Uveitis is a general term describing a group of inflammatory diseases that produces swelling and destroys eye tissues. These diseases can slightly reduce vision or lead to severe vision loss.
The term “uveitis” is used because the diseases often affect a part of the eye called the uvea. Nevertheless, uveitis is not limited to the uvea. These diseases also affect the lens, retina, optic nerve, and vitreous, producing reduced vision or blindness.
Uveitis may be caused by problems or diseases occurring in the eye or it can be part of an inflammatory disease affecting other parts of the body.
It can happen at all ages and primarily affects people between 20 ñ 60 years old.
Uveitis can last for a short (acute) or a long (chronic) time. The severest forms of uveitis reoccur many times.
Eye care professionals may describe the disease more specifically as:
- Anterior uveitis
- Intermediate uveitis
- Posterior uveitis
- Panuveitis uveitis
Eye care professionals may also describe the disease as infectious or noninfectious uveitis.
What is the Uvea and What Parts of the Eye are Most Affected by Uveitis?
The uvea is the middle layer of the eye which contains much of the eye’s blood vessels (see diagram). This is one way that inflammatory cells can enter the eye.
Located between the sclera, the eye’s white outer coat, and the inner layer of the eye, called the retina, the uvea consists of the iris, ciliary body, and choroid:
Iris: The colored circle at the front of the eye. It defines eye color, secretes nutrients to keep the lens healthy, and controls the amount of light that enters the eye by adjusting the size of the pupil.
Ciliary Body: It is located between the iris and the choroid. It helps the eye focus by controlling the shape of the lens and it provides nutrients to keep the lens healthy.
Choroid: A thin, spongy network of blood vessels, which primarily provides nutrients to the retina.
Uveitis disrupts vision by primarily causing problems with the lens, retina, optic nerve, and vitreous.
Permanent loss of vision is most commonly seen in patients with chronic cystoid macular edema (CME). Every effort must be made to eradicate CME when present. Other less common causes of visual loss include rhegmatogenous retinal detachment, glaucoma, band keratopathy, cataracts, vitreous hemorrhage, epiretinal membrane, and choroidal neovascularization.
No racial predilection exists for this disease.
The incidence of intermediate uveitis is equal in men and women.
Although intermediate uveitis can develop at any age, it primarily afflicts children and young adults. There is a bimodal distribution with one peak in the second decade and another peak in the third or fourth decade.
In the pediatric age group, intermediate uveitis is associated with a worse presenting visual acuity. Poorer outcomes may be related to delayed presentation/diagnosis, the inherent difficulties of immunosuppression in children, or a more aggressive disease.
What Causes Uveitis?
Uveitis is caused by inflammatory responses inside the eye.
Inflammation is the body’s natural response to tissue damage, germs, or toxins. It produces swelling, redness, heat, and destroys tissues as certain white blood cells rush to the affected part of the body to contain or eliminate the insult.
Uveitis may be caused by:
- An attack from the body’s own immune system (autoimmunity).
- Infections or tumors occurring within the eye or in other parts of the body.
- Bruises to the eye.
- Toxins that may penetrate the eye.
The disease will cause symptoms, such as decreased vision, pain, light sensitivity, and increased floaters. In many cases the cause is unknown.
Uveitis is usually classified by where it occurs in the eye.
What is Anterior Uveitis?
Anterior uveitis occurs in the front of the eye. It is the most common form of uveitis, predominantly occurring in young and middle-aged people.
Many cases occur in healthy people and may only affect one eye but some are associated with rheumatologic, skin, gastrointestinal, lung and infectious diseases.
What is Intermediate Uveitis?
Intermediate uveitis is commonly seen in young adults. The center of the inflammation often appears in the vitreous (see diagram). It has been linked to several disorders including, sarcoidosis and multiple sclerosis.
What is Posterior Uveitis?
Posterior uveitis is the least common form of uveitis. It primarily occurs in the back of the eye, often involving both the retina and the choroid. It is often called choroditis or chorioretinitis. There are many infectious and non-infectious causes to posterior uveitis.
What is Pan-Uveitis?
Pan-uveitis is a term used when all three major parts of the eye are affected by inflammation. Behcet’s disease is one of the most well-known forms of pan-uveitis and it greatly damages the retina.
Intermediate, posterior, and pan-uveitis are the most severe and highly recurrent forms of uveitis. They often cause blindness if left untreated.
Diseases Associated with Uveitis
Uveitis can be associated with many diseases including:
- Ankylosing spondylitis
- Behcet’s syndrome
- CMV retinitis
- Herpes zoster infection
- Kawasaki disease
- Multiple sclerosis
- Reactive arthritis
- Rheumatoid arthritis
- Ulcerative colitis
- Vogt Koyanagi Harada’s disease
What are the Symptoms?
Uveitis can affect one or both eyes. Symptoms may develop rapidly and can include:
- Blurred vision
- Dark, floating spots in the vision (floaters)
- Eye pain
- Redness of the eye
- Sensitivity to light (photophobia)
Anyone suffering eye pain, severe light sensitivity, and any change in vision should immediately be examined by an ophthalmologist.
The signs and symptoms of uveitis depend on the type of inflammation.
Acute anterior uveitis may occur in one or both eyes and in adults is characterized by eye pain, blurred vision, sensitivity to light, a small pupil, and redness.
