Background

Eales disease, idiopathic recurrent retinal vasculitis, is a rare and poorly understood eye disorder primarily affecting young adults. It is characterized by inflammation, ischemia (inadequate blood supply), and neovascularization (abnormal blood vessel growth) in the retina. The exact cause of Eales disease remains unknown, yet it is thought to involve a combination of genetic and environmental factors.

Symptoms: The initial symptoms of Eales disease often include blurred vision, floaters (spots or cobweb-like shapes in the visual field), and diminished visual acuity. As the disease progresses, patients may experience recurrent episodes of retinal hemorrhages (bleeding), retinal vessel occlusions (blockages), and retinal detachment, leading to severe vision loss or blindness if left untreated.

Epidemiology

Eales disease is predominantly documented in Asia region, particularly in India. Instances of Eales disease in the western countries are exceedingly infrequent. It predominantly affects male individuals, with a higher incidence compared to females. The typical age of onset for males is between 20 and 40 years.

In 90% of cases, Eales disease manifests bilaterally, while the other 10% experience the unilateral involvement. The occurrence of an asymmetrically bilateral presentation is typically common. Although uncommon, the pediatric individuals can also be affected by the Eales disease.

Anatomy

Pathophysiology

The pathophysiology of Eales’s disease, also known as idiopathic recurrent retinal vasculitis, is not entirely understood. Yet, several theories have been proposed to explain the development and progression of this condition. Here is an overview of the possible pathophysiological mechanisms involved:

• Inflammation and Vasculitis: Eales disease is believed to involve inflammation of the retinal blood vessels, leading to vasculitis (inflammation of blood vessels). The exact trigger for this inflammatory response is unknown, but it is thought to involve an abnormal immune response or an underlying genetic predisposition.
• Ischemia and Retinal Hypoxia: The inflammation and vasculitis in Eales disease can lead to the narrowing or blockage of retinal blood vessels. This obstruction disrupts the blood supply to the retina, causing ischemia (inadequate blood flow) and subsequent retinal hypoxia (oxygen deprivation). The retinal cells become stressed and release factors that generally promote the growth of new blood vessels.
• Neovascularization: In response to the ischemic state, the retina releases angiogenic factors such as vascular endothelial growth factor (VEGF). These factors stimulate the growth of new blood vessels, a process called neovascularization. However, the newly formed vessels are abnormal and fragile, making them prone to leakage and bleeding.
• Vitreous Involvement: The vitreous gel, which fills the space between the lens and retina, can also be affected in Eales disease. Inflammation and neovascularization can lead to the formation of fibrous bands and tractional forces within the vitreous, which can cause retinal detachment.
• Reactive Hyperplasia: In some cases, Eales’s disease may be associated with reactive hyperplasia of the peripheral lymphatics. This hyperplasia leads to the formation of abnormal lymphatic vessels, which can contribute to the development of retinal neovascularization.

Etiology

The exact etiology (cause) of Eales disease remains unknown. It is an idiopathic condition that arises spontaneously without an identified cause. However, several factors have been suggested to play a role in the development of Eales disease. Here are some potential etiological factors that have been proposed:

• Immunological Factors: Abnormal immune responses or autoimmune mechanisms have been proposed as potential contributors to Eales’s disease. It is believed that an immune-mediated inflammatory response may trigger the vascular changes and subsequent neovascularization seen in the condition. However, the specific immune mechanisms involved have not been fully elucidated.
• Genetic Factors: Evidence suggests that genetic factors may influence susceptibility to Eales disease. Studies have shown that particular human leukocyte antigen (HLA) alleles, particularly HLA-DR2 and HLA-B5, may increase the risk of developing the disease. However, the exact genetic mechanisms and their contribution to Eales disease are still being investigated.
• Infectious Agents: Infections have been proposed as potential triggers for Eales disease, although the evidence is inconclusive. Some studies have suggested an association between Eales disease and certain infections such as tuberculosis (TB). It is thought that the infectious agent or the host’s immune response to the infection may lead to the inflammatory and vascular changes seen in the disease. However, the role of infectious agents in Eales disease remains a subject of debate, and further research is needed.
• Oxidative Stress: It occurs when there is imbalance between the production of ROS (reactive oxygen species) and the body’s antioxidant defenses and has been suggested as a possible etiological factor in Eales disease. Increased oxidative stress may contribute to vascular damage and inflammation in the retina, leading to the development of the disease. However, more research is needed to understand oxidative stress’s role in Eales disease fully.

