Congenital Microphthalmia Research Articles

Indications for Pediatric Ocular Prosthesis Fitting at a Referral Center in the Middle East.

Trauma is the major reason for globe loss in adults; however, there are less data regarding the causes for globe loss in children. We reviewed the underlying diagnoses of children who underwent ocular prosthesis fitting over a 1-year period at a referral eye hospital in the Middle East and found retinoblastoma, trauma, and congenital microphthalmia or anophthalmia to be the most common diagnoses, respectively. Enucleation and evisceration were the most common procedures and were exclusively performed for retinoblastoma and trauma, respectively. Ocular morbidity from the most common diagnoses related to pediatric globe loss in the region could be decreased by improved family education, safety precautions, and genetic counseling.

Peculiarities of ocular prosthetics in congenital anophthalmia and microphthalmia

Aim to determine optimal terms of the primary ocular prosthetics, to develop the most auspicious regimen of adaptation to the ocular prosthesis in children with congenital anophthalmia and microphthalmia.
 Material and methods. A total of 46 children aged from 1 month to 16 years with congenital defect were under observation. Among patients with congenital microphthalmia, only unpromising eyes were subject to ocular prosthetics. Examination methods in the laboratory included external examination of the orbit, palpebral fissure, and eyelids. The state of the cul-de-sac of eyelids, the configuration of the conjunctival cavity, the anterior segment of the abnormally small eyeball were assessed. Photography was performed to achieve a dynamic control of external prosthetics signs of, and to evaluate the face symmetry.
 Results. Best results were observed at early stepwise ocular prosthetics with consideration of features of the ocular prosthesis material, without prior surgery. Long-term cosmetic performance of children with congenital anophthalmia and microphthalmia directly depended on age at which the non-surgical treatment began, on the timely replacement of the ocular prosthesis, compliance to the regimen developed for the adaptation to the prosthesis.
 Conclusion. This study showed that the terms of primary ocular prosthetics are of crucial importance for the symmetrical development of soft tissues and facial skeleton. Prosthetics for patients with congenital anophthalmia should be started at the first month of life. The optimal term for primary prosthetics in congenital microphthalmia depends on the length of the antero-posterior axis at birth. If the axial length is less than 7.5 mm, prosthetics should be started at the first month of life, if the axis is longer than 10 mm no later than from the fourth month of life.

A novel mutation in the CRYAA gene associated with congenital cataract and microphthalmia in a Chinese family

BackgroundCongenital cataract is the leading cause of blindness in children worldwide. Approximately half of all congenital cataracts have a genetic basis. Protein aggregation is the single most important factor in cataract formation.MethodsA four-generation Chinese family diagnosed with autosomal dominant congenital cataracts and microphthalmia was recruited at the Shengjing Hospital of China Medical University. Genomic DNA was extracted from the peripheral blood of the participants. All coding exons and flanking regions of seven candidate genes (CRYAA, CRYBA4, CRYBB2, CRYGC, GJA8, MAF, and PITX3) were amplified and sequenced. Restriction fragment length polymorphism (RFLP) assays were performed to confirm the candidate causative variant, c.35G > T in the CRYAA gene. We constructed pcDNA3.1(+)-CRYAA expression plasmids containing either the wild-type or the R12L mutant alleles and respectively transfected them into HEK293T cells and into HeLa cells. Western blotting was performed to determine protein expression levels and protein solubility. Immunofluorescence was performed to determine protein sub-cellular localization.ResultsA heterozygous variant c.35G > T was identified in exon 1 of CRYAA, which resulted in a substitution of arginine to leucine at codon 12 (p.R12L). The nucleotide substitution c.35G > T was co-segregated with the disease phenotype in the family. The mutant R12L-CRYAA in HEK293T cells showed a significant increase in the expression level of the CRYAA protein compared with the wild-type cells. Moreover, a large amount of the mutant protein aggregated in the precipitate where the wild-type protein was not detected. Immunofluorescence studies showed that the overexpressed mutant CRYAA in HeLa cells formed large cytoplasmic aggregates and aggresomes.ConclusionsIn summary, we described a case of human congenital cataract and microphthalmia caused by a novel mutation in the CRYAA gene, which substituted an arginine at position 12 in the N-terminal region of αA-crystallin. The molecular mechanisms that underlie the pathogenesis of human congenital cataract may be characterized by the prominent effects of the p.R12L mutation on αA-crystallin aggregation and solubility. Our study also expands the spectrum of known CRYAA mutations.

