Man presents with unilateral decreased vision

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A 30-year-old man presented to the New England Eye Center for decreased vision with a central black spot in his vision for 1 week. He denied flashes, floaters, pain and headache.

His ocular history was significant for high myopia without history of eye surgery or trauma. His medical history included mild asthma. He was a daily cigarette smoker and was sexually active with one female partner for the past 3 years. He had no history of intravenous drug use. He did not have any other symptoms, including skin changes or joint pain.

Examination

Christine Benador-Shen
Christine Benador-Shen
Malgorzata Dymerska Peterson
Malgorzata Dymerska Peterson

Visual acuity was finger counting at 2 feet in the right eye and 20/30 in the left eye. The right eye had an afferent pupillary defect while the left was briskly reactive to light with no afferent pupillary defect. IOPs were 12 mm Hg in the right eye and 13 mm Hg in the left eye. Confrontation visual fields showed a central scotoma in the right eye while the left was full. Extraocular movements were normal in both eyes.

Anterior segment exam of both eyes was unremarkable with no anterior chamber cell or keratic precipitates. In the right eye, there was optic disc edema, a yellow-white placoid-appearing lesion encompassing the macula, and small white dots centrally and along the inferior arcade (Figure 1a). There were no vitreous cells or opacities. Autofluorescence showed hyperautofluorescence corresponding to the placoid lesion, with small circular dots of hypoautofluorescence within the larger lesion and inferiorly (Figure 1b). Fundus exam and autofluorescence of the left eye were normal (Figures 1c and 1d).

color fundus and Autofluorescence
Figure 1. Color fundus photo of the right eye (a) shows disc edema and a yellow-white placoid-appearing macular lesion with small white dots centrally and along the inferior arcade. Autofluorescence of the right eye (b) demonstrates hyperautofluorescence corresponding to the placoid lesion, with speckled hypoautofluorescence most inferiorly. The left retina is normal with no lesions (c and d).

Source: Christine Benador-Shen, MD, and Michelle C. Liang, MD

OCT of the macula
Figure 2. OCT of the macula in the right eye (a) reveals diffuse ELM and photoreceptor disruption with subretinal deposits. OCT imaging of the left eye (b) is unremarkable.

OCT of the macula in the right eye showed diffuse external limiting membrane (ELM) and photoreceptor disruption with subretinal deposits (Figure 2a). The left macular OCT was unremarkable (Figure 2b). Fluorescein angiography (FA) of the right eye showed early hypofluorescent spots in the inferonasal macula and scattered smaller hyperfluorescent lesions throughout the macula. Late frames showed inferotemporal vasculitis and disc leakage (Figure 3). OCT showed diffuse retinal nerve fiber layer (RNFL) thickening of the right eye and normal measurements in the left eye (Figure 4).

FA of the right eye
Figure 3. FA of the right eye shows early hypofluorescent spots in the inferonasal macula and scattered smaller hyperfluorescent lesions throughout the macula. Late frames demonstrate inferotemporal vasculitis and disc leakage.
OCT of both eyes
Figure 4. OCT of both eyes with an average RNFL thickness of 146 µm in the right eye and diffuse edema. The left eye is normal.

What is your diagnosis?

See answer below.

Decreased vision

Our patient was diagnosed with acute syphilitic posterior placoid chorioretinitis (ASPPC). The differential diagnosis of a yellow-white placoid chorioretinal macular lesion with outer retinal loss, vasculitis and optic nerve edema includes inflammatory, infectious and autoimmune etiologies.

ASPPC is most likely in this patient due to the classic circular macular lesion and outer retina disruption with retinal pigment epithelium (RPE) thickening on OCT. Inflammatory etiologies that may cause similar white lesions include multiple evanescent white dot syndrome (MEWDS), acute posterior multifocal placoid pigment epitheliopathy (APMPPE) and persistent placoid maculopathy (PPM). In contrast to this presentation, these etiologies often follow a flu-like illness and present with smaller, less diffuse lesions than seen in our patient. MEWDS can also present with significant photoreceptor disruption but is more multifocal and less placoid in appearance. There is classically wreath-like hyperfluorescence on FA. APMPPE also presents with multiple smaller lesions compared with our patient. It is often bilateral, although it can present asymmetrically, and OCT will show hyperreflectivity of the outer retina in the acute phase with more photoreceptor and RPE atrophy in the later phases. PPM can have similar white lesions in the posterior pole, but they are usually not well-defined like the discrete circular lesion in our patient, and the lesions tend to avoid the peripapillary area. Serpiginous and tuberculosis serpiginous-like choroiditis, primary toxoplasmosis and sarcoid posterior uveitis could also be considered but are less likely.

