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Ophthalmic outcomes after prenatal and postnatal treatment of congenital toxoplasmosis.

PURPOSE: To describe the ophthalmologic outcomes of cases of congenital toxoplasmosis treated prenatally and postnatally. DESIGN: Observational case series. METHOD: Follow-up ophthalmologic examinations of 18 children born to mothers who were infected before 25 weeks gestation were performed concurrently by two ophthalmologists. The infection in these children was first suspected when their mothers seroconverted during gestation. Toxoplasmic infection of the fetus was diagnosed by fetal blood or amniotic fluid analysis. Mothers were treated by a regimen of alternating pyrimethamine-sulfonamides and spiramycin during gestation. Pyrimethamine-sulfonamides treatment was continued from birth to 1 year of age. RESULTS: The median age of the children was 4.5 years (range 1-11), when the follow-up ophthalmologic examinations were performed. Visual acuity was decreased in only one child, who had extensive bilateral macular and peripheral lesions. A posterior pole scar was noted in four eyes (four children) for whom visual acuity remained normal. Peripheral lesions were observed in nine eyes (five children). Both eyes were normal in 11 of 18 (61%) of the children. CONCLUSIONS: In these children at a high risk for congenital toxoplasmic retinochoroiditis, a favorable visual outcome was observed in all but one case.

Antiprotozoal Agents↗

Surgery for subfoveal choroidal neovascularization in toxoplasmic retinochoroiditis.

PURPOSE: To report a case of subfoveal choroidal neovascularization in a patient with toxoplasmic retinochoroiditis who underwent surgical excision. DESIGN: Interventional case report. METHODS: A 36-year-old woman with toxoplasmic retinochoroiditis presented with sudden dimness of vision and metamorphopsia in the left eye. The patient was examined with ophthalmoscopy and fluorescein angiography. RESULTS: Fundus examination and fluorescein angiography of the left eye revealed a subfoveal choroidal neovascularization. Pars plana vitrectomy with submacular surgery was performed, with a postoperative improvement of visual acuity and resolution of the distortion. CONCLUSIONS: This case report describes a case of subfoveal choroidal neovascularization associated with toxoplasmic retinochoroiditis that responded remarkably well to vitrectomy surgery.

Adult↗

Eye manifestations of congenital toxoplasmosis.

PURPOSE: To determine the natural history of treated and untreated congenital toxoplasmosis and impact of this infection on vision. METHODS: In this prospective, longitudinal study, 76 newborns were treated with pyrimethamine and sulfadiazine for approximately one year, and 18 individuals not treated during their first year of life entered the study after age 1 year (historical patients). RESULTS: Chorioretinal scars were the most common eye finding in all patients and were most common in the periphery (58% of treated and 82% of historical patients). Macular scars were present in 54% of the treated patients; 41% were bilateral. Macular scars were present in 76% of the historical patients; 23% were bilateral. Visual acuity in the presence of macular lesions ranged from 20/20 to 20/400. Of the patients followed up from the newborn period and treated, 29% had bilateral visual impairment, with visual acuity for the best eye of less than 20/40. Causes for this visual impairment in eyes with quiescent lesions included macular scars, dragging of the macula secondary to a peripheral lesion, retinal detachment, optic atrophy, cataract, amblyopia, and phthisis. There were recurrences in both treated (13%, 7/54) and previously untreated historical patients (44%, 8/18). The total, median, and range of years of follow-up during which recurrences were observed were, for treated patients, 189 years (total), five years (median) and three to ten years (range) and, for historical, untreated patients, 160 years (total), 11 years (median), and three to 24 years (range). New lesions occurred in previously normal retinas and also contiguous to older scars. Active lesions appeared to become quiescent within ten to 14 days after beginning pyrimethamine and sulfadiazine therapy. CONCLUSION: Many children with congenital toxoplasmosis have substantial retinal damage at birth and consequent loss of vision. Nonetheless, vision may be remarkably good in the presence of large macular scars. Active lesions become quiescent with treatment.

Adolescent↗

Toxoplasmic retinochoroiditis: new insights provided by indocyanine green angiography.

PURPOSE: To analyze features of indocyanine green angiography associated with recurrent toxoplasmic retinochoroiditis. METHODS: Indocyanine green angiography was performed according to a standard protocol and correlated with clinical signs and fluorescein angiography in 12 eyes of 12 consecutive patients with recurrent toxoplasmic retinochoroiditis. RESULTS: In 10 of 12 eyes with recurrent toxoplasmic retinochoroiditis, indocyanine green angiography showed multiple satellite dark dots not seen on fluorescein angiography or clinical examination of the fundus. CONCLUSION: Indocyanine green angiography shows that recurrent toxoplasmic retinochoroiditis is more widespread than clinically visible lesions indicate. Indocyanine green angiography is useful in assessing the extent of involvement of recurrent toxoplasmic retinochoroiditis and the evolution of lesions and might also provide insights into the pathophysiology of the disease.

Angiography↗

Eye manifestations of congenital toxoplasmosis.

