Published in Retina

The Great Imitator: Retinal Manifestations of Ocular Syphilis

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12 min read

In this episode of Ready, Set, Retina, Daniel Epshtein, OD, FAAO, joins David Almeida, MD, MBA, PhD, to discuss a case report of a patient with ocular syphilis.

In this episode of Ready, Set, Retina, Daniel Epshtein, OD, FAAO, sits down with David Almeida, MD, MBA, PhD, to review a case report of a patient with ocular syphilis that highlights the broad range of variable clinical symptoms that make syphilis “The Great Imitator.”

The current state of syphilis infections in the United States

Syphilis is a sexually transmitted infection (STI) that derives from Treponema pallidum and can affect various systems of the body, resulting in chronic manifestations such as neurosyphilis, ocular syphilis, otosyphilis, and cardiovascular syphilis.1 Of note, the Centers for Disease Control and Prevention (CDC) defines ocular syphilis as neurosyphilis.
According to the CDC, syphilis infections are at a 30-year-high in the United States, with numbers rising tenfold since 2012 and increasing 75% since 2017.2 Further, there are rising rates of co-infection between syphilis and human immunodeficiency virus (HIV) and a “unique synergy” between the two in which syphilis facilitates the transmission and acquisition of HIV, and HIV has been shown to accelerate the natural history of syphilis.3
To make matters worse, there is currently a national shortage of injectable penicillin G.4 Considering this growing public health concern, it is critical that eyecare practitioners keep ocular syphilis in mind when treating patients with nonspecific symptoms to detect syphilis early before it can progress to becoming vision- and potentially even life-threatening in late stages if left untreated.1

Ocular syphilis case report

A 47-year-old male presented to the clinic with a 3-month history of progressively worsening bilateral redness, pain, and photophobia. Other related symptoms at baseline included headaches, unilateral hearing loss, and prominent neck and abdominal lymphadenopathy consistent with a subacute infection of undetermined origin.
Ophthalmic exam findings included:
  • Vision: 20/25 OD and OS, despite reports of significant vision deficits from the patient
  • Anterior Segment: Mild cell and flare OU
  • Posterior Segment:
    • Mild vitritis
    • Posterior subretinal white plaques OU (OD>OS)
    • Optic nerve head (ONH) swelling (OS>OD)
    • Cotton wool spots and vascular sheathing OD

Initial fundus and OCT imaging

Funduscopic examination

Figure 1 is a fundus photograph of the patient’s right eye (OD) at baseline. The disc margin looks a bit blurred in the superior optic nerve, though it is difficult to visualize clearly, and there are prominent white plaques.
Baseline Fundus OD
Figure 1: Courtesy of David RP Almeida, MD, MBA, PhD.
Figure 2 is a fundus photograph of the patient’s left eye (OS) at baseline. Optic nerve edema can be clearly appreciated as all the margins have been lost, and microhemorrhages can be seen. There is also macular plaque and vascular abnormalities, such as prominent retinal arteriovenous (AV) nicking.
Baseline Fundus OS
Figure 2: Courtesy of David RP Almeida, MD, MBA, PhD.

Optical coherence tomography (OCT) imaging

Figures 3 and 4 show OCT imaging OD and OS, respectively, at baseline. The hyaloid is attached in both eyes, and there is no posterior vitreous detachment (PVD). There are flecks in the darkness of the intravitreal space consistent with vitritis.
Baseline OCT OD
Figure 3: Courtesy of David RP Almeida, MD, MBA, PhD.
Baseline OCT OS
Figure 4: Courtesy of David RP Almeida, MD, MBA, PhD.


Dr. Almeida proceeded to obtain a lymph node biopsy; the initial report suggested probable B-cell lymphoma, which led him to believe that the patient likely had intraocular lymphoma. The next steps were to order repeat magnetic resonance imaging (MRI) of the head as well as a lumbar puncture to rule out infections, and topical prednisolone drops to manage the anterior chamber inflammation.
He explained that this is a typical approach he utilizes to comprehensively evaluate patients when the cause of their symptoms is indeterminate so as to avoid prescribing systemic, intravitreal, or intravenous corticosteroids in the case of a possible infection.
Figure 5 is a fundus photograph OD following treatment with topical prednisolone. The clinical picture is relatively unchanged, and the patient’s vision is now 20/25 OD.
Prednisolone Fundus OD
Figure 5: Courtesy of David RP Almeida, MD, MBA, PhD.
Figure 6 is a fundus photograph OS following treatment with topical prednisolone. Of note, the disc edema and plaques remain present, and the patient’s vision has been drastically reduced to 20/400 OS.
Prednisolone Fundus OS
Figure 6: Courtesy of David RP Almeida, MD, MBA, PhD.
Figure 7 is OCT imaging OS after treatment with topical prednisolone, demonstrating obvious worsening of the condition. There are notable changes from the initial presentation, including significant subretinal alterations in the macula. Most of the ellipsoid zone has been lost in the foveal region, consistent with photoreceptor loss in the outer segments. Clearly, the patient’s condition has worsened on this therapy.
Prednisolone OCT OS
Figure 7: Courtesy of David RP Almeida, MD, MBA, PhD.


