Eales disease was first reported in 1880 by the British ophthalmologist Henry Eales as recurrent vitreous hemorrhage in healthy young men. It is an idiopathic occlusive retinal vasculitis characterized by peripheral retinal phlebitis, vascular occlusion, and neovascularization.
The incidence varies greatly by region. It is rare in North America, but relatively common in areas with high tuberculosis infection rates such as India, the Middle East, and Asia 1). It predominantly affects men in their 20s to 30s, with a male-to-female ratio of about 20:1. Up to 87% of cases are bilateral 1).
It is a diagnosis of exclusion, confirmed after ruling out other retinal vasculitis, systemic diseases, and diabetes.
It is very rare in North America, but relatively common in tuberculosis-endemic regions such as India and the Middle East 1). The male-to-female ratio is about 20:1, with a strong male predominance, and up to 87% of cases are bilateral.
In the early stage, the disease is often asymptomatic, and there are no subjective symptoms during the peripheral phlebitis phase. As the disease progresses, the following symptoms appear.
Eales disease progresses through three stages: inflammatory, ischemic, and proliferative1).
Inflammatory Stage
Peripheral periphlebitis: White sheathing along peripheral retinal veins. Perivascular inflammatory cell infiltration.
Retinal hemorrhages: Punctate and flame-shaped hemorrhages in the periphery.
Venous leakage on FA: Active inflammation can be confirmed on fluorescein angiography.
Ischemic Stage
Capillary nonperfusion: Formation of extensive nonperfused areas in the periphery.
Arteriovenous shunts: Compensatory vascular changes in response to ischemia.
Venous beading: Alternating irregular dilation and constriction of veins.
Proliferative Stage
Neovascularization (sea-fan like): Proliferative new vessels arising adjacent to ischemic areas.
Vitreous hemorrhage: Recurrent bleeding due to rupture of new vessels.
Tractional retinal detachment (TRD): Traction caused by fibrovascular proliferative membranes. It can also lead to mixed retinal detachment, neovascular glaucoma, cataract, and optic atrophy4).
The Saxena classification subdivides the disease into 7 stages from Ia to IVb. Ia/Ib: peripheral phlebitis; IIa: ischemia/non-perfusion; IIb: neovascularization; IIIa/IIIb: degree of vitreous hemorrhage; IVa/IVb: extent of TRD.
Macular edema is observed in 58.2% of cases4) and is an important complication directly linked to visual prognosis.
Fluorescein angiography (FA) can evaluate venous leakage in active inflammation, wall staining in the chronic sclerotic phase, and the extent of non-perfusion areas.
The cause is unknown and considered idiopathic, but a hypersensitivity reaction to tuberculous protein is the most likely etiological theory.
PCR for Mycobacterium is reported positive in 50–70% of cases of epiretinal membrane, but the bacteria are not detected by culture 3). The pathogenesis is thought to be an immunological hypersensitivity reaction to non-viable bacteria or DNA fragments, rather than direct infection by live bacteria. Therefore, combination therapy with anti-tuberculosis drugs is recommended in patients with a positive Mantoux test.
Eales disease is a diagnosis of exclusion. The diagnosis is confirmed after excluding other retinal vasculitides and systemic diseases 1).
The main examination findings are shown below.
| Test Item | Purpose / Conditions to Exclude |
|---|---|
| QuantiFERON / Mantoux | Evaluation of tuberculosis infection |
| ANA / ANCA / anti-dsDNA antibody | SLE / Vasculitis |
| Serum ACE / Lysozyme | Sarcoidosis |
| Blood glucose / HbA1c | Diabetic retinopathy |
| Blood tests (CBC, coagulation) | Sickle cell disease, coagulation abnormalities |
| Syphilis serology / Lyme disease | Infectious vasculitis |
Differential diagnoses include diabetic retinopathy, branch retinal vein occlusion (BRVO), Coats disease, sarcoidosis, SLE, sickle cell retinopathy, and Behçet’s disease1)4).
