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Biomedical subjects

A Rothova

Publications and source records attributed to A Rothova.

At least 19 recordsLinked to original sources

Fuchs' heterochromic iridocyclitis is not associated with ocular toxoplasmosis.

To analyze the association between Fuchs' heterochromic iridocyclitis (FHI) and toxoplasmosis, we performed ocular examinations and used various specific laboratory tests to establish a role for Toxoplasma gondii in the pathogenesis of FHI. Results were compared with those for other types of uveitis and healthy controls. Of the 88 patients with FHI, nine (10.2%) had toxoplasmosislike scars, but an association could not be proved by the indirect immunofluorescence antibody test or enzyme-linked immunosorbent assay, or by a test for cellular immunity to Toxoplasma antigen. Analysis of aqueous humor samples for Toxoplasma antibodies in patients with FHI also yielded negative results. On the basis of the negative results of these laboratory tests, we concluded that FHI is not associated with ocular toxoplasmosis.

Adolescent

Uveitis and systemic disease.

A prospective study was conducted of 865 patients with uveitis to determine the frequency of associated systemic diseases and to assess the value of limited laboratory screening of these patients. All patients underwent a standard diagnostic protocol followed--when indicated--by special tests and procedures performed in order of likelihood ('tailored approach'). For 628 patients (73%) a specific diagnosis was established based on history, ophthalmologic examination, and laboratory and radiographic studies. A definite association with systemic disease was determined for 220 patients (26%). A relationship with a subclinical systemic disorder could be presumed in 201 cases (23%) and a well-established clinical uveitis entity without a recognisable systemic disorder was present in 207 cases (24%). For 237 patients (27%) a diagnosis could not be determined. The most frequently observed systemic diseases were sarcoidosis (7%) and HLA-B27-associated seronegative spondylarthropathies (6%). Presumed or definite toxoplasmosis was encountered in 10% of cases. HLA-B27-associated acute anterior uveitis was the most common clinical entity (17%). In the majority of cases the presence of a systemic disease was not suspected prior to eye involvement and was only recognised after the subsequent diagnostic procedures.

Adolescent

Intermediate uveitis and Lyme borreliosis.

A case of chronic intermediate uveitis and associated classic snowbanking (pars planitis) with severe cystoid macular oedema probably due to Lyme borreliosis is reported. Despite a disease duration of 10 years the patient's ocular symptoms and visual acuity responded promptly to intravenous ceftriaxone treatment. This case demonstrates that periodic reevaluation of patients with intermediate uveitis is necessary to obtain a specific diagnosis which may include Lyme borreliosis.

Adult

Anticardiolipin antibodies in uveitis.

Anticardiolipin antibodies (ACA) have been described in association with thrombosis and several vascular diseases and may be involved in retinal vasculitis. To investigate this question we tested sera from 86 patients with posterior uveitis and 100 healthy controls for the presence of anticardiolipin antibodies. The antibody was present in 15 patients: in 7 of the patients with acute retinal necrosis (n = 24), in 4 with idiopathic retinal vasculitis (n = 10), 3 with syphilis (n = 6) and in one SLE patient with retinal vasculitis. Ten patients had IgA-type anticardiolipin antibodies, 6 had IgM-type and 4 had IgG-type anticardiolipin antibodies. Anticardiolipin antibodies could not be detected in sera from uveitis patients with Behçet's disease (n = 10), sarcoid (n = 9), toxoplasmosis (n = 7), multiple sclerosis (n = 3) or Birdshot chorioretinopathy (n = 10). Ten of the healthy controls had cardiolipin antibodies of the IgM class. The exact role of these auto-antibodies in the pathogenesis of retinal vasculitis remains to be resolved.

Antibodies, Anticardiolipin

Fuchs's heterochromic cyclitis in congenital ocular toxoplasmosis.

We report a follow-up after 25 years of a patient with a congenital bilateral ocular toxoplasmosis who developed Fuchs's heterochromic cyclitis in her left eye. Whether Toxoplasma gondii can cause the development of Fuchs's heterochromic cyclitis, as our case suggests, or whether the iridocyclitis is a secondary ocular response to other agents, is not yet clear.

