Eales Disease: Pathology, Symptoms, and Treatment Approaches

Eales disease is a rare, idiopathic condition that primarily affects the retinal blood vessels, leading to inflammation, vascular changes, and potential vision loss. It typically occurs in young adults, more commonly in males. While the exact cause remains unclear, immune-mediated mechanisms and environmental factors are suspected contributors. Early detection is crucial, as progression can lead to severe complications such as vitreous hemorrhage or retinal detachment.

Understanding the pathological changes and clinical manifestations of Eales disease is essential for effective diagnosis and management.

Retinal Exudation And Inflammation

Retinal exudation and inflammation play a central role in disease progression, often serving as early indicators of vascular dysfunction. The inflammatory process primarily affects the peripheral retina, where perivascular infiltration of inflammatory cells damages vessel walls and increases permeability. This disruption allows plasma proteins, lipids, and immune mediators to leak into surrounding tissue, forming exudates that impair retinal function. Fluorescein angiography frequently reveals areas of vascular leakage, highlighting the extent of exudation.

As inflammation persists, exudates accumulate, leading to retinal thickening and localized edema that compromise visual acuity. Hard exudates, composed of lipid and protein deposits, are often observed in the mid-peripheral retina, while soft exudates, or cotton-wool spots, indicate localized ischemia due to capillary occlusion. These changes exacerbate retinal hypoxia, creating a cycle of inflammation and vascular damage. Optical coherence tomography (OCT) provides detailed cross-sectional views of these exudative changes, aiding in assessment and treatment response.

The breakdown of the blood-retinal barrier (BRB) further amplifies inflammation. Inflammatory cytokines such as vascular endothelial growth factor (VEGF) and tumor necrosis factor-alpha (TNF-α) become upregulated, promoting vascular permeability and worsening exudation. This inflammatory cascade increases the risk of secondary complications, including neovascularization and hemorrhagic events. Anti-inflammatory therapies, such as corticosteroids, have been explored to mitigate these effects, though their long-term efficacy remains under investigation.

Retinal Vascular Changes

Eales disease is characterized by distinct alterations in the retinal vasculature, primarily affecting the peripheral retinal veins. Periphlebitis, marked by inflammation and sheathing of the retinal veins, leads to segmental or diffuse narrowing. As the disease progresses, venous occlusions may develop, disrupting blood flow and contributing to retinal ischemia. This triggers pathological processes that further compromise vascular integrity. Fluorescein angiography reveals areas of capillary non-perfusion, guiding clinical management.

Ischemic insult from vascular occlusion promotes compensatory but pathological responses, including collateral vessel formation and neovascularization. These fragile, newly formed vessels are prone to rupture, increasing the likelihood of recurrent vitreous hemorrhages. Unlike stable retinal vasculature, these aberrant vessels lack proper endothelial tight junctions, making them highly permeable and prone to leakage, leading to intraocular hemorrhages. Over time, fibrovascular membranes may exert traction on the retina, increasing the risk of retinal detachment.

The severity and extent of vascular involvement dictate therapeutic interventions. Panretinal photocoagulation (PRP) aims to reduce ischemia-driven neovascularization by selectively ablating non-perfused retinal areas. This decreases angiogenic factor production and stabilizes vascular structures, reducing hemorrhagic risk. In cases where extensive neovascularization has led to vitreous hemorrhage, pars plana vitrectomy may be necessary to clear the opacified vitreous and restore vision.

Potential Contributing Factors

The development of Eales disease appears to be influenced by genetic predisposition, environmental exposures, and systemic conditions affecting retinal vascular health. While no single gene has been definitively linked, familial clustering suggests a hereditary component. Variants in genes associated with vascular stability and endothelial function, particularly those involved in angiogenesis and oxidative stress regulation, may contribute to susceptibility. Genetic polymorphisms affecting VEGF expression, implicated in other retinal vascular disorders, could play a role.

Environmental factors may also contribute. High-altitude hypoxia, particularly in individuals residing in mountainous regions, has been suggested as a potential trigger. Hypoxic conditions induce retinal ischemia, leading to compensatory vascular changes. Additionally, chronic exposure to air pollution, particularly fine particulate matter (PM2.5), has been linked to systemic vascular inflammation, which could predispose individuals to retinal vascular dysfunction. While direct evidence connecting pollution to Eales disease is limited, the broader link between environmental toxins and vascular health warrants further study.

Metabolic disorders such as insulin resistance and dyslipidemia may exacerbate endothelial dysfunction. Elevated lipid levels impair vascular integrity, increasing the likelihood of retinal vessel abnormalities. Some studies have noted an association between abnormal lipid metabolism and retinal exudation, a hallmark feature of Eales disease. Hyperhomocysteinemia—an independent risk factor for vascular disease—has also been observed in some patients with retinal vasculitis, suggesting that elevated homocysteine levels could aggravate vascular inflammation.

Immune-Related Processes

The immune system plays a significant role in the pathophysiology of Eales disease, with evidence suggesting an aberrant immune response targeting the retinal vasculature. T-cell–mediated mechanisms, particularly delayed-type hypersensitivity reactions, are implicated in disease progression. Elevated levels of circulating immune complexes and increased expression of pro-inflammatory cytokines such as interferon-gamma (IFN-γ) and TNF-α indicate a sustained inflammatory response contributing to vascular injury.

Autoimmune mechanisms have also been considered, with studies identifying anti-retinal antibodies in some patients. These autoantibodies may initiate an immune attack on retinal structures, compounding vascular damage. Similarities between Eales disease and autoimmune-mediated vasculitides, such as Behçet’s disease, suggest overlapping immunopathological features. While direct causation has not been established, shared pathways with systemic autoimmune disorders remain an area of interest.

Ocular Manifestations And Vision Changes

The impact of Eales disease on vision depends on the extent and location of retinal involvement. Early stages may be asymptomatic, but as vascular inflammation and ischemic changes progress, symptoms such as floaters, blurred vision, or sudden disturbances due to vitreous hemorrhages can occur. These hemorrhages, resulting from fragile neovascular vessels rupturing, range from mild opacities to dense bleeding that significantly impairs vision. Patients may report transient visual obscurations that fluctuate in severity depending on hemorrhagic resorption. In severe cases, recurrent bleeding can lead to prolonged impairment, requiring surgical intervention.

Long-term complications, including tractional retinal detachment and macular involvement, pose significant threats to vision. As fibrovascular proliferation advances, contractile forces exert traction on the retina, potentially leading to detachment if untreated. When the macula is affected, central vision deteriorates, impacting daily activities such as reading and recognizing faces. Persistent retinal ischemia can also contribute to optic disc pallor and secondary atrophic changes, further reducing visual acuity. While treatments such as laser photocoagulation and vitrectomy can stabilize or improve vision, irreversible damage may occur if intervention is delayed. Early recognition of symptoms and timely treatment are critical in preserving visual outcomes.