Ocular syphilis: Clinical characteristics,HIV status,and outcomes in a 10-year case series from Türkiye

Abstract

Background

Ocular syphilis is a rare but potentially sight-threatening manifestation of Treponema pallidum. Despite increased awareness related to the global resurgence of syphilis and its association with HIV, data from Türkiye remain limited.

Methods

This case series included patients diagnosed with ocular syphilis at two tertiary centers in Türkiye. We evaluated their clinical, ophthalmologic, serologic, CSF, HIV-related data, treatment, and visual outcomes.

Results

Twenty-four patients (43 affected eyes) were included; 92% were male, with a median age of 46 years (IQR, 31.0–52.8). Ocular involvement was the initial clinical manifestation of syphilis in 92% of patients, and 54% had no systemic symptoms at presentation. Bilateral disease was observed in 19 patients (79%). Among the 43 affected eyes, posterior uveitis and panuveitis were the most common anatomical patterns, each observed in 15 eyes (35%). Fifty-eight percent of patients were people living with HIV (PLWH), half of whom were newly diagnosed at presentation. PLWH were significantly younger than those without HIV (median 37.0 vs 52.0 years; p = 0.012) and were more frequently men who have sex with men (64% vs 0%; p = 0.002). Lumbar puncture revealed at least one cerebrospinal fluid (CSF) abnormality in 71% of individuals; elevated CSF protein levels were more common among PLWH (85% vs 25%; p = 0.017). All individuals received neurosyphilis-equivalent therapy, resulting in significant improvement in visual acuity (median ΔlogMAR −0.56; p < 0.001).

Conclusions

Ocular syphilis frequently presents without systemic symptoms and is often associated with HIV. In patients presenting with posterior uveitis or panuveitis, routine syphilis and HIV testing is essential for accurate diagnosis and timely management.

Keywords

ocular syphilis syphilis uveitis HIV infection co-infection

Introduction

Syphilis, caused by Treponema pallidum, remains a major global public health concern, with a markedly increasing incidence over the past two decades. According to the World Health Organization (WHO), an estimated 7.1 million new syphilis cases occurred among adults aged 15–49 years worldwide in 2020, rising to approximately 8 million in 2022.¹ In Europe, reported cases increased by 34% in 2022 compared with 2021 and by 41% compared with 2018.² In Türkiye, Ministry of Health data demonstrate a steady rise in confirmed syphilis cases since 2017, reaching 3646 cases in 2023 following a transient decline during the COVID-19 pandemic.³

Ocular syphilis is an uncommon clinical manifestation, occurring in only 0.6–2.6% of all syphilis cases, yet it can lead to severe and irreversible vision loss if left untreated.^4–6 Known as the “great imitator,” it may present with a broad spectrum of ocular findings, including anterior or posterior uveitis, panuveitis, chorioretinitis, retinal vasculitis, and optic neuropathy.⁷ Ocular involvement can occur at any stage of the infection and may constitute the first or only clinical manifestation in the absence of systemic symptoms.⁸

Co-infection with human immunodeficiency virus (HIV) has emerged as an important modifier of the clinical course of ocular syphilis. People living with HIV (PLWH) more frequently exhibit posterior segment involvement, bilateral presentation, and atypical clinical features. Delayed diagnosis and altered immune responses may contribute to poorer visual outcomes in PLWH compared with individuals without HIV.^9–12

Given the global resurgence of syphilis and the vision-threatening nature of ocular involvement, early recognition and timely management are essential. However, data on ocular syphilis in Türkiye remain limited. The aim of this study was to describe the clinical characteristics, cerebrospinal fluid findings, HIV status, treatment approaches, and visual outcomes of patients diagnosed with ocular syphilis at two tertiary centers in Türkiye.

