Associated anomalies in anophthalmia and microphthalmia.

Infants with anophthalmia and microphthalmia (an/microphthalmia) have often other associated congenital anomalies. The reported frequency and the types of these associated anomalies vary between different studies. The purpose of this investigation was to assess the frequency and the types of associated anomalies among cases with an/microphthalmia in a geographically well defined population of northeastern France of 387,067 consecutive pregnancies from 1979 to 2007. Of the 98 infants with an/microphthalmia born during this period (prevalence at birth of 2.53 per 10,000), 88.8 % had associated anomalies. Cases with associated anomalies were divided into recognizable conditions (25 (25.5%) cases with chromosomal and 17 (17.3%) cases with non chromosomal conditions), and non recognizable conditions (45-45.9%- cases with multiple congenital anomalies -MCA). Trisomy 13 and trisomy 18 were the most frequent chromosomal abnormalities. Amniotic bands sequence, oculo-auriculo-vertebral spectrum, CHARGE syndrome and VACTERL association were most often present in recognizable non chromosomal conditions. Anomalies in the musculoskeletal, cardiovascular and central nervous systems were the most common other anomalies in cases with MCA and non recognizable conditions. However, given the limitation of the limited numbers of cases there should be urging caution in interpreting these results. In conclusion the frequency of associated anomalies in infants with anophthalmia and microphthalmia emphasizes the need for a thorough investigation of these cases. Routine screening for other anomalies especially musculoskeletal, cardiac and central nervous systems anomalies may need to be considered in infants with anophthalmia and microphthalmia, and referral of these cases for genetic counselling seems warranty.

Exome sequencing identifies genetic variants in anophthalmia and microphthalmia.

Anophthalmia and microphthalmia (A/M) are rare birth defects affecting up to 2 per 10,000 live births. These conditions are manifested by the absence of an eye or reduced eye volumes within the orbit leading to vision loss. Although clinical case series suggest a strong genetic component in A/M, few systematic investigations have been conducted on potential genetic contributions owing to low population prevalence. To overcome this challenge, we utilized DNA samples and data collected as part of the National Birth Defects Prevention Study (NBDPS). The NBDPS employed multi-center ascertainment of infants affected by A/M. We performed exome sequencing on 67 family trios and identified numerous genes affected by rare deleterious nonsense and missense variants in this cohort, including de novo variants. We identified 9 nonsense changes and 86 missense variants that are absent from the reference human population (Genome Aggregation Database), and we suggest that these are high priority candidate genes for A/M. We also performed literature curation, single cell transcriptome comparisons, and molecular pathway analysis on the candidate genes and performed protein structure modeling to determine the potential pathogenic variant consequences on PAX6 in this disease.

Anophthalmia and microphthalmia in children: associated ocular, somatic and genetic morbidities and quality of life.

PURPOSE: To report ocular outcome, somatic co-morbidities, genetics, and quality of life in children born with anophthalmia (A) or microphthalmia (M). METHODS: Thirty-five children (19 boys) with A/M underwent ophthalmological examinations and a review of medical records. Parents of 12/22 cases completed the Pediatric Quality of Life Inventory (PedsQL). RESULTS: Age at examination ranged from 7 months to 18 years (median 2.3 years). Ten cases were totally blind or had light perception. Isolated A/M occurred in 16/35 cases, while somatic, psychomotor, neuroradiological and/or genetic pathology occurred in 19/35 cases both in the bilateral (7/9) and in the unilateral group (12/26). Among 26 unilateral cases, 4/16 with one normal eye had associated problems compared to 9/10 if the contralateral eye was pathological (p < .01). There was an increased risk for heart defects in children with psychomotor delay (p = .04). Pathogenic genetic abnormalities were identified in 10/24 cases. Neuroimaging demonstrated pathology in 14/20 cases with corpus callosum dysgenesis (6/20) being the most common. The median total PedsQL score of parent reports for ages 2-12 was 52.4 (range 22.6-100). CONCLUSIONS: Somatic, psychomotor and/or neuroradiological pathologies were more common in bila-teral than unilateral cases, but the difference was not significant. There was decreased risk in unilateral cases with one normal eye. Genetic defects occurred in both unilateral and bilateral cases. Health-related quality of life was reduced.

