Relationship between neural crest cell specification and rare ocular diseases.

Development of the eye is closely associated with neural crest cell migration and specification. Eye development is extremely complex, as it requires the working of a combination of local factors, receptors, inductors, and signaling interactions between tissues such as the optic cup and periocular mesenchyme (POM). The POM is comprised of neural crest-derived mesenchymal progenitor cells that give rise to numerous important ocular structures including those tissues that form the optic cup and anterior segment of the eye. A number of genes are involved in the migration and specification of the POM such as PITX2, PITX3, FOXC1, FOXE3, PAX6, LMX1B, GPR48, TFAP2A, and TFAP2B. In this review, we will discuss the relevance of these genes in the development of the POM and how mutations and defects result in rare ocular diseases.

Choroid plexus in the eye: a case study.

PURPOSE: The purpose of this report is to describe a pediatric case of total retinal detachment (RD) with secondary glaucoma in the setting of posterior coloboma with the metaplastic retinal pigment epithelium showing abrupt transition to choroid plexus tissue. METHODS: Retrospective case report. RESULTS: A 3-month-old patient presented with leukocoria and enlarged right eye. She was found to have a funnel RD with anterior displacement of lens-iris diaphragm and secondary glaucoma. Orbital imaging ruled out retinoblastoma, and posterior coloboma was identified. Intraocular pressures remained significantly elevated despite maximal medical therapy on glaucoma drops and transscleral cycloablation, and the eye was enucleated for comfort. Histologic analysis confirmed neovascularization of the iris, total RD, and posterior coloboma with the associated metaplastic retinal pigment epithelium showing abrupt transition to choroid plexus tissue. CONCLUSION: This is the first reported case of choroid plexus in the human eye. A close association of choroid plexus with coloboma and RD raises possibility that this tissue may have functionally contributed to pathogenesis of RD by secreting cerebrospinal fluid within subretinal space.

Systemic diagnostic testing in patients with apparently isolated uveal coloboma.

PURPOSE: To investigate the frequency and types of systemic findings in patients with apparently isolated uveal coloboma. DESIGN: Cross-sectional observational study. METHODS: setting: Single-center ophthalmic genetics clinic. study population: Ninety-nine patients with uveal coloboma seen at the National Eye Institute. observational procedure: Results of audiology testing, echocardiogram, brain magnetic resonance imaging, renal ultrasound, and total spine radiographs. main outcome measure: Prevalence of abnormal findings on systemic testing. RESULTS: Uveal coloboma affected only the anterior segment in 8 patients, only the posterior segment in 23 patients, and both anterior and posterior segments in 68 patients. Best-corrected visual acuity (BCVA) of eyes with coloboma was ≥20/40 in 45% of eyes; 23% of eyes had BCVA of ≤20/400. The majority of patients (74%) had good vision (>20/60) in at least 1 eye. Ten of the 19 patients (53%) who underwent echocardiography had abnormalities, with ventral septal defects being the most prevalent. Abnormal findings were observed in 5 of 72 patients (7%) who had a renal ultrasound and in 5 of 29 patients (17%) who underwent a brain MRI. Audiology testing revealed abnormalities in 13 of 75 patients (17%), and spine radiographs showed anomalies in 10 of 77 patients (13%). Most findings required no acute intervention. CONCLUSIONS: Although some patients with coloboma had evidence of extraocular abnormalities, the majority of findings on routine clinical examination did not require acute intervention, but some warranted follow-up. Results from the systemic evaluation of patients with coloboma should be interpreted with caution and in view of their clinical context.

[Ocular malformation and paediatric retinal detachment]. / Okuläre Malformation und Netzhautablösung im Kindesalter.

A range of posterior segment abnormalities, especially anomalies of the optic papilla, coloboma, and persistent hyperplastic primary vitreous are associated with the high risk to develop a retinal detachment. Most of these retinal detachments develop in the first and second decade of life. In most cases of retinal detachment caused by malformations, vitreoretinal surgery is indicated. Results of surgery depend on the nature of malformations. In spite of an anatomic re-attachment of the retina, in some eyes the functional results are limited. Especially in cases of severe PHPV, the aim of vitrectomy is only to prevent complications. Vitreoretinal surgery should not be performed in eyes with no light perception, without papillary light reflex, and/or with unrecordable visually evoked potential.

