Chiasmal misrouting and foveal hypoplasia without albinism.

BACKGROUND/AIMS: To present the ophthalmological and electrophysiological characteristics of three darkly pigmented, female patients with misrouting and foveal hypoplasia. One of the patients had primary ciliary dyskinesia and situs inversus totalis (Kartagener syndrome). METHODS: Fundus photographs were taken and the angles at which the main temporal arterial branches leave the optic nerve head (ONH) were analysed. Optical coherence tomography (OCT) was performed through the presumed foveal region. Pattern onset visually evoked potentials (VEPs) (check sizes 60', 40/400 ms) were recorded and the chiasmal coefficient was calculated to detect misrouting. RESULTS: Fundus photography showed normally pigmented fundi with absence of the usual foveal hyperpigmentation, foveal avascular zone, and macular and foveal reflexes. On OCT no foveal pit was found. The VEP recordings showed the largest positive CI component over the right hemisphere for the left eye, and over the left hemisphere for the right eye, with the CI almost absent over the ipsilateral hemispheres. The differential derivations showed opposite polarity for the recordings of the two eyes. The chiasmal coefficients of all three patients were significantly indicative of misrouting (-0.99, -0.91, and -0.99, respectively). CONCLUSION: Based on the investigations in these patients the authors propose the hypothesis that foveal hypoplasia and misrouting exist as a distinct entity, and do not comprise the exclusive hallmark of albinism. The findings suggest that misrouting may exert a retrograde influence on foveal development.

Ophthalmologic and systemic features of the Alström syndrome: report of 9 cases.

The Alström syndrome is a rare autosomal recessive disorder characterized by pigmentary retinopathy, diabetes mellitus, sensorineural deafness and obesity. A normal intelligence is often present. We report 9 patients.

Lenticonus.

Lenticonus is a bulging of the lens capsule and the underlying cortex. The diagnosis of lenticonus is essentially a clinical diagnosis which is made by biomicroscopic examination. According to the localization of the conus a distinction is made between lenticonus anterior and lenticonus posterior. Whereas lenticonus anterior is part of the Alport syndrome, lenticonus posterior is not associated with systemic disease. A case report of each of both types is presented and the clinical presentation, the aetiology, the pathogenesis and the treatment are discussed.

Prevalence of AIPL1 mutations in inherited retinal degenerative disease.

Leber congenital amaurosis (LCA) is the most severe form of inherited retinal dystrophy and the most frequent cause of inherited blindness in children. LCA is usually inherited in an autosomal recessive fashion, although rare dominant cases have been reported. One form of LCA, LCA4, maps to chromosome 17p13 and is genetically distinct from other forms of LCA. We recently identified the gene associated with LCA4, AIPL1 (aryl-hydrocarbon interacting protein-like 1) and identified three mutations that were the cause of blindness in five families with LCA. In this study, AIPL1 was screened for mutations in 512 unrelated probands with a range of retinal degenerative diseases to determine if AIPL1 mutations cause other forms of inherited retinal degeneration and to determine the relative contribution of AIPL1 mutations to inherited retinal disorders in populations worldwide. We identified 11 LCA families whose retinal disorder is caused by homozygous or compound heterozygous AIPL1 mutations. We also identified affected individuals in two apparently dominant families, diagnosed with juvenile retinitis pigmentosa or dominant cone-rod dystrophy, respectively, who are heterozygous for a 12-bp AIPL1 deletion. Our results suggest that AIPL1 mutations cause approximately 7% of LCA worldwide and may cause dominant retinopathy.

Indocyanine green angiography in Sorsby's fundus dystrophy.

PURPOSE: To report the indocyanine green angiographic findings in patients with a fundus dystrophy characterized by subretinal deposits, macular atrophic or neovascular degeneration and peripheral chorioretinal atrophy which is most likely Sorsby's fundus dystrophy. METHODS: A series of 11 clinically affected patients and 4 asymptomatic carriers, belonging to one autosomal dominant pedigree were examined with stereoscopic funduscopy, fluorescein and indocyanine green angiography. RESULTS: Subretinal deposits were found in 20 eyes of 10 patients. These deposits stained slightly on indocyanine green angiography, causing a reticular pattern. Two eyes had a disciform lesion and 3 geographic atrophy in the macula. A peripheral disciform lesion was found in 1 eye. Indocyanine green angiography identified peripapillary choroidal neovascularization in 2 eyes. Peripheral chorioretinal atrophy was found in 8 eyes of 4 patients, associated with peripheral plaques that could only be identified by indocyanine green angiography in 6 eyes of 3 patients. CONCLUSION: Indocyanine green angiography in Sorsby's fundus dystrophy may indicate the presence of homogeneously staining, well-demarcated peripheral areas of hyperfluorescence associated with chorioretinal atrophy. These plaques correspond in our opinion to choroidal neovascularization which is otherwise unsuspected.

