Non-infectious posterior and panuveitides (NIPUs) comprise a heterogeneous group of inflammatory disorders of the outer retina and choroid, historically referred to as "white dot syndromes." Recent consensus efforts by the Multimodal Imaging in Uveitis (MUV) Task Force have established standardized diagnostic criteria for the major NIPUs, including multiple evanescent white dot syndrome (MEWDS), multifocal choroiditis and panuveitis/punctate inner choroiditis (MFCPU/PIC), acute posterior multifocal placoid pigment epitheliopathy (APMPPE), serpiginous choroiditis, and birdshot chorioretinopathy (BSCR). Nevertheless, a substantial proportion of cases deviate from classical presentations and fall into diagnostic "grey zones", blurring boundaries between diseases entities and complicating both differential diagnosis and management. This review aims to describe the broad spectrum of atypical, variant, and secondary forms of NIPUs as well as masquerade syndromes. Atypical MEWDS includes bilateral presentations or complicated courses, while MFCPU/PIC with outer retinal atrophy emerges as a notable entity with unclear therapeutic implications. Inflammatory reactions resembling both MEWDS and MFCPU/PIC may also occur as secondary phenomena, triggered by other chorioretinal disorders, most notably inherited retinal diseases (IRDs). Placoid chorioretinopathies, including APMPPE, persistent placoid maculopathy, serpiginous choroiditis, and relentless placoid chorioretinitis, are often distinguished only a posteriori based on disease course, but likely represent a continuum of disorders unified by choroidal ischemia. Atypical presentations of BSCR may feature extensive outer retinal damage, mimicking IRDs. Equally important is the consideration of masquerade syndromes in all suspected cases of NIPUs, as they can present with similar features yet require entirely different treatments. Infectious masquerades include tuberculosis-associated serpiginous-like choroiditis, acute syphilitic posterior placoid chorioretinopathy, and West Nile virus chorioretinitis, whereas vitreoretinal lymphoma is the most frequent neoplastic masquerade. In conclusion, integrating clinical context with high-quality multimodal imaging remains essential to navigate the jungle of differential diagnosis in NIPUs, while future studies should aim to link imaging phenotypes with immune and molecular biomarkers to refine classification and guide targeted therapies.

To describe clinical and multimodal imaging features of patients with Acute Posterior Multifocal Placoid Pigmented Epitheliopathy (APMPPE) and identify distinctive characteristics guiding in the differentiation between APMPPE and other placoid conditions (non-APMPPE). Retrospective single-center observational study of all patients diagnosed with APMPPE in the Uveitis Service of Moorfields Eye Hospital between 2002 and 2022. Sixty patients with presumed APMPPE at presentation were included, of whom 37 had a confirmed diagnosis of APMPPE, and 23 received a different diagnosis (non-APMPPE) during the follow-up. Non-APMPPE included ampiginous choroiditis (6 patients), idiopathic multifocal choroiditis (5 patients), tubercular multifocal choroiditis (5 patients), serpiginous choroiditis (1 patient), tubercular serpiginous-like choroiditis (3 patients), sarcoidosis (2 patients) and persistent placoid maculopathy (1 patient). Compared to non-APMPPE, APMPPE was more commonly observed in individuals of white ethnicity (p = 0.025), had shorter duration of symptoms (11.3 days, p = 0.02) and was associated with a viral prodrome (p < 0.001). APMPPE course was more commonly non-relapsing compared to non-APMPPE (p = 0.02), although relapses were observed in 18.9% of APMPPE cases. Mean final BCVA was significantly better in the APMPPE group (p = 0.04). Subfoveal choroidal thickness at presentation and final visit was significantly greater in APMPPE compared to non-APMPPE (p < 0.001), both in the eyes affected and fellow eyes that became affected later. In addition to the established clinical features and multimodal imaging characteristics, ethnicity, duration of symptoms, viral prodrome and subfoveal choroidal thickness can add useful information in guiding physicians in differentiating APMPPE from other mimicking placoid conditions.

