Syphilis is a sexually transmitted disease caused by the Gram-negative spirochete Treponema pallidum. With effective antibiotic treatment, its incidence had reduced, even though there has recently been a resurgence of the disease coinciding with the new era of the human immunodeficiency virus (HIV) coinfection.1–4 Ocular involvement occurs most often during the secondary and tertiary stages of syphilis, although it has been reported at all stages of the disease.5 The most common ocular manifestation is represented by chorioretinitis.6 Gass et al. coined the term “acute syphilitic posterior placoid chorioretinitis (ASPPC)” to describe a large, yellowish, circular, or oval placoid lesion at the level of the retinal pigment epithelium (RPE), typically located in the macular area.2 Fluorescein angiography (FA), indocyanine green angiography (ICGA), and spectral-domain optical coherence tomography (SD-OCT) provide useful information regarding the pathologic processes of this condition.2–10
We present a multimodal imaging analysis of a case of ASPPC occurring in a 51-year-old man who was unaware of being affected by syphilis.
A 51-year-old Caucasian man reported a sudden decrease of visual acuity (VA) in his right eye (OD). Best-corrected VA (BCVA) was 0.5 and 0.8 OD and in the left eye (OS), respectively. SD-OCT revealed the absence of intraretinal or subretinal fluid but showed the disruption of the inner segment/outer segment (IS/OS) junction associated with thickening and granular irregular hyperreflectivity of the RPE and loss of the external limiting membrane (ELM) (Figure 1). Fundus autofluorescence (FAF) showed hyperautofluorescent areas corresponding to the irregularity of the RPE observed in the SD-OCT scans (Figure 2). FA revealed central hypofluorescence in the early stages followed by progressive hyperfluorescence in the area of the lesion in the mid- and late-phases (Figures 3A and 3B). ICGA showed hypofluorescent areas in the early stages corresponding to the lesion of SD-OCT; this hypofluorescence persisted in the late stages, as well (Figures 4A and 4B). All of these findings were suggestive of the diagnosis of ASPPC. Interestingly, the patient was unaware of being affected by syphilis. Serological tests confirmed the diagnosis of syphilis but excluded the presence of anti-HIV antibodies. The patient received intravenous penicillin G at a dosage of 24 million units per day for 14 days. In addition, oral prednisone (1 mg/kg/day, gradually tapered) was given to decrease the infection-induced inflammation within the retina. At 1 month, BCVA improved to 0.7 in the affected eye. SD-OCT scans showed complete restoration of the IS/OS junction and the normalization of the contour of the RPE layer, whereas FAF showed the persistence of hyperautofluorescent areas (Figures 5A and 5B). At 3 months, SD-OCT images confirmed the complete morphologic restoration of the outer retinal layers, and FAF returned to normal (Figures 6A and 6B). ICGA showed the disappearance of hypofluorescent areas in the early stages, whereas in the late stages, there was a marked decrease of hypofluorescent areas detected 3 months before (Figures 7A and 7B). The final BCVA was 1.0 OD and 0.9 OS.
Spectral-domain optical coherence tomography imaging showing the disruption of the inner segment/outer segment junction associated with thickening and granular irregular hyperreflectivity of the retinal pigment epithelium and loss of the external limiting membrane.
Fundus autofluorescence imaging showing hyperautofluorescent areas corresponding to the irregularity of the retinal pigment epithelium observed in the spectral-domain optical coherence tomography scans.
(A, B) Fluorescein angiography revealing a central hypofluorescence in the early stages (A) followed by a progressive hyperfluorescence in the area of the lesion in the mid- and late-phases of examination (B).
(A, B) Indocyanine green angiography showed hypofluorescent areas in the early stages corresponding to the lesion of spectral-domain optical coherence tomography (A). This hypofluorescence persisted also in the late stages of the examination (B).
(A, B) At 1 month from presentation, spectral-domain optical coherence tomography scans showed complete restoration of the inner segment/outer segment junction and normalization of the contour of the retinal pigment epithelium layer (A); fundus autofluorescence showed the persistence of hyperautofluorescent areas (B).
