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Opportunistic toxoplasmic retinochoroiditis following chemotherapy for systemic lymphoma. A light and electron microscopic study.

After a prolonged period of chemotherapy for a disseminated nodular lymphoma, a 51-year-old woman developed a white lesion in the left macular region, in the absence of any overt lymphomatous disease elsewhere. The initial retinal diagnosis was nonetheless a lymphomatous infiltrate. Due to her severely immunocompromised state, the patient developed pneumonia and died. The involved left eye was examined postmortem by light and electron microscopy. The retinal lesion was discovered to be caused by infection with Toxoplasma gondii, which on postmortem evaluation was also found in the brain together with subclinical lymphomatous disease and multifocal leucoencelphalopathy. Many viable and intact cysts were observed floating within the necrotic retina as well as lodged within recognizable retinal cells. Most of the organisms were encysted bradyzoites, although a rare tachyzoite was discovered in the extracellular space. Unusual features examined ultrastructurally were a preretinal membrane formed exclusively by glial cells, residual proliferating glial cells within the retina that were frequently related to surviving capillaries, and a multilaminar spindle cell placoid proliferation of pigment epithelial cells, assuming almost pseudo-sarcomatous proportions. Banded extracellular membrane material was focally observed between the proliferating pigment epithelial cells. No neoplastic lymphoreticular cells were discovered within the choroid, but a curious feature was the production of basement membranes by the surviving choroidal melanocytes. Toxoplasmosis should therefore be considered along with fungi and viruses in the differential diagnosis of white retinal lesions appearing in immunocompromised patients.

Antineoplastic Agents↗

Toxoplasmic scleritis.

Although toxoplasmosis is the most common infectious cause of posterior intraocular inflammation, it is rarely described in association with scleritis. The authors present five cases of toxoplasmosis with scleritis. Two of the five cases were diagnosed clinically and serologically as having toxoplasmosis. Their retinochoroiditis and scleritis responded well to medical therapy. Retinochroiditis and scleritis that was refractory to treatment developed in the other three patients, two of whom had been receiving immunosuppressive therapy for systemic diseases. Their therapeutic regimens did not include treatment for toxoplasmosis. All three eyes became blind and were enucleated. Results of pathologic examination of all three enucleated eyes showed Toxoplasma gondii in the retina. There was severe inflammation of the retina, choroid, and sclera. Toxoplasmosis should be considered in the clinical differential diagnosis of scleritis associated with retinochoroiditis, particularly in immunosuppressed patients.

Adult↗

Toxoplasma gondii retinochoroiditis and optic neuritis in acquired immune deficiency syndrome. Report of a case.

A 29-year-old man with acquired immune deficiency syndrome (AIDS) was found to have a retinochoroiditis and optic neuritis of his left eye. Results of fundus examination showed inflammatory and hemorrhagic retinal lesions consistent with retinitis due to cytomegalovirus infection. A computed tomographic (CT) scan demonstrated enlargement of the optic nerve. The eye was enucleated and results of histopathologic examination showed retinal necrosis with underlying choroiditis and an optic neuritis. Numerous encysted Toxoplasma gondii organisms were present in the retina and tachyzoites were present in the optic nerve. To the authors' knowledge this is the second histologically documented case of Toxoplasma optic neuritis in a patient with AIDS.

Acquired Immunodeficiency Syndrome↗

Multiple cases of acquired toxoplasmosis retinitis presenting in an outbreak.

OBJECTIVE: The purpose of the study was to examine the variability in presentation and outcome of individuals presenting with acquired toxoplasmosis retinitis in the setting of an outbreak of the disease. DESIGN: The study design was a case series. PARTICIPANTS: Twenty-one eyes of 20 patients with equal gender distribution and a mean age of 54 years followed for 38 to 170 weeks (mean 113.7 weeks) were studied. INTERVENTION: Systemic antimicrobials and corticosteroids when indicated were given. MAIN OUTCOME MEASURES: Visual acuity, media inflammation and clarity, resolution of active retinitis, and appearance of recurrence were observed. RESULTS: Fifteen of 21 lesions were active, and 7 of the total number of lesions fell within the macula-peripapillary region. Overall, vision improved with treatment except in cases of macular involvement (3 cases) and persistent vitritis (3 cases). Four recurrences have occurred to date. CONCLUSIONS: This is the largest reported outbreak of acquired toxoplasmosis retinitis occurring within a single outbreak. Twenty-one eyes of 20 patients presented with retinal lesions, and on average, those treated for active retinitis had improvement in vision.

