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.

Frequência da microftalmia associada à catarata congênita, sua frequência etiológica e o resultado visual pós-cirúrgico / Frequency and ethiological frequency of congenital cataract associated with microphthalmia and postoperative visual results

Resumo Objetivo: Determinar a frequência da microftalmia associada à catarata congênita e sua frequência etiológica. Comparar o resultado visual após a cirurgia da catarata congênita em olhos microftálmicos, com o resultado visual obtido em olhos não microftálmicos. Método: Estudo retrospectivo de 76 pacientes portadores de microftalmia e catarata congênita, selecionados após análise de 1050 prontuários dos pacientes atendidos no ambulatório de catarata congênita da UNIFESP. A microftalmia foi determinada pela ecobiometria ultrassonica. Exames oculares e complementares foram feitos para esclarecer a causa etiológica. O resultado visual pós- operatório do Grupo I (com microftalmia) foi confrontado com o resultado visual obtido no Grupo II (sem microftalmia). Resultados: O diâmetro ântero-posterior dos olhos microftálmicos variou de 13 à 21 mm. A frequência etiológica da catarata congênita associada aos olhos microftálmicos foi assim distribuída: doenças infecciosas (55,3%); seguidos de idiopáticas (26,3%), colobomas (7,9%), hereditárias (6,6%), persistência do vítreo primário hiperplásico (2,6%) e associada à síndrome de Lenz (1,3%) .A frequência da microftalmia foi de 7,23 %. 68,3% de olhos afácicos microftálmicos atingiram visão melhor e ou igual à 20/200. Conclusão: A frequência da microftalmia associada à catarata congênita foi de 7,23%. A maior frequência etiológica ocorreu nas doenças infecciosas (55,3%), Embora os olhos microftálmicos tenham tendência para piores resultados visuais quando comparados aos não microftálmicos, nesta pesquisa os olhos microftálmicos afácicos que atingiram visão melhor ou igual a 20/200 foram de 68,3%.

Abstract Objective: To determine the frequency of microphthalmia associated with congenital cataract and its etiological frequency. Compare the result of visual acuity in aphakic microphthalmus eyes, with the visual acuity result obtained in non microphthalmus eyes. Methods: Retrospective study of 76 patients with microphthalmia and congenital cataract, selected after analysis of 1050 medical records of patients seen in congenital cataract clinic of UNIFESP. All patients underwent complete ophthalmologic examination and microphthalmia determined by ultrasound biometry. Investigations were made to clarify the etiological cause. The postoperative visual outcome of Group I (with microphthalmia) was faced with the visual results obtained in Group II (control group without microphthalmia). Results: The anteroposterior diameter of microphthalmus eyes ranged from 13 to 21 mm. The etiological frequency of microphthalmia and congenital cataract was distributed as follows: infectious diseases (55.3%), idiopathic (26.3%), colobomas (7.9%), hereditary (6.6%), persistent hyperplastic vitreous (2.6%) and linked to the Lenz's syndrome (1.3%). The visual acuity in aphakic eyes that reached better view and or equal to 20/200 was 68.3%. Conclusion: The frequency of microphthalmia associated with congenital cataract was 7.23%. The etiological occurred more frequently in infectious disease (55.3%). The aphakics eyes with microphthalmia tend to have worse visual acuity results than the eyes without microphthalmia. If we consider the visual results same and above 20/200 as successful in this search, aphakic eyes with microphthalmia that hit these indices are 68.3%.

Chornobyl 30 years later: Radiation, pregnancies, and developmental anomalies in Rivne, Ukraine.

In the 30 years since the Chornobyl nuclear power plant disaster, there is evidence of persistent levels of incorporated ionizing radiation in adults, children and pregnant women in the surrounding area. Measured levels of Cesium-137 vary by region, and may be influenced by dietary and water sources as well as proximity to nuclear power plants. Since 2000, comprehensive, population-based birth defects monitoring has been performed in selected regions of Ukraine to evaluate trends and to generate hypotheses regarding potential causes of unexplained variations in defect rates. Significantly higher rates of microcephaly, neural tube defects, and microphthalmia have been identified in selected regions of Ukraine collectively known as Polissia compared to adjacent regions collectively termed non-Polissia, and these significantly higher rates were evident particularly in the years 2000-2009. The Polissia regions have also demonstrated higher mean whole body counts of Cesium-137 compared to values in individuals residing in other non-Polissia regions. The potential causal relationship between persistent ionizing radiation pollution and selected congenital anomaly rates supports the need for a more thorough, targeted investigation of the sources of persistent ionizing radiation and the biological plausibility of a potential teratogenic effect.