The lymph node biopsy was performed again and came back as a granulomatous process, possibly due to atypical bacteria. The patient’s internal medicine team decided to query tularemia as a potential cause, so they initiated systemic antibiotics (moxifloxacin and doxycycline) and ordered an urgent consult with an infectious disease specialist.
During the consultation, the doctor performed a thorough history and comprehensive physical exam, which revealed the presence of both penile and oral ulcers. This clinical finding pointed strongly toward Behçet’s disease, so high-dose corticosteroids were prescribed.
This case highlights the importance of collaborative medical care, as ophthalmologists can detect issues that indicate systemic infections or diseases that would have otherwise gone undiagnosed and unaddressed.
Dr. Almeida remarked that you would usually expect corticosteroid treatment to work relatively quickly (though not completely, with residual smoldering) for Behçet’s disease; however, after 3 days of high-dose corticosteroids, there was extensive worsening of the plaque OS (seen below).
Figure 8 is a fundus photograph OD 3 days after beginning treatment with high-dose corticosteroids for suspected Behçet’s disease. There are minimal changes from the previous funduscopic exam.
Corticosteroid Fundus OD
Figure 8: Courtesy of David RP Almeida, MD, MBA, PhD.
Figure 9 is a fundus photograph OS 3 days after starting corticosteroid therapy. As we can see, there is now extensive worsening of the subretinal plaque OS.
Corticosteroid Fundus OS
Figure 9: Courtesy of David RP Almeida, MD, MBA, PhD.
At this point, it was suspected that the patient might be experiencing a Jarisch-Herxheimer reaction (i.e., a sudden, transient reaction that may occur within 24 hours of being administered antibiotics for a spirochete-associated infection). To combat this, the patient was prescribed oral prednisone 60mg/day, with the goal of suppressing the inflammatory response.
Six days later, the CDC reported that the patient had tested positive for syphilis infection, allowing the team to finally reconcile all of the ocular and systemic findings.

Syphilis treatment

The patient was then prescribed a full course of intravenous (IV) penicillin G to address the syphilis infection.
Figure 10 is a fundus image OD shortly after beginning penicillin therapy. His vision in this eye remained stable at 20/25.
Post-antibiotic Fundus OD
Figure 10: Courtesy of David RP Almeida, MD, MBA, PhD.
Figure 11 is a fundus photograph OS, shortly after beginning penicillin therapy. In addition to the obvious clinical resolution, the vision in this eye quickly improved to 20/80. This rapid return of vision following the initiation of appropriate antibiotic therapy is typical for earlier stages of syphilis.5
Post-antibiotic Fundus OS
Figure 11: Courtesy of David RP Almeida, MD, MBA, PhD.
Figure 12 is a fundus photograph OD later in the course of the penicillin treatment. There is no remaining plaque visible, and the patient’s vision improved to 20/20 OD.
Post-antibiotic 2 Fundus OD
Figure 12: Courtesy of David RP Almeida, MD, MBA, PhD.
Figure 13 is a fundus photograph OS later in the course of the penicillin treatment. The patient’s vision had improved to 20/30 OS (from a documented 20/400)—demonstrating a near-complete recovery of vision.
Post-antibiotic 2 Fundus OS
Figure 13: Courtesy of David RP Almeida, MD, MBA, PhD.
Figure 14 is OCT imaging OS following the treatment course of penicillin for syphilis. It clearly shows the resolution of the subretinal changes noted in the earlier OCT. While the foveal region is greatly improved, we can still see evidence of slight irregularity at the level of the ellipsoid zone.
Post-antibiotic 2 OCT OS
Figure 14: Courtesy of David RP Almeida, MD, MBA, PhD.
Dr. Almeida noted that based on his clinical experience, syphilis patients’ vision tends to return when the ellipsoid zone returns. He added that in patients with advanced secondary, tertiary, or untreated syphilis, even when they are treated appropriately, the ellipsoid zone is not guaranteed to return. This can result in permanent vision loss, some cases of which may be profound.