Materials and methods

Study design and participants

This case series included patients diagnosed with ocular syphilis between January 1, 2015, and November 25, 2025, at Sisli Hamidiye Etfal Training and Research Hospital and, after May 2020, Basaksehir Cam and Sakura City Hospital. For each patient, demographic characteristics, clinical findings, laboratory results, treatment protocols, and follow-up outcomes were recorded.

Diagnostic criteria and classification

Ocular syphilis was defined as the presence of ocular findings in conjunction with positive syphilis serology, in the absence of any alternative cause of ocular involvement.¹³ Positive syphilis serology required at least one reactive treponemal test (TPHA or FTA-ABS), regardless of nontreponemal test (VDRL or RPR) reactivity. According to the 2018 CDC case definition, only patients with both reactive treponemal and nontreponemal tests can be classified within surveillance categories; therefore, patients with nonreactive nontreponemal tests were categorized as clinically compatible ocular syphilis.¹³

All patients underwent routine HIV screening. HIV status was determined based on documented test results at the time of syphilis diagnosis or medical record review. For PLWH, the date of HIV diagnosis, CD4 cell count, and viral load measurements obtained within 6 months before syphilis diagnosis, or the closest available results, were recorded. HIV coinfection was classified as previously diagnosed when HIV was identified more than 30 days before syphilis diagnosis, and as concurrently diagnosed when identified within 30 days.

Cerebrospinal fluid (CSF) analysis was performed by lumbar puncture in patients with neurological symptoms and in selected cases when clinically indicated. Pleocytosis was defined as ≥20 cells/µL in PLWH and ≥5 cells/mL in individuals without HIV.^14,15 CSF protein levels >45 mg/dL were considered elevated.

Ophthalmologic evaluation

A comprehensive ophthalmologic examination was performed in all patients. Depending on the anatomical site of involvement, patients were evaluated by uvea or cornea specialists, and some cases additionally underwent assessment by a neuro-ophthalmologist. The ophthalmologic evaluation included best-corrected visual acuity (BCVA), intraocular pressure, anterior chamber and vitreous inflammation, and funduscopic findings.

Ocular involvement was classified according to the anatomical distribution based on the Standardization of Uveitis Nomenclature (SUN) guidelines as anterior uveitis, intermediate uveitis, posterior uveitis, panuveitis, or optic neuropathy.¹⁶ BCVA was measured using the Snellen chart at presentation and after treatment. Snellen values were converted to logMAR units for statistical analysis. “Counting fingers,” “hand motion,” and “light perception” vision were assigned logMAR values of 1.6, 2.0, and 2.5, respectively.

Statistical analysis

Statistical analyses were performed using SPSS version 15.0. Continuous variables were summarized as median (IQR or range), and categorical variables as counts and percentages. Group comparisons were conducted using Student’s t-test or the Mann–Whitney U test, as appropriate, while categorical variables were compared using the Chi-square or Fisher’s exact test. VDRL titers were analyzed as numerical values corresponding to the highest reactive dilution. A p-value <0.05 was considered statistically significant.

Results

Baseline demographic and clinical characteristics

A total of 24 patients (43 affected eyes) were evaluated during the study period. Most patients were male (n = 22, 92%), and the median age was 46 years (IQR, 31.0–52.8; range, 22–71). All patients were of Turkish origin. Nineteen cases were managed at Sisli Hamidiye Etfal Training and Research Hospital, and five at Basaksehir Cam and Sakura City Hospital. Baseline systemic and epidemiologic characteristics of the cohort are presented in Table 1.

Table 1.

Systemic and epidemiologic characteristics of patients with ocular syphilis (n = 24).

Characteristic	n (%)
Sexual orientation
Men who have sex with men	9 (38%)
Heterosexual	8 (33%)
Unknown	7 (29%)
Intravenous drug use	2 (8%)
Systemic manifestations at presentation
Macular rash	7 (29%)
Headache	9 (38%)
Mucocutaneous lesions	3 (13%)
No systemic symptoms	13 (54%)
Early syphilis stage	9 (38%)
Living with HIV	14 (58%)
Comorbid conditions
Diabetes mellitus	3 (13%)
Hypertension	2 (8%)
Chronic kidney disease	2 (8%)
Other immunosuppressive conditions^a	2 (8%)
Immunocompetent	7 (29%)

^aTemporal arteritis (n = 1) and psoriasis with prior methotrexate use (n = 1).

