Treatments
- Nelson Santos
- Mar 25, 2020
- 11 min read
Updated: Apr 3, 2022
Tere are multiple treatments for uveitis. Your doctor will choose the most appropriate one for you based on the following criteria: the cause of the inflammation, the location, its reactivation time and the severity of the symptoms. Of the factors mentioned above, the most important when choosing the treatment is: the cause of the uveitis. All treatments require great responsibility and discipline on the part of the patients, especially those cases that are treated long term.
Treatments for uveitis can be classified as either specific or non-specific. Specific treatments are used against infectious diseases and are designed to eradicate or control the exact cause of the infection. In contrast, non-specific treatments are used to treat non-infectious diseases. They help to suppress the autoimmune inflammatory mechanisms and thus remedy the symptoms caused by the disease. However, they do not cure the disease completely: the disease is "treated but not cured". Systemic administration of nonspecific treatments helps not only to improve the symptoms of uveitis, but also those symptoms in different parts of the body that could be associated with a systemic autoimmune disease. One of the peculiarities of ocular immunology is that there is no formula that can be applied to all cases of uveitis, although certain therapeutic conventions have been established for the management of these cases. Therefore, treatment is unique to each patient and is chosen at the discretion of the physician.
Cause of uveitis
Uveitis is mainly classified as infectious or non-infectious. This measure allows the physician to choose the most appropriate treatment quickly without risking the development of other complications. Infectious uveitis is treated with anti-infective drugs, which target the type of organism causing the infection (bacteria, fungus, virus or parasite). In appropriate cases, anti- infective medications may be accompanied by corticosteroids. In contrast, treatment for non- infectious uveitis is usually implemented as a “stepladder approach”: corticosteroids immunomodulators, surgery. The first therapeutic alternative for uveitis is usually corticosteroids. These can be administered in the following forms depending on the cause and location of the inflammation: drops, pills, periocular injections, intraocular injections or intravenous infusion However, corticosteroids are not considered a suitable long-term treatment due to the series of side effects they may cause, especially in children or people with other health conditions. For this reason, immunomodulators are the next therapeutic alternative in cases of non-infectious uveitis that meet the following criteria: the uveitis does not respond adequately to steroid treatment, requires long-term treatment or is associated with an autoimmune disease of local or systemic involvement. There are several types of immunomodulators that target specific elements of the immune system: antimetabolites, t-cell inhibitors, alkylating agents and biologic agents. These are available as pills, subcutaneous injections or intravenous infusion. The medical community emphasizes the importance of the use of immunomodulators as an alternative that spares the excessive use of corticosteroids in cases of non-infectious uveitis. Especially those that are recurrent or chronic. Finally, surgeries are the last therapeutic alternative for ocular inflammation and its sequelae. Generally, this alternative is reserved for cases that have not responded to other treatments or to correct complications that may have arisen from treatments or prolonged inflammation. Your doctors will choose the most appropriate treatment for you after evaluating you.
Anatomic location of inflammation
The administration of corticosteroids in non-infectious cases depends on the severity and location of the inflammation. Anterior uveitis is usually treated with topical corticosteroids (drops). Occasionally, this treatment may be accompanied by mydriatics or cycloplegics if the patient has ocular synechia. Peculiarly, intermediate uveitis does not always require treatment. In the absence of complications that could jeopardize the patient's vision, this type of uveitis gradually improves without the need for treatment. However, cases of intermediate uveitis that are associated with a systemic autoimmune disease and/or have complications, such as optic nerve or macular inflammation, are treated with corticosteroids administered as ocular injections or systemic routes. Topical corticosteroids, in the form of drops, are not an effective treatment for intermediate and posterior uveitis as they do not penetrate the inner areas of the eye.
Posterior uveitis is treated with corticosteroid medications administered in one of the following forms: pills, peri-ocular injections, intraocular injections or intravenous infusion. Some of the factors that determine the administration of corticosteroids are: severity of inflammation, health condition, intolerance, age, unilateral or bilateral uveitis, association with systemic autoimmune disease, patient preference. Ocular injections are preferred in patients intolerant to systemic corticosteroids or with unilateral inflammation, but should be avoided if infection is suspected; and corneal ulcers should always be ruled out before starting corticosteroid therapy. Corticosteroids administered systemically, in addition to rapidly controlling inflammation, suppress the immune-mediated inflammatory reaction. Thus, they are advantageous for treating posterior uveitis in both eyes (bilateral), correcting systemic symptoms associated with autoimmunity and modulating the immune system.