Clinical spectrum of non-syndromic microphthalmos, anophthalmos and coloboma in the paediatric population: a multicentric study from North India.

AIMS: To describe the clinical features, visual acuity and causes of ocular morbidity in children (0-18 years) with microphthalmos, anophthalmos, and coloboma (MAC) from North India. METHODS: A retrospective study conducted between October 2017 and September 2018 in three tertiary eye institutes, part of the Bodhya Eye Consortium with consensus led common pro formas. Children with complete clinical data and without syndromic/systemic involvement were included. The clinical phenotype was divided into isolated ocular coloboma (CB), coloboma with microcornea (CBMC), colobomatous microphthalmos (CBMO), non-colobomatous microphthalmos (MO) and anophthalmos (AO). RESULTS: A total of 532 children with MAC were examined. Seventeen records were excluded due to incomplete data (0.2%). 515 children (845 eyes) were included: 54.4% males and 45.6% females. MAC was unilateral in 36% and bilateral in 64%. CB, CBMC, CBMO, MO and AO were seen in 26.4%, 31%, 22%, 8% and 12.5% of eyes, respectively. Nystagmus was found in 40%, strabismus in 23%, cataract in 18.7% and retinal detachment in 15%. Best-corrected visual acuity (BCVA) of <3/60 was seen in 62.4% eyes. Blindness (BCVA <3/60 in better eye) was seen in 42.8% of bilateral patients. Those with microcornea or microphthalmos with coloboma had worse BCVA (p<0.001). There were regional differences in the type of MAC phenotype presenting to the three institutes. CONCLUSION: The MAC group of disorders cause significant ocular morbidity. The presence of microcornea or microphthalmos with coloboma predicts worse BCVA. The variation of the MAC phenotype with the district of origin of the patient raises questions of aetiology and is subject to further studies.

A Comprehensive Assessment of Co-occurring Birth Defects among Infants with Non-Syndromic Anophthalmia or Microphthalmia.

PURPOSE: Infants with anophthalmia or microphthalmia frequently have co-occurring birth defects. Nonetheless, there have been few investigations of birth defect patterns among these children. Such studies may identify novel multiple malformation syndromes, which could inform future research into the developmental processes that lead to anophthalmia/microphthalmia and assist physicians in determining whether further testing is appropriate. METHODS: This study includes cases with anophthalmia/microphthalmia identified by the Texas Birth Defects Registry from 1999 to 2014 without clinical or chromosomal diagnoses of recognized syndromes. We calculated adjusted observed-to-expected ratios for two - through five-way birth defect combinations involving anophthalmia/microphthalmia to estimate whether these combinations co-occur more often than would be expected if they were independent. We report combinations observed in ≥5 cases. RESULTS: We identified 653 eligible cases with anophthalmia/microphthalmia (514 [79%] with co-occurring birth defects), and 111 birth defect combinations, of which 44 were two-way combinations, 61 were three-way combinations, six were four-way combinations and none were five-way combinations. Combinations with the largest observed-to-expected ratios were those involving central nervous system (CNS) defects, head/neck defects, and orofacial clefts. We also observed multiple combinations involving cardiovascular and musculoskeletal defects. CONCLUSION: Consistent with previous reports, we observed that a large proportion of children diagnosed with anophthalmia/microphthalmia have co-occurring birth defects. While some of these defects may be part of a sequence involving anophthalmia/microphthalmia (e.g., CNS defects), other combinations could point to as yet undescribed susceptibility patterns (e.g., musculoskeletal defects). Data from population-based birth defect registries may be useful for accelerating the discovery of previously uncharacterized malformation syndromes.

The prevalence of anophthalmic socket syndrome and its relation to patient quality of life.

