Eales Disease

What is Eales Disease?

Eales disease is a medical condition that typically leads to repeat occurrences of bleeding within the eye’s “jelly” (vitreous hemorrhage) in younger adults. This disease is most common in Indian regions. One of its main characteristics is inflammation and damage to the blood vessels in the retina, particularly in the outer part of the back of the eye (peripheral fundus). It was first identified by Sir Henry Eales in 1880 in a group of young men who repeatedly experienced this eye bleeding, along with headaches, constipation, and nosebleeds.

When someone has inflammation in the veins of the outer retina (retinal periphlebitis), it’s necessary to rule out the potential causes, such as tuberculosis and sarcoidosis. Eales disease can take different forms, and how it’s managed will depend on the specific stage of the disease. Treatment generally includes medications, like steroids, taken orally or applied around or inside the eye, to control the bilateral retinal inflammation. A procedure called laser photocoagulation is used for stages involving retinal starvation of oxygen and new, abnormal blood vessel growth. In cases where the eye bleeding continues for several months or the retina begins to detach, a surgery called vitrectomy might be necessary, usually with quite satisfactory outcomes. As for the use of antituberculosis treatment for this eye condition, when no other parts of the body are affected, is still up for debate and requires more study.

What Causes Eales Disease?

Eales disease, named after Sir Henry Eales, is related to inflammation of the retina. However, the exact cause of this disease is still not well understood, despite many studies, and is often referred to as an immune system reaction to an outside agent. No specific cause has been identified yet, which means the disease is mostly regarded as idiopathic – a term for diseases with unknown cause. However, there seems to be some connection between Eales disease and exposure to tuberculosis.

Some studies proposed that certain types of bacteria, rapidly growing nontuberculous mycobacteria specifically, may be tied to Eales disease. For example, one study found a significant link between Eales disease and one bacterium in particular, M. fortuitum.

A specific gene in the M. tuberculosis bacterium translates into a protein that triggers a strong immune response. This gene, MPT64, has been successfully used to diagnose some cases. An interesting study found that 38.7% of patients with Eales disease were positive for the MPT64 gene. These patients also had higher results in tests for erythrocyte sedimentation rate (ESR), and tuberculin skin test (TST), reflecting an active immune response and potential infection.

Additional studies reported presence of Mycobacteria, the bacterial group that includes tuberculosis, in the eye fluid (vitreous humor) of patients with Eales disease. These findings suggest that Eales disease may be related to tuberculosis which might not show signs until late stages of the disease. However, these bacteria may not be alive or may simply be residue of past infections, questions still remain.

Mantoux test, which is a skin test for tuberculosis, was reported positive in many patients with Eales disease. But since it is also common in healthy adults in some populations, and Eales disease is also seen in people with negative Mantoux results, this link continues to be questionable.

Another astonishing finding was neurological symptoms in some Eales disease patients. These symptoms included transient ischemic attacks (temporary blood supply loss to parts of the brain), cerebral stroke, and few other serious conditions, thought to be due to inflammation in the membrane surrounding the central nervous system.

Some other potential causes included genetic mutations, infections, and blood disorders that could cause clotting. Furthermore, research has found certain immune response-related mechanisms that may play a part. For instance, increased levels of certain oxidative stress markers (caused by an imbalance between free radicals and antioxidants in the body) and decrease in essential antioxidants might be factors. Certain types of proteins, possibly involved in Eales disease, might be used as ‘biomarkers’ to diagnose the disease in future.

Lastly, retinal neovascularization, or new abnormal blood vessels growth in the retina, is assumed to occur due to increased levels of a protein called Vascular Endothelial Growth Factor (VEGF), known for its role in blood vessel formation. Various studies have pointed out the involvement of certain growth factors and enzymes in eye neovascularization, but their exact roles in Eales disease are not yet confirmed.

Risk Factors and Frequency for Eales Disease

Eales disease is mostly found in Asia, particularly the Indian subcontinent, and it’s quite rare in the western world. This disease typically affects males between the ages of 20 to 40. It’s worth noting that 90% of people with Eales disease experience it in both eyes (bilateral), while the remaining 10% only have it in one eye (unilateral). Even though it can occur in children, it’s not common in this age group.