Animals

Analysis of aqueous humour in ocular onchocerciasis.

The development of an onchocercal chorioretinopathy from the first detectable signs to a full blown oncho fundus is not fully understood. We investigated the intraocular humoral immune response against Onchocerca volvulus, human S-antigen, IRBP and crude retinal extract (using an ELISA) by examining paired aqueous humour and serum samples obtained from onchocerciasis patients (without [n = 10] and with ocular symptoms [n = 8]) and endemic controls [n = 14] from Sierra Leone (West Africa). A local intraocular anti-retinal IgG antibody production could not be demonstrated in onchocerciasis patients, whether they had ocular symptoms or not. A significantly higher level of O. volvulus antibodies and IgG was measured in the aqueous of onchocerciasis patients with ocular involvement, as compared to patients without ocular symptoms (Mann-Whitney ranksum test; p less than 0.001 and p less than 0.02 respectively). Since interleukin-6 (IL-6) plays an essential role in the differentiation of B cells into immunoglobulin producing plasma cells, we therefore measured this cytokine in paired aqueous and serum samples. Elevated IL-6 levels were found in the aqueous of two out of eight onchocerciasis patients tested. In view of these findings it seems improbable that retinal autoimmunity is a major factor in the pathogenesis of onchocercal chorioretinopathy. The high intraocular levels of antibodies against the parasite suggest a direct involvement of the parasite in the pathogenesis of onchocercal chorioretinopathy.

Adult

The lifetime cumulative incidence of acute anterior uveitis in a normal population and its relation to ankylosing spondylitis and histocompatibility antigen HLA-B27.

The lifetime cumulative incidence of acute anterior uveitis (AAU) was determined in a sample of a large population (n = 10,500). Nine hundred seventeen subjects, who answered the question "Have you ever had a red eye" in the affirmative in 1977, were asked to participate in a follow-up study 10 years later. From the 917 respondents, 539 were studied completely. A questionnaire was used to collect historic data, and confirmation of these data was obtained from the treating ophthalmologists and physicians. From these data, subjects were selected for an ophthalmologic examination. The respondents also underwent a rheumatologic examination. The results revealed that the lifetime cumulative incidence of definite AAU is approximately 0.2% in the general population and 1% in the histocompatibility antigen HLA-B27-positive population. In one third of the definite AAU patients, the cause of the disease was known. The lifetime cumulative incidence of definite AAU of unknown cause was 0.15% in the general population. When possible and probable AAU are included, the lifetime cumulative incidence of AAU in the general population is about 0.4%. The observed frequency of the concurrence of AAU and ankylosing spondylitis (AS) was 0.4% in the HLA-B27-positive population and 0.02% in the HLA-B27-negative population. Comparison with the expected frequency of the concurrence of AAU and AS revealed that AAU and AS probably are related diseases irrespective of the association of both diseases with HLA-B27.

Acute Disease

Ocular involvement in patients with onchocerciasis after repeated treatment with ivermectin.

We assessed ocular changes after therapy at six and 12 months with ivermectin (150 micrograms/kg of body weight) in a 12-month prospective study of 29 patients with ocular onchocerciasis and 15 patients with onchocerciasis without ocular involvement. The patients lived in a hyperendemic area in Sierra Leone, West Africa, where no vector control was instituted. Five months after initial treatment, the microfilarial load in skin and eyes had decreased significantly (P less than .0000), but 28 of 44 (63%) patients had positive skin-snip test results and nine of 29 (31%) patients with ocular involvement had active ocular disease. Twelve months after initial treatment, 15 of 41 (37%) patients had positive skin-snip test results and eight of 26 (31%) showed active ocular involvement. All patients with persistent ocular disease after therapy showed evidence of active onchocerciasis at that time, which suggests that a dose of ivermectin at six-month intervals is not sufficient for intensely infested patients with severe ocular disease. We developed an ocular involvement score to evaluate the patient's total ocular status and observed a significant relation between the pretreatment severity of ocular involvement and the persistence of active ocular disease after treatment with ivermectin.

Adolescent

Decrease in adverse reactions after repeated ivermectin treatment in onchocerciasis.

