Uveitis: what is it, causes, symptoms and treatment, prognosis

general information

Uveitis Is a condition that involves inflammation of the uveal tract (iris, ciliary body, choroid) or adjacent structures of the eye (retina, optic nerve, vitreous, sclera). In most cases, the etiology (cause) of the disease remains unclear, often being autoimmune in nature. When the etiology is known, infectious agents or trauma are the most important causes.

• Patient with anterior uveitis has eye pain, erythema, photophobia, excessive tearing and blurred vision. Pain usually develops after a few hours or days, except in cases of injury. Anterior chronic uveitis manifests itself as blurred vision, minimal chemosis, moderate pain or photophobia, except in an acute episode.
• Posterior uveitis
  causes blurred vision. Pain, chemosis and photophobia, symptoms of anterior uveitis are absent. Symptoms of posterior uveitis and pain suggest anterior chamber injury, bacterial endophthalmitis, or posterior scleritis.
• When intermediate uveitis the symptoms are similar to those of posterior uveitis: no pain and blurred vision.

With a sufficient history, a detailed physical examination, the use of diagnostic procedures and laboratory tests, an ophthalmologist can diagnose the disease in 80% of cases. The goal of uveitis treatment is to prevent vision loss, discomfort and eye disease. Initial therapy is nonspecific and consists of mydriatic agents - cycloplegic, corticosteroid, immunomodulatory and non-steroidal anti-inflammatory drugs. The dexamethasone (Ozurdex) intravitreal implant is approved and indicated for the treatment of non-infectious uveitis affecting the posterior segment of the eye.

Later, depending on the results of laboratory tests and special tests, a specific treatment may be prescribed. However, in most cases, only nonspecific treatment is required.

Forecast, generally good for patients receiving prompt treatment. Severe complications - cataract, glaucoma, keratopathy, macular edema, and permanent loss of vision can occur if the condition is left untreated. The type of uveitis, as well as the severity, duration, and response to treatment or other comorbid conditions, remain predictive factors.

Classification of uveitis

The most widely used classification of uveitis is according to the anatomical location of the inflammation. This classification includes:

• anterior uveitis (iritis, iridocyclitis, anterior cyclitis);
• intermediate uveitis (for planite, posterior cyclitis, hyalitis);
• posterior uveitis (focal, multifocal or diffuse choroiditis, choriortinitis, retinitis and neuroretinitis).

Another clinical classification of uveitis takes into account etiological criteria. It has three main categories:

• infectious uveitis (bacterial, fungal, viral, parasitic);
• non-infectious uveitis (known systemic associations, no known systemic associations);
• masquerade syndrome (neoplastic, non-tumor).

After anatomical classification uveitis is described as follows:

• onset (sudden or slow);
• duration (limited - up to 3 months or long-term - more than 3 months);
• development (acute, recurrent, or chronic);
• laterality (unilateral, bilateral).

Localization of the inflammatory process

Anatomical localization of the inflammatory process is one of the most important indications for pathogenesis and treatment.

Front.

Anterior uveitis involves inflammation of the anterior segment of the eye. This is the most common form of intraocular inflammation. Most patients do not have systemic disease. In 50% of patients with inflammation, anterior ocular disease is also predominant, caused either by trauma or, most commonly, idiopathic post-viral syndrome.

Uveitis syndromes associated with predominantly anterior segment involvement include HLA-B27 syndromes, herpes simplex virus infection, and shingles, Fuchs' heterochromic iridocyclitis and multiple arthritic syndromes. Secondary iatrogenic disease is observed in the postoperative period, especially with surgical complications, injuries, seton or sclerotic implants, corneal transplantation, capsule rupture or implantation of fixed intraocular lenses.

Intermediate.

The term intermediate uveitis is used when the main site of inflammation is in the middle part of the eyeball and includes posterior cyclitis, hyalite, choroiditis and chorioretinitis. The term intermediate is used if there is a concurrent infection (Lyme disease) or a systemic disease (sarcoidosis). Sometimes inflammation of the anterior vitreous cells may occur, indicating an earlier primary source of the disease. Intermediate uveitis or cyclitis is usually associated with underlying granulomatous diseases (tuberculosis, sarcoidosis, Lyme disease, syphilis).

Rear.