Genetics

Prognostic Factors

The prognosis of Eales disease, a rare eye disorder characterized by retinal inflammation and vasculitis, can vary among individuals. Several prognostic factors have been identified that can influence the course and outcomes of the disease. Here are some of the critical prognostic factors in Eales disease:

• Severity of Vasculitis: As assessed by clinical examination and imaging studies, the extent and severity of retinal vasculitis are important prognostic factors. Extensive and severe vasculitis involvement is associated with a higher risk of complications and poorer visual outcomes.
• Neovascularization: The presence and extent of neovascularization (abnormal blood vessel growth) in the retina is another prognostic factor. Extensive neovascularization increases the risk of complications such as vitreous hemorrhage, retinal detachment, and macular edema, which can significantly impact vision.
• Recurrence of Disease: Eales disease is characterized by recurrent episodes of inflammation and vascular changes. The frequency and severity of recurrences can influence the prognosis. Individuals with frequent and severe recurrences are more likely to experience vision-threatening complications and have a poorer long-term prognosis.
• Delayed Diagnosis and Treatment: Early diagnosis and prompt appropriate treatment initiation are crucial for effectively managing Eales’s disease. Delayed diagnosis and treatment can lead to more extensive retinal damage and complications, resulting in poorer visual outcomes.
• Complications: The development of complications, such as vitreous hemorrhage, retinal detachment, and macular edema, can significantly impact the prognosis of Eales’s disease. These complications often require additional interventions and can result in permanent vision loss if not managed promptly and effectively.
• Response to Treatment: The response to treatment can also be a prognostic factor. Individuals who respond well to treatment and achieve control of inflammation, neovascularization, and complications tend to have better visual outcomes than those who have a poor response or inadequate control of the disease despite treatment.

Clinical History

Clinical history

Clinical presentation of Eales disease, a rare eye disorder characterized by inflammation and vasculitis of the retina, can vary among individuals. However, certain standard features are typically observed in patients with Eales disease. Here are the critical aspects of its clinical presentation:

Age Group: Eales disease primarily affects young adults, typically between 20 and 40. It is relatively uncommon in children and older individuals.

Physical Examination

Physical examination

The physical examination of Eales’s disease involves a comprehensive evaluation of the eye and its structures. Here are the critical components of the physical examination for Eales disease:

• Visual Acuity Assessment: Visual acuity is measured using an eye chart to assess the clarity of vision. The patient is asked to read letters or symbols at various distances while covering one eye at a time.
• Slit Lamp Examination: A slit lamp biomicroscope is used to assess the anterior segment of the eye, including the cornea, iris, and lens. This allows the ophthalmologist to assess any signs of inflammation, such as cells or flares in the anterior chamber.
• Dilated Fundus Examination: The ophthalmologist administers eye drops to dilate the pupil, allowing for a detailed investigation of the posterior segment of the eye, including the optic nerve, retina, and blood vessels. A unique lens or indirect ophthalmoscope visualizes the fundus (back of the eye).
• Retinal Findings: During the dilated fundus examination, the ophthalmologist looks for characteristic signs of Eales disease, including retinal hemorrhages (bleeding), venous dilation, tortuosity, or narrowing, and areas of retinal ischemia (inadequate blood supply). These findings may be localized or diffuse.
• Fluorescein Angiography: Fluorescein angiography involves injecting a dye (fluorescein) into a vein in the arm, followed by capturing sequential photographs of the retina as the dye circulates through the blood vessels. This test helps evaluate the retinal blood flow, detect areas of vascular leakage, and identify abnormal blood vessel growth (neovascularization).
• Optical Coherence Tomography (OCT): OCT is a non-invasive imaging test that provides cross-sectional retina images, allowing for a detailed assessment of retinal thickness, integrity, and macular edema (swelling). OCT can also help detect tractional forces or fibrous membranes within the vitreous gel.
• Intraocular Pressure Measurement: The pressure inside the eye, known as intraocular pressure (IOP), may be measured using a tonometer. Elevated IOP can be associated with certain complications of Eales disease, such as neovascular glaucoma.

