Like many other retinal vasculopathies, an early diagnosis of Eales disease is essential for immediate treatment and to avoid further visual damage. These groups of diseases show similar signs and symptoms upon examination.¹

Eales' disease: overview

Eales’ disease causes inflammation in the retinal blood vessels for reasons we don’t know, and is mostly seen in individuals aged between 14 and 35 years. The disease has a course of three overlapping stages, impacting the retina (the thin inner lining of the eyeball), inflammation in veins (vasculitis), blockage of healthy blood vessels, and formation of abnormal blood vessels in the retina. Consequently, the disease is characterised by recurrent haemorrhage in the vitreous part of the eye, leading to sudden vision loss. Frequency-wise, Eales' disease is more prevalent in males, but it can impact all sexes. Geographically, it is common in South Asia and the subcontinent when compared to the rest of the world.¹

Clinical relevance

Eales’ disease is clinically important because it causes extreme visual problems that can reappear multiple times, and it can be easily misdiagnosed with other retinal eye conditions. Making an accurate diagnosis of a particular type and stage of retinal vasculopathy is essential to start targeted intervention and prevent the risk of permanent vision loss. Based on disease stage and progression, a doctor might opt for medication, injection or laser interventions.  

Purpose of the article

This article will help clinicians, ophthalmologists, and researchers in differentiating Eales’ disease from other clinically relevant disorders. By identifying and highlighting specific aspects of high-risk populations, clinical features, and research-backed diagnostic criteria. This article aims to foster immediate recognition, precise treatment, and better patient outcomes for those suffering from Eales’ disease and other types of vasculopathies. 

Understanding Eales’ disease

Pathophysiology and hallmark clinical features

Here is a step-by-step explanation of how Eales' disease starts and progresses: 

Idiopathic retinal periphlebitis

The disease starts with retinal phlebitis, inflammation targeting retinal veins, with no known cause. This inflammation results in swelling and damage, subsequently impeding the normal blood flow within the affected retinal veins. As this inflammation advances, so does the swelling, which ultimately leads to partial or complete vascular occlusion of retinal veins, significantly blocking blood and nutrient supply. A prolonged obstruction of the blood nutrient and oxygen supply creates an ischaemic state in the retinal veins. Depending on the duration of ischemia, it can cause reversible and irreversible damage to retinal tissue and vision.^2,3

Recurrent vitreous haemorrhage 

To compensate for ischaemia and a lack of oxygen, the body responds by creating new blood vessels through the process of neovascularisation or the production of abnormal and weak blood vessels. However, these vessels are delicate and prone to breakage. When these newly formed abnormal blood vessels rupture, they release blood into the vitreous part of the eye, which is a clear gel-like substance that fills the inside of the eye. This leakage of blood is called a vitreous haemorrhage. It is often associated with visual impairments, and recurrent episodes can lead to permanent vision loss.^4,5

Other findings 

It can be caused by neovascularisation (as explained above) or by sclerotic vessels, which are blood vessels that have become hard due to fibrosis from repeated damage and disease.⁶ Only in 24% of the patients suffering from Eales’ disease can macular changes develop. The macula is the central part of the eye responsible for detailed, central vision. Macular changes can range from swelling to scarring.⁵

Key risk factors and demographic profile

Here are ten detailed points elaborating the key risk factors and demographic profile of Eales’ disease, based on current clinical and epidemiological evidence:^3,6

• Most affected individuals are generally in good health, and the disease often emerges during adolescence and early adulthood, between 14 and 35 years
• While both males and females may develop the disease, it is more commonly observed in males
• The majority of the patients diagnosed with this disease reside in India, Pakistan, and Bangladesh. This shows how environmental factors (extreme weather conditions) can be contributors, as there are rare reported cases of Eales’ disease outside of this geographical boundary
• The disease usually affects both eyes. However, it often appears earlier in one eye before it travels to the other one
• Patients often experience an abrupt, painless visual loss or appearance of floaters. Both of these are frequently caused by recurrent bleeding into the vitreous
• Most patients do not have any underlying systemic health problems, such as autoimmune or metabolic syndrome. This is significant because systemic conditions are usually risk factors in other vasculopathies
• A pattern of positive Mantoux test is observed, linking Eales’ disease to hypersensitivity to Mycobacterium tuberculosis (TB). This frequently occurring outcome highlights how a previous TB exposure is a predisposing factor to this retinal vasculopathy
• Researchers are actively looking for specific genes or immune markers that can make people more susceptible to this disease. However, they haven’t been able to find any clear links to race, ethnicity, or family history yet

