Neurologic and developmental outcome in treated congenital toxoplasmosis.

BACKGROUND: Earlier studies have shown that infants with untreated congenital toxoplasmosis and generalized or neurologic abnormalities at presentation almost uniformly develop mental retardation, seizures, and spasticity. Children with untreated subclinical disease at birth have developed seizures, significant cognitive and motor deficits, and diminution in cognitive function over time. OBJECTIVE: To determine neurologic, cognitive, and motor outcomes for children with congenital toxoplasmosis who were treated for approximately 1 year with pyrimethamine and sulfadiazine. DESIGN AND METHODS: Systematic, prospective, and longitudinal neurologic, cognitive, and motor evaluations were performed for 36 individuals with congenital toxoplasmosis. These infants were born between December 1981 and January 1991 and were treated with pyrimethamine and sulfadiazine for approximately 1 year beginning in the first months of life. Compliance with medications was documented. These individuals were evaluated in a standardized manner in a single center in the first months of life and at approximately 1, 3.5, 5, 7.5, and 10 years of age. Their cognitive function was compared with the cognitive function of a nearest-age, same-sex sibling when such siblings older than 3.5 years were available for study. RESULTS: Signs of active central nervous system infection (eg, cerebrospinal fluid [CSF] pleiocytosis, hypoglycorrhachia, elevated CSF protein, and, in some instances, seizures and motor abnormalities) resolved during therapy. Six of the 36 children had perinatal seizures. Four had their anticonvulsant therapy discontinued successfully within the first months of life, and two additional children developed new seizures at 3 and 5 years of age. Tone and motor abnormalities resolved by 1 year of age in 12 of 20 infants who exhibited abnormalities of tone and motor function at their initial neonatal evaluation. By February 1992, 29 of the 36 children had been evaluated when they were 1 year old, and 23 (79%) had a mean +/- standard deviation Mental Developmental Index (MDI) of 102 +/- 22 (range, 59 to 140). Six (21%) had a measure of their cognitive function that was less than 50. Results of sequential IQ tests, performed at 1.5 year intervals or greater, did not differ significantly over time (P > .05). Seven children with MDIs greater than 50 were compared with sibling controls; they had scores of 87 +/- 11 (range, 68 to 97) and their siblings had scores of 112 +/- 15 (range, 85 to 132) (P = .008). Seventeen of 18 children without hydrocephalus and six of eight children with obstructive hydrocephalus responsive to shunting had normal or near-normal neurologic and developmental outcomes. Children with hydrocephalus ex vacuo present at birth, with high CSF protein, and with lack of response to shunting have done less well. CONCLUSIONS: Neurologic and developmental outcomes were significantly better for most of these treated children than outcomes reported for untreated children or those treated for only 1 month (P < .001). Although the level of cognitive function for treated children was less than for their uninfected siblings (P < .008), there was no significant deterioration in neurologic and cognitive function of the treated children tested sequentially. These favorable treatment outcomes justify systematic identification and treatment of pregnant women with acute gestational Toxoplasma infection and young infants with congenital toxoplasmosis.

Fenestrated sheen macular dystrophy.

Fenestrated sheen macular dystrophy is an autosomal dominant macular disorder characterized by the presence in the central macular zone of a golden sheen with tiny red fenestrations. Even in the later stages, only a mild functional disturbance has been observed. There were five patients manifesting this dystrophy in two generations of a family. They represent the third family so described.

Leber's congenital amaurosis. Retrospective review of 43 cases and a new fundus finding in two cases.

Leber's congenital amaurosis is a hereditary clinical disorder that may be associated with several different diseases. This study consists of a retrospective review of 43 cases. Twenty of our patients had fundus appearances that resembled retinitis pigmentosa. Five had normal-appearing fundi. The remainder had other, previously reported fundus abnormalities, with the exception of two patients who demonstrated a new fundus finding, a nummular pigmentary pattern. Other associated eye anomalies included cataracts, keratoconus, ptosis, and strabismus. The most frequent systemic associations were mental retardation, cystic renal disease, skeletal disorders, and hydrocephalus.

Normal endothelial cell density range in childhood.

