Seeing the Invisible: New Global Consensus on Using Advanced Imaging to Track Uveitis Activity

Introduction and Context

Non-infectious posterior uveitis (NIPU) represents a complex spectrum of inflammatory ocular diseases that primarily affect the retina, choroid, and vitreous. For decades, clinicians have relied on the Standardization of Uveitis Nomenclature (SUN) criteria, established in 2005, to assess disease activity. However, the SUN criteria were largely based on clinical examination findings, such as the presence of inflammatory cells in the aqueous humor or vitreous. As our understanding of ocular anatomy has evolved, it has become increasingly clear that traditional slit-lamp examinations alone often fail to capture the full extent of sub-retinal or choroidal inflammation.

The emergence of multimodal imaging (MMI)—including Optical Coherence Tomography (OCT), Fluorescein Angiography (FA), Indocyanine Green Angiography (ICGA), and Fundus Autofluorescence (FAF)—has revolutionized the way ophthalmologists view the posterior segment. Despite these advancements, there has been a lack of standardized definitions for what constitutes “active” versus “inactive” disease on an image. To address this, the Multimodal Imaging in Uveitis (MUV) Taskforce was established. Their latest publication, Report 10, provides a definitive framework for using imaging measures to assess disease activity in NIPU, offering a bridge between clinical observation and objective data.

New Guideline Highlights

The primary objective of the MUV Taskforce’s Report 10 was to categorize specific imaging features into three distinct buckets: Suggestive of Active Disease (SAD), Suggestive of Inactive Disease (SID), or Equivocal (findings that require further study or are currently inconclusive). The report focused on five major NIPU entities:

• Vogt-Koyanagi-Harada (VKH) disease
• Birdshot Chorioretinopathy
• Serpiginous Choroiditis
• Multifocal Choroiditis (MFC)
• Placoid Disorders

By defining these parameters, the task force aims to standardize outcomes for both routine clinical care and future clinical trials, ensuring that “remission” and “flare” are defined by more than just subjective vitreous cell counts.

The Consensus Process: Methodology

The task force employed a rigorous mixed-methods design using the Nominal Group Technique (NGT). This involved an expert committee reviewing previous recommendations from MUV subcommittees. A total of 49 imaging statements were deliberated over two rounds of structured voting. This methodical approach ensured that the recommendations were not just based on individual opinions but represented a broad, international expert consensus.

Topic-by-Topic Recommendations

The consensus identified 21 imaging features as SAD and 12 as SID. Below are the core recommendations categorized by imaging modality and clinical implication.

1. Optical Coherence Tomography (OCT)

OCT remains the workhorse of NIPU assessment. The task force highlighted several key biomarkers:

• Suggestive of Active Disease (SAD): The presence of subretinal fluid (SRF), intraretinal fluid (IRF), or a “bacillary layer detachment”—a specific type of retinal separation often seen in VKH—is a strong indicator of active inflammation.
• Suggestive of Inactive Disease (SID): Retinal thinning, loss of the ellipsoid zone (EZ), and the presence of subretinal fibrosis (scarring) without fluid are hallmarks of inactive, chronic stages.

2. Fluorescein Angiography (FA) and ICGA

While OCT looks at structure, FA and ICGA look at blood flow and vascular integrity.

• Active Indicators: Leakage from the optic disc, retinal vascular leakage (vasculitis), and “hot” or hyperfluorescent spots in the choroid during the late phase of ICGA suggest ongoing disease.
• Inactive Indicators: “Staining” of a scar without progressive leakage and stable, well-defined hypofluorescent spots that do not change over time indicate quiescent disease.

3. Fundus Autofluorescence (FAF)

FAF is particularly useful for assessing the health of the Retinal Pigment Epithelium (RPE).

• Active Indicators: A “fuzzy” hyperautofluorescent border around a lesion often suggests that the inflammation is creeping into new, healthy tissue.
• Inactive Indicators: A well-demarcated area of “hypoautofluorescence” (darkness), signifying RPE atrophy or a mature scar, is suggestive of inactive disease.

Key Recommendations Table

Category	Imaging Feature (SAD)	Imaging Feature (SID)
Retinal Structure	Subretinal fluid, Bacillary detachment	Subretinal fibrosis, RPE atrophy
Vascularity	Active vascular leakage, Disc edema	Vascular staining (no leakage)
Choroidal Health	Fuzzy ICGA spots, Choroidal thickening	Stable hypofluorescent spots

A Patient Vignette: Applying the Consensus

Consider “Sarah,” a 38-year-old teacher diagnosed with Vogt-Koyanagi-Harada (VKH) disease. Under the old SUN criteria, if Sarah’s eyes showed no cells in the vitreous, she might be considered in remission. However, Sarah complains of persistent “dimming” in her vision. Using the new MUV Taskforce recommendations, her ophthalmologist performs an Enhanced Depth Imaging (EDI) OCT. The scan reveals significant choroidal thickening and a small pocket of subretinal fluid—both classified as SAD (Suggestive of Active Disease). Despite the lack of cells on a clinical exam, the imaging confirms the disease is still active, leading to an adjustment in her immunosuppressive therapy to prevent permanent vision loss.

Expert Commentary and Insights

The MUV Taskforce experts emphasized that while imaging is powerful, it must be used in conjunction with clinical judgment. A key area of controversy and discussion involved the 16 “equivocal” statements. These included features like certain patterns of hyper-reflective dots on OCT or subtle changes in autofluorescence that could either represent early activity or slow-healing tissue.

Dr. Aniruddha Agarwal, a lead author, noted that the goal of Report 10 is to “extend the SUN work through the integration of additional multimodal imaging information.” The panel agreed that as imaging technology—such as OCT Angiography (OCTA)—continues to mature, many of these equivocal features will eventually be reclassified as either active or inactive.

Practical Implications

For clinicians, these guidelines mean that the definition of “treatment success” is shifting. It is no longer enough to achieve a “quiet eye” on examination; clinicians should aim for the resolution of active imaging biomarkers. For the pharmaceutical industry and researchers, these standardized measures provide clear, objective endpoints for clinical trials testing new biologics or steroid-sparing agents.

Ultimately, Report 10 represents a major step toward precision medicine in ophthalmology. By standardizing the language of imaging, the MUV Taskforce ensures that a uveitis specialist in London, Tokyo, or New York can look at the same scan and reach the same conclusion regarding a patient’s disease status.

References

1. Agarwal A, Ramtohul P, Invernizzi A, et al. Imaging Measures for the Assessment of Disease Activity in Non-Infectious Posterior Uveitis – Multimodal Imaging in Uveitis (MUV) Taskforce: Report 10. American Journal of Ophthalmology. 2026. PMID: 41861898.
2. Jabs DA, Nussenblatt RB, Rosenbaum JT; Standardization of Uveitis Nomenclature (SUN) Working Group. Standardization of uveitis nomenclature for reporting clinical data. Results of the First International Workshop. Am J Ophthalmol. 2005;140(3):509-516.
3. Invernizzi A, Agarwal A, et al. The Multimodal Imaging in Uveitis (MUV) Initiative: A Roadmap for Standardizing Imaging Outcomes. Ophthalmology. 2023.