Retina Society 2026: Ocular syphilis, HIV co-infection, and RPR titers

Ocular syphilis may be a condition that retina specialists do not necessarily see every day—but leveraging a federated database like TriNetX allows for a more holistic picture of how it presents across the country. That was the approach taken by Mark P. Breazzano, MD, FACS, associate professor and vitreoretinal fellowship director at the Flaum Eye Institute at the University of Rochester in Rochester, New York, who presented findings from a multicenter database study examining the relationship between ocular syphilis and HIV co-infection at the 59th Annual Scientific Meeting of The Retina Society, September 23-26, 2026, in Los Angeles, California.

Breazzano explained that the impetus for the study came from a case he encountered while at Wilmer Eye Institute at Johns Hopkins University School of Medicine in Baltimore, Maryland, in which ocular syphilis was not immediately apparent in a patient with HIV positivity. In that case, published in JAMA, the serology was actually negative—and the diagnosis was only confirmed days later when a skin biopsy revealed spirochetes on histology. The reason, he explained, was that the HIV had progressed to AIDS to a degree where the immune response was insufficient to produce a detectable RPR—or rapid plasma reagin—result, the indirect test commonly used to diagnose syphilis.

A large real-world dataset

To examine this relationship more broadly, Breazzano and colleagues leveraged the TriNetX federated multicenter database to identify patients with ocular syphilis across the country. The initial cohort included approximately 3,000 patients with syphilis. After applying checks to confirm laboratory confirmation and the availability of RPR testing for further analysis, the working cohort narrowed to approximately 130 to 140 patients—still a meaningful number to work with, he noted.

Using multivariable logistic regression and controlling for region, sex, race, and ethnicity, HIV emerged as the primary predictor of RPR titer levels. On average, RPR titers were about 400 units greater in HIV-positive patients compared with their HIV-negative counterparts—though Breazzano noted that the standard deviation was high, reflecting significant variability across the cohort. He described this finding as most likely reflecting a combination of reduced treatment response and increased disease severity, though the database’s level of clinical detail made it difficult to definitively distinguish between the two.

He acknowledged that one of the key limitations of large federated databases is the loss of more nuanced clinical data, noting that the question of whether RPR titer levels correlate with the severity or extent of ocular involvement remains unanswered. “Hopefully, as these databases grow in popularity and clinical data gets more robust, we can answer that more carefully,” he said.

Clinical takeaways

Breazzano offered 2 key practical messages for retina specialists. First, HIV status should always be considered and tested for in patients presenting with ocular syphilis—a recommendation aligned with CDC guidance that all patients with ocular syphilis, regardless of known HIV status or prior negative testing, should undergo HIV testing. Second, while elevated RPR titers are more commonly seen in HIV-positive patients, clinicians should remain alert to the possibility of a falsely negative serologic response in patients with advanced immunosuppression, as the absence of an immune response does not rule out active syphilitic infection. “It can still be syphilis,” he said.

He noted that while infectious disease specialists or primary care physicians typically manage the systemic aspects of treatment, ocular manifestations can affect any layer of the eye—and often show up in the retina as well as in the general comprehensive ophthalmologist’s clinic—making recognition and coordinated care important.