An international expert panel established consensus definitions for retinal vasculitis and related vascular conditions, emphasizing that vascular leakage alone is insufficient to diagnose retinal vasculitis and that diagnosis should instead integrate evidence of intraocular inflammation, retinal vascular abnormalities, and/or retinal damage attributable to inflammatory involvement of the vessel wall.

The modified Delphi consensus study, published in JAMA Ophthalmology, was designed to address inconsistent use of retinal vasculitis terminology across ophthalmology and other specialties. Ophthalmologists may interpret fluorescein leakage as evidence of retinal vasculitis, whereas rheumatologists, internists, neurologists, and other nonophthalmic specialists generally reserve the term vasculitis for conditions defined by inflammatory injury to the vessel wall.

The authors said this divergence in terminology has contributed to persistent inconsistencies in the description, classification, and clinical interpretation of retinal vascular inflammation. The International Uveitis Study Group developed the consensus process after a literature review that generated seven peer-reviewed publications, including systematic reviews, meta-analyses, a scoping review, an international survey on diagnostic and management practices in retinal vasculitis, and a commentary addressing terminology gaps.

The panel included 27 international specialists in ophthalmology, rheumatology, pathology, imaging, and research methodology. Five members involved in developing the preliminary definitions did not vote, leaving 22 independent experts who completed both Delphi rounds. Participants anonymously rated statements on a 5-point Likert scale and provided free-text comments.

Consensus was predefined as agreement by at least 75% of respondents after neutral responses were excluded from the calculation. All 10 core statements exceeded the consensus threshold in the first round, with agreement ranging from 83% for the definition of noninfectious retinal vasculitis to 96% for the retinal vasculitis definition. However, variation in the strength of endorsement and requests for clearer wording prompted a second round. After revisions, agreement on the refined statements ranged from 95% to 100%, producing 8 final consensus definitions.

Defining Retinal Vasculitis

The panel defined retinal vasculitis as a group of diseases characterized by inflammation of retinal blood vessels, with infiltration of arteriolar, venular, and/or capillary walls by inflammatory cells, accompanied by retinal damage. Because histopathological confirmation is rarely feasible, the diagnosis is clinical and is based on evidence of intraocular inflammation together with retinal vascular abnormalities and/or retinal damage attributable to inflammatory involvement of the vessel wall.

Supportive findings can include inflammatory vascular sheathing, anterior chamber inflammation, vitreous cells or haze, and optic disc hyperfluorescence on fluorescein angiography, but the panel cautioned that these findings are not independently diagnostic of retinal vasculitis. Retinal damage may include retinal capillary nonperfusion, vascular occlusion, retinal hemorrhages, ischemic changes, infarction, or other structural retinal abnormalities attributable to inflammatory vascular injury.

The panel also acknowledged that inflammation may precede overt structural retinal injury. The distinction between vasculitis and vascular leakage was central to the framework. Vascular leakage was defined descriptively as fluorescein leakage on angiography. Such leakage can result from retinal vasculitis, inflammation in adjacent structures, or hydrostatic factors without vessel wall damage and therefore should not independently establish a vasculitis diagnosis.

Separating Related Vascular Conditions

The consensus framework also defines infectious retinal vasculitis as retinal vasculitis occurring in the presence of confirmed or presumed infectious etiology and noninfectious retinal vasculitis as retinal vasculitis occurring in the absence of confirmed or presumed infectious etiology. Primary retinal vasculitis refers to inflammation that meets the criteria for retinal vasculitis but occurs without any identifiable infectious or systemic association.

Retinal perivasculitis, in contrast, refers to inflammation localized to the perivascular tissues adjacent to retinal vessels, without infiltration or destruction of the vessel wall.

Retinal vasculopathy describes vascular abnormalities affecting the retinal vessels that are presumed not to result from retinal vasculitis or perivasculitis. Features may include areas of retinal capillary nonperfusion, microaneurysms, intraretinal hemorrhages, leakage, or nonperfusion. Retinal vasculopathy may occur as an isolated ocular disease or as part of systemic conditions such as coagulopathies, metabolic disorders, drug-induced vascular injury, or other vascular diseases.

The panel did not reach consensus on classifying Susac syndrome as either retinal vasculitis or retinal vasculopathy. Although limited neuropathologic evidence suggests the systemic disease may represent vasculitis, the retinal manifestations were considered less clearly defined, leading the group to leave the condition unassigned pending additional pathophysiologic and imaging research.

The experts also cautioned against overinterpreting far-peripheral findings on ultra-widefield fluorescein angiography. Loss of capillary detail, terminal capillary network leakage, and ground-glass hyperfluorescence can occur incidentally in normal eyes and mimic retinal vasculitis, requiring correlation with the broader clinical context and other imaging.

Limitations and Next Steps

The authors noted that the definitions reflect expert consensus rather than direct empirical or histopathologic validation and remain dependent on the perspectives of invited specialists. Distinguishing retinal vasculitis from retinal perivasculitis, isolated vascular leakage, or noninflammatory vasculopathy may remain difficult, particularly early in disease or when ischemic or structural damage is absent. No single imaging modality currently provides definitive confirmation of retinal vasculitis in all situations.

The framework also has not been prospectively validated in research or routine practice. The authors called for studies assessing reproducibility, clinical applicability, and interobserver reliability across diverse patient populations and imaging platforms. They said standardized terminology could eventually support more consistent clinical trial reporting as well as development of imaging biomarkers and artificial intelligence-based diagnostic approaches.

For physicians interpreting retinal imaging, the central message of the consensus is captured in the panel's recommendation that "vascular leakage alone is insufficient to diagnose retinal vasculitis." Instead, the authors proposed a framework intended to distinguish leakage, perivascular inflammation, and true vessel wall disease while recognizing that the definitions will require validation and may evolve as imaging and biological understanding advance. RP