(A, B) At 3 months from presentation, spectral-domain optical coherence tomography images confirmed the complete morphologic restoration of the outer retinal layers (A); moreover, fundus autofluorescence returned to normal appearance (B).
(A, B) Indocyanine green angiography revealing in the early stages of examination the disappearance of hypofluorescent areas (A); the late stages demonstrated a marked decrease of hypofluorescent areas detected 3 months before (B).
ASPPC is an uncommon ocular manifestation of syphilis characterized by the development of one or more large, deep, yellowish circular or oval placoid lesions at the level of the posterior pole. Particularly, these lesions involve the outer retinal layers (ORLs), including the RPE, and rarely extend beyond the temporal vascular arcades.
SD-OCT imaging revealed the disruption of the IS/OS junction and of the ELM, associated with thickening and granular irregular hyperreflectivity of the RPE. These morphological findings are typical characteristics of ASPPC, as assessed by Pichi et al., who described similar outer retinal abnormalities in 30 eyes of 19 patients on SD-OCT scans 1 week after presentation. Differing from our case, Pichi et al. found in 13 of the 30 eyes a small amount of subretinal fluid under the fovea 1 or 2 days after presentation. Interestingly, no ELM disruption was observed at this early stage in these 13 eyes, and subretinal fluid spontaneously resolved in each of the eyes. Similarly to our case, vision improved and all abnormalities reversed after treatment of neurosyphilis in most of the patients.
Brito et al. described SD-OCT features in a single patient with ASPPC; they found, together with anatomical abnormalities of ORLs, a diffuse choroidal infiltration associated with reduction of the diameter, and a number of the usual vascular spaces 1 day after presentation.9 This choroidal pattern was slightly improved, and stratification of the ORLs after 2 weeks was completely restored with only an oral treatment with dexamethasone and amoxicillin due to a throat inflammation. Interestingly, our case did not show this acute choroidal alteration.
FAF imaging showed hyperautofluorescent areas corresponding to the irregularity of the RPE observed in the SD-OCT scans. These features are probably due to an accumulation of lipofuscin or incomplete phagocytosis of outer segments, as previously assessed by Spaide et al.11 Other authors have explained such hyperautofluorescence as a result of an accumulation of fibrin, platelets, and inflammatory cellular debris.12,13 Angiographic findings consisted of an early central hypofluorescence followed by a progressive hyperfluorescent staining in the late stages on FA. ICGA demonstrated hypofluorescent areas in the early stages corresponding to the lesion of SD-OCT and FAF that persisted also in the late stages of the examination. This hypofluorescence could be explained by a local choroidal hypoperfusion or by blockage of the choroidal fluorescence due to the overlying infected RPE.
Some reports have suggested an association between ASPPC and HIV infection,14–16 even though a few cases were reported in immunocompetent individuals, similarly to our patient.17,18 Moreover, Eandi et al. did not find any difference in the clinical characteristics or in the long-term visual outcome in HIV-positive versus HIV-negative patients in a large cohort of cases of ASPPC.19 Hence, although HIV coinfection is common in patients affected with ASPPC and testing the presence of anti-HIV antibodies is useful, it seems not to modify the clinical presentation and the prognosis of disease.
Finally, it is noteworthy that initiation of systemic penicillin therapy leads to a rapid improvement of VA associated with restoration of outer retinal and choroidal anatomy, as already described by some authors.12 Moreover, a corticosteroid treatment tapered over a period of at least 1 month seems to be useful to reduce the immune reaction related to T. pallidum.
In conclusion, ASPPC is a rare manifestation of syphilis that has some distinctive anatomical characteristics that are detectable early on with SD-OCT, FAF, and angiographic examinations. As shown in our case, ASPPC could be the first manifestation of syphilis, and for this reason, ophthalmologists have an important role in the detection, diagnosis, and treatment of this disease, also considering that adequate therapy results in good visual recovery.
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