Finally, immunomodulators are a valuable therapeutic alternative for cases of non-infectious uveitis but, unlike corticosteroids, their effect is not immediate. They are usually administered systemically, through oral route (pills), subcutaneous injections or intravenous infusion. Occasionally, a combination of immunomodulators is implemented to treat uveitis and may be accompanied by corticosteroids, especially if there is an active episode of uveitis. The goal with this treatment is to progressively decrease and eliminate the use of corticosteroids.
The following table by Dr. Albert Vitale provides a summary of the administration of treatments according to the anatomical location of the inflammation:
Recurrences of inflammatory episodes
Corticosteroids are the first therapeutic alternative in acute cases of non-infectious uveitis. However, although they are very effective in controlling ocular inflammation quickly, they are not a recommended long-term treatment due to the side effects they produce. Therefore, immunomodulators are an alternative that should be strongly considered in recurrent cases of non-infectious uveitis, especially if they are associated with an autoimmune disease. In this way, the risk of structural damage to the eyes caused by the reactivation of inflammation and the occurrence of complications caused by the side effects of corticosteroids can be reduced.
Treatment against recurrent or chronic uveitis is longer than treatment against acute uveitis. This is because symptoms last longer and are sometimes more difficult to control, due to reactivation of inflammatory episodes. These cases should be routinely evaluated and treatment should be long-term. The prognosis of uveitis cases cannot be accurately determined as reactivation of inflammation is unpredictable. However, some diseases that may be causing uveitis are associated with a more aggressive course than others. Although most cases are idiopathic, the prognosis of those that are recurrent or chronic can be improved if the immune-mediated disease causing the inflammation is identified and effective treatment is implemented to induce inactivation of the uveitis episodes.
Severity of symptoms
All uveitis symptoms are serious but there are some that are more complex and require immediate treatment, especially if they compromise the patient's vision. Acute cases of non-infectious anterior uveitis are usually treated with corticosteroid eye drops. Acute cases of non-infectious posterior uveitis, on the other hand, may be treated with moderate/high doses of corticosteroids systemically or locally. This measure is necessary because posterior uveitis has a high risk of compromising the patient's vision and tends to become chronic, especially if there is inflammation of the macula. In this way, irreversible damage and/or the development of complications can be avoided. In addition, early implementation of immunomodulatory agents is of great advantage particularly in cases whose prognosis is aggressive or who have not responded to corticosteroid treatment. The goal of uveitis management is to preserve vision, avoid complications and side effects that may arise due to treatments.
Anti-infective agents
Infectious uveitis is primarily treated with anti-infective agents. There is a wide variety of anti-infective agents aimed at eradicating the infection caused by the organism, specifically. The medications used are: antibiotics, antivirals, antifungals and dewormers. In appropriate cases, these medications may be accompanied by corticosteroids to ameliorate the symptoms of inflammation. The use of corticosteroids as a non-specific treatment of uveitis is contraindicated in infectious cases. Therefore, treatment for infectious uveitis should be specific, aimed at curing the infection. Commonly used drugs:
Triple-sulfa, Sulfadiazine, Pyrimethamine, Clindamycin, Trimethoprim-sulfamethoxazole, Spiromycin, Atovaquone, Azithromycin, Clarithromycin, Minocycline, Tobramycin and Dexamethasone.
The side effects of anti-infective agents are varied, but most are manageable. It is extremely important to complete the treatment according to your doctor's instructions. Do not stop taking these medications even after your symptoms have disappeared and you feel better.
Corticosteroids
The first alternative to treat non-infectious uveitis is corticosteroids. Corticosteroids are anti-
inflammatory drugs derived from cholesterol. They are very effective in controlling inflammation rapidly, but their prolonged use is contraindicated. Despite being an excellent anti-inflammatory, they produce a number of unpleasant side effects. Some of these side effects may be severe, especially if used for a long time. The greatest effectiveness of corticosteroids is achieved by implementing sufficiently high doses for the shortest amount of time possible. Corticosteroids can also be implemented for a short period of time together with immunomodulatory therapy in cases that require it. To ensure proper record keeping of doses and their gradual decreases, you can download and print the following systemic corticosteroid registry in Documents.
