Leny Luyendijk

Detection of intraocular antibody production to herpesviruses in acute retinal necrosis syndrome

In order to improve the determination of the causative agent in acute retinal necrosis syndrome, we evaluated the detection of intraocular antibody production to herpesviruses in 28 patients with this disease. Intraocular antibody production was determined by calculation of the Goldmann-Witmer coefficient whereby specific antibody titers in the inflamed eye and circulation are related to the total IgG content in ocular fluid and serum. Specific antibody titers to herpesviruses and Toxoplasma were determined by the indirect immunofluorescence technique. Thirty-five patients with ocular toxoplasmosis, cataract, or proliferative vitreoretinal disorders were tested as controls. By this technique, intraocular antibody production to varicella zoster virus or herpes simplex virus could be established in 16 (57%) of the patients with the typical clinical features of acute retinal necrosis, compared to none of the controls. Of the 33 affected eyes, 21 (64%) had a visual outcome of less than 20/200. We concluded that detection of intraocular antibody production to herpesviruses may be a useful diagnostic tool in establishing the causative agents in acute retinal necrosis.

AQUEOUS-HUMOR ANALYSIS AS A DIAGNOSTIC-TOOL IN TOXOPLASMA UVEITIS

Analysis of local toxoplasma antibody production to confirm a suspected clinical diagnosis of toxoplasma chorioretinitis is a valuable diagnostic tool. Determination of toxoplasma antibodies in the blood of the patient is of limited use. When blood toxoplasma tests are negative this indicates that toxoplasma as a causative organism in the pathogenesis of uveitis is unlikely.A positive blood test is a sensitive test (100% patients positive) but not a specific test since so many healthy individuals already have undergone subclinical infection and have acquired humoral immunity against the parasite.We analysed 93 paired aqueous and serum samples for toxoplasma antibodies and total IgG and determined the Goldmann-Wittmer coefficient. In patients retrospectively diagnosed as having toxoplasma chorioretinitis 16 out of 22 had a positive coefficient, indicating local parasite antibody production. In one patient with AIDS we also found a positive toxoplasma coefficient. Three out of 15 patients with posterior uveitis of unknown origin also had a positive coefficient. None of the cataract patients tested (n=32) had a positive coefficient. Major drawbacks of aqueous humor analysis are that a false negative antibody coefficient can occur when a massive blood aqueous barrier breakdown has occurred.

Elevated serum IL-8 levels are associated with disease activity in idiopathic intermediate uveitis

AIM To find a laboratory indicator for systemic involvement in intermediate uveitis. METHODS Interleukin 8 (IL-8) and C reactive protein (CRP) serum levels were measured in patients with idiopathic intermediate uveitis (n=61), uveitis controls (n=143), and normal controls (n=29). The records of those with intermediate uveitis were reviewed with the emphasis on disease activity and severity as characterised by the presence of cystoid macular oedema, vitreous exudates or snowbank formation, papillitis, and periphlebitis. RESULTS Increased serum IL-8 (⩾20 pg/ml) was found in 27 out of 61 patients with intermediate uveitis (p< 0.01), 12 of 27 patients with sarcoid uveitis (p<0.05), in 19 of 30 patients with HLA-B27 associated acute anterior uveitis (p<0.05), and in five of 29 healthy controls. Raised IL-8 levels in intermediate uveitis were significantly associated with active disease (p<0.001) and the presence of vitreous exudates (p<0.001), papillitis, and periphlebitis (p<0.01). Elevated CRP levels were found in 12 of the 143 uveitis controls but in none of the intermediate uveitis patients or normal controls. During follow up an associated systemic disease was more frequently noticed in patients with an elevated serum IL-8 at entry into the study. CONCLUSIONS Elevated IL-8 serum levels were found in patients with active intermediate uveitis of unknown origin. An elevated IL-8 level seems to predispose the patient to a later development of associated systemic disease.

Analysis of Local Antibody Productionin the Vitreous Humor of Patients With Severe Uveitis

We analyzed the local antibody production in vitreous humor samples collected during vitrectomy in patients with severe vision-threatening uveitis. In 24 patients, paired serum and undiluted vitreous humor samples were collected and tested for antibodies against Toxoplasma gondii, herpes simplex virus, varicella-zoster virus, cytomegalovirus, Epstein-Barr virus, and Toxocara canis. Total IgG and the Goldmann-Witmer coefficient were determined. The initial diagnosis of ocular toxoplasmosis could be confirmed in six of the seven patients. The seventh patient showed a local antibody production against herpes simplex virus. One of the three patients with chronic panuveitis at initial diagnosis showed a local antibody production against T. gondii. These last two findings resulted in a change in medical treatment. Analysis of local antibody production in vitreous humor samples is a valuable diagnostic tool.