Parental Mosaicism in PAX6 Causes Intra-Familial Variability: Implications for Genetic Counseling of Congenital Aniridia and Microphthalmia.

Mutations in PAX6 are involved in several developmental eye disorders. These disorders have considerable phenotypic variability, ranging from panocular forms of congenital aniridia and microphthalmia to isolated anomalies of the anterior or posterior segment. Here, we describe 3 families with variable inter-generational ocular expression of aniridia, iris coloboma, or microphthalmia, and an unusual transmission of PAX6 mutations from an unaffected or mildly affected parent; all of which raised suspicion of gonosomal mosaicism. We first identified two previously known nonsense mutations and one novel likely pathogenic missense variant in PAX6 in probands by means of targeted NGS. The subsequent segregation analysis by Sanger sequencing evidenced the presence of highly probable mosaic events in paternal blood samples. Mosaicism was further confirmed by droplet digital PCR analysis in several somatic tissues of mosaic fathers. Quantification of the mutant allele fraction in parental samples showed a marked deviation from 50%, with a range between 12 and 29% depending on cell type. Gonosomal mosaicsm was definitively confirmed in one of the families thanks to the availability of a sperm sample from the mosaic father. Thus, the recurrence risk in this family was estimated to be about one-third. This is the first report confirming parental PAX6 mosaicism as a cause of disease recurrence in aniridia and other related phenotypes. In addition, we demonstrated that post-zygotic mosaicism is a frequent and underestimated pathogenic mechanism in aniridia, explaining intra-familial phenotypic variability in many cases. Our findings may have substantial implications for genetic counseling in congenital aniridia. Thus, we also highlight the importance of comprehensive genetic screening of parents for new sporadic cases with aniridia or related developmental eye disease to more accurately assess recurrence risk. In conclusion, somatic and/or gonosomal mosaicism should be taken into consideration as a genetic factor to explain not only families with unaffected parents despite multiple affected children but also variable expressivity, apparent de novo cases, and even uncharacterized cases of aniridia and related developmental eye disorders, apparently lacking PAX6 mutations.

This issue of ACTA

This issue of ACTA

Computed tomography imaging parameters of 82 Chinese patients with congenital microphthalmia

Objective: To observe computed tomography (CT) imaging parameters of congenitally blind microphthalmia in Chinese patients and to provide clinical reference data for the Chinese population. Methods: It was a retrospective study for a consecutive case series of congenitally blind microphthalmia from July 2011 to July 2013. All of the patients were diagnosed in the Ocular Plastic Department, Tongren Eye Center, Beijing Tongren Hospital. We employed multi-section helical CT imaging with a computer-aided design system to observe and measure the imaging features in 82 Chinese patients (85 eyes). The paired T-test was applied for comparing the axial lengths, transverse diameters, and vertical diameters between the both sides in patients with congenital microphthalmia. The Pearson correlation was used for analyzing the relationship between the axial length and the age of the patients. Results: In the 82 patients, the age ranged from 1 month to 40 years old. Forty-one patients were male and 41 were female. The disease was unilateral in 96.34% of the patients. The orbital cysts were observed in 12.94% of them, and 76.47% of them presented basic structures on the CT scan. The abnormalities of the lens (62.35% of the eyes) and vitreous (82.35% of the eyes) were observed. The mean maximum axial length of the affected eyes (85 eyes) was (14.52±0.56) mm and the mean axial length of the unaffected eyes (79 eyes) was (22.79±0.36) mm. There was significantly statistical difference in the ocular size between the affected and unaffected eyes (t= 1.156, P<0.001) . Conclusions: Congenitally blind microphthalmia is usually complicated with the abnormalities of the lens and vitreous. The ocular size decreases significantly. The results of the present study provide a clinical reference for evaluating congenitally blind microphthalmia.(Chin J Ophthalmol, 2018, 54: 199-204).

New GJA8 variants and phenotypes highlight its critical role in a broad spectrum of eye anomalies.