Local therapy: topicals, injectables or implants
Topical corticosteroids:
Topical corticosteroids, in the form of drops/eye drops, are used to treat anterior uveitis. They are usually prescribed to be administered every few hours during the day on a case-by-case basis.
Medications:
Prednisolone acetate 1% - every one to two hour
Difluprednate 0.05% - four to eight times a day
Rimexolone acetate 1% - every one to two hours
Periocular or intraocular injections:
Corticosteroids can also be administered through ocular injections. They are usually used in acute and remitting cases of intermediate, posterior or diffuse uveitis; when the inflammation is unilateral, the macula is inflamed, systemic treatment is contraindicated or the patient is already under systemic treatment. Corticosteroids administered through ocular injections produce fewer side effects than systemic corticosteroids, since the treatment is localized. Intraocular injections are used as a second alternative to periocular injections when these have been ineffective, the uveitis is severe and has not responded to systemic treatments.
Medications for periocular injections:
Triamcinolone acetate: 40mg/mL
Methylprednisolone: 20mg/mL-40mg/mL
Medications for intraocular injections:
Triamcinolone acetonide: 2-4mg/0.05-0.1cc
Implants:
Corticosteroids can also be administered through the surgical placement of an implant in the eye that delivers the drug in a sustained manner. It is an alternative reserved for cases of non-infectious intermediate, posterior or diffuse non-infectious uveitis (panuveitis). It may be beneficial in cases where the inflammation cannot be controlled with the other alternatives, patients show intolerance to systemic therapy or due to individual case factors.
Medications:
Dexamethasone DDS (Ozurdex®)
Fluocinolone acetonide (Retisert®)
Fluocinolone acetonide intravitreal insert (Yutig®)
Systemic therapy: pills or infusions
Systemic corticosteroids in pill form:
Systemic corticosteroids are used to treat intermediate, posterior or diffuse uveitis. Generally, they are used when the inflammation occurs in both eyes (bilateral), affects structures essential for vision or is very severe. Both their anti-inflammatory effect and their side effects are reflected throughout the body, because the medication "travels" through the blood. Therefore, the use of systemic corticosteroids may not only help improve uveitis but also help alleviate systemic symptoms associated with autoimmune inflammatory processes. Systemic corticosteroids are administered in moderate or high doses, which are gradually tapered over weeks or months.
Medications:
Prednisolone: 1.0mg/kg/day
Intravenous infusion
Intravenous infusions are performed in person at a hospital or medical facility.
Medication:
IV Pulse methylprednisolone: 1.0gm/day for 2-3hrs for three days
It is extremely important not to discontinue the use of these medications suddenly, as it may cause rebound inflammation or health complications. Follow your doctors' instructions and comply with the treatment exactly as directed in order to avoid complications. Remember that you should not consume alcohol if you are under treatment with systemic corticosteroids.
Immunomodulators
Immunomodulators are a therapeutic alternative of great benefit in cases of uveitis that require them. They often cause apprehension, but most patients tolerate the side effects well and maintain a good quality of life. Administered responsibly, these drugs are highly effective in managing chronic cases of non-infectious uveitis. They are a safe alternative as a long-term treatment. Immunomodulators are drugs that target specific aspects of the immune system. Their effect is gradual, as opposed to corticosteroids. For this reason, they are often initially implemented in conjunction with corticosteroid medications, particularly if there are active episodes of uveitis. There is a wide variety of immunomodulators available, but the most commonly used to treat uveitis are: antimetabolites, t-cell inhibitors, alkylating agents and biologic agents. Generally, immunomodulatory therapy is used on a long-term basis and sometimes involves more than a single drug.
Cases of non-infectious uveitis that meet the following criteria should be evaluated as candidates for immunomodulatory treatment:
Association with autoimmune disease - Identifying the exact cause of the inflammation may improve the prognosis of some cases, as some immune-mediated diseases are associated with a more aggressive course and respond poorly to corticosteroid treatment. These causes are: serpiginous choroiditis, multifocal choroiditis and panuveitis (MCP), Birdshot chorioretinopathy, Vogt-Koyanagi-Harada syndrome and Behçet's disease.
Inflammation does not respond to corticosteroid treatment and recurs - Patient has inflammation even while on corticosteroid treatment, so the dose cannot be decreased to less than 10mg within three months of starting treatment.
