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Middle East African Journal of... Apr 2011Childhood blindness has an adverse effect on growth, development, social, and economic opportunities. Severe visual impairment (SVI) and blindness in infants must be...
Childhood blindness has an adverse effect on growth, development, social, and economic opportunities. Severe visual impairment (SVI) and blindness in infants must be detected as early as possible to initiate immediate treatment to prevent deep amblyopia. Although difficult, measurement of visual acuity of an infant is possible. The causes of SVI and blindness may be prenatal, perinatal, and postnatal. Congenital anomalies such as anophthalmos, microphthalmos, coloboma, congenital cataract, infantile glaucoma, and neuro-ophthalmic lesions are causes of impairment present at birth. Ophthalmia neonatorum, retinopathy of prematurity, and cortical visual impairment are acquired during the perinatal period. Leukocoria or white pupillary reflex can be cause by congenital cataract, persistent hyperplastic primary vitreous, or retinoblastoma. While few medical or surgical options are available for congenital anomalies or neuro-ophthalmic disorders, many affected infants can still benefit from low vision aids and rehabilitation. Ideally, surgery for congenital cataracts should occur within the first 4 months of life. Anterior vitrectomy and primary posterior capsulotomy are required, followed by aphakic glasses with secondary intraocular lens implantation at a later date. The treatment of infantile glaucoma is surgery followed by anti-glaucoma medication. Retinopathy of prematurity is a proliferation of the retinal vasculature in response to relative hypoxia in a premature infant. Screening in the first few weeks of life can prevent blindness. Retinoblastoma can be debulked with chemotherapy; however, enucleation may still be required. Neonatologists, pediatricians, traditional birth attendants, nurses, and ophthalmologists should be sensitive to a parent's complaints of poor vision in an infant and ensure adequate follow-up to determine the cause. If required, evaluation under anesthesia should be performed, which includes funduscopy, refraction, corneal diameter measurement, and measurement of intraocular pressure.
PubMed: 21731320
DOI: 10.4103/0974-9233.80698 -
Clinical Genetics Nov 2020Next-generation sequencing strategies have resulted in mutation detection rates of 21% to 61% in small cohorts of patients with microphthalmia, anophthalmia and coloboma...
Next-generation sequencing strategies have resulted in mutation detection rates of 21% to 61% in small cohorts of patients with microphthalmia, anophthalmia and coloboma (MAC), but despite progress in identifying novel causative genes, many patients remain without a genetic diagnosis. We studied a cohort of 19 patients with MAC who were ascertained from a population with high rates of consanguinity. Using single nucleotide polymorphism (SNP) arrays and whole exome sequencing (WES), we identified one pathogenic variant in TENM3 in a patient with cataracts in addition to MAC. We also detected novel variants of unknown significance in genes that have previously been associated with MAC, including KIF26B, MICU1 and CDON, and identified variants in candidate genes for MAC from the Wnt signaling pathway, comprising LRP6, WNT2B and IQGAP1, but our findings do not prove causality. Plausible variants were not found for many of the cases, indicating that our current understanding of the pathogenesis of MAC, a highly heterogeneous group of ocular defects, remains incomplete.
Topics: Anophthalmos; Calcium-Binding Proteins; Cation Transport Proteins; Cell Adhesion Molecules; Coloboma; Consanguinity; Exome; Female; High-Throughput Nucleotide Sequencing; Humans; Kinesins; Male; Membrane Proteins; Microphthalmos; Mitochondrial Membrane Transport Proteins; Mutation; Nerve Tissue Proteins; Polymorphism, Single Nucleotide; Tumor Suppressor Proteins; Exome Sequencing
PubMed: 32799327
DOI: 10.1111/cge.13830 -
Case Reports in Surgery 2013To be human is great; to look human is wonderful! It is nature's greatest gift! Mother nature's womb is the safest place on earth for any life, but the calamity strikes...
To be human is great; to look human is wonderful! It is nature's greatest gift! Mother nature's womb is the safest place on earth for any life, but the calamity strikes and no one knows how Hence, Treasure your exceptions!, since nature seems nowhere accustomed more openly to display, its secret mysteries than in cases where it shows traces of its workings apart from the beaten path. A dismorphological pattern of congenital oro-craniofacial and limb defects which is a rare form of amniotic rupture sequence required persistent coordinated efforts of multiple disciplines and had manifested as bizarre orofacial clefting, cat eye syndrome with an ectopic eye, and aberrant tissue band lesions on limb. The challenge was to meet the child's clamour for functional demands on premature exposure to open world and was overcome through a phased treatment implementation. Anophthalmos resulting from multiple ophthalmic surgeries for aberrant ectopic left eye and cat eye syndrome of right eye required a staged sequential preemptive planning for a successful outcome. Every phase of fabrication of orbital prosthesis comes with an impending challenge. Thus, a well-defined technique eliminating the common errors and creating a natural looking prosthesis, in the face of limitations, is imperative.
PubMed: 23762737
DOI: 10.1155/2013/809479 -
Molecular Genetics & Genomic Medicine Sep 2020Syndromic microphthalmia-9 (MCOPS9) is a rare autosomal recessive disorder caused by mutations in STRA6, an important regulator of vitamin A and retinoic acid...