Posterior uveitis is inflammation of the choroid, retina, and optic nerve and includes retinochoroiditis, retinitis, and neuroretinitis. Retinitis is manifested by a toxoplasmic or herpes infection. Choroiditis can occur with any granulomatous uveitis (tuberculosis, sarcoidosis, syphilis), histoplasmosis, or more common syndromes such as serpigous chorioretinitis. At toxoplasmosis, viral retinitis, lymphoma, or sarcoidosis, optic papillitis may occur.

Panuveit.

The term is used for situations where there is no preferential localization of inflammation, but inflammation is observed in the anterior chamber, vitreous humor and retina / choroid. Diffuse uveitis, panuveitis, or endophthalmitis usually occurs with generalized infections such as childhood toxocariasis, postoperative bacterial endophthalmitis, or severe toxoplasmosis.

Pathophysiological mechanism

The etiology of uveitis is often idiopathic (spontaneous). However, it is known that genetic, traumatic or infectious mechanisms contribute to the onset of the disease. Diseases that predispose a patient to uveitis include:

• inflammatory bowel disease;
• rheumatoid arthritis;
• systemic lupus erythematosus;
• sarcoidosis;
• tuberculosis;
• syphilis;
• AIDS.

Traumatic mechanism is considered a combination of microbial contamination and the accumulation of necrotic products at the site of injury, stimulating pro-inflammatory processes.

For infectious etiology in uveitis, it is assumed that an immune response directed against foreign molecules or antigens can damage the vessels and cells of the uveal tract.

When uveitis is found along with autoimmune conditions, the mechanism may be a hypersensitivity reaction involving the accumulation of immune complexes in the uveal tract.

Risk factors

Although uveitis is commonly associated with systemic disease, approximately 50% of patients have idiopathic uveitis, which is not associated with any other clinical syndrome. Acute non-rangulomatous uveitis has been associated with diseases associated with the B27 human leukocyte antigen, including:

• ankylosing spondylitis;
• inflammatory bowel disease;
• reactive arthritis;
• psoriatic arthritis;
• Behcet's disease.

Herpes simplex, herpes zoster, Lyme disease, and trauma are also associated with acute nongranulomatous uveitis.

Chronic nonrangulomatous uveitis associated with rheumatoid arthritis, chronic renal iridocyclitis and heterochromic Fuchs iridocyclitis. Chronic granulomatous uveitis occurs in sarcoidosis, syphilis, and tuberculosis.

Posterior uveitis is found along with toxoplasmosis, ocular histoplasmosis, syphilis, sarcoidosis and in people with immunodeficiency herpes infection, candidiasis or cytomegalovirus. Embolic retinitis can also cause posterior uveitis.

Signs and symptoms

Symptoms and signs can be subtle and can vary depending on the location and severity of the inflammation.

• Anterior uveitis usually most symptomatic, usually with pain, redness, photophobia, and decreased visual acuity. Signs include flushing of the conjunctiva adjacent to the cornea.
• Intermediate uveitis as a rule, painless and accompanied by myodesiosis and decreased visual acuity. Visual acuity can be reduced due to myodesopsis or cystoid macular edema, which occurs as a result of extravasation of blood from the blood vessels into the macula.
• Posterior uveitis can cause various symptoms, but most often it causes myodesopsis and decreased visual acuity, as in the case of intermediate uveitis. Signs present include cells in the vitreous humor, white or yellowish lesions in the retina (retinitis) and / or in the choroid (choroiditis), exudative retinal detachments, retinal vasculitis and visual edema papilla.
• Diffuse uveitis may cause one or all of the above symptoms and signs.

The consequences of uveitis include profound and irreversible loss of vision, especially when it is not recognized and / or improperly handled. The most common complications include

• cataracts;
• glaucoma;
• retinal detachment;
• neovascularization of the retina, optic nerve or iris;
• cystic macular edema, which is the most common cause of decreased visual acuity in uveitis.

Diagnostics

Laboratory research

The following laboratory tests may be required:

• treponema-specific serology, such as fluorescence absorption assay of treponemal antibodies (FTA-ABS), for the diagnosis of syphilis
• sedimentation rate of erythrocytes, serum lysozyme and angiotensin-converting enzyme may aid in the assessment of patients with sarcoidosis; however, they are not specific or sensitive;
• HLA-B27 genetic typing;
• analysis of antibodies to nuclear antigens (ANA) and rheumatoid factor (RF) can be appointed if suspected juvenile idiopathic arthritis;
• Lyme serology should be performed if Lyme disease is suspected;
• serum creatinine, Analysis of urineincluding beta-2 microglobulin levels;
• ELISA test for toxoplasmosis with posterior uveitis.

