2200
Refers to a intraocular inflammation which may be related to an infectious agent or an immune mediated process.
Site threatening intraocular inflammation that is the fifth most common cause of severe vision loss in high income nations.
It is estimated to be responsible for 10-15% of all cases of blindness in the US.
Affects 38 to 714 per 100,000 people worldwide and is reported to be associated with up to 1/4 of cases of blindness in low and middle income countries and 3 to 10% of vision impairment in the US and Europe.
The uvea, the middle part of the eye consists of the iris, ciliary body, and choroid.
Can be associated with a systemic disease or eye limited disease.
A healthy eye possesses immune privilege, allowing it to suppress immune responses against endogenous antigens that stop excess sensing of light, and exogenous antigens such as bacterial proteins.
The immune privilege is maintained by the blood-retina barrier and cellular mechanisms that include regulatory, T cells and cytokinine mechanisms, including transforming growth factor beta and IL-10.
Non-infectious uveitis is hypothesized to result from reduced immune tolerance to retinal proteins, leading to inflammation, while infectious uveitis the infectious organism breaches the blood-retina barrier and may contain proteins resembling retinal proteins, exacerbating the inflammatory response.
Naïve CD4 T Cells are activated and differentiate into Th1 and TH17 subsets and migrate to the retina.
These T cells release pro-inflammatory cytokines triggering a cytokine cascade that recruits immune cells such as macrophages, and neutrophils leading to chorioretinitis, vasculitis, and edema.
Affects people of all ages.
Most commonly affects young and middle age adults age 20 to 50 years.
May lead to a greater years of vision loss than other age related diseases.
It is diagnosed when there is inflammation of the uvea, such as chorioretinitis, or when leukocytes are present in the anterior chamber of the eye or in the vitreous humor.
It is classified according to the inflamed portion of the uvea: anterior, intermediate, and posterior uveitis, as well as panuveitis.
The cause of uveitis is associated with the location of the inflammation in the uveal tract.
Symptoms include eye redness, pain, photophobia, floaters, and blurred vision.
Pain is sharp and worsened by bright light or reading and there is periimbal redness.
Up to 50% of patients with anterior uveitis have vision loss.
With posterior uveitis patients may present with vision loss and patient report, painless floaters, and blurred vision.
Untreated uveitis may cause cataracts, glaucoma, macular edema, retinal detachment, optic nerve damage, and vision loss.
Causes of uveitis are divided into categories including: infection, immune mediated, reaction to medication, trauma, and syndromes that masquerade as uveitis such as cancer, usually B-cell lymphoma.
Etiologies, including autoimmune diseases-multiple sclerosis (one percent), systemic immune mediated inflammatory diseases-sarcoidosis (2-17%) and auto inflammatory diseases, such as rare, genetic disorders, infections, including tuberculosis (1 – 13%, syphilis (1-4%) HIV (1-4%), and toxoplasmosis (5-7%) , adverse reactions to medications -immune checkpoint inhibitors (less than 0.5%).
More common in females
May be associated with systemic diseases such as sarcoidosis or a spondyloarthritis, or eye limited and presumed to be autoimmune or auto inflammatory along with an infectious nature.
Uveitis inflammation includes the uveal tract, and related structures including the retina, sclera and orbit.
Geographic variation in the etiology and presentation is related to the prevalence of risk factors such as infections, air pollution, smoking, and genetic variables.
The underlying cause of uveitis is unidentified in 27 to 51% of cases.
Uveitis may occur at any age, but most frequently occurs and young and middle-age adults in 60 to 80% of cases with ages 20 to 50 years.
It is more common in females than males, particularly in patients with multiple sclerosis, which makes up 75% in females, juvenile, idiopathic arthritis, and sarcoidosis.
Toxoplasmosis related and herpes related uveitis are the most common infectious causes of uveitis in high income countries with tuberculosis and HIV related more prevalent and low and middle income countries.
The most common cause of uveitis in Turkey is Behcet’s disease.
Its association with HLA-B 27 is more common in men.
In the US and Europe 37 to 49% of cases are associated with systemic disease such as axial spondyloarthritis.
Classified by the predominant location of inflammation, anterior uveitis, if in the anterior chamber, intermediate uveitis if in the vitreous, and posterior uveitis in the retina or choroid.
Panuveitis refers to inflammation in all of the above sites.
In US and Europe, an anterior uveitis is the most common followed by posterior, intermediate, and panuveitis.
Limited type disease refers to uveitis of less than three months duration or persistent type that lasst longer than three months.
The prevalence of posterior uveitis 0.004%.
Anterior uveitis is the most common type and manifests with sudden onset of severe photosensitivity, eye pain, blurred vision, and red eye.
Anterior uveitis affects the iris and ciliary body, intermediate uveitis affects the pars plana and peripheral retina, the posterior uveitis involves the choroid and retina, and panuveitis involves all uveal layers.
