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Water balance influences soil development, and consequently plant communities, by driving weathering of soil minerals and leaching of plant nutrients from the soil. Along gradients in water balance, soils exhibit process domains where chemical properties are relatively stable punctuated by pedogenic thresholds where soil chemical properties change rapidly with little additional change in water balance. We ask if plant macronutrient concentrations in leaves also exhibit non-linear trends along water balance gradients, and if so, how these non-linearities relate to those in soils. We analyze foliar nutrient concentrations and foliar N:P ratios from eight species that span a range of growth forms along three water balance gradients (three of the species are found on multiple gradients). The gradients are located on basaltic substrate of different ages and have previously been characterized by studies on soil development. We find that maximum concentrations of foliar macronutrients occur at an intermediate water balance. As with soil nutrients, time mediates the effect of water balance on foliar nutrients, such that plants on older soils attain maximum nutrient concentrations at a lower water balance. On both a young, 20 ky and an old, 4100 ky water balance gradient, foliar nutrients reach peak concentrations at a water balance greater than the threshold for depletion of rock-derived nutrients in surface soils. Our findings suggest that plant acquisition of essential nutrients is imperfectly predicted by overall soil nutrient availability because the regulation of internal nutrient pools by plants makes nutrient pools within leaves partially independent of soil nutrient availability., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Purpose: Enhancing diversity on boards has been linked to greater profitability and innovation. Unfortunately, there remains an underrepresentation of women in executive management and leadership positions in the ophthalmic corporate world. The purpose of these analyses was to examine the gender composition of directors for boards associated with the discipline of ophthalmology., Design: Cross-sectional research design., Methods: Using contemporary data, we examined a specific cohort, the American Academy of Ophthalmology (AAO) Foundation Ophthalmic Business Council corporate members as reported in the annual 2019 meeting program (N = 23). The board composition was analyzed using an online search of publicly available information in January and February 2020. The specific outcome measures included the number and percentage of women board members and their roles., Results: There were a total of 23 Ophthalmic Business Council members with publicly available data; 37 of 195 total directorship seats (19%) were held by women, and 9 of 23 companies (39%) listed women as previous or current chairs of committees or outside corporations. Four of the 23 (17%) members of the Ophthalmic Business Council corporations had no women directors., Conclusions: The boards of directors of the AAO Foundation Ophthalmic Business Council corporate members remain predominately male. Despite the increasing number of women entering the specialty, women remain underrepresented in the corporate world of ophthalmology. Gender parity on boards is essential for the economic well-being of ophthalmic corporations as well as the relationship of the Ophthalmic Business Council with AAO members, health care systems, insurance carriers, government officials, and the public., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Rationale: Clumped isotope geochemistry examines the pairing or clumping of heavy isotopes in molecules and provides information about the thermodynamic and kinetic controls on their formation. The first clumped isotope measurements of carbonate minerals were first published 15 years ago, and since then, interlaboratory offsets have been observed, and laboratory and community practices for measurement, data analysis, and instrumentation have evolved. Here we briefly review historical and recent developments for measurements, share Tripati Lab practices for four different instrument configurations, test a recently published proposal for carbonate-based standardization on multiple instruments using multi-year data sets, and report values for 21 different carbonate standards that allow for recalculations of previously published data sets., Methods: We examine data from 4628 standard measurements on Thermo MAT 253 and Nu Perspective IS mass spectrometers, using a common acid bath (90°C) and small-sample (70°C) individual reaction vessels. Each configuration was investigated by treating some standards as anchors (working standards) and the remainder as unknowns (consistency standards)., Results: We show that different acid digestion systems and mass spectrometer models yield indistinguishable results when instrument drift is well characterized. For linearity correction, mixed gas-and-carbonate standardization or carbonate-only standardization yields similar results. No difference is observed in the use of three or eight working standards for the construction of transfer functions., Conclusions: We show that all configurations yield similar results if instrument drift is robustly characterized and validate a recent proposal for carbonate-based standardization using large multiyear data sets. Δ 47 values are reported for 21 carbonate standards on both the absolute reference frame (ARF; also refered to as the Carbon Dioxide Equilibrated Scale or CDES) and the new InterCarb-Carbon Dioxide Equilibrium Scale (I-CDES) reference frame, facilitating intercomparison of data from a diversity of labs and instrument configurations and restandardization of a broad range of sample sets between 2006, when the first carbonate measurements were published, and the present., (© 2021 The Authors. Rapid Communications in Mass Spectrometry published by John Wiley & Sons Ltd.)