GJA8 encodes connexin 50 (Cx50), a transmembrane protein involved in the formation of lens gap junctions. GJA8 mutations have been linked to early onset cataracts in humans and animal models. In mice, missense mutations and homozygous Gja8 deletions lead to smaller lenses and microphthalmia in addition to cataract, suggesting that Gja8 may play a role in both lens development and ocular growth. Following screening of GJA8 in a cohort of 426 individuals with severe congenital eye anomalies, primarily anophthalmia, microphthalmia and coloboma, we identified four known [p.(Thr39Arg), p.(Trp45Leu), p.(Asp51Asn), and p.(Gly94Arg)] and two novel [p.(Phe70Leu) and p.(Val97Gly)] likely pathogenic variants in seven families. Five of these co-segregated with cataracts and microphthalmia, whereas the variant p.(Gly94Arg) was identified in an individual with congenital aphakia, sclerocornea, microphthalmia and coloboma. Four missense variants of unknown or unlikely clinical significance were also identified. Furthermore, the screening of GJA8 structural variants in a subgroup of 188 individuals identified heterozygous 1q21 microdeletions in five families with coloboma and other ocular and/or extraocular findings. However, the exact genotype-phenotype correlation of these structural variants remains to be established. Our data expand the spectrum of GJA8 variants and associated phenotypes, confirming the importance of this gene in early eye development.

Evaluating the association of bone morphogenetic protein 4-V152A and SIX homeobox 6-H141N polymorphisms with congenital cataract and microphthalmia in Western Indian population.

Background:Congenital cataract and microphthalmia are highly heterogeneous congenital eye disorders that affect normal vision. Although mutation in several genes has been shown to cause congenital cataract and microphthalmia, genetic studies associating single-nucleotide polymorphisms with these conditions is scarce. Hence, the present study aims to investigate the association of bone morphogenetic protein 4 (BMP4)-V152A (rs17563), and SIX homeobox 6 (SIX6)-H141N (rs33912345) polymorphisms with congenital cataract and microphthalmia in Western Indian cohorts.Materials and Methods:BMP4-V152A and SIX6-H141N were genotyped in 561 participants comprising of 242 congenital cataracts, 52 microphthalmia, and 267 controls using polymerase chain reaction (PCR) and allele specific oligonucleotide (ASO)-PCR method, respectively.Results:The frequency of BMP4- 152A was found to be significantly different between the cases and controls (Odds ratio (OR) 95% confidence interval [CI] = 1.4 [1.03–1.76], P = 0.0275). The frequency of BMP4- 152AA genotype was found to be significantly higher in congenital cataract cases as compared to controls (OR [95% CI] = 2.1 [1.14–3.67], P = 0.0154. The V-N haplotype of BMP4-V152A and SIX6-H141N was found to have a protective effect toward congenital cataract (OR [95% CI] = 0.72 [0.56–0.94], P = 0.0163) and microphthalmia (OR [95% CI] = 0.63 [0.40–1.01, P = 0.0541).Conclusions:The BMP4- 152AA genotype might play role in the causation of congenital cataract, whereas BMP4-SIX6 V-N haplotype might play a protective role toward the development of congenital cataract and microphthalmia.

Association of FOXE3-p.Ala170Ala and PITX3-p.Ile95Ile Polymorphisms with Congenital Cataract and Microphthalmia.

Purpose:To investigate the association of FOXE3-p.Ala170Ala (rs34082359) and PITX3-p.Ile95Ile (rs2281983) polymorphisms with congenital cataract and microphthalmia in a western Indian population.Methods:FOXE3-p.Ala170Ala (c.510C>T) and PITX3-p.Ile95Ile (c.285C>T) polymorphisms were genotyped in 561 subjects consisting of 242 cases with congenital cataract, 52 with microphthalmia, and 267 controls using polymerase chain reaction-restriction fragment length polymorphism. Approximately 10% of samples were randomly sequenced for each single nucleotide polymorphism to confirm the genotypes. The prediction of mRNA secondary structure for polymorphism FOXE3-p.Ala170Ala and PITX3-p.Ile95Ile was performed.Results:A significantly high frequency of T allele and a borderline significance in the frequency of TT genotype of FOXE3-p.Ala170Ala was observed in microphthalmia cases, as compared to controls [T allele: OR: [CI] = 1.8 [1.15-2.72], P = 0.0115; TT: OR [CI] = 2.9 [1.14-7.16], P = 0.0291). The frequency of CC genotype was significantly low in microphthalmia cases when compared to controls (CC: OR [CI] = 0.5 [0.24-0.86, P = 0.0150). There was no significant difference in the allele and genotype frequencies of PITX3-p.Ile95Ile between cases and controls. A slight free energy change was observed in the secondary structure of mRNA between the FOXE3-p.Ala170Ala C-allele (-917.60 kcal/mol) and T-allele (-916.80 kcal/mol) and between PITX3-p.Ile95Ile C-allele (-659.80 kcal/mol) and T-allele (-658.40 kcal/mol).Conclusion:The present findings indicate that FOXE3-p.Ala170Ala ‘T’ allele and ‘TT’ genotype could be predisposing factors for microphthalmia while ‘CC’ genotype might play a protective role against it. A reduction in the free energy change associated with FOXE3-p.Ala170Ala ‘T’ allele could further contribute towards disease risk.

