Comparison of measured astigmatic retinoscopies from different lid specula.

PURPOSE: We wanted to study the effects of different lid specula on retinoscopy readings in the pediatric population. METHODS: We prospectively enrolled 29 patients from the Eye Clinic at The Children's Hospital of Denver who were being examined under anesthesia and met the inclusion criteria for the study. Any patient with ocular pathology that could affect the pliability of the sclera of both eyes was excluded. Patients with preexisting lid abnormalities or adnexal masses were also excluded. Cycloplegic retinoscopies were performed under anesthesia with the Barraquer wire and the Lancaster solid-blade specula. The amounts and the axes of the astigmatism were tabulated and statistically analyzed with the paired t test. RESULTS: A statistically significant difference occurred in the retinoscopies obtained from the 2 lid specula. The Barraquer lid speculum seemed to induce the least amount of astigmatism (P =.0001). CONCLUSIONS: There was a statistically significant difference in the amount of astigmatism found with each lid speculum. The choice of lid speculum in performing retinoscopies on the pediatric population can influence the final refraction and may have implications for visual outcome.

Identification and functional consequences of a new mutation (E155G) in the gene for GCAP1 that causes autosomal dominant cone dystrophy.

Mutations in the gene for guanylate cyclase-activating protein-1 (GCAP1) (GUCA1A) have been associated with autosomal dominant cone dystrophy (COD3). In the present study, a severe disease phenotype in a large white family was initially shown to map to chromosome 6p21.1, the location of GUCA1A. Subsequent single-stranded conformation polymorphism analysis and direct sequencing revealed an A464G transition, causing an E155G substitution within the EF4 domain of GCAP1. Modeling of the protein structure shows that the mutation eliminates a bidentate amino acid side chain essential for Ca2+ binding. This represents the first disease-associated mutation in GCAP1, or any neuron-specific calcium-binding protein within an EF-hand domain, that directly coordinates Ca2+. The functional consequences of this substitution were investigated in an in vitro assay of retinal guanylate cyclase activation. The mutant protein activates the cyclase at low Ca2+ concentrations but fails to inactivate at high Ca2+ concentrations. The overall effect of this would be the constitutive activation of guanylate cyclase in photoreceptors, even at the high Ca2+ concentrations of the dark-adapted state, which may explain the dominant disease phenotype.

Ocular colobomata.

Ocular colobomata present diagnostic and therapeutic challenges in patients of all ages, but especially in young children. The "typical" coloboma, caused by defective closure of the fetal fissure, is located in the inferonasal quadrant, and it may affect any part of the globe traversed by the fissure from the iris to the optic nerve. Ocular colobomata are often associated with microphthalmia, and they may be idiopathic or associated with various syndromes. Types and severity of complications vary depending on the location and size of the colobomata. This article reviews the pathogeneses, categorization, genetic bases, differential diagnoses and management of ocular coloboma.

Acute megakaryoblastic leukemia in Down syndrome: orbital infiltration.

PURPOSE: To describe an uncommon ocular presentation of acute megakaryoblastic leukemia in a child with Down syndrome. METHOD: Case report. Initial manifestation of disease was bilateral proptosis with secondary exposure keratitis caused by leukemic infiltration of the orbits. RESULTS: Bone marrow biopsy and immunophenotyping established the diagnosis of acute megakaryoblastic leukemia (FAB-M7). The leukemia was treated successfully with chemotherapy, with resolution of proptosis. The patient remained in remission more than 1 year after cessation of treatment. CONCLUSIONS: Bilateral proptosis can be a presenting sign of acute megakaryoblastic leukemia, a malignancy associated with Down syndrome.

A new betaA1-crystallin splice junction mutation in autosomal dominant cataract.

PURPOSE: To map the locus for autosomal dominant cataracts (ADCs) in a Brazilian family using candidate gene linkage analyses, describe the clinical variability, and identify potential mutations in the human betaA1-crystallin gene (CRYBA1), a candidate gene identified through linkage studies demonstrating cosegregation with markers on chromosome 17. METHODS: Members of a Brazilian family with ADC were studied. Clinical examinations and linkage analyses with polymerase chain reaction (PCR) polymorphisms of 22 anonymous markers and 2 within the neurofibromatosis type 1 gene were performed; two-point lod scores were calculated. DNA sequences of all 6 exons and 12 exon-intron boundaries of the betaA1-crystallin gene, a proximal candidate gene mapped to 17q11.1-q12 in one unaffected and two affected individuals, were screened and new variants assessed for cosegregation with the disease. RESULTS: Affected individuals exhibited variable expressivity of pulverulent opacities in the embryonal nucleus and sutures; star-shaped, shieldlike, or radial opacities in the posterior embryonal nucleus; and/or midcortical opacities. All known loci for ADC in this family on chromosomes 1 and 13 were excluded. A positive lod score on chromosome 17 was calculated. This ADC locus was mapped to two potential regions on the long arm with an intervening recombination. The only known candidate gene in these regions was betaA1-crystallin. Three previously unreported single nucleotide variants were found in this gene, one in the donor splice junction site of intron C. This variant was found in all affected members and is presumed to be the causative mutation. CONCLUSIONS: An ADC locus was mapped in a Brazilian family with variable expressivity to either 17q23.1-23.2 or 17q11.1-12 based on linkage analyses. Analyses of DNA sequences of the betaA1-crystallin gene in this family revealed three new variants, one of which is within a donor splice junction and cosegregates with affected members.