BACKGROUND: Following removal of the eye, soft tissue changes of the eyelids and orbit may develop into an anophthalmic socket (AS) syndrome, which is often attributed to orbital volume deficiency. While adequate primary orbital volume replacement is nowadays standard of care, patients may still present with facial asymmetry. The aim of this study is to provide insights into these changes and their impact on patient quality of life (QoL). METHODS: Cross-sectional study of 59 patients with longstanding ocular prosthetic wear after enucleation or evisceration surgery. The alignment, function, and laxity of the eyelids of the anophthalmic side were compared to those of the fellow side. The QoL was assessed with a 4-item questionnaire specific for the prosthetic condition. The different aspects of AS syndrome were analysed in relation to disease-specific and prosthetic data and to the patient QoL scores. RESULTS: Clinical AS syndrome was prevalent in 53% of patients with acquired anophthalmia. The anophthalmic side was statistically significantly different from the fellow side for the known AS syndrome features such as superior sulcus depression, margin reflex distance 1, and enophthalmia, but also for new features such as levator muscle function and lagophthalmia (P < 0.05). The difference was correlated with duration of prosthetic wear, prior orbital radiotherapy, and size of the prosthesis (P < 0.05). QoL scores were not correlated to the separate features of AS syndrome, except for a positive correlation between wearing comfort of the prosthesis and upper eyelid ptosis (P < 0.05). CONCLUSION: Patients with an ocular prosthesis show a relatively high prevalence of one or more distinct clinical features of AS syndrome, which do not negatively affect patient QoL. These findings underscore the importance to tailor prosthetic and surgical treatment to the patient's perceived QoL rather than to the objective clinical findings.

Population-based birth defects data in the United States, 2011-2015: A focus on eye and ear defects.

BACKGROUND/OBJECTIVES: In this data brief, we examine major eye and ear anomalies (anophthalmia/microphthalmia, anotia/microtia, and congenital cataract) for a recent 5-year birth cohort using data from 30 population-based birth defects surveillance programs in the United States. METHODS: As a special call for data for the 2018 NBDPN Annual Report, state programs reported expanded data on eye/ear anomalies for birth years 2011-2015. We calculated the combined overall prevalence (per 10,000 live births) and 95% confidence intervals (CI), for the three anomalies as well as by maternal age, maternal race/ethnicity, infant sex, laterality, presence/absence of other major birth defects, and case ascertainment methodology utilized by the program (active vs. passive). RESULTS: The overall prevalence estimate (per 10,000 live births) was 1.5 (95% CI: 1.4-1.5) for anophthalmia/microphthalmia, 1.5 (95% CI: 1.4-1.6) for congenital cataract, and 1.8 (95% CI: 1.7-1.8) for anotia/microtia. Congenital cataract prevalence varied little by maternal race/ethnicity, infant sex, or case ascertainment methodology; prevalence differences were more apparent across strata for anophthalmia/microphthalmia and anotia/microtia. Prevalence among active vs. passive ascertainment programs was 50% higher for anophthalmia/microphthalmia (1.9 vs. 1.2) and two-fold higher for anotia/microtia (2.6 vs. 1.2). Anophthalmia/microphthalmia was more likely than other conditions to co-occur with other birth defects. All conditions were more frequent among older mothers (40+ years). CONCLUSIONS: This data brief provides recent prevalence estimates for anophthalmia/microphthalmia, congenital cataract, and anotia/microtia that address a data gap by examining pooled data from 30 population-based surveillance systems, covering a five-year birth cohort of about 12.4 million births.

An application of data mining to identify potential risk factors for anophthalmia and microphthalmia.

BACKGROUND: We examined a large number of variables to generate new hypotheses regarding a wider range of risk factors for anophthalmia/microphthalmia using data mining. METHODS: Data were from the National Birth Defects Prevention Study, a multicentre, case-control study from 10 centres in the United States. There were 134 cases of "isolated" and 87 "nonisolated" (with other major birth defects) of anophthalmia/microphthalmia and 11 052 nonmalformed controls with delivery dates October 1997-December 2011. Using random forest, a data mining procedure, we compared the two case types with controls for 201 variables. Variables considered important ranked by random forest were included in a multivariable logistic regression model to estimate odds ratios and 95% confidence intervals. RESULTS: Predictors for isolated cases included paternal race/ethnicity, maternal intake of certain nutrients and foods, and childhood health problems in relatives. Using regression, inverse associations were observed with greater maternal education and with increasing intake of folate and potatoes. Odds were slightly higher with greater paternal education, for increased intake of carbohydrates and beans, and if relatives had a childhood health problem. For nonisolated cases, predictors included paternal race/ethnicity, maternal intake of certain nutrients, and smoking in the home the month before conception. Odds were higher for Hispanic fathers and smoking in the home and NSAID use the month before conception. CONCLUSIONS: Results appear to support previously hypothesised risk factors, socio-economic status, NSAID use, and inadequate folate intake, and potentially provide new areas such as passive smoking pre-pregnancy, and paternal education and ethnicity, to explore for further understanding of anophthalmia/microphthalmia.