Ophthalmologic symptoms and clinical findings

The median duration from onset of ocular symptoms to diagnosis was 17.5 days (IQR, 7–33.8; range, 2–180 days). Blurred vision was reported by 58% of patients and constituted the leading ocular complaint, followed by visual field defects (42%) and ocular pain or stinging sensations (13%). Ocular involvement served as the initial clinical manifestation of syphilis in 22 patients (92%), whereas only two patients had a previously documented diagnosis of syphilis.

Bilateral involvement occurred in 19 patients (79%). Posterior uveitis and panuveitis were the most prominent patterns, each diagnosed in 15 of 43 affected eyes (35%). Optic neuropathy accompanying uveitis was observed in seven patients (Table 2). At presentation, the affected eyes had a median logMAR visual acuity of 0.76 (IQR, 0.15–1.60).

Table 2.

Characteristics of uveitic involvement (Patients, n = 24; affected eyes, n = 43).

Variable	Findings
Laterality
Unilateral involvement	5 patients (21%)
Right eye	2 (8%)
Left eye	3 (13%)
Bilateral involvement	19 patients (79%)
Baseline visual acuity (logMAR), median (IQR)	0.76 (0.15–1.60)
Anatomical classification of uveitis
Anterior uveitis (isolated)	3 eyes (7%)
Anterior and intermediate uveitis	6 eyes (14%)
Isolated intermediate uveitis	4 eyes (9%)
Posterior uveitis	15 eyes (35%)
Panuveitis	15 eyes (35%)
Optic neuropathy	7 eyes (16%)

Ocular complications during follow-up included retinal detachment (n = 6), macular edema (n = 3), and endophthalmitis, posterior synechiae, and retinal atrophy (each n = 2), as well as chronic vitreous changes (n = 1).

Serologic and cerebrospinal fluid findings

All patients tested positive on treponemal assays (TPHA). Serum non-treponemal testing was reactive in 20 of 24 individuals (83%). Lumbar puncture (LP) was performed in 21 patients (88%). Among these, at least one abnormal CSF finding—positive CSF-VDRL, pleocytosis, or elevated protein—was identified in 17 patients (81%). Pleocytosis was observed in 7 patients (33%), and elevated CSF protein (>45 mg/dL) was present in 14 patients (67%). Among the 21 patients who underwent lumbar puncture, CSF-VDRL was negative in 19 (91%) and positive in 2 (10%). CSF FTA-ABS positivity was observed in 11 patients (52%) and was more frequent among PLWH than among individuals without HIV (69% vs 25%); however, this difference was not statistically significant.

Clinical and laboratory characteristics according to HIV Status

Fourteen patients (58%) in the cohort were living with HIV. Of these, seven individuals (50%) were newly diagnosed with HIV at the time of ocular syphilis presentation. Five individuals (36%) were receiving antiretroviral therapy at admission, whereas two patients (14%) had voluntarily discontinued ART and were lost to follow-up.

Among PLWH, the median CD4 T-lymphocyte count was 331 cells/mm³ (IQR, 198–451; range, 4–866), and the median HIV RNA level was 38,928 copies/mL (IQR, 675–222,750; range, 0–384,000).

Individuals living with HIV were significantly younger than those without HIV (median 37.0 vs 52.0 years; p = 0.012) and were more frequently men who have sex with men (64% vs 0%; p = 0.002). In contrast, bilateral ocular involvement, duration of ocular symptoms at presentation, and serum non-treponemal test titers were comparable between groups and did not differ significantly according to HIV status (Table 3).

Table 3.

Demographic and clinical characteristics of all patients and according to HIV status.

