Frosted Branch Angiitis: Key Facts, Diagnosis, and Management

Frosted branch angiitis is a rare but serious inflammatory condition affecting the retinal blood vessels. It can lead to vision loss if not promptly identified and managed. Initially described in otherwise healthy individuals, it has also been linked to various systemic and ocular diseases.

Clinical Findings

Patients typically present with sudden, painless vision loss, often accompanied by floaters or blurred vision. The hallmark feature is the striking appearance of retinal vasculitis, where both arteries and veins exhibit a diffuse, white sheathing resembling frost-covered tree branches. This vascular inflammation is usually bilateral, though unilateral cases have been reported. Fundoscopic examination reveals widespread perivascular exudation, retinal hemorrhages, and optic disc swelling, all contributing to visual impairment.

Fluorescein angiography demonstrates significant vascular leakage, confirming active inflammation. The extent of leakage correlates with disease severity, with more pronounced cases showing extensive dye pooling. Optical coherence tomography (OCT) may reveal retinal thickening and cystoid macular edema, exacerbating visual disturbances. In some cases, vitreous cells and haze indicate concurrent vitritis, suggesting inflammation extends beyond the vasculature.

Patients may also experience mild anterior segment involvement, such as anterior chamber cells or keratic precipitates, though these are less common. Intraocular pressure is typically normal, but secondary complications like neovascularization or macular ischemia can arise in severe cases. Electroretinography (ERG) findings may show reduced amplitudes in both a- and b-waves, reflecting retinal dysfunction that can persist even after clinical resolution.

Associated Systemic And Ocular Causes

Frosted branch angiitis has been linked to various systemic and ocular conditions. Infectious etiologies include viral agents such as cytomegalovirus (CMV), Epstein-Barr virus (EBV), varicella-zoster virus (VZV), and human immunodeficiency virus (HIV), often in immunocompromised individuals. Bacterial and fungal infections, including tuberculosis and syphilis, have also been implicated, highlighting the need for thorough serologic and microbiologic testing.

Autoimmune and inflammatory disorders further expand the spectrum of associations. Conditions such as systemic lupus erythematosus (SLE), Behçet’s disease, and sarcoidosis can manifest as retinal vasculitis. In some cases, retinal findings precede systemic symptoms, making early ophthalmic evaluation crucial. Hematologic malignancies, particularly leukemia and lymphoma, have also been documented, necessitating a high index of suspicion in patients with unexplained fever, lymphadenopathy, or weight loss.

Ocular conditions associated with frosted branch angiitis include idiopathic retinal vasculitis, intermediate uveitis, and paraneoplastic syndromes. Some cases present as isolated ocular phenomena without an identifiable systemic cause, suggesting a localized inflammatory response. Ocular infections such as toxoplasmosis or viral retinitis must be differentiated from immune-mediated vasculitis. Additionally, intravitreal injections and systemic medications have been reported as potential triggers.

Immunological And Inflammatory Mechanisms

The inflammatory cascade involves a complex interplay of cellular and molecular mediators leading to widespread retinal vascular damage. The perivascular sheathing suggests a dysregulated immune response targeting the retinal vasculature. Histopathologic analyses of similar conditions reveal perivascular infiltration by lymphocytes and macrophages, indicating an immune-mediated process. Elevated levels of pro-inflammatory cytokines, such as interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α), reinforce the role of cytokine-driven endothelial dysfunction.

Endothelial activation plays a central role, as inflammatory mediators promote upregulation of adhesion molecules like intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1). These molecules facilitate leukocyte adhesion to the vascular endothelium, triggering further immune cell recruitment. The resulting disruption of the blood-retinal barrier leads to increased vascular permeability, manifesting as fluorescein leakage. Oxidative stress compounds the inflammatory insult, with reactive oxygen species (ROS) contributing to endothelial injury and vascular remodeling.

In some cases, immune complex deposition along the retinal vasculature may serve as an additional inflammatory trigger. Circulating immune complexes, formed in response to infectious or autoimmune stimuli, can deposit on vascular walls, initiating complement activation. Complement components such as C3a and C5a act as potent chemoattractants, drawing neutrophils and monocytes into the perivascular space. This complement-mediated inflammation may explain the extensive vascular involvement seen in severe cases.

Diagnostic Methods

Evaluation requires a combination of clinical assessment and advanced imaging techniques. A comprehensive ophthalmic examination is the first step, with fundoscopy revealing the characteristic diffuse vascular sheathing. The presence of perivascular exudation, hemorrhages, and optic disc swelling further supports the diagnosis. Differentiating frosted branch angiitis from infectious or neoplastic causes of retinal inflammation is a priority.

Fluorescein angiography assesses vascular integrity, often demonstrating significant dye leakage along affected vessels, indicative of endothelial dysfunction. This imaging modality helps delineate vascular involvement and can reveal areas of capillary nonperfusion, suggesting concurrent ischemia. Optical coherence tomography (OCT) frequently shows retinal thickening and cystoid macular edema, which correlate with disease severity and guide treatment decisions. Enhanced depth imaging OCT may also detect subtle choroidal involvement.

Treatment Options

Managing frosted branch angiitis requires addressing both the inflammatory process and any underlying systemic or infectious causes. Corticosteroids are the cornerstone of treatment, typically administered systemically in moderate to high doses. Oral prednisone is commonly prescribed at an initial dose of 1 mg/kg per day, with gradual tapering based on clinical response. In severe cases, intravenous methylprednisolone may be used for rapid control before transitioning to oral therapy. Close monitoring is necessary to assess response and mitigate corticosteroid-related complications such as hyperglycemia, hypertension, and osteoporosis.

For infectious cases, antimicrobial therapy is essential alongside immunosuppressive treatment. Viral-associated cases, such as those linked to cytomegalovirus or varicella-zoster virus, may require antiviral agents like ganciclovir or valganciclovir. Bacterial infections are treated with targeted antibiotic regimens. Immunomodulatory agents, such as methotrexate or mycophenolate mofetil, are considered in refractory cases, particularly when an underlying autoimmune disorder is identified. Biologic therapies, including tumor necrosis factor inhibitors or interleukin-6 antagonists, have been explored in autoimmune-associated vasculitis. Given the risk of secondary complications, adjunctive therapies such as anti-vascular endothelial growth factor (anti-VEGF) injections may be indicated for managing macular edema or neovascularization.

Prognosis

Visual outcomes depend on the severity of vascular inflammation and complications such as retinal ischemia or macular edema. Many patients experience significant improvement with prompt treatment, with reports indicating that visual acuity can recover to near-baseline levels in mild to moderate cases. However, widespread vascular occlusion or severe macular involvement can result in permanent visual impairment. Long-term follow-up is necessary to detect late complications such as epiretinal membrane formation, retinal atrophy, or recurrence.

For cases associated with systemic disease, prognosis is influenced by the underlying condition. Patients with autoimmune disorders may require ongoing immunosuppressive therapy to prevent relapse, while those with infectious causes often see resolution following appropriate antimicrobial treatment. Retinal function assessments, including electroretinography and optical coherence tomography, provide valuable insights into potential long-term sequelae. Careful monitoring and interdisciplinary collaboration between ophthalmologists, infectious disease specialists, and rheumatologists are essential to optimize outcomes and prevent recurrence.