Timely diagnosis and management of ocular syphilis to prevent permanent visual loss

Image credit: AdobeStock/ChristophBurgstedt

Ocular syphilis, a potential manifestation of secondary or tertiary syphilis, is rare, but serious nonetheless.

Arslan J. Khan, DO, and Stephen DiGiuseppe, PhD, both from the Edward Via College of Osteopathic Medicine, Monroe, LA, and Moneeb Mustafa, MD, from the Rapid Regional Medical Center, Alexandria, LA, described a case¹ of ocular syphilis and its diagnostic challenges. These challenges exist because syphilis progresses through distinct clinical stages, each characterized by unique pathophysiologic mechanisms, they explained.

Syphilic stages

Primary syphilis results from Treponema pallidum invasion, which occurs most often in the genitals, but extragenital lesions can develop on the digits, nipples, tonsils, and oral mucosa. When untreated, primary syphilis progresses to secondary syphilis due to hematogenous dissemination of T. pallidum, which is characterized by mucocutaneous involvement (macular rash, condyloma lata, and lesions on the hands and feet), headache, myalgia, arthralgia, pharyngitis, hepatosplenomegaly, and malaise.

The primary phase can resolve spontaneously if not treated, leading to clinically asymptomatic latent phases, early (infections acquired within a year) and late (that persisting for more than a year), only detectable through serologic testing.² Some patients can be asymptomatic in this phase, but others can develop tertiary syphilis.

Tertiary syphilis, which can develop years to decades after the initial infection, is characterized by chronic inflammatory damage affecting multiple organ systems, the most prevalent of which are cardiovascular syphilis, gummatous syphilis, and central nervous system syphilis, ie, neurosyphilis.² Tertiary syphilis also can cause eye diseases such as ocular syphilis and retinal detachment.

Neurosyphilis can develop during early or late infection, although the presentation can differ at each stage. Syphilitic uveitis is the most common ocular manifestation of syphilis, and although rare, it can result in irreversible vision loss.³

As they explained in their case report,¹ “The diagnosis of ocular syphilis often poses a formidable challenge owing to its rare occurrences and the presence of nonspecific clinical findings in patients with a negative HIV status. In such instances, it becomes crucial to promptly employ serologic testing, such as rapid plasma reagin titers, and a thorough patient history aligned with the presenting symptoms. In certain scenarios, lumbar punctures may also be necessary to definitively confirm the diagnosis.”

Management strategies for patients with ocular syphilis primarily involve antibiotic treatment achieved using high-dose intravenous or intramuscular penicillin. Therefore, a comprehensive strategy that integrates vigilant diagnostic evaluation and customized symptomatic treatment is essential for effectively addressing this uncommon progression of disease.

Case report

A 28-year-old man with an unremarkable medical history presented to an ophthalmology clinic but was transferred to the emergency department (ED) because of suspected late-stage tertiary syphilis.

He reported sudden onset of pain, blurry vision, multiple floaters, and vision loss in his left eye that suggested a retinal detachment and suspected ocular syphilis. His visual disturbance resulted in a fall during the clinic visit.

In the ED, he reported having had a painless genital lesion 2 years previously that resolved spontaneously. He denied fever, weight loss, or rashes but admitted to having had multiple sexual partners.

Examination showed a dilated left pupil and reduced visual acuity of 20/200; the vision in the right eye was 20/20. A dilated funduscopic examination showed an extensive retinal detachment in the left eye, with subretinal fluid and undulating folds, consistent with macular involvement. Fluorescein angiography (FA) images revealed an inflammatory etiology, including diffuse retinal vascular leakage, optic disc hyperfluorescence, and focal retinal inflammation.

“These findings reflect the widespread and severe inflammatory process caused by tertiary syphilis, emphasizing the critical need for timely diagnosis and treatment,” the authors emphasized.

The findings on imaging were correlated with the blurred vision and photopsia, confirming the posterior uveitis and vasculitis as the primary contributors to visual disturbances. FA imaging of the right eye was used to reveal diffuse hyperfluorescence of the retinal vasculature, indicative of vasculature inflammation due to an infectious etiology.

The results of the clinical examination, lumbar punctures, and serologic testing led to the diagnosis of tertiary syphilis-induced ocular syphilis complicated by retinal detachment, which was treated with penicillin G intravenously daily. The patient was transferred to a long-term acute care facility with an ophthalmologic follow-up after admission.

In these cases, management depends on the HIV status, if the disease is in the latent symptomatic or asymptomatic stage, and if the patient has any penicillin allergies. Specific algorithms have been outlined for the workup and treatment of neurosyphilis based on the management criteria mentioned previously.⁴

This case highlights the importance of recognizing and emphasizing timely diagnosis of ocular syphilis and proper disease management as a crucial factor in preventing permanent vision loss.

The authors emphasized the need for a comprehensive strategy that integrates vigilant diagnostic evaluation and customized symptomatic treatment, to effectively address this uncommon progression of disease.

References:

1. Khan A, DiGiuseppe S, Mustafa M. Tertiary syphilis-induced ocular syphilis complicated by retinal detachment. Cureus. 2025;17:e81240. doi:10.7759/cureus.81240

2. Tudor ME, Al Aboud AM, Leslie SW, Gossman W. Syphilis. StatPearls Publishing, Treasure Island, FL; 2024.

3. Mir TA, Kim SJ, Fang W, Harvey J, Hinkle DM. Rising incidence of syphilitic uveitis-related hospitalizations in the US. JAMA Ophthalmol. 2024, 142:7-14. 10.1001/jamaophthalmol.2023.5386

4. Balba GP, Kumar PN, James AN, et al. Ocular syphilis in HIV-positive patients receiving highly active antiretroviral therapy. Am J Med. 2006, 119:448.e21-5. 10.1016/j.amjmed.2005.11.016