[Homozygous E387K (1159G>A) mutation of the CYP1B1 gene in a Roma boy affected with primary congenital glaucoma. Case report]. / A CYP1B1 gén E387K (1159G>A) homozigóta mutációja primer congenitalis glaucomában szenvedo roma gyermekben.

Primary congenital glaucoma was diagnosed in a son (born in 2009) of a healthy, non-consanguineous Roma couple. This couple terminated their next two pregnancies because of the 25% recurrence risk of this autosomal recessive ophthalmological abnormality. Molecular genetic analysis showed the homozygote E387K mutation of the CYP1B1 gene in the proband and the presence of this gene mutation in heterozygous form in both parents. This gene mutation is characteristic for Slovakian Roma population. There are two objectives of this case report. On one hand this finding indicates the genetic relationship of Slovakian and Hungarian Romas. On the other hand, the couple plans to have further pregnancies, and prenatal genetic test may help to assess the possible recurrence risk of this hereditary disease.

Biosimilar SB11 versus reference ranibizumab in neovascular age-related macular degeneration: 1-year phase III randomised clinical trial outcomes.

BACKGROUND/AIMS: To provide longer-term data on efficacy, safety, immunogenicity and pharmacokinetics (PK) of ranibizumab biosimilar SB11 compared with the reference ranibizumab (RBZ) in patients with neovascular age-related macular degeneration (nAMD). METHODS: Setting: Multicentre. Design: Randomised, double-masked, parallel-group, phase III equivalence study. Patient population: ≥50 years old participants with nAMD (n=705), one 'study eye'. INTERVENTION: 1:1 randomisation to monthly intravitreal injection of 0.5 mg SB11 or RBZ. Main outcome measures: Visual efficacy endpoints, safety, immunogenicity and PK up to 52 weeks. RESULTS: Baseline and disease characteristics were comparable between treatment groups. Of 705 randomised participants (SB11: n=351; RBZ: n=354), 634 participants (89.9%; SB11: n=307; RBZ: n=327) completed the study until week 52. Previously reported equivalence in primary efficacy remained stable up to week 52 and were comparable between SB11 and RBZ. The adjusted treatment difference between SB11 and RBZ in full analysis set at week 52 of change from baseline in best-corrected visual acuity was -0.6 letters (90% CI -2.1 to 0.9) and of change from baseline in central subfield thickness was -14.9 µm (95% CI -25.3 to -4.5). The incidence of ocular treatment-emergent adverse events (TEAEs) (SB11: 32.0% vs RBZ: 29.7%) and serious ocular TEAE (SB11: 2.9% vs RBZ: 2.3%) appeared comparable between treatment groups, and no new safety concerns were observed. The PK and immunogenicity profiles were comparable, with a 4.2% and 5.5% cumulative incidence of antidrug antibodies up to week 52 for SB11 and RBZ, respectively. CONCLUSIONS: Longer-term results of this study further support the biosimilarity established between SB11 and RBZ.

Birth characteristics of different ocular congenital abnormalities in hungary.

AIMS: The aim of the study was to estimate the prevalence at birth of different ocular congenital abnormalities and to describe their birth characteristics in Hungary. METHODS: Two data sets were evaluated: the national-based Hungarian Congenital Abnormality Registry and the Hungarian Case-Control Surveillance of Congenital Abnormalities which include cases with ocular abnormalities and patient controls with other (non-ocular) congenital abnormalities, and population controls without abnormalities from the National Birth Registry. RESULTS: Seven hundred twelve cases were found with ocular abnormalities in the data set of the Hungarian Congenital Abnormality Registry (2.62 per 10,000 live births), while that of the Hungarian Case-Control Surveillance of Congenital Abnormalities included 314 cases with ocular defects among 2.7 million live births in Hungary between 1980 and 2002. There was an obvious underascertainment and/or notification of cases with ocular defects because an extra effort to ascertain all cases with ocular abnormalities resulted in a birth prevalence of 6.31 per 10,000 live births in 1999. The main birth characteristics of cases were male excess, shorter mean gestational age and smaller mean birth weight with a larger proportion of preterm birth and low birthweight. CONCLUSIONS: Earlier diagnosis of ocular abnormalities is necessary with a more complete notification of these cases to the Hungarian Congenital Abnormality Registry. The birth characteristics of cases with ocular abnormalities may have some associations with the origin of ocular defects; therefore, these variables will require further studies in case-control approach.

