1.Eales Disease Dr Gyanendra Lamichhane, Dr I. Kansakar Lumbini Eye InstituteBhairahawa,Nepal

2. References:

Retina and vitreous AAO (2004-2005)

Prospective study on idiopathic retinal vasculitis (Joshi S.N)

Clinical ophthalmology- 5 thedition (Jack J Kanski)

Retina 3 rdedition (Stephen J Ryan)

Atlas of ophthalmology (R.K. Parrish)

Principle and practice of ophthalmology (Peymen)

Eales disease An update Major Review (J. Biswas)

Survey of ophthalmology 2002

3. Introduction:

In 1880 and 1882,Henry Eales- primary recurrent retinal hemorrhage.

Similar conditions of retinal and vitreous hemorrhage were described under the name ofEales Disease.

Eales didnt mention any inflammatory signs preceding or accompanying the hemorrhages.

4.

In 1887Wadsworthreported on signs of inflammation of the retinal vasculature - Eales disease and periphlebitis

Elliotinitially suggested that the disease be calledperiphlebitis retinae.

5.

Currently, Eales disease is considered to be anidiopathic inflammatory venous occlusionthat primarily affects the peripheral retina.

Retinal changes includeperivasculitis, mainly periphlebitis, and peripheral non-perfusion.

This inflammation induced vascular occlusion can lead to a proliferative vascular retinopathy, with sequelae such as recurrent vitreous hemorrhage and traction retinal detachment.

6. Aetiopathogenesis:

Recognized as primary vasculitis of unknown etiology occurring in young adults.

Retinal vasculitis and peripheral retinal neovascularisation associated with various systemic and ocular disease could mimic Eales disease.

7. Systemic disease associated with Eales disease:

Systemic disorders associated with Eales disease:

Tuberculosis

Hypersensitivity to tuberculoprotein

Thromboangitis obliterans

Neurologic disease

Hematological abnormalities

8. Tuberculosis:

The assumption of tubercular aetiologyis based on active or healed tuberculosis in some patient with Eales disease.

Ophthalmoscopic evaluation in patient with active or healed TB showed1.3% had Eales disease .

9. Tuberculosis: contd

Presence of Tubercular bacilli DNA in epiretinal membrane(Madahavan et al)

2010 eyes with active pulmonary or extra pulmonary TB no Eales disease(Biswas J et al)

32 patient with Eales disease were followed up for 37 years, only one patient had active tuberculosis(William et al)

10. Hypersensitivity to tuberculoprotein:

Allergic reaction to tuberculosis has been reported by many authors till date.

Positive Mantoux reaction which is as high as 90% in some series.

11. Hypersensitivity to tuberculoprotein: contd

Ashton retina sensitized against tuberculoprotein andre-exposure leads to retinal vasculitis.

Ealesdiease has been reported in Mantoux negative patients and mantoux test positive in67-90%of healthy individuals.

12. Systemic disease:

Several studies have shown association between neurological and hematological disease.

bilateral hearing loss 48%(Renie et al), 25%(William et al).

2 pt with Eales disease had progressive worsening of neurological deficit(Rodier G).

Myelopathy with Eales disease has been described by many.

13. Immunological studies in Eales disease:

Immune mediated mechanism has been suggested by many authors as a possible cause of Eales disease.

Acute onset, steroid responsiveness, lymphocytic infiltration and abnormal immunological parameters all indicate an immunological basis of disease.

14. Immunological studies in Eales disease: contd

Altered immune response of type III and/or IV reaction to an infectious agent(Muthukaruppan et al).

Raised IgG and IgA levels(Johnson et al) , elevated levels of circulating immune complexes and antiretinal antibody(Kasp et al), immunophenotyping predominant T cell CD4

Higher frequencies of HLA B5(B51), DR1 and DR4(Biswas et al)

15. Biochemical studies in Eales disease:

Raised alpha-globulins and reduced albumin levels in the serum samples.

PDGF, IGF1, EDF, TGFa and TGFb play a key role in neovascularisation.

Raised serum alpha1 acid glycoproteins in 27 patients of Eales disease(Sen et al).

16. Stages of Eales disease

Stage I (inflammatory stage)

Localized areas of peripheral retinal edema with sheathing of the smaller caliber vascular branches.

