Ophthalmology Dx: The Great Pretender

Slideshow

  • Figure 1. This slit lamp photograph shows a dense vitreous cell in the left eye.

  • Figure 2. Bilateral fundus photographs show bilateral optic nerve edema without any hemorrhages or vessel obscuration. The retina in both eyes is otherwise unremarkable.

  • Figure 3. Autofluorescence imaging shows patchy areas of hyperautofluorescence in the posterior pole and macula of both eyes.

  • Figure 3. Autofluorescence imaging shows patchy areas of hyperautofluorescence in the posterior pole and macula of both eyes.

  • Figure 4. Fluorescein angiography of the right eye (1:15 minutes) and left eye (13:55 minutes) show irregular background hyperfluorescence and disc leakage in both eyes.

  • Figure 4. Fluorescein angiography of the right eye (1:15 minutes) and left eye (13:55 minutes) show irregular background hyperfluorescence and disc leakage in both eyes.

  • Figure 5. Optical coherence tomography imaging shows outer retinal subfoveal granular deposits and loss of the ellipsoid zone in both eyes.

  • Figure 5. Optical coherence tomography imaging shows outer retinal subfoveal granular deposits and loss of the ellipsoid zone in both eyes.

A 47-year-old male patient presented with 2 months of blurry vision in his left eye and 2 days of blurry vision in the right eye. His medical history was significant for hypotestosteronism, atrial fibrillation, cardiomyopathy of unclear etiology with a mildly reduced ejection fraction, and a basal cell carcinoma on the scalp. 

On examination, his visual acuity was 20/25 in the right eye and 20/200 in the left eye. His intraocular pressures (IOP) were 17 mm Hg in the right eye and 18 mm Hg in the left eye. He saw 8/8 Ishihara color plates in the right eye and 0/8 in the left eye (control plate only). His pupils were bilaterally reactive with early release in the left eye, concerning for a mild relative afferent pupillary defect on the left. 

Upon examination, his anterior segment appeared unremarkable. Dilated funduscopic examination showed mild vitreous cell, in the left eye greater than the right (Figure 1). He also had bilateral 360-degree disc edema, without hemorrhages or vessel obscuration in either eye (Figure 2). 

Additional testing revealed bilateral large patches of hyperautofluorescence in the posterior pole (Figure 3). These corresponded to the hyperfluorescent staining patches and leaking from the optic disc in both eyes on fluorescein angiography (Figure 4). Optical coherence tomography (OCT) revealed subretinal granular deposits and loss of the ellipsoid zone in the macula of both eyes (Figure 5).

Syphilis is a sexually transmitted disease caused by the spirochete Treponema pallidum. Syphilis can affect almost any part of the eye and is notorious for mimicking other inflammatory conditions with its posterior manifestations mimicking white dot syndromes, sarcoidosis, IBD-associated disease,...

Submit your diagnosis to see full explanation.

Syphilis is a sexually transmitted disease caused by the spirochete Treponema pallidum. Syphilis can affect almost any part of the eye and is notorious for mimicking other inflammatory conditions with its posterior manifestations mimicking white dot syndromes, sarcoidosis, IBD-associated disease, intraocular lymphoma or other malignancies, papilledema such as in elevated intracranial pressure, or infection with Bartonella, tuberculosis, or Borrelia, among others. As such, syphilis is routinely tested in cases of intraocular inflammation. 

Testing for syphilis includes nontreponemal and treponemal-specific tests. The nontreponemal tests, which include venereal disease research laboratory test (VDRL) and rapid plasma reagin (RPR), are relatively sensitive but not specific. These tests detect IgG/IgM antibodies that are raised against antigens that are released by damaged host cells in response to bacteria. The treponemal-specific tests, on the other hand, include fluorescent treponemal antibody absorption test (FTA-Abs), microhemagglutination T pallidum test (MHA-TA), and T pallidum particle agglutination assay (TTPA). These tests are much more specific but they cannot distinguish active from chronic infection.1 

Syphilis has primary, secondary, latent, and tertiary stages — and ocular syphilis may occur at any of these stages, although is most common during the phase of secondary syphilis. Primary syphilis is essentially always associated with 1 or more painless genital ulcers, known as chancres, which often go unnoticed and heal spontaneously, with eye involvement being rare in this stage. 

