Treatment of uveitis

In cases of uveitis, early etiological diagnosis, timely initiation of etiotropic and pathogenetic treatment using immunocorrective agents and replacement immunotherapy are important for preventing chronic progression, bilateral eye damage and relapses of uveitis.

The main thing in the treatment of uveitis is to prevent the development of complications that threaten vision loss and to treat the disease underlying the pathological changes (if possible). There are 3 groups of drugs: mydriatics, steroids, systemic immunosuppressive drugs. Antimicrobial and antiviral drugs are also used to treat uveitis of infectious etiology.

Mydriatics

Short-acting drugs

• Tropicamide (0.5% and 1%), duration of action up to 6 hours.
• Cyclopentol (0.5% and 1%), duration of action up to 24 hours.
• Phenylephrine (2.5% and 10%), duration of action up to 3 hours, but without cycloplegic effect.

Long-acting: atropine 1% has a strong cycloplegic and mydriatic effect, duration of action is about 2 weeks.

Indications for use

1. To relieve discomfort, eliminate spasm of the ciliary muscle and sphincter, atropine is used, but it is not recommended to use it more than 1-2 med. If signs of weakening of the inflammatory process appear, it is necessary to replace this drug with a short-acting mydriatic, such as tropicamide or cyclopentolate.
2. Short-acting mydriatics are used to prevent the formation of posterior synechiae. In chronic anterior uveitis and moderate inflammation, they are instilled once at night to avoid accommodation disturbance. However, posterior synechiae can also form with a long-term dilated pupil. In children, long-term atropinization can cause the development of amblyopia.
3. To rupture formed adhesions, intensive instillation of mydriatics (atropine, phenylephrine) or their subconjunctival injections (adrenaline, atropine and procaine) are used.

Steroid drugs in the treatment of uveitis

Steroids are the main component of uveitis treatment. The options for administration are: locally, in the form of drops or ointments, parabulbar injections, intravitreal injections, systemically. Initially, regardless of the method of administration, steroids are prescribed in high doses with subsequent gradual reduction depending on the activity of the inflammatory process.

Topical steroid therapy for uveitis

Steroids are prescribed locally for anterior uveitis, since their therapeutic concentration is formed in front of the lens. It is preferable to use strong steroid drugs, such as dexamethasone, betamethasone and prednisolone, as opposed to fluorometholone. Solutions of drugs penetrate the cornea better than suspensions or ointments. However, the ointment can be applied at night. The frequency of instillation of eye drops depends on the severity of the inflammatory process and can vary from 1 drop every 5 minutes to 1 drop once a day.

Treatment of acute anterior uveitis depends on the severity of the inflammatory process. Initially, treatment is carried out every 15 minutes for several hours, and then the dose is gradually reduced to 4 times a day for several days. If the activity of the inflammatory process subsides, the frequency of instillations is reduced to 1 drop per week and instillation is stopped after 5-6 weeks. In order to dissolve the fibrinous exudate and prevent the subsequent development of glaucoma with pupillary block, tissue plasminogen activator (12.5 mcg in 0.1 ml) is injected into the anterior chamber using a needle.

Treatment of chronic anterior uveitis is quite complicated due to the existence of the inflammatory process for several months, and sometimes years. In case of exacerbation of the process (cells in the anterior chamber fluid +4), treatment is carried out as in acute anterior uveitis. When the process subsides (cells in the fluid to +1), the number of instillations is reduced to 1 drop per month with subsequent cancellation.

After stopping treatment, the patient should be examined within a few days to confirm the absence of signs of recurrent uveitis.

Complications of steroid use

• glaucoma;
• cataracts caused by the use of steroid drugs, both locally and systemically. The risk of developing cataracts depends on the dose and regimen of the drug;
• Corneal complications are uncommon and include secondary bacterial or fungal infections, herpes simplex virus keratitis, and corneal melting due to inhibition of collagen synthesis;
• Systemic complications caused by long-term drug use are common in children.

Parabulbar steroid injections

Advantages over local application:

• They help achieve therapeutic concentration behind the lens.
• Aqueous solutions of drugs are not able to penetrate the cornea when applied locally, but penetrate transsclerally when given parabulbar injections.
• A long-term effect is achieved by administering drugs such as triamcinolone acetonide (kenalog) or methylprednisolone acetate (denomedrone).

Indications for use

• Severe acute anterior uveitis, especially in patients with ankylosing spondylitis, with the presence of fibrinous exudate in the anterior chamber or hypopyon.
• As an additional treatment for chronic anterior uveitis, in the absence of positive dynamics from local and systemic therapy.
• Peripheral uveitis.
• Lack of patient consent for the use of local or systemic therapy.
• Surgical intervention for uveitis.

Conjunctival anesthesia

• instillation of a local anesthetic, such as amethocaine, every minute at 5-minute intervals;
• A small cotton ball soaked in a solution of amethocaine or another substance is placed in the conjunctival sac on the injection side for 5 minutes.

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Anterior sub-Tenon injection

• 1 ml of the steroid drug is drawn into a 2 ml syringe and a 10 mm long needle is inserted;
• the patient is asked to look in the direction opposite to the injection site (usually up);
• Using anatomical tweezers, grasp and lift the conjunctiva with Tenon's capsule;
• at some distance from the eyeball, a needle is inserted through the conjunctiva and Tenon's capsule at the point of their capture;
• 0.5 ml of the drug is slowly injected.

