EVEREST study report 3: diagnostic challenges of polypoidal choroidal vasculopathy. Lessons learnt from screening failures in the EVEREST study

PURPOSE: To describe screening failures in the EVEREST study by examining the imaging characteristics that enabled differentiation of polypoidal choroidal vasculopathy (PCV) from cases that were subsequently diagnosed not to be PCV. METHODS: Post-hoc analysis of 34 patients with PCV reported as screening failures from EVEREST study. Standardised confocal scanning laser indocyanine green angiography (ICGA) images were graded by the Central Reading Centre to confirm PCV diagnosis based on the presence of early focal sub-retinal hyperfluorescence on ICGA and at least one of the following six diagnostic criteria: (1) nodular appearance of polyp(s) on stereoscopic examination, (2) hypofluorescent halo around nodule(s), (3) presence of a branching vascular network, (4) pulsation of polyp(s) on dynamic ICGA, (5) orange sub-retinal nodules on colour fundus photography, or (6) massive sub-macular haemorrhage (≥4 disc areas in size). Additional detailed image grading was performed with stereo-imaging and dynamic early-phase ICGA. RESULTS: Of the 95 screened PCV cases, 34 were excluded: (1) cases not suitable for recruitment as per the study protocol (n = 14), (2) equivocal lesions on ICGA characterised by small hyperfluorescent dots (n = 9), and (3) cases that were definitely not PCV (non-PCV, n = 11), identified by definitive diagnoses which included one case each of micro-aneurysm, retinal angiomatous proliferation, retino-choroidal anastomosis, small type-2 choroidal neovascularisation, retinal pigment epithelial (RPE) window defect and disciform scar; two cases of lesions where the choroidal vessel changed its course; and three cases of late-onset RPE staining. CONCLUSIONS: Standardised image grading techniques used in EVEREST study enabled effective differentiation of non-PCV from actual PCV. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1007/s00417-016-3333-y) contains supplementary material, which is available to authorized users.