Variable/Characteristic	Overall (n = 24)	People without HIV (n = 10)	People living with HIV (n = 14)	p-value
Demographics
Age at diagnosis, median [IQR], years	45.5 (31.0–52.8)	52.0 (42.25–59.25)	37.0 (27.75–48.75)	0.012
Gender (male), n (%)	22 (91%)	8 (80%)	14 (100%)	—
Sexual orientation, n (%)				0.002
MSM	9 (38%)	0 (0%)	9 (64%)
Heterosexual	8 (33%)	4 (40%)	4 (29%)
Unknown	7 (29%)	6 (60%)	1 (7%)
Disease features
Bilateral involvement, n (%)	19 (79%)	7 (70%)	12 (86%)	0.614
Duration of ocular symptoms at diagnosis, median [IQR], days	17 (7–33)	14 (11–27)	25 (5–41)	0.883
Serum non-treponemal test titer, median (range)	32 (0–512)	20 (0–256)	48 (0–512)	0.423
CSF findings & lumbar puncture
Lumbar puncture performed, n (%)	21 (88%)	8 (80%)	13 (93%)	0.55
CSF Abnormality (≥1 finding), n (%)^a	15 (71%)	4 (40%)	11 (85%)	0.146
CSF-VDRL positivity, n (%)	2 (10%)	2 (25%)	0 (0%)	—
CSF FTA-ABS positivity, n (%)	11 (52%)	2 (25%)	9 (69%)	0.08
Protein elevation, n (%)	13 (62%)	2 (25%)	11 (85%)	0.017
Pleocytosis, n (%)	6 (29%)	2 (25%)	4 (31%)	1.000
Treatment
Corticosteroid treatment, n (%)	8 (33%)	2 (20%)	6 (43%)	0.3875
Visual acuity (BCVA, logMAR)
Presenting	0.76 (0.15–1.60)	0.82 (0.45–1.80)	1.0 (0.15 – 1.6)	0.52
Final	0.15 (0.00–0.40)	0.15 (0.10–0.40)	0.30 (0.045 – 0.605)	0.24
Improvement (Δ logMAR)	−0.56 (−1.26 to −0.15)	−0.60 (−1.70 to −0.07)	−0.48 (−1.21 to −0.15)	0.71

Abbreviations: MSM, men who have sex with men; CSF, cerebrospinal fluid; LP, lumbar puncture; BCVA, best-corrected visual acuity; HIV, human immunodeficiency virus.

Pleocytosis thresholds: ≥20 cells/mL for PLWH and ≥5 cells/mL for individuals without HIV, in line with CDC neurosyphilis criteria.*p-values were calculated using the Mann–Whitney U test for continuous variables and Fisher’s exact test for categorical variables. —p-value not calculated due to small subgroup sizes. Bold values indicate statistically significant results (p < 0.05).

^aDefined as presence of pleocytosis and/or elevated protein.

Lumbar puncture was performed in most individuals in both groups. CSF abnormalities were more frequently observed among PLWH, primarily driven by a significantly higher rate of CSF protein elevation. Rates of pleocytosis and CSF serologic test positivity were comparable between groups, while CSF-VDRL positivity was observed only among individuals without HIV (Table 3).

The distribution of anatomical patterns of ocular involvement did not differ according to HIV status. Similarly, presenting, final, and Δ logMAR best-corrected visual acuity outcomes were comparable between individuals with and without HIV (Table 3).

Treatment and outcomes

A total of 22 patients (92%) were treated with intravenous crystalline penicillin G (18–24 million units/day). Two patients (8%) with a documented penicillin allergy received intravenous ceftriaxone (2 g/day) as an alternative regimen. In four patients (13%), oral doxycycline (200 mg/day) was administered following intravenous penicillin therapy and continued during the systemic corticosteroid course. Oral corticosteroids were added for anti-inflammatory purposes in eight patients (33%), particularly in the presence of significant vitritis or macular/optic disc edema.