Thiamine-responsive megaloblastic anemia syndrome (TRMA) with cone-rod dystrophy.

Thiamine-responsive megaloblastic anemia (TRMA) is an autosomal recessive disease in which the active thiamine uptake into cells is disturbed. The molecular basis underlying the disorder has been related to mutations in the gene SLC19A2 on chromosome 1q23.3 that encodes a functional thiamine transporter. The protein is predicted to have 12 transmembrane domains. TRMA is characterized by sensorineural deafness, diabetes mellitus, megaloblastic anemia, and cardiomyopathy. Optic nerve atrophy and retinal dystrophy have been reported in a small number of patients. We report a 15-year-old girl with TRMA and cone-rod dystrophy and confirm that retinal dystrophy may form part of the syndrome. Differential diagnosis of syndromes with deafness, diabetes mellitus, and optic nerve atrophy or retinal dystrophy are discussed. The authors suggest that ERG be performed in all patients with TRMA.

Vasoproliferative retinal tumors associated with peripheral chorioretinal scars in presumed congenital toxoplasmosis.

BACKGROUND: The purpose of this retrospective clinical study was to demonstrate vascularization of peripheral hyperplastic chorioretinal scars in presumed congenital toxoplasmosis by choroidal vessels and secondly to report vasoproliferative tumors of the sensory retina seen in association with such lesions. METHODS: Retrospective study of a cohort of 13 patients with peripheral hypertrophic chorioretinal scars, including fluorescein angiography (eight eyes) and indocyanine green angiography (seven eyes). Congenital toxoplasmosis was serologically confirmed in seven cases and suspected on clinical grounds in six cases. RESULTS: Sixteen eyes exhibited a peripheral complex scar with a posterior atrophic and an anterior hypertrophic part. These scars were vascularized from the choroid. In eight of these eyes an additional vasoproliferative tumor was seen within or adjacent to the scar and in one fellow eye a vasoproliferative retinal tumor was found as well. These eyes experience visual loss, resulting from vitritis and exudative/traction retinal detachment. Regression of exudation was seen in five of seven cryocoagulated or endophotocoagulated tumors. CONCLUSION: Peripheral hypertrophic scars in presumed congenital toxoplasmosis can be vascularized from the choroid. A vasoproliferative tumor of the sensory retina, secondary to presumed congenital toxoplasmosis scars, can cause vitritis and exudative/traction retinal detachment. Early coagulation of this lesion may prevent a poor outcome.

Isolated Norrie disease in a female caused by a balanced translocation t(X,6).

This is the second report of Norrie disease in a female patient with a de-novo balanced translocation t(X,6) with breakpoint at the location of the Norrie gene. At the age of 3 months, a girl was referred for suspected congenital glaucoma. The right eye was microphthalmic and ultrasonography was compatible with persistent hyperplasia of the primary vitreous. The left eye was also microphthalmic. The left cornea was larger than the right. The anterior chamber was virtual and leukocoria was evident. The eye felt hard digitally. Ultrasonography indicated an organized retinal detachment. The pathologic findings are reported and are compatible with Norrie disease.

Mental retardation in amaurosis congenita of Leber.

A group of 229 patients with Leber's congenital amaurosis (ACL) was investigated for associated defects. We especially looked for the occurrence of mental retardation because the literature gives varying frequencies for this association. A percentage of 19.8% was found. This finding has consequences for genetic counseling. Special attention was given to how frequently sibling pairs occurred in which one patient was mentally retarded whereas the other functioned normally. We found 11 sibling pairs that were discordant with regard to their mental state. This observation proves that mental retardation could be one variable expression of ACL.

Retinopathy following measles, mumps, and rubella vaccination in an immuno-incompetent girl.