PURPOSE: To determine the natural history of treated and untreated congenital toxoplasmosis and impact of this infection on vision. METHODS: In this prospective, longitudinal study, 76 newborns were treated with pyrimethamine and sulfadiazine for approximately one year, and 18 individuals not treated during their first year of life entered the study after age 1 year (historical patients). RESULTS: Chorioretinal scars were the most common eye finding in all patients and were most common in the periphery (58% of treated and 82% of historical patients). Macular scars were present in 54% of the treated patients; 41% were bilateral. Macular scars were present in 76% of the historical patients; 23% were bilateral. Visual acuity in the presence of macular lesions ranged from 20/20 to 20/400. Of the patients followed up from the newborn period and treated, 29% had bilateral visual impairment, with visual acuity for the best eye of less than 20/40. Causes for this visual impairment in eyes with quiescent lesions included macular scars, dragging of the macula secondary to a peripheral lesion, retinal detachment, optic atrophy, cataract, amblyopia, and phthisis. There were recurrences in both treated (13%, 7/54) and previously untreated historical patients (44%, 8/18). The total, median, and range of years of follow-up during which recurrences were observed were, for treated patients, 189 years (total), five years (median), and three to ten years (range) and, for historical, untreated patients, 160 years (total), 11 years (median), and three to 24 years (range). New lesions occurred in previously normal retinas and also contiguous to older scars. Active lesions appeared to become quiescent within ten to 14 days after beginning pyrimethamine and sulfadiazine therapy. CONCLUSION: Many children with congenital toxoplasmosis have substantial retinal damage at birth and consequent loss of vision. Nonetheless, vision may be remarkably good in the presence of large macular scars. Active lesions become quiescent with treatment.

Adolescent↗

Factors related to the initiation and recurrence of uveitis. XL Edward Jackson memorial lecture.

Uveitis comprises a complex group of diseases in which morbidity may depend on the nature of the initial inflammation as well as on the genetic, hormonal, and emotional background of the patient. Uveitis is initiated in every instance by some form of tissue injury. This may occur as an attack on individual cells by organisms such as Toxoplasma gondii or Herpesvirus hominis. Autoimmune disease may be produced as a late result of microbe-induced injury. The development of specific forms of autoimmunity seems to be dependent upon genetic as well as hormonal factors, particularly estrogens. Tissue injury of immunologic origin takes several forms, such as cytotoxic damage from sensitized lymphocytes, immune complex-mediated injury, and injury from the oxidative products of inflammatory cells. In some cases, permanent alteration of uveal vascular permeability results. Recurrent uveitis may be attributed in some instances to the reappearance of infectious organisms in the target tissue. In other cases, recurrence of inflammation may be attributed to the localization of immune complexes in the uveal tract. Changes in immunoregulation can be attributed to pregnancy, aging, and emotional factors. Neurohumoral pathways related to stress-mediated changes in immunoregulation have recently been described in laboratory animals. These pathways may be linked with stress-related recurrences of uveitis in humans.

Aged↗

Changing patterns of uveitis.

We conducted a retrospective analysis of 600 patients with uveitis seen at the Estelle Doheny Eye Center to determine the frequency of occurrence of the various forms of uveitis and to see if the causes of uveitis have changed as compared with previous studies. In 402 cases (67.0%) we established a specific diagnosis based on history, physical findings, and laboratory studies: 167 cases (27.8%) involved primarily the anterior segment, 230 (38.4%) the posterior segment, and 111 (18.4%) occurred as panuveitis. Intermediate uveitis (pars planitis) was the single most frequently diagnosed uveitic entity and accounted for 92 cases (15.4%). We compared our findings with those of previously published studies and found that, as new diseases occur and improved diagnostic techniques become available, the differential diagnosis of uveitis continues to change.

Choroiditis↗

The ultrastructural pathology of congenital murine toxoplasmic retinochoroiditis. Part II: The morphology of the inflammatory changes.

A congenital murine model of toxoplasmic retinochoroiditis was employed to study the ultrastructural pathology of retinal parasitization by Toxoplasma gondii. Forty-two eyes from infected mice (18-22-weeks-old) and 24 eyes from control animals were studied by light microscopy (semithin sections). Twenty-six of the eyes from infected animals and six from the control group were subsequently selected for transmission electron microscopy. Control tissues showed no significant abnormality. The pathological changes in diseased tissues ranged in severity from low-grade mononuclear cell infiltration in the subretinal space to complete destruction of the outer retina, the retinal pigment epithelium and the choroid in the presence of a granulomatous inflammatory reaction. Phagocytosis of photoreceptor outer segments by macrophages was observed. Both macrophages and lymphocytes appeared to mediate photoreceptor lysis in eyes which were moderately affected by the disease. Severely affected eyes exhibited vasculitis and inflammatory cell invasion into the vitreous. A lymphoplasmacytoid cell infiltrate was present in the outer retina and choroid in these eyes. There was no evidence that Toxoplasma cysts provided foci for inflammatory cell attack.

Animals↗

Congenital toxoplasmosis in twins: a series of 14 pairs of twins: absence of infection in one twin in two pairs.