Specular microscopy of the in vivo corneal endothelium of 214 clinically normal eyes in children ranging from 5 to 14 years of age showed a regular mosaic of hexagonal cells. The cell population density of individuals presented some variation, as it doses in older subjects. Quantitative analysis permitted us to determine the normal range of the endothelial cell count at each age. The mean (+/- SD) value ranged from 3591 +/- 399 cells per square millimeter at age 5 years to 2697 +/- 246 cells per square millimeter for the oldest subjects. Our data show a rapid decrease in cell density up to age 10 years. We estimate from our data a decrease in cell density of 13% between ages 5 and 7 years and an additional decrease of 12% by age 10 years.

X-linked congenital stationary night blindness. Review and report of a family with hyperopia.

X-linked congenital stationary night blindness is almost always associated with myopia. We have reviewed all previously reported pedigrees and have found only two with patients without myopia. A recently proposed classification of night blindness includes a complete type associated with myopia and an incomplete type in which both hyperopia and myopia were found. Complete and incomplete types did not occur within the same pedigree. We report on a family in which three of the five affected members had hyperopia and could be classified as the incomplete type and in which a fourth member with myopia was more consistent with the complete type. The lack of myopia in three members of our pedigree can be explained by two hypotheses: crossing over of the night blindness and myopic genes on the X-chromosome, or an autosomal dominant hyperopic gene that masks the myopic gene. The data from our family support the first of these two hypotheses.

Anomalies of retinal architecture in Aicardi syndrome.

Eyes obtained at autopsy from a female infant with Aicardi syndrome (chorioretinal lacunae, agenesis of the corpus callosum, and seizures) were studied by light and electron microscopy. The retinal insertion was displaced anteriorly over the ciliary body, the choroid was attenuated, and the retinal pigment epithelium showed hyperplasia and pigment migration throughout the sensory retina. Rosettes of photoreceptorlike cells and inversion of the photoreceptor layer were found. A hole within a lacuna showed total absence of the sensory retina. Optic disc epipapillary tissue consisted of glial and fibrous elements with a vascular core. The mechanism of photoreceptor folding is considered. The continuity of the external limiting membrane with the retinal pigment epithelium at sites of photoreceptor folding seen in our case suggests defective early development.

Histopathological features of ocular toxoplasmosis in the fetus and infant.

BACKGROUND: Ocular disease is a frequent manifestation of congenital Toxoplasma gondii infection. There are only limited data available in the literature concerning early stages of this disease in fetuses and infants. The purpose of our study was to characterize histopathological features in the eyes of 10 fetuses and 2 infants with congenital toxoplasmosis. METHODS: Fifteen eyes from 10 fetuses, 3 eyes from 2 premature infants, and both eyes from a 2-year-old child with congenital toxoplasmosis were examined by light microscopy. Immunohistochemical analysis to identify inflammatory cells and T gondii antigens was performed. The findings in infected eyes were compared with those of age-matched control eyes. RESULTS: Retinitis (10/18 eyes), retinal necrosis (4/18 eyes), disruption of the retinal pigment epithelium (12/18 eyes), and choroidal inflammation and congestion (15/18 eyes) were characteristic findings. Optic neuritis was present in 5 of 8 fetal eyes with associated optic nerve available for evaluation. An eye obtained from a 32-week-old fetus showed retinal rosettes at the edge of a scar. T cells predominated in retinal lesions and choroid. Parasites were identified by immunohistochemical analysis in 10 of 18 eyes. CONCLUSIONS: Ocular toxoplasmosis causes irreversible damage to the retina in utero. The fetus and infant mount inflammatory responses that may contribute to ocular damage. These findings have important implications for serological screening programs and in utero therapy.

The eye and the chromosome.

The first linkage of disease traits on the human X-chromosome was reported in 1937, and the first assignment of a human disease to an autosome was made 26 years later in 1963. Now, after only 19 years, there are at least 338 assignments to loci on the human chromosome map. This amazing expansion of information extends to eye diseases. In this review, basic mechanisms of mutation are discussed, and the basic methodologies used for gene assignments are explained. All of the eye-related, definite, autosomal assignments are presented. The diseases that have regional assignments on the X-chromosome are discussed, and the remaining X-linked eye diseases are listed in table form.

Ocular deviation after retinal detachment surgery.

Thirty patients with untreated rhegmatogenous retinal detachments underwent complete ocular muscle examinations before scleral buckling procedures. The examination was repeated three weeks, six weeks, three months, and six months after surgery. We found a high incidence of heterotropia after surgery; in most cases this resolved during the first six postoperative months. This resolution progressed from heterotropia to heterophoria to orthophoria. We believe this change results from phoria adaptation. Diplopia occurred in three patients. We found no statistically significant association between this diplopia and the type of surgery used.