Our patient’s lab workup included treponemal antibody with reflex RPR, angiotensin converting enzyme, lysozyme and QuantiFERON Gold. Treponemal antibody was positive with a reactive RPR of 1:64. Sarcoid and tuberculosis tests were negative. The patient was admitted to the hospital for treatment of neurosyphilis with penicillin G 4 million units IV every 4 hours. He also had a lumbar puncture with reactive CSF VDRL 1:16. He was negative for HIV coinfection.

Discussion

ASPPC is one manifestation with characteristic features that are unique to syphilitic uveitis. In ASPPC, Treponema pallidum is thought to spread hematogenously to the choroidal circulation, leading to choriocapillaris and overlying RPE and outer retinal inflammation. Forty percent to 60% of patients have a concomitant diagnosis of HIV.

The severity of vision loss in ASPPC varies greatly, ranging from 20/20 to no light perception in a literature review of 44 patients. In a study of 16 patients, 56% presented with bilateral chorioretinal lesions. On examination, the typical retinal lesion is circular, yellow-white and usually centered on the macula. Multiple lesions may be present within one eye. Anterior chamber inflammation or vitritis may be present, as well as other findings of ocular syphilis such as periphlebitis or optic disc edema, as in our patient. It is important to perform a thorough social history and review of systems to evaluate the patient for exposure risks as well as systemic symptoms of syphilis, such as presence of a chancre, rash, or cardiac and neurologic symptoms.

The diagnosis of ASPPC is made based on its characteristic appearance on biomicroscopy as well as typical imaging findings. OCT through the lesion demonstrates loss or discontinuity of the IS/OS junction as well as focal areas of RPE thickening forming small nodular lesions. The ELM may also be disrupted, as in our patient. Some patients have a small amount of transient submacular fluid on presentation. Autofluorescence shows hyperautofluorescence in the area of the placoid lesion with overlying stippled hypoautofluorescence. Fluorescein angiography demonstrates early hypofluorescence and late staining. A characteristic pattern called “leopard spotting” refers to the speckled hyper- and hypofluorescence in late frames. Indocyanine green angiography shows hypocyanescence in the area of the placoid lesion.

Confirmation of syphilitic infection is performed using a combination of nontreponemal and treponemal tests. If a placoid retinal lesion is identified and there is high suspicion for ocular syphilis, treponemal testing (FTA-ABS, TPPA or TP-EIA) followed by nontreponemal testing (RPR or VDRL) should be performed. Positive CSF VDRL is confirmatory for neurosyphilis, and the titer can be followed for treatment response.

ASPPC is treated as neurosyphilis: penicillin G 3 million units to 4 million units IV every 4 hours for 10 to 14 days. In patients who may have late or late latent syphilis, some infectious disease specialists recommend an additional one to three weekly intramuscular doses of penicillin G benzathine 2.4 million units. Topical corticosteroids may be used in the treatment of intraocular inflammation, while oral corticosteroids may be considered in cases of concurrent cystoid macular edema, vasculitis or optic nerve edema. Associated choroidal neovascular membranes have been reported and can be treated with anti-VEGF therapy.

In most cases, the outer retina recovers after treatment with the above regimen. In one study of 30 eyes with ASPPC, 93.3% of eyes had normalization of the outer retinal complex 1 month after treatment with penicillin, along with improvement of visual acuity. The eyes that had 20/200 vision after treatment also had persistent disruption of the IS/OS junction, RPE and ELM. The high rate of recovery highlights the importance of quick recognition of ASPPC and initiation of treatment.

Fundus photograph and OCT macula
Figure 5. Fundus photograph and OCT macula of the right eye over the course of 6 weeks after treatment. The patient had slow improvement of the placoid lesion in the right macula as well as partial recovery of the IS/OS junction with decrease in the density of nodular RPE lesions on OCT.

Clinical course continued

Our patient received a total of 16 days of intravenous penicillin followed by one dose of intramuscular penicillin because the onset of syphilis infection was unknown. Two weeks after his initial presentation, the patient’s vision was still finger counting with some recovery of the outer retinal layers on OCT (Figure 5). Repeat FA at this visit demonstrated persistent vasculitis and leakage from the optic nerve. He was started on oral prednisone 40 mg daily with a slow taper over several weeks. His vision improved to 20/200 in the right eye 6 weeks after presentation with resolution of optic nerve edema and continued improvement of the ellipsoid zone on OCT.