Among 23 patients with available treatment duration data, 19 (83%) received antibiotics for 14 days. Two patients (9%) were treated for 28 days, and two patients (9%) for 35 days. The median duration of antibiotic therapy was 14 days (range, 14–3 days).

Post-treatment serologic follow-up was available at month 3 in 17 patients (71%), at month 6 in 15 patients (63%), and at month 12 in 11 patients (46%). A fourfold decline in VDRL titers was observed in 88% at month 3, and a sixteenfold decline in 47% at month 6. By the end of the first year, 91% (n = 10) of the 11 evaluated patients achieved VDRL seroreversion. Overall, visual acuity significantly improved after treatment (median ΔlogMAR = −0.56 (IQR –1.26 to −0.15); p < 0.001).

Discussion

This multicenter case series highlights that ocular syphilis most commonly presents as an isolated ocular manifestation, frequently in the absence of systemic symptoms, and is characterized by a predominance of posterior and bilateral involvement. Rather than representing a late complication of systemic disease, our findings suggest that ocular syphilis may constitute an early and sometimes the sole clinical manifestation of syphilis, thereby posing a significant diagnostic challenge in routine clinical practice. In this context, ocular inflammation may provide an important opportunity to diagnose both syphilis and previously undiagnosed HIV, underscoring the need for heightened clinical awareness and a multidisciplinary approach.

The ocular phenotype observed in our study was predominantly characterized by posterior segment involvement, with most cases presenting as posterior uveitis or panuveitis, and approximately three-quarters showing bilateral disease. This distribution aligns with findings from large-scale studies and systematic reviews across different geographic regions, where posterior segment involvement is reported as the most common clinical presentation of ocular syphilis in the current era.^8,11,17 Although systemic manifestations such as rash, headache, or mucocutaneous lesions were present in some patients, more than half of the cohort lacked systemic symptoms. This complicates the diagnostic process and may delay the consideration of syphilis in patients presenting with posterior segment inflammation, potentially resulting in diagnostic delays of several weeks or even months. This challenge is further compounded by the absence of pathognomonic ocular findings and the broad spectrum of posterior segment manifestations, making ocular syphilis a well-recognized masquerader in uveitis practice. Our findings underscore the importance of including syphilis early in the differential diagnosis of unexplained posterior uveitis or panuveitis, even in the absence of systemic signs.

A substantial proportion of patients in our cohort were living with HIV, and notably, half received their HIV diagnosis at the time of presentation with ocular syphilis. This finding reflects the well-recognized epidemiologic association between syphilis and HIV, particularly among MSM populations. The younger age and higher proportion of MSM among PLWH likely represent shared transmission dynamics rather than differences in ocular disease characteristics. These observations support the importance of routine HIV testing in patients diagnosed with syphilis, in accordance with current international guidelines.^18,19

Immunological parameters offer additional context in evaluating disease expression. CD4 + T lymphocyte count and HIV RNA level are recognized as key immunological parameters that may influence the development and clinical presentation of ocular syphilis. In our study, PLWH had a median CD4 + T-cell count of 331 cells/mm³ and a median HIV RNA level of 38,928 copies/mL, reflecting heterogeneous immune status within the cohort. These values were higher than those reported in previous ocular syphilis series.^20,21

Although previous studies suggest that low CD4 + T-cell counts and uncontrolled HIV viral load may be associated with more severe ocular involvement,^22,23 our findings did not reveal significant differences in the patterns of ocular involvement, disease severity, or visual outcomes between patients with and without HIV co-infection. This is consistent with evidence indicating that, when appropriate therapy is initiated in a timely manner, HIV status does not appear to be an independent predictor of poor visual prognosis. A large systematic review similarly concluded that HIV status, CD4 + T-cell count, and HIV RNA level do not significantly predict visual acuity outcomes in treated ocular syphilis.²⁴ Our findings suggest that, in ocular syphilis, delayed diagnosis and treatment may be key determinants of visual outcomes, with HIV status likely representing a facilitating rather than a primary factor in the disease course.