Epidemiology of anophthalmia and microphthalmia: Prevalence and patterns in Texas, 1999-2009.

Anophthalmia and microphthalmia are a set of rare, yet severe, birth defects considered to be part of a spectrum of developmental ocular malformations ranging from smaller than average to completely absent eyes. Despite their clinical significance, little is known about the etiologies of these conditions. The goal of this study was to expand our understanding of the epidemiology of anophthalmia and microphthalmia. Data for this population-based assessment were obtained from the Texas Birth Defects Registry (TBDR) and Center for Health Statistics for the period 1999-2009. Descriptive analyses and estimates of birth prevalence and prevalence ratios (PR) were determined for this defect. There were 1,262 definite anophthalmia and microphthalmia patients identified in the TBDR, with an overall combined prevalence of 3.0 per 10,000 live births. More than half (55.7%) of the patients had at least one chromosome abnormality or syndrome. In addition, 92.4% of nonsyndromic patients (i.e., have no recorded chromosome abnormalities or syndromes) had at least one additional birth defect. After adjustment for multiple factors, the prevalence of nonsyndromic anophthalmia and microphthalmia was higher among mothers who had ≥2 previous fetal deaths (PR = 1.43, 95% confidence interval [CI]: 1.03-1.97) and among mothers with any reported diabetes (PR = 2.08, 95% CI: 1.49-2.90). Our results confirm that children with anophthalmia and microphthalmia frequently have genetic syndromes or are born with other major birth defects. Our findings add to the limited body of literature on anophthalmia and microphthalmia as well as help define subgroups of women who are more likely to have children with this malformation.

Survey of Ocular Prosthetics Rehabilitation in the United Kingdom, Part 1: Anophthalmic Patients' Aetiology, Opinions, and Attitudes.

PURPOSE: Ocular prostheses are constructed to aid cosmetic, functional, and psychological rehabilitation of anophthalmic patients. Part-1 of this study aimed to evaluate anophthalmic patients' opinions, attitudes, and experience about aspects related to their postfit ocular prostheses. METHODS: One hundred sixty questionnaires were delivered to anophthalmic patients inquiring about different information such as age, gender, occupation, eye-loss cause, prosthesis type, prosthesis-wearing frequency, prosthesis-cleaning frequency, and problems encountered. A total of 126 questionnaires were returned (response rate was 78.8%). Data was analyzed using SPSS software (P <0.05). RESULTS: The patients were 74 males and 52 females (57.55 years ±â€Š17.57). Almost 50% of the patients lost their eye due to trauma that was the highest among other causes (P <0.05). High proportion clean their prosthesis daily (37.4%) which was the highest among other cleaning regimes (P <0.05). Almost 30.3% experienced having problems with their prosthetic eye. Patients who clean their prosthetic eye every 6 months have experienced more problems (P <0.05). Majority of patients wear their prosthetic eyes 24 hours (92%) (P <0.05). Half of patients who received a prosthetic eye for the first time experienced problems with it (P <0.05) such as excess discharge (45%), infection (25%), and soreness (20%). However, the problems were independent of prosthesis-type (P >0.05). CONCLUSIONS: Trauma is the most common cause of anophthalmic patients in the North-West of England. Anophthalmic patients are likely to experience problems with their prosthetic eye if they have lost their natural eye due to disease; it is their first prosthesis; or if they clean it once every 6 months.

Trends over time in the incidence of congenital anophthalmia, microphthalmia and orbital malformation in England: database study.

