. 17(6): p. 562-6.
8. Harper, K.N., et al., The origin and antiquity of syphilis revisited: an appraisal of Old World pre-Columbian evidence for treponemal infection. Am J Phys Anthropol, 2011. 146 Suppl 53: p. 99-133.
9. Hughes, E.H., et al., Syphilitic retinitis and uveitis in HIV-positive adults. Clin Experiment Ophthalmol, 2010. 38(9): p. 851-6.
10. Kiss, S., F.M. Damico, and L.H. Young, Ocular manifestations and treatment of syphilis. Semin Ophthalmol, 2005. 20(3): p. 161-7.
11. Mathew, R.G., B.T. Goh, and M.C. Westcott, British Ocular Syphilis Study (BOSS): 2-year national surveillance study of intraocular inflammation secondary to ocular syphilis. Invest Ophthalmol Vis Sci, 2014. 55(8): p. 5394-400.
12. Tampa, M., et al., Brief history of syphilis. J Med Life, 2014. 7(1): p. 4-10.
13. Woolston, S., et al., A Cluster of Ocular Syphilis Cases - Seattle, Washington, and San Francisco, California, 2014-2015. MMWR Morb Mortal Wkly Rep, 2015. 64(40): p. 1150-1.