Ocular findings in partial trisomy 10q syndrome.

We examined three siblings with partial trisomy 10q born to a mother carrying a balanced translocation between chromosomes 4 and 10. Our patients had many of the phenotypic abnormalities characteristic of this syndrome, and their chromosomal abnormality was confirmed by karyotypes of peripheral blood lymphocytes. Two ophthalmoscopic abnormalities not previously reported in this syndrome were noted in our patients. One child had bilateral enlarged, gray optic disks with elevated, blurred margins and distended retinal vessels. Another child had bilateral punctate yellow deposits scattered around the macula and optic disk.

Lymphocytic choriomeningitis virus: an underdiagnosed cause of congenital chorioretinitis.

PURPOSE: To elucidate the role and clinical spectrum of congenital lymphocytic choriomeningitis virus infection as a cause of chorioretinopathy, congenital hydrocephalus, and macrocephaly or microcephaly in the United States. METHODS: We performed complete ophthalmologic surveys of all residents at Misericordia, a home for the severely mentally retarded in Chicago, and prospectively evaluated all patients with chorioretinitis or chorioretinal scars during a 36-month period at Children's Memorial Hospital, also located in Chicago. Sera for patients demonstrating chorioretinal scars (a sign of intrauterine infection) were tested for Toxoplasma gondii, rubella virus, cytomegalovirus, and herpes simplex virus and lymphocytic choriomeningitis virus antibodies. RESULTS: Four of 95 patients examined at the home had chorioretinal scars, and two of these patients had normal T. gondii, rubella virus, cytomegalovirus, and herpes simplex virus titers and dramatically elevated titers for lymphocytic choriomeningitis virus. Three of 14 cases of chorioretinitis at the hospital had normal T. gondii, rubella virus, cytomegalovirus, and herpes sim-plex virus titers and elevated lymphocytic choriomeningitis virus antibody titers. (A fourth case, diagnosed in 1996, was reported 2 years ago.) CONCLUSIONS: Lymphocytic choriomeningitis virus was responsible for visual loss in two of four children secondary to chorioretinitis in a population of severely retarded children. The six new cases of lymphocytic choriomeningitis virus chorioretinitis identified in these two populations over the last 3 years, compared with the total number ever reported in the United States (10 cases), suggests that lymphocytic choriomeningitis virus may be a more common cause of congenital chorioretinitis than previously believed. Because its consequences for visual and psychomotor development are devastating, we conclude that the workup for congenital chorioretinitis should include lymphocytic choriomeningitis virus serology, especially if T. gondii, rubella virus, cytomegalovirus, and herpes simplex virus titers are negative.

Lymphocytic choriomeningitis virus chorioretinitis mimicking ocular toxoplasmosis in two otherwise normal children.

PURPOSE: To report unilateral macular lesions, mimicking toxoplasmic scars, in two children with serological evidence for lymphocytic choriomeningitis virus infection. METHODS: Case reports. RESULTS: Patients were 4 and 5 years old, with negative toxoplasma serologies and no sign of rubella, cytomegalovirus, or herpes simplex infection (TORCH evaluation). Lymphocytic choriomeningitis virus infection was detected in both cases by enzyme-linked immunosorbent assay and confirmed by Western immunoblotting. The modes of infection were unknown; no history of symptomatic systemic lymphocytic choriomeningitis virus infection was reported, and lymphocytic choriomeningitis virus serologies were negative in the mothers of the patients. Neurological examinations and brain magnetic resonance imaging were normal. CONCLUSION: Our observations suggest that chorioretinal scars can be an isolated manifestation of lymphocytic choriomeningitis virus infection.

Infantile glaucoma in Down's syndrome (trisomy 21).

We examined five patients with Down's syndrome and bilateral infantile glaucoma. In the first few months of life four patients had large cloudy corneas, breaks in Descemet's membrane, increased intraocular pressure, photophobia, and tearing. In one patient the diagnosis was delayed until 3 1/2 years of age because of concomitant nasolacrimal duct obstruction. Two patients developed cataracts and retinal detachment and have undergone multiple surgical procedures. The clinical course in these two older patients suggests that coexistence of congenital glaucoma, severe myopia, and cataracts in patients with trisomy 21 strongly predisposes for the development of retinal detachment and poor visual outcome.

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.