AIMS: To study trends over time in the incidence of congenital anophthalmia, microphthalmia and orbital malformations in England, along with changes in hospital admission rates for these conditions. METHODS: Using English National Hospital Episode Statistics (1999-2011), the annual rate of hospital admissions related to anophthalmia, microphthalmia and congenital malformations of orbit/lacrimal apparatus was calculated per 100 000 infants. The records were person-linked, which enabled patients' 'first record' rates to be calculated as proxies for incidence. Similar analyses on pre-1999 datasets were also undertaken for microphthalmia. RESULTS: There was no systematic increase or decrease over time in the incidence of these conditions, but there was some fluctuation from year to year. The incidence of congenital anophthalmia ranged from 2.4 (95% CI 1.3 to 4.0) per 100 000 infants in 1999 to 0.4 (0 to 1.3) in 2011. The annual incidence of congenital microphthalmia was 10.8 (8.2 to 13.5) in 1999 and 10.0 (7.6 to 12.4) in 2011. The annual incidence of congenital orbital/lacrimal malformations was 0.5 (0 to 1.1) in 1999 and 0.7 (0 to 1.4) in 2011. Including multiple admissions per person, admission rates for microphthalmia showed a linear increase over time from 1999. The earlier data for microphthalmia indicated an increase in admission rates, but no change in incidence, from 1971 to 2011. CONCLUSIONS: The incidence of these conditions has remained stable in England in recent years. Although the incidence of microphthalmia was stable, hospital admission rates for it increased over time reflecting an increase in multiple admissions per affected person. These data may be useful for planning service provision.

Congenital Microphthalmia, Anophthalmia and Coloboma among Live Births in Denmark.

PURPOSE: This study aims to quantify the occurrence of the congenital eye malformations anophthalmia (AO), microphthalmia (MO) and coloboma among liveborn infants in Denmark, and to estimate the rate of chromosomal abnormalities in this group of patients. METHODS: A cohort of patients born in 1995-2012 with diagnoses of MO/AO or coloboma was identified from the Danish National Patient Registry (DNPR), and their ocular and extra-ocular diagnoses were reviewed. In order to assess the occurrence of chromosomal abnormalities in the cohort, the data were cross-referenced with the Danish Cytogenetic Central Registry (DCCR). RESULTS: We identified 415 patients with MO/AO/coloboma in the DNPR. The total number of live births from 1995-2012 was 1,174,299, and the average birth prevalence of MO/AO/coloboma was 3.6/10,000 live births and of MO/AO was 1.2/10,000 live births. Extra-ocular abnormalities were observed in 32.1% of MO/AO cases and 21.7% of coloboma cases. Chromosome analysis was performed in 36.1% of the cohort, and 14.7% of cases had an abnormal karyotype. In 8.7% of the cohort, a chromosome microarray analysis was performed, and in 44.4% of cases, a possibly pathogenic copy number variation was observed. CONCLUSION: The birth prevalence of MO/AO/coloboma in Denmark has been steady at 3.6/10,000 live births during the last 17 years. The rate of syndromic cases was lower compared to other studies. A relatively high rate of pathogenic chromosomal aberrations was observed, suggesting an important role for cytogenetic analysis in this group of patients.

Genetic analysis of consanguineous families presenting with congenital ocular defects.

Anophthalmia and microphthalmia (A/M) are a group of rare developmental disorders that affect the size of the ocular globe. A/M may present as the sole clinical feature, but are also frequently found in a variety of syndromes. A/M is genetically heterogeneous and can be caused by chromosomal aberrations, copy number variations and single gene mutations. To date, A/M has been caused by mutations in at least 20 genes that show different modes of inheritance. In this study, we enrolled eight consanguineous families with A/M, including seven from Pakistan and one from India. Sanger and exome sequencing of DNA samples from these families identified three novel mutations including two mutations in the Aldehyde Dehydrogenase 1 Family Member A3 (ALDH1A3) gene, [c.1310_1311delAT; p.(Tyr437Trpfs*44) and c.964G > A; p.(Val322Met)] and a single missense mutation in Forkhead Box E3 (FOXE3) gene, [c.289A > G p.(Ile97Val)]. Additionally two previously reported mutations were identified in FOXE3 and in Visual System Homeobox 2 (VSX2). This is the first comprehensive study on families with A/M from the Indian subcontinent which provides further evidence for the involvement of known genes with novel and recurrent mutations.

[Frequency of occurrence of anophthalmic socket in the Middle West region of the state of São Paulo and the carriers characteristics]. / Frequência de ocorrência de cavidade anoftálmica na região centro-oeste paulista e características dos portadores.