Approaches to LP indications in ocular syphilis vary across the literature and international guidelines. The Centers for Disease Control and Prevention (CDC) recommends lumbar puncture primarily in individuals with neurologic, ocular, or otic symptoms, and also considers it in cases of treatment failure or in PLWH with a serum RPR titer ≥1:32 and/or a CD4 + T-cell count ≤350 cells/mm³.¹⁹ However, several recent studies have highlighted the diagnostic value of performing lumbar puncture not only in symptomatic cases but also more broadly, particularly in PLWH, due to the increased risk of asymptomatic neurosyphilis.^25,26

In our study, LP was performed at a notably high rate (88%), reflecting a high level of clinical awareness regarding potential central nervous system involvement. CSF analysis revealed abnormalities in 85% of PLWH compared with 40% in those without HIV. The most striking difference was observed in CSF protein elevation, which was significantly more common among PLWH (85% vs 25%; p = 0.017), suggesting enhanced neuroinflammatory activity possibly related to HIV-associated immune dysregulation.

The limited sensitivity of CSF-VDRL testing, widely reported in previous studies,²⁷ was also evident in our cohort, with only two positive results (10%)—both occurring in individuals without HIV. In contrast, CSF FTA-ABS positivity was higher among PLWH (69% vs 25%), showing a near-significant difference (p = 0.08). Pleocytosis rates were similar between groups, suggesting that cellular responses may not vary significantly by HIV status.

These findings support a broader role for LP in the diagnostic workup of ocular syphilis, particularly in high-risk groups such as PLWH. CSF protein elevation and serologic findings, even in the absence of overt neurological symptoms, may offer critical clues for detecting subclinical neurosyphilis and guiding timely therapeutic intervention.

Although visual outcomes were favorable following timely intravenous penicillin-based therapy, ocular syphilis remains a condition with potential for relapse or delayed complications, particularly in immunocompromised individuals. This highlights the importance of structured post-treatment follow-up, including clinical ophthalmologic assessment and serologic monitoring. Similarly, a recent case series from Türkiye emphasized that prompt diagnosis and appropriate antimicrobial therapy are critical in preventing severe ocular complications, underscoring the need for close post-treatment surveillance.²⁸ In PLWH, long-term surveillance may be especially relevant to detect late recurrences or progression to neurologic involvement, even after apparent initial recovery.

This study has several limitations. Its retrospective design may have led to incomplete or non-standardized data collection, introducing potential information bias. The small sample size limits statistical power, particularly in subgroup analyses according to HIV status, and precluded multivariable adjustment for potential confounders. As a tertiary-center–based series, selection bias is possible, and milder cases managed elsewhere may not have been captured. In addition, incomplete long-term follow-up in some patients restricts assessment of relapse rates and sustained visual outcomes. Therefore, observed associations—particularly those related to HIV status and CSF findings—should be interpreted cautiously.

Conclusion

In conclusion, ocular syphilis should be considered in the differential diagnosis of unexplained posterior uveitis or panuveitis, even in the absence of systemic findings. Regardless of HIV status, early diagnosis and timely initiation of appropriate treatment are critical for achieving favorable visual outcomes. Incorporating routine HIV testing into the evaluation of patients diagnosed with ocular syphilis contributes to timely diagnosis and appropriate management.

Footnotes

ORCID iDs

Nazife Duygu Demirbas

Dilek Yildiz Sevgi

Ethical considerations

The study was approved by the Ethics Committee of Şişli Hamidiye Etfal Training and Research Hospital (approval number 3032, dated November 25, 2025). The study was conducted in accordance with the principles of the Declaration of Helsinki.

Consent to participate

Due to the retrospective nature of the study, the requirement for informed consent from individual participants was waived by the relevant ethics committee.