Inflammation cannot be controlled under corticosteroid treatment for a period of six months.
Three or more episodes of uveitis occur per year. Some patients show resistance to corticosteroid treatment.
Intolerance to corticosteroids - The patient has a health condition that contraindicates steroid treatment (hypertension, diabetes, osteoporosis, depression, anxiety, etc)
Uveitis requires chronic treatment with corticosteroids: minimum dose of 7.5mg/day for three months or more.
Age - Pediatric cases should be carefully evaluated and systemic steroid therapy should be excluded or limited. Immunomodulatory treatment should be promptly considered
Detrimental side effects caused by corticosteroids.
Antimetabolites
Antimetabolites are drugs that inhibit the proliferation of metabolites by altering DNA synthesis and certain metabolic processes.
Among them are:
Methotrexate (MTX): 2.5mg-20.0mg orally, once a week 15mg/mL-25mg/mL subcutaneous injection once a week
Mycophenolate Mofetil (MMF): 500mg-3,000mg orally, daily
Azathioprine (AZA): 2.0-3.0mg/kg/day orally
T-cell inhibitors
T-cell inhibitors, as their name suggests, inhibit the functioning of t-cell, an enzyme essential in autoimmune inflammatory reactions,
Among them are:
Cyclosporin: 2.5-5.0mg/kg/day orally
Tacrolimus: 1.0mg-3.0mg orally, daily
Alkylating agents
Alkylating agents work directly on the DNA of cells to inhibit their life cycle. Of all the immunomodulators, they produce the most dangerous side effects. For this reason, they are usually reserved for severe and complex cases.
Among them are:
Chlorambucil: 0.1mg/kg/day
Cyclophosphamide: 1.0-2.0mg/kg/day 500mg-kg/m2 once a month. orally. Maximum dose of 250mg/day
Biological agents: tumor necrosis factor alpha inhibitors.
Biologic agents are a type of immunomodulator that has recently been implemented as a treatment for uveitis. They have been a successful alternative in cases of uveitis that have not responded to treatment with other immunomodulatory drugs. They are not agents that induce complete remission of uveitis, as some patients have recurrences when the drug is removed, but they help to control it effectively. There are different types of biologic agents, but the most commonly used to treat uveitis is the tumor necrosis factor alpha inhibitor, or anti-TNF. Tumor necrosis factor-alpha is an inflammatory cytokine that plays an important role in many of the body's inflammatory responses and changes vascular permeability. Biological agents can also be implemented in combination with other types of immunomodulators.
Among them are:
Adalimumab (Humira®): an initial dose of 80mg/1.6mL, then a bi-weekly dose of 40mg/0.8mL.
Infliximab (Remicade®) intravenous infusions performed by healthcare professionals in a hospital ward every few months. The doses of this drug may be modified.
Surgeries
Surgeries are usually reserved as a last therapeutic measure to remedy some complications that may arise from uveitis or its treatments.
Glaucoma
Cataract
Retinal detachment
Vitrectomy
Cryotherapy
Laser photocoagulation
Other
It is not unusual for uveitis treatment to also include medications to treat other symptoms, complications or side effects associated with ocular inflammation. These may include: mydriatic and cycloplegic agents, non-steroidal anti-inflammatory drugs (NSAIDs) or medications to treat intraocular pressure.
Mydriatics and cycloplegics
Mydriatic and cycloplegic agents are used in the form of drops or subconjunctival injections to treat ocular synechia, a condition in which the iris sticks to the cornea (anterior) or crystalline lens (posterior). This condition is extremely painful and usually occurs in cases of anterior uveitis, but not always. The function of this medication is to dilate the pupil in order to reduce the pain associated with the inflammation.
Medications:
Atropine 1%: 1-2 times a day
Scopolamine 0.25%: 1-2 times daily
Cyclopentolate 1%: 1-4 times daily
Nonsteroidal anti-inflammatory agents (NSAIDs)
Nonsteroidal anti-inflammatory agents are anti-inflammatory drugs that do not come from cholesterol. They are generally used to treat postoperative inflammation and macular edema, but can also be implemented as an alternative to steroid treatment. They are available in the form of pills or prescription drops.
Medications:
Topical: ketorolac, tromethamine, nepafenac, diclofenac
Pills: naproxen, celecoxib, indomethacin, meloxicam
Ocular injections: subconjunctival injection
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