Minute retinal hemorrhages as well as minute vascular brackets or hooklets connecting two adjoining vessels.

active periphlebitis with subhyaloid hemorrhage over the macula. 17. Active periphlebitis with tortuosity of veins as wellas multiple superficial retinal hemorrhage 18. Montage fundus photograph showing an active perivasculitis involving predominantly the peripheral retina of an Eales disease patient. 19.

Stage II (ischemic stage)

Involvement of larger vessels and extend more posteriorly

Veins as well as arterioles may be sheathed

Widespread retinal hemorrhages and vitreous looks hazy

20.

Stage III (stage of neovascularisation)

Peripheral new blood vessels with numerous vitreous and retinal hemorrhages.

The hemorrhages frequently recurs.

21. Sea fanlike neovascularisation of the retina. 22.

Stage IV (complicated stage)

Massive retinal proliferans

associated retinal and massive vitreous hemorrhage.

With this advanced disease the neovascular frond can cause tractional rhegmatogenous retinal detachment.

23. 24. Clinical features:

Usually occurs inyoung, healthy people, with a peak incidence between the ages of30 and 40years.

It occurs more frequently in males 80-90%.

75%cases it presents before 49 years.

Can be unilateral or bilateral.90% bilateral (Duke Elder)

56.14%had bilateral retinal vasculitis ( O.K Malla and coworkers)

25.

Vitreous floaters or blurring of vision, symptoms attributable to recurrent vitreous hemorrhages.

80%between the age of 20-40 years and95%were male(O.K Malla and co workers)

54.34% between 20-30 years and 94.73% male

Rare in more developed countries.

26.

More commonly reported from Indian subcontinent. The reported incidence in India is1 in 200-250patient

Anterior uveitis/Vitritis

Active perivasculitis with exudates around the veins in one or more quadrants. Arterioles may be affected.

27. Healed perivasculitis as sheathing of the veins Macular changes uncommon Peripheral retinal neovascularisation reported in 36-84% of cases Recurrent vitreous hemorrhages, the hall mark of the disease Some vitreous hemorrhages resolve, some do not( organize with multiple VR adhesions & RRD/TRD) Some patient specially with multiple sclerosis are asymptomatic. 28. Proliferative stage 29. Vitreous hemorrhage 30.

Eales disease

Exacerbations and remissions quiescent Rubeosis iridis Hemorrhagic glaucoma cataract Loss of eye Tractional RD Macular distortion Detachment Cystoid macular degenerationand Macular holes Tractional retinal breaks andRhegmatogenous RD 31. Healed perivasculitis with anastomotic arteriovenous shunt 32. Fibrovascular proliferation causing tractional retinal detachment 33. Healed perivasculitis with sclerosed vein and multiplechorioretinal atrophic patches 34. 35. 36. Fundus fluorescein angiography

To delineate areas of capillary nonperfusion, peripheral retinal nonperfusion is present in all patients with Eales disease.

Retinal or disc neovascularisation

Macular edema

Helps in monitoring the regression and disappearance of new vessels during treatment and follow up.

37. 38. FFA following laser photocoagulation of neovascular frond 39. Multiple veno venous shunts in late AV phase 40. Pathology:

Patchy perivascular or intramural infiltration of lymphocytes or granulation tissue sometimes with or without giant cells

Plasma cells are occasionally present.

Veins are primarily affected

The vascular changes are usually seen on retinal periphery.

41.

Hyalinization and thinning of vein wall

Narrowing and obstruction of the lumen

Endothelial cell proliferation

Thrombosis and rupture of the vein

Intravitreal new vessel formationand

Marked thickening of internal limiting membrane have been reported.

42. Diagnostic studies performed on patients with Eales disease

To rule out leukemia and hematological condition:

Hemoglobin and hematocrit

Total RBC count

Total WBC and Differential count

43.

II. Others tests:

Platelet count

ESR

Reticulocyte count

Blood sugar

Stool analysis

Mantoux test

Basic coagulation test

Sickle cell preparation

44.