A clinical study of Aicardi syndrome in Northern Ireland: the spectrum of ophthalmic findings.

PurposeAicardi syndrome is a rare disorder, affecting ~1 in 100 000 live births. Chorioretinal lacunae feature alongside agenesis of the corpus callosum and spasms in flexion to make up a diagnostic triad. Recently ophthalmic findings such as microphthalmia and optic disc anomalies have been recognised in association with Aicardi syndrome. This population study aims to determine the presence of ocular findings and identifies some novel associations in these patients.MethodsA retrospective review of charts for seven patients with Aicardi syndrome was carried out.ResultsThe incidence of Aicardi syndrome in Northern Ireland was found to be 1 in 110 000 live births. Four patients who had microphthalmus also had iris abnormalities; two patients with bilateral microphthalmus had partial aniridia and two patients with unilateral microphthalmus had iris coloboma in the same eye. Optic disc abnormalities were found in 11 eyes of six patients. Two patients were found to have areas of fibrovascular proliferation with a thickened white ridge and avascular zone beyond. Both of these patients developed retinal detachments.ConclusionsOur review of patients with Aicardi syndrome in Northern Ireland has revealed some novel clinical findings, including aniridia in two cases. We also found a higher than previously reported rate of excavated disc anomalies of 50% in our cohort. We found two cases of peripheral retinal dysplasia, which has not been previously reported. This finding was associated with microphthalmus and severe optic disc abnormalities, and we feel this warrants early EUA to enable early treatment and hopefully result in better visual prognosis.

Elevated congenital anomaly rates and incorporated cesium-137 in the Polissia region of Ukraine.

BACKGROUND: Investigations soon after the 1986 Chornobyl (Chernobyl in Russian) accident of exposed populations residing elsewhere in Europe led government and international agencies to conclude that exposures to cesium-137 (Cs-137) were not teratogenic. Our observations of elevated population rates of neural tube defects (NTDs) and microcephaly and microphthalmia (M/M) in the Rivne Province in Ukraine, which were among the highest in Europe, prompted this follow-up investigation inclusive of whole-body counts (WBCs) of Cs-137 among ambulatory patients and pregnant women residing in Polissia, the most polluted region in Rivne. METHODS: Yearly (2000-2012) population rates of NTDs and M/M and WBC patterns of ambulatory patients (2001-2010) and pregnant women (2011-2013) in Polissia and non-Polissia regions of Rivne were analyzed. RESULTS: The NTD and M/M population rates in Rivne remain elevated and are statistically significantly higher in Polissia than in non-Polissia. The WBCs among residents in Polissia are statistically significantly higher than among those from non-Polissia. CONCLUSION: NTD and M/M rates are highest in the Polissia region of Rivne and are among the highest in Europe. In Polissia, the WBCs of Cs-137 are above officially set permissible upper limits. The results are based on aggregate data of NTDs and M/Ms and average WBC values. Further investigations of causality of the high rates of NTDs and M/Ms are needed and urgent strengthening policies and implementations to reduce exposures to teratogens, in particular radioactive nuclides and alcohol, and consumption of folic acid supplements are indicated.

Blastopathies and microcephaly in a Chornobyl impacted region of Ukraine.

This population-based descriptive epidemiology study demonstrates that rates of conjoined twins, teratomas, neural tube defects, microcephaly, and microphthalmia in the Rivne province of Ukraine are among the highest in Europe. The province is 200 km distant from the Chornobyl site and its northern half, a region known as Polissia, is significantly polluted by ionizing radiation. The rates of neural tube defects, microcephaly and microphthalmia in Polissia are statistically significantly higher than in the rest of the province. A survey of at-birth head size showed that values were statistically smaller in males and females born in one Polissia county than among neonates born in the capital city. These observations provide clues for confirmatory and cause-effect prospective investigations. The strength of this study stems from a reliance on international standards prevalent in Europe and a decade-long population-based surveillance of congenital malformations in two distinct large populations. The limitations of this study, as those of other descriptive epidemiology investigations, is that identified cause-effect associations require further assessment by specific prospective investigations designed to address specific teratogenic factors.

[Cataract surgery in nanophthalmic eyes]. / Phakoemulsifikation bei nanophthalmischen Augen.