Persistent placoid maculopathy is a rare clinical entity defined as idiopathic bilateral chorioretinopathy. We report four different clinical presentations of this pathology. Case 1: A 63-year-old man presented with a persistent bilateral central scotoma. Persistent placoid maculopathy was diagnosed based on ophthalmological manifestations and multimodal imaging. A history of scalp tenderness and jaw claudication a week before visual symptoms was reported associated with increased C-reactive protein. A temporal artery biopsy confirmed the diagnosis of giant cell arteritis. Despite corticosteroid treatment, complete macular chorioretinal atrophy followed. Case 2: A 65-year-old woman was referred for bilateral blurred vision for one month. Visual acuity was 20/20 in both eyes and multimodal imaging confirmed the diagnosis of persistent placoid maculopathy. The patient was lost to follow-up due to the COVID-19 pandemic and presented one year later with decreased vision in the left eye of 20/200. Type 2 choroidal neovascularization was observed and treated with sub-tenon triamcinolone injection followed by intravitreal injection of Aflibercept allowing an improvement in visual acuity. Case 3: A 61-year-old man presented with sudden loss of vision in his right eye. A large submacular hemorrhage was observed on the right eye and hypopigmented white/yellowish plaque-like macular lesions on the other eye. Surgery with pneumatic displacement and intravitreal injection of Aflibercept was performed. No improvement in visual acuity was observed. Five months later, the contralateral eye was complicated by choroidal neovascularization and required intravitreal injections. Case 4: A 49-year-old man receiving immunosuppressive therapy after liver transplant was referred for bilateral decreased vision. The diagnosis of persistent placoid maculopathy was made, and corticosteroid treatment was initiated. After three months, chorioretinal lesions decreased and vision recovered. We report the first case series of clinical presentations of persistent placoid maculopathy, which expand upon the reported ocular manifestations of this condition.

To report eight cases of acute posterior multifocal placoid pigment epitheliopathy (APMPPE) or persistent placoid maculopathy (PPM) initially masquerading as age-related macular degeneration in elderly individuals. APMPPE or PPM eyes in patients above age 55 years with macular retinal pigment epithelium disruption including drusenoid lesions on macular examination and/or with multimodal imaging were included. At least one method of multimodal imaging including fluorescein angiography (FA), indocyanine green angiography, optical coherence tomography (OCT), and OCT angiography (OCTA) was performed in all eyes for diagnosis and to monitor for macular neovascularization. Eight elderly male patients presented with vision loss and were all initially diagnosed with non-neovascular or neovascular age-related macular degeneration. With the aid of multimodal retinal imaging, a final diagnosis of either APMPPE or PPM was rendered. With FA and indocyanine green angiography, choroidal hypoperfusion was detected in all but one eye. With OCT, the angular sign of Henle fiber layer hyperreflectivity was identified in >50% of eyes. With OCTA, inner choroidal flow deficits were detected in all eyes. Macular neovascularization requiring anti-vascular endothelial growth factor injection therapy complicated three of eight cases. Both APMPPE and PPM may develop in elderly individuals and may masquerade as age-related macular degeneration on presentation. Multimodal imaging including FA, indocyanine green angiography, and OCTA are important diagnostic modalities to assess for inner choroidal hypoperfusion to arrive at an accurate diagnosis and to detect macular neovascularization, which frequently complicates APMPPE and PPM. In these patients, serial anti-vascular endothelial growth factor intravitreal injections are essential in treating macular neovascularization and in preventing significant vision loss.

To report the novel imaging findings in persistent placoid maculopathy (PPM) from the first case series of Asian subjects. Retrospective observational case series. Patients with PPM from 2013 to 2023. Medical records and multimodal images from each visit were analyzed. Imaging and follow-up findings. Twenty-one eyes of 16 patients were included. Mean age was 61 (range, 48-84) years old. Five patients showed bilateral involvement. Persistent placoid maculopathy lesions were unremarkable on color fundus photography, autofluorescence, and fluorescein angiography. Hypofluorescent spots with a lichen-like appearance presented in all phases of indocyanine green angiography, which were most prominent in the late phase and presented in a fused (71%) or clustered (29%) pattern. The hypofluorescence correlated with the lesions between the retinal pigment epithelium (RPE) and Bruch's membrane (BM) with moderate reflectivity on OCT, and the thickness ranged from slit-like to mound-like. The intensity of hypofluorescence sometimes varied in the same eye and correlated with the thickness of sub-RPE lesions on OCT. No abnormal blood flow signals were detected in either the sub-RPE space or choriocapillaris slab of OCT angiography across the PPM lesions. Peripapillary (5 eyes, 24%) and extra posterior pole (2 eyes, 10%) involvements were seen, the former sparing the β zones of optic discs. Ten eyes of 7 patients were followed up (median, 26 months; range, 2-121 months). During follow-up, the lichen-like lesions spread and migrated slowly without changing the plane patterns of the first visit and were limited to sub-RPE growth. The fused lichen-like pattern sprawled around the enlarged base. The clustered lichen-like pattern gradually loosened. Ten eyes (48%, 9 eyes in the fused pattern, 1 eye in the clustered pattern) had secondary choroidal neovascularization (CNV) at the first visit, with type I (6 eyes, 5 of which were polypoidal choroidal vasculopathy) and type II (4 eyes). No new CNV developed during follow-up. Persistent placoid maculopathy lesions were located in the sub-RPE space, as determined by multimodal imaging. Spreading and migration between the RPE and BM may account for their unique lichen-like appearance and progression pattern. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.