CRISPR/Cas9-Mediated Mutation of αA-Crystallin Gene Induces Congenital Cataracts in Rabbits.

The present study aimed to investigate the role of the αA-crystallin gene in inducing congenital cataracts in rabbits and to construct a novel animal model for characterization and pathologic analysis of congenital cataracts for future research. We generated αA-crystallin gene knockout rabbits with congenital cataracts by coinjection of Cas9 mRNA and sgRNA into zygotes. Cataract phenotypes were investigated in a repeated study of 19 F0-generation and 11 F1-generation rabbits with αA-crystallin gene mutations. Heritability was analyzed by PCR, sequencing, slim lamp, hematoxylin eosin staining, immunohistochemistry, and Western blot. We found αA-crystallin gene mutations in all 19 F0-generation pups (100%) with indel mutations in the αA-crystallin gene ranging from 3 to 52 bp. Off-target assay revealed that none of the potential off-target sites exhibited mutations, demonstrating that off-target mutagenesis was not induced by cytoplasmic microinjection of in vitro-transcribed Cas9 mRNA. Slim lamp assay revealed that 15 of 19 live pups (78.9%) exhibited typical phenotypes, including congenital cataracts, microphthalmia, obscurity, and early atrophy of the lens, and failed differentiation of lens fibers. Histologic hematoxylin and eosin staining showed that αA-crystallin gene knockout rabbits exhibited smaller lenses. Production of the αA-crystallin protein was determined to be dramatically reduced in αA-crystallin gene knockout rabbits. We induced αA-crystallin gene mutations and phenotypes in F1-generation rabbits. Our data suggest that CRISPR/Cas9-mediated mutation of the αA-crystallin gene in rabbits recapitulates phenotypes of congenital cataracts, microphthalmia, obscurity, and early atrophy of the lens, and failed differentiation of lens fibers. These findings suggest the possibility of a new animal model of congenital cataracts, which should be used to further investigate the association between mutations in αA-crystallin gene and congenital cataracts in humans.

Diagnosis and treatment of herpes simplex 1 virus infection in pregnancy.

A nulliparous woman presented at 21 weeks' gestation with a 72-h history of a rash on her left arm. Initially isolated to the forearm, it had quickly spread, becoming multiple itchy fluid-filled blisters. Blood tests showed mild neutrophilia and raised CRP. Skin swabs demonstrated the presence of herpes simplex virus type 1 (HSV1) DNA. There was no history of previous HSV1 exposure. There is scant literature on uncomplicated cutaneous HSV1 since the majority is oral/genital. The incidence of transmission varies and is dependent on site of infection and immunological status. Type-specific serological testing is recommended to identify a primary first episode infection due to the 30-60% vertical transmission rate. Infection is associated with morbidity and mortality for both mother and fetus including maternal encephalitis, acute retinal necrosis, pneumonia and hepatitis. Neonatal disease can be congenital (cutaneous lesions, microcephaly, hydranencephaly, intracranial calcifications, chorioretinitis, microphthalmia and optic nerve atrophy) or acquired (skin, eyes and mouth disease or central nervous system disease or disseminated disease). Prophylactic aciclovir reduces the number of women with active genital lesions at the time of delivery. If primary infection occurs outside of the first trimester and active genital lesions are present, then vaginal delivery should be avoided. If infection has occurred in the first trimester, vaginal birth can be attempted even in the presence of active lesions. There is no available guidance on prophylactic treatment of non-genital HSV1 in pregnancy.