We assessed the side-effects after multiple single-dose treatment with ivermectin (150 micrograms/kg) in onchocerciasis patients form a hyperendemic area in Sierra Leone, in order to investigate whether medical surveillance was always necessary. After initial treatment 87 onchocerciasis patients were examined for adverse reactions. Fourty-four of these 87 patients (51%) received a second dose of ivermectin 5 months later and thirty-five (40%) received a third dose one year later. The side-effects after the second and third doses were significantly diminished, when compared with the initial dose of ivermectin in the treatment of onchocerciasis (chi2 test p less than 0.005, resp. p less than 0.008). Side-effects requiring therapy were observed in 32% of patients after the first dose, in 18% after the second dose and in 11% after the third dose of ivermectin. Severe side-effects (9%) were only seen after the initial ivermectin dose. All the severe adverse reactions appeared within 48 hours. In view of our findings, it seems necessary that the first treatment with ivermectin should take place under strict medical supervision during at least two days. Five months after treatment with a single dose of ivermectin 29 out of 44 patients (66%) still had a positive skin-snip test. Seven months after the second dose 15 of 35 patients (43%) had a positive skin-snip count. Since almost half of the patients had a positive skin-snip test despite two treatments with ivermectin, it could be argued that in hyperendemic areas treatment should consist of at least two doses in the first year.

Administration, Oral

Laboratory tests in uveitis. New developments in the analysis of local antibody production.

Analysis of local intraocular antibody production is a valuable tool with which to confirm a suspected clinical diagnosis in uveitis. We have analysed paired serum and aqueous samples for the presence of specific antibodies against toxoplasma, cytomegalovirus, herpes simplex virus and varicella zoster virus. Of the patients retrospectively diagnosed as having toxoplasma chorioretinitis 75% had a positive antibody coefficient indicating specific antibody production in the eye. Local antibody production in the eye directed against CMV confirmed the suspected diagnosis of CMV retinitis in 50% of the AIDS patients investigated. So far we have not been able to demonstrate local antibody production against herpes simplex virus (26 samples tested). Two of three patients with acute retinal necrosis had a positive antibody coefficient against varicella zoster virus. Both of these patients had an even higher titer in the aqueous than in serum. Since the choice of therapy, in infectious uveitis, depends on the causative organisms, it is very important to confirm a suspected clinical diagnosis by means of aqueous humor analysis.

Antibodies, Protozoan

Cyclosporin in the treatment of severe chronic idiopathic uveitis.

In a randomised double-masked study of 27 patients with a severe chronic idiopathic uveitis we evaluated the efficacy, safety, and tolerability of cyclosporin. All received prednisone in a low dose (0.3 mg/kg/day). In 14 patients this was combined with cyclosporin in a single daily dose of 10 mg/kg/day, while 13 patients received a placebo. The dosages were tapered off in accordance with a protocol, and we compared the number of months of successful therapy before the uveitis relapsed. The efficacy results, as expressed in a Kaplan-Meier curve, were in favour of cyclosporin. Owing to the small sample size, however, this difference did not reach statistical significance. The immunosuppressive effect of cyclosporin was not permanent, and in all but one patient the intraocular inflammation relapsed on reduction of dosage. Rather small cumulative doses of cyclosporin proved to be nephrotoxic, but subjective tolerability for cyclosporin was good.

Adult

Detection of locally produced antibodies to herpes viruses in the aqueous of patients with acquired immune deficiency syndrome (AIDS) or acute retinal necrosis syndrome (ARN).

Intraocular synthesis of IgG antibodies against HSV (herpes simplex virus), CMV (cytomegalovirus) and VZV (varicella zoster virus) is considered as an indirect proof of uveoretinal infection. Paired serum and aqueous samples obtained from 16 patients with retinitis associated with AIDS, 3 patients with ARN, 8 patients with posterior uveitis not related to AIDS or ARN and 5 patients with senile cataract were tested for total immunoglobulin G levels and antibodies to HSV, CMV and VZV by the fixed cell immunofluorescence technique. Since therapy must often be started before results of cultures are available, rapid detection of locally produced anti-Herpes Virus antibodies can be a precious tool in the diagnosis of ocular viral infection. Using this technique we were able to confirm the clinically suspected diagnosis in more than 50% of AIDS patients with retinitis and in two out of three patients with ARN.

