Syphilitic Outer Retinopathy: A Case Report and Review of the Literature

Abstract

Purpose:

This work presents a case of syphilitic outer retinopathy with findings similar to those of acute zonal occult outer retinopathy (AZOOR). We also discuss the clinical characteristics, treatment, and prognosis of this entity.

Methods:

A case report and systematic literature review are presented.

Results:

A 56-year-old woman presented with acute vision loss, localized photopsia, a central scotoma, and retinal findings that were all consistent with AZOOR. A further workup led to a diagnosis of syphilis. Oral prednisone and intravenous penicillin resulted in the resolution of the posterior uveitis and the restoration of visual acuity. However, the central scotoma remained at the 3-year follow-up visit.

Conclusions:

Syphilitic outer retinopathy is a distinct entity characterized by the disruption of the ellipsoid zone visible on optical coherence tomography and a corresponding increase in fundus hyperautofluorescence in the affected areas. Although some patients may present with a demarcation line, as is seen with AZOOR, the fundus is oftentimes unremarkable or may show only subtle retinal pigment epithelium changes. Uveitis resolution and visual acuity restoration may be expected following treatment; however, visual field disturbances may persist.

Introduction

Syphilis is a sexually transmitted disease caused by the bacterium Treponema pallidum. Despite the existence of effective methods to prevent, diagnose, and treat the disease, the rates of primary and secondary syphilis in the United States have been rising since 2001. ¹ In 2018, the total case count was the highest recorded since 1991. ² That year, the Centers for Disease Control and Prevention reported 10.8 cases of primary and secondary syphilis per 100 000 population, representing a 14.9% increase over 2017. ² The upsurge in cases was attributed mainly to men who have sex with men, although the rates among women have increased substantially as well. ²

Syphilis is known as “the great imitator” because its presentation may take the form of any 1 or more of several ocular diseases, including scleritis, keratitis, neuroretinitis, and, most commonly, uveitis. ³ True to its pseudonym, syphilis remains in the differential of all the anatomical subtypes of uveitis. ³ Typically, posterior segment involvement may reveal distinctive preretinal yellowish aggregates, which are theorized to be treponemal bacterial and inflammatory precipitates. ⁴ However, syphilis may masquerade as other well-defined uveitides, such as multiple evanescent white-dot syndrome, Vogt-Koyanagi-Harada syndrome, or acute posterior multifocal placoid pigment epitheliopathy. ^3,5

Recently, several cases of syphilitic outer retinopathy (SOR) presenting as acute zonular occult outer retinopathy (AZOOR) have been described in the literature. ^{5 -11} Here we provide an overview of those cases and their respective findings of SOR presenting as AZOOR. We also discuss its prognosis, the treatment options available for this condition, and the possible role of adjunctive therapy with corticosteroids. In addition, we report on the case of a 56-year-old Black Hispanic female patient with SOR with features similar to those of AZOOR. In our case, the treatment consisted of intravenous (IV) penicillin G and prednisone and resulted in the resolution of posterior uveitis, the restoration of visual acuity (VA), and a significant improvement of her scotoma.

Methods

Case Report

A 56-year-old Black Hispanic female with a history of arterial hypertension, osteoarthritis, and moderate myopia presented with a 1-week history of acute vision loss in the left eye that was associated with localized photopsia. The review of systems was negative for fever, chills, arthralgia, skin rash, imbalance, and headache. She reported having had unprotected sexual intercourse with a new, heterosexual partner 2 months before the onset of symptoms. Her social and family histories were otherwise unremarkable.

Her best-corrected VA (BCVA) was 20/20 OD and 20/400 OS. Intraocular pressure was 14 mm Hg OD and 15 mm Hg OS. The pupils were round and reactive to light, and the left one had an afferent pupillary defect of +1. A slitlamp examination revealed mild nuclear sclerosis of both lenses but otherwise had normal findings. The vitreous of the right eye was clear; the left eye had 1+ vitreous cells. The fundus examination showed normal discs and revealed scattered, small, hard drusen, and posterior staphyloma that presented bilaterally. However, in the left eye, there was a subtle area of white discoloration with a demarcation line superior to the disc and the macula along the midperiphery; there were also further retinal pigment epithelium (RPE) changes in the macula (Figure 1A). A physical examination revealed symmetric brownish macules, papules, and plaques with collarettes of scales on the soles of both feet (Figure 2).

Figure 1.