Intermediate uveitis causes blurred vision and floaters. Usually it is not associated with pain.
Posterior uveitis can produce vision loss. This type of uveitis can only be detected during an eye examination.
How is uveitis detected?
Diagnosis of uveitis includes a thorough examination and the recording of the patient’s complete medical history. Laboratory tests may be done to rule out an infection or an autoimmune disorder.
A central nervous system evaluation will often be performed on patients with a subgroup of intermediate uveitis, called pars planitis, to determine whether they have multiple sclerosis which is often associated with pars planitis.
The eye exams used, include:
An Eye Chart or Visual Acuity Test: This test measures whether a patient’s vision has decreased.
- A Funduscopic Exam: The pupil is widened (dilated) with eye drops and then a light is shown through with an instrument called an ophthalmoscope to noninvasively inspect the back, inside part of the eye.
- Ocular Pressure: An instrument, such a tonometer or a tonopen, measures the pressure inside the eye. Drops that numb the eye may be used for this test.
- A Slit Lamp Exam: A slit lamp noninvasively inspects much of the eye. It can inspect the front and back parts of the eye and some lamps may be equipped with a tonometer to measure eye pressure. A dye called fluorescein, which makes blood vessels easier to see, may be added to the eye during the examination. The dye only temporarily stains the eye.
Treatment of intermediate uveitis is undertaken to prevent permanent structural damage to vital ocular tissue, and, as a consequence, the method outlined by Kaplan is outdated.
While mild asymptomatic vitreous cell may not require immediate treatment, any evidence of CME, neovascularization of the peripheral retina, extensive vasculitis, or significant vitreous cell requires treatment.
Treatment is no longer based on an arbitrary level of vision. As with most forms of uveitis, corticosteroids are the mainstay of therapy.
Topical therapy with prednisolone acetate 1% or prednisolone sodium phosphate 1% is only helpful in the treatment of the anterior segment inflammation. The intravitreal concentration of administered topically is too low to be efficacious in the face of moderate-to-severe vitritis, especially in the phakic patient.
Periocular injections of corticosteroids are preferentially given in unilateral cases and occasionally in bilateral cases. Triamcinolone acetonide can be administered superotemporally into the sub-Tenon space or through the inferior eyelid into the retroseptal space
. If the disease is not controlled after 2-3 injections given over an 8-week period, systemic prednisone should be considered. Some authorities advocate the use of a combination of betamethasone and depot methylprednisolone in an effort to achieve early onset and prolonged duration of action.
Oral prednisone may be the preferred treatment in patients with bilateral intermediate uveitis or in cases resistant to topical or periocular steroids. A purified protein derivative (PPD) test is imperative prior to starting any patient on systemic corticosteroids if there are any risk factors for TB.
Once the inflammation stabilizes, the oral dose is tapered according to disease activity. An H2 blocker (Tagamet or Zantac) or a proton pump inhibitor (Prilosec or Prevacid) can be prescribed adjunctively to oral steroids.
Intravitreal triamcinolone acetonide injections have been used to treat CME. In a case series by Hogewind et al, of 33 eyes with intermediate or posterior uveitis and refractory CME, 50% improved greater than 2 lines at 3 months; but, by 12 months, the proportion of improved eyes declined to 40%.
Several small case series have explored the use of somatostatin analogues (Octreotide) IM and intravitreal bevacizumab (Avastin) in patients with refractory uveitic CME.
For recalcitrant cases with high corticosteroid requirements to control the inflammation, the surgical implantation of a device releasing fluocinolone acetonide in the vitreous can be considered (see Surgical Care).
In the event that corticosteroids cannot control the intermediate uveitis or in those whose disease invariably flares when steroids are discontinued, immunosuppressive therapy often is attempted.
Immunosuppression or immune-modulation is also used as part of the concept of steroid-sparing therapy in an effort to reduce the patient’s requirement for systemic corticosteroids and, therefore, to diminish the adverse effects of systemic corticosteroid therapy.
Cyclosporine, tacrolimus, azathioprine, and methotrexate are the most commonly used agents with documented efficacy in many uveitic conditions. Chlorambucil can be considered for intractable cases. They can be used concurrently with corticosteroids as steroid sparing agents or alone.
Murphy et al prospectively evaluated the efficacy and the safety of cyclosporine and tacrolimus in patients with posterior and intermediate uveitis.
The 2 agents did show a similar response rate (approximately 67%), but cyclosporine was associated with a higher incidence of adverse effects.
The use of infliximab, an anti-tumor necrosis factor (anti-TNF) monoclonal antibody, has been shown to be effective in improving macular thickness and visual acuity in patients with uveitic refractory CME due to intermediate uveitis or other noninfectious uveitis.
Initial successful reports by Markomichelakis et al were duplicated by Rajaraman et al in a pediatric population in which infliximab achieved reduction in intraocular inflammation with concurrent elimination or decrease in steroid requirements.
Daclizumab, an interleukin-2 receptor blocking antibody, has been shown to be effective in noninfectious uveitis in a multicenter nonrandomized interventional case series. It allowed control of ocular inflammation with stability in visual acuity with reduction of concomitant immunosuppression by at least 50%.
Finally, interferon-beta (INF-beta), which has an established value in the treatment of MS, appears to have a positive effect in terms of visual acuity, CME, and aqueous and vitreous inflammation in intermediate uveitis associated with MS.