Differentiating Eales’ disease vasculopathy from other retinal vasculopathies

Below is a structured overview of key retinal vasculopathies commonly considered in the differential diagnosis of Eales’ disease, each section including relevant primary keywords and distinguishing features:

Differentiating Eales’ disease from diabetic retinopathy

Key difference 

Diabetic retinopathy is a complication of diabetes mellitus. Unlike Eales’ disease, there is significant involvement of an underlying metabolic disease.⁷

Eye exam findings 

Shows small blood vessel bulges (microaneurysms), micro- or dot-blot haemorrhages, fatty deposits (hard exudates), areas of nerve fibre loss (cotton-wool spots), and abnormal blood vessel formation (neovascularisation).⁸

Blood examination 

The presence of other diabetic complications (neuropathy, nephropathy) and elevated glucose levels reflects that diabetes can affect multiple systems of the body, not just the eyes.^9,10

Differentiating Eales' Disease from Retinal Vein Occlusion

Primary difference 

Retinal occlusion is caused by a blockage in the retinal vein or artery. The disease is characterised by recurrent, painless and asymptomatic vision impairment. However, it is usually unilateral in contrast to Eales’ disease, which is bilateral.^2,11

Eye exam findings 

On examination, dilated, tortuous veins are observed due to restricted blood flow and the resultant increase in pressure. Small haemorrhages are observed, as many veins are bleeding throughout the retina, giving a characteristic “blood and thunder” appearance to the affected eye. Moreover, tiny fluffy white patches appear in the retina from small ischaemic areas, creating cotton-wool spots.¹¹

Risk factors

Retinal occlusion is accompanied by high blood pressure (hypertension), heart disease (cardiovascular disease), and blood-clotting disorders (hypercoagulable states), which are often present. Retinal occlusion is not typically seen in the young and generally healthy population that is affected by Eales’ disease.¹²

Differentiating Eales’ disease from ocular sarcoidosis

Primary Difference 

Ocular sarcoidosis is an autoimmune disorder that exhibits the formation of immune cell clusters in the uvea (a middle, highly vascular layer of the eye between the sclera and retina) and Retinal vein phlebitis (inflammation around the vein instead of in it).¹³

Eye exam findings 

Candle-wax drippings (waxy yellow-white deposits along veins due to inflammation around the veins), broad-based synechiae (formation of adhesion between the iris and any other part of the eye), and multifocal choroidal lesions (lesions in the choroid part of the eye).

Blood exam 

Appearance of noncaseating granulomas (granulomas that do not have a central dead tissue or cessation) in other organs, most commonly the lungs and skin. These are visible through abnormal chest imaging and high ACE levels in the blood.

Differentiating Eales’ disease from tubercular retinal vasculitis

Primary distinction 

Documented history of TB, positive Mantoux test (a skin test where tuberculosis proteins (PPD) are injected under the skin and a firm raised swelling appears in the next 48 to 72 hours) or Interferon-Gamma Release Assays (a blood test that measures the release of interferon-gamma by immune cells when exposed to tuberculosis antigen).¹⁴

Fundus findings 

Retinal periphlebitis (inflammation around the veins of the eyes), choroidal tubercles (small yellowish nodules found in the highly vascular choroid part of the eye), and multifocal serpiginous-like lesions (irregularly shaped inflammations that create several lesions in the pigmented part of the retina and choroid).¹⁵

Systemic clues 

May have coexisting tuberculosis in the lungs and other parts of the body. A PCR test may highlight Mycobacterium tuberculosis DNA in eye fluids. 

Differentiating Eales’ disease from sickle cell retinopathy

Primary distinction 

Mostly reported by individuals of African, Mediterranean, or Middle Eastern origin with sickle cell haemoglobin genetic disorder.^16,17

Retinal Findings 

“Sea-fan”-shaped neovascularisation (formation of new abnormal blood vessels) present at the parts away from the centre of the eye, black sunburst lesions (small dark radiating patches due to pigmentation, clumping or migration beneath the retina), salmon-patch (oval-shaped pink spots seen on the retina), and haemorrhages.¹⁸

Systemic Clues 

Prior diagnosis of sickle cell disease, presence of haemolytic anaemia, vaso-occlusive crisis, splenic abnormalities, and other organ involvement.

Summary

Eales’ disease is an idiopathic retinal vasculopathy that must be diligently distinguished from other types of retinal vasculopathies, such as diabetic retinopathy, retinal vein occlusion, sarcoidosis, and tuberculosis-related vasculitis. An accurate diagnosis can be made based on clinical clues, eye examination, and systemic evaluation. The diagnosis of Eales’ disease is made by exclusion, i.e., by systematically ruling out other possible conditions. Proper identification guidelines are essential for preventing permanent vision damage and facilitating progressive treatment.