New Research: Uveitis, an Inflammatory Eye Disease, May Signal the Onset of Multiple Sclerosis

Several research projects addressing inflammation as a source of eye disease have received attention recently.

In the genetic arena, European researchers investigating the link between inflammation and age-related macular degeneration (AMD) identified a protein, called FHL-1, that functions as a “regulator” to protect the eye from immune system attacks.

And last month, at the 2014 American Academy of Ophthalmology Annual Meeting, American and European researchers presented results from Characterization of Uveitis in Patients with Multiple Sclerosis, a large retrospective study which revealed that nearly 60 percent of persons with both uveitis, an inflammatory eye disease, and multiple sclerosis (MS) are diagnosed with each within a five-year span. In other words, uveitis may be a warning sign that could help doctors detect MS earlier in the course of the disease.

The British Journal of Ophthalmology

The supporting data and research for this retrospective study, also entitled Characterisation of uveitis in association with multiple sclerosis, has been published online ahead-of-print in the British Journal of Ophthalmology (BJO). BJO is an international peer-reviewed journal for ophthalmologists and visual science specialists that publishes clinical investigations, clinical observations, and clinically relevant laboratory investigations related to ophthalmology.

[Editor’s note: A retrospective study collects data from past records and does not follow up with patients in the present, which can be a limitation in some studies.]

The authors are Wyatt Messenger, Lena Hildebrandt, Friederike Mackensen, Eric Suhler, Matthias Becker, and James T. Rosenbaum, who represent the following United States and European institutions: Casey Eye Institute, Oregon Health & Science University; University of Heidelberg, Germany; Tremlispital, Zurich, Switzerland; and Legacy Devers Eye Institute, Portland, Oregon.

What is Uveitis?

According to WebMD, uveitis (pronounced you-vee-EYE-tis) is an internal inflammation of the eye (pictured left). Uveitis involves the middle layers of the eye, also called the uveal tract or uvea.

The uveal tract contains veins and arteries that transport blood to the parts of the eye that are critical for vision. It includes the following parts of the eye:

Iris: A tissue containing muscles that adjust the size of the pupil opening and thus regulate the amount of light that enters the eye. The iris also determines eye color.
Choroid: A dark brown membrane that is rich with blood vessels. It supplies blood and nutrients to the retina and nourishes all other structures within the eye.
Ciliary body: Contains the ciliary muscles, which change the lens shape and curvature, and the ciliary processes, which produce aqueous humor, a clear, watery fluid that provides nutrients to all parts of the eye.

Uveitis has many potential causes, including inflammatory disease affecting other parts of the body; a viral infection; bacteria; a fungal infection; a parasite, or an injury to the eye. Symptoms of uveitis include eye redness and irritation; blurred vision; eye pain; and increased sensitivity to light.

Complications of uveitis can include glaucoma; cataracts; abnormal growth of blood vessels in the eyes that interfere with vision; fluid within the retina; and vision loss. Early diagnosis and treatment is critical.

What is Multiple Sclerosis (MS)?

From A Definition of MS, via the National Multiple Sclerosis Society:

Multiple sclerosis (MS) is an unpredictable, often disabling disease of the central nervous system that disrupts the flow of information within the brain, and between the brain and body. The cause of MS is still unknown – scientists believe the disease is triggered by as-yet-unidentified environmental factor(s) in a person who is genetically predisposed to respond.

MS involves a process in which an abnormal response of the body’s immune system is directed against the central nervous system (CNS), which is made up of the brain, spinal cord and optic nerves. The exact antigen — or target that the immune cells are sensitized to attack — remains unknown.

Within the CNS, the immune system attacks myelin — the fatty substance that surrounds and insulates the nerve fibers — as well as the nerve fibers themselves. The damaged myelin forms scar tissue (sclerosis), which gives the disease its name.

When any part of the myelin sheath or nerve fiber is damaged or destroyed, nerve impulses traveling to and from the brain and spinal cord are distorted or interrupted, producing a wide variety of symptoms. People with MS typically experience one of four disease courses, which can be mild, moderate or severe.

