Virus-induced uveitis is a rare clinical picture in contrast to viral diseases of the ocular surface and cornea.
Virus-induced uveitis is quite often associated with complications such as after-cataracts and glaucoma and a chronic course or frequent recurrences. Thus, virus-induced uveitis plays an important role in the clinical routine as well as for the affected patients. First, a brief differentiation from ocular surface diseases is made, followed by a presentation of the different forms of viral uveitis.
VIRAL DISEASES OF THE OCULAR SURFACE
Among the viral diseases of the ocular surface, conjunctivitis caused by adenovirus or influenza virus is the most prominent. This is due to its high infection and rapid spread, as is typical for influenza viruses. This has also earned it the name conjunctivitis epidemica. Like all adenoviral diseases, epidemic conjunctivitis heals spontaneously. There is no specific therapy. Occasionally, however, the cornea is attacked, and a so-called nummular corneal inflammation develops, which can sometimes cause considerable visual disturbances. In most cases, however, this too comes to rest relatively quickly without severe scarring, so that permanent visual disorders are rather unlikely. This distinguishes it from a herpes infection of the eye surface, which first attacks the eyelids, then the conjunctiva and finally the cornea. It is typically recurrent and often causes considerable visual disturbances in the long term. The herpetic infection of the eyelids and ocular surface is often not recognized. The diagnosis of keratitis dendritica (tree-like inflammation of the cornea) is made only when the cornea is involved and shows the typical tree-like pattern. This is so typical of a herpes infection of the cornea that the diagnosis can be considered confirmed. It heals without scarring, but in the course of the disease it typically recurs and at some point, the herpes virus is able to penetrate even deeper corneal layers. The corneal inflammation that then develops no longer heals without scarring. This means that there is a considerable risk of permanent visual disturbances, so that early diagnosis and therapy is crucial. Already primarily or also in the further course of the disease the inner eye can be involved. Then a so-called herpetic keratouveitis develops, which is discussed below.
Among the diseases of the ocular surface, the facial rose, the zoster ophthalmicus, also plays a major role. Fortunately, it occurs quite rarely with involvement of the inner eye. If it does, however, long-term complications and frequent recurrences are of grave concern. The risk of involvement of the interior of the eye can be recognized by the presence of zoster blisters in the area of the tip of the nose. In this case, the risk of involvement of the interior of the eye is many times higher. Zoster ophthalmicus does not normally occur in younger, healthy patients, but typically in older patients, those with immune deficiency or tumor diseases. As soon as facial erythema is suspected, the ophthalmologist should be consulted immediately to rule out involvement of the inner eye. In addition, it is strongly recommended to start antiviral therapy as early as possible, as the risk of severe permanent symptoms is high with untreated zoster. This also applies if there is no eye involvement. Therefore, in case of doubt, the family doctor should always be consulted.
THE VIRUS-INDUCED UVEITIS
The virus-induced uveitis is difficult to diagnose and therefore probably a rare, and unfortunately rarely diagnosed clinical picture. There are no clear diagnostic criteria, nor can the diagnosis usually be confirmed by laboratory tests. So, in most cases the diagnosis is only made in the course of the disease through the occurrence of recurrences. As with any form of uveitis, the classification is categorized into anterior and posterior uveitis, whereby the course depends mainly on the immune system of the affected person and the expected complications on the localization. The causally responsible viruses are different in immunocompetent patients and in people with immune deficiency. The course is significantly influenced by the immune system, so that the patient’s defenses are a decisive factor in the course. Typical problems of anterior uveitis are on one hand the involvement of the cornea (keratouveitis). Secondary is glaucoma, damage to the iris with adhesion of the pupil and after-cataract (cataracta complicata). It mainly leads to severe inflammatory vitreous opacities and carries a high risk of developing a retinal detachment. In the viral uveitis of immunocompetent individuals, the destruction is probably mainly caused by the immune system, whereas in the viral uveitis of patients with immune defects (HIV infection or severe immunosuppression) the virus itself is responsible for the tissue damage. Thus, the viral uveitis of immunocompetent patients differs fundamentally from that of patients with immunodeficiency. This is also reflected in the spectrum of viruses involved. In immunocompetent patients it is typically the herpes simplex virus (HSV) and the shingles or varicella zoster virus (VZV), while in patients with immune deficiency it is mainly varicella zoster virus and cytomegalovirus (CMV) that are responsible for the occurrence of viral uveitis.
VIRUSES THAT CAN CAUSE UVEITIS
Adenoviruses are the viruses that attack the eye with the most frequency by far. It is known of individual strains, that they regularly cause not only flu symptoms but also conjunctivitis (types 1, 7, 8, 19). However, adenoviral uveitis has not yet been diagnosed.
The viruses of the herpes family, in particular the herpes simplex virus type 1 (HSV-1) and varicella zoster virus (VZV) are the viruses most frequently diagnosed in connection with uveitis. The other viruses of the herpes family (HSV-II, CMV or cytomegalovirus and the Epstein Barr virus (EBV)) are not believed to be able to induce inflammation of the inside of the eye in immunocompetent individuals. However, in patients with immunodeficiency, these viruses, especially CMV, can cause severe uveitis leading to blindness and destroy the retina. EBV is known to affect the lacrimal gland. Uveitis caused by EBV has been suspected in the past but has never been proven. Measles and mumps virus probably play no role in the development of uveitis, but a possible connection with a certain form of uveitis (Fuchs heterochromic cyclitis) has recently been demonstrated in a large series of cases. If these results are confirmed, one will have to reckon with rubella virus as a cause of iritis in the future.