Pedogenic thresholds describe where soil properties or processes change in an abrupt/nonlinear fashion in response to small changes in environmental forcing. Contrastingly, soil process domains refer to the space between thresholds where soil properties are either unchanged, or change gradually, across a broad range of environmental forcing. Here, we test quantitatively for the presence of thresholds in patterns of soil properties across a climatic gradient on soils developed from ~20 ky old basaltic substrate on the Island of Hawai'i. From multiple soil properties, we quantitatively identified a threshold at ~750 mm/y of water balance (precipitation minus potential evapotranspiration), delineating the upper water balance boundary of soil fertility in these soils. From the threshold in the ratio of exchangeable Ca to total Ca we identified the lower water balance boundary of soil fertility in these soils at -1000 mm/y, however this threshold was qualitatively described as it lies near the limit of the climate gradient data where the statistical approach can not be applied. These two results represent the first time that pedogenic thresholds have been identified using statistically rigorous methods and the limitations of said methods, respectively. Comparing the 20 ky soils to soils that developed on basaltic substrates of 1.2 ky, 7.5 ky, 150 ky, and 4100 ky in a time-climate matrix, we found that our quantitative analysis supports previous qualitatively identified thresholds in the soils developed from older substrates. We also identified the 20 ky as the transition from kinetic to supply limitation for plant nutrients in soil in this system.

Importance: The study establishes the importance of genetic background for the expression of Down syndrome phenotype., Objective: To define the ocular manifestations of Down syndrome in infants and children in Cairo, Egypt, a historically isolated region, and compare them with systemic features and with findings in other geographic groups., Design and Participants: We prospectively studied the ocular status and systemic features of 90 infants and children with Down syndrome and monitored all patients for 3 years. The complete ophthalmic examinations were performed along with ultrasonography, if media opacities were evident. Thyroid and cardiac status were assessed. An extensive literature search for comparison was performed., Setting: Outpatient clinical genetics department at the National Research Centre in Cairo, Egypt., Main Outcomes and Measures: Ocular and systemic manifestations of Down syndrome in infants and children in Cairo, and comparison of these features with patients with this anomaly from other geographic regions and ethnic populations., Results: Fifty-two infants or children (58%) had at least 1 abnormal ocular finding identified at the first visit. Significant refractive errors (in 37 [41%] patients) were the most common. Nasolacrimal duct obstruction, blepharoconjuctivitis, or conjunctivitis was found in 18 (20%), strabismus in 13 (14%), cataract in 5 (6%), nystagmus in 3 (3%), and optic nerve dysplasia in 2 (2%). Brushfield spots were not found. Additional ocular features developed over time. Thirty-six patients (40%) had congenital heart defects, and many (31 [86%]) had associated ocular disorders; a statistically significant correlation with myopia was established. Chromosomal translocations were high. The phenotype in Cairo was distinct., Conclusions and Relevance: More than half of infants and children with Down syndrome in Cairo had ophthalmic abnormalities; myopia was correlated with congenital heart defects. Comparison of the specific ocular features in our population with those in previous worldwide studies shows differences that may be related to overexpression or polymorphisms of key, modifying genes or other mutations in this historically isolated region along the Nile River. Down syndrome is more common in the highly consanguineous and multiparous Middle Eastern populations, and our Cairo findings underscore regional differences.

Purpose: To report the association of Duane syndrome with nystagmus and a patterned hyperpigmentation of the retinal pigment epithelium, developmental delay, micro- and pachygyria and craniopharyngioma., Case Report: We describe a 12-year old girl with developmental delay, hearing loss, cortical micro- and pachygyria, and a cystic craniopharyngioma; her ocular features include unilateral Duane syndrome, monocular nystagmus under binocular conditions, and a patterned hyperpigmentation of the retinal pigment epithelium. Her mother had similar retinal pigment epithelial abnormalities., Conclusions: The combination of two neuronal migrational disorders, the unusual retinal pigment epithelial abnormalities in the proband and her mother, and evidence that each feature may be genetic and are suggestive of a genetic basis for this constellation of features.

