Jyotirmay Biswas, MD
DIFFERENTIAL DIAGNOSIS AND INVESTIGATION
Eales’ disease was first described by Henry Eales in 1880 (1). The patient presents
with retinal perivasculitis predominantly affecting the peripheral retina (inflammatory
stage), then sclerosis of retinal veins indicating retinal ischemia (ischemic stage), and
finally retinal or optic disk neovascularization, recurrent vitreous hemorrhage with or
without retinal detachment (proliferative stage) (2–4).
The disease is seen more commonly in the Indian subcontinent and the Middle
Eastern countries. It commonly affects healthy young males. The predominant age of
onset of symptoms is between 20 and 30 yr (5).
Patients are often asymptomatic in the initial stages of retinal perivasculitis. Some
patients may develop symptoms such as floaters, blurring of vision, or even gross diminu-
tion of vision due to massive vitreous hemorrhage. Vision in these patients can be normal
to hand movements or light perception only. Bilaterality is quite common (50–90% of
patients) (2,3). Clinical manifestation of this disease is due to three basic pathological
From: Ophthalmology: Ocular Angiogenesis: Diseases, Mechanisms, and Therapeutics
Edited by: J. Tombran-Tink and C. J. Barnstable © Humana Press Inc., Totowa, NJ
changes: inflammation (peripheral retinal perivasculitis); ischemic changes (peripheral
retinal capillary nonperfusion); and neovascularization of the retina or disk, which often
leads to vitreous hemorrhage as well as multiple superficial retinal hemorrhages.
Anterior uveitis is uncommon in Eales’ disease. However, in the severe active
periphlebitis stage, spillover anterior uveitis may occur. Such anterior uveitis is always
nongranulomatous. The presence of granulomatous anterior uveitis should lead one to
suspect sarcoid uveitis, which mimics Eales’ disease. Hypopyon is not seen in Eales’
disease, and hypopyon with retinal vasculitis may indicate Behçet’s disease (6) 6 .
Ophthalmoscopic findings in Eales’ disease often vary and depend on the stage of
the disease. Arterioles are sometimes affected along with the veins. Typically, active
perivasculitis with exudates around the retinal veins is seen involving one or more
quadrants. Such exudates are often found to be associated with superficial retinal
hemorrhages (Fig. 1).
Healed perivasculitis is often seen as the sheathing of the retinal veins. Other vascu-
lar changes includes sclerosed cord of venules, irregularity of vein caliber, pigmenta-
tion along venules, kinky venules, abnormal vascular anastomosis, and veins pulled
into the vitreous cavity (2,3,7) 7 .
Active or healed choroiditis is not seen in Eales’ disease. However, a few small
chorioretinal atrophic patches close to the retinal vessels are seen (7) 7 .
Central retinal periphlebitis is markedly uncommon compared with peripheral retinal
periphlebitis (2,3,8). Such central involvement is often limited to one or more venous
trunks. This is classified as central Eales, a variant of classical Eales’disease (8). Macular
changes are relatively uncommon (9). The most common macular change seen is macular
edema. Other changes included exudates in the macula and epimacular membrane.
Peripheral retinal neovascularization of the retina is quite frequently seen in Eales’
disease (2,3,7) 7 (Fig. 2). Optic disk neovascularization is significantly uncommon (2–4).
Dense vitritis is uncommon in Eales’ disease. However, mild overlying vitreous haze
Fig. 1. Montage fundus photograph of a case of Eales’ disease showing multiple patches
of active retinal periphlebitis. See color version on companion CD.
can be seen in the area of active retinal vasculitis. Recurrent vitreous hemorrhage is
often the hallmark of this disease. The cause of vitreous hemorrhage in such eyes is
often bleeding from retinal or disk neovascularization, but it can also occur due to rupture
of capillaries or large venules during the active inflammatory stage (10).
Fundus Fluorescein Angiography
Though not routinely needed to distinguish all cases of Eales’ disease, fundus fluo-
rescein angiography (FFA) is particularly beneficial in the ischemic stage to delineate
areas of capillary nonperfusion, retinal and/or optic disk neovascularization, and ques-
tionable macular edema. In cases of active retinal vasculitis, staining of the veins can
be seen in the early venous phase with extravasation of the dye in the late phase. Venous
obstruction and venous stasis can be well visualized by FFA, which will show complete
nonperfusion, or relative dilation and tortuosity of veins distal to the stasis. Areas of
capillary closure, engorged and tortous capillaries, and venovenous shunts can also be
seen in the ischemic stage of the disease.