The human immunodeficiency virus (HIV) is only rarely responsible for unspecific anterior uveitis, but in HIV and AIDS patients, uveitis is usually a matter of immune deficiency and so-called opportunistic infections. These include infection with cytomegalovirus (CMV), varicella zoster virus (VZV), Epstein Barr virus (EBV), which is also associated with certain malignancies, usually lymphomas, which can typically be confused with uveitis, and finally HHV-8, which cannot cause uveitis but can cause Karposi sarcomas.
VIRAL UVEITIS OF THE ANTERIOR SEGMENTS OF THE EYE
If one speaks of viral uveitis of the anterior segments of the eye, the uveitis caused by HSV-1 or VZV is usually mentioned. This is typically a predominantly cellular inflammation of the iris with increased irrigation of the iris. Also typical is bleeding into the tissue of the iris, which, if present, is almost conclusive for the diagnosis of herpetic uveitis, as well as an accompanying secondary glaucoma in almost half of the cases. All other forms of anterior viral uveitis are rarities and will therefore not be discussed in this context.
THE POSTERIOR VIRAL UVEITIS
The viral disease of the posterior segment of the eye is usually a dramatic disease, associated with a high risk of blindness and in immunocompetent individuals an acute occurring disease. It is caused by the viruses of the herpes family, especially Herpes simplex type 1 and Varicella zoster virus. Clinically it manifests itself as acute, i.e. within a few hours to days, progressive inflammation of the vitreous cavity until the most severe visual impairment is reached, which hardly allows an assessment of the retina. Since it classically affects healthy individuals and is initially only unilateral and is also accompanied by no other recognizable signs of disease, the diagnosis is often missed in the early stages when treatment is available. Only the earliest possible antiviral treatment has a chance of maintaining residual function and influencing the risk of retinal detachment. The latter is to be expected in 70% of the cases despite treatment. This because of the severe retinal damage caused by the viral disease on the one hand, and the most severe inflammatory vitreous alterations on the other hand, which lead to a shrinking of the vitreous and thus tearing at the retina. The prognosis of treatment for this retinal detachment is usually poor, so that in most cases no more than the preservation of the eyeball can be achieved. Therefore, as soon as the virustatic therapy is initiated, a high-dose systemic cortisone therapy must be started as early as possible to control the inflammatory reaction and to influence the acute shrinking of the vitreous body. In 1/3 of the cases, untreated involvement of the second eye must be expected. The only differential diagnosis for acute retinal necrosis is uveitis in Behçet’s disease, which is similarly highly acute and can lead to severe visual disturbances. All other diseases in question are less aggressive and more protracted, so that they can be distinguished with relative reliability on their own.
Infection of the second eye can occur long after the inflammation in the first affected eye has subsided if virustatic therapy is not continued for at least three months. It is not known why some individuals develop this sight-threatening disease while others do not show any eye involvement despite recurrent herpes. Presumably, it is related to the aggressiveness of the viruses on the one hand, but also to the patient’s specific resistance to the virus on the other. However, all investigations to date have shown no evidence that the patients affected have a detectable immune deficiency. The situation is different in the case of viral retinitis of the immunocompromised patient. In patients after chemotherapy for cancer, this is typically caused by VZV, whereas patients with severe immunosuppression and AIDS are more likely to develop cytomegalovirus retinitis. In contrast to the acute retinal necrosis of immunocompetent patients, this typically starts peripherally, spreads like a forest fire over days to weeks within the retina towards the center without causing a severe inflammation of the vitreous cavity. In contrast to acute retinal necrosis, the retina can be assessed very well, and the clinical picture can be clearly classified for those who have seen it once. Since the severe inflammatory vitreous infiltration is absent and the retinal fall is much slower than in acute retinal necrosis of the immunocompetent patient, the risk of retinal detachment is comparatively low at 15%. Nevertheless, close monitoring and long-term virustatic therapy, including prophylaxis of recurrences up to the restoration of immunocompetence, are necessary to avoid blindness and involvement of the partner eye. In any case, in a patient with such a disease in whom an immune deficiency is not known, further clarification of the immune competence including HIV testing must be carried out to prevent further complications of the immune deficiency.
Finally, pseudouveitis or the uveitis masquerade syndrome in intraocular lymphomas should be mentioned in this context. This is a rarity, but increasing in frequency, and is usually misinterpreted primarily as uveitis, since it is also associated with severe inflammatory cell accumulation inside the eye. Only a timely diagnosis can ensure long-term survival. This disease may also be caused by viruses.
Viral uveitis is a rare and even more rarely diagnosed disease, which is mainly caused by the viruses of the herpes family. Anterior uveitis is typically accompanied by a sectorial attack of the iris, secondary to iris atrophy and an increase in intraocular pressure. It likes to relapse. Posterior uveitis caused by viruses is mainly herpes related. A distinction is made between highly acute retinal necrosis as a result of viral infestation in immunocompetent individuals and viral retinitis in patients with immunodeficiency, which is much less aggressive, but nevertheless shows a high risk of blindness. The great difficulty in the diagnosis of viral uveitis is that there are practically no tests that can confirm the diagnosis, so it is based mainly on the clinical experience of the examiner, although there are typical signs that point in the direction of the diagnosis. Once the diagnosis is made, an antiviral therapy is started and is usually able to control the viral infection. In addition, however, the reaction of the immune system must be treated, which in the case of viral diseases often leads to greater tissue destruction than the viral infection itself. Antiviral therapy has no influence on the secondary complications of viral uveitis, which must be treated independently. These include in particular the secondary glaucoma in anterior uveitis and retinal detachment in posterior uveitis.