UVEITIS: OCULAR INFLAMMATORY DISEASE

BY: AMIT CHANDANSHIVEF.Y.M.PHARM.

GUIDE: Mrs. VIJAYA BHOGALE.

Content INTRO OF EYE STRUCTURE AND FUNCTION. INTRO OF UVEITIS. SIGNS AND SYMPTOMS. CAUSES. PATHOPHYSIOLOGY. DIAGNOSIS. TREATMENT. ROLE OF SOME NATURAL PRODUCT IN UVEITIS. PROGNOSIS. EPIDEMIOLOGY.CONCLUSION. REFERENCES.

Introduction to Eye

Most complicated organ in the human body.

A number of parts fitted together in a near-spherical

structure.

Each part in the system is responsible for a certain action.

Classification of Eye Structure External structure .

Internal structure .

External structure of Eye

Sclera: protects the inner parts of Eye.

Conjunctiva: Thin transparent membrane spread across the sclera.

Cornea: job of cornea is to refract the light that enters the eyes.

Iris: to control the size of the pupil.

Pupil: small opening located at the middle of the Iris.

Internal structure of Eye

Retina: Photosensitive cells that detect dim and colored lights.

Lens: Focuses light to the retina.

Aqueous Humor: Watery fluid present in area bet lens and cornea.

Vitreous Humor: Transparent semi-solid, jelly-like substance that

fills the interior of the eyes.

Optic nerve: Responsible for carrying the nerve impulses from

the photoreceptors to brain.

INTRODUCTION OF UVEITIS• Inflammation of the uvea.

• Twentieth century referred ‘‘ophthalmia.”

• Pigmented layer that lies between inner retina and

outer sclera and cornea.

• Uvea consists of middle layer of pigmented vascular

structures of the eye,

• Includes the iris, ciliary body, and choroid.

CLASSIFICATION OF UVEITIS

• ANTERIOR• INTERMEDIATE• POSTERIOR• PAN UVEITIC

Anterior uveitis Includes iridocyclitis and iritis.

Iritis is inflammation of the anterior chamber and iris.

Iridocyclitis presents the same symptoms as iritis, but also includes inflammation

in the ciliary body.

From two-thirds to 90% of uveitis cases are anterior in location.

This condition can occur as a single episode and subside with proper treatment.

Intermediate uveitis Known as pars planitis. Consists of vitritis -inflammation of cells in vitreous cavity. Deposition of inflammatory material on the pars plana. "Snowballs“,Inflammatory cells in the vitreous.

Posterior uveitis Chorioretinitis.

The inflammation of the retina and choroid.

Pan-uveitis Is the inflammation of all layers of the uvea.

SYMPTOMS AND SIGNS Anterior uveitis

Burning.

Redness.

Blurred vision.

Headaches.

Irregular pupil.

Eye pain.

Photophobia or sensitivity to light.

Floaters, which are dark spots that float in the visual field.

Intermediate uveitis

Most common:

Floaters.

Blurred vision.

Posterior uveitis Floaters.

Blurred vision.

Photopsia or seeing flashing lights.

CAUSES

Widely administered vaccines cause uveitis.

Noninfectious Causes.

Infectious causes.

Associated with systemic diseases.

Drug related side effects.

Noninfectious Causes Behcet disease.

Crohn's disease.

HLA-B27 related uveitis.

Sarcoidosis.

Spondyloarthritis.

Sympathetic ophthalmia.

Infectious Causes Brucellosis.

Leptospirosis.

Lyme disease.

Syphilis.

Tuberculosis.

Zika Fever.

Associated with systemic diseases

Inflammatory Bowel Disease.

Kawasaki's Disease.

Multiple Sclerosis.

Reactive Arthritis.

Sarcoidosis.

Whipple's Disease.

Drug related side effects

Rifabutin, a derivative of Rifampin has been

shown to cause uveitis.

Quinolones especially Moxifloxacin may lead

to uveitis.

All of the widely administered vaccines have

been reported to cause uveitis.

PATHOPHYSIOLOGY

Immunologic factors

Genetic Factors

Infectious agents

Immunologic factors Uveitis Is Driven By Th17t Cell Sub-population That Bear T-cell

Receptors Specific For Proteins Found In The Eye.

Not Detected Centrally Whether Due To Ocular Antigen Not Being Presented In

The Thymus.

Autoreactive T Cells Must Normally Be Held In Check By The Suppressive

Environment Produced By Microglia And Dendritic Cells In The Eye.

These Cells Produce Large Amounts Of TGF Beta And Other

Suppressive Cytokines,

Including IL-10, To Prevent Damage To The Eye By Reducing Inflammation

And Causing T Cells To Differentiate To Inducible T Reg Cells.

Cont…. Immune stimulation by bacteria and cellular stress is normally

suppressed by myeloid suppression while inducible T reg cells

prevention and clonal expansion of the autoreactive Th1 and

Th 17 cells that possess potential to cause damage to the eye.

Infection or other causes, this balance can be upset and auto

reactive T cells allowed to proliferate and migrate to the eye.

Entry to the eye, these cells may be returned to an inducible T

reg state by the presence of IL-10 and TGF-beta from

microglia.

Genetic Factors

The cause of non-infectious uveitis is unknown.

But there are some strong genetic factors that predispose

disease onset .

Including HLA-B27 and the PTPN22 genotype.  

Infectious agents

Recent evidence has pointed to reactivation of herpes

simplex, varicella zoster and other viruses as

important causes.

Bacterial infection is another significant contributing

factor in developing uveitis.

DIAGNOSIS Diagnosis includes dilated fundus examination to rule out

posterior uveitis, which presents with white spots across the retina along with retinitis and vasculitis.

