Long-term multimodal imaging in acute posterior multifocal placoid pigment epitheliopathy and association with coxsackievirus exposure

Abstract

The purpose of this study was to evaluate potential insights into the pathogenesis of acute posterior multifocal placoid pigment epitheliopathy (APMPPE) using multimodal diagnostic imaging and laboratory evaluation in long-term follow-up. A retrospective, single-center case series was conducted on seven consecutive patients (14 eyes) who were given a diagnosis of APMPPE from March 1, 2011, through June 30, 2019 with at least three months of follow-up. Clinical characteristics (age, symptoms, visual acuity [VA]), laboratory testing including coxsackievirus titers, and multimodal imaging from fundus photography, spectraldomain optical coherence tomography (SD-OCT), fundus autofluorescence (FAF), fluorescein angiography (FA), and indocyanine green angiography (ICG) were analyzed for each patient. The initial median VA was 20/71 and final median VA was 20/22. Coxsackievirus B (CVB) titers were elevated (� 1:80) in six of seven patients, with a four-fold increase in convalescent titers seen in two patients suggestive of recent infection. All patients were treated with oral corticosteroids, and five patients underwent corticosteroid-sparing immunomodulatory therapy. Initially, multifocal deep choroidal lesions were observed in the posterior pole corresponding to patches of hypocyanescence on ICG. Overlying retinal pigment epithelium (RPE) disease was observed on FAF, although this finding was not universally observed, suggesting that RPE disease may occur as a sequelae to unchecked choroidal inflammation. SD-OCT architectural changes confirmed outer retina and ellipsoid zone disruption. FA of active lesions showed early hypofluorescence and late hyperfluorescence with surrounding leakage while inactive disease showed areas of staining. Long-term follow-up of multimodal diagnostic imaging in APMPPE revealed that choroidal inflammation likely precedes RPE change and photoreceptor damage. Elevation of coxsackievirus titers with seroconversion may be associated with an infectious trigger in concert with immune-mediated disease in this posterior uveitis syndrome.

Choroidal Vascular Changes in Acute Idiopathic Maculopathy as Demonstrated by Multimodal Imaging including Optical Coherence Tomography Angiography

“…Acute idiopathic maculopathy is a rare, self-limited, macular disease disproportionately affecting young men [ 1 ]. It has been postulated that AIM exists on a spectrum of acute multifocal placoid pigment epitheliopathy (APMPPE) [ 5 ] and our case illustrates this point. The lesions in APMPPE clinically appear yellow-white and may have a complex outer boundary due to confluence of smaller lesions.…”

Unilateral acute posterior multifocal placoid pigment epitheliopathy in a convalescent COVID-19 patient

“…Its cause has not been clearly elucidated yet since the incidence of these syndromes is very low. However, Coxsackie antibody titers in acute and treated cases seem to correlate in some series [16].…”

“…Using multimodal imaging in APMPPE, some authors have found choroidal inflammation as a preceding and necessary factor for RPE, and subsequent damage in cones [16]. This choroidal inflammation may be generated solely by the entry of SARS-CoV-2 via the angiotensin-converting enzyme 2 receptor (ACE) in the endothelium.…”

Acute posterior multifocal placoid pigment epitheliopathy (APMPPE)

“…APMPPE lesions show initial hypoautofluorescence corresponding to the hyper-reflectance of the outer retinal layers on SD-OCT, likely secondary to its masking effect (Fig. 3 A) [55]. A progressive increase in hyperautofluorescence is observed later on in the course of the disease when outer retinal findings progress to disruption of the RPE layer, with a mixed pattern of hypoautofluorescence and hyperautofluorescence (Fig.…”

“…A progressive increase in hyperautofluorescence is observed later on in the course of the disease when outer retinal findings progress to disruption of the RPE layer, with a mixed pattern of hypoautofluorescence and hyperautofluorescence (Fig. 3 B) [55,56]. Later in the disease course, a more homogenous hypoautofluorescent pattern suggesting focal areas of photoreceptors/RPE atrophy might develop [55,56].…”