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.

Iridocorneal adhesions in patients with the Marfan syndrome.

Marfan syndrome is an autosomal dominant connective tissue disorder characterized by skeletal, cardiovascular, and ocular anomalies. Ectopia lentis is the most common ocular manifestation. We report an ocular sign not previously described in Marfan syndrome, iridocorneal adhesions secondary to anterior lens subluxation. Three patients with the Marfan syndrome had iridocorneal adhesions on slit-lamp examination. One patient developed adhesions following treatment with pilocarpine. She underwent pars plana vitrectomy and lensectomy in both eyes due to progression of the iridocorneal adhesions. Treatment with miotics rotates the lens-iris diaphragm anteriorly and may contribute to the formation of such adhesions. The two other patients remained stable and did not received lensectomy or vitrectomy. Careful slit-lamp examination of the anterior segment should be conducted in patients with dislocated lenses.

Human albinos can discriminate spatial frequency and phase as accurately as normal subjects.

Previous experiments testing grating and vernier acuities in albino central vision are consistent with the hypothesis that the deficit in their monocular spatial processing is mainly due to the increased spacing of their foveal cones. This was tested by measuring albino spatial frequency discrimination over the range 0.25-4.0 cpd. The same experiments were performed on three normal subjects both in the fovea and at a peripheral locus at which their grating acuity was identical to that of the albino subjects. Spatial frequency discrimination thresholds averaged 3.71% for albinos, 5.18% for the normal fovea, and 8.81% for the normal periphery, the latter being over 2.3 times greater than albino thresholds. A comparable pattern of results was observed in phase discrimination experiments. These data reject the possibility that albino central vision is similar to normal peripheral vision, but the results are predictable on the hypothesis that the central retina of albinos is a spatially magnified (underdeveloped) version of the normal fovea.

Albino spatial vision as an instance of arrested visual development.

Adult albinos and human infants share a number of common visual characteristics: both have low grating acuity, both lack a foveal pit (foveal hypoplasia), and both have much lower central cone densities than in the normal adult. We have explored the consequences of these characteristics by measuring both spatial and temporal contrast sensitivity in the central retina and by comparing central and peripheral grating and vernier acuities in two young adult albino subjects. To compensate for nystagmus, horizontally oriented patterns were employed. Both subjects had normal flicker sensitivities, but their central grating and vernier acuities were approximately five times worse than normal. At 10.0 degrees in the inferior visual field, however, vernier and grating acuities were normal for both subjects. Finally, the ratio of grating to vernier acuity in albino central vision fell within the normal foveal range, suggesting that albino central vision does not resemble the adult periphery. These results are consistent with the hypothesis that spatial processing deficiencies in albino central vision are a direct consequence of the increased spacing of their central cones. Our data are comparable to available psychophysical results obtained from infants of approx. 10 months of age, thus suggesting that the albino visual system may represent a case of arrested development.

Spatial frequency and orientation tuning of spatial visual mechanisms in human albinos.

A masking paradigm was used to measure the spatial frequency and orientation tuning of spatial mechanisms in the albino visual system. Threshold elevation curves obtained in this manner at test spatial frequencies of 0.25 cycles/deg (cpd), 0.50 cpd, and 1 cpd have the same shape as curves obtained from normal subjects at test frequencies two octaves higher. Additional masking studies showed that contrast processing in albinos obeys the same compressive power law as in normals. Thus, spatial mechanisms in albino central vision have normal spatial frequency and orientation bandwidths. As central cones in the albino are spaced 3-4 times further apart than in the normal fovea, these results support the hypothesis that monocular spatial vision in albinos is primarily limited by this increased receptor spacing. It is hypothesized that this, in turn, is the result of arrested development of the albino retina.

Eye manifestations of intrauterine infections.

The eye finding most characteristic of a prenatal, and therefore, congenital infection is a chorioretinal scar or an active chorioretinitis as can be seen in congenital toxoplasmosis, CMV, HSV, lymphocytic choriomeningitis virus, or varicella zoster infections. Congenital cataracts are suggestive, but less specific for congenital infection. They may be a relatively isolated finding in rubella, syphilis, varicella zoster, and Epstein-Barr virus infections. When they are present in congenital toxoplasmosis, HSV, and CMV, they are associated with extensive eye involvement. Other manifestations are less common as discussed above. The mechanism of action of these agents appears to be both a direct toxic and a teratogenic effect.