We studied 28 individuals from a four-generation Chilean family (ADC54) including 13 affected individuals with cataracts, microcornea and/or corneal opacity. All individuals underwent a complete ophthalmologic exam. We screened with a panel of polymorphic DNA markers for known loci that cause autosomal dominant cataracts, if mutated, and refined the locus using the ABI Prism Linkage Mapping Set Version 2.5, and calculated two-point lod scores. Novel PCR primers were designed for the three coding exons, including intron-exon borders, of the candidate gene alpha A crystallin (CRYAA). Clinically, affected individuals had diverse and novel cataracts with variable morphology (anterior polar, cortical, embryonal, fan-shaped, anterior subcapsular). Microcornea and corneal opacity was evident in some. Marker D21S171 gave a lod score of 4.89 (theta(m) = theta(f) = 0). CRYAA had a G414A transition that segregated with the disease and resulted in an amino acid alteration (R116H). The phenotypic variability within this family was significant with novel features of the cataracts and a corneal opacity. With the exception of iris coloboma, the clinical features in all six previously reported families with mutations in the CRYAA gene were found in this family. We identified a novel G414A transition in exon 3 of CRYAA that co-segregated with an autosomal dominant phenotype. The resulting amino acid change R116H is in a highly conserved region and represents a change in charge. The genotype-phenotype correlation of this previously unreported mutation provides evidence that other factors, genetic and/or environmental, may influence the development of cataract as a result of this alteration., (Copyright 2008 Wiley-Liss, Inc.)

ALDH3A1 (aldehyde dehydrogenase 3A1) is abundant in the mouse cornea but undetectable in the lens, and ALDH1A1 is present at lower (catalytic) levels in the cornea and lens. To test the hypothesis that ALDH3A1 and ALDH1A1 protect the anterior segment of the eye against environmentally induced oxidative damage, Aldh1a1(-/-)/Aldh3a1(-/-) double knock-out and Aldh1a1(-/-) and Aldh3a1(-/-) single knock-out mice were evaluated for biochemical changes and cataract formation (lens opacification). The Aldh1a1/Aldh3a1- and Aldh3a1-null mice develop cataracts in the anterior and posterior subcapsular regions as well as punctate opacities in the cortex by 1 month of age. The Aldh1a1-null mice also develop cataracts later in life (6-9 months of age). One- to three-month-old Aldh-null mice exposed to UVB exhibited accelerated anterior lens subcapsular opacification, which was more pronounced in Aldh3a1(-/-) and Aldh3a1(-/-)/Aldh1a1(-/-) mice compared with Aldh1a1(-/-) and wild type animals. Cataract formation was associated with decreased proteasomal activity, increased protein oxidation, increased GSH levels, and increased levels of 4-hydroxy-2-nonenal- and malondialdehyde-protein adducts. In conclusion, these findings support the hypothesis that corneal ALDH3A1 and lens ALDH1A1 protect the eye against cataract formation via nonenzymatic (light filtering) and enzymatic (detoxification) functions.

Purpose: To map and identify the mutated gene for autosomal dominant cataract (ADC) in a large Chilean family (ADC53)., Design: Experimental study., Participants: Large Chilean family with ADCs., Methods: Linkage analyses using genome-wide polymorphic DNA markers were performed on a family with variable expression of cataracts to map the mutated gene to a chromosome; 2-point lod scores were calculated. Candidate genes in the region of the maximum lod score were sequenced. We compared haplotypes (alleles at closely linked markers) in families with previously reported mutations of the crystallin, beta-B2 gene (CRYBB2)., Main Outcome Measures: Identification of the causative mutation in the ADC53 family., Results: The ADC locus mapped to chromosome 22 in the region of a cluster of lens beta crystallin genes (CRYBB3, CRYBB2, CRYBB1, and CRYBA4 and the pseudogene CRYBB2P1). We sequenced CRYBB1 and CRYBB2 and found a previously reported mutation and a variant in exon 6 of CRYBB2 that cosegregate with the disease; these changes in CRYBB2 are in the reference (normal) sequence of an adjacent gene CRYBB2P1, a pseudogene. The haplotypes in the ADC53 Chilean family were different from the 2 previously reported families with the mutation., Conclusions: The cataracts in the ADC53 Chilean family are caused by a mutation in the CRYBB2 gene; as the 2 variations in CRYBB2 are identical to the reference sequence of pseudogene CRYBB2P1, which has over 97% homology to CRYBB2, a gene conversion probably has occurred. Based on haplotype analyses, the mutation and variant are likely to be caused by independent gene conversions in our family and the previously reported families.