PURPOSE: The aim of this study was to determine the prevalence of nanophthalmos among cataract patients and to evaluate intraoperative and postoperative complications in nanophthalmic eyes. PATIENTS AND METHODS: Medical and operating records of all 3287 patients who had undergone clear cornea phacoemulsification cataract surgery with foldable acrylic IOL implantation during a period of two years (January 2009 to December 2010) were retrospectively reviewed. Nanophthalmos was diagnosed according to a shorter axial length than 20 mm, a shallow anterior chamber, hyperopia and scleral thickness greater than 1.7 mm as determined by echography. Before surgery all patients received an intravenous 20 % mannitol solution. RESULTS: From 3287 eyes, six eyes of four patients were identified as nanophthalmic with an axial length below 20 mm and a scleral thickness greater than 1.7 mm. The prevalence of nanophthalmos was 0.18 %. The average hyperopia was + 7.87 D (+ 6.0 to + 9.50). The mean axial length was 19.58 mm (18.94 to 20.00). The mean biometry calculation was 33.16 D (31.5 to 36.0). In all cases no complications were observed during the surgery. In two eyes a mild iritis was observed one day after surgery. During a follow-up of 3 months no further complications occurred. CONCLUSIONS: Surgical manipulation in a narrow and crowded anterior chamber in nanophthalmic eyes with increased vitreous pressure is always a challenge and must be performed by an experienced surgeon. Preoperative examination of scleral thickness and preoperative administration of hyper-osmotic solution for reduction of vitreous pressure are very important to prevent unexpected complications. There was no need for a prophylactic surgical procedure in our patients.

Survey of microphthalmia in Japan.

PURPOSE: To report the current status of patients with microphthalmia based on a cross-sectional survey of patient hospital visits. METHODS: A questionnaire was sent to the departments of ophthalmology in 1,151 major Japanese hospitals to survey the following: the number of patients with microphthalmia who visited the outpatient clinics between January 2008 and December 2009; gender; age; family history; associated ocular anomalies; complications and systemic diseases; surgical treatment; vision and management. A retrospective quantitative registry of 1,254 microphthalmic eyes (851 patients) from 454 hospitals (39.4%) was compiled. RESULTS: Of the patients for whom data were available, 50% ranged in age from 0 to 9 years. The major ocular findings were nanophthalmos, coloboma, and vitreoretinal malformations. Ocular complications frequently developed, including cataracts, glaucoma, and retinal detachment. Surgery was performed in 21.4% of all cases, and systemic diseases were present in 31% of all cases. The vision associated with microphthalmia exceeded 0.1 in about 30% of the eyes. Glasses and low vision aids were used by 21.6% of patients. CONCLUSIONS: Patients with microphthalmia often have ocular and systemic anomalies. Early assessment and preservation of vision and long-term complication management are needed.

Anophthalmia and microphthalmia.

Anophthalmia and microphthalmia describe, respectively, the absence of an eye and the presence of a small eye within the orbit. The combined birth prevalence of these conditions is up to 30 per 100,000 population, with microphthalmia reported in up to 11% of blind children. High-resolution cranial imaging, post-mortem examination and genetic studies suggest that these conditions represent a phenotypic continuum. Both anophthalmia and microphthalmia may occur in isolation or as part of a syndrome, as in one-third of cases. Anophthalmia/microphthalmia have complex aetiology with chromosomal, monogenic and environmental causes identified. Chromosomal duplications, deletions and translocations are implicated. Of monogenic causes only SOX2 has been identified as a major causative gene. Other linked genes include PAX6, OTX2, CHX10 and RAX. SOX2 and PAX6 mutations may act through causing lens induction failure. FOXE3 mutations, associated with lens agenesis, have been observed in a few microphthalmic patients. OTX2, CHX10 and RAX have retinal expression and may result in anophthalmia/microphthalmia through failure of retinal differentiation. Environmental factors also play a contributory role. The strongest evidence appears to be with gestational-acquired infections, but may also include maternal vitamin A deficiency, exposure to X-rays, solvent misuse and thalidomide exposure. Diagnosis can be made pre- and post-natally using a combination of clinical features, imaging (ultrasonography and CT/MR scanning) and genetic analysis. Genetic counselling can be challenging due to the extensive range of genes responsible and wide variation in phenotypic expression. Appropriate counselling is indicated if the mode of inheritance can be identified. Differential diagnoses include cryptophthalmos, cyclopia and synophthalmia, and congenital cystic eye. Patients are often managed within multi-disciplinary teams consisting of ophthalmologists, paediatricians and/or clinical geneticists, especially for syndromic cases. Treatment is directed towards maximising existing vision and improving cosmesis through simultaneous stimulation of both soft tissue and bony orbital growth. Mild to moderate microphthalmia is managed conservatively with conformers. Severe microphthalmia and anophthalmia rely upon additional remodelling strategies of endo-orbital volume replacement (with implants, expanders and dermis-fat grafts) and soft tissue reconstruction. The potential for visual development in microphthalmic patients is dependent upon retinal development and other ocular characteristics.

