Ocular Syphilis With Phlebitis and Paravenous Pigmentary Retinopathy

Abstract

Purpose:

Ocular syphilis can present as a wide variety of clinical phenotypes, among them panuveitis with vasculitis. Primary retinal phlebitis with resulting paravenous atrophy and pigmentary retinal degeneration is a rare presentation.

Methods:

A 53-year-old man presented with a 1-year history of bilateral blurry vision. Physical examination demonstrated bilateral anterior chamber and vitreous cell with vitreous haze, hyperemic optic nerves, and atrophic-appearing retina. The left eye demonstrated a nasal area of perivenular vascular sheathing with adjacent retinal whitening. Ancillary testing demonstrated predominantly perivenular leakage involvement.

Results:

Uveitic workup was positive for syphilis and HIV. The patient was treated with antiretroviral therapy and intravenous penicillin G. He developed progressive paravenous pigmentary changes and atrophy.

Conclusions:

Syphilis can present with a wide variety of phenotypic manifestations and should also be considered in patients presenting with acute retinal phlebitis or paravenous atrophy in long-standing cases.

Introduction

Ocular syphilis can present as a wide range of clinical phenotypes. Recognition of rarely recognized clinical presentations can lead to timely diagnoses to avoid significant vision loss. When presenting as retinitis, syphilis tends to primarily involve arteries or both arteries and veins. ¹ Syphilis with primary venous involvement is an atypical presentation. ^{2 -7} Previously reported cases lack widefield imaging and primarily described only focal venous involvement rather than diffuse involvement as seen in this case. Ocular syphilis with a resulting atrophic pigmentary retinopathy is an even more atypical outcome after treatment. We present the case of a patient newly diagnosed with HIV and ocular syphilis who presented with predominantly venous involvement and a dramatic progression, despite treatment, to a paravenous pigmentary retinopathy.

Methods

Case Report

A 53-year-old man presented with a 1-year history of bilateral blurry vision with intermittent flashes, floaters, and photophobia. His visual acuity was 20/100 and 20/60 with intraocular pressures (IOPs) of 13 and 12 mm Hg in the right and left eyes, respectively. Anterior segment examination demonstrated nongranulomatous keratic precipitates with 1+ anterior chamber cell and 2+ vitreous cells in both eyes. Fundus findings in both eyes demonstrated vitreous haze, hyperemic optic nerves, and atrophic-appearing retina. The right eye also demonstrated hemorrhages in the temporal periphery, and the left eye demonstrated a nasal area of perivenular vascular sheathing with adjacent retinal whitening (Figure 1, A and B). Notably absent were paravenous bony corpuscle pigmentary changes. Fluorescein angiography (FA) of both eyes revealed perivenular stippled hyperfluorescence with venous leakage as well as optic nerve leakage (Figure 1, C and D). Fundus autofluorescence demonstrated perivenular hypoautofluorescence in both eyes (Figure 2, A and B).

Figure 1.

Widefield fundus photography of the (A) right and (B) left eyes demonstrates vitreous haze, hyperemic optic nerves, and atrophic-appearing retina. The left eye demonstrated a nasal area of perivenular vascular sheathing with adjacent retinal whitening (arrow). Widefield fluorescein angiography of the (C) right and (D) left eyes revealed significant paravenous stippled hyperfluorescence with late venous leakage as well as optic nerve leakage.

Figure 2.

Widefield fundus autofluorescence of the (A) right and (B) left eyes at presentation demonstrated paravenous hypoautofluorescence. One year after presentation, fundus autofluorescence of the (C) right and (D) left eyes reveal increased paravenous hypoautofluorescence suggestive of progressive retinal pigment epithelium atrophy.

Optical coherence tomography of both maculae demonstrated vitreous cells, epiretinal membrane, superficial retinal precipitates, peripapillary inner retinal thickening, and loss of integrity of the external limiting membrane and ellipsoid zone with sparing of the subfoveal region (Figure 3). An extensive uveitic workup was positive for treponemal immunoglobulin G antibody with elevated rapid plasma reagin (RPR) titers (1:128), and an antigen and antibody test was positive for HIV with a CD4 count of 783 cells/μL. QuantiFERON-Tb Gold and angiotensin-converting enzyme testing had negative results. Lumbar puncture revealed a cerebrospinal fluid (CSF) VDRL test with positive results (1:16). The patient was admitted and treated with 4 million units of intravenous (IV) penicillin G for 14 days and started antiretroviral therapy and topical corticosteroids. A tapered course of high-dose oral prednisone was administered shortly after IV penicillin was started. He initially responded well with a 4-fold decrease in RPR titers to 1:32. A second lumbar puncture at 6 months also revealed decreased CSF VDRL test results (1:4).

Figure 3.

Optical coherence tomography of the (A) right and (B) left macula demonstrate vitreous cells, epiretinal membranes, superficial retinal precipitates, peripapillary inner retinal thickening, and loss of integrity of the external limiting membrane and ellipsoid zone with sparing of the subfoveal regions. One year later, the (C) right and (D) left macula demonstrate increased reconstitution of the ellipsoid zone, resolution of vitreous cells, and mild cystoid macular edema.