Fourteen pairs of twins with congenital toxoplasmosis were observed. In two pairs, one twin was infected and had symptoms of chorioretinitis or encephalomyelitis, while the other had a negative dye test upon repeated examination: this phenomenon has not previously been reported. In three of the other twelve pairs of twins, one of each pair died; two of them had evidence of toxoplasmosis; in the cotwin the diagnosis was based on serologic data. Clincial and biologic follow-up extended from 19 months to 8 years in five pairs. Marked discrepancies in the individual clinical patterns of the two children in each of six sets of twins were observed, with evidence of infection in one twin and subclinical infection in the other. These clinical findings correlated well with serologic data in the children in whom sufficient follow-up was permitted. The clinical pattern of congenital toxoplasmosis in twins is extremely similar in monochorial pregnancies, but discrepancies are almost the rule in bichorial pregnancies. The importance of placental lesions in determining the extent of fetal involvement is well illustrated by studies of toxoplasmosis in twins.

Child↗

Pediatric uveitis.

Uveitis in children is an entity most pediatricians and ophthalmologists seldom encounter. It is prevalent in society, however, and the high incidence of sight-threatening complications in untreated children warrants a baseline knowl-edge of the diseases and disorders involved as well as a sense of when to refer to a specialist.

Arthritis, Juvenile↗

Molecular diagnosis of toxoplasmosis.

Toxoplasmosis is an anthropozoonotic disease endemic world-wide, caused by the apicomplexan Toxoplasma gondii. Although the course of infection is generally benign, it can cause significant morbidity and mortality in the developing fetus and in immunocompromised individuals. Biological diagnosis classically relies upon serology and direct detection of the parasite by inoculation to laboratory animals. In the past decade, the use of the polymerase chain reaction (PCR) has made a significant improvement in both the prenatal diagnosis of congenital toxoplasmosis and the detection of acute disease in the immunocompromised patient. Nevertheless, like many 'in-house' PCR assays, the PCR-Toxoplasma suffers from lack of standardization and variable performance according to the laboratory. A wide variety of primers has been used in different assays, but few comparative tests have been performed. Moreover, in contrast to other parasitic diseases, PCR-Toxoplasma has not yet attained a sufficient level of sensitivity, regardless of the clinical condition considered. These drawbacks are discussed, together with the undoubted gain that PCR has brought to this difficult diagnosis.

Humans↗

Antibiotics for toxoplasmic retinochoroiditis: an evidence-based systematic review.

PURPOSE: To determine the effectiveness of systemic antibiotic treatment for toxoplasmic retinochoroiditis. CLINICAL RELEVANCE: Toxoplasma retinochoroiditis is a significant cause of visual morbidity. Multiple different antibiotic regimens are used, but controversy about treatment effectiveness remains. LITERATURE REVIEWED: Searches were conducted of Cochrane Controlled Trials Register, Medline (1966 onward), Embase (1980 onward), Dissertation Abstracts (1861 onward), Lilacs (1982 onward), and Pascal (1984 onward). Pharmaceutical companies were contacted for unpublished data. Any randomized controlled trials that compared antibiotics versus placebo in immunocompetent patients with toxoplasmic retinochoroiditis were retrieved. Primary outcome measures were long-term visual acuity and risk of recurrent retinochoroiditis. Secondary outcomes included duration and severity of acute symptoms, size of the lesion at end of follow-up, and adverse effects of treatment. RESULTS: Only 3 studies (total of 173 participants) were randomized controlled trials and hence met the inclusion criteria (level II). All 3 were methodologically poor, and 2 were carried out more than 35 years ago. None reported the effect on long-term visual outcome. We found no evidence for a beneficial effect on the duration and severity of signs of acute toxoplasmic retinochoroiditis (A,II). There was weak evidence for an effect of long-term treatment for chronic recurrent toxoplasmic retinochoroiditis on lesion recurrence. Treatment was associated with adverse effects. CONCLUSIONS: There is a lack of evidence to support routine antibiotic treatment for acute toxoplasmic retinochoroiditis. Placebo-controlled randomized trials of antibiotic treatment in patients presenting with acute or chronic toxoplasmic retinochoroiditis arising in any part of the retina are required.

Acute Disease↗

Toxoplasmosis neuroretinitis.

BACKGROUND: Neuroretinitis is a distinct clinical entity consisting of moderate to severe visual loss, optic nerve head edema, macular exudate in a stellate pattern, and variable vitreous inflammation. Although the etiology is usually postviral or idiopathic, an acute infectious cause occasionally is demonstrated. METHODS: Five juvenile or young adult patients with neuroretinitis are presented with serologic evidence of Toxoplasma gondii infection. Four of the five patients were treated with systemic antibiotics and corticosteroids; one patient was not treated. RESULTS: With a mean follow-up period of 50 months, visual acuity returned to 20/25 or better in four patients, with one patient regaining visual acuity of 20/60. Two patients had one or more recurrent episodes of neuroretinitis, distinguishing toxoplasmosis from idiopathic neuroretinitis, which is usually a monophasic illness. CONCLUSION: Toxoplasmosis infection is a rare, but potentially treatable, form of neuroretinitis and should be included in the differential diagnosis of "Leber's idiopathic stellate retinopathy."

Adult↗