Pigmented and depigmented lesions of the ocular fundus.

Purpose Of Review: Pigmented and depigmented ocular fundus lesions (de-POFLs) can be isolated and clinically insignificant, or they may be the hallmark of associated serious systemic disorders such as familial polyposis. The ophthalmologist is often called upon to look for these retinal lesions, or may encounter them in the course of routine examination when appropriate medical referral becomes essential.

Recent Findings: The ophthalmoscopic and location differences between grouped pigmentation of the retinal pigment epithelium (bear tracks) and multiple POFLs associated with familial adenomatous polyposis is reviewed.

Genetic diagnostic methods for inherited eye diseases.

Accurate molecular diagnosis of genetic eye diseases has proven to be of great importance because of the prognostic and therapeutic value of an accurate ascertainment of the underlying genetic mutation. Efforts continue in diagnostic laboratories to develop strategies that allow the discovery of responsible gene/mutations in the individual patient using the least number of assays and economizing on the expenses and time involved in the process. Once the ophthalmologist has made the best possible clinical diagnosis, blood samples are obtained for genetic testing.

CNGA3 mutations in two United Arab Emirates families with achromatopsia.

Purpose: ACHROMATOPSIA RESULTS FROM MUTATIONS IN ONE OF THREE GENES: cyclic nucleotide-gated channel, alpha-3 (CNGA3); cyclic nucleotide-gated channel, beta-3 (CNGB3); and guanine nucleotide-binding protein, alpha-transducing activity polypeptide 2 (GNAT2). We report the responsible mutations in two United Arab Emirates families who have this autosomal recessive disease.

Methods: Clinical examinations were performed in seven patients from three nuclear families.

N965S is a common ABCA4 variant in Stargardt-related retinopathies in the Danish population.

Purpose: The study was conducted to resolve the spectrum of ABCA4 mutations in a cohort of unrelated Danish residents with early-onset macular dystrophy.

Methods: A microarray technique was used to analyze known ABCA4 mutations in genomic DNA from a selected group of 161 unrelated individuals referred to the national low vision clinic. The clinical observation time varied from a single examination to follow-up over 35 years.

Cohen syndrome: report of nine cases and review of the literature, with emphasis on ophthalmic features.

Purpose: To review the clinical features of reported cases of Cohen syndrome with a focus on ophthalmic features and report nine new cases.

Methods: Retrospective case series and literature review.

Results: Cohen syndrome is a rare autosomal-recessive condition with about 136 reported cases.

Idiopathic macular hypoplasia: a report of four cases and refinement of the phenotype of so-called ateliotic macula.

Purpose: To refine the phenotype of idiopathic macular hypoplasia, also referred to as ateliotic macula, by describing a series of cases with this diagnosis.

Methods: A review of the clinical characteristics of four patients as documented in medical records with regard to refractive error, visual acuity, anterior segment examination, retinal findings, and ancillary tests such as electroretinography (ERG).

Results: All patients had oval circumscribed or diffuse areas in the posterior pole where the retina appeared not to have developed normally; the fovea was involved in three patients with reduced visual acuity, and one patient had parafoveal lesions with preserved visual acuity.

Polychromasia capsulare (multicolored capsule): report of three families.

Purpose: To describe the familial occurrence of a peripheral ring of anterior lens capsule discoloration and iridescence in three families.

Methods: Clinical ophthalmologic examination with visual acuity, slit-lamp biomicroscopy, and dilated ophthalmoscopy. Pedigree construction and evaluation for possible mode(s) of inheritance.

Optic disc coloboma and localized chorioretinal defects in constitutional partial trisomy 8 mosaicism.

Constitutional partial trisomy 8 mosaicism is a rare chromosomal multisystem disorder with systemic and ophthalmologic manifestations. We report the case of a 15-year-old female mosaic for trisomy 8 who has unilateral colobomatous microphthalmia and multiple chorioretinal defects. These congenital anomalies have not been previously reported in association with constitutional partial trisomy 8 mosaicism.

Ocular abnormalities in mice lacking the Ski proto-oncogene.

Purpose: Persistent hyperplastic primary vitreous (PHPV) is a developmental ocular malformation often associated with additional ocular abnormalities. This study involved a novel mouse model of PHPV, generated by a null mutation of the Ski proto-oncogene, that displays other anterior segment and retinal malformations often found in human cases of PHPV.

Methods: Morphologic and histologic analyses of Ski-/- mice were used to document ocular abnormalities in comparison to those of normal littermates.

Congenital abnormalities of cranial nerve development: overview, molecular mechanisms, and further evidence of heterogeneity and complexity of syndromes with congenital limitation of eye movements.

Purpose: The clinical and molecular genetic classification of syndromes with congenital limitation of eye movements and evidence of cranial nerve dysgenesis continues to evolve. This monograph details clinical and molecular genetic data on a number of families and isolated patients with congenital fibrosis of the extraocular muscles (CFEOM) and related disorders, and presents an overview of the mechanisms of abnormal patterns of motor and sensory cranial nerve development in these rare syndromes.

Methods: Clinical examination of one patient with CFEOM1, one family with clinical features of CFEOM2, one family with recessive CFEOM3, one family with horizontal gaze palsy and progressive scoliosis (HGPPS), and four patients with various combinations of congenital cranial nerve abnormalities.

Classification and surgical management of patients with familial and sporadic forms of congenital fibrosis of the extraocular muscles.

Purpose: To outline the clinical features and surgical treatment of patients with familial and sporadic (simplex) forms of congenital fibrosis of extraocular muscles (CFEOM) from 2 countries, and to classify them according to phenotype and mode of inheritance.