Ultra-widefield fundus imaging and optical coherence tomography of the left eye on presentation. (A) Color photographs show a white area of discoloration with a demarcation line that is superior to the disc and the macula. Further macular retinal pigment epithelial changes are also noted. (B) Fundus autofluorescence is markedly increased within the posterior pole, up to the level of the demarcation line, superiorly, and extending temporally up to the midperiphery. (C) A late-phase intravenous fluorescein angiogram revealed late-phase disc hyperfluorescence, macular and perivenular leakage within the posterior pole and on the temporal periphery, and marked hyperfluorescence with associated leakage of the demarcation line. (D) Late-phase indocyanine green angiography revealed a geographic area of hypocyanescence. (E) Spectral-domain optical coherence tomography revealed posterior hyaloid separation, vitreous cells, and ellipsoid zone disruption as well as subretinal drusenoid deposits.

Figure 2.

Color photograph taken at presentation shows the presence of symmetric brownish macules, papules, and plaques with collarettes of scales on the soles of both feet.

The fundus autofluorescence (FAF) was within normal limits in the right eye; however, in the left eye, it was markedly increased within the posterior pole, up to the level of the demarcation line, superiorly, and extending up to the temporal midperiphery (Figure 1B). The IV fluorescein angiogram showed normal findings in the right eye; in the left eye, it revealed late-phase disc hyperfluorescence, macular and perivenular leakage within the posterior pole and on the temporal periphery, and marked hyperfluorescence of the demarcation line with associated leakage (Figure 1C). That patient’s indocyanine green angiography (ICGA) was within normal limits in the right eye; in the left eye, it was remarkable for a geographic area of hypocyanescence, the borders of which emerged during the early to middle phases and became pronounced during the late phase of the angiogram (Figure 1D). Spectral-domain optical coherence tomography revealed posterior hyaloid separation, vitreous cells, and ellipsoid zone disruption as well as subretinal drusenoid deposits (Figure 1E). The Humphrey visual field examination was within normal limits in the right eye; however, it revealed a central scotoma with a temporal extension in the left eye (Figure 3A).

Figure 3.

Left-eye visual field progression (Humphrey, central 30-2 threshold test, stimulus III, white, SITA Fast). (A) On presentation, there was a profound central scotoma with a temporal extension. (B) Six months and (C) 3 years after the conclusion of therapy, the scotoma improved markedly but nevertheless persisted. ASB indicates apostilbs; DC, double cylinder; DS, double sphere; GHT, glaucoma hemifield test; MD, mean deviation; NEG, negative; POS, positive; PSD, pattern standard deviation; VFI, visual field index.

Provided the clinical and ancillary testing results, we had a high suspicion that the patient might be suffering from AZOOR or an AZOOR-like syndrome, and we ordered a workup to rule out secondary causes of posterior uveitis, in particular syphilis. The fluorescent treponemal antibody absorption, rapid plasma reagin, and T pallidum passive particle agglutination tests were all positive for and consistent with a diagnosis of syphilis. HIV serology and a cerebrospinal fluid Venerial Disease Research Laboratory test results were negative. A further workup was performed, including a complete blood count, serum chemistry, urinalysis, and chest x-ray, and the results were normal. The patient was diagnosed with SOR presenting as AZOOR. She received a 14-day course of IV penicillin G. Concomitant oral prednisone was started at a dosage of 60 mg daily and was gradually tapered completely over the following 14 weeks.

Three months following treatment, the patient’s BCVA improved to 20/25 in the left eye. Fundus examination of the left eye revealed the resolution of the retinitis and the disappearance of the demarcation line. The corresponding OCT images of the left eye showed the restoration of the inner segment/outer segment junction area, the resolution of the drusenoid deposits, and a paucity of vitreous cells. The FAF revealed marked improvement of the macular hyperautofluorescence, with only slight hyperfluorescence superior to the disc remaining. The IV fluorescein angiogram revealed the resolution of the disc, macular, and perivascular leakage, as well as the absence of a hyperfluorescent demarcation line. However, the ICGA revealed a residual area of late hypocyanescence encompassing the fovea and nasal macula, which extended superior to the disc. Still, compared with when she presented, the patient was found to have improved significantly (Figure 4).

Figure 4.