Acquired Immunodeficiency Syndrome

Humoral and cellular immune reactions against retinal antigens in clinical disease.

Autoimmune reactions against retinal antigens have been suggested to play an important role in clinical uveitis in man. As yet the evidence for this assertion is very weak. Sympathetic Ophthalmia is a disease entity which comes closest to acceptance as an autoimmune disease although the autoantigen involved has not been identified. Both cellular and humoral autoreactivity against retinal antigens have been found both in uveitis patients as well as in healthy controls. Very high levels of retinal antibodies were found in onchocerciasis patients but no relation was observed with the occurrence of chorioretinitis. Differences were observed when testing patient sera against human or bovine retinal antigens (S-antigen or IRBP) emphasizing the need for using human tissue when investigating autoimmune responses. Circumstantial evidence in favor of an autoimmune etiology of uveitis include the morphology of the inflammatory infiltrate, effect of immuno-suppressive therapy and especially the establishment of experimental animal models. The experimental models of S-antigen or IRBP induced uveitis are primarily T cell mediated and also show pineal gland involvement. As yet no "established" human autoimmune disease has been described with a dominant role for T cells. Furthermore there is no evidence for pineal gland involvement in clinical uveitis. Analysis of the specificity of the T cell infiltrate or deposited immunoglobulins obtained from the diseased tissues may provide conclusive evidence for a possible autoimmune character of certain clinical uveitis entities.

Animals

Serum antibody response to human and bovine IRBP in uveitis.

Interphotoreceptor retinoid binding protein (IRBP) is a 136,000 molecular weight photoreceptor cell protein capable of inducing an experimental autoimmune uveitis (EAU) in susceptible animal strains. The occurrence of serum antibodies against human (Hu) or bovine (Bo) IRBP was investigated in patients with uveitis and healthy controls. A sensitive ELISA detected anti-IRBP in approximately 50% of patients and controls, without apparent differences in the mean level, titre or avidity and irrespective of the origin of the antigen. Although the correlation (p less than 0.001) between anti-HuIRBP and anti-BoIRBP levels in uveitis sera suggested the presence of crossreacting antibodies, these sera also contained antibodies specific for either the human or the bovine antigen. The only difference between patients and controls was the greater ability of antibodies in uveitis sera (p less than 0.05) to recognize a synthetic peptide of HuIRBP, which induces severe EAU in rats. We conclude that autoantibodies to IRBP occur naturally in man and are not increased in patients with uveitis.

Amino Acid Sequence

Cell-mediated immunity against human retinal extract, S-antigen, and interphotoreceptor retinoid binding protein in onchocercal chorioretinopathy.

Autoimmune mechanisms are thought to be involved in the pathogenesis of onchocercal chorioretinopathy. Cell-mediated immune responses to human retinal S-antigen, interphotoreceptor retinoid binding protein (IRBP), and crude retinal extract were investigated in patients with onchocerciasis from Sierra Leone, West Africa using a two-step migration-inhibition factor assay. Patients were subdivided into three groups: (1) without ocular involvement (n = 10), (2) with ocular onchocerciasis limited to the anterior segment (n = 19), and (3) with onchocercal chorioretinopathy (n = 21). A group of endemic controls (n = 25) from Sierra Leone were also studied. The cellular immune response to concanavalin A (Con A) was measured to assess the general capacity of lymphocytes to respond to a mitogen. Four of 50 (8%) patients with onchocerciasis and four of 25 (16%) endemic controls reacted with at least one retinal antigen. From the patients with onchocercal chorioretinopathy two of 21 (10%) showed a positive cellular response. The general mitogen response tested with Con A was positive in all these individuals. A role for an antiretinal autoimmune mechanism in the pathogenesis of onchocercal chorioretinopathy, as studied with human S-antigen, IRBP, or crude retinal extract, could not be shown because the cellular response to these antigens did not differ in patients with or without onchocercal chorioretinopathy or in endemic controls.

Adolescent