PURPOSE: To observe the frequency of the occurrence of the anophthalmic socket in the Middle West region of the state of São Paulo and to describe the demographic profile of the carriers in a population-based data. METHODS: A cross-sectional study involve a random sampling carried out in twelve cities of the Middle West region of the state of São Paulo, for which the reference center is the city of Botucatu was done. The participators were chosen by assortment which considered the houses of these people. It was established a sampling with 11,453 people. All the exams were realized using a Mobile Ophthalmologic Unit. The research protocol included the demographic data and the complete ophthalmologic exam (anamnesis, ocular and systemic antecedents, familiar antecedents, visual acuity with and without correction, tonometry, biomicroscopy, fundoscopy, and refraction exam). All the data were transferred to an Excel spreadsheet and submitted to a descriptive analysis and were presented by the frequency of the occurrence. RESULTS: Ophthalmic socket frequency in the Middle West region of the state of São Paulo was 0.96‰. We found 11 cases of anophthalmic socket, with involvement of 0.7 ‰ in females and 1.3 ‰, male. The most common causes of anophthalmic socket were glaucoma (blind painful eye), microphthalmia, trauma, and endophthalmitis. The majority of the people were 40 years old or more, and we found just one person younger than 19 years old. CONCLUSION: The anophthalmic socket occurred in 0.96‰ of the habitants of the Middle West region of São Paulo State, occurring mainly in male and with large variety of the affected ages.

Frequência de ocorrência de cavidade anoftálmica na região centro-oeste paulista e características dos portadores / Frequency of occurrence of anophthalmic socket in the Middle West region of the state of São Paulo and the carriers characteristics

OBJETIVO: Observar a frequência de ocorrência de casos de cavidade anoftálmica na região centro-oeste paulista e descrever o perfil demográfico dos portadores em estudo populacional. MÉTODOS: Estudo transversal, de caráter observacional e de amostragem aleatória, realizado em 12 cidades da região centro-oeste do estado de São Paulo, para as quais o centro de referência é a cidade de Botucatu. Os participantes foram determinados por sorteio que levou em conta o local de moradia, tendo sido estabelecida uma amostra de 11.453 indivíduos. Todos os exames foram feitos utilizando uma Unidade Oftalmológica Móvel. O protocolo da pesquisa consistiu de dados demográficos e exame oftalmológico completo (anamnese, antecedentes oculares e sistêmicos, antecedentes familiares, avaliação da acuidade visual com e sem correção, tonometria, biomicroscopia, fundoscopia e exame refracional). Todos os dados obtidos foram transferidos para tabela Excel e submetidos à análise descritiva e apresentados como frequência de ocorrência. RESULTADOS: A frequência de ocorrência de cavidade anoftálmica na região centro-oeste paulista foi de 0,96‰. Dentre os sujeitos examinados, foram encontrados 11 casos de cavidade anoftálmica, com acometimento de 0,7‰, no sexo feminino e 1,3‰, do sexo masculino. Dentre as causas de cavidade anoftálmica foram encontradas glaucoma (olho cego doloroso), microftalmia, trauma e endoftalmite. Os indivíduos eram, em sua maioria, de idade superior ou igual a 40 anos, tendo sido encontrado apenas um caso com idade abaixo de 19 anos. CONCLUSÃO: A cavidade anoftálmica ocorreu em 0,96‰ dos habitantes da região centro-oeste paulista, acometendo mais frequentemente os homens e com grande variação de idade de acometimento.

PURPOSE: To observe the frequency of the occurrence of the anophthalmic socket in the Middle West region of the state of São Paulo and to describe the demographic profile of the carriers in a population-based data. METHODS: A cross-sectional study involve a random sampling carried out in twelve cities of the Middle West region of the state of São Paulo, for which the reference center is the city of Botucatu was done. The participators were chosen by assortment which considered the houses of these people. It was established a sampling with 11,453 people. All the exams were realized using a Mobile Ophthalmologic Unit. The research protocol included the demographic data and the complete ophthalmologic exam (anamnesis, ocular and systemic antecedents, familiar antecedents, visual acuity with and without correction, tonometry, biomicroscopy, fundoscopy, and refraction exam). All the data were transferred to an Excel spreadsheet and submitted to a descriptive analysis and were presented by the frequency of the occurrence. RESULTS: Ophthalmic socket frequency in the Middle West region of the state of São Paulo was 0.96‰. We found 11 cases of anophthalmic socket, with involvement of 0.7 ‰ in females and 1.3 ‰, male. The most common causes of anophthalmic socket were glaucoma (blind painful eye), microphthalmia, trauma, and endophthalmitis. The majority of the people were 40 years old or more, and we found just one person younger than 19 years old. CONCLUSION:The anophthalmic socket occurred in 0.96‰ of the habitants of the Middle West region of São Paulo State, occurring mainly in male and with large variety of the affected ages.

