Beyond White Dot Syndromes: Multimodal Imaging Redefines Six Posterior Uveitis Entities

Study design: Expert taskforce perspective review integrating published evidence and multimodal imaging observations, not an interventional study or a systematic meta-analysis. Scope: Six noninfectious posterior uveitis entities historically labeled white dot syndromes: MEWDS, multifocal choroiditis with panuveitis (MFCPU), punctate inner choroiditis (PIC), acute posterior multifocal placoid pigment epitheliopathy (APMPPE), serpiginous choroiditis (SC), and birdshot chorioretinitis (BSCR). Imaging: Structural OCT, OCT angiography (OCTA), indocyanine green angiography (ICGA), fundus autofluorescence (FAF), and fluorescein angiography (FFA). Principal thesis: Similar-appearing pale fundus lesions conceal distinct anatomical patterns and potentially different mechanisms of injury; a disease-specific nomenclature is more informative than a single white-dot umbrella.

Historically, white dot syndromes grouped inflammatory diseases by the appearance of white, cream, or yellow lesions on fundus examination. The MUV Taskforce argues that shared appearance does not establish shared pathogenesis. The review focuses on six entities for which Standardization of Uveitis Nomenclature classification criteria and MUV imaging guidance exist. The authors report that nearly 90% of surveyed uveitis experts regarded the terminology as outdated, while acknowledging its continued widespread use. The paper proposes a conceptual change rather than a formally validated replacement classification.

• MEWDS: Predominant photoreceptor and RPE alterations, including ellipsoid-zone disruption, with Bruch’s membrane and choriocapillaris generally appearing preserved.
• MFCPU and PIC: Hyperreflective material extending from the inner choroid into the outer retina with focal Bruch’s membrane disruption; lesion size and distribution help distinguish the two clinical entities.
• APMPPE: Outer retinal and RPE injury with an intact Bruch’s membrane and abnormalities of the underlying choriocapillaris; Henle fiber layer hyperreflectivity may occur.
• Serpiginous choroiditis: Changes involving the choriocapillaris and deeper Sattler’s layer, with preservation of Bruch’s membrane during active lesions and subsequent choroidal atrophy/scarring.
• Birdshot chorioretinitis: Deep choroidal hyporeflective infiltrates with relative preservation of overlying choriocapillaris and outer retinal structures at the lesion site, especially early; inner retinal perivasculitis can coexist.

The side-by-side OCT illustrations in Figure 2 emphasize that lesion depth, Bruch’s membrane integrity, and choroidal layer involvement are more discriminating than the visible white lesion itself.

OCTA depicts relatively preserved choriocapillaris flow in typical MEWDS lesions, localized flow abnormalities in MFCPU/PIC, marked choriocapillaris flow deficits in APMPPE, deeper choroidal involvement in SC, and reduced deep choroidal signal in BSCR. However, OCTA cannot by itself separate primary occlusion from flow displacement or secondary impairment.

ICGA temporal behavior adds pathophysiological context: APMPPE lesions tend to become increasingly hypofluorescent, consistent with marked choriocapillaris hypoperfusion. Active SC lesions can resemble APMPPE, but inactive SC may retain late hypofluorescence consistent with severe choriocapillaris loss. MFCPU/PIC lesions can become less hypofluorescent as dye enters inflammatory infiltrates, favoring a mass-effect interpretation rather than complete vascular occlusion. Birdshot lesions remain moderately hypofluorescent into late phases, possibly reflecting deep, non-granulomatous choroidal infiltration with partial dye diffusion. In MEWDS, late ICGA hypofluorescence has competing interpretations, including RPE dysfunction and subtle choriocapillaris perfusion abnormalities; the debate is not fully settled.

In MEWDS, increased FAF may reflect transient photopigment dysfunction and can diminish after photobleaching, supporting a potentially reversible outer retinal process. APMPPE and SC can progress from increased to decreased FAF as RPE injury and atrophy develop. MFCPU/PIC may show central hypoautofluorescence with a hyperautofluorescent rim in active lesions, progressing to hypoautofluorescent scars. FAF is less specific for the primary deep choroidal lesions of birdshot.

FFA remains useful for retinal vascular leakage and blood–retinal barrier assessment, particularly in birdshot. The authors also discuss visual field recovery in MEWDS and electroretinographic abnormalities in birdshot, but functional assessments were not comprehensively evaluated in this perspective.

The authors suggest that MEWDS may involve transient outer retinal/RPE inflammation, possibly following an infectious trigger; MFCPU/PIC may involve sustained antigen exposure associated with structural breaks or degenerative changes; APMPPE may involve an inflammatory occlusive process targeting the choriocapillaris; SC may reflect a broader choroidal ischemic and immune-mediated process; and BSCR may involve HLA-A29-associated immune susceptibility affecting choroid and inner retina.

Important distinction: These are proposed mechanisms, not experimentally proven causal pathways. The review explicitly recognizes competing interpretations, the potential for infectious mimics (including tubercular serpiginous-like choroiditis), and uncertainty about triggers and antigenic targets.

• Classify patients using the full pattern of lesion location, Bruch’s membrane integrity, OCTA flow distribution, ICGA phase behavior, and retinal vascular involvement rather than fundus appearance alone.
• Interpret an OCTA flow deficit alongside structural OCT and dye angiography before labeling a lesion as primarily ischemic.
• Recognize that different conditions carry different risks of tissue loss and functional impairment; imaging features should inform disease-specific assessment and follow-up.
• Keep infectious and inflammatory mimics in the differential diagnosis, particularly when serpiginous-like lesions occur in atypical distributions.

This paper does not compare treatment strategies or demonstrate that adopting a new nomenclature improves patient outcomes. Its contribution is chiefly diagnostic and conceptual.

This is a narrative expert perspective, not a controlled comparison of diagnostic algorithms. Mechanistic conclusions are inferred largely from imaging and prior literature rather than direct experimental verification. Only six historically grouped disorders were addressed; the authors explicitly exclude AZOOR, acute macular neuroretinopathy, relentless placoid chorioretinitis, persistent placoid maculopathy, and acute idiopathic blind-spot enlargement syndrome. Functional testing was not explored in depth. The review therefore supports a more anatomically precise framework, but should not be presented as proof of disease etiology or as a validated replacement classification.

The MUV Taskforce recommends moving away from a single appearance-based white dot syndromes category toward separate disease entities characterized by their anatomical targets, vascular findings, and plausible mechanisms of inflammation. The most practical message is to read multimodal imaging as a pattern of tissue injury—not merely as confirmation of the presence of white spots.