Analysis of ocular fluids for local antibody production in uveitis.

Uveitis or intraocular inflammation is a potentially blinding disorder that is initiated by a diverse group of diseases. Concepts of uveitis have evolved rapidly over the past few years, but many questions about the aetiology still remain unanswered. Uveitis is associated with several systemic diseases but the frequency of systemic diseases among uveitis patients is dependent on age of onset and type of uveitis.1 2 In a white population the most common systemic disorders associated with uveitis are seronegative spondylarthropathy and sarcoidosis.1 3 Several types of uveitis are associated with histocompatibility leucocyte antigens (HIA) for instance, acute anterior uveitis with HIA B27 and birdshot chorioretinopathy with HLA A29.4 The reason why these HLA types increase the relative risk for uveitis is unclear but in the case ofHLA B27 infections with Gram negative bacteria might be an influence.5 Autoimmune mechanisms are also thought to participate in the pathogenesis of uveitis since the eye harbours autoimmune inducing or uveitogenic material such as retinal S-antigen and interphotoreceptor retinoid binding protein.4 After immunisation with adjuvants these antigens induce ocular inflammation in several species. Infectious diseases might indirectly play a role in autoimmune uveitis by triggering the immune response against autoantigens.4 Furthermore, infectious diseases are able to induce directly intraocular inflammation.6 The retina consists of neural tissue, making it particularly prone to infection with neurotropic organisms such as Toxoplasma gondii and herpesviruses. Other infectious diseases that can induce uveitis are tuberculosis, syphilis, and Lyme borreliosis. In some forms of infectious uveitis for example, ocular toxoplasmosis, autoimmune mechanisms are thought to participate in the ocular manifestations of the disease.7-9 Discrimination between the infectious or non-infectious aetiology of uveitis is important since the treatment is different. Immunosuppressive therapy is often essential but it might be deleterious in direct infectious uveitis entities without specific antimicrobial treatment. In various infectious ocular diseases, such as ocular toxoplasmosis or acute retinal necrosis, there are no signs of a systemic infection. Investigation of serum antibody titres therefore gives little if any information about the aetiology of the uveitis. 10 Instead of looking in the general circulation, it might be

Soluble ICAM-1 serum levels in patients with intermediate uveitis

AIM To investigate whether serum levels of soluble intercellular adhesion molecule 1 (sICAM-1) can serve as a marker of the presence of systemic disease in intermediate uveitis. METHODS In a multicentre study sICAM-1 serum levels were measured in 61 patients with idiopathic intermediate uveitis, controls included 56 uveitis patients with a systemic disease (26 sarcoid associated uveitis and 30 HLA-B27 positive acute anterior uveitis), 58 uveitis patients without systemic disease (30 toxoplasma chorioretinitis and 28 Fuchs’ hetrochromic cyclitis), and 21 normal controls. The clinical records of the patients with intermediate uveitis were analysed for disease characteristics at the time of blood sampling and for a relation with the development of a systemic disease after a mean follow up of 4.5 years. RESULTS Increased serum levels of sICAM-1 were found in 34 out of 61 patients with intermediate uveitis and were significantly different when compared with toxoplasmosis, Fuchs’ cyclitis, and healthy controls (p<0.001). Elevated sICAM-1 levels were also found in 18 out of 26 patients with sarcoid uveitis and in 11 out of 30 patients with HLA-B27 associated anterior uveitis. Raised sICAM-1 levels in the intermediate uveitis group were significantly associated with active ocular disease (p<0.01) and the presence of vitreous exudates (p<0.05). Increased levels of sICAM-1 correlated with interleukin 8 levels (IL-8) (tested in a previous study in the same group of intermediate uveitis patients) in patients with active systemic involvement. Follow up of the patients showed that an established or suspected systemic disease was found more often in the 21 intermediate uveitis patients with increased sICAM-1 and IL-8 levels compared with the other 40 patients with intermediate uveitis (p<0.01). CONCLUSIONS The measurement of both sICAM-1 and IL-8 can be used as a marker for ocular disease activity and for a predisposition of developing an associated systemic disease in intermediate uveitis patients.