More about the Research

Excerpted from Research Reveals Likelihood and Onset of Multiple Sclerosis Diagnosis among Patients with Inflammatory Eye Disease, via PRNewswire:

The results of the largest retrospective study of multiple sclerosis (MS) in uveitis patients has revealed that nearly 60 percent of patients with both diseases were diagnosed with each within a five-year span. While it has long been known that there is an association between the eye condition and MS, this is the first study to provide a detailed description of the relative onset of uveitis and MS and to calculate the likelihood of an MS diagnosis among uveitis patients.

Diagnosed in approximately 38,000 Americans a year, uveitis causes swelling and irritation of the middle layer of the eye and can lead to permanent vision loss if left untreated.

It is well established in the medical community that uveitis can be a sign of MS and it is estimated that 1 to 10 percent of MS patients have uveitis. MS affects approximately 2.3 million people worldwide, causes irreversible nerve deterioration, and is notoriously difficult to diagnose.

To achieve a better understanding of the association of the two diseases, researchers from Casey Eye Institute at the Oregon Health and Science University and the University of Heidelberg, Germany conducted a database search of approximately 3,000 patients with uveitis from the Casey Eye Institute and 5,319 patients from the University of Heidelberg between 1985 and 2013.

Of these, 24 patients from the Casey Eye Institute and 89 patients from the University of Heidelberg fulfilled the inclusion criteria of diagnoses for both uveitis and MS and were included in the study.

Based on the prevalence of MS in American and European populations, the researchers found that MS is 18 times and 21 times more likely in an American and European population with uveitis, respectively, relative to the general population.

The study found that MS was diagnosed before uveitis in 28 (29 percent) of patients, simultaneously in 15 (15 percent) of patients and after uveitis diagnosis in 54 (56 percent) of patients.

“With a population size four times larger than any study to date on this topic, our study provides a wealth of clinical information to allow clinicians to make more accurate diagnoses while giving patients a better understanding of their prognosis,” said Wyatt Messenger, M.D., lead researcher from the Casey Eye Institute. “Knowing more about the onset may enable patients to seek treatment earlier, therefore slowing the progression of the disease and limiting the damage done to the nervous system.”

The researchers noted that a major limitation of the study is the lack of availability of brain magnetic resonance images on all of the patients or detailed neurological studies, which would have allowed correlation of the patient’s uveitis with their neurological disease.

From the British Journal of Ophthalmology

From the article abstract:

Purpose: To characterise uveitis in association with multiple sclerosis (MS)

Methods: We conducted a retrospective chart review of patients with uveitis and MS at two uveitis centres (Portland, Oregon, USA and Heidelberg, Germany). Baseline characteristics and ophthalmic data were collected at the patient’s first and last visits. Additionally, neurological records were obtained when possible.

Results: We identified 113 patients (196 eyes) with uveitis and MS. Of these, 53 had a diagnosis of MS confirmed by review of neurological records, 50 additional patients fulfilled the Poser criteria for MS, and 10 with MS were referred by an outside neurologist.

Among them, 83 (73%) were women and the mean age of presentation was 40.6 years (range 13-64 years). The average visual acuity in affected eyes at presentation was 20/39. There were 90 patients (80%) who presented with intermediate uveitis and 24 patients (15%) with anterior uveitis. Posterior and pan-uveitis were found in four patients (3%) and two patients (2%), respectively.

Compared with our location-matched controls with idiopathic [i.e., of uncertain or unknown origin] intermediate uveitis (n=16), patients with MS and intermediate uveitis were significantly older when diagnosed with uveitis and more likely to be female.

Conclusions: Uveitis with MS generally presents as intermediate uveitis with a minority presenting with anterior uveitis. Patients are significantly older and more likely to be women than patients with idiopathic intermediate uveitis. The visual prognosis is generally favourable.

Additional Information on Inflammatory Eye Disease

Acknowledgment

Anterior uveitis photo is a Wikimedia Commons file, used in accordance with the Creative Commons Attribution 3.0 Unported license.