Ocular Syphilis in Patients With Nonreactive Rapid Plasma Reagin and Positive Treponemal Serologies: A Retrospective Observational Cohort Study

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Abstract
Background: Screening for syphilis increasingly relies on positive treponemal rather than nontreponemal tests (rapid plasma reagin [RPR]). We compared ocular syphilis in patients with nonreactive versus positive RPR. Methods: We conducted a retrospective observational cohort study of ocular syphilis treated at 2 New England hospitals during 1996–2021 based on ophthalmologist-diagnosed eye findings and positive treponemal serology, regardless of RPR. We excluded patients with alternative diagnoses. We categorized RPR into nonreactive RPR, low-titer RPR (<1:8), and high-titer RPR (≥1:8) and compared early and long-term response to therapy. Results: Our sample included 115 patients with ocular syphilis (median follow-up, 2.5 years): 25 (22%) with nonreactive RPR, 21 (18%) low-titer RPR, and 69 (60%) high-titer RPR. Compared with nonreactive and low-titer RPR, people with high-titer RPR were younger (mean 47 years, P < .001), more likely to be male (93%, P < .001) and more likely to be diagnosed with human immunodeficiency virus (49%, P < .001). People with nonreactive and low-titer RPR were less likely than those with high-titer RPR to have posterior uveitis/panuveitis (32% and 29% vs 75%, P < .001) or abnormal cerebrospinal fluid (26% and 35% vs 75%, P < .001), and more likely to present with chronic eye findings (20% and 29% vs 1%, P < .001). In long-term follow-up, eye findings improved and did not recur in most patients (62% nonreactive, 68% low-titer, 96% high-titer RPR); improved but recurred in 29%, 11%, and 4%, respectively; and were stable in 10%, 21%, and 0%, respectively. Conclusions: Patients with ocular syphilis and nonreactive RPR are similar to patients with low-titer RPR, and antibiotic therapy is beneficial in most.

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