Laboratory testing is usually used to diagnose specific underlying diseases, including rheumatologic tests (e.g. antinuclear antibody, rheumatoid factor, angiotensin converting enzyme inhibitor) Serology for infectious diseases (e.g. Syphilis, Toxoplasmosis, Tuberculosis).

fig. Keratic precipitates

TREATMENT What should treatment achieve?

1. Relieve pain and discomfort.2. Prevent sight loss due to the disease or its

complications.3. Treat the cause of the disease where possible, that is,

treat the inflammation. The drugs used to treat uveitis fall into 3 main groups. 1) Steroids 2) Immunosuppressant. 3) Mydriatics.

STEROIDS Steroids have wide ranging effects but their action may be looked on as being anti-inflammatory and immunosuppressant". They are used in different forms: • Eye drops. • Periocular injections. • By oral (tablets).• Intra-venous infusion (drip).

Eye Drops:

Used for Anterior Uveitis.

Drops can penetrate the part of the eye in front of the lens, where anterior uveitis occurs.

Frequency of taking the drops depending on severity of the uveitis.

Severe Cases strongest drop-every hour .

Mild inflammation weakest drop once or twice a day.

Periocular Injections:

Use of injections around the eye to deliver the steroid treatment.

In certain situations injections offer a better way than either tablets or drops.

They are used along with other forms of treatment.

Situations where injections are used include:

• Severe cases of anterior uveitis which can not be controlled by drops alone.

• Intermediate uveitis.

Systemic Steroids:

• Oral Steroids E.g. Prednisolone Tablet.

• The use of systemic steroids is more serious than, steroid drops because in this form

there are potentially significant side effects.

• Many different situations in which oral steroids are considered.

• If anterior uveitis is resistant to treatment with drops and injections then systemic

steroids considered.

• The main use of oral steroids is to treat posterior uveitis , panuveitis.

Dosage: Prednisolone tablet 1mg and 5mg.

Intra-venous Steroids:

E.g. Methylprednisolone.

• when rapid control of inflammation is needed high dosage of steroid needs to be

delivered quickly.

Side Effects Of Steroids

Nausea , Dyspepsia

Increased Appetite ,

Weight Gain, Fluid

Retention

Diabetes , Osteoporo

sis

Glaucoma , Cataract.

IMMUNOSUPPRESSANT Steroids do suppress the immune system,but there are

a different group of drugs that may be used to treat uveitis.

These drugs tend to target the immune system more precisely than steroids.

They are usually used in conjunction with steroids. The main examples are: Cyclosporine. Azathioprine (Imuran). Methotrexate. Mycophenolate mofetil (cellcept). Tacrolimus (Prograf 500). 

MYDRIATICS Mydriatics have 2 main aims:-

To relieve pain and light sensitivity.

To prevent sight threatening complications.

Mydriatic eye drops, Eg. Atropine and Cyclopentolate are used.

It works by "paralyzing" the muscles of the iris and the ciliary body.

It taken their effect the pupils will be dilated. This may cause

Blurring of the vision.

Useful because they help prevent complication which may occur in

anterior uveitis.

ROLE OF SOME NATURAL PRODUCT IN UVEITIS

TURMERIC:

Benefits for Uveitis:

From 2010.

Antioxidant properties, protect and boost the functioning of the

immune system.

Turmeric help in the reduction of chronic uveitis symptoms.

Research studies which have found that turmeric can prove

beneficial for uveitis.

Study study on a curcumin-phosphatidyl choline compound called

Meriva or Norflo tablets, treating chronic anterior uveitis. given twice daily to patients with differing etiologies of this

condition. There were 106 patients studied over a 12 month period. They were divided into 3 groups Autoimmune Uveitis. Herpetic Uveitis. Different Uveitis Etiologies. results found that all patients well tolerated Meriva Tablet. It reduced eye discomfort in around 80% of patients after a few

weeks. Conclusion: curcumin based medications could benefit those

with anterior uveitis .

Dosage: 375mg Tablet 3 times daily.Precautions: Diabetes or Gall Bladder problems must avoid turmeric

supplements. Taken in excess, it can cause Diarrhea Or Nausea. Contraindicated in Pregnant and Breastfeeding women.

MARKETED PREPARATION: Uvical pills. Curcumin phytosome 500mg caps. Turmeric curcumin 500mg caps.

PROGNOSIS: Prognosis is good for those who receive prompt diagnosis and treatment. But serious complication including Cataracts, Glaucoma, And Permanent

Vision Loss may result.

EPIDEMIOLOGY: Uveitis affects approximately 1 in 4500 people and is most common

between the ages 20 to 60 with men and women affected equally. In western countries, anterior uveitis accounts for between 50% -90% , in

Asian countries the proportion is between 28% -50%. Uveitis is responsible for approximately 10%-20% of the Blindness in the

United States.

CONCLUSION: Corticosteroids is the main stay of treatment in uveitis. Immunosuppressives have the treatment in chronic uveitis.

Better understanding of immunology and uveitic diseases help providing more targeted treatment in uveitis.

The future holds great promise for uveitis with continuing development of newer drugs.

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4. Larson, T; Nussenblatt, RB; Sen, HN (June 2011)."Emerging drugs for uveitis". Expert opinion on emerging drugs. PMC 3102121.PMID 21210752.

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6. CDC: Department of Human Services (9 September 1994). "Uveitis Associated with Rifabutin Therapy". 43(35);658: Morbidity and Mortality Weekly Report. Retrieved 5 May 2013.

7. Risk for Uveitis With Oral Moxifloxacin". JAMA Ophthalmology online. 2 October 2014.