A new locus for autosomal dominant cataract on chromosome 12q13.

PURPOSE: To map the gene for autosomal dominant cataracts (ADC) in an American white family of European descent. METHODS: Ophthalmic examinations and linkage analyses using a variety of polymorphisms were performed; two-point lod scores calculated. RESULTS: Affected individuals (14 studied) exhibited variable expressivity of embryonal nuclear opacities based on morphology, location within the lens, and density. This ADC locus to 12q13 was mapped on the basis of statistically significantly positive lod scores and no recombinations (theta(m) = theta(f) = 0) with markers D12S368, D12S270, D12S96, D12S359, D12S1586, D12S312, D12S1632, D12S90, and D12S83; assuming full penetrance, a maximum lod score of 4.73 was calculated between the disease locus and D12S90. CONCLUSIONS: The disease in this family represents the first ADC locus on chromosome 12; major intrinsic protein of lens fiber (MIP) is a candidate gene.

Selective B-wave reduction with congenital cataract in neurofibromatosis-2.

OBJECTIVE: To electroretinographically evaluate a case of neurofibromatosis-2 (NF-2). DESIGN: Case report and literature review. PARTICIPANT: A 29-year-old man diagnosed with NF-2. MAIN OUTCOME MEASURES: Electroretinography (ERG), ophthalmic biomicroscopy, and ultrasound examination results were reviewed. RESULTS: The ERG of one eye showed selective reduction of b-wave amplitudes. A characteristic posterior subcapsular lens opacity also was observed in that eye. A dense white congenital cataract and a retinal detachment were detected in the fellow eye. CONCLUSIONS: An inner retinal dysfunction, as evidenced by an abnormal ERG, may occur in NF-2. Further ERG evaluation of other patients with NF-2 is indicated to determine possible associations between NF-2 and selective b-wave reduction.

Menkes disease. New ocular and electroretinographic findings.

OBJECTIVE: The authors describe new ocular and electroretinographic (ERG) features in Menkes disease. DESIGN: The study design is a case report. PARTICIPANTS: The authors studied two patients with Menkes disease. INTERVENTION: The authors performed complete ophthalmologic and ERG evaluations in both patients. MAIN OUTCOME MEASURES: The parameters used were slit-lamp biomicroscopy and ERG recordings. RESULTS: Aberrant lashes and anterior stromal hypoplasia of the iris are new findings, and profound delays in b-wave implicit time in well-developed photopic responses may be added as new ERG features. CONCLUSIONS: Patients with Menkes disease may have aberrant lashes, anterior stromal hypoplasia, and retinal degeneration.

Optic nerve hypoplasia secondary to intracranial teratoma.

PURPOSE: To postulate a causal relation between optic nerve hypoplasia and a suprasellar teratoma. METHOD: Case report. RESULTS: A 6-month-old infant with suprasellar teratoma was visually inattentive and had searching nystagmus. He had moderately severe, bilateral optic nerve hypoplasia with the left eye being somewhat worse than the right eye. CONCLUSIONS: Optic nerve hypoplasia is a major cause of impaired vision in children and rarely has been attributed to an intracranial tumor. Our case, involving a patient with a suprasellar teratoma and optic nerve hypoplasia, supports a causal relation between the two.

Favorable visual outcome in cryptococcal meningitis.

PURPOSE: To describe an unusual, favorable visual outcome in a patient with lupus erythematosus and cryptococcal meningitis and to present bilateral superior oblique muscle paresis. METHODS: Case report. A 15-year-old girl with lupus erythematosus and cryptococcal meningitis had bilateral superior oblique paresis, bilateral optic nerve head swelling, and increased intracranial pressure. She developed a visual acuity of no light perception in the right eye. RESULTS: Treatment with oral fluconazole, acetazolamide, and dexamethasone, as well as repeated lumbar punctures to reduce intracranial pressure, was followed by recovery to a visual acuity of 20/20 in both eyes and normal ocular motility. CONCLUSION: With appropriate treatment, visual loss associated with cryptococcal meningitis may have a favorable outcome.

Endogenous endophthalmitis caused by Streptococcus mitis.

PURPOSE: To report endogenous endophthalmitis caused by Streptococcus mitis. METHODS: A 3-year-old girl was hospitalized for possible retinoblastoma after she suddenly developed a red and sensitive left eye. After administration of anesthesia, we examined the patient and obtained samples of aqueous, vitreous, and blood for culture. RESULTS: Blood and vitreous cultures grew S mitis. Intravenous and intravitreal injections of antibiotics were used to treat the infection. CONCLUSIONS: Streptococcus mitis should be considered a cause of endogenous endophthalmitis.

