Fern-Like Retinal Vasculopathy in Intermediate Uveitis: Pathogenesis, Natural History, and Clinical Implications

Purpose: To investigate peripheral vascular changes and their progression in intermediate uveitis characterized by a fern-like leakage pattern and examine their relationship with macular vascular changes to elucidate their pathogenesis, natural history, and clinical implications. Design: Retrospective, observational case series with healthy-eyes comparison. Participants: 43 eyes (28 patients) with intermediate uveitis (mean age 31±16 years, 58% female) followed for an average of 18 months, compared with 41 healthy control eyes. Methods: Ultra-widefield fluorescein angiography (UWF-FA) images were analyzed. Vessel Length Density (VLD), Fractal Dimension (FD), and Branchpoints Density (BPD) were compared across different leakage extents (posterior pole/diffuse[Zone 1], mid-periphery[Zone 2], and far periphery[Zone 3]) and control eyes using linear mixed-effects models. The foveal avascular zone (FAZ) was manually traced. Mean outcome measures: Qualitative retinal changes and quantitative measures of VLD, FD, and BPD across 3 concentric temporal retina sectors. Results: 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](interaction p-values: 0.04 for VLD, 0.007 for FD, and 0.045 for BPD). Negative correlations were observed between these vascular metrics and enlarged FAZ areas, suggesting a potential association between peripheral and macular perfusion (all p < 0.05). Fern-like leakage persisted with reduced intensity despite immunosuppression; some vascular changes progressed, while others, such as non-perfusion and neovascularization, showed possible reversibility. Conclusion: This study identifies “Fern-Like Retinal Vasculopathy” as a distinctive vascular pattern observed in at least some forms of intermediate uveitis, characterized by chronic vascular remodeling. 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.