Consent for publication

This study does not contain any individually identifiable patient data, images, or videos. Therefore, additional informed consent for publication was not required.

Author contributions

Conceptualization: N.D. Demirbas, A. Bascı.

Data curation: N.D. Demirbas, A. Bascı, A. Gunduz, G. Kuran, O. Altuntas Aydin.

Formal analysis: N.D. Demirbas.

Writing – original draft: N.D. Demirbas.

Writing – review & editing: S.T. Demir, D.Y. Sevgi, O. Altuntas Aydin.

All authors approved the final version of the manuscript.

Funding

The authors received no financial support for the research, authorship, and/or publication of this article.

Declaration of conflicting interests

The authors declare that they have no conflicts of interest related to the research, authorship, and/or publication of this article.

Data Availability Statement

The data supporting the findings of this study are not publicly available due to ethical and legal restrictions but are available from the corresponding author upon reasonable request.*

References

World Health Organization . Global progress report on HIV, viral hepatitis and sexually transmitted infections, 2023 [Internet]. Geneva: World Health Organization; 2024. Available from: https://www.who.int/teams/global-hiv-hepatitis-and-stis-programmes/stis/strategic-information

European Centre for Disease Prevention and Control . Syphilis: annual epidemiological report for 2022. ECDC, 2024. https://www.ecdc.europa.eu/en/publications-data/syphilis-annual-epidemiological-report-2022

Republic of Türkiye, Ministry of Health, General Directorate of Public Health . Syphilis infection statistics, Türkiye 2006–2023. Ankara: Ministry of Health, 2024. https://hsgm.saglik.gov.tr/depo/birimler/bulasici-hastaliklar-ve-erken-uyari.

Gao

Yan

, et al. The importance of proper and prompt treatment of ocular syphilis: a lesson from permanent vision loss in 52 eyes. J Eur Acad Dermatol Venereol 2020; 34(7): 1569–1578. https://doi.org/10.1111/jdv.16347

Oliver

Aubin

Atwell

, et al. Ocular syphilis—eight jurisdictions, United States, 2014–2015. MMWR Morb Mortal Wkly Rep 2016; 65: 1185–1188. https://doi.org/10.15585/mmwr.mm6543a2

Oliver

Cope

Rinsky

, et al. Increases in ocular syphilis—North Carolina, 2014–2015. Clin Infect Dis 2017; 65(10): 1676–1682. https://doi.org/10.1093/cid/cix604

Centers for Disease Control and Prevention . Clinical advisory: ocular syphilis in the United States [Internet]. Atlanta: Centers for Disease Control and Prevention; 2016. Available from: https://www.cdc.gov/std/stats16/CDC_2016_STDS_Reportfor508WebSep21_2017_1644.pdf

Yang

Zou

, et al. Syphilis and the eye: clinical features, diagnostic challenges, and evolving therapeutic paradigms. Pathogens 2025; 14(9): 852. https://doi.org/10.3390/pathogens14090852

Zhang

Zhu

. Clinical features and treatments of syphilitic uveitis: a systematic review and meta‐analysis. J Ophthalmol 2017; 2017(1): 6594849. https://doi.org/10.1155/2017/6594849

10.

Amaratunge

Camuglia

Hall

. Syphilitic uveitis: a review of clinical manifestations and treatment outcomes of syphilitic uveitis in human immunodeficiency virus‐positive and negative patients. Clin Exp Ophthalmol 2010; 38(1): 68–74. https://doi.org/10.1111/j.1442-9071.2010.02203.x

11.

Kong

Ruan

Xie

, et al. Clinical manifestations and treatment prognosis of patients with co-infection of ocular syphilis and HIV. BMC Ophthalmol 2025; 25(1): 652. https://doi.org/10.1186/s12886-025-04475-0

12.

Tucker

Lobo

, et al. Ocular syphilis among HIV-infected individuals. Clin Infect Dis 2010; 51(4): 468–471. https://doi.org/10.1086/654797

13.