The influence of the central corneal thickness on the characteristics of the ophthalmic tone in the children presenting with congenital microphthalmia

Objective. To evaluate the influence of the central corneal thickness on the characteristics of the ophthalmic tone in the children presenting with congenital microphthalmia of different severity and to describe its clinical significance for diagnostics of glaucoma and prescription of hypotensive therapy. Materials and methods. A total of 40 children (80 eyes) at the age from 5 to 17 years presenting with congenital microphthalmia of different severity were available for the examination. The children remained under the examination during 10 and more years. They were divided into three groups in terms of severity of microphthalmia. Thirteen children were admitted with the diagnosis of “glaucoma”. The comprehensive ophthalmological examination was supplemented by the measurement of the central corneal thickness. Results. The analysis of the results of the examination gave evidence of the increased central corneal thickness in all the patients with grade 1 - III microphthalmia included in the study. The measurement of the central corneal thickness is important for the establishment of the diagnosis of “glaucoma” because it exerts the direct influence on the characteristics of the ophthalmic tone in the children presenting with congenital microphthalmia. Conclusion. The present study has demonstrated the fairly well apparent relationship between the central corneal thickness, the severity of microphthalmia and intraocular pressure (IOP) in the children presenting with congenital microphthalmia. The higher the severity of microphthalmia the greater the central corneal thickness and the intraocular pressure.

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

AimsTo 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.MethodsUsing English National Hospital...

Congenital Microphthalmia, Anophthalmia and Coloboma among Live Births in Denmark

ABSTRACTPurpose: 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.

ASPP2 deficiency causes features of 1q41q42 microdeletion syndrome.

Chromosomal abnormalities are implicated in a substantial number of human developmental syndromes, but for many such disorders little is known about the causative genes. The recently described 1q41q42 microdeletion syndrome is characterized by characteristic dysmorphic features, intellectual disability and brain morphological abnormalities, but the precise genetic basis for these abnormalities remains unknown. Here, our detailed analysis of the genetic abnormalities of 1q41q42 microdeletion cases identified TP53BP2, which encodes apoptosis-stimulating protein of p53 2 (ASPP2), as a candidate gene for brain abnormalities. Consistent with this, Trp53bp2-deficient mice show dilation of lateral ventricles resembling the phenotype of 1q41q42 microdeletion patients. Trp53bp2 deficiency causes 100% neonatal lethality in the C57BL/6 background associated with a high incidence of neural tube defects and a range of developmental abnormalities such as congenital heart defects, coloboma, microphthalmia, urogenital and craniofacial abnormalities. Interestingly, abnormalities show a high degree of overlap with 1q41q42 microdeletion-associated abnormalities. These findings identify TP53BP2 as a strong candidate causative gene for central nervous system (CNS) defects in 1q41q42 microdeletion syndrome, and open new avenues for investigation of the mechanisms underlying CNS abnormalities.

Screening and early treatment on ophthalmopathy of premature infant

Objective To investigate the clinical significance of screening and early treatment on the eye disease of premature infant. Methods The fundus examination results with children wide-area digital fundus imaging system and photographs of 2852 eyes of 1426 premature infants from July 2013 to July 2015 in our hospital were taken. The data were analyzed and the early treatment was given. Results Among the fundus of 2852 eyes of premature infants, there were 182 eyes of retinopathy of prematurity, 18 eyes of congenital cataract, 5 eyes of familial exudative vitreoretinopathy, 4 eyes of persistent hyperplastic primary vitreous, 3 eyes of congenital choroidal coloboma, 2 eyes of congenital optic disc dysplasia, and 2 eye of congenital microphthalmia. There were 216 (7.57%) infants suffering from ophthalmopathy in total. In the 182 eyes of retinopathy of prematurity, 37 eyes received retinal laser photocoagulation, 16 eyes received intravitreal injection, 15 eyes received intravitreal injection combined with retinal laser photocoagulation, 5 eyes received vitrectomy combined with retinal laser photocoagulation, and some infants gave up the treatment. Conclusion Screening and early treatment on oculopathy of premature infant improve the vision and survival quality. Key words: Ophthalmopathy, prematurity; Screening; Children wide-area digital fundus imaging system; Treatment, early; Vitrectomy

RNA-binding proteins in eye development and disease: implication of conserved RNA granule components.