Eales disease is primarily reported in Asia, especially the Indian subcontinent.
It’s less common in the western world.
This disease usually affects males between 20 and 40 years of age.
90% of patients experience the disease in both eyes.
About 10% of patients have the disease only in one eye.
It is possible for children to get Eales disease, but it is not common.

Signs and Symptoms of Eales Disease

Eales disease is a condition that mostly affects young males, and it often goes unnoticed during its early stages. Patients with this disease usually start to see floaters, or cobweb-like figures floating in their vision, and they might experience diminished sight or photopsia, which means seeing flashes of light. The condition commonly affects both eyes and is mostly painless. Three major changes happen in the retina due to Eales disease: inflammation (known as peripheral vasculitis), poor blood flow (due to peripheral capillary non-perfusion), and development of new blood vessels (in the optic disc and elsewhere).

During a physical examination for Eales disease, doctors usually check two things:

Visual clarity or acuity – Since the disease mostly affects the outer areas of the retina and leaves the part responsible for clear, focused vision (the macula) untouched, most patients still possess a relatively normal vision of 20/40 or better at the time of presentation. However, vision can be severely impaired in cases with bleeding in the vitreous (the gel-like substance that fills the eye) or swelling in the macula. Some patients with chronic retinal detachment or neovascular glaucoma (a type of glaucoma caused by new blood vessels growing on the iris) may not perceive any light at all.
Anterior segment – The presence of anterior uveitis (inflammation of the middle layer of the eye) is quite rare and is generally non-granulomatous (not featuring small nodules). If granulomatous uveitis is seen, it may indicate sarcoidosis, another condition that causes inflammation in different parts of the body. Hypopyon (accumulation of white blood cells in the front of the eye) might make Behcet disease a more likely diagnosis. Later stages of the disease may show signs of new blood vessel growth in the iris.

In Eales disease, vitreous inflammation is unusual. You might observe mild vitreous haze over areas of inflammation in the blood vessels. In advanced stages, recurrent vitreous hemorrhages occur, making it hard to visualize the back of the eyeball or fundus. New, fragile blood vessels usually cause this vitreous blood leakage.

The optic nerve might show new blood vessel development in the late stages of Eales disease, leading to fading of the optic disc color in cases of neovascular glaucoma.

The progression of Eales disease generally happens in three stages:

Early (Inflammatory) Stage – This stage is characterized by inflammation of tiny veins (periphlebitis). Veins are more prone to damagethan arteries. You can see this in multiple quadrants of the eye. White fuzzy infiltrates (exudates) along the blood vessel and venous dilation are signs of active inflammation. Healing of the inflammation leaves behind scars, which are evident as vein sheathing, venous sclerosis, pigmentation, uneven vein diameter, or abnormal vascular connections.
Middle (Ischemic) Stage – In this stage, a lack of sufficient blood supply to the capillaries (ischemia) is observed. This leads to increased production of VEGF (a protein that stimulates the formation of blood vessels), causing macular swelling, or the proliferative stage.
Late (Proliferative) Stage – This is characterized by the development of new blood vessels (neovascularization) at the interface of the non-perfused and perfused retina. This can cause recurring vitreous hemorrhages, possibly accompanied by retinal detachment. It’s less common to see optic disc neovascularization as compared to neovascularization elsewhere in the eye.

Testing for Eales Disease

Fundus Fluorescein Angiography (FFA) is a diagnostic technique often used to identify Eales disease, a rare eye condition. This tool allows doctors to monitor changes in the blood vessels of the eye that suggest the presence of Eales disease. For example, if a delay in blood flow (venous filling) is observed, this could signal an obstruction in the blood vessel. Early on, this method may reveal inflammation of the vessel walls. Later, dye used in this procedure may leak out of the blood vessels, signifying new vessel growth, or neovascularization.