Spectral domain optical coherence tomography findings in retinal folds associated with posterior microphthalmos.

Posterior microphthalmos is a rare congenital malformation characterized by normal anterior segment dimensions with an abnormally small posterior segment resulting in high hyperopia. Reduced visual acuity in these cases is sometimes caused by the presence of papillomacular retinal folds. We report two cases of posterior microphthalmos in which the papillomacular folds could be visualized on spectral domain optical coherence tomography with sufficient detail to illustrate that only the layers of neural retina within the external limiting membrane were involved.

Novel compound heterozygous mutations in the MFRP gene in a Japanese patient with posterior microphthalmos.

PURPOSE: To report a case of posterior microphthalmos caused by novel compound heterozygous mutations in the membrane-type frizzled-related protein (MFRP) gene. METHODS: A 9-year-old girl with posterior microphthalmos underwent a standard ophthalmological examination and genetic screening by direct sequencing. RESULTS: The patient had a short axial length, high hyperopia, crowded optic discs, and dilation and tortuosity of the retinal vessels. No signs of retinitis pigmentosa were present. A diagnosis of posterior microphthalmos rather than nanophthalmos was made because the corneal diameter and anterior chamber depth were normal. Genetic analysis revealed two novel nonsense mutations in the MFRP gene, Q123X and W443X. Her parents were heterozygous carriers of one of the mutations. CONCLUSIONS: Posterior microphthalmos can be caused by nonsense compound heterozygous mutations in the MFRP gene.

A distinct autosomal recessive ocular anomaly in Chaharborj, Islamic Republic of Iran.

In Chaharborj, a village in north-eastern ofthe Islamic Republic of Iran, a high prevalence of congenital blindness (1.1%) has been reported. The clinical findings have not been fully described. We therefore assessed the clinical aspects of this condition in a case series of 20 congenitally blind patients and 24 of their parents. All patients had been blind since birth. There was anterior segment dysgenesis and retinal non-attachment in all patients. There were no systemic anomalies. Histopathologically, there was iridocorneal adhesion, normal angle structure and retinal dysplasia. No significant difference was found in the frequency of different HLA class I alleles compared with the general population. The anomaly causing congenital blindness in these patients has components of both anterior and posterior segment dysgenesis. It appears to be a distinct entity with an autosomal recessive pattern of inheritance.

Incidence, ocular findings, and systemic associations of ocular coloboma: a population-based study.

OBJECTIVE: To describe the incidence, ocular findings, and systemic associations of coloboma in a population-based cohort of children. METHODS: We retrospectively reviewed the medical records of pediatric (aged <19 years) patients diagnosed as having ocular coloboma from January 1, 1968, through December 31, 2007, as residents of Olmsted County, Minnesota. RESULTS: Thirty-three children were newly diagnosed as having ocular coloboma (annual incidence, 2.4 per 100,000 residents <19 years old; prevalence, 1 in 2077 live births). Median patient age at diagnosis was 3.9 months (range, 2 days to 18.4 years), and 22 patients (67%) had unilateral involvement. Twelve patients (36%) had involvement of the anterior segment only, 13 (39%) of the posterior segment only, and 8 (24%) of both. During median ophthalmologic follow-up of 9.2 years (range, 13 days to 35.9 years), 19 patients (58%) had other ocular disorders, including amblyopia in 11 (33%) and strabismus in 10 (30%). During median medical follow-up of 16.8 years, 22 patients (67%) were diagnosed as having a nonocular disorder, including abnormal development in 12 (36%) and CHARGE (coloboma, heart defects, choanal atresia, retarded growth and development, genital abnormalities, and ear anomalies) syndrome in 4 (12%). CONCLUSIONS: Ocular coloboma occurred in 1 in 2077 live births. More than half of the patients were diagnosed as having an ocular disorder other than coloboma, including strabismus and amblyopia in approximately one-third. Two-thirds of patients were diagnosed as having a nonocular disorder, including CHARGE syndrome in 1 in 8 patients.