Experts Argue for Updating Terms Describing Retinal Vasculitis

While retinal vasculitis could be solely immune-mediated, retinal vasculitis is also characteristic of a variety of active infections. In contrast, systemic vasculitis is almost always considered an immune-mediated disease. Photo: Sota J, et al. Mediators Inflamm. May 15, 2020. Click image to enlarge. Recent studies have identified a unique pattern of fundus autofluorescence (FA) leakage in intermediate uveitis, termed "fern-like leakage," resembling the one observed in retinal vein occlusion (RVO). Researchers in Milan examined the specific anatomical changes in eyes with intermediate uveitis exhibiting fern-like leakage. By comparing vascular parameters from ultra-widefield (UWF) FA between affected individuals and age- and sex-matched healthy controls, their study assessed whether these specific signs on FA correlate with morphological alterations in the retinal vasculature. It determined that "fern-like retinal vasculopathy" is a distinctive vascular pattern observed in at least some forms of intermediate uveitis. The researchers noted that recognizing these peripheral vascular changes is clinically important, as emphasizing such patterns in practice may refine treatment strategies, reduce unnecessary long-term immunosuppression and improve the management of young adults affected by this condition.1This retrospective, observational case series, which was published in American Journal of Ophthalmology, followed 43 eyes (28 patients) with intermediate uveitis (mean age 31 years, 58% female) for an average of 18 months, compared with 41 healthy control eyes. Ultra-widefield fluorescein angiography (UWF-FA) images were analyzed. Vessel length density, fractal dimension and branchpoints density were compared across different leakage extents (posterior pole/diffuse [Zone 1], mid-periphery [Zone 2] and far periphery [Zone 3]).Early-phase UWF-FA revealed substantial alterations in study eyes, including dilated capillary channels, reduced capillary branching, delayed venous filling and telangiectatic post-capillary dilations, primarily in non-perfused regions. Eyes with intermediate uveitis showed significantly lower VLD, FD and BPD than controls, particularly in the far peripheral retina, with the most pronounced reductions in eyes with diffuse leakage (Zone 1). Negative correlations were observed between these vascular metrics and enlarged foveal avascular zone areas, suggesting a potential association between peripheral and macular perfusion. Fern-like leakage persisted with reduced intensity despite immunosuppression; some vascular changes progressed, while others, such as non-perfusion and neovascularization, showed possible reversibility.“Our focus on the far and mid-periphery revealed distinctive patterns of vascular rarefaction in affected eyes. These patterns go beyond the physiological nonperfusion seen in healthy subjects,” the researchers wrote in their paper. “While intermediate uveitis primarily involves the vitreous and pars plana, peripheral retinal involvement is also frequently observed, as ischemic and inflammatory damage can extend to this region.”Together, these histopathological observations underscored how inflammation may lead to chronic venous dysfunction and vascular remodeling, providing a plausible explanation for the peripheral vascular rarefaction described in this cohort.“Our research indicates that these changes are not solely indicative of active uveitis but may persist even after the initiation of immunosuppressive therapy,” the researchers concluded. “This observation highlights the need for a more nuanced approach to treatment, suggesting that detecting this pattern does not automatically justify escalated therapeutic interventions.”1The diagnosis of retinal vasculitis mistakenly implies to many internists, rheumatologists and some eyecare professionals that systemic vasculitis is likely to be present. An editorial in American Journal of Ophthalmology emphasized that, “The authors’ observations add to the understanding of this association while reminding us of the challenge to distinguish vasculitis, characterized by active inflammation involving the vessel wall, from noninflammatory forms of vasculopathy within the retina.”2The editorial authors noted that The International Uveitis Study Group has appointed a team of experts to derive classification criteria for retinal vasculitis by identifying clinical or imaging findings associated with a disease and assigning each item a numerical value, with higher values indicating a greater likelihood of discriminating between the target disease and other diagnoses.They highlighted that, “objective and reproducible criteria with face validity should distinguish non-inflammatory retinal vasculopathy from true retinal vasculitis. In addition, retinal vasculitis in association with an active intraocular infection must be clearly identified so that the underlying infection is treated.”2Click here for the journal source. 1. Cicinelli MV, Barresi C, Ziafati M, et al. Fern-like retinal vasculopathy in intermediate uveitis: pathogenesis, natural history and clinical implications. Am J Ophthalmol. May 12, 2025. [Epub ahead of print].2. Rosenbaum JT, Rojas-Carabali W, Cifuentes-González C, et al. The terms retinal vasculopathy and retinal vasculitis require clarification. Am J Ophthalmol. May 16, 2025. [Epub ahead of print].