The uveal tract, which is the middle layer of the eye, is that part of the eye that becomes inflamed in uveitis. As shown in the figure the uveal tract extends from the very back of the eye to the very front, ending as the iris (the colored part of the eye surrounding the pupil).  In uveitis associated with juvenile arthritis the inflammation of the uveal tract is usually restricted to just the front part of the eye (involving the iris and ciliary body, as shown on the figure).  When the entire uveal tract is involved, from the very back of the eye to the very front, it is referred to as pan uveitis. \

While pan uveitis can occur in children with arthritis it is much less common that the uveitis that is restricted just to the front part of the eye (the iris and ciliary body involvement only, which is referred to as anterior uveitis). In addition to occurring in association with juvenile arthritis and other autoimmune diseases, pan uveitis can occur in association with certain infections, and eye injury or surgery, as examples. The inflammatory process involved with pan uveitis and anterior uveitis seems to be similar but further research is required to better explain why some children have anterior uveitis and others pan uveitis.

The course and outcomes of uveitis, including uveitis associated with juvenile arthritis, are variable; some children will have ongoing lingering disease activity and others can go into long-term control (remission).  At the present time we can make decisions about treatments based on experiences from large groups of patients with similar conditions.  However, the conclusions we make about the diseases and the treatments from studying the group as a whole do not always precisely apply to individual patients within the group, there is considerable variability in how individual patients will respond to treatment.

Now, with new knowledge and technologies, we are beginning to aim for personalized approaches to therapy so that we can select therapies based on the individual’s genetic, lifestyle and environmental factors.  We think this personalized approach will result in more uniform and effective responses to therapy.  In general, older data suggests that about 1/3 of patients with uveitis associated with juvenile arthritis  will have mild or no active disease long term, 1/3 may continue to have mild to moderate disease, and 1/3 will have substantial long term visual impairment.  However, more recently, with earlier diagnosis, more rigorous follow up and monitoring of patients, and dramatically improved treatments, we anticipate the long-term outcomes will greatly improve.

We don’t have enough information to answer this question precisely but it is almost certainly true that with early diagnosis, careful monitoring and use of new medications the possibility of permanent remission increases. I wouldn’t say children can “outgrow” uveitis exactly but with proper treatment the abnormal process that gives rise to the uveitis could be stopped with therapy.  We hope permanent remission of uveitis can occur with early treatment and new treatments.

The course and outcomes of uveitis, including uveitis associated with juvenile arthritis, are variable; some children will have ongoing lingering disease activity and others can go into long-term control (remission).  Now, with new knowledge and technologies, we are beginning to aim for personalized approaches to therapy so that we can select therapies based on the individual’s genetic, lifestyle and environmental factors.  We think this personalized approach will result in more uniform and effective responses to therapy.  In general, older data suggests that about 1/3 of patients with uveitis associated with juvenile arthritis  will have mild or no active disease long term, 1/3 may continue to have mild to moderate disease, and 1/3 will have substantial long term visual impairment.  However, with earlier diagnosis, more rigorous follow up and monitoring of patients, and dramatically improved treatments, we now anticipate that long-term outcomes will greatly improve.

Assessing the microbiome is a complex, laboratory-based process. Doctors cannot effectively assess the microbiome by asking the patient questions or by findings on a physical examination.  To effectively assess the intestinal microbiome a stool sample needs to be collected and processed in the laboratory so that the molecular and genetic characteristics of the bacteria in the sample can be determined.  To determine which bacteria are in the sample from the intestine the laboratory will determine the genetic characteristics of each of the bacteria.  We are also beginning a study that will be investigating the oral microbiome by collecting saliva samples and samples from around the teeth and gums as we suspect that the oral microbiome might have some influence on juvenile arthritis.  We don’t know if the oral microbiome might be associated with uveitis but our study should help improve understanding of this possible connection.

This is a fascinating question and one for which there is accumulating but still minimal information.  There is some evidence that maternal use of antibiotics either before or during pregnancy or at the time of labor might result in changes in the microbiome of the child born to that mother. There have been no studies done specifically to investigate if maternal antibiotic use during pregnancy might affect the risk of the child developing JIA or uveitis.  We are currently doing a research study to investigate how inflammation during pregnancy might influence future disease in the offspring.  One facet of this study is to look at antibiotic use during pregnancy and the risk of the offspring having certain diseases later in life. We are also just about to begin a research project to study if the microbiome in the mouth influences the occurrence and course of JIA and if there is any connection with the oral microbiome and uveitis.

Long term effects of uveitis can be minimized by prompt diagnosis, consistent monitoring, and appropriate use of medications.  Some of the main effects that can occur and which we try to avoid with therapy include the following:

• Decrease in vision:  When there is inflammation in the eye, such as occurs with uveitis, there can be increased amounts of protein and inflammatory cells in the eye that interfere with light passing through the eye.  As a result, the ability to see clearly can be reduced.

• Cataracts:   A cataract is a painless clouding of the usually crystal clear lens of the eye. The lens sits behind the pupil of the eye as shown in the figure. Cataracts block light, making it difficult to see clearly.