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Posterior sub-Tenon injection

• 1.5 ml of the steroid drug is drawn into a 2 ml syringe and a 16 mm long needle is inserted;
• the patient is asked to look in the direction opposite to the injection site: most often - towards the nose if the injection is made in the superotemporal quadrant;
• the puncture of the bulbar conjunctiva is made in close proximity to the eyeball, the needle is directed towards the orbital vault;
• Slowly advance the needle backwards, keeping it as close to the eyeball as possible. To prevent damage to the eyeball, make light, intermittent movements with the needle and observe the limbus area: displacement of the limbus area indicates perforation of the sclera.
• If it is impossible to advance the needle further, pull the plunger slightly towards you and, if there is no blood in the syringe, inject 1 ml of the preparation. If the needle is far from the eyeball, sufficient absorption of the steroid substance through the sclera may not occur.

An alternative method is to incise the conjunctiva and Tenon's capsule and inject the drug using a blind sub-Tenon's or lacrimal cannula.

Intravitreal steroid injection

Intravitreal injection of the steroid triamcinolone acetonide (2 mg in 0.05 ml) continues to be studied. The drug has been used successfully to treat cystoid macular edema in chronic uveitis.

Systemic steroid therapy

Systemic drugs for uveitis therapy:

• prednisolone 5 mg orally. Patients with increased acidity of gastric juice are prescribed film-coated tablets;
• Injections of adrenocorticotropic hormone are prescribed to patients if there is no effect from taking the drug orally.

Indications for the use of systemic therapy for uveitis

• Persistent anterior uveitis resistant to local therapy, including injection therapy.
• Peripheral uveitis refractory to posterior sub-Tenon injection.
• Certain episodes of posterior uveitis or panuveitis, especially with severe bilateral involvement.

General rules for prescribing drugs:

• They start with large doses of the drug, gradually reducing them.
• The recommended starting dose of predisolone is 1 mg per kg of body weight, taken once in the morning.
• As the activity of the inflammatory process decreases, the dose of the drug is gradually reduced over several weeks.
• When prescribing the drug for a period of less than 2 weeks, there is no need to gradually reduce the dose.

Side effects of systemic therapy depend on the duration of drug administration:

• Short-term therapy may lead to dyspeptic and mental disorders, electrolyte imbalance, aseptic necrosis of the scalp and thighs. Sometimes hyperosmolar hyperglycemic coma develops;
• Long-term therapy leads to the development of Cushingoid status, osteoporosis, growth retardation in children, exacerbation of diseases such as tuberculosis, diabetes, myopathy, and the appearance of cataracts.

Immunosuppressive drugs

Immunosuppressive drugs are divided into: antimetabolite (cytotoxic), T-cell inhibitors.

Indications for use:

1. Uveitis with the threat of vision loss, bilateral, non-infectious etiology, with frequent exacerbations, in the absence of effect from steroid therapy.
2. Pronounced side effects due to the use of steroid drugs. When initially prescribed a correctly selected dose of an immunosuppressive drug, the duration of administration is 6-24 months. Then the dose is gradually reduced and discontinued over the next 6-12 months. However, some patients need longer administration of the drug when monitoring the activity of the inflammatory process.

Antimetabolic agents

Azathioprine

• Indications: Behcet's disease:
• Dose: 1-3 mg per 1 kg of body weight (50 mg tablets) in the morning or the dose is selected individually;
• side effects: suppression of bone growth, gastrointestinal and hepatotoxic complications;
• control: complete blood count every 4-6 months and liver function tests every 12 days.

Methotrexate

• Indications: a group of chronic uveitis of non-infectious etiology, resistant to steroid therapy;
• Dose: 7.5-25 mg once a week;
• side effects: suppression of bone growth, hepatotoxic manifestations, pneumonia. When taking the drug in small doses, they are rare, gastrointestinal disorders are more often observed;
• control: complete blood count and liver function tests every 1-2 months.

Mycophenolate mofetil

• Indications: Not fully studied. Suggested for use as an alternative remedy;
• Dosage: 1 g 2 times a day;
• side effects: gastrointestinal disturbances and suppression of bone growth;
• control: general blood test initially weekly for 4 weeks, then less frequently.

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T cell inhibitors

Cyclosporine

• indications: Behcet's disease, peripheral uveitis, Vogt-Koyanagi-Harada syndrome, Birdshoi chorioretinitis, sympathetic ophthalmia, retinal vasculitis;
• Dose: 2-5 mg per 1 kg of body weight once every 2 doses;
• side effects: hypertensia, hirsutism, hyperplasia of the gingival mucosa, nephro- and hepatotoxic disorders;
• control: measurement of blood pressure, complete blood count and determination of liver and kidney function.

Tacrolimus (FK 506)

• Indications: not fully studied. Used as an alternative to cyclosporines in the absence of a positive effect from their use or the development of severe side effects;
• dose: 0.05-0.15 mg per 1 kg of body weight once a day;
• side effects: nephrotoxic and gastrointestinal disorders, hyperglycemia, neurological disorders;
• control: monitoring of blood pressure, kidney function, determination of blood glucose weekly, then less frequently.

Prevention of uveitis

Prevention of uveitis is a complex problem associated with the elimination of the impact of unfavorable environmental factors, as well as strengthening the defense mechanisms. Since intrauterine and early infection of children, as well as chronic contamination of humans with various viral and bacterial pathogens due to their widespread distribution in nature, are possible, the main measures to prevent uveitis should include:

1. prevention of new diseases and exacerbations of chronic infections (toxoplasmosis, tuberculosis, herpes, cytomegalovirus, rubella, influenza, etc.) in pregnant women, especially in family and other foci of infections;
2. elimination of the effects of unfavorable environmental factors (hypothermia, overheating, occupational hazards, stress, alcohol, eye injuries), especially in people suffering from frequent colds, chronic infections, various manifestations of allergies, syndromic diseases, meningoencephalitis;
3. prevention of transmission of infection to susceptible individuals, taking into account the sources and routes of infection in relation to the type of infectious agent, especially during the period of epidemic spread of viral and bacterial infections in children's groups and medical institutions.