From white dot syndromes to primary inflammatory choriocapillaropathies (PICCPs): updating and expanding the spectrum through multimodal imaging.

BACKGROUND: The term "white dot syndromes" (WDS) has historically been used as a descriptive label to encompass a heterogeneous group of inflammatory chorioretinal disorders characterized by multifocal whitish fundus lesions. Although clinically convenient, this classification relied predominantly on ophthalmoscopic appearance and fluorescein angiography findings and failed to identify the primary anatomical site of inflammation or the underlying pathogenic mechanisms. Consequently, profoundly disparate entities-such as acute posterior multifocal placoid pigment epitheliopathy (APMPPE), diffuse unilateral subacute neuroretinitis (DUSN), and HLA-A29 birdshot retinochoroiditis, among others-were inappropriately grouped together despite fundamentally different immunological substrates and target tissues.

METHODS: This narrative review revisits the historical evolution of the WDS concept and synthesizes evidence derived from multimodal retinal and choroidal imaging, including fundus autofluorescence, indocyanine green angiography, optical coherence tomography, and optical coherence tomography angiography, to identify shared pathogenic mechanisms and clinically relevant distinctions among them.

RESULTS: Advances in multimodal imaging over the past two decades have substantially reshaped the understanding of these disorders, demonstrating that a subset of conditions previously classified as WDS share a common pathogenic mechanism characterized by primary inflammatory ischemia of the choriocapillaris, with secondary involvement of the outer retina and retinal pigment epithelium. These findings support grouping these disorders under the concept of primary inflammatory choriocapillaropathies (PICCPs). Conventionally, this group includes APMPPE, idiopathic multifocal chorioretinitis, relentless placoid chorioretinitis, and serpiginous choroiditis (SC). Multiple evanescent white dot syndrome (MEWDS) is likewise included, although its pathophysiology remains debated, particularly regarding whether the primary target is the choriocapillaris or the photoreceptors. MEWDS is included in this review given the clinical and imaging overlap with classical PICCPs. Another rare entity that shares overlapping clinical and imaging features with SC-known as persistent placoid maculopathy (PPM)-may also be considered within this spectrum.

CONCLUSION: This paper revisits the concept of PICCPs, which more accurately reflects the underlying pathophysiology of this group of disorders than the outdated WDS classification. Emphasis is placed on the role of multimodal imaging in refining disease classification, assessing disease activity and reversibility of ischemic injury, and guiding therapeutic decision-making. We also propose extending the PICCPs spectrum to include PPM. Adoption of a mechanism-based framework has important clinical implications for diagnosis, management, and prognosis.