Associated malformations among infants with anophthalmia and microphthalmia.

BACKGROUND: Infants with anophthalmia and microphthalmia frequently have other associated congenital anomalies. The reported frequency and types of associated malformations vary among different studies. METHODS: The purpose of this investigation was to assess the frequency and types of associated malformations among infants with anophthalmia and microphthalmia in a geographically well defined population from 1979 to 2004 of 346,831 consecutive births. RESULTS: Of the 87 infants with anophthalmia and microphthalmia born during this period (prevalence at birth, 2.5 per 10,000), 90% had associated malformations. Infants with associated malformation were divided into recognizable conditions (22 infants [25%] with chromosomal and 15 infants [17%] with nonchromosomal conditions), and nonrecognizable conditions (41 infants [47%] with multiple malformations). Trisomies 13 and 18 were the most frequent chromosomal abnormalities. Amniotic bands sequence, CHARGE syndrome, Meckel-Gruber syndrome, and VACTERL association were most often present in recognizable nonchromosomal conditions. Malformations in the musculoskeletal, cardiovascular, and central nervous systems were the most common other anomalies in infants with multiple malformations and nonrecognizable conditions. CONCLUSIONS: The frequency of associated malformations in infants with anophthalmia or microphthalmia emphasizes the need for a thorough investigation of these infants. Routine screening for other malformations-especially musculoskeletal, cardiac, and central nervous system anomalies-may need to be considered in infants with anophthalmia or microphthalmia, and referral of these infants for genetics evaluation and counseling seems warranted.

Anophthalmos, microphthalmos, and Coloboma in the United kingdom: clinical features, results of investigations, and early management.

PURPOSE: To describe the clinical features of children with anophthalmos, microphthalmos, and typical coloboma (AMC). DESIGN: Descriptive, observational, cross-sectional study of the United Kingdom. PARTICIPANTS: A total of 135 children with AMC newly diagnosed over an 18-month period beginning in October 2006. METHODS: Cases were identified using active surveillance through an established ophthalmic surveillance system. Eligible cases were followed up 6 months after first notification. MAIN OUTCOME MEASURES: Phenotypic characteristics, both ocular and systemic, clinical investigations, causes, and interventions. RESULTS: A total of 210 eyes (of 135 children) were affected by AMC, of which 153 had isolated coloboma or coloboma with microphthalmos. The most common colobomatous anomaly was a chorioretinal defect present in 109 eyes (71.2%). Some 44% of children were bilaterally visually impaired. Systemic abnormalities were present in 59.7% of children, with craniofacial anomalies being the most common. Children with bilateral disease had a 2.7 times higher odds (95% confidence interval, 1.3-5.5, P = 0.006) of having systemic involvement than unilaterally affected children. Neurologic imaging was the most frequent investigation (58.5%) performed. Less than one third (30.3%) of the children with microphthalmos had ocular axial lengths measured. Eight children had confirmed genetic mutations. Approximately half (49.2%) of the children required ocular intervention. CONCLUSIONS: Colobomatous defects were the most common phenotype within this spectrum of anomalies in the United Kingdom. The high frequency of posterior segment colobomatous involvement means that a dilated fundal examination should be made in all cases. The significant visual and systemic morbidity in affected children underlines the importance of a multidisciplinary approach to management.

Anophthalmos, microphthalmos, and typical coloboma in the United Kingdom: a prospective study of incidence and risk.