Ultra-widefield fundus imaging and optical coherence tomography of the left eye 3 months following the completion of therapy. (A) Color photograph reveals the resolution of the retinitis and the disappearance of the demarcation line. (B) Fundus autofluorescence shows a marked improvement of the macular hyperautofluorescence, with only slight hyperfluorescence remaining superior to the disc. (C) A late-phase fluorescein angiogram shows the resolution of the disc, macular, and perivascular leakage, and the absence of a hyperfluorescent demarcation line. (D) Late-phase indocyanine green angiography reveals a residual area of late hypocyanescence encompassing the fovea and nasal macula and extending superior to the disc. (E) Spectral-domain optical coherence tomography reveals the restoration of the inner segment/outer segment junction area, the resolution of the drusenoid deposits, and a paucity of vitreous cells.

Three years after the initial presentation, the patient remained in remission, with a BCVA of 20/25 and no clinical evidence of uveitis recurrence; however, her Humphrey visual field examination revealed a persistent scotoma (Figure 3, B and C).

Results

From February through September 2020, we explored the current literature on SOR presenting as AZOOR. Using the search engines Google Scholar and PubMed, we searched for the phrases “syphilitic outer retinopathy,” “acute zonal occult outer retinopathy,” “syphilitic uveitis presenting as AZOOR,” “ocular syphilis presenting as AZOOR,” and “syphilitic outer retinopathy presenting as AZOOR.” Our search was restricted to manuscripts written in the English language. We found 6 reports that described 10 cases of SOR presenting as AZOOR; these reports were published from 2014 through 2020. Table 1 summarizes their characteristics, including demographics, examination findings, imaging and laboratory results, and the treatment(s) used in each case.

Table 1.

Literature Review of Syphilitic Outer Retinopathy.