The epidemiology of anophthalmia and microphthalmia in Sweden.

Infants with a clinical diagnosis of anophthalmia or microphthalmia were identified from four health registers in Sweden, covering different parts of the period 1965-2001. During the observation period, the rate of anophthalmia decreased from the early 1970s from 0.4 to 0.2 per 10,000 births. The registered rate of microphthalmia increased markedly during the observation period to reach a maximum in 1987 of about 1.5 per 10,000. About 10% of the 432 identified children had a chromosome anomaly. There was no geographical variation in prevalence and infants born in urban or rural districts had, if anything, a lower risk than infants born in cities (0.93 and 1.13 per 10,000, respectively). Non-eye malformations were more common at anophthalmia (63%) than at microphthalmia (30%). Sex ratio was normal and no statistically significant variation between sub-groups (anophthalmia, microphthalmia, isolated, associated with non-eye malformations) could be demonstrated. There was a marked risk increase with maternal age but no certain parity effect, no effect of maternal education, but a possible association with subfertility. Maternal smoking in early pregnancy seemed to increase the risk for anophthalmia or microphthalmia in the absence of a coloboma.

Cataract surgery in relative anterior microphthalmos.

PURPOSE: To determine the prevalence of relative anterior microphthalmos (RAM) and evaluate intraoperative performance and surgical outcome in eyes with RAM undergoing cataract surgery. DESIGN: Nested case-control series. PARTICIPANTS: One thousand four hundred consecutive patients undergoing cataract surgery were evaluated to determine the prevalence of RAM. Relative anterior microphthalmos is defined as horizontal corneal diameter (HCD) < or =11 mm, anterior chamber depth (ACD) < or =2.2 mm, and axial length (AL) >20 mm, with no other morphologic malformation. METHODS: Patients were examined preoperatively for HCD, ACD, and AL. Horizontal corneal diameter was measured with calipers. Anterior chamber depth and AL were measured with immersion shell with water. Associated ocular pathologic conditions were recorded. Two control groups were identified. Group I (normal eyes; n = 84) had HCD >11 mm, ACD >2.2 mm, and AL >20 mm. Group II (eyes with small corneal diameter; n = 84) had HCD < or =11 mm, ACD >2.2 mm, and AL >20 mm. MAIN OUTCOME MEASURES: Patients with RAM and controls were evaluated for intraoperative performance and postoperative outcome. The 2-tailed Fisher exact test was applied to compare the performance of RAM with each of the control groups. The odds ratio (OR) with 95% confidence intervals (95% CI) was determined. RESULTS: The prevalence of RAM was 6% (84 of 1400 eyes; 95%CI, 0.048-0.074). Relative anterior microphthalmos was associated with the presence of small pupil, 34 (40.48%); corneal guttae, 31 (36.9%); glaucoma, 29 (34.5%); and pseudoexfoliation, 6 (7.14%). Intraoperatively, RAM was associated with overall surgical difficulty because of less working space in 59 eyes (70.24%; OR, 63.7; 95% CI, 18.3-221; P<0.001) compared with control groups I and II; uveal trauma in 12 (14.28%); Descemet's detachment in 5 (5.95%); and posterior capsule rupture in 2 (2.38%). Postoperatively, RAM was associated with transient corneal edema in 63 eyes (75%; OR, 9.0; 95% CI, 4.4-18.0; P<0.001; OR, 5.4; 95% CI, 2.7-10.5; P<0.001) on the first postoperative day. CONCLUSIONS: The prevalence of RAM was 6%. Relative anterior microphthalmos with its associations posed significant intraoperative difficulties. The occurrence of transient corneal edema was frequent.

Anophthalmia and microphthalmia in the Alberta Congenital Anomalies Surveillance System.