Conjunctival biopsy in infantile neuroaxonal dystrophy.

PURPOSE: To describe a case of infantile neuroaxonal dystrophy with optic nerve atrophy and to discuss the diagnostic role of conjunctival biopsy. METHODS: We performed a complete ophthalmologic examination and a diagnostic conjunctival biopsy on a girl with a neurodegenerative disease. RESULTS: On the basis of "spheroid" inclusions in the unmyelinated axons, we diagnosed infantile neuoroaxonal dystrophy. CONCLUSIONS: Optic atrophy is an important finding in infantile neuroaxonal dystrophy, and conjunctival biopsy is a reliable and very convenient diagnostic test.

Ophthalmologic findings in patients with ataxia.

PURPOSE: To determine the frequency and spectrum of ophthalmologic findings in a large, heterogeneous group of patients with ataxia. METHODS: Medical records of 184 patients from a university-based ataxia clinic were retrospectively reviewed. Patients were classified as having Friedreich's ataxia, spinocerebellar degeneration, cerebellar degeneration, familial or sporadic olivo-pontocerebellar atrophy, multisystem atrophy, spastic ataxia, myoclonic ataxia, or other diagnoses such as mitochondrial myopathy. All had complete ophthalmologic examinations, and 107 underwent electro-oculography. RESULTS: Among 184 patients with ataxia, diplopia was present in 52 (28%), best-corrected visual acuity was decreased in 29 (16%), and oscillopsia was present in 10 (5%). Diplopia was usually caused by an intermittent, small-angle heterotropia. The reduction in best-corrected visual acuity varied from mild to profound and was caused by optic atrophy, retinal degeneration, or both. Optic atrophy was present most frequently in spastic ataxia (five of 22 patients) and myoclonic ataxia (two of eight patients), followed by Friedreich's ataxia (three of 26 patients). Retinal degeneration and ophthalmoplegia were most characteristically associated with familial olivopontocerebellar atrophy and mitochondrial myopathy. Laboratory testing of ocular motility showed frequent abnormalities in all groups. Fixation instability was most characteristic of Friedreich's ataxia, whereas saccadic slowing was noticeably absent from patients with purely cerebellar degenerations. CONCLUSIONS: The ataxias may be associated with visual dysfunction caused by retinal degeneration, optic atrophy, oculomotor disturbance, or a combination of these.

Regional mapping of the human MP70 (Cx50; connexin 50) gene by fluorescence in situ hybridization to 1q21.1.

PURPOSE: Gap junctions play a critical role in the metabolic homeostasis and maintenance of transparency of fibers within the ocular lens. As part of a long-term effort to establish the relationship between lens gap junction proteins, normal lens development, and cataractogenesis, we report here the regional localization of the human MP70 (Connexin 50) gene. METHODS: Fluorescence in situ hybridization (FISH) was used to regionally map the human MP70 gene. The DNA probe contained the entire MP70 coding region within a clone isolated from a human genomic DNA library. RESULTS: The human gene encoding the lens intrinsic membrane protein MP70 was regionally mapped to q21.1 on the long arm of chromosome 1. CONCLUSIONS: This study confirms the previous provisional assignment of MP70 to human chromosome 1 and regionally localizes the gene to 1q21.1. When combined with previous mapping information, these data are consistent with the hypothesis that a genetic lesion in the gene encoding the lens intrinsic membrane protein MP70 may be the underlying molecular defect for zonular pulverulent (Coppock) cataract. Furthermore, these combined data support the hypothesis that other forms of human hereditary cataract may be the result of a mutation in one or more of the genes encoding gap junction proteins found in the ocular lens.

Cataract in early onset and classic Cockayne syndrome.

PURPOSE: To describe cataracts in classic and early onset Cockayne syndrome (CS). Classic CS typically has an onset after the first year of life; intrauterine growth failure and severe neurologic dysfunction from birth distinguishes the less common early onset CS from the classic form. METHODS: A complete ophthalmic evaluation was performed in four affected patients, one with the early onset and three with classic CS. RESULTS: We report cataract in all patients and glaucoma in one, the latter never previously reported in CS. CONCLUSION: CS should be considered in babies with low birth weight and congenital cataract.

Autosomal-dominant anomalies of the iris pigment epithelium.

PURPOSE: The authors document two families in which anomalies of the iris pigment epithelium occur as an autosomal dominant trait. METHODS: Eyes of members of two families were examined for the presence of anomalies of the iris pigment epithelium. RESULTS: In both families, anomalies characterized by iris pigment epithelial cysts and peripupillary ruffles were observed in successive generations. In one family, the proband was 3 months of age, and both cysts and ruffles were present in affected individuals. CONCLUSIONS: Anomalies of the iris pigment epithelium can be inherited in an autosomal-dominant pattern. The cystic and ruffled phenotypes represent variable expressivity and may be evident in infancy.