New Trends In Management Of Uveitis

Agenda

General Considerations

• Classification Anatomical Clinical Pathological• Etiology/Pathogenesis •Symptoms •Signs •Complications

Investigations

•Overview •Differential Diagnosis •Lines Of Investigations (General & Special :Skin tests SerologyEnzyme assay HistopathologyImagingHLA typing

• Non-specific treatment mydriatics Steroids Systemic Immunosuppressive agents Interferons physical measures

• Specific treatment of the cause • Treatment of complications :

Inflammatory glaucomaPost-inflammatory glaucoma Complicated cataract Retinal detachment of exudative type Phthisis bulbi

• Surgical management

Management

Anterior uveitis

Intermediate uveitis

Posterior uveitis

Anatomical

Acute uveitis

Chronic uveitis

Clinical

General Considerations

Classification

General Considerations

Classification

Suppurative or purulent uveitis

Non-suppurative uveitis *Non-granulomatous uveitis *Granulomatous Uveitis

Pathological

General Considerations

Etiology

Infective

Non-Infective Syndromes of

unknown etiology

Exogenous Endogenous

Traumatic Allergic or Autoimmune

Sympathetic ophthalmitis

General Considerations

Symptoms

Post.Uveitis (Choroiditis)

Ant. Uveitis (Iridocyclitis )

Patients are free of pain, although they report blurred vision and floaters

Choroiditis is painless, as the choroid is devoid of sensory nerve fibers.

Acute: • Dull pain in the eye or forehead• Impaired vision• photophobia•E xcessive tearing (epiphora).

Chronic: may exhibit minimal symptoms

General Considerations

Signs

Acute Iridocyclitis Intense circum-corneal ciliary injection small Pupil Keratic precipitates (KPs) – endothelium dusting

by myriads of cells Flare and cells ( often intense ) Fibrinous exudate ( if severe ) Hypopyon ( if very severe ) The iris is usually unremarkable; occasionally

shows dilated capillaries

•

General Considerations

Signs

Chronic Iridocyclitis

Injection ……… mild or absent Pupil ………. Unremarkable KPs........ mutton-fat in granulomatous disease Flare and cells …….. Variable Fibrinous exudate ……. absent

General Considerations

Signs

Post.uveitis (Choroiditis) Vasculitis of retinal vessels is possible Isolated or multiple choroiditis foci. Occasionally the major choroidal vessels will be

visible through the atrophic scars No cells will be found in the vitreous body in a

primary choroidal process .However, inflammation proceeding from the retina (retinochoroiditis) will exhibit cellular infiltration of the vitreous body

Post.Uveitis Ant. Uveitis

Depends on the underlying disease and severity of the disease The inflammatory foci will heal within 2–6 weeks and form chorioretinal scars.

The scars will result in localized scotomas that will reduce visual acuity if the macula is affected

Acute: *Posterior synechiae (PS) …..> rare at

presentation but may form later *Cataract ….> absent

Glaucoma …..> rare

Chronic: *PS – common at presentation

*Cataract – rare at presentation but may develop later

*Glaucoma – rare at presentation but may develop later

General Considerations

Complications

Differential Diagnosis

It is important to note that uveitis can be caused or mimicked by the following:

“Masquerade Syndromes”- neoplasms mimicking uveitis Ocular malignant melanoma Retinoblastoma Reticulum Cell Sarcoma (Primary Intraocular Lymphoma) Leukaemia - Lymphoma - Ocular Metastasis Endophthalmitis Retinal detachment Intraocular foreign body

Investigations

General Investigations

ESR / Plasma Viscosity/ C Reactive Protein CXR / FBC / Syphilis Serology: TPHA, VDRL Urine analysis (Diabetes Mellitus)

Skin Tests:Tuberclin skin testspathergy test : for diagnosis of Behcet's syndrome

Serology:

Investigations

Special Investigations

Toxoplasmosis

*Dye test (Sabin-Feldeman) * Immunoflurescent antibody

* Heamagglutination tests *ELISA

Syphilis

*Non treponemal :RPR & VDRL *Treponemal : FTA-ABS &

MHA-TP

Investigations

Special Investigations

Enzyme assay

*(ACE)*Lysozyme has good

sensitivity but lessspecificity than ACE

Imaging

*Flurescin angiography

*Iodocyanine green angiography

*Ultrasonography (US) *Optical coherence

tornography (OCT)

Biopsy:Ocular biopsies:

*Conjunctiva and lacrimal gland

*Aqueous sample *Vitreous biopsy

*Retinal and Choroidal biopsies.

