It is important in the treatment of uveitis to establish both immediate control and long term control over the disease process. Treatments for each disease are chosen based on their efficacy and tolerability by the patient. Medications that are well suited for immediate control may not be appropriate for long term control, and vice versa.
Immediate control refers to eliminating active inflammation , using therapy that may not be sustainable for the long term—often high dose corticosteroids in some form. Immediate control is the essential first step in managing ocular inflammation.
Long-term control involves preventing inflammation from reactivating after it has been rendered inactive. It is made difficult by the fact that corticosteroids, which are almost always the therapy used to achieve immediate control, have numerous side effects making them unsuitable for long term use. Long-term control thus requires finding the therapy that has the fewest side effects, but is still able to prevent disease recurrence. This may include low dose corticosteroids, corticosteroid injections, implants, or immunosuppressive drugs. Most practitioners find long term control to be the most challenging part of uveitis management.
No class of drugs is as rapid or as efficacious as corticosteroids in achieving immediate control of inflammation. Thus, when patients present with ocular inflammation that we believe is not infectious, corticosteroids are the first drugs that we use. This drug class includes a number of different agents, which are selected based on their potency and side effect profile. Side effects of corticosteroid eyedrops include elevations of intraocular pressure (IOP) and cataract formation, which limits their utility for long-term control of inflammatory processes.
Once we have found topical steroids effective and safe in a particular patient, we consider giving a periocular steroid injection. This modality of administration is useful for a sustained, local anti-inflammatory effect. The choice of medication for periocular injection is based on its potency and side effects. Periocular injections are perfomed routinely in the office setting once the eye has been anesthetized. Patients report these injections to be largely pain-free. Side effects of periocular steroid injections are the same as for topical steroids, including elevations of IOP and cataract formation, as well as the risks of the injection itself, including bleeding and inadvertent damage to the eye. Patients should be aware that the use of corticosteroids for periocular injection is off-label. Certain conditions are also amenable to systemic oral treatment or intraocular injections of corticosteroids.
Immunomodulators and Biologics
While some patients can maintain long term control of their ocular inflammation with corticosteroids alone, patients with chronic disease of any severity often benefit from steroid-sparing immunomodulatory drugs. Chemotherapeutic anti-cancer agents, immunosuppressive drugs, and “biologic” drugs (usually synthesized antibodies or cytokine receptors) can play a useful role in the long term management of uveitis and scleritis. They can eliminate the need for a prolonged corticosteroid course, which often is fraught with an even greater side effect profile and more immunosuppression than these drugs. These drugs are indicated in patients who need long-term control of their inflammation in the following circumstances:
In cases of steroid intolerance, usually due either to intraocular pressure elevation or to cataract formation.
In situations with disease in multiple organ systems, such as children with juvenile idiopathic (juvenile rheumatoid) arthritis who have iritis and arthritis, or patients with sarcoid uveitis who active pulmonary (or any bodily) inflammation.
In certain very severe uveitic entities, which are an indication for immediate immunomodulatory therapy, namely: 1) Sympathetic Ophthalmia, 2) Vogt-Koyanagi-Harada syndrome, 3) Behcet disease, and 4) Rheumatoid scleritis.
The choice of immunomodulatory drug is based on the severity and type of inflammation, any associated systemic diseases, as well as the patient's age and any family planning issues.
Patients are reasonable candidates for these agents if they are capable of adhering to sometimes complicated treatment and laboratory regimens, they understand the risks and benefits of therapy, and they want to take the drug. The pros and cons of immunomodulatory therapy versus corticosteroids must be carefully considered. While the patient can avoid the side effects of corticosteroids by using this therapy, these drugs all carry their own side effects, they take several weeks to show an effect, and they are less reliably effective than corticosteroids. They are not approved by the FDA for eye disease, and all use is considered “off-label.”
