Proposing a Neurotropic Etiology for Acute Posterior Multifocal Placoid Pigment Epitheliopathy and Relentless Placoid Choroidopathy

Abstract

Purpose : Controversy currently exists over the underlying pathology in acute posterior multifocal placoid pigment epitheliopathy (APMPPE) and the related condition, relentless placoid chorioretinitis (RPC). We performed a retrospective case series imaging evaluation to reassess the clinical signs and current etiological hypotheses for these conditions.

Methods : Cases were identified from three tertiary uveitis centers in the UK between 2016 and 2020. We defined APMPPE using the following criteria: 1) The appearance of >1 creamy chorioretinal lesion; and 2) Evidence of choriocapillaris hypoperfusion, and; 3) An OCT appearance in keeping with the two described phenotypes. We defined RPC as fulfilling criteria 1-3 but with a clinical course exceeding 60 days and greater than 50 lesions. Qualitative comparative analysis of available multimodal imaging modalities was conducted. Serial imaging afforded the opportunity to analyse preclinical changes in eyes with sequential involvement.

Results : A total 14 patients (9 with bilateral disease) met the diagnostic criteria. 10 patients (17 eyes) had features consistent with APMPPE. 4 patients (6 eyes) had features consistent with RPC. 7/14 patients were female. Median age at presentation was 26.5 years (range, 20-57 years). Changes within the retinal nerve fiber layer precede the occurrence of clinical lesions and associated choriocapillaris hypoperfusion. Optic disc edema occurs proportionally to the extent of retinal lesions, and mirrors the sectoral distribution, suggesting an associated disruption of axoplasmic flow. Areas of choriocapillaris hypoperfusion correspond to zones of separation of the overlying retinal pigment epithelium (RPE) from Bruch’s membrane (BM). Transient, hyperreflective foci occur within the outer nuclear layer above the area of RPE/BM separation during acute lesions, and follow the neurons which constitute the Henle’s fiber layer orientation. Pathological disruption of retinal layers (following the initial RPE/BM separation) occurs in a descending sequence with ONL/ellipsoid zone disruption preceding the loss of RPE structure.

Conclusions : Our evidence suggests a primary neuronal pathogenesis with a descending progression through the retina, as opposed to a primary disorder of the choriocapillaris.

This is a 2021 ARVO Annual Meeting abstract.