Centers for Disease Control and Prevention. Syphilis (Treponema pallidum) 2018 case definition . National notifiable diseases surveillance system (NNDSS). U.S. Department of Health and Human Services, 2018. https://ndc.services.cdc.gov/case-definitions/syphilis-2018/.

14.

Collier

Marra

Coombs

, et al. Central nervous system manifestations in human immunodeficiency virus infection without AIDS. JAIDS J Acquir Immune Defic Syndr 1992; 5(3): 229–241.

15.

Marshall

Brey

Butzin

, et al. CSF changes in a longitudinal study of 124 neurologically normal HIV-1-infected US air force personnel. JAIDS J Acquir Immune Defic Syndr 1991; 4(8): 777–781.

16.

Standardization of Uveitis Nomenclature (SUN) Working Group . Standardization of uveitis nomenclature for reporting clinical data. Results of the first international workshop. Am J Ophthalmol. 2005; 140(3): 509–516.

17.

Dutta

Chen

Shah

, et al. Ocular syphilis: an update. Ocul Immunol Inflamm 2019; 27(1): 117–125. https://doi.org/10.1080/09273948.2017.1371765

18.

World Health Organization . WHO guidelines for the treatment of Treponema pallidum (Syphilis). Geneva: World Health Organization, 2016. https://apps.who.int/iris/bitstream/10665/249572/1/9789241549806-eng.pdf?ua=1.

19.

Centers for Disease Control and Prevention (CDC) . Sexually transmitted infections treatment guidelines, 2021. MMWR Recomm Rep 2021; 70(4): 1–187. https://www.cdc.gov/std/treatment-guidelines/default.htm

20.

Cope

Mobley

Oliver

, et al. Ocular syphilis and human immunodeficiency virus coinfection among syphilis patients in North Carolina, 2014–2016. Sex Transm Dis 2019; 46(2): 80–85. https://doi.org/10.1097/OLQ.0000000000000910

21.

Lee

Cheng

Rodger

, et al. Clinical and laboratory characteristics of ocular syphilis: a new face in the era of HIV co-infection. J Ophthalmic Inflamm Infect 2015; 5(1): 26. https://doi.org/10.1186/s12348-015-0056-x

22.

Sudharshan

Kaleemunnisha

Banu

, et al. Ocular lesions in 1,000 consecutive HIV-positive patients in India: a long-term study. J Ophthalmic Inflamm Infect 2013; 3(1): 2. https://doi.org/10.1186/1869-5760-3-2

23.

Biotti

Bidot

Mahy

, et al. Ocular syphilis and HIV infection. Sex Transm Dis 2010; 37(1): 41–43. https://doi.org/10.1097/OLQ.0b013e3181b3e4d8

24.

Orlowski

Karunatilake

, et al. Prognostic effect of HIV on visual acuity in ocular syphilis: a systematic review. Eye 2023; 37(15): 3271–3281. https://doi.org/10.1038/s41433-023-02504-0

25.

Libois

De Wit

Bé

, et al. HIV and syphilis: when to perform a lumbar puncture. Sex Transm Dis 2007; 34(3): 141–144. https://doi.org/10.1097/01.olq.0000230481.28936.e5

26.

Ghanem

Moore

Rompalo

, et al. Lumbar puncture in HIV-infected patients with syphilis and no neurologic symptoms. Clin Infect Dis 2009; 48(6): 816–821. https://doi.org/10.1086/597096

27.

Smith

Goldmeier

Migdal

. Neurosyphilis with optic neuritis: an update. Postgrad Med J 2006; 82(963): 36–39. https://doi.org/10.1136/pgmj.2004.020875

28.

Köksaldı

Nazlı

Kaya

, et al. Never forget ocular syphilis: a case series from a single tertiary centre. Int J STD AIDS 2023; 34(11): 817–822. https://doi.org/10.1177/09564624231195674