The molecular biology of metazoan eye development is an area of intense investigation. These efforts have led to the surprising recognition that although insect and vertebrate eyes have dramatically different structures, the orthologs or family members of several conserved transcription and signaling regulators such as Pax6, Six3, Prox1, and Bmp4 are commonly required for their development. In contrast, our understanding of posttranscriptional regulation in eye development and disease, particularly regarding the function of RNA-binding proteins (RBPs), is limited. We examine the present knowledge of RBPs in eye development in the insect model Drosophila as well as several vertebrate models such as fish, frog, chicken, and mouse. Interestingly, of the 42 RBPs that have been investigated for their expression or function in vertebrate eye development, 24 (~60%) are recognized in eukaryotic cells as components of RNA granules such as processing bodies, stress granules, or other specialized ribonucleoprotein (RNP) complexes. We discuss the distinct developmental and cellular events that may necessitate potential RBP/RNA granule-associated RNA regulon models to facilitate posttranscriptional control of gene expression in eye morphogenesis. In support of these hypotheses, three RBPs and RNP/RNA granule components Tdrd7, Caprin2, and Stau2 are linked to ocular developmental defects such as congenital cataract, Peters anomaly, and microphthalmia in human patients or animal models. We conclude by discussing the utility of interdisciplinary approaches such as the bioinformatics tool iSyTE (integrated Systems Tool for Eye gene discovery) to prioritize RBPs for deriving posttranscriptional regulatory networks in eye development and disease. WIREs RNA 2016, 7:527-557. doi: 10.1002/wrna.1355 For further resources related to this article, please visit the WIREs website.

Digital evaluation of orbital development after self-inflating hydrogel expansion in Chinese children with congenital microphthalmia

Assessment of the growth of bony orbit in children with blind microphthalmia is essential to its management. In this study, variables were measured to evaluate the development of the bony microphthalmic orbits after treatment with self-inflating hydrogel expanders. This is a retrospective study with an interventional case series. Thirteen pediatric patients with congenital unilateral blind microphthalmia who had undergone tissue expansion with hydrogel expanders and computed tomography (CT) scanning before and after operation were included in the study. The orbital volume, depth, width, and height and retardation of the orbital rims before and after treatment were measured and analyzed using the iPlan Cranial Software. The mean age at the time of first implantation was 44 months (range, 3-113 months). Of the 13 patients, eleven received orbital expansion, while two received socket expansion. In the orbital expansion group, the mean microphthalmic/contralateral ratio (MCR) of orbital volume was 79.3% before surgery, which increased to 89.8% 3 years post operation (P<0.001). The mean MCR of orbital width also increased from 88.8% to 91.8% (P=0.003). The development of inferior and lateral rims showed the greatest retardation before treatment; the retardation of these two rims decreased significantly at the final measurement (P=0.004). It is also noted that the development of the microphthalmic orbits was limited in the two patients who only underwent socket expansion. The affected orbit enlarged in children with congenital blind microphthalmia following treatment with hydrogel expanders; this suggested that microphthalmia-associated orbital asymmetry can be treated with self-inflating hydrogel expanders.

Clinical and anatomical features of congenital microphthalmia and anophthalmia in children and conservative methods of rehabilitation

To develop a comprehensive classification system of distinctive clinical and anatomical features of congenital microphthalmia and anophthalmia in children and to specify indications, contraindications, and optimal timing of the primary and subsequent prosthetic treatment. A total of 70 patients with congenital micro- or anophthalmia aged from 1 month to 12 years were examined. Besides the routine ophthalmic examination, all patients underwent eye and orbit ultrasound (axial length measurement and B-scan), computed tomography of the orbits and skull, and immunological tests for infectious diseases (enzyme-linked immunosorbent assays). Basing on the examination we have determined the common types of congenital micro- and anophthalmia in children. We have also developed a stepwise prosthetic treatment aimed at better cosmetic rehabilitation. Indications and contraindications for the use of ocular prostheses in children with congenital micro- and anophthalmia have been identified. The proposed method of stepwise prosthetics is the principal option for conservative rehabilitation of children with congenital micro- or anophthalmia.

Computational analyses of the length and compositional variations of the FNBP4 gene across 10 different species

Formin binding protein 4 (FNBP4) interacts with formins and other proteins via its WW domains. Previously, we reported the structural and phylogenetic clustering of FNBP4 across a wide range of organisms from different taxonomic groups along with characterizing its plant variant (Arabidopsis thaliana F4JC80). Recently, the FNBP4 gene is reported to be associated with a congenital disorder Microphthalmia with Limb Anomalies. Except these reports, FNBP4 is mostly uncharacterized, especially the FNBP4 gene. In this context, we have attempted to characterize the FNBP4 gene in terms of its length and compositional variations across 10 different organisms from different taxonomic groups. Our findings highlight that the length of the FNBP4 gene varies greatly among different species. Introns, UTRs and the entire gene were AT rich while CDS and mRNAs were GC rich. The RSCU values were also different for the different organisms indicating a possible impact on translational efficiency of this protein. Comparative analyses highlight gene element and base proportions related characteristics specific to highly expression regulated genes like FNBP4.