Radiology:1 .Chest radiographs are to exclude tuberculosis and sarcoidosis.

2 .Sacroiliac joint x ray is helpful in the presence of a spondyloarthropathy in the presence of symptoms of low back pain and uveitis.

3 -CT and MRI of the brain and thorax are useful in sarcoidosis , multiple sclerosis and primary intraocular lymphomaHLA typing:

Investigations

Special Investigations

Associated disease

HLA type

Ankylosing spondylitisBircishot chorioretinopathyBehcet syndromePOHS and APMPPE

B27A29B51HLA - B7& DR2

Management

Non-specific treatment mydriatics Steroids Systemic Immunosuppressive agents AntimetabolitesInterferons physical measures

Specific treatment of the cause Treatment of complications :

Inflammatory glaucomaPost-inflammatory glaucoma Complicated cataract Retinal detachment of exudative type Phthisis bulbi

Surgical management

Mydriatics

Steroids

Systemic Immunosuppressive Agents

Interferons

Physical measures

I.Non-specific treatment

Mydriatics

Short-acting

Tropicamide (0. 5% and 1 %)..> 6h

Cyclopentolate (0. 5% and 1 %)..>24 h

Phenylephrine (2.5% and l0%) ..> 3h‘’ but no cycloplegic effects ‘’

Long –acting

Atropine 1%

is the most powerful cycloplegic and mydriatic with a duration of action lasting up to 2 weeks

Mydriatics

Indications

To relieving spasm of the ciliary muscle and pupillary sphincter ( usually with atropine )

To reduce exudation by decreasing hyperaemia and vascular permeability

To increases the blood supply to anterior uvea

To prevent formation of posterior synechiae by using a short-acting mydriatic which keeps the

pupil mobile.To break down recently formed synechiae with

intensive topical mydriatics (atropine. phenylephrine) or subconjunctival injections of

Mydricaine

Steroids

Route of administ

ration

Topical eyedrops or ointment

periocular injection Intravitreal

injection Systemic

Steroids

Indications

Treatment of acute anterior uveitisFrequently then gradually tapered . Often

discontinued by 5-6 weeks

Treatment of chronic anterior uveitisis more difficult because the inflammation may

last for months and even

Topical Steroids

Complications

Glaucoma Cataract Corneal

complications

systemic side effects

Steroids

Periocular injections

Advantages over topical steroids

Therapeutic concentrations behind the lens may be achieved.

water-soluble drugs incapable of penetrating the cornea when given topically, can enter the eye trans-sclerally. when given by periocular

injection

along-lasting effect can be achieved with depot preparations such as (methylprednisolone

acetate " Depomedrone" ).

Steroids

Periocular injections

Indications

Severe acute anterior uveitis

Intermediate uveitis

As an adjunct to topical or systemic therapy in resistant chronic anterior uveitis

Poor patient compliance with topical or systemic medication

At the time of surgery in eyes with uveitis

Steroids

Intravitreal injection

*Intravitreal steroid injection of is currently under evaluation.

* It has been used successfully in resistant uveitic chronic cystoid macular oedema.

Preparations

1- Oral prednisolone

* 5 mg is the main preparation.* Enteric coated tablets are useful in patients with acidpeptic disease.

2. Injections of (ACTH] * Useful in patients intolerant to oral steroids.

Indications

• Intractable anterior uveitis resistant to topical therapy and anterior sub-Tenon injections.

• Intermediate uveitis unresponsive to posterior subTenon injections.

•Certain types of posterior or panuveitis, particularly with severe bilateral involvement.

Steroids

Systemic therapy

General rules of administration • Start with a large dose and then reduce .

• A reasonable starting dose of prednisolone is 1mg/kg per day given in a single morning dose.

• Once the inflammation is brought under control , reduce the dose gradually over several weeks.

•If steroids aregiven for less than 2weeks , there is no need for gradual reduction.