	Case 1	Case 2	Case 3	Case 4	Case 5	Case 6	Case 7	Case 8	Case 9	Case 10	Case 11
Publication	Lima et al, 2014 6	Lima et al, 2014 6	Kim et al, 2014 10	Kroloff et al, 2017 9	Saleh et al, 2017 11	Saleh et al, 2017 11	Saleh et al, 2017 11	Li and Chen, 2020 7	Li and Chen, 2020 7	Almeida et al, 2020 8	Our case
Age, y	44	48	59	71	57	45	51	47	44	45	56
Sex	M	M	M	M	M	M	M	M	F	M	F
Race/ethnicity	White	White	Korean	Not documented	White	White	White	Not documented	Not documented	Not documented	Hispanic
Laterality	Unilateral	Unilateral	Unilateral	Bilateral	Bilateral	Unilateral	Unilateral	Bilateral	Unilateral, progressed to bilateral 5 d later	Bilateral	Unilateral
Symptoms	Photopsia and progressively enlarging scotoma for 1 wk	Blurred vision and floaters for 10 d	Blurred vision for 2 wk	Blurred vision for 4 mo	Blurred vision and impaired color perception for 3 wk	Redness, irritation, and loss of central vision for 10 d	Photopsia and sudden vision loss for 10 d	Blurred vision for 1 mo	Blurred vision for 4 d	Painless vision loss, photopsia, peripheral scotomas for 1 wk	Acute vision loss and photopsia for 1 wk
Initial VA	20/160	CF	20/50	20/125 // 20/50	20/40 // HM	CF at 5 in (12 cm)	20/200	20/100 // 20/60	20/20 // 20/20; 20/20 // 20/400 after 2 wk	20/60 // 20/40	20/400
Anterior segment	Normal	1+ cell	Normal	Not documented	Normal	Conjunctival injection, small keratic precipitates, 0.5+ cell	Normal	Normal	Normal	Normal	Normal
Fundus examination	Pale yellow curvilinear demarcation line in macula	1+ vitreous cells, demarcated subretinal punctate curvilinear infiltrate around macula	Normal	Not documented	Bilateral RPE mottling in macula and RPE atrophy in posterior pole	1+ vitreous cell, mild optic disc edema, large zonal area of flat, outer retinal whitish-yellow discoloration	1+ vitreous cell and pigment, optic disc hyperemia, macula and superonasal peripheral retina RPE changes	No remarkable change	Normal	Normal	1+ vitreous cells, demarcation line superior to disc and macular along midperiphery; macula RPE changes
Ancillary testing
Visual field	Superonasal defect	Not documented	Superior-central defect	Central threshold elevations and scattered areas of reduced sensitivity	Not performed	Not performed	Not performed	Bilateral paracentral scotoma	Normal	Bilateral tubular visual field	Central scotoma with temporal extension
Optical coherence tomography	Loss of IS/OS junction	Loss of IS/OS junction and RPE irregularities	Loss of IS/OS junction and subretinal deposits	Bilateral macular ellipsoid zone disruption	Diffuse loss of IS ellipsoid zone, external limiting membrane reflectivity, and CME	Diffuse ellipsoid zone and external limiting membrane disruption and RPE level excrescences throughout macula	Ellipsoid zone disruption and nodular thickening of RPE	Ellipsoid zone disruption	Ellipsoid zone disruption, right eye	Areas of discontinuity and irregularity of external retinal layers; focal loss of ellipsoid line	Posterior hyaloid separation, vitreous cells, ellipsoid zone disruption, IS/OS disruption, subretinal drusenoid deposits
Fundus autofluorescence	Mild hyperfluorescence	Hyperfluorescence	Hyperfluorescence	Bilateral macular ellipsoid zone disruption	Large peripapillary area of hypoautofluorescence and diffuse hyperautofluorescence throughout fovea/perifovea	Hyperautofluorescence	Macula and superonasal hyperautofluorescence	Hyperautofluorescence at macula and peripapillary area	Hyperautofluorescence at central macular area right eye	Discretely hypofluorescent subretinal punctate spots	Hyperfluorescence
Fluorescein angiography	Normal	Phlebitis and staining of punctate lesions	Normal	Not performed	Not performed	Not performed	Not performed	Diffuse phlebitis with venous leakage in both eyes	Phlebitis and disc staining in both eyes	Multiple hyperfluorescent foci in intermediate phases with residual leakage in late phases	Marked hyperfluorescence of demarcation line with associated leakage; late-phase disc hyperfluorescence, localized phlebitis
ICG	Not performed	Large, round patch of hypocyanescence	Not performed	Not performed	Not performed	Not performed	Not performed	Not performed	Not performed	Hypocyanescent subretinal punctate spots	Geographic area of hypocyanescence
ERG	Normal	Not performed	Multifocal ERG: reduced amplitudes in corresponding areas; normal full-field ERG	Not performed	Not performed	Not performed	Not performed	Reduced a-wave and b-wave amplitudes in combined response and cone response	Not performed	Not performed	Not performed
EOG	Normal	Not performed	Not performed	Not performed	Not performed	Not performed	Not performed	Not performed	Not performed	Not performed	Not performed
Laboratory positive results	RPR, syphilis IgG, lupus anticoagulant, and anticardiolipin Ab	RPR, TP-PA, CMIA	VDRL, FTA-ABS	RPR, TP-PA	RPR, FTA-ABS	RPR, Treponema pallidum IgG, chlamydia	RPR, FTA-ABS	RPR, TP-PA	RPR, TP-PA	RPR, syphilis IgM	RPR, TP-PA, FTA-ABS
Spinal tap	Not performed	Not performed	Not performed	(+) VDRL	(+) VDRL	(–)	Not performed	(−)	Not performed	(–)	(–)
HIV	(–)	(+)	Not documented	(–)	(–)	(–)	(+)	Not performed	Not performed	(–)	(–)
Treatment	IV penicillin G for 6 wk. Prednisone 80 mg orally, daily; changed to 20 mg orally, daily, after syphilis diagnosis	IV penicillin G for 14 d, 1× dose of IM penicillin G	IM penicillin G, 3×/wk	IV penicillin G for 14 d	IV penicillin G for 14 d. Oral prednisone subsequently added to treat CME. 1 y after initial treatment, IV penicillin G for 4 wk given for persistently positive RPR	IV penicillin G for 3 wk and prednisolone eye drops, 4×/d, left eye, with standard tapering	IV penicillin G for 14 d	IV ceftriaxone, 2000 mg, daily, and oral doxycycline, 100 mg, 2×/d for 10 d (due to penicillin shortage); oral prednisolone, 45 mg, daily, added day 4 and slowly tapered down after discharge	Oral prednisone, 20 mg, daily, tapered down to 10 mg after syphilis diagnosis was made. Patient given “syphilis treatment” but specific medication not mentioned. Sub-Tenon injection of triamcinolone 40 mg OS, given 2 wk after initial presentation	IV ceftriaxone for 14 d (penicillin allergy present)	IV penicillin G for 14 d; oral prednisone, gradually tapered down over 14 wk
Final VA	20/20 after therapy	20/20 at 6 mo	20/20 at 3 mo	20/30 // 20/25 at 4 mo	20/40 // 20/30 at 14 mo	20/30 at 3 mo	20/20 at 3 mo	20/20 // 20/20 at 6 mo	20/20 // 20/20 at 1 mo	20/20 // 20/20 at 2 y	20/25 at 3 y

