Gender Diversity on Corporate Boards Associated with Ophthalmology.

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.

Distinct ocular expression in infants and children with Down syndrome in Cairo, Egypt: myopia and heart disease.

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.

Duane retraction syndrome, nystagmus, retinal pigment epitheliopathy and epiretinal membrane with micro- and pachygyria, developmental delay, hearing loss and craniopharyngioma.

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.

Clinical variability of autosomal dominant cataract, microcornea and corneal opacity and novel mutation in the alpha A crystallin gene (CRYAA).

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.

Multiple and additive functions of ALDH3A1 and ALDH1A1: cataract phenotype and ocular oxidative damage in Aldh3a1(-/-)/Aldh1a1(-/-) knock-out mice.

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.

Gene conversion mutation in crystallin, beta-B2 (CRYBB2) in a Chilean family with autosomal dominant cataract.

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.

A new locus for autosomal dominant cataract on chromosome 19: linkage analyses and screening of candidate genes.

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.

Autosomal dominant cataract: intrafamilial phenotypic variability, interocular asymmetry, and variable progression in four Chilean families.

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.

Novel single-base deletional mutation in major intrinsic protein (MIP) in autosomal dominant cataract.

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.

Infantile cataract in the collaborative perinatal project: prevalence and risk factors.

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.

Eye disease and care in Latin America and the Caribbean.

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.

Resultado visual favorável em meningite criptocócica e presença de paresia bilateral do músculo oblíquo superior / Favorable visual outcome in cryptococcal meningitis and bilateral superior oblique muscle paresis

Objetivo: Relatar um resultado visual favorável incomum em um paciente com meningite criptocócica, e paresia bilateral do músculo oblíquo superior como nova complicaçäo deste quadro. Relato de caso: Paciente de 15 anos, portadora de lúpus eritematoso e meningite criptocócica apresentou paresia bilateral do músculo oblíquo superior, edema bilateral do nervo óptico e pressäo intracraniana elevada, evoluindo com ausência de percepçäo luminosa no olho direito. Resultado: Com tratamento com fluconazol, acetazolamida e dexametasona, assim como repetidas punçöes lombares para reduzir a pressäo intracraniana, se obteve recuperaçäo da acuidade visual de 20/20 em ambos os olhos e restauraçäo da motilidade ocular. Conclusäo: Com tratamento apropriado, a perda visual associada à meningite criptocócica pode ter um resultado favorável.

Síndrome de Menkes: novos achados oculares / Menkes syndrome: new ocular findings

A Síndrome de Menkes é uma desordem neurodegenerativa progressiva ligada ao cromossona X; uma mutaçäo no gene de Menkes (MNK) causa a doença por alterar o transporte de cobre do citosol para as organelas celulares. Apesar da síndrome näo ser rara, o diagnóstico é raramente feito em nosso meio. Déficit de crescimento, convulsöes e um cabelo peculiar säo achados precoces da síndrome. A visäo deteriora a despeito de um exame ocular praticamente normal. Sem tratamento, os pacientes raramente sobrevivem além de três anos de idade. Foram estudadas as manifestaçöes oculares em três pacientes com a Síndrome de Menkes e adicionadas hipoplasia do estroma anterior da íris e cílios aberrantes como novas manifestaçöes da doença. Uma vez familiarizados com esta síndrome, os oftalmologistas teräo um grande papel no seu diagnóstico precoce e seu eventual tratamento