new trends in management of uveitis
DESCRIPTION
This is appt presentation done by me and my colleagues zakaria Abul-Nasser and Sara Hassan ( agroup of medical undergarduates , school of Medicine, Ain-shams university , Cairo , Egypt ) ... This work was presented at the end of our Ophthalmolgy clinical round .. I Hope every one to get the best out of the presentaion ..Any commentaries are even more appreciated :)TRANSCRIPT
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) .