FFA is also helpful in planning the patient’s treatment. If new vessels are growing or parts of the retina are not receiving enough blood, further treatment with a technique called laser photocoagulation may be needed. This involves using a laser to seal off the abnormal blood vessels. Additionally, if fluid build-up is detected at the back of the eye, steroid injections might be necessary.

However, FFA has certain limitations; it can only visualize a small section of the retina, potentially missing parts where the disease is very active. Wide-field angiography overcomes this limitation by imaging a larger portion of the retina, providing clearer pictures and better monitoring of changes over time.

When doctors cannot view the back of the eye due to blood build-up (vitreous hemorrhage), an ultrasound (B-scan) might be used. This method helps identify if there’s a detachment in the retina. Scans can also reveal whether there’s abnormal thickening of the retina or pockets of fluid beneath the retina.

Optical Coherence Tomography (OCT) can help quantify the extent of fluid build-up and monitor its resolution with treatment.

Before making a diagnosis of Eales disease, doctors must rule out other conditions that can cause similar symptoms. These may include leukemia, tuberculosis, sarcoidosis, and systemic lupus erythematosus (SLE), among others. Therefore, they might order a series of tests, including complete blood count, erythrocytic sedimentation rate (ESR), blood sugar, coagulation profile, and chest x-rays or scans. Tests may also be carried out to exclude conditions such as sickle cell disease and syphilis. If there are indications of retinitis or other suggestive symptoms, HIV serology might also be performed.

Treatment Options for Eales Disease

The treatment for Eales disease largely depends on the stage of the condition, which can differ for each eye of a patient. Therefore, different treatment methods may be necessary.

Monitoring

Patients without active peripheral vasculitis, which is inflammation of blood vessels in the outer sides of the retina, are usually observed and revisited every 6 to 12 months. For those with a fresh vitreous hemorrhage, or internal eye bleeding, but an attached retina, they should have reviews every 2 to 6 weeks. This type of internal eye bleeding normally clears up over a 6 week period.

Medical Treatment

In the early stages of Eales disease marked by inflammation, steroids are the primary choice of treatment. These can be administered orally to address inflammation in both eyes, or delivered directly into the eye, especially when the macula, a part of the retina, is swollen due to inflammation. Using steroids directly in the eye avoids potential side effects from oral administration, but presents a risk of glaucoma, an eye condition that can lead to blindness.

Oral prednisolone, a type of steroid, is normally given based on body weight and is gradually reduced over a period of 6-8 weeks. Some patients may require a maintenance dose for up to 2 months. Most Eales disease patients respond extremely well to steroids and rarely require other immunosuppressive drugs. However, some patients may require cyclosporine or azathioprine if they do not respond to steroids or cannot tolerate them due to side effects.

In certain patients with active perivasculitis and a positive Mantoux test for tuberculosis, oral steroids and anti-tuberculosis treatment may be given together. This approach should be considered carefully due to its associated side effects. It is usually reserved for severe cases.

In some cases, where the disease is not responding to conventional treatment, eye injections with anti-VEGF agents or slow-release dexamethasone implants may be used.

Patients with vitreous hemorrhage that prevents the back of the eye from being seen, should have ocular ultrasound scans every 2 to 6 weeks to monitor for retinal detachment, which requires immediate surgery.

Laser Treatment

Laser treatment is generally recommended for advanced stages of Eales disease. Argon green laser or a specific green YAG laser are most commonly used, although a red krypton laser might be used for cases with significant cataract or vitreous hemorrhage. The goal of laser treatment is to redirect blood flow from deprived areas to the healthy retina. This type of treatment is recommended for severe capillary nonperfusion, or imbalanced blood flow in the capillaries.

Surgery

Vitrectomy, a procedure to remove the vitreous, is indicated in cases with persistent bloody vitreous and with or without retinal detachment. This usually clears between 6 to 8 weeks. Non-clearing vitreous hemorrhage, which impairs central vision for 3 months, might necessitate vitrectomy.