Purpose: To map and identify the mutated gene for autosomal dominant cataract (ADC) in family ADC4., Methods: Ophthalmic evaluations were performed on an American family with ADC and a panel of polymorphic DNA sequence-tagged site (STS) markers for known ADC loci and other genome-wide polymorphic markers were used to map the gene; two-point lod scores were calculated. Fine mapping was undertaken in the chromosomal regions of maximum lod scores, and candidate genes were sequenced., Results: A four-generation American family with ADC was studied. The only phakic individual exhibited white and vacuolated opacities in the cortical region. This ADC locus mapped to several suggestive chromosomal regions. Assuming full penetrance, the highest calculated maximum lod score was 3.91 with D19S903 [corrected] On chromosome 12, we sequenced all exons and the exon-intron borders of the membrane intrinsic protein (MIP) gene. On chromosome 19, all exons and the exon-intron borders of genes for lens intrinsic membrane2 (LIM2), ferritin light chain (FTL), and the human homologue of the Drosophila sine oculis homeobox 5 (SIX5) were sequenced, and the 3' untranslated repeat region (UTR) of the dystrophy (DMPK) gene and both the 5' and 3' UTRs of the SIX5 genes were amplified; the promoter for LIM2 was sequenced. For these genes, the sequence matched that in the reference libraries, and the DMPK gene had a normal number of CTG repeats., Conclusions: The mutated gene in ADC4 probably represents a new, not yet identified locus on chromosome 19. In one phakic member, the cortical cataracts were punctate and vacuolated.

Purpose: To further elucidate the cataract phenotype, and identify the gene and mutation for autosomal dominant cataract (ADC) in an American family of European descent (ADC2) by sequencing the major intrinsic protein gene (MIP), a candidate based on linkage to chromosome 12q13., Design: Observational case series and laboratory experimental study., Methods: We examined two at-risk individuals in ADC2. We PCR-amplified and sequenced all four exons and all intron-exon boundaries of the MIP gene from genomic and cloned DNA in affected members to confirm one variant as the putative mutation., Results: We found a novel single deletion of nucleotide (nt) 3223 (within codon 235) in exon four, causing a frameshift that alters 41 of 45 subsequent amino acids and creates a premature stop codon., Conclusions: We identified a novel single base pair deletion in the MIP gene and conclude that it is a pathogenic sequence alteration.

Purpose: To document intrafamilial and interocular phenotypic variability of autosomal dominant cataract (ADC)., Design: Prospective observational case series., Methods: We performed ophthalmologic examination in four Chilean ADC families., Results: The families exhibited variability with respect to morphology, location with the lens, color and density of cataracts among affected members. We documented asymmetry between eyes in the morphology, location within the lens, color and density of cataracts, and a variable rate of progression., Conclusions: The cataracts in these families exhibit wide intrafamilial and interocular phenotypic variability, supporting the premise that the mutated genes are expressed differentially in individuals and between eyes; other genes or environmental factors may be the bases for this variability. Marked progression among some family members underscores the variable clinical course of a common mutation within a family. Like retinitis pigmentosa, classification of ADC will be most useful if based on the gene and specific mutation.

Objectives: To estimate the prevalence of 4 categories of infantile cataract in subjects surviving the neonatal period in a US cohort, and to investigate risk factors for isolated infantile cataract., Design: Prospective study of 55 908 pregnancies enrolled in the Collaborative Perinatal Project from 1959 to 1965 at 12 university medical centers., Methods: We gathered data on demographic, lifestyle, and prenatal and perinatal obstetrical and postnatal factors using a standardized protocol. Pediatricians and neurologists examined infants at birth, 4 months, 1 year, and 7 years. We used exact logistic regression methods to compare putative risk factors in infants with isolated cataract with those in infants with no history of cataract., Outcome Measures: Infantile cataract as diagnosed using a standardized dilated ophthalmic examination., Results: Infantile cataract occurred in 13.6 per 10 000 infants (95% confidence interval [CI], 10.7-17.1). Isolated infantile cataract occurred 3.8 times as often among infants born at weights at or below 2500 g than among those born at or above 2500 g (95% CI, 1.5-8.6; P<.001), after controlling for a set of covariates; we observed similar results for bilateral isolated cataract (odds ratio = 4.4; 95% CI, 1.2-13.9). No risk factor identified in bivariate analyses was independently associated with the odds of developing isolated unilateral infantile cataract., Conclusions: Infantile cataract is a rare disorder occurring during childhood. Prevalence estimates reported here are within the limits of those from large-cohort studies in economically developed nations. Infants born at weights at or below 2500 g have a 3- to 4-fold increased odds of developing infantile cataract.

In the last decade, health indicators in Latin America and the Caribbean reflect advances. The per capita public expenditure on health care has increased in many countries. Despite these improvements, it is estimated that for every million population in Latin America and the Caribbean, 5,000 are blind and 20,000 are visually impaired; at least 66% of the blindness is attributable to treatable conditions such as cataract. The cataract surgery rate in the region remains low as compared to the industrialized countries, although it is higher than many other regions of the world. The availability of eye care services varies from country to country within the region, and the number of ophthalmologists per million population in the richest countries may be nine times more than in the poorest. Access, defined as the distance between the consumer and the services, is problematic in countries with isolated areas in the rainforest or high mountains, poor road systems, or lack of public transportation. Affordability is an important issue that limits utilization of services by the poorest segments of the population in nearly all countries in Latin America and the Caribbean.