Abbreviations: Ab, antibody; CF, counting fingers; CME, cystoid macular edema; CMIA, chemiluminescent microparticle immunoassay; EOG, electrooculogram; ERG, electroretinogram; F, female; FTA-ABS, fluorescent treponemal antibody absorption; HIV, human immunodeficiency virus; HM, hand motion; ICG, indocyanine green angiography; IgG, immunoglobulin G; IgM, immunoglobulin M; IM, intramuscular; IS/OS, inner segment/outer segment; IV, intravenous; M, male; OD, right eye; OS, left eye; RPE, retinal pigment epithelium; RPR, rapid plasma reagin; TP-PA, Treponema pallidum particle agglutination; VA, visual acuity; VDRL, venereal disease research laboratory test; (+), positive test result; (−), negative test result.

SOR is characterized by the disruption of the ellipsoid zone, which is observed on OCT imaging, and a corresponding increase in fundus hyperautofluorescence in the affected areas, both of which features have been present in all the reported cases, including the one presented herein. ^{6 -11} Clinically, there is a paucity of fundus findings; of the 10 previously reported cases, 4 described the fundus examination as unremarkable, and 2 reported subtle RPE changes, as were present in our patient. ^7,8,10,11 A demarcation line, a feature that is common in AZOOR, was noted in our patient (see Figure 1, A and C), as well as in one of the previously reported cases. ^6,12 Remarkably, phlebitis, mainly within the zone of active outer retinitis, was noted in 3 of the 6 cases of SOR in which a fluoroscein angiogram was performed. ^6,7 This angiographic feature, which was also present in our patient (see Figure 1C), seems to be characteristic of SOR and may serve to differentiate it from AZOOR.^7,12

The median age of presentation for all the reported cases, including ours, was 48 years (range, 44-71 years), and 82% were male. Sixty-four percent of the cases were unilateral at presentation, although one case progressed to bilateral disease. ⁷ All patients complained of blurred vision, while 4 patients (36%), including ours, complained of photopsia. ^6,8,11 Of the 16 affected eyes, 6 (37.5%) had a VA of 20/200 or worse on presentation, and 4 eyes (25%) were 20/50 or better. Seven patients underwent visual field testing; of these, 6 had subnormal test results. ^{6 -10} The scotomas varied among the cases; however, they seemed to correspond with the area of retinal involvement. ^{6 -10}

Some less specific clinical findings have been reported in some patients with SOR. While the anterior segment examination was usually unremarkable, 2 patients had mild iritis, with 1 of them having a conjunctival injection and small keratic precipitates in the involved eye. ⁶ , ¹¹ Four eyes of 4 patients, including ours, had 1+ vitritis; notably, all of these eyes had a VA of 20/200 or worse at presentation. ^6,11 ICGA was performed in 3 patients, including ours, and all were found to have abnormal lesions. ^6,8 In 2 patients, these ICGA-detected lesions emerged in the late views as large, round areas of hypocyanescence (see Figure 1D), while 1 case had multiple hypocyanescent spots. ^6,8 Nodular thickening of the RPE (also known as drusenoid deposits) has also been described in 3 patients with SOR presenting as AZOOR, including ours (see Figure 1E).

Three patients with SOR underwent full-field electroretinography (ERG); 1 patient showed reduced a-wave and b-wave amplitudes in the combined and cone responses, whereas these amplitudes were normal in the other 2. ^6,7,10 Remarkably, one of the patients who had normal findings from a full-field ERG underwent multifocal ERG testing that revealed reduced amplitudes in the areas corresponding with the visual field defect. ¹⁰ The other patient who had normal results from a full-field ERG also had normal findings from an electrooculogram. ⁶

SOR seemed to have a favorable prognosis, as all the reported eyes had a remarkable improvement in VA following treatment. Notably, 10 of 16 eyes (63%) attained a VA of 20/20 after treatment, while all the eyes had a posttreatment VA of at least 20/40. The median follow-up for all cases was 4 months, with only 4 cases surpassing 1 year of follow-up, suggesting that most of the improvement occurred soon after the initial therapy course. ^8,11 However, 1 patient showed continued improvement of the ellipsoid zone, with its almost complete restoration by 18 months. ⁷ Another patient showed continued improvement in the visual field over 2 years of follow-up. ⁸ These 2 cases suggest that structural and functional improvements may continue to occur long after the treatment is completed. By contrast, our patient showed a persistent scotoma 3 years after therapy, suggesting that some of the damage caused by SOR may be persistent.