The extent and location of neovascularization can be precisely delineated by FFA.
Neovascularization, if present, can be quite characteristic with a sea-fan appearance with
intense hyperfluorescence in the early arteriovenous phases of the fundus fluorescein
angiogram (Fig. 3). Such neovascularization, when located in the far periphery, can be
missed on routine FFA, unless a wide-angle lens is used.
FFA often helps to delineate the location and extent of retinal ischemia and can be of
guidance while performing laser photocoagulation. It also helps to evaluate the ade-
quacy of photocoagulation and the need for additional laser photocoagulation, when
FFA is repeated on a follow-up visit.
Fig. 2. Fundus photograph of case of Eales’disease in proliferative stage showing neovascular
frond in the periphery. See color version on companion CD.
Ultrasonography (USG) is needed to rule out any associated retinal detachment,
either tractional, rhegmatogenous, or combined, in an eye with opaque media. Early
vitreous surgery is indicated if such association is demonstrated. USG usually reveals
echoes of variable density, depending on the compaction of vitreous hemorrhage.
Subhyaloid echoes may also be seen. Both incomplete and complete posterior vitreous
detachment with or without tractional retinal detachment can be seen. Membranes in
the vitreous cavity, vitreoschisis, and fibrovascular proliferation may be demonstrated.
Associated retinal detachment, usually tractional or combined, is sometimes seen.
The natural course of Eales’ disease is quite variable. Classically, an active perivas-
culitis stage leads to an ischemic stage followed by neovascularization of the retina and
subsequent recurrent vitreous hemorrhage. Some patients may lose vision significantly
due to recurrent episodes of vitreous hemorrhage, macular changes, and tractional or
combined retinal detachment involving macula. In others, a temporary or permanent
regression of the disease is noted. Blindness due to Eales’ disease is rare (10).
Charmis has classified Eales’ disease into four stages (12):
Stage I: Very early in evolution and characterized by mild periphlebitis of small peripheral
retinal capillaries, arterioles, and venules detected by ophthalmoscopy.
Stage II: Perivasculitis of the venous capillary system is widespread, larger veins are affected,
as are the arterioles lying by the side of affected veins. Vitreous haze is manifested.
Fig. 3. Montage photograph of fundus fluorescein angiogram showing areas of capillary
closure, engorged and tortuous capillaries, venovenous shunts, and leaking neovascular frond
in lower nasal quadrant.
Stage III: New vessel formation with abundant hemorrhage in the retina and vitreous humor
Stage IV: End result of massive and recurrent vitreous hemorrhages with retinitis prolifer-
ans and traction retinal detachment.
Saxena and Kumar (51) have recently proposed a new classification system:
Peripheral disease consists of four stages:
Stage 1 is periphlebitis of small (1a) and large (1b) caliber vessels with superficial retinal
Stage 2a denotes capillary nonperfusion and 2b neovascularization elsewhere/of the disk.
Stage 3a is classified as fibrovascular proliferation and 3b vitreous hemorrhage.
Stage 4a is traction/combined rhegmatogenous retinal detachment, whereas 4b is rubeosis
iridis, neovascular glaucoma, complicated cataract, and optic atrophy (peripheral type).
The etiopathogenesis of Eales’disease still remains unclear in spite of several clinical
and basic studies. Systemic association with several diseases, in particular tuberculosis,
has been described (7,13–15).
The list of the systemic diseases associated with Eales’ disease is summarized in
Table 1 (3).
Several biochemical studies have been done on the serum and vitreous samples of
patients with Eales’disease. Raised globulins and decreased albumin levels in the serum
Systemic Diseases Associated With Eales’ Disease
Hypersensitivity to tuberculoprotein
Acute or subacute myelopathy
Multifocal white matter abnormality
Increased plasma viscosity, erythrocyte rigidity, and erythrocyte aggregation
Blood coagulation disorder
Impaired oxygen release from blood
Raised fibrinolytic activity
Parasitic infection (amoebiasis, ascariasis)