We describe a 4-year-old girl with subnormal visual acuity due to a bilateral retinopathy. The child had a history of encephalitis following MMR vaccination. Temporary retinopathy associated with measles, mumps, and rubella (MMR) vaccination has been described. Recently an idiopathic CD4+ T lymphocytopenia in the child was diagnosed. This cellular immunodeficiency supports our hypothesis of measles retinopathy after vaccination of an immuno-deficient child.

Microcephaly with chorioretinopathy. A report of two dominant families and three sporadic cases.

This is a report of seven new cases of microcephaly with chorioretinopathy. Three cases were sporadic and four were dominant: a father and son, and a father and daughter. Their ophthalmological, neurological, and systemic findings are discussed as are the genetics of the syndrome. Chorioretinopathy with characteristic punched-out lesions was observed in both entities. Body height emerges as a possible distinguishing feature between the dominant and recessive forms. In addition, locomotor disturbances are more frequently seen in patients with the recessive form.

Neurological disorders in members of families with Leber's hereditary optic neuropathy (LHON) caused by different mitochondrial mutations.

Neurological abnormalities have been occasionally associated with Leber's hereditary optic neuropathy (LHON). We describe four patients with spastic dystonia from two of our 35 LHON families. Magnetic resonance imaging revealed signal alterations of globus pallidus, putamen, internal capsula, and substantia nigra. Neuropathological findings in one of the patients with dystonia are described. Each of the dystonia families carries a different mtDNA mutation; one at np 3460 and one at np 11778. Periventricular multiple sclerosis-like white matter lesions were observed in one individual from a third family with the mtDNA 3460 mutation. Neurological disorders are probably underestimated in association with LHON.

Biometry in X linked megalocornea: pathognomonic findings.

Biometric study in a series of 11 affected males provides characteristic findings. The patients present with a large cornea with short radius, very deep anterior chamber depth (AC depth) exceeding the normal mean value of plus 2 SD, and a short vitreous length. Calculation of the postlimbal depth, a method applied in this study to obtain information about positioning of the iris and the lens, reveals a posterior positioning of the iris and lens. The posterior positioning of the iris and lens was proved to occur at the expense of the vitreous. The importance of biometric data for diagnosis and for differential diagnosis in primary infantile glaucoma and other diseases with megalocornea is discussed.

X linked progressive cone dystrophy. Localisation of the gene locus to Xp21-p11.1 by linkage analysis.

Six affected males, three female carriers, and two possible carriers were evaluated from a three generation pedigree with X linked progressive cone dystrophy. The affected males presented with progressive decrease of visual acuity, impairment of colour vision, and deterioration of electroretinogram, which ranged from absent response to red light in all young patients to abnormal cone-rod responses in the elderly ones. In most affected males dark adaptation curves were monophasic and the electro-oculogram values were reduced. While some obligate carriers showed functional anomalies, they all had reduced electroretinogram response to red light. The a1/aT ratio for 1 joule white light was an appropriate indicator for carrier state. The family was studied with seven DNA markers from the proximal part of the short arm of the human X chromosome. So far, significant linkage has been found between three DNA markers and COD1, which assigns the progressive cone dystrophy gene (COD1) in this family to Xp21-p11.1. Differential diagnosis with congenital cone dystrophies is discussed.

Lens dislocation and optic nerve hypoplasia in ring chromosome 21 mosaicism.

Data on the physical and cognitive development of patients with chromosomal aberrations are scarce. In this report the authors present data on the longterm evolution in a boy with 45, XY,-21/46, XY, r(21) mosaicism, from birth up to the age of 14 years. Ophthalmological examination revealed lens dislocation and optic nerve hypoplasia.

Autosomal dominant congenital miosis with megalocornea.

A family with AD congenital miosis is presented. The ocular symptoms were: megalocornea, iris translucency, microcoria with poor pupillary dilatation and goniodysgenesis with anterior insertion of the iris. This observation confirms that in congenital miosis abnormal development of the whole anterior eye segment may occur. The patients have an increased risk to develop glaucoma. If retinoscopy is impossible due to pin-point pupils, ultrasonic biometry to determine the axial length is recommended. An optical iridectomy could improve visual performance at low illumination; the complaints of photophobia, which are related to the iris translucency, persist.