[A population-based case-control study of isolated congenital cataract]. / Izolált congenitalis cataracta eset-kontroll vizsgálata.

BACKGROUND: To detect the possible etiological factors in the origin of isolated congenital cataracts. METHOD: The data set of the Hungarian Case-Control Surveillance of Congenital Abnormalities, 1980-2002, contained 111 cases with isolated congenital cataract and their 111 matched control pairs without defect, 22744 patient controls with other non-ocular abnormalities and 37837 population controls without any defects. Exposure data and family history were based on (i) medical records, (ii) retrospective maternal information and (iii) information obtained by regional nurses at home visit of nonrespondent families. RESULTS: Positive family history indicated autosomal dominant origin in 9,9% of the cases. Rubella infections occurred more frequently in case mothers than in control mothers before the vaccination against rubella virus. A higher prevalence of influenza/common cold (55.9% in the case and 18.5% in the population control group, adjusted OR with 95% CI: 5.8, 4.0-8.4 and 21.7% in the malformation control group: 4.7, 3.2-6.9) and acute infectious diseases of respiratory system (26.1% in the case and 9.1% in the population control group: 3.8, 2.5-5.8 and 9.3% in the malformation control group: 3.4, 2.2-5.3) related with fever was found during the pregnancy of the case mothers. In addition the higher risk of isolated congenital cataract was prevented by antifever therapy. CONCLUSIONS: Some part of isolated congenital cataract is preventable by rubella vaccination and probably by influenza vaccination in the epidemic period, in addition it is worth using an effective antifever therapy of fever related respiratory diseases to restrict the teratogenic risk of fever.

A population-based case-control study of isolated ocular coloboma.

AIMS: To attempt the detection of possible etiological factors in the origin of isolated ocular, mainly iris coloboma. METHODS: The data set of the Hungarian Case-Control Surveillance of Congenital Abnormalities, 1980-2002, was used. Exposure data and family history were based on (1) prospective medical records, (2) retrospective maternal information, and (3) information obtained by regional nurses at home visit. RESULTS: Of 46 cases, 40 were affected with iris coloboma and 19 had bilateral manifestation. The positive family history indicated a hereditary origin in 4.3% (2/46) of cases. An association was found between the isolated ocular coloboma and hydroxyethylrutoside treatment (adjusted POR with 95% CI: 5.4, 2.2-12.9). Another association was seen between isolated ocular coloboma and hypothyroidism (adjusted OR with 95% CI = 12.6, 3.0-52.7), but it was based only on two cases. CONCLUSIONS: It is necessary to study the preventable environmental factors in the origin of these ocular defects.

Maternal demographic and socioeconomic characteristics of live-born infants with isolated ocular congenital abnormalities.

PURPOSE: To evaluate maternal age and birth order, in addition socioeconomic status and finally occupational background of mothers who delivered babies with different isolated ocular congenital abnormalities. METHODS: The data set of the Hungarian Case-Control Surveillance of Congenital Abnormalities, 1980-2002 was used and the evaluation of maternal variables was based on both medical records and maternal information. RESULTS: Mean maternal age and birth order was lower in the mothers of cases with isolated an/microphthalmia. The mean birth order was also lower in the mothers with isolated congenital cataract compared with the control groups. The mothers of cases with isolated coloboma had the usual mean maternal age with a very high proportion of second birth order. The proportion of unmarried women, low maternal socio-economic status and unemployment was larger in the groups of isolated an/microphthalmia and isolated primary congenital glaucoma and these mothers frequently worked in the agriculture. CONCLUSIONS: Cases with different isolated ocular congenital abnormalities showed different maternal characteristics as the reference controls, therefore it is necessary to evaluate each isolated ocular congenital abnormality separately and maternal characteristics can be considered as potential confounders in the analyses of ocular congenital abnormalities.

A population-based case-control study of isolated primary congenital glaucoma.

