Can retinal vasculitis be cured

Uveitis is treatable

Intraocular inflammation

Uveitis is treatable

By Matthias Becker


With around 400,000 people affected and 8,000 to 15,000 new cases per year, uveitis is the fourth most common cause of blindness in Germany, as in other industrialized nations, after age-related macular degeneration, glaucoma and diabetic retinopathy.


In contrast to macular degeneration, glaucoma and diabetic retinopathy, the incidence of which increases with age, uveitis, with a disease peak at around 39 years of age, is a disease mainly of young people. About 13 percent of all patients in uveitis consultations are children and adolescents.


Numerous systemic diseases are often associated with uveitis. In the case of children, diseases of the rheumatic type, i.e. children's rheumatism, are in the foreground. The interdisciplinary cooperation between ophthalmology and disciplines such as internal medicine, pediatrics, neurobiology or microbiology, as successfully practiced in uveitis centers, is crucial for successful therapy.


Classification as an aid


The uvea, the middle layer of the wall that encompasses the entire eye, lies between the dermis (sclera), which forms the stable outer shell of the eye with the cornea, and the retina. In the front part of the eye it consists of the iris and the ciliary body (corpus ciliare), in the rear part of the choroid.


Triggered by infectious agents or pathological reactions, for example in the context of immune diseases, mononuclear cells and proteins can extravasate into the uvea, the anterior chamber and the vitreous humor. The presence of free inflammatory cells in the anterior chamber or vitreous, which can be seen biomicroscopically by the slit lamp for the ophthalmologist, generally defines the presence of uveitis as intraocular inflammation.


One possibility of classifying the uveitis forms is differentiation with the help of clinical classification according to the anatomical location and the focus of the activity of the inflammation, i.e. according to the location where the density of free inflammatory cells is highest.


Anterior uveitis, which affects 50 percent of all patients, is an inflammation of the anterior region of the uvea, especially the iris and the ciliary muscle. Iritis is when inflammatory cells are only found in the anterior chamber of the eye. Iridocyclitis is when a few cells also exist behind the lens, especially in the anterior vitreous. Macular edema or edema of the optic nerve papilla can also occur.


Intermediate uveitis (23 percent) affects the middle part of the uvea. The highest density of free inflammatory cells is found in the vitreous humor. However, there may be a few cells in the anterior chamber.


Pars planitis is a special form of intermediate uveitis, in which inflammatory deposits or agglomerations occur, especially in the lower transition area between the retina and the ciliary body. Here, too, macular or papillary edema as well as inflammation of the retinal veins and vasculitis can occur.


Posterior uveitis (18 percent) describes changes caused by the infiltration of inflammatory cells on the retina and choroid. Depending on the infestation, a distinction is made between retinitis, choroiditis, chorioretinitis and retinochoroiditis. In panuveitis (9 percent), inflammatory cells are found in all three areas described, although this does not say anything about the severity of the inflammation.


Secondary and primary forms


A classification of the uveitis forms can also be made by distinguishing between "primary" and "secondary". Primary forms are all forms of intraocular inflammation for which no "label" can be found, in other words: which cannot be "explained", i.e. for which no "cause" can be found. In the past, the primary forms were also called "endogenous" or "idiopathic".


Secondary uveitis, which affects around 60 percent of all patients, is associated with extraocular diseases (48 percent) such as sarcoid, spondyloarthropathies, Beh├žet's disease as a rheumatic disease or multiple sclerosis, ocular syndromes (34 percent) such as Fuchs' uveitis Syndrome or white dot syndromes as well as infectious diseases (18 percent) such as herpes or toxoplasmosis.


The underlying systemic diseases can lead to inflammation of more than one compartment of the eye. The anatomical classification can, however, serve as an aid in finding the diagnosis. It is not uncommon for the various clinical pictures in the eye to be so characteristic that they can provide clues to specific associated diseases. The frequency of occurrence, the unilateral or bilateral nature, the course and the type of complications in various diseases may be typical and can point the way for the assignment.


The Masquerade syndromes are to be distinguished, i.e. forms that at first only look like uveitis, but in reality have no inflammatory genesis and free inflammatory cells in the vitreous or anterior chamber. The supposed inflammatory cells can be tumor cells or pigment cells, for example. Masquerade syndromes can occur in intraocular lymphomas, in leukemia and in primary eye diseases such as retinitis pigmentosa or pigment dispersion syndrome.


The diagnosis of intraocular lymphoma, for example, which can still manifest itself intracerebrally outside the eye (oculocerebral lymphoma), can ultimately only be confirmed by a diagnostic vitreous removal (vitrectomy) with cytological and molecular biological assessment of the cells obtained.


Numerous secondary forms of uveitis are infectious. A large number of infectious agents such as viruses, bacteria, fungi and also rare parasites can lead to endophthalmitis as an inflammation of the interior of the eye with exogenous and endogenous bacterial colonization. Opportunistic infections are important in immunosuppressed patients or in patients after trauma or surgery. Infections of the eye wall can also develop exogenously in contact lens wearers through infestation with acanthamoeba. These can cause very painful corneal inflammation and are not infrequently associated with considerable loss of vision.