Age group

Associated comorbidity

Associated Comorbidity or Activity:

Eales disease is often idiopathic, meaning it arises spontaneously without an identifiable cause. However, certain factors may be associated with the disease. For example, individuals with a history of tuberculosis (TB) or exposure to TB infection have been found to have a higher prevalence of Eales disease. Other associated conditions or activities have yet to be consistently identified.

Associated activity

Acuity of presentation

Acuity of Presentation:

The initial visual symptoms of Eales disease can vary in severity. Some individuals may present with mild visual disturbances, such as blurred vision or decreased visual acuity. Others may experience more pronounced visual impairments, including severe visual loss or even blindness, mainly if complications like retinal detachment or vitreous hemorrhage have occurred.

• Floaters and Blurred Vision: Floaters, which are specks or cobweb-like shapes that move across the visual field, is a common complaint in Eales disease. These floaters are caused by blood cells or inflammatory debris within the vitreous gel. Blurred vision, resulting from retinal inflammation and vascular involvement, is another common symptom.
• Retinal Hemorrhages: Eales disease is characterized by retinal hemorrhages, which are areas of bleeding within the retina. These hemorrhages can manifest as red spots or patches seen during a dilated eye examination. The extent and location of the hemorrhages can vary, and they may be recurrent.
• Retinal Vasculitis and Neovascularization: Inflammation and vasculitis affecting the retinal blood vessels are hallmark features of Eales disease. The affected blood vessels may appear dilated, tortuous, or narrowed. In some cases, abnormal blood vessel growth, known as neovascularization, may occur, forming fragile, leaky blood vessels.
• Recurrent Episodes: Eales disease is typically characterized by recurrent episodes of inflammation, vasculitis, and associated complications. These episodes may occur irregularly, leading to cumulative retinal damage over time.

Differential Diagnoses

Differential Diagnosis

The clinical presentation of Eales disease can overlap with other retinal disorders, making the differential diagnosis necessary for accurate diagnosis and appropriate management. Here are some conditions that may be considered in the differential diagnosis of Eales disease:

• Retinal Vasculitis: Other forms of retinal vasculitis, such as Behcet’s disease, sarcoidosis, syphilis, and systemic lupus erythematosus (SLE), can present with similar retinal inflammation and vascular involvement. Differentiating Eales disease from these conditions requires a thorough medical history, clinical examination, laboratory tests, and sometimes specific diagnostic criteria.
• Diabetic Retinopathy: In diabetic retinopathy, there can be retinal vascular changes, including hemorrhages and neovascularization. However, a known history of diabetes, characteristic retinal findings (such as microaneurysms and hard exudates), and the absence of recurrent inflammatory episodes can help differentiate diabetic retinopathy from Eales’s disease.
• Retinal Vein Occlusion: Retinal vein occlusion, either central or branch, can lead to retinal hemorrhages, edema, and neovascularization. However, in Eales disease, the retinal vasculitis and inflammation are typically more diffuse, affecting multiple areas of the retina, whereas vein occlusion is more localized.
• Retinal Arterial Macroaneurysm: Retinal arterial macroaneurysm is characterized by a focal dilatation of a retinal artery, often associated with hemorrhages or exudates. It can mimic some aspects of Eales disease, but it usually presents in older individuals and lacks the diffuse retinal vasculitis seen in Eales disease.
• Ocular Tuberculosis: Tuberculosis (TB) can involve the eye and cause retinal vasculitis, neovascularization, and hemorrhages. Ocular TB may have overlapping features with Eales disease, particularly in areas with a high prevalence of TB. Carefully evaluating systemic symptoms, chest X-ray findings, and laboratory tests, including TB-specific investigations, can help differentiate the two.
• Retinal Malignancies: Rarely, certain retinal malignancies, such as retinoblastoma or intraocular lymphoma, can present with retinal vascular abnormalities and hemorrhages. The presence of atypical features, associated systemic symptoms, and additional imaging studies can aid in distinguishing these malignancies from Eales’s disease.
• Other Inflammatory Conditions: Other inflammatory conditions, such as posterior uveitis, intermediate uveitis, and autoimmune retinopathies, can manifest with retinal inflammation, vasculitis, and hemorrhages. Clinical examination findings, systemic symptoms, and additional investigations are essential for differentiating these conditions from Eales’s disease.