Cataracts. The formation of cataracts is a common complication of uveitis, occurring in 50% of patients. Cataracts are more frequent in chronic anterior and intermediate uveitis. Up to 83% of patients with juvenile idiopathic arthritis (JIA) and 50% of patients with pars planitis and Fuch’s heterochromic cyclitis will develop cataracts. Patients with uveitis tend to develop cataracts at an earlier age than other age-matched patients. Cataract formation is related to the localization, severity, and chronicity of the inflammation. The decision for cataract extraction in uveitis patients are often judge on a case by case basis dependent on the severity of disease, time frame of last uveitis flare up, management of additional ocular comorbidities (amblyopia, cystoid macular edema, glaucoma, retinitis, and retinochoroiditis). The placement of an intraocular lens (IOL) at the time of cataract extraction is an equally difficult decision and is also made on an individual basis. Certain uveitic entities such as JIA typically do not tolerate IOL placement at the time of surgery. A secondary IOL implantation at a later stage is usually recommended in these chronic recalcitrant uveitis cases.
Glaucoma. The concept of uveitic glaucoma was first introduced by Priestly Smith in 1891. However, the first reported association between uveitis and glaucoma was in 1813 by Joseph Beer. Later, specific types of uveitic glaucoma were described in 1906 by Fuchs (Fuch’s heterochromic uveitis) and in 1948 by Posner and Schlossman (glaucomatocyclitic crisis). Secondary glaucoma is seen in 10% of patients with uveitis. Prevalence of glaucoma varies with the type of uveitis, age of the patient, chronicity of the disease, and severity of the uveitis. Common causes of increase intraocular pressure associated uveitis is related to inflammation of the trabecular meshwork, clogging of the drainage system due to inflammatory cells and pigment, peripheral anterior synechiae, and posterior synechiae, formation of pupillary membranes and steroid response. Treatment options start with a range of topical therapeutics to reduce the intraocular pressure. Surgical options are indicated when medical management has failed. Preparation for intraocular surgery should include perioperative topical and occasionally systemic corticosteroids to avoid exacerbation of the uveitis leading to failure of the surgery. If possible, inflammation should be quiescent for at least three months prior to any surgical procedure. Perioperative course of systemic steroids may include 0.5 to 1.0 mg/kg/day of oral prednisone or 40mg of infraorbital methylprednisolone at the conclusion of the surgery. In cases of steroid-induced glaucoma, temporary immunosuppressive/cytotoxic agents may need to be substituted to control inflammation in the perioperative period. Surgical options, depending on the cause and severity of the glaucoma, include the following:
Trabeculectomy with or without Wound Modulation Therapy
Ab Interno Laser Sclerostomy
Glaucoma Drainage Device Implantation (Molteno, Baerveldt, Krupin, and Ahmed valves)
Cystoid Macular Edema (CME). Cystoid macular edema (CME) is the most common cause of visual loss in patients with uveitis. The incidence varies between the different uveitis syndromes. CME is the more prevalent cause of vision loss in adults with uveitis compared to pediatric uveitis. This difference is felt secondary to the higher resistance of young tissues to external damage. The overall incidence of visual impairment secondary to macular edema in uveitic patients is 41%. Chronic cystoid macular edema can lead to permanent damage to the retina leading to lamellar macular holes, full thickness macular holes, and cystoid macular degeneration.
Choroidal neovascularization. Choroidal neovascularization is an uncommon complication of posterior uveitis that can have devastating visual consequences. Diagnosis can be difficult as active choroiditis may appear similar to CNV lesions on slit-lamp examination and fluorescein angiogram. The use of ICG angiography is invaluable in helping to distinguish between the two. The treatment of this complex problem is not simple nor is the decision making process. Few prospective studies have been done directly looking at the outcomes of treatment for uveitic-related CNV. Most treatment studies have looked at presumed ocular histoplasmosis syndrome and recommendations for other uveitic-related CNV are extrapolated from those data.
Retinal detachment. Retinal detachment is separated into three uniquely different categories of tractional, serous and rhegmatogenous retinal detachments. The pathogenesis of retinal detachment is related to the infiltration of vitreous cells, posterior vitreous detachment, formation of preretinal fibrosis, and active choroiditis with exudative leakage of subretinal fluid. The proper diagnosis of the cause of the retinal detachment is critical for the treatment of the disease. Serous retinal detachment demonstrates smooth doomed retinal elevation with shifting subretinal fluid. Rhegmatogenous retinal detachment (RRD) occurs in 3.1% of patients with uveitis and is related to the early and rapid vitreous synuresis in patients with posterior uveitis. Up to 30% of patients with uveitis and RRD have concurrent proliferative vitreoretinopathy (PVR) versus 12% in patients without uveitis. Tractional retinal detachment is commonly seen with partial vitreous separation and dense preretinal fibrosis.