Appraisal of vitreous syphilis antibody as a novel biomarker for the diagnosis of syphilitic uveitis: a prospective case-control study

Abstract

Purpose: To determine the sensitivity and specificity of syphilis antibody tests in vitreous samples and to propose an algorithm using vitreous syphilis antibody as a supplementary test to confirm syphilitic uveitis (SU).

Methods: A prospective case-control study was conducted at the Retina and Uveitis Clinic from May 2017 to January 2020. Initially, patients were classified based on syphilis serology into group 1 (positive testing) and group 2 (negative testing). Group 1 was further divided into 2 subgroups (group 1A and 1B) depending on their relevant clinical manifestations and clinical improvement. Group 2 served as a control group.

Results: Thirty-eight patients were enrolled in the study: 14 in group 1A, 5 in group 1B, and 19 in group 2B. No patient was assigned to group 2A. All patients in group 1A, representing definite SU, completed syphilis test (rapid plasma reagin [RPR], enzyme immunoassay [EIA], and fluorescent treponemal antibody-absorption [FTA-ABS]) for vitreous, and all vitreous samples yielded positive results. Of the 5 subjects in group 1B, 3 cases were considered to be not SU with different conditions, and 2 were indeterminate for SU. They presented with different features not typical of SU, and they had variable and fewer positive syphilis antibody responses. The most sensitive test for detecting syphilis antibodies in vitreous was EIA (90.9%), followed by RPR (80.0%) and FTA-ABS IgG (78.9%). EIA and FTA-ABS had the highest specificity, detecting 100% of the syphilis antibody.

Conclusions: Vitreous analysis of syphilis antibody can serve as a supplementary test to confirm SU in selected cases as the proposed algorithm.

Fig. 1. Multimodal imaging of selected cases in group 1A and group 1B.

A–D show multimodal imaging of case 1 (group 1A). A SD-OCT image of the left eye shows disorganized outer nuclear and outer plexiform layer, focal defect of external limiting membrane, generalized ellipsoid zone disruption, and localized pigment epithelial detachment. B Two weeks after initiation of penicillin G, improvement was evident from the decrement of inner and outer retina irregularities in SD-OCT. There was no change in central choroidal thickness. C Mid-phase fluorescein angiogram of the left eye demonstrates perivascular and disc leakage. D Perifoveal leakage decreased after initiation of penicillin G. E and F show mid-phase fluorescein angiogram (FA) of case 7 (group 1A). E Though pre-treatment FA image is unclear due to the vitritis, it reveals disc leakage with diffuse venous leakage F Two weeks after the completion of intravenous ceftriaxone, the angiogram was clear, and there was significant reduction of leakage from optic disc and retinal veins. G–J show multimodal imaging of the patients in group 1B. G and H Case 15 complained of floaters in the right eye with BCVA 20/20. The OCT image of the right eye shows relatively normal macula, and fluorescein angiogram reveals several leaking microaneurysms and capillary nonperfusion areas, which is characteristic of diabetic retinopathy. I and J Case 17 presented with unilateral retinal vasculitis which was focused in the macula (I). After a 2-week course of ceftriaxone monotherapy without visual improvement, oral prednisolone (1 mg/kg daily) was prescribed and showed good results in terms of visual gain and significant reduction of angiographic leakage at 1 week after corticosteroid treatment (J).