Visualization studies

• A chest x-ray can help rule out sarcoidosis and tuberculosis. However, it is not very specific or sensitive.
• High-resolution CT is more sensitive than conventional x-rays for detecting sarcoidosis, and its should be done if x-ray is negative and sarcoidosis is suspected as an etiology inflammation of the eyes.
• X-rays of the sacroiliac, lumbar, and thoracolumbar spine may be required if ankylosing spondylitis is suspected.
• MRI of the brain may help in cases of suspected intraocular lymphoma or multiple sclerosis, and these two conditions are associated with intermediate and vitreous uveitis or subretinal lesions.

Additional procedures

• A biopsy of any subconjunctival nodes or lacrimal glands can help diagnose sarcoidosis.
• Vitreous biopsy may be indicated if there is a diagnostic dilemma or if an infection or masquerade syndrome is suspected.
• A lumbar puncture may be required to rule out intraocular lymphoma.

Uveitis treatment

Pharmacological therapy

Cycloplegic agents.

A long-acting cycloplegic agent such as scopolamine, homatropin, cyclopentolate, or even atropine, should be used to prevent posterior synechia formation in symptomatic acute anterior uveitis. Long-term use of strong cycloplegic drops is not recommended.

Corticosteroids.

This group of drugs should be actively used at the initial stage of therapy. In most cases of acute anterior uveitis (associated with HLA-B27), topical corticosteroids, such as prednisolone acetate 1%, are administered every hour first. Difluprednate can be used in less frequent doses and may be useful when a stronger effect is desired. Subconjunctival injection of late-acting steroids may be helpful if the patient is not receiving topical therapy or the irritation is not responding to topical corticosteroids alone. Subtenon injection of a long-acting corticosteroid such as triamcinolone acetate intended for more severe episodes, especially if associated with cystoid yellow edema spots.

In severe cases of anterior uveitis, the addition of an oral corticosteroid to the topical regimen may be necessary. High intraocular pressure therapy is performed as directed. For anterior viral uveitis, antiviral therapy may be helpful, including valganciclovir to suppress cytomegalovirus. In chronic cases, such as anterior uveitis associated with juvenile rheumatoid arthritis, systemic immunomodulatory agents may be required.

Systemic immunomodulators.

Immunomodulatory and immunosuppressive drugs may be helpful in patients who do not respond to corticosteroids who have chronic uveitis or who develop severe side effects after use corticosteroids. Various agents have been used including methotrexate, azathioprine, cyclosporin A, mycophenolate mofetil, cyclophosphamide, and chlorambucil. Myelosuppression and secondary infections are the most common side effects of these agents.

Tumor necrosis factor alpha (TNF-alpha) inhibitors may be useful in patients with seronegative spondyloarthropathy, including ankylosing spondylitis. These agents include infliximab, etanercept, and adalimumab. Infliximab is effective in reducing the number of previous episodes of uveitis in patients with ankylosing spondylitis. And adalimumab can be effective.

Surgical therapy

Surgical intervention includes treatment of complications (cataracts, retinal detachment, glaucoma) or targeted treatment in case of severe intraocular inflammation by implantation at the level of the vitreous body of certain devices that release locally powerful anti-inflammatory drugs.

In most cases, after correct treatment, uveitis heals without complications, but this requires the patient's full cooperation with a doctor who must inform the attending physician of any changes in symptoms, follow the recommendations of the ophthalmologist and do everything necessary.

Course and prognosis

Patients need medical supervisionas steroid therapy is gradually reduced until the inflammation is completely eliminated. The patient will be re-evaluated 2-3 weeks after stopping all medication to confirm that there is no sign of inflammation.

At chronic granulomatous irritation corticosteroid therapy should be continued for a longer period, 2-3 years. Some diseases are chronic and require very long-term treatment. After the termination of the action of immunomodulators, the disease can recur within a few months.

Repeated episodes of irritation and secondary therapy can lead to cataract formation and glaucoma. Prolonged hypotension due to dysfunction of the ciliary body (atrophy and detachment) is rare.

In cases granulomatous uveitis most patients will have recurrent inflammation. The overall visual prognosis for patients with recurrent irritation is good in the absence of cataracts, glaucoma, or posterior uveitis.