With advances in vitreoretinal surgery, earlier interventions might be performed depending on the patient’s visual needs. Vitrectomy clears the vitreous opacities and allows the evaluation of the fundus, which is the back interior of the eye. After the surgery in Eales disease, visual results are generally very good. However, complications can occur, including repeated vitreous hemorrhage, retinal detachment, neovascularization of the iris, cataract, and neovascular glaucoma.

Alternatively, anterior retinal cryoablation, a process of freezing the retina, can be done in cases with poor visual prognosis and clouded ocular media, which is commonly due to after cataracts or vitreous hemorrhage, and in cases with a small non-dilating pupil. Nowadays, laser treatments have mostly replaced this method.

The diagnosis of Eales disease, a type of eye condition, often needs to be differentiated from other similar diseases. The diagnoses that can be considered include:

Vascular conditions such as retinal vein occlusion or Bechet syndrome.
Infections like syphilis, Lyme disease, or cytomegalovirus retinal inflammation.
Autoimmune conditions, such as sarcoidosis.
Conditions with unknown causes (idiopathic), like Coats disease.
Cancerous conditions, such as leukemia.
Inherited conditions like familial exudative vitreoretinopathy.
Endocrine conditions, notably, diabetic retinopathy.

Each of these conditions can cause symptoms that resemble Eales disease. For example, occlusion or blockages in the retina can occur in not only Eales disease but also conditions like retinal vein occlusion, which mostly happens in individuals with high blood pressure. However, blockages in Eales disease can occur anywhere in the vein, while in retinal vein occlusion, they usually happen at the intersection of an artery and a vein.

Several diseases like tuberculosis, sarcoidosis, Lyme disease and multiple sclerosis commonly cause inflammation of the veins and may need to be ruled out when diagnosing Eales disease.

Another disease, Pars planitis, shows symptoms like swelling close to the retina, inflammation inside the eye, and fluid-filled cysts in the retina.

A type of inflammation caused by tuberculosis, called tubercular retinal vasculitis, may be seen in younger individuals, predominantly in males, can affect either or both eyes, and may show a variety of symptoms such as inflammation, blood vessels growing in the retina, retinal bleeding, inflammation of the retina and nerve, localized inflammation in layer under the retina, or build-up of fluid under the retina.

What to expect with Eales Disease

Eales disease generally has a positive outcome with the right treatment. It’s rare for it to cause severe vision loss. However, blindness can occur as a result, if the retina detaches or there is a development of a specific type of glaucoma called neovascular glaucoma.

Possible Complications When Diagnosed with Eales Disease

Eales disease can have several complications, such as:

Repeated bleeding in the jelly-like substance that fills the back half of the eye (recurrent vitreous hemorrhage)
A type of eye disease that damages the optic nerve (neovascular glaucoma)
Separation of the retina from the back of the eye (retinal detachment)
Swelling in the macula, the part of the eye responsible for detailed, central vision (macular edema)
A fibrous layer that forms on the surface of the retina (epiretinal membrane)
New and abnormal blood vessels grow under the retina and choroid (choroidal neovascularization)

Preventing Eales Disease

Eales disease doesn’t have any known preventive methods. If patients experience symptoms like floating spots, sudden flashes of light, or a sudden decrease in vision, it’s critical for them to urgently seek help from a retina specialist. This specialist is trained to treat eye conditions and can provide the appropriate care.

Frequently asked questions

Eales Disease is a medical condition that leads to repeat occurrences of bleeding within the eye's "jelly" (vitreous hemorrhage) in younger adults.

Eales disease is less common in the western world.