It is not uncommon for the diagnosis of uveitis to be based on a typical ophthalmological picture and anamnesis. However, to identify the pathogen, the doctor often has to rely on additional laboratory tests and targeted microbiological testing after material has been extracted from the anterior chamber or the vitreous humor.


Conventional microbiological methods can fail here. The value of serodiagnostics is often limited when there is a high degree of infection due to a lack of specificity in identifying active infections. With the help of the polymerase chain reaction (PCR), for example, DNA and RNA-specific infectious agents can be quickly identified from small amounts of material obtained through vitreous biopsies or anterior chamber punctures. In addition to microbiological detection, PCR is becoming increasingly important in clinical terms, particularly in the rapid diagnosis of postoperative, traumatic or septic endophthalmitis.


Associated with systemic diseases


Secondary forms of uveitis can be caused, among other things, by systemic diseases such as spondyloarthropathies. Spondyloarthropathies including reactive arthritis (formerly: Reiter's syndrome) and ankylosing spondylitis (formerly: Bechterew's disease) are the most common systemic diseases associated with uveitis in Western countries and are found in up to 21 percent of uveitis patients.


Spondyloarthropathies, two-thirds of which affect men, often cause characteristic changes in the eye in the form of often fibrinous iritis or iridocyclitis up to hypopyon, i.e. an accumulation of pus in the anterior chamber. The disease occurs acutely, is accompanied by redness, pain and sensitivity to light of the eye and tends to recur in periodic attacks with irritation-free intervals.


In 95 percent of cases, the anterior uveitis initially occurs unilaterally in the context of spondyloarthropathy, but can then also recur in the other eye, typically again unilaterally. 70 percent of patients with acute anterior and unilateral uveitis carry the human leukocyte antigen (HLA) B27. HLA-B27 plays an important role in the body's immunological defense reactions.


30 to 90 percent of these patients have spondyloarthropathies, which are either symptomatic as peripheral oligoarthritis or sacroileitis or other manifestations of the disease or will develop accordingly in the next few years. HLA-B27-associated anterior uveitis can also occur in isolation without joint involvement.


Sarcoid, in which the eye is affected almost as often as the lungs, can also cause an extremely variable picture of the inflammation in all parts of the eye. Granulomatous corneal precipitates, multifocal perivenous deposits with chorioretinitic foci and choroidal granulomas are relatively typical.


Because of its variable picture and its frequency, sarcoid must also be considered in the differential diagnosis of all other manifestations of uveitis. A chest x-ray to detect the characteristic biliary lymphadenopathy or an interstitial lung disease is part of the standard program of every uveitis evaluation.


With typical biliary lymphadenopathy and the corresponding eye findings, the diagnosis of sarcoid can be assumed with sufficient certainty. In less clear-cut cases, however, histological confirmation of the diagnosis should be sought, if necessary by means of a transbronchial biopsy or mediastinoscopic lymph node removal.


Systemic lupus erythematosus (SLE) can cause severe retinopathy in around 1.7 percent of cases, which typically manifests itself in numerous "cotton wool" foci, i.e. changes in the fundus with white, blurred spots caused by capillary occlusions in the retina, and intraretinal hemorrhages .


About 1 to 2 percent of patients with inflammatory bowel disease as well as patients with psoriasis develop anterior uveitis, which is very similar to spondyloarthropathies as unilateral, suddenly occurring and recurrent anterior uveitis or as more chronic uveitis, also affecting the posterior segments of the eye can express.


Multiple sclerosis is one of the neurological diseases associated with uveitis. In addition to the typical retrobulbar neuritis, the ocular involvement is most frequently manifested by intermediate uveitis, often with retinal vasculitis or rarely with a stronger anterior component.


Childhood complications


A variety of other systemic diseases can be associated with uveitis. While the diagnosis of uveitis in childhood was previously equated with a high probability of blindness, the number of young patients with visual loss is currently very small due to improved ophthalmological screening and early therapy involving immunosuppressants. The complications of typical iridocyclitis arise from the chronic intraocular irritation.


Children with ANA-positive oligoarthritis in the context of juvenile idiopathic arthritis are particularly affected. This dangerous form causes mostly bilateral, insidious anterior uveitis in around 24 percent of children. Antinuclear antibodies (ANA) are directed against various components of the cell nucleus and can lead to disturbances of nuclear and cell functions.


A large number of complications such as synechiae, i.e. adhesions of the iris with the posterior surface of the cornea, or ligamentous keratopathy, cataracts and glaucoma can rob these mostly symptom-free, little patients of the eyesight, as these typical complications are often discovered late, for example through pupillary distortions as a result of the adhesions become. Close-knit ophthalmic examinations, which may be weekly depending on the findings, are therefore often absolutely necessary for affected children.


As a classic example of an ocular syndrome, the Fuchs 'uveitis syndrome (former name: Fuchs' heterochromic cyclitis) was also mentioned as a secondary form of uveitis, which is characterized by an almost always unilateral infestation with mild, chronic inflammation of the anterior chamber or vitreous humor. The diffuse distribution of star-shaped corneal precipitates and the absence of posterior synechiae are characteristic. Fuchs' uveitis syndrome can be diagnosed solely on the basis of the ophthalmological picture.