Laboratory Studies

Imaging Studies

Procedures

Histologic Findings

Staging

Treatment Paradigm

Eales disease is a rare inflammatory eye disorder that primarily affects the retina’s blood vessels, leading to vision loss and potential complications like retinal detachment or vitreous hemorrhage. The management of Eales disease involves various approaches, including modification of the environment, administration of pharmaceutical agents, and intervention with procedures. The phase of management depends on the severity and progression of the disease.

• Modification of environment: This phase focuses on reducing potential triggers and promoting a healthy eye environment. It may include:
• Lifestyle modifications: Encouraging patients to quit smoking and adopt a healthy lifestyle, together with regular exercise and a balanced diet, can positively impact the disease progression.
• Occupational adjustments: If the patient’s occupation involves prolonged periods of near work or exposure to harmful substances, appropriate modifications may be recommended to minimize eye strain and potential aggravation of the condition.
• Sun protection: Encouraging the use of sunglasses with ultraviolet (UV) protection and hats to shield the eyes from excessive sunlight and potential UV damage.
• Administration of pharmaceutical agents: Medical management is essential to Eales disease treatment. It typically involves using medication to control inflammation and reduce the risk of complications. Common pharmaceutical agents used include:
• Corticosteroids: Systemic or local corticosteroids or intraocular injections may be prescribed to reduce inflammation and edema in the retinal blood vessels.
• Immunosuppressive agents: Medications like Immunosuppressive agents may be considered in severe cases to suppress the immune response and prevent further damage.
• Anti-VEGF therapy: Intravitreal injections of anti-vascular endothelial growth factor (anti-VEGF) agents may be used to manage complications like neovascularization and macular edema.
• Intervention with a procedure: In advanced cases or when complications arise, intervention with surgical procedures may be necessary. These procedures aim to manage complications and preserve or restore vision. Some common interventions include:
• Laser photocoagulation: Laser therapy can seal leaking blood vessels, reduce neovascularization, or treat retinal breaks or tears.
• Vitrectomy: A surgical procedure may be performed in cases of vitreous hemorrhage or retinal detachment. It involves removing the vitreous gel and addressing any retinal issues.
• Retinal detachment repair: If retinal detachment occurs, surgical repair is necessary to reattach the retina to the underlying tissue and restore visual function.

Phase of management

• Acute phase: The acute phase focuses on managing the active inflammation and associated symptoms. The primary goals during this phase are to control the disease activity and prevent complications with medications like Corticosteroids, Nonsteroidal anti-inflammatory drugs (NSAIDs), and topical steroids.
• Maintenance phase: Once the disease activity is controlled, the treatment shifts to the maintenance phase, which aims to prevent recurrence and manage long-term complications. The following approaches are commonly used:
• Regular monitoring: During the maintenance phase, regular follow-up visits with an ophthalmologist are essential to monitor disease activity, assess treatment response, and identify any potential complications.
• Follow-up phase: The follow-up phase involves long-term monitoring and managing the disease to ensure stable vision and detect any relapses or complications. It includes the following:
• Ophthalmic examinations: Regular eye examinations, including visual acuity tests, fundus evaluation, and imaging studies like optical coherence tomography (OCT), are conducted to assess the overall condition of the retina and detect any changes or relapses.
• Lifestyle modifications: Encouraging a healthy lifestyle, including regular exercise, a balanced diet, and smoking cessation, is vital for overall ocular health.
• Patient education: Providing information and educating the patient about the disease, its management, medication compliance, and follow-up visits.

by Stage

by Modality

Chemotherapy

Radiation Therapy

Surgical Interventions

Hormone Therapy

Immunotherapy

Hyperthermia

Photodynamic Therapy

Stem Cell Transplant

Targeted Therapy

Palliative Care

Medication

Future Trends

Media Gallary

References

Unilateral Eales’ disease a case report – PMC (nih.gov)

Eales disease in a young adult man Case report – PMC (nih.gov)

Eales Disease – StatPearls – NCBI Bookshelf (nih.gov)