His symptoms resolved and his vision in the right and left eyes improved to 20/50 and 20/25, respectively. He developed postinfectious cystoid macular edema (CME) that was controlled with oral and topical corticosteroids but led to steroid-responsive IOP increases in both eyes that were unable to be controlled with topical IOP-lowering medication. He received a gonioscopy-assisted transluminal trabecutomy in the right eye and a Kahook Dual Blade (New World Medical) in the left eye, which controlled his IOP back to reference ranges in both eyes. He never developed visual field deficits. One year after initial diagnosis his CME began to worsen and symptoms of photophobia and photopsia returned with a recurrence of vitreous cell in both eyes. Another round of testing revealed a 1-fold increase in RPR titers (1:64), which was concerning because of the incomplete response to the initial course of IV penicillin. The patient’s CD4 counts were stable, and he was compliant with his antiretroviral medications. A second course of IV penicillin was administered.

Concurrently during this period, his fundus findings began to progress and he developed perivenular pigmentary changes and pigment clumping, which were absent on his initial presentation (Figure 4, A and B). His FA highlighted significant venular attenuation with perivenular stippled hyperfluorescence and blockage in the areas of clumped hyperpigmentation, as well as petaloid leakage in the left macula (Figure 4, C and D). The venous and disc leakage had resolved. His fundus autofluorescence demonstrating increased paravenous hypoautofluorescence was suggestive of progressive retinal pigment epithelium atrophy (Figure 2, C and D).

Figure 4.

Widefield fundus photography 1 year after presentation of the (A) right and (B) left eyes demonstrate paravenous clumped pigmentary changes and atrophy absent from initial presentation. Widefield fluorescein angiography of the (C) right and (D) left eyes at this time highlight the significant venular attenuation with paravenous stippled hyperfluorescence and blockage in the areas of clumped hyperpigmentation classically seen with pigmented paravenous retinochoroidal atrophy, as well as petaloid leakage in the left macula.

Results

The patient continued to be treated for postinfectious uveitis CME with topical corticosteroids. Visual acuity at his most recent follow-up 2 years after presentation was 20/40 and 20/50 in the right and left eye, respectively.

Conclusions

Ocular involvement of syphilis is uncommon, presenting in only 0.6% of syphilis cases. Diagnosis is crucial, however, as mismanagement can lead to severe vision loss. As highlighted by this case, testing for HIV should be performed in all cases of ocular syphilis given the association. ⁸ Ocular syphilis in patients with HIV has been shown to have more diffuse ocular inflammation, which was also seen in our patient. ^5,9 Interestingly, a few other reported cases of ocular syphilis with predominantly venous involvement also occurred in a patient coinfected with HIV. ^5,6

While ocular syphilis affecting the posterior segment classically manifests with predominantly retinal arterial involvement or combined arterial and venous involvement, cases of syphilitic phlebitis, especially in the context of concurrent HIV infection, have been rarely reported. ^{2 -7} A resulting paravenous pigmentary retinopathy has not been reported in these prior cases. Why syphilis can present with a predominant venous phenotype in some cases is unclear, perhaps relating to specific immune responses and disruptions in the blood-brain barrier in some patients. Our patient continued to develop a paravenous pigmentary retinopathy even after appropriate treatment of his chronic infectious panuveitis, suggesting inflammatory sequelae.

Infectious and inflammatory uveitic conditions have been reported to result in permanent predominantly paravenous pigmentary phenotypes. Pigmented paravenous retinochoroidal atrophy (PPRCA) is a rare chorioretinal disorder with a characteristic finding of perivenular bone corpuscle pigmentary changes with adjacent chorioretinal atrophy. The first case was described in 1937 under the term retinochoroiditis radiata and was secondary to a possible case of tuberculosis with ocular involvement. ¹⁰ Numerous conditions have been associated with this rare entity and can be a result of perivascular inflammation secondary to infectious or inflammatory insults. ¹⁰ Only 1 case, reported in 1948, found a suggested association between serologically proven syphilis and retinochoroiditis radiata in a 36-year-old woman and included only a unilateral retinal drawing of the posterior pole. ¹¹

PPRCA is a clinical diagnosis based on characteristic fundus findings confirmed by ancillary testing with FA and fundus autofluorescence. ¹² While our case has dramatic paravenous pigmentary changes, it lacks classic bony corpuscle pigmentary changes so we avoided attributing this dramatic phenotype to PPRCA. Bony spicule-like changes as seen in retinitis pigmentosa have also been rarely reported in cases of suboptimally treated neurosyphilis. ¹³

The temporal association, paravenous and disc leakage at time of presentation with positive syphilis serology and CSF testing results, and rapid progression of paravenous retinochoroidal atrophy over the course of 1 year support the causal relationship in this case of the patient’s ocular syphilis diagnosis with his resulting paravenous atrophic phenotype. Our case also highlights the importance of continued infectious disease follow-up in these patients, as our patient initially demonstrated a 4-fold titer reduction and then developed relapsing disease. Distinguishing between disease recurrence after treatment and reinfection is often difficult. Serologic-defined treatment failure is not an uncommon occurrence, especially in patients with HIV. ¹⁴

We present seldomly reported ultra-widefield imaging findings of ocular syphilis acutely manifesting with predominantly venous involvement and chronically manifesting with a bilateral paravenous pigmentary retinopathy. True to its moniker as “the great masquerader,” syphilis can present with an impressively wide variety of phenotypic manifestations. While classically associated with arterial involvement, syphilis should also be ruled out in uveitis with venous involvement. This case highlights the venous changes that can occur in patients with chronic ocular syphilis disease and the need to rule out infectious causes in patients with chronic-appearing fundus changes.