All patients diagnosed with syphilis that exhibit ocular manifestations should immediately be treated for neurosyphilis and be referred for formal ophthalmologic examination. Education of both patients and providers is critical to identify ocular manifestations of syphilis and manage disease sequelae.

Eight jurisdictions that reviewed syphilis surveillance and case investigation data from 2014, 2015, or both found that in 0.6% of syphilis cases, the patient had symptoms consistent with ocular syphilis. Most suspected cases were in males, and half were in HIV-positive persons. Severe outcomes, including blindness, occurred in both HIV-positive and HIV-negative patients.

Ocular syphilis, an infrequent manifestation of syphilis infection, can cause a variety of eye symptoms, including vision loss. Clusters of ocular syphilis were reported from late 2014 to 2015. In the United States, syphilis rates have increased since 2000, but little is known about ocular syphilis cases.

Ocular syphilis, a manifestation of Treponema pallidum infection, can cause a variety of ocular signs and symptoms, including eye redness, blurry vision, and vision loss. Although syphilis is nationally notifiable, ocular manifestations are not reportable to CDC. Syphilis rates have increased in the United States since 2000. After ocular syphilis clusters were reported in early 2015, CDC issued a clinical advisory (1) in April 2015 and published a description of the cases in October 2015 (2). Because of concerns about an increase in ocular syphilis, eight jurisdictions (California, excluding Los Angeles and San Francisco, Florida, Indiana, Maryland, New York City, North Carolina, Texas, and Washington) reviewed syphilis surveillance and case investigation data from 2014, 2015, or both to ascertain syphilis cases with ocular manifestations. A total of 388 suspected ocular syphilis cases were identified, 157 in 2014 and 231 in 2015. Overall, among total syphilis surveillance cases in the jurisdictions evaluated, 0.53% in 2014 and 0.65% in 2015 indicated ocular symptoms. Five jurisdictions described an increase in suspected ocular syphilis cases in 2014 and 2015. The predominance of cases in men (93%), proportion of those who are men who have sex with men (MSM), and percentage who are HIV-positive (51%) are consistent with the epidemiology of syphilis in the United States. It is important for clinicians to be aware of potential visual complications related to syphilis infections. Prompt identification of potential ocular syphilis, ophthalmologic evaluation, and appropriate treatment are critical to prevent or manage visual symptoms and sequelae of ocular syphilis.

In early 2015, clusters of ocular syphilis cases were reported in Washington and California. CDC issued a clinical advisory, notifying clinical providers and health departments of a potential increase in suspected ocular syphilis cases. After this advisory, eight jurisdictions performed a review of syphilis surveillance and case investigation data to identify syphilis cases with ocular manifestations. Seven jurisdictions reviewed data from January 1, 2014 to December 31, 2015; Indiana reviewed data from 2015 only. A patient whose illness met the surveillance case definition of syphilis (3) was considered to have a suspected case of ocular syphilis if the patient had concurrent ocular signs or symptoms noted in the surveillance database from a local syphilis case investigation or reported by a local health care provider. A standard form was used to abstract de-identified information on each case, including demographic information, syphilis stage and treatment, and any information on extent of ocular involvement. Each jurisdiction also provided a total number of syphilis surveillance cases, including numbers from all stages of syphilis, as defined by the surveillance case definitions (3).

A total of 388 suspected ocular syphilis cases were identified, 157 cases in 2014 and 231 cases in 2015 (Table 1). Overall, 0.60% of total syphilis cases were identified as suspected ocular syphilis cases, 0.53% in 2014 and 0.65% in 2015. The percentage of total syphilis cases with ocular manifestation varied by jurisdiction, ranging from 0.17% to 3.9%. Five jurisdictions described an increase in suspected ocular syphilis cases in 2014 and 2015.

Most patients with suspected ocular syphilis were male (93%), and 249 (69%) of those with information on sex partners were MSM (Table 2). The mean age of patients was 44 years (range = 17–79 years). Approximately one half of the cases met surveillance criteria for early syphilis (primary, secondary, and early latent syphilis) (Table 3); stage of syphilis was not associated with any specific symptom, diagnosis, or extent of eye involvement. Overall, patients with suspected ocular syphilis had high rapid plasma reagin (RPR) titers, with a median titer of 128 (range = 1–16,384). Approximately 22% of patients reported additional symptoms of neurosyphilis, including headache, neck pain, altered mental status, or changes in hearing.

Specific symptoms were reported by 326 (84%) persons suspected of having ocular syphilis; 54% of patients reported blurry vision, and 28% of patients reported at least some vision loss. Specific ocular diagnoses were available for 158 (41%) patients, and uveitis (n = 72) was the most common diagnosis. More serious diagnoses were also recorded, including retinitis (n = 20), optic neuritis (n = 18), and retinal detachment (n = 6). Of 136 (35%) patients with available information on which eye was affected, one eye was involved in 64 (47%) patients, and both eyes were affected in 72 (53%) patients.

Among 174 patients with cerebrospinal fluid (CSF) test results, 122 (70%) had a reactive CSF Venereal Disease Research Laboratory (VDRL) test. Patients with a reactive CSF VDRL test were not more likely than patients with a nonreactive CSF VDRL to report additional neurologic symptoms, have vision loss or bilateral eye involvement, or be diagnosed with severe disease, including retinitis, optic neuritis, or retinal detachment.

Recommended treatment for neurosyphilis and ocular syphilis is 18–24 million units intravenous (IV) aqueous penicillin G, administered daily as a continuous infusion, or divided into every 4-hour dosing, for 10–14 days (4). Approximately 60% of patients with suspected ocular syphilis received IV penicillin, and the other 38% received varied treatments, most commonly benzathine penicillin given as an intramuscular injection (Table 3).

One half of patients with suspected ocular syphilis were HIV-positive (n = 198). Of those persons, 62 (32%) were first diagnosed with HIV at the time of their ocular syphilis diagnosis. Compared with HIV-negative patients, HIV-positive patients had a higher median RPR titer (256 versus 128, p<0.001), more often received a lumbar puncture (57.1% versus 40.8%, p = 0.005), and were more often treated with IV penicillin (66.7% versus 44.2%, p<0.001). Patients with HIV infection did not differ significantly from HIV-negative patients in proportion having a reactive CSF VDRL, both eyes involved, additional symptoms of neurosyphilis, or an ophthalmologic exam. CD4 count was available for 126 patients; 84 (67%) had a CD4 count <500 cells/μL. Compared with patients with higher CD4 counts, those with a CD4 count <500 cells/μL more often received a lumbar puncture (65.5% versus 45.2%, p = 0.03), had a reactive CSF VDRL (84.0% versus 50.0%, p = 0.006), and had both eyes involved (35.7% versus 7.1%, p = 0.003), but did not differ in proportion with blurry vision or vision loss.