Adolescent↗

Elevated interleukin 6 activity in aqueous humor of cats with uveitis.

The purpose of this study was to assess the role of interleukin 6 (IL-6) in feline uveitis by measuring IL-6 activity in the serum and aqueous humor of cats. Serum and aqueous humor was collected from clinically normal, random source cats (n = 10); clinically normal, specific-pathogen free cats experimentally inoculated with Toxoplasma gondii strain ME49 and sampled sequentially for 20 months (n = 4); and client-owned cats with uveitis (n = 27). Interleukin 6 activity was measured in each sample. Client-owned cats with uveitis were also evaluated for evidence of present or prior exposure to T. gondii, feline leukemia virus, feline immunodeficiency virus, and feline coronaviruses. Interleukin 6 activity was non-detectable or low in serum from cats of each group. Interleukin 6 activity was not detected in aqueous humor of clinically normal cats. Interleukin 6 activity was detected in 22/27 (81.5%) aqueous humor samples from cats with uveitis, with a range of 28.9 U ml(-1)-15702.9 U ml(-1) (mean = 1911.9 U ml[-1], SD = 3946.7 U ml[-1]). Serologic evidence of exposure to T gondii, feline immunodeficiency virus, feline leukemia virus, or a coronavirus was present in 21/27 (77.8%) cats with uveitis. Interleukin 6 was detected in the aqueous humor of 18/21 (85.7%) and 3/6 (50%) of the cats with and without serologic evidence of exposure to one to the infectious diseases, respectively. Statistically significant increases in mean IL-6 activity in aqueous humor were found for cats with any evidence of infection with T. gondii, for cats with T. gondii antigen in aqueous humor and for cats with coronavirus antibody titers > or = 1:100. Aqueous humor IL-6 activity was greater than corresponding serum IL-6 activity in 21/27 cats. These results show that IL-6 is produced intraocularly in some cats with uveitis and that IL-6 may be a mediator of uveitis in cats.

Animals↗

Polymerase chain reaction for the detection of Toxoplasma gondii within aqueous humor of experimentally-inoculated cats.

The purpose of this study was to determine the temporal appearance of T. gondii in aqueous humor of cats orally inoculated with T. gondii using polymerase chain reaction (PCR) for the detection of the B1 gene. Serum and aqueous humor were collected from five SPF cats prior to oral inoculation with T. gondii and days 7, 14, 21, 28, 42, 84, 140, 147, 154, 161, 168, and 182 after inoculation. Cats were inoculated orally with T. gondii tissue cysts on day 0 and day 140. T. gondii-specific IgM and IgG were measured in serum and aqueous humor from the cats at each sample data. T. gondii B1 gene PCR was performed on all the aqueous humor samples and the amplified DNA was detected by Southern blotting. Chorioretinitis developed in three out of the five cats, but anterior uveitis was not detected. All cats developed T. gondii-specific IgG titers in serum, and had T. gondii-specific IgG C-values > 1 in both eyes at varying times during the study. T. gondii was detected by PCR and Southern blotting in aqueous humor in both eyes of all cats at times varying from days 14-84 after primary inoculation and days 14-42 after challenge inoculation.

Administration, Oral↗

Ophthalmological findings in children with congenital toxoplasmosis. Report from a Swedish prospective screening study of congenital toxoplasmosis with two years of follow-up.

UNLABELLED: Congenital toxoplasmosis may lead to severe visual impairment or neurological sequelae in the child. PURPOSE: To study the severity of the primary and late ophthalmological dysfunction during a prospective incidence study of congenital toxoplasmosis in the Stockholm and Skåne counties. METHODS: Blood collected on phenylketonuria (PKU) cards from 40,978 consecutively born children were investigated for antitoxoplasma antibodies. Children with verified congenital toxoplasmosis were treated for 12 months with antiparasitic therapy and followed ophthalmologically, neurologically and serologically every third month. RESULTS: Three children had congenital toxoplasmosis. Two of these were asymptomatic at birth and would have escaped early detection without screening. One child had unilateral severe visual impairment and CNS involvement. The incidence of congenital toxoplasmosis was less than 1:10,000. CONCLUSION: Neonatal screening is of importance to diagnose asymptomatic infected children with congenital toxoplasmosis as treatment has been shown to reduce long-term sequelae. Ophthalmological investigations should start early and continue in co-operation with paediatricians.

Adult↗

An investigation of the general immune status and specific immune responsiveness to retinal-(S)-antigen in patients with chronic posterior uveitis.