• Synechiae:  Synechiae can occur as a result of uveitis. Synechiae are adhesions of the iris so the lens becomes stuck to either the lens below or the cornea in front (the cornea is a clear membrane window that lies in front of the pupil). When such adhesions occur, the iris will not move as freely.  Normally the iris will dilate (spread out) so the pupil enlarges when the environment is darker (allowing more light to enter the eye) and in bright light will constrict (come together) so the public gets smaller limiting the amount of light entering the eye.  When synechiae are present the movement of the iris is impeded and this can result in difficulty in adapting to light changes in the environment.

• Band Keratophathy: Band keratopathy is a line or band that appears across the center of the cornea. The band forms when calcium deposits collect in this area. Band keratopathy can reduce vision and sometimes causes eye irritation or redness.

• Increased eye pressure (glaucoma): Glaucoma can occur in some children with uveitis because the normal flow of fluids in the eye might be limited because of the inflamed tissues. Steroid medications can sometimes increase the eye pressure.

This is a very interesting and important question.  Yes, uveitis can result from injury to the eye such as a blunt force to the eye or a foreign body in the eye. This usually results in iritis, which is inflammation of the colored part of the eye that surrounds the pupil.  The iris is also one  part of the eye that is typically inflamed in uveitis associated with JIA. There is also information from laboratory experiments suggesting that trauma in a joint can result in changes in certain molecules in the cornea of the eye (a part of the eye which is not primarily involved in uveitis associated with JIA).  More research needs to be done to understand how trauma to the eye or in the joint might be associated with chronic uveitis as is seen in association with JIA.

There are seven different types of Juvenile Idiopathic Arthritis..  It is uncommon for most forms of JIA to occur in siblings; children who present with the type of JIA referred to as ERA (Enthesitis Related Arthritis ; enthesitis refers to inflammation where ligaments and tendons insert onto bone), which tends to occur in older children and is more common in boy, are more likely than other JIA subtypes be found in siblings.  In children with the type of JIA referred to as oligoarticular JIA (children with fewer than 5 joints involved; the word “oligo” comes from the Greek word meaning “few”) are the most likely to have uveitis that is chronic and generally not associated with symptoms such as redness of the eyes or eye pain . Oligoarticular JIA occurs uncommonly in siblings but it can occur. The occurrence of oligoarticular JIA with associated uveitis is even more rare but again it can occur. The type of uveitis associated with ERA tends to be associated with symptoms and intermittent brief courses; this type of arthritis is thought to be somewhat more likely to occur in siblings with the ERA type of JIA but the occurrence is still uncommon.  The fact that JIA and JIA with uveitis can occur in siblings, although rarely, suggest the possibility of a genetic influence on the occurrence of the disease or an environmental exposure or, perhaps more likely,  an interaction of genes with the environment.  More research is required to answer this important question.  Because JIA and JIA with uveitis occur rarely in siblings,  international research collaboration, such as that which is being led by Canadian pediatric rheumatologists and ophthalmologists, will be important to help answer this question more thoroughly.

At present, we can decide treatments based on experiences from large groups of patients with similar conditions.  However, the conclusions we make about the diseases and the treatments from studying the group as a whole do not always precisely apply to individual patients within the group; there is considerable variability in how individual patients will respond to treatment. Now, with new knowledge and technologies,  we are beginning to aim for personalized approaches to therapy so that we can select therapies based on the individual’s genetic, lifestyle, and environmental factors.  We think this personalized approach will result in more uniform and effective responses to therapy.  In general, older data suggests that about 1/3 of patients with uveitis associated with juvenile arthritis will have mild or no active disease long term, 1/3 may continue to have mild to moderate disease, and 1/3 will have substantial long term visual impairment.  However, more recently, earlier diagnosis, more rigorous follow-up and monitoring of patients, and dramatically improved treatments, makes us believe that the long term outcomes will significantly improve.

The new treatments that are available to treat uveitis (and arthritis) have transformed care and outcomes. The new treatments are referred to as biologic drugs because they are designed to target the precise molecules that participate in inflammation. At the present time these biologic drugs target molecules in the body that usually participate in inflammation.  However, with more research we hope to be able to identify exactly what molecule or molecules participate in inflammation in the individual patient so that the exact correct choice of the biologic drug can be selected for that patient.  Also, with more research we hope to be able to know better when the biologic drug should be started and when the medication can be safely stopped without causing the disease to recur.  Of course, we are continuing to investigate what factors might be involved in causing uveitis to occur in the first place so that we can consider ways to prevent uveitis from occurring.

Our Canadian research, looking at over 1,000 children newly diagnosed with JIA, has shown that the most important contributors to probability of uveitis are a positive ANA and being diagnosed at a young age.  Uveitis was most commonly seen in children with either oligoarthritis or polyarticular rheumatoid factor negative JIA. We also saw that there was an incidence of new uveitis among these children of 2.8% per year for the 5 years of the study. This means that children with JIA need to continue to be screened for uveitis for at least 5 years after diagnosis.