Signs and symptoms of Eales Disease include: - Floaters: Patients with Eales Disease often start to see floaters, which are cobweb-like figures floating in their vision. - Diminished sight: Patients may experience diminished sight or a decrease in visual acuity. - Photopsia: This refers to seeing flashes of light. - Commonly affects both eyes: Eales Disease typically affects both eyes. - Painless: The condition is mostly painless. - Inflammation: Inflammation, known as peripheral vasculitis, occurs in the retina. - Poor blood flow: Peripheral capillary non-perfusion leads to poor blood flow in the retina. - Development of new blood vessels: New blood vessels develop in the optic disc and elsewhere in the eye. - Visual clarity or acuity: Doctors check visual clarity or acuity during a physical examination. Most patients still have relatively normal vision, but severe impairment can occur in certain cases. - Anterior segment: Doctors also examine the anterior segment of the eye, looking for signs of inflammation or other conditions such as uveitis or glaucoma. - Vitreous inflammation: Vitreous inflammation is unusual in Eales Disease, but mild vitreous haze may be observed over areas of inflammation in the blood vessels. - Optic nerve involvement: In late stages of the disease, new blood vessel development can affect the optic nerve, leading to fading of the optic disc color. - Progression in three stages: Eales Disease progresses through an early (inflammatory) stage, a middle (ischemic) stage, and a late (proliferative) stage. Each stage is characterized by different changes in the retina and blood vessels.

The exact cause of Eales disease is still not well understood, but it is believed to be an immune system reaction to an outside agent. No specific cause has been identified yet, but there seems to be some connection between Eales disease and exposure to tuberculosis. Other potential causes include genetic mutations, infections, blood disorders, and certain immune response-related mechanisms.

The doctor needs to rule out the following conditions when diagnosing Eales Disease: 1. Retinal vein occlusion or Bechet syndrome (vascular conditions) 2. Syphilis, Lyme disease, or cytomegalovirus retinal inflammation (infections) 3. Sarcoidosis (autoimmune condition) 4. Coats disease (condition with unknown causes) 5. Leukemia (cancerous condition) 6. Familial exudative vitreoretinopathy (inherited condition) 7. Diabetic retinopathy (endocrine condition) 8. Pars planitis (another disease with similar symptoms) 9. Tubercular retinal vasculitis (inflammation caused by tuberculosis)

To properly diagnose Eales disease, doctors may order the following tests: - Fundus Fluorescein Angiography (FFA) to monitor changes in the blood vessels of the eye - Wide-field angiography to visualize a larger portion of the retina - Ultrasound (B-scan) to view the back of the eye in cases of blood build-up - Optical Coherence Tomography (OCT) to quantify fluid build-up and monitor its resolution - Complete blood count, erythrocytic sedimentation rate (ESR), blood sugar, coagulation profile, and chest x-rays or scans to rule out other conditions - Tests to exclude conditions such as sickle cell disease, syphilis, and HIV serology if there are indications of retinitis or suggestive symptoms

The treatment for Eales Disease depends on the stage of the condition. For patients without active peripheral vasculitis, monitoring and regular check-ups every 6 to 12 months are usually recommended. In the early stages marked by inflammation, steroids are the primary choice of treatment. They can be administered orally or directly into the eye. Laser treatment is generally recommended for advanced stages of the disease to redirect blood flow to the healthy retina. In some cases, surgery may be necessary, such as vitrectomy to remove the vitreous. Alternatively, anterior retinal cryoablation, a process of freezing the retina, can be done in certain cases.

When treating Eales Disease, there can be potential side effects depending on the treatment method used. Here are the possible side effects: - Side effects of oral administration of steroids: These can include weight gain, mood changes, increased blood pressure, increased blood sugar levels, and increased risk of infections. - Side effects of using steroids directly in the eye: This can include a risk of glaucoma, which can lead to blindness. - Side effects of cyclosporine or azathioprine: These immunosuppressive drugs can have side effects such as increased risk of infections and liver or kidney problems. - Side effects of anti-VEGF agents or slow-release dexamethasone implants: These can include eye irritation, inflammation, and increased risk of infections. - Side effects of oral steroids and anti-tuberculosis treatment together: This approach should be considered carefully due to its associated side effects, which can include increased risk of infections and liver or kidney problems. It is important to note that not all patients will experience side effects, and the benefits of treatment usually outweigh the potential risks. The specific side effects and risks should be discussed with a healthcare professional.

The prognosis for Eales Disease is generally positive with the right treatment. It is rare for the disease to cause severe vision loss. However, blindness can occur if the retina detaches or if there is a development of neovascular glaucoma.

An ophthalmologist or a retina specialist.

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