Immunological abnormalities in endogenous posterior uveitis are widely reported but difficult to verify. We have therefore studied several immunological parameters in 14 patients with chronic posterior uveitis and compared the results with 14 healthy controls. Both the general immune status and the specific immune responsiveness to retinal S-antigen have been investigated. Results for the patient group as a whole were not significantly different from the control group. However the patients with severe eye disease (n = 4) had a reduced proliferative response to streptokinase-streptodornase antigen and two further individuals showed a general deficiency in functional cell mediated immunity. Circulating T-helper cells were marginally but not significantly reduced in patients. Responsiveness to bovine retinal S-antigen varied to a similar degree in both the patient and control groups. These findings indicate that, although severe uveitis may be associated with functional defects in cellular immunity in certain cases, in general the measurement of immune responsiveness of peripheral blood lymphocytes is unlikely to aid in the diagnosis or management of chronic posterior uveitis.

Adolescent↗

The value of laboratory testing in uveitis.

Accurate diagnosis of uveitis is of great importance since the treatment for the various uveitis entities may differ considerably. In a large number of cases the clinical picture is sufficient to make an adequate diagnosis. There are cases in which the diagnosis cannot be made on clinical grounds alone and support is needed from laboratory tests. Only a limited number of tests have been proven to be useful as a diagnostic or prognostic aid. These include HLA-B27 typing in patients presenting with anterior uveitis and testing for angiotensin converting enzyme and lysozyme in case of suspected sarcoid uveitis. Toxoplasma serology is only useful to exclude the diagnosis and a positive test has very low specific value. Analysis of local intraocular antibody production is a valuable tool to confirm a suspected clinical diagnosis in uveitis. It is now possible to analyse paired serum and aqueous samples for the presence of specific antibodies against toxoplasma, cytomegalovirus, herpes simplex virus and varicella zoster virus using commercially available kits. Of the patients retrospectively diagnosed as having toxoplasma chorioretinitis 75% were shown to have a positive antibody coefficient indicating specific intraocular antibody production. Local antibody production in the eye directed against CMV confirmed the suspected diagnosis of CMV retinitis in 50% of the AIDS patients investigated. Until now we have not been able to measure 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 even had a higher titre in the aqueous than in serum. Since the choice of treatment, in infectious uveitis, depends on the causative organisms, it is very important to confirm a suspected clinical diagnosis with aqueous humor analysis.

Antibodies, Protozoan↗

Disruption of the choroidoretinal interface by toxoplasma.

Toxoplasmosis is a common zoonotic infection of the retina caused by Toxoplasma gondii. The disease causes severe damage that affects the retina and subjacent choroid. Invasion of the retinal cells by the parasite leads to the major damage seen in the retina. Subsequent reactions to the invasion by toxoplasma leads to the influx of inflammatory cells. Although hypersensitivity reactions have been described to both toxoplasma and to retinal autoantigens, the major disruption of the choroidoretinal interface is probably secondary to the tissue invasion by the parasite. Patients with AIDS may show extensive necrosis of the retina in the absence of inflammatory cells. Healing of the active lesion leads to scar formation. Toxoplasma retinochoroiditis may be pigmented, nonpigmented or punched-out. Vascular anastomoses between the retina and choroid, retinal and subretinal neovascularization may occur in the aftermath of choroidoretinal interface disruption.

Animals↗

Transforming growth factor-beta expression in human retinal pigment epithelial cells is enhanced by Toxoplasma gondii: a possible role in the immunopathogenesis of retinochoroiditis.

Retinochoroiditis caused by Toxoplasma gondii infection results in inflammation and necrosis of the retina. We have used human retinal pigment epithelial cultures (HRPE) as an in vitro model to investigate the role of TGF-beta in T. gondii-induced retinochoroiditis. RT-PCR analyses showed enhanced steady state levels of TGF-beta1 and TGF-beta2 mRNA in T. gondii-infected HRPE. Uninfected HRPE secrete TGF-beta1 in a latent form while 10-30% of the secreted TGF-beta2 was in the active form. T. gondii infection induced a significant increase (P < 0.01) in total TGF-beta1 and TGF-beta2 secretion by HRPE. In addition, soluble extracts of T. gondii (ST) stimulated secretion of both TGF-beta1 and TGF-beta2 significantly (P < 0.01). Interestingly, T. gondii infection as well as ST of the parasites completely inhibited secretion of the active form of TGF-beta2. Studies evaluating the effect of TGF-beta on T. gondii replication in HRPE revealed that TGF-beta enhanced parasite replication. The interactions between host retinal cells and T. gondii may play an active role in the pathogenesis of retinochoroiditis.

Animals↗