We studied the possible etiological factors of isolated primary congenital glaucoma (IPCG) using data from the Hungarian Case-Control Surveillance of Congenital Abnormalities, 1980-2002. The study group consisted of 52 cases with IPCG compared to 52 matched control pairs without any defects, and 22,744 malformed controls with non-ocular defects and 37,837 population controls with no defect. Exposure data and family history were collected (i) prospectively by prenatal logbook and other medical records, (ii) retrospectively through a structured questionnaire completed by mothers, and (iii) from supplementary information obtained by regional nurses visiting the homes of non-respondent mothers. Autosomal recessive inheritance of IPCG was suspected on the basis of sib occurrence and parental consanguinity in 15% of cases. The shorter gestational age (with high proportion of preterm birth), higher birth order, large proportion of births among unmarried women, low socioeconomic status, and high rate of unemployment may be related to Gypsy origin of at least 54% of cases of IPCG. We conclude that the higher incidence of IPCG in the Hungarian Gypsy population is associated with their inbreeding and the possible founder effect of a gene mutation.

A population-based case-control study of isolated anophthalmia and microphthalmia.

The purpose of the study was to reveal the etiological factors in the origin of isolated an/microphthalmia. The dataset of the Hungarian Case-Control Surveillance of Congenital Abnormalities, 1980-2002 containing 56 cases with isolated an/microphthalmia and 22,744 malformed controls with other non-ocular defects from the Hungarian Congenital Abnormality Registry, in addition of 56 matched control pairs and 37,837 population controls without defects from the National Birth Registry, was evaluated. Exposure data and family history were collected (i) prospectively by prenatal logbook and other medical records, (ii) retrospectively through a structured questionnaire filled-in by mothers, and (iii) information obtained by regional nurses at home visit of non-respondent mothers. The autosomal recessive origin of isolated an/microphthalmia was indicated in about 10% of cases on the basis of sib recurrence. Cases with isolated an/microphthalmia had a much shorter mean gestational age and smaller mean birth weight, a much larger proportion of preterm birth and low birthweight. Their mothers were younger with a predominance of first birth order, frequently unmarried with low socioeconomic status. These findings are in agreement with a much higher prevalence at birth of cases with isolated an/microphthalmia in the gypsy population probably due to the interaction of inbreeding effect and low socioeconomic status. Further molecular genetic studies are needed to identify gene mutations of isolated an/microphthalmia in the Hungarian gypsy population.

Population-based case-control study of isolated congenital cataract.

BACKGROUND: The aim of this study was to detect possible etiological factors in the origin of isolated congenital cataracts. METHODS: The data set of the Hungarian Case-Control Surveillance of Congenital Abnormalities, 1980-2002, contains 111 cases of isolated congenital cataract and 111 matched control pairs without the defect, 37,837 population controls without any defects, and 22,744 malformed controls with other nonocular abnormalities. Exposure data and family history are based on prospective medical records, retrospective maternal information, and information obtained by regional nurses during a home visit with nonrespondent mothers. RESULTS: A positive family history indicated an autosomal-dominant origin in 10% of cases. Rubella infections occurred more frequently in case mothers than in control mothers before vaccination against rubella virus was instituted. A higher prevalence of influenza or common cold during pregnancy was found in the case group (55.9%) than in the population control group (18.5%; adjusted odds ratios [ORs], 5.8; 95% confidence interval (CI), 4.0-8.4) or in the malformed control group (21.7%; adjusted OR, 4.7; 95% CI, 3.2-6.9). The prevalence of acute infectious diseases of the respiratory system during pregnancy was also higher in the case group (26.1%) than in the population control group (9.1%; adjusted OR, 3.8; 95% CI, 2.5-5.8), or the malformed control group (9.3%; adjusted OR, 3.4; 95% CI, 2.3-5.3). The higher risk for isolated congenital cataract in cases of mothers with influenza or common cold and acute infectious diseases of the respiratory system during pregnancy was not found after administration of antifever therapy. CONCLUSIONS: Some isolated congenital cataracts are preventable by rubella vaccination and probably by influenza vaccination in the epidemic period. In addition, our results suggest that using antifever therapy for fever-related respiratory diseases may restrict the teratogenic risk of hyperthermia.