Secondary syphilis develops 4 to 10 weeks after the chancre develops if left untreated and is characterized by a diffuse maculopapular rash that involves the palms and soles, as well as fever, lymphadenopathy, and headache. In the eye, there may be anterior uveitis (either granulomatous or nongranulomatous), episcleritis, scleritis, chorioretinitis, vitritis, retinal vasculitis, or papillitis. Involvement of the posterior segment of the eye tends to occur later in secondary syphilis.2 An essentially pathognomic manifestation of posterior involvement is known as acute posterior placoid chorioretinopathy, which affects the retinal pigment epithelium (RPE). Although our case does not reveal yellow posterior plaques on fundus imaging, other classic imaging findings of placoid syphilis are present in our case – patches of hyperautofluorescence, hyperfluorescent staining of the placoid area on fluorescein angiography, and subretinal granular deposits with loss of the ellipsoid zone. Secondary syphilis may last for up to a couple of years if untreated, after which the manifestations will eventually disappear but progression to tertiary syphilis can occur. 

Tertiary syphilis can cause widespread damage, including cardiovascular complications and neurologic involvement. In the eye, tertiary syphilis may cause eyelid-involving gummas of the anterior or posterior segment including the optic nerve, Argyll Robertson pupils, anterior and posterior uveitis, retinal vasculitis, keratitis, scleritis, or ischemic optic nerve involvement.2,3

Serologic testing in this patient showed reactive RPR at 1:128 and positive fluorescent treponemal antibodies. MRI/MRA ruled out any intracranial mass lesions nor evidence of increased intracranial pressure. He was diagnosed with ocular syphilis causing bilateral papillitis and vitritis, and was treated with the Centers for Disease Control and Prevention (CDC) recommended IV penicillin 18 to 24 million units per day for 10 to 14 days, which is the regimen for neurosyphilis.1 

Management of any case of syphilis must also include testing for HIV and other sexually transmitted diseases, as HIV coinfection may increase the risk of ocular syphilis.4 Notably, as of 2021, lumbar puncture is no longer recommended by the CDC for patients with ocular syphilis but no neurologic signs or symptoms.1 This patient tested negative for HIV. His vision, vitritis, and optic nerve swelling ultimately improved with IV penicillin therapy. 

This case was contributed by Melissa Yuan, MD, an ophthalmology resident at Massachusetts Eye and Ear and Harvard Medical School in Boston, MA.

The case was edited by Grayson W. Armstrong, MD, MPH, an instructor of ophthalmology at Massachusetts Eye and Ear and Harvard Medical School and Director of Ophthalmology Emergency Service.

References

1. Sexually Transmitted Infections Treatment Guidelines, 2021. Neurosyphilis, Ocular Syphilis, and Otosyphilis. Centers for Disease Control and Prevention. www.cdc.gov/std/treatment-guidelines/neurosyphilis.htm. Accessed March 9, 2023.

2. Moradi A, Salek S, Daniel E, et al. Clinical features and incidence rates of ocular complications in patients with ocular syphilis. Am J Ophthalmol. 2015;159(2):334-43. doi:10.1016/j.ajo.2014.10.030

3. Gu X, Gao Y, Yan Y, et al. The importance of proper and prompt treatment of ocular syphilis: a lesson from permanent vision loss in 52 eyes. J Eur Acad Dermatol Venereol. 2020;34(7):1569–1578. doi:10.1111/jdv.16347 

4. Cope AB, Mobley VL, Oliver SE, et al. Ocular syphilis and HIV coinfection among syphilis patients in North Carolina, 2014-2016. Sex Transm Dis. 2019;46(2):80–85. doi:10.1097/OLQ.0000000000000910