Introduction

Eales' disease is an uncommon eye disorder that primarily occurs in young adults, particularly males, aged between 15 and 40 years. It is an idiopathic, inflammatory and occlusive retinal venous disease. In other words, it is a condition where the veins in the retina (the light-sensitive tissue at the back of the eye) get inflamed, plugged and damaged, resulting in bleeding and the development of new abnormal blood vessels.

The disease was initially described in 1880 in young healthy men who presented with repeated bouts of bleeding within the eye (vitreous haemorrhage) by Henry Eales. Numerous studies have since been conducted, and the disease has been identified as a significant cause of avoidable blindness among young adults in specific parts of the world, especially India and South Asia.

The precise aetiology of Eales disease is not fully understood, but it has been speculated to be associated with hypersensitivity to Mycobacterium tuberculosis proteins, autoimmune mechanisms and hereditary factors.

The clinical presentation (patient presentation with signs and symptoms) and the natural history (the course and progression of the disease if untreated) will be highlighted in this article for two principal topics.

Clinical presentation of eales disease

The clinical presentation of Eales disease is staged based on the changes occurring in the retina and the symptoms presented by the patient. The stages are the inflammatory stage, the occlusive stage and the proliferative stage. Each stage has a different set of clinical characteristics.

General symptoms

• Floaters: Patients complain of seeing black spots, cobwebs or flying shadows in vision as a result of vitreous haemorrhage
• Sudden painless loss of vision: It is a presenting symptom and typically results from vitreous haemorrhage or retinal detachment
• Blurring of vision: Can present in early stages because of macular oedema (swelling of the central part of the retina)
• Photopsia (flashes of light): Result of traction on the retina by fibrous tissue
• Recurrent episodes: Patients present with recurrent attacks of sudden vision loss, which partially recover between episodes
• The condition is typically bilateral but asymmetric, i.e., both eyes are involved but not equally

Inflammatory stage (Periphlebitis)

• The first clinical feature is periphlebitis, i.e., inflammation around the veins of the retina
• Fundus examination reveals white sheathing or cuffing of retinal veins. This is in the form of a whitish rim around the vessels
• Segmental periphlebitis is common, involving the peripheral retinal veins
• Small haemorrhages of the retina can occur beside the involved vessels
• Mild vitreous cells (inflammatory cells in the vitreous) can also be present
• A few patients might be free of significant symptoms at this stage, and the disease might be found on a routine eye examination

Occlusive stage (Ischemic changes)

• With progression of the disease, inflammation results in occlusion of the retinal veins. Obstruction of blood flow ensues
• Retinal ischemia develops, i.e., sections of the retina are not adequately oxygenated and nourished
• Clinical findings are:
  • Regions of capillary non-perfusion observed on fluorescein angiography
• Venous tortuosity and beading
• Cotton wool spots owing to retinal ischemia are localised
• By this time, patients can experience more visual phenomena like increased floaters, blurring, or sudden loss of vision

Proliferative stage (Neovascularisation)

• Chronic retinal ischemia triggers the release of angiogenic factors like VEGF (Vascular Endothelial Growth Factor)
• This results in neovascularisation, i.e., development of new abnormal retinal and optic disc blood vessels
• These new vessels are weak and tend to rupture, resulting in recurring vitreous haemorrhage
• Fibrous proliferation frequently follows neovascularisation, resulting in the development of fibrovascular membranes
• Retinal traction by fibrous tissue can result in tractional retinal detachment
• Clinical presentations are:
  • Recurrent or ongoing vitreous haemorrhage
  • Retinal neovascularisation, typically at the boundary between the perfused and non-perfused retina
  • Fibrovascular proliferation extending into the vitreous
  • Macular oedema, leading to central visual loss

Advanced stage and complications

• Untreated Eales disease may advance to serious complications
• Non-resolving vitreous haemorrhage: Ongoing blood within the vitreous cavity, impairing vision
• Recurrent haemorrhages: Frequent bleeding attacks over months or years
• Tractional retinal detachment: Fibrous membranes exert traction on the retina
• Rhegmatogenous retinal detachment: Tears or holes in the retina may result from traction
• Neovascular glaucoma: Development of new blood vessels on the iris and angle of the eye, resulting in elevated intraocular pressure and symptomatic loss of vision
• Blindness: End result in untreated or advanced cases

Natural history of eales disease

The natural history of Eales' disease is progressive and unpredictable. The disease is not the same in each patient, but typically it goes through the following sequence if left alone:

Stage 1: Periphlebitis (Inflammatory stage)

• The disease typically starts in the peripheral retina with segmental periphlebitis
• The inflammation is local, with venous sheathing and sporadic minute haemorrhages
• This stage can be silent or asymptomatic
• With time, repeated inflammation induces injury to the vessel wall, resulting in occlusion

Stage 2: Venous occlusion and ischemia

• Chronic inflammation leads to venous occlusion
• There is a dropout of retinal capillaries with extensive areas of ischemia
• Hypoxia in the retina leads to the release of VEGF and other growth factors
• This stage lays the foundation for neovascularisation

Stage 3: Proliferative changes

• New vessels form at the border of the perfused and non-perfused retina
• Recurrent vitreous haemorrhage ensues because these thin-walled vessels are easily torn
• Fibrous tissue grows along with the new vessels
• Recurrent episodes of bleeding result in oscillating vision loss
• Most patients report to the clinic at this point, usually following abrupt vision loss from vitreous haemorrhage

Stage 4: Complicated and end-stage

• Severe vitreoretinal traction is caused by fibrovascular proliferation
• Tractional retinal detachment forms, particularly in the periphery of the retina
• This can progress to combined tractional and rhegmatogenous detachment if left untreated
• Chronic retinal ischemia can also result in neovascular glaucoma, which is blinding and painful
• Blindness caused by unresolved complications is the end stage of the disease

Summary

Eales' disease is an uncommon, chronic retinal disease that predominantly occurs in healthy young adults, particularly men. The disease typically starts unilaterally with inflammation of the peripheral retinal veins, followed by early manifestations of floaters, flashes, and blurred vision. With continued progression of the disease, there is occlusion of the retinal vessels and ischemia, which causes abnormal new vessel growth. These blood vessels tend to break and bleed repeatedly, resulting in recurrent vitreous haemorrhage and acute, painless loss of vision. In the advanced stages, fibrous tissue growth can cause traction of the retina and cause tractional retinal detachment or neovascular glaucoma. If left untreated, the above complications can lead to severe, irreversible loss of vision. Early detection by fundus examination and prompt treatment with corticosteroids, laser photocoagulation, or surgery can restore useful vision and greatly enhance prognosis.