As with all ocular syphilis, SOR should be treated as neurosyphilis, optimally with a 2-week course of IV penicillin. ³ The recommended adult dosage is 18 to 24 million units of penicillin G per day administered IV in 3 to 4 million units every 4 hours for 10 to 14 days. ³ However, a recent study at the University of Washington of 150 individuals with neurosyphilis showed there to be no difference in clinical outcomes regardless of the route of penicillin administration. ¹³ The dosage of procaine penicillin G used for the Washington study was 2.4 U administered intramuscularly every 24 hours for 10 to 14 days, along with probenecid (0.5 g orally, 4 times daily). ¹³ Notably, 2 patients with SOR were treated successfully with IV ceftriaxone for 10 and 14 days, respectively. ^7,8 Although ceftriaxone may be a valuable alternative for treating ocular syphilis and neurosyphilis in patients who are allergic to penicillin, a failure rate of 23% has been noted, specifically in HIV-infected patients. ¹⁴

In 5 of the 11 cases of SOR, oral prednisone was used concomitantly with the antibiotic therapy. ^6,7,11 Interestingly, in 3 patients, systemic corticosteroids were prescribed prior to the syphilis diagnosis (and the antibiotic therapy) because of a high suspicion that they might be suffering from AZOOR. ^6,7 In one of the cases, VA improved from 20/160 to 20/32 while on oral prednisone only, leading the authors to theorize about the potential role of an autoimmune reaction caused by molecular mimicry in the etiology of SOR. ⁶ However, one case developed cystoid macular edema during a 14-day course of IV penicillin that resolved following a 5-week course of oral prednisone. ¹¹ This worsening of the cystoid macular edema following penicillin therapy was ascribed by the author to the release of treponemal antigens from dead organisms, such as may occur with a Jarisch-Herxheimer reaction. ¹¹ Remarkably, 6 patients did not receive systemic prednisone yet still experienced remarkable improvement, emphasizing the role of active syphilis infection in this condition. ^{6,8 -11}

SOR should be considered as a clinical entity of its own because its presentation stands out from other forms of syphilitic posterior uveitis. For instance, acute syphilitic posterior placoid chorioretinitis is characterized by the presence of 1 or more flat, yellow, outer retinal lesions that most commonly occur in the macula and are frequently associated with HIV coinfection. ¹⁵ Acute syphilitic posterior placoid chorioretinitis is also associated with anterior chamber or vitreous inflammation in most patients. ¹⁵ This contrasts significantly with the subtle RPE changes, or normal fundus appearance, that are often observed in patients with SOR. Nonetheless, HIV coinfection is common in patients with syphilis, stressing the importance of testing for HIV in patients with all types of syphilitic uveitis. ³ , ^4,15 In our review, one patient’s being diagnosed with SOR later led to him also being diagnosed with HIV, while another patient with SOR had a concomitant HIV infection. ^6,11

Conclusions

SOR is a distinct form of syphilitic posterior uveitis, and its aspects are similar to those of AZOOR. Although clinical examination typically shows subtle changes and often has normal findings, SOR’s characteristic features, such as the disruption of the ellipsoid zone and increased FAF, seemed to be universally present, as could be observed in our case. Patients with SOR appeared to respond favorably to antibiotic therapy. The role of systemic steroids in the treatment of SOR remains undetermined. However, their use did not seem to be harmful and instead appeared useful in instances of reactive inflammation following the use of parenteral antibiotics. ^6,7,11

As with all patients with uveitis, individuals suspected of having AZOOR or an AZOOR complex–associated condition should be tested for syphilis. ^{3 -5} Such testing should be performed with a treponemal-specific test, such as the fluorescent treponemal antibody absorption test or the T pallidum passive particle agglutination assay; some patients with ocular manifestations of syphilis may have negative results from a rapid plasma reagin or Venerial Disease Research Laboratory test owing to their lower sensitivity. ³ Likewise, all patients with ocular syphilis should be tested for HIV, as the conditions share multiple risk factors and coinfection is common. ^3,4,15