Steroids

Systemic therapy

Steroids

Systemic therapy

• Dyspepsia • Mental changes

• Electrolye imbalance• Aseptic necrosis of the head of the

femur , and very rarely • Hyperosmolar , Hyperglycemic non-

ketotic coma

short term

therapy

• A Cushngoid state • Osteoporosis • Reactivation of infections such as TB • Cataract • Limitation of growth in children

Long term

therapy

Side effects

Antimetabolites T-cell inhibitors

Indications of Immunsuppressives: 1. Sight-threatening uveitis. Which is usually bilateral , non-

infectious , reversible and has failed to respond to adequate steroid therapy.

2 .Steroid-sparing therapy in patients with intolerable side effects from systemic steroids.

Systemic Immunosuppressive agents

Mycophenolate mofetil

Methotrexate Azathioprine

alternative to other anti- metabolites

include variety of chronic non-infectious uveitis

mainly Behçet disease Indications

1 g per day is 7.5-25mg in a single dose once weekly

1-3 mg/kg per day (50 mg tabletet) orally once daily or in divided doses.

Dose

•gastrointestinal disturbance • bone marrow suppression.

•bone marrow suppression •hepatotoxicity and •Pneumonitis are serious but rarely occur with low-dose administration. The most common side effects are gastrointestinal.

• bone marrow suppression• gastrointestinal disturbances and hepatotoxicity.

Side effects

full blood counts and liver function tests every 1-2 months

full blood counts and liver function tests

every 1-2 months .

complete blood count every 4-6 weeks and liver function tests every 12 weeks

Monitoring

Antimetabolites

Systemic Immunosuppressive agents

Interferons

Indications

recombinant human IFN-α has been used with success to treat a variety of posterior uveitides, including those associated with •Behçet• Vogt-Koyanagi-Harada disease •sympathetic ophthalmia and idiopathic causes.

Routes of administration & Dose

• Interferon-α is given by subcutaneous injection

• started as a high dose of daily injections then tapered to lower-dose intermittent injections

• With this regimen, corticosteroids are tapered to as low doses as possible, and other immunosuppressants are discontinued prior to initiation of IFN-α therapy

Interferons

Side effects •The most common side effect of IFN-α therapy is flu-like symptom

Significant adverse effects•leukopenia,• alopecia, •elevated hepatic enzymes, •depression, and other central nervous system (CNS) effects• Drug-induced lupus

1-Hot fomentation It is very soothingdiminishes pain and increases circulation, and thus reduces the venous stasis. As a result more antibodies are brought and toxins are rained.

Hot fomentation can be done by dry heat or wet heat.

2 -Dark goggles These give a feeling of comfort, by reducing photophobia, lacrimation and

blepharospasm .

Physical measures

II. Specific treatment of the cause

• Unfortunately, in spite of the advanced diagnostic tests, still it is not possible to ascertain the cause in a large number of cases.

• So a full course of antitubercular drugs for underlying Koch’s disease, adequate treatment for syphilis, toxoplasmosis etc…, when detected should be carried out.

• When no cause is ascertained, a full course of broad

spectrum antibiotics may be helpful by eradicating some masked focus of infection in patients with non-granulomatous uveitis.

III. Treatment of complications

Inflammatory glaucoma (hypertensive uveitis)

0.5 % timolol maleate eyedrops twice aday

tablet acetazolamide (250 mg thrice a day)

Pilocarpine and latanoprost eye drops are contraindicated in inflammatory glaucoma

Post-inflammatory glaucoma

laser iridotomy

Surgical iridectomy may be done when laser is not available.

However, surgery should be performed in a quiet eye under high doses of corticosteroids

Complicated cataract

lens extraction

The presence of fresh KPs is considered a contraindication for intraocular surgery

III. Treatment of complications

Retinal detachment of exudative type

settles itself if uveitis is treated aggressively.

A tractional detachment requires vitrectomy and management of complicated retinal detachment, with poor visual prognosis

Phthisis bulbi

especially when painful, requires removal by

enucleation operation

IV. surgical management of patient with uveitis

Surgical indications in the management of uveitis include

visual rehabilitation diagnostic biopsy when findings may change the treatment plan removal of media opacities to monitor the posterior segment

Despite advances in anti-inflammatory and immunomodulatory therapy, permanent structural changes can occur in the eye that are best managed with surgery (e.g. cataract formation, secondary glaucoma, retinal detachment)

In preparing the eye for surgery, medical treatment should be intensified for a minimum of 3 months to achieve complete quiescence of inflammation (i.e. complete eradication of anterior

chamber cells, active vitreous cells) .