Hemoglobin Electrophoresis

VDRL and TPHA test

Anti nuclear antibody

Serum ACE

Lysosome

45. Sarcoidosis Wegener Granulomatosis III. Radiological tests: 46. Differential diagnosis: Vasculitis mimicking Eales disease

Systemic Ocular

Behcets disease Birdshot retinochoroidopathy

Leukemia Coats disease

Lyme Borreliosis Pars planitis

Multiple sclerosis Viral retinitis

Sarcoidosis

Systemic lupus erythematosus

Toxocariasis

Toxoplasmosis

Tuberculosis

Wegeners granulomatosis

47. Proliferative vascular retinopathy mimicking Eales disease:

Systemic Ocular

Diabetes mellitus BRVO

Sarcoidosis CRVO

Sickle cell disease Coats disease

Pars planitis

ROP

48. Sarcoidosis Sarcoid nodules Bilateral hilar lymphadenopathy 49. Candle wax dipping 50. Vitritis and snowball Peripheral neovascularisation 51. leukemia 52. Sickle cell retinopathy Seafan neovascularisation 53. 54. Behcet disease Aphthous ulceration Erythema nodusum like lesions 55. Dermatographism Hypopyon 56. Occlusive vasculitis Retinal exudation and vascular occlusion 57. Treatment:

Symptomatic treatment.

Treatment aim

reducingretinal perivasculitisand associatedvitritis ;

reducing risk ofvitreous hemorrhagefrom new vessels by retinal ablation and surgical removal of non resolving vitreous hemorrhage and/or vitreous membranes.

58. Treatment of Eales disease:

Observation.

Medical

• Corticosteroids

• Antituberculosis drugs

• Immunosuppressive drugs.

Retinal ablation

• Photocoagulation

• cryotherapy

Surgical

• vitrectomy

59. Observation:

Patient with inactive retinal vasculitis

Follow up 6 months to 1 year interval.

Patient with fresh vitreous hemorrhage if retina is found to be attached.

Such vitreous hemorrhage usually clears by 6 to 8 weeks.

60. Medical therapy:

Corticosteroids are mainstay of therapy in active perivasculitis stage of Eales disease.

Majority of cases 1mg/kg body weight, tapered to 10mg/week over 6 to 8 weeks.

Maintenance 15 to 20mg/day for 1 to 2 months.

Periocular depot steroid injection may be added for associated macular edema.

61.

Systemic and Periocular steroid useful in patient having 3 quadrants involvement with macular edema.

Systemic steroid only if less than 3 quadrant involvement.

No difference in response between Mantoux positive and negative cases.

62.

Immunosuppressive therapy in patient unresponsive or have unacceptable side effects.

(Azathioprine and cyclosporine)

Some investigators have recommended ATT (Rifampicin and Isoniazid) for 9 months.

63. Photocoagulation:

Mainstay of therapy in proliferative stage of Eales disease.

The aim

Regulate the circulation

To obliterate surface neovascularisation and

Close leaking intraretinal microvascular abnormalities.

64.

Sectoral laser for capillary non perfusion and PRP for neovascularisation of disc.

Occasional massive hemorrhage can occur.

After laser, regressing neovascularisation can cause macular distortion and retinal tear.

Laser not advised in active inflammatory stage 65. FFA following laser photocoagulation of neovascular frond 66. Vitreoretinal surgery:

Vitrectomy alone or combined with other vitreoretinal surgical procedures is often required.

Nonresolving vitreous hemorrhage with obscuration of central vision of 3 mo duration may be subjected to vitrectomy.

67.

Vitrectomy done between 3 to 6 mo has better results than done after 6 months(Kumar et al).

Early vitrectomy in patient with TRD, extensive vitreous membranes or epimacular membranes.

Endolasercan be given along with vitrectomy.

68. Tractional radial retinal fold after vitrectomy 69. Summary and conclusions:

Characteristic clinical findings and angiographic pattern.

Mimic several ocular or systemic disease presenting as retinal vasculitis or proliferative retinal vasculopathy.

Hypersensitivity to tubercular protein has been considered a prime cause of Eales disease .

70.

Probable multifactorial etiology.

HLA, retinal autoimmunity, mycobacterium genome, free radical mediated damage.

Corticosteroids in active disease and laser photocoagulation in ischemic and proliferative stage.

Results of vitrectomy in non resolving vitreous hemorrhage with or without retinal detachment are satisfactory.

71. Thankyou Thankyou