Design: Observational and experimental study.

Methods: Twenty-eight affected individuals from 20 families with familial or sporadic CFEOM underwent assessment of ocular motility, visual acuity, slit-lamp biomicroscopy, tonometry, and ophthalmoscopy.

Thirty-year follow-up of a patient with leber congenital amaurosis and novel RPE65 mutations.

Purpose: To present long-term follow-up on a North American patient with Leber congenital amaurosis (LCA) and novel compound heterozygous mutations in the RPE65 gene.

Design: Case report.

Methods: RPE65 mutation screening and search for sequence changes using Single Strand Conformation Polymorphism and direct DNA sequencing.

A novel PHOX2A/ARIX mutation in an Iranian family with congenital fibrosis of extraocular muscles type 2 (CFEOM2).

Purpose: To describe the clinical features of two affected members of an Iranian family with autosomal recessive congenital fibrosis of the extraocular muscles (CFEOM2) and to report their novel mutation in the PHOX2A/ARIX gene.

Design: Experimental study.

Setting: Institutional practice.

Relationship between the axis and degree of high astigmatism and obliquity of palpebral fissure.

Purpose: To investigate a possible relationship between the slanting of palpebral fissures and the magnitude and axis of astigmatism in children with astigmatism.

Methods: Cross-sectional study at a referral center of 53 children with astigmatism of more than +1.50 D in at least 1 eye.

Presenting signs and clinical diagnosis in individuals referred to rule out Marfan syndrome.

Objective: To evaluate presenting signs and clinical diagnosis in a cohort of patients referred to rule out Marfan syndrome.

Methods: A retrospective chart review was performed on patients referred to the Cleveland Clinic Foundation between November 1993 and July 2001 to rule out Marfan syndrome. Clinical findings necessary for the diagnosis of the disorder according to current criteria (De Paepe et al.

Lymphedema-distichiasis syndrome and FOXC2 gene mutation.

Purpose: To describe the clinical characteristics of a family with autosomal dominant lymphedema-distichiasis syndrome and to report the results of analysis of the FOXC2 gene

Design: Observational and experimental study.

Methods: The setting was a clinical practice. The study population was 17 members of a family with lymphedema-distichiasis.

Dominant radial drusen and Arg345Trp EFEMP1 mutation.

Purpose: To report a new North American family with dominant radial drusen and Arg345Trp mutation in the EFEMP1 gene.

Methods: Clinical and molecular genetic family study.

Results: Four family members had macular drusen, and one had submacular fibrosis and visual loss.

A patient with de Morsier and Duane syndromes.

de Morsier syndrome, or septo-optic dysplasia, is a developmental malformation complex characterized by optic nerve hypoplasia, dysgenesis of the septum pellucidum, and hypothalamic-pituitary dysfunction. (1,2) In Duane retraction syndrome, there is absence of the sixth nerve nucleus with congenital retraction of the globe and narrowing of the lid fissure in adduction, frequent abduction deficiency, and variable limitation to adduction of the affected eye. (3) The purpose of this report is to present a patient with the uncommon and previously unreported concurrence of both of these congenital malformation complexes, presumably because of a common disturbance of neuronal development.

Choroidal rupture associated with forceps delivery.

Purpose: To report a case of choroidal rupture associated with forceps delivery.

Method: Case report.

Results: We examined a 4-year-old boy with a history of a retinal scar in the right eye.

Evidence of genetic heterogeneity in autosomal recessive congenital fibrosis of the extraocular muscles.

Purpose: Autosomal recessive congenital fibrosis of the extraocular muscles (CFEOM2) has been described in families from Saudi Arabia. Affected individuals have ptosis and exotropic ophthalmoplegia, and their disease has been mapped to chromosome 11q13. Here, we describe the phenotypic findings in a similarly affected Yemenite family and analyze the family for linkage to the CFEOM2 locus, as well as to the autosomal dominant CFEOM1 and CFEOM3 loci on chromosomes 12cen and 16q24, respectively.

Morning glory disk anomaly, choroidal coloboma, and congenital constrictive malformations of the internal carotid arteries (moyamoya disease).

Purpose: To report a patient with congenital constrictive malformations of the internal carotid arteries and a morning glory disc anomaly (MGDA).

Methods: Descriptive case report.

Results: A 14-year-old girl underwent serial ophthalmologic examinations since the age of seven years because of blurred vision and floaters.

Ocular malformations and developmental genes.

New insights into the pathogenesis of ocular malformations came with the discovery of transcription factors that determine the fate of cells in the developing eye. Several malformations have been matched to individual developmental genes that share conserved DNA sequences such as the homeobox. These disease/gene matches include the oculorenal syndrome and PAX2; aniridia and PAX6; Rieger syndrome and RIEG1/PITX2; cyclopia and Sonic hedgehog; cone-rod dystrophy, Leber's congenital amaurosis and CRX; and recessive septooptic dysplasia and HESX1.

Ocular malformations, moyamoya disease, and midline cranial defects: a distinct syndrome.

Purpose: To report a 10-year-old girl with developmental anomalies of both optic disks, a chorioretinal coloboma, sphenopharyngeal meningoencephalocele, and moyamoya disease.

Methods: A full ophthalmologic examination, cranial magnetic resonance imaging and magnetic resonance angiography, and cerebral angiography were performed.

Results: The patient had a morning glory disk anomaly and microphthalmos of the right eye and optic nerve hypoplasia and retinochoroidal coloboma in the left eye.