PURPOSE: Anophthalmos, microphthalmos, and typical coloboma (AMC) form an interrelated spectrum of congenital eye anomalies that can cause significant visual loss and cosmetic disfigurement in children. This prospective study of children born in the United Kingdom was undertaken to determine the incidence of AMC diagnosed by ophthalmologists and to explore sociodemographic risks. METHODS: Recruitment was achieved though an established active surveillance system of U.K. ophthalmologists supported by a new research network of interested specialists, the Surveillance of Eye Anomalies (SEA-UK) Special Interest Group. It started October 1, 2006, and continued over 18 months. RESULTS: One hundred thirty-five children were newly diagnosed with AMC. Typical colobomatous defects were the commonest phenotype, and anophthalmos was rare (n = 7). Both eyes were affected in 55.5% of the children. The cumulative incidence of AMC by age 16 years was 11.9 per 100,000 (95% CI, 10.9-15.4). Of the children examined, 41.5% had not seen an ophthalmologist by 3 months of age. The incidence in Scotland was nearly double that in England and Wales. The children of Pakistani ethnicity had a 3.7 (95% CI, 1.9-7.5) times higher risk of AMC than did white children. There was some evidence to suggest a higher incidence in the more socioeconomically deprived. The sibling risk ratio was 210 (95% CI, 25-722). CONCLUSIONS: This is the first prospective study of AMC, and it establishes the frequency across the United Kingdom. Comparisons with data quoted in the literature are difficult because study methodologies differ, but the frequency appears to be lower than that quoted for other developed countries. There are geographic and ethnic variations in incidence that warrant further investigation.

Microphthalmia and anophthalmia in Chuuk State, Federated States of Micronesia.

Microphthalmia ('small eye') and anophthalmia ('no eye') are rare congenital defects of eye development. Previous studies utilizing a variety of methodologies have estimated their combined incidence at anywhere from 4 to 30 cases per 100,000 live births. In Chuuk, Federated States of Micronesia, there have been 42 cases detected since 1988, yielding an estimated incidence of 140 cases per 100,000. A number of putative genetic and environmental causes have previously been associated with microphthalmia and anophthalmia, including vitamin A deficiency. To date, it is unclear which of these factors may play a role in the alarmingly high rates observed in Chuuk. The Chuuk Division of Public Health has proposed a study to explore these potential causes, which will hopefully shed light on the prevention of these rare but debilitating conditions.

Intracranial and extracranial malformations in patients with craniofacial anomalies.

BACKGROUND: Craniofacial structures have an intimate relationship with the central nervous system in the embryologic development period and the developmental abnormalities of the face and skull that are frequently associated with malformations of the central nervous system. Additional intracranial and extracranial malformations in a patient with craniofacial deformity may negatively affect the outcome of the surgery and the quality of life. PATIENTS AND METHODS: A retrospective analysis of a total of 123 patients with craniofacial anomalies was performed. Physical examination notes, ophthalmologic findings, computed tomography, and magnetic resonance imaging reports were retrospectively analyzed, and intracranial and extracranial malformations and ophthalmologic problems in each group were categorized. RESULTS: Of the patients with nonsyndromic craniosynostosis, 29% had intracranial and extracranial malformations. Of them, 17% had ophthalmologic problems. Of the patients with syndromic craniosynostosis, 34% had intracranial and 31% had extracranial malformations. In the patients with craniofacial cleft, 60% had intracranial and 30% had extracranial malformations. The most common intracranial malformations are hydrocephaly, Chiari type 1 malformation, and corpus callosum disorders. CONCLUSIONS: A multidisciplinary approach is essential in the evaluation and follow-up of individuals with craniofacial abnormalities. Conventional radiography and three-dimensional computed tomography of the bony skeleton and axial scanning of the soft tissues is our first-step routine. Brain magnetic resonance imaging should be performed in patients with multiple-suture synostosis, syndromic synostosis, and craniofacial clefts to rule out central nervous system and soft tissue malformations. During the postoperative first year, conventional x-rays are sufficient to evaluate the craniofacial area. Central nervous system disorders may cause major headaches, muscle weakness, hearing problems, extreme fatigue, poor motor coordination, and cognitive and social disabilities even when their intelligence quotient is normal. Therefore, every effort should be performed to search and treat additional malformations. Prevention of additional morbidities improves surgical and social outcomes.