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.

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 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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Purpose: To report the presence of posterior segment neovascularization in eyes with optic nerve aplasia., Methods: Three eyes in two patients with clinical optic nerve aplasia were studied., Results: Examination disclosed posterior segment neovascularization in one eye and progressive posterior segment neovascularization in two eyes., Conclusions: Posterior segment neovascularization may occur in association with optic nerve aplasia. Retinal ischemia or retinochoroidal anatomic disorganization, or both, may provide the stimulus for neovascularization in such eyes.

Purpose: To identify ophthalmologic manifestations of the blue rubber bleb nevus syndrome, a rare cutaneovisceral hemangiomatosis., Methods: The authors report two patients with a diagnosis of blue rubber bleb nevus syndrome with orbital hemangiomas., Results: In one patient, the orbital lesion presented with signs and symptoms similar to an orbital varix and in the other with lid ecchymosis from an eyelid lesion., Conclusion: Patients with the blue rubber bleb nevus syndrome may have vascular orbital lesions associated with intermittent proptosis. Ophthalmologists should be familiar with the syndrome and its life-threatening complication of gastrointestinal hemorrhage.

In order to elucidate the genetic basis of autosomal dominant retinitis pigmentosa (adRP) in a large eight-generation family (UCLA-RP09) of British descent, we assessed linkage between the UCLA-RP09 adRP gene and numerous genetic loci, including eight adRP candidate genes, five anonymous adRP-linked DNA loci, and 20 phenotypic markers. Linkage to the UCLA-RP09 disease gene was excluded for all eight candidate genes analyzed, including rhodopsin (RP4) and peripherin/RDS (RP7), for the four adRP loci RP1, RP9, RP10 and RP11, as well as for 17 phenotypic markers. The anonymous DNA marker locus D17S938, linked to adRP locus RP13 on chromosome 17p13.1, yielded a suggestive but not statistically significant positive lod score. Linkage was confirmed between the UCLA-RP09 adRP gene and markers distal to D17S938 in the chromosomal region 17p13.3. A reanalysis of the original RP13 data from a South African adRP family of British descent, in conjunction with our UCLA-RP09 data, suggests that only one adRP locus exists on 17p but that it maps to a more telomeric position, at band 17p13.3, than previously reported. Confirmation of the involvement of RP13 in two presumably unrelated adRP families, both of British descent, suggests that this locus is a distinct adRP gene in a proportion of British, and possibly other, adRP families.

Background: The prevalence of ocular disease among children in one school district in Los Angeles, California was studied to better understand the types of eye disorders among this population as well as to develop appropriate preventive programs., Methods: A computer-assisted retrospective analysis of date was performed from charts of 2,204 first grade children examined in the UCLA Mobile Eye Clinic., Results: One or more ocular disorders were observed in 22.3 percent of the subjects. Uncorrected best monocular visual acuity was 20/40 or worse in 3.4 percent of the children. Refractive errors were diagnosed in 15.7 percent of the subjects, astigmatism in 7.6 percent, hyperopia in 6.2 percent, and myopia in 6.0 percent. Color vision deficiencies (red-green) were found in 2.6 percent of boys. The prevalences of heterophorias and heterotropias were 1.2 percent and 1.3 percent, respectively., Conclusions: The variety of ocular disorders diagnosed in this demographic setting attests to the importance of performing early and effective screening eye examinations for children.

Three females in 2 families were originally diagnosed with Spielmeyer-Vogt disease (SVD). The clinical course was different from SVD, with vision well preserved until age 10 years, and learning rather than visual difficulties the marker at the onset. Later, regression was unusually rapid, including global dementia, blindness, aphasia, and finally loss of self-feeding and ambulation between ages 12-18 years. MRI scan in patient 3 documented brain atrophy between ages 8-10 years. Position Emission Tomography (PET) scanning with fluorodeoxyglucose in patients 2 and 3 showed diffusely decreased or absent cortical glucose metabolism, comparable at ages 12 and 18 years, respectively, to the results found in the oldest typical SVD case tested at age 29 years. Fine granular inclusions, instead of the expected fingerprint inclusions, were demonstrated by electron microscopy of lymphocytes, conjunctiva, and skin. Usual markers on chromosome 16p12 were not present in the first family tested. The clinical course, with nonspecific initial behavior difficulties, late onset of visual decline followed by fast global regression, progressive brain atrophy, decreased cortical glucose utilization as shown by PET scanning, and granular tissue inclusions, suggest a genetic variant of SVD.