BACKGROUND: A higher than expected rate of anophthalmia/microphthalmia (A/M) for 1999 was noted in both the Alberta Congenital Anomalies Surveillance System (ACASS) and the Canadian Congenital Anomalies Surveillance System (CCASS). Since this increase was at variance with the previous 19 years, we performed a review to determine whether the increase was true and, if so, the possible explanation. METHODS: We reviewed the records of the cases of A/M in the ACASS together with the accompanying attachments (e.g., consultant, autopsy and chromosome reports) for 1991-2001. In addition, we contacted all 91 registered ophthalmologists in Alberta. Letters were also written to the Edmonton and Calgary offices of the Canadian National Institute for the Blind (CNIB). RESULTS: Sixty cases of A/M were ascertained over the study period. Of the 88 active ophthalmologists in the province, 21 (24%) replied, but no new cases were ascertained from this source. No replies were received from the CNIB. We constructed five categories of clinical phenotypes for the 60 cases: 20 had a chromosomal etiology, 13 had a recognized syndrome or association, 16 had extraocular malformations, 5 had other eye anomalies, and 6 had A/M only. Pregnancy terminations were not included. The higher rate in 1999 was mainly due to cases with a chromosomal etiology or a recognized syndrome or association. There was no indication that a teratogen was causing a cluster of A/M cases, as our annual rates were comparable to those for other jurisdictions not only in Canada but also in other countries. INTERPRETATION: Our review confirmed that the rate of A/M in Alberta in 1999 was high but that the increase was mainly due to five cases of trisomy 13 together with one case associated with a syndrome (Meckel-Gruber). Our findings provide reassurance that there was no environmental cause of clustering of anophthalmia or microphthalmia. This review demonstrates the importance of ongoing population-based surveillance in providing baseline birth prevalence rates for evaluating trends and clusters.

An epidemiological and clinical study of ocular manifestations of congenital rubella syndrome in Omani children.

OBJECTIVE: To conduct a follow-up study in patients with congenital rubella syndrome (CRS) in Oman and analyze the prevalence of ophthalmic disorders and associated systemic problems. METHODS: This historical prospective cohort study included review of 32 surviving patients with CRS reported by the surveillance system in Oman from 1987 through 2002. All patients underwent a complete ophthalmic examination that included visual acuity estimation, refraction and anterior and posterior segment evaluation, and intraocular pressure measurement. Pediatric and otorhinolaryngologic consultations were also performed. RESULTS: The age-adjusted prevalence of CRS in Oman was 73.2 per million in the Omani population younger than 20 years, and the incidence was 0.6 per 1000 live births. Cataract, retinitis, microphthalmos, and glaucoma were observed in 11, 16, 6, and 4 patients, respectively. Keratoconus, corneal hydrops, and spontaneous resorption of lens were found in 1 patient each. Vision testing was possible in 16 children; 4 were bilaterally blind. Patients who had undergone eye surgery had significantly lower visual acuity, as compared with those who had not undergone surgery (relative risk 2.53; 95% confidence interval, 1.07-6.13). Among the 11 patients with CRS with cataract, we found hearing loss, cardiac anomalies, and neuropsychologic anomalies in 7, 4, and 6 children, respectively. CONCLUSIONS: Congenital rubella syndrome has a wide variety of severe ophthalmic and systemic complications. High clinical vigilance for signs of CRS and regular observation of surviving patients with CRS is desirable. In patients with cataract, the functional results of surgery, despite state-of-the-art ophthalmic care, continue to be poor. Because of a high prevalence of visual, audiologic, and neurologic disabilities, surviving patients with CRS pose a burden on the medical and social communities. Emphasis in management ought to be prevention of CRS through effective immunization programs.

Síndrome de Hallermann*Streiff*Francois: a propósito de 7 casos

En el servicio de Oftalmología del Complejo Hospitalario `Daniel Alcides Carrión' del Callao, entre los años 1981 y 1983 han sido estudiados 7 casos portadores del síndrome Hallerman-Streiff-Francois. Este síndrome está caracterizado por discefalia con cara de pájaro, anomalías dentales, nanismo proporcionado, hipotricosis, atrofia de piel, microftalmía y catarata congénita bilateral. De ellos, 2 casos asistieron espontáneamente al servicio, 4 proceden del Centro de Educación Especial ` San Francisco de Asís', 1 procedente del centro de Educación Especial `Santa Lucía'. Estos dos últimos centros educativos están dedicados a la enseñanza de niños con ceguera y visión subnormal. En todos ellos se ha practicado examen clínico general y estudio oftalmológico, prestando especial atención a los antecedentes personales y familiares