Uveitis is classified as non-infectious or infectious, with toxoplasmosis, herpes, tuberculosis, and HIV.
The incidence and prevalence of uveitis are influenced by genetic factors-HLAB 27, environmental factors of air pollution and infection rates.
In the US and Europe, 27 to 51% of cases are idiopathic and 37 to 49% are associated with systemic diseases such as axial spondylarthritis.
Anterior uveitis is associated with systemic disease diseases, such as axiospondyloarthritis and tuberculosis.
Intermediate uveitis is associated with multiple sclerosis.
Causes of posterior uveitis include toxoplasmosis and sarcoidosis.
Panuveitisn is also associated with toxoplasmosis and sarcoidosis.
Clinical examination with anterior uveitis reveals decreased vision, limbal injection, corneal endothelial precipitates, anterior chamber reaction with white cells and light scattering caused by increased protein concentration.
Anterior uveitis is associated with juvenile idiopathic arthritis.
Anterior uveitis is commonly idiopathic, but it may be associated with HLA B 27.
Anterior uveitis associated with psoriatic arthropathy, Reiter’s syndrome, inflammatory bowel disease, Behcet’s syndrome, SLE, granulomatous polyangitis, and sarcoidosis.
Anterior uveitis may be caused by postsurgical infectious endophthalmitis.
May be assoiated with lymphomas.
Infectious agents that can cause anterior uveitis include tuberculosis, syphilis, Lyme disease, herpes simplex virus, toxoplasmosis, tuberculosis, B henselae, and varicella-zoster virus.
Diagnosis requires history and dilated funduscopy.
Differential diagnosis includes: sarcoidosis, syphilis, tuberculosis, and herpetic infections.
Diagnosis requires a slit lamp to examine the anterior segment of the eye and the handheld lens for the fundus.
The anterior of uveitis on slip lamp exam includes a cellular infiltrate in the anterior chamber and chronic precipitates.
In an intermediate uveitis cellular infiltrate appears in the vitreous humor.
In posterior uveitis, choroid and/or retinal inflammation occur in the ocular fundus.
Patients who present with unilateral anterior uveitis without systemic findings, including autoimmune disease, do not require additional testing.
Patients with recurrent or bilateral anterior uveitis, intermediate uveitis, posterior uveitis, or pan uveitis are tested for infection and systemic disease diseases.
Aqueous humor, and or vitreous sampling should be performed if infection is suspected.
Treatment:
Treatment goals are to induce and maintain remission while minimizing corticosteroid use.
Usually responds to topical and systemic corticosteroids.
Inflammatory disorders associated with uveitis should be treated.
Treatment depends on subtype of disease, infectious exposures, age, comorbidities, country of origin, signs of infection, and site threatening features of uveitis.
Anterior uveitis is treated with topical corticosteroids and mild intermediate uveitis may be monitored without initial treatment.
With moderate to severe intermediate uveitis and posterior uveitis and panuveitis are at high risk for sight threatening complications and requires systemic or intravitreal corticosteroids and immunosuppressive agents.
Systemic corticosteroids are recommended for severe non-infectious anterior uveitis that does not improve or worsens with topical or regional corticosteroids.
Timely management is critical to prevent permanent vision loss.
Ocular, hypertension, glaucoma and cataracts can develop from prolonged topical, periocular, intravitreal implant, and systemic corticosteroid use.
Systemic corticosteroids are typically used to achieve remission in patients with non-infectious posterior uveitis, regardless of its cause.
Guidelines recommend systemic corticosteroids in combination with disease modifying antirheumatic drugs (DMARDd) as first line therapy for non-infectious posterior uveitis to control severe/persistent inflammation and decrease the risk of complications.
Anti-metabolite methotrexate and mycophenolaye mofetil commonly used in posterior uveitis as an initial corticosteroid sparing treatments before progressing to biologic therapies.
For patients with poorly controlled, non-infectious posterior uveitis despite treatment with DMARDs, biologic therapy is the second line treatment with adalimumab having the strongest evidence of effectiveness.
In patients who do not improve or worsen with first line therapies adalimumab extends time to treatment failure.
Golimumab and certolizumab are biologic agents that block tumor necrosis factor and are associated with a reduction in anterior uveitis in patients with axial spondyloarthritis.
In patients with infectious uveitis treating the underlying infection with systemic and a local antimicrobials are required: Corticosteroids may be added, depending on clinical findings, but should not be used alone for viral retinitis or toxoplasmosis.
Ocular hypertension, glaucoma, and cataracts can develop from prolonged topical, periocular, intravitreal implant, and systemic corticosteroid use.
Treatment of infectious panuveitos (endophthalmitis) varies based on whether the source of infection is exogenous or endigenous.
Exogenous cases require intravitreal antimicrobials,while endogenous cases are treated with systemic antimicrobialtarget infection management.
Tuberculosis associated uveitis is treated as tuberculosis infection elsewhere.
Syphilitic uveitis is treated with benzathine penicillin.