Co-managing ocular syphilis

Dr. Epshtein reiterated the value of collaborative care, as patients may not feel comfortable sharing information about their genitourinary and reproductive health with an eye doctor. He highlighted the importance of looking at not just the retina and choroid on OCT but also the vitreous because you can see signs of disease that can’t always be appreciated with imaging.
He remarked that this case report was a great example of seeing how initial nonspecific test results and symptoms can lead doctors to different treatment approaches. In this case, ocular syphilis evaded diagnosis due to the B-cell reaction, tularemia test result, and the worsening plaque after high-dose corticosteroids.

Patient compliance with syphilis treatment

When co-managing a patient with syphilis, Dr. Almeida explained that having a clearly defined chain of communication is critical so that information can be easily shared between doctors. He mentioned observing changes in patient compliance with syphilis treatments, as initially, patients were admitted to a hospital to begin IV penicillin—which uses hospital resources but ensures patient compliance.
However, now he sees more patients who are not admitted to a hospital, receive treatment at an outpatient infusion center, and then are eventually transitioned to oral penicillin.
With this setup, there have been slightly more issues with patient compliance as he has lost a couple of patients to follow-up—which is a significant issue with an infection like syphilis where contact tracing is necessary. As a potential alternative, Dr. Epshtein noted that he has also seen patients ask for visiting nurses who provide the infusions at home.


This case report is a great reminder of the broad variety of symptoms that can accompany syphilis, aka “The Great Imitator,” and how collaborative care can accelerate the detection of tricky diagnoses.
Considering the many barriers that patients with syphilis can face when seeking healthcare, it is crucial that eyecare practitioners keep the characteristics of ocular syphilis in mind to facilitate early detection before the infection can progress to being vision- or even life-threatening.
  1. Wu Y, Zhu W, Sun C, et al. Prevalence of Syphilis Among People Living With HIV and Its Implication for Enhanced Coinfection Monitoring and Management in China: A Meta-Analysis. Front Public Health. 2022;10:1002342. doi:10.3389/fpubh.2022.1002342
  2. Delaney-Gesing A. CDC Reports Rare Cluster of Ocular Syphilis in the US. Glance by Eyes On Eyecare. Published November 29, 2023.
  3. Ren M, Dashwood T, Walmsley S. The Intersection of HIV and Syphilis: Update on the Key Considerations in Testing and Management. Curr HIV/AIDS Rep. 2021;18(4):280-288. doi:10.1007/s11904-021-00564-z
  4. Mir TA, Kim SJ, Fang W. Rising Incidence of Syphilitic Uveitis-Related Hospitalizations in the US. JAMA Ophthalmol. 2024;142(1):7-14. doi:10.1001/jamaophthalmol.2023.5386
  5. Bollemeijer JG, Wieringa WG, Missotten TOAR, et al. Clinical Manifestations and Outcome of Syphilitic Uveitis. Invest Ophthalmol Vis Sci. 2016;57(2):404-411. doi:10.1167/iovs.15-17906
Daniel Epshtein, OD, FAAO
About Daniel Epshtein, OD, FAAO

Dr. Daniel Epshtein is an assistant professor in the ophthalmology department of Mount Sinai Morningside in New York City. Previously, he held a position in a high-volume multispecialty ophthalmology practice where he supervised fourth-year optometry students as an adjunct assistant clinical professor of the SUNY College of Optometry. Dr. Epshtein’s research focuses on using the latest ophthalmic imaging technologies to elucidate ocular disease processes and to simplify equivocal clinical diagnoses. He developed and lectures in the perioperative care course at the SUNY College of Optometry. Dr. Epshtein writes and lectures on numerous topics including glaucoma, retinal disease, multimodal imaging, ocular surface disease, and perioperative care.

Daniel Epshtein, OD, FAAO
David RP Almeida, MD, MBA, PhD
About David RP Almeida, MD, MBA, PhD

David Almeida MD MBA PhD is a vitreoretinal eye surgeon offering a unique voice that combines a passion for ophthalmology, vision for business innovation, and expertise in ophthalmic and biomedical research. He is part of Erie Retinal Surgery, a retina-only private practice with an esteemed reputation for excellence in Pennsylvania. Dr. Almeida and Erie Retinal Surgery diagnose and treat all medical and surgical conditions of the vitreous, retina and macula.

David RP Almeida, MD, MBA, PhD
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