It is a diagnosis of exclusion, made after ruling out systemic diseases such as diabetes, sarcoidosis, and SLE through blood tests and imaging1). Fluorescein angiography (FA) is the most important test, confirming peripheral periphlebitis, non-perfusion areas, and neovascularization.
Treatment is selected according to disease stage. Main treatments by stage are shown below.
| Stage | Main treatment | Adjuvant treatment |
|---|---|---|
| Inflammatory phase | Oral steroids | ATT (if Mantoux positive) |
| Ischemic phase | Retinal photocoagulation (PRP) | Anti-VEGF injection |
| Proliferative phase | Vitrectomy and photocoagulation | Anti-VEGF injection |
Oral steroids are the first-line treatment. A regimen starting with prednisone 40 mg/day and gradually tapering is used 1). There is also a report of achieving a final visual acuity of 20/20 with dexamethasone 1 mg/kg/day tapered over 4 months 4). A large study by Biswas et al. (500 patients, 898 eyes) showed that steroid administration during the acute inflammatory phase significantly improved visual acuity 2)4).
For cystoid macular edema (CME), intravitreal injection of dexamethasone implant (Ozurdex) is effective 2).
For patients with a positive Mantoux test, antitubercular drugs are added. A regimen of RIPE (rifampicin, isoniazid, pyrazinamide, ethambutol) for 4 months, followed by isoniazid alone for 5 months, for a total of 9 months, is used 2)3). The international consensus (COTS guidelines) serves as a reference for the ATT initiation algorithm when tuberculosis infection is suspected 2).
With early and appropriate treatment, a good visual prognosis can be expected. There are reports of maintaining 20/20 vision for 33 years after vitrectomy 2). On the other hand, delayed treatment can lead to tractional retinal detachment, neovascular glaucoma, cataract, and optic atrophy 4).
The pathology of Eales disease is understood as a stepwise progression starting from peripheral periphlebitis 1)2).
Stage 1 (Inflammation): Inflammatory cell infiltration and periphlebitis occur along the peripheral retinal veins. PCR for Mycobacterium tuberculosis is positive in 50–70% of epiretinal membranes, but cultures do not detect the bacteria 3). It is thought that non-viable organisms or DNA fragments activate the host immune system, causing reactive inflammation 1).
Stage 2 (Ischemia): Inflammation-induced vascular wall damage leads to thrombus formation and vascular occlusion. Capillary non-perfusion areas expand, and ischemia progresses.
Stage 3 (Neovascularization): Large amounts of VEGF are secreted from the ischemic retina 3). In addition to VEGF, high concentrations of IL-6, IL-8, and MCP-1 are detected in the vitreous, forming a sustained loop of pathological neovascularization and inflammation 3). Sea-fan-shaped neovascularization appears at the border of ischemia, and repeated bleeding from fragile new vessels occurs.
Eales disease and tuberculosis-related retinal vasculitis (TRV) are clinically almost indistinguishable, and it has been suggested that they may be on a spectrum 2).
Cocaine promotes thrombus formation through vasoconstriction and endothelial damage, and may act as an immunological trigger 4). Heterozygosity for the factor V Leiden mutation increases thrombotic risk approximately 7-fold and is a genetic risk factor for vascular occlusion 4).
International consensus guidelines (COTS) are organizing the management algorithm for TRV (tuberculosis-related retinal vasculitis) 2). Eales disease and TRV have been treated as separate diseases, but their boundary is being reconsidered, and the continuity of clinical features and etiology is being discussed 2).
Cases have been reported where aflibercept was used for Eales disease refractory to ranibizumab, maintaining 20/25 after 43 months and 20/20 with repeated administration every 3 months for 28 months 3). This is the first case report of aflibercept use for Eales disease, and by simultaneously binding VEGF-A, VEGF-B, and PlGF, it may be effective in cases resistant to existing anti-VEGF drugs 3).
New risk factors such as cocaine abuse and factor V Leiden mutation have been identified in individual cases 4), and further elucidation of immunological and genetic predispositions is expected in the future.