BACKGROUND
Syndromic microphthalmia-9 (MCOPS9) is a rare autosomal recessive disorder caused by mutations in STRA6, an important regulator of vitamin A and retinoic acid metabolism. This disorder is characterized by bilateral clinical anophthalmia, pulmonary hypoplasia/aplasia, cardiac malformations, and diaphragmatic defects. The clinical characteristics of this disorder have not been fully determined because of the rarity of clinical reports.
METHODS
A comprehensive genotyping examination including copy number variation sequencing (CNV-Seq) and whole-exome sequencing (WES) was applied to a fetus of Han Chinese with bilateral anophthalmia, bilateral pulmonary agenesis, interrupted aortic arch type A, and left ventricular non-compaction (LVNC).
RESULTS
No aneuploidy or pathogenic CNV were identified by CNV-seq. WES analysis revealed a previously reported homozygous splice site (NM_022369.4:c.113+3_113+4del) in the STRA6 gene. This variant was confirmed by Sanger sequencing. The diagnosis of MCOPS9 was confirmed given the identification of the STRA6 mutation and the association of bilateral anophthalmia, pulmonary agenesis, and cardiac malformations.
CONCLUSION
This case adds to the phenotypic spectrum of MCOPS9, supporting the association with LVNC, and the presence of interruption of aortic arch further demonstrates the variability of the cardiac malformations.
Topics: Adult; Anophthalmos; Female; Fetal Diseases; Humans; Isolated Noncompaction of the Ventricular Myocardium; Lung Diseases; Membrane Proteins; Microphthalmos; Phenotype; Pregnancy; Syndrome
PubMed: 32597569
DOI: 10.1002/mgg3.1377 -
Contact Lens & Anterior Eye : the... Jun 2024To assess which signs and eye prosthesis care habits are related to subjective discomfort in patients with dry anophthalmic socket syndrome (DASS), using standardized...
PURPOSE
To assess which signs and eye prosthesis care habits are related to subjective discomfort in patients with dry anophthalmic socket syndrome (DASS), using standardized tools from daily practice.
METHODS
62 anophthalmic sockets were compared with their healthy fellow eye using the Standard Patient Evaluation of Eye Dryness (SPEED) score. The correlations between SPEED questionnaire and the prosthesis care, discharge characteristics score, conjunctival inflammation score, meibomian gland dysfunction (MGD) scores and Schirmer I test were studied.
RESULT
The anophthalmic sockets group achieved a higher SPEED test score (p < 0.01), discharge score (p < 0.01), conjunctival inflammation score (p < 0.01), MGD scores (p < 0.01) and lower Schirmer I test (p < 0.01) compared with their fellow, healthy eye. Patients with a prosthesis replacement of one year or less, those with a current fit time of one year or less and those with a cleaning frequency above one month reported better SPEED, (p < 0.01), conjunctiva inflammation (p < 0.01) and MGD scores (p < 0.01).
CONCLUSION
Most anophthalmic patients suffer mild to severe DASS, which seems related to discharge, conjunctival inflammation and MGD. Moreover, certain practices related to the care of the prosthesis such as replacing with a frequency lower than yearly, current fitting time inferior to one year and a removing and cleaning regime above one month, were related to a lower discomfort sensation, conjunctival inflammation and MGD. Clinicians should consider the DASS when facing patients with anophthalmic socket and discomfort symptoms.
Topics: Humans; Female; Male; Eye, Artificial; Middle Aged; Dry Eye Syndromes; Adult; Anophthalmos; Aged; Surveys and Questionnaires; Orbital Implants; Aged, 80 and over; Young Adult
PubMed: 38521700
DOI: 10.1016/j.clae.2024.102149 -
BMC Oral Health Dec 2023This study aims to assess the influence of using 3D-printed acrylic resin versus conventional Poly-methyl methacrylate (PMMA) for fabricating ocular prostheses on the... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
This study aims to assess the influence of using 3D-printed acrylic resin versus conventional Poly-methyl methacrylate (PMMA) for fabricating ocular prostheses on the biofilm and microbial flora of anophthalmic socket.
METHODS
A randomized controlled trial was designed as a parallel group study. Participants were allocated randomly into two groups: the control group, which received conventionally fabricated ocular prostheses (CG, n = 11), and the test group, which received digitally 3D-printed ocular prostheses (DG, n = 11). Microbiological analysis was conducted before prosthesis insertion and three months after using the ocular prosthesis. Swab samples were inoculated on blood agar, MacConkey's agar, and Sabouraud's dextrose agar (SDA) for isolating Gram-positive, Gram-negative, and fungal organisms, respectively. Subsequently, the plates were incubated at 37 degrees Celsius for 48 h. Additionally, a validated questionnaire was used for subjective clinical evaluation, including parameters such as comfort level, socket discharge, lacrimation, and frequency of lubrication for each ocular prosthesis patient in both groups.
RESULTS
Test group (DG, n = 11) exhibited a positive, though statistically insignificant, difference (p > 0.001) in microbial growth when compared to the control group (CG, n = 11). A statistically significant difference was observed in comfort levels between the two groups, with more comfort level within group II (test group) patients. While parameters such as discharge amount, discharge location, lacrimation and lubrication frequency displayed statistically insignificant differences between the two groups, all parameters showed improved results after three months of prosthesis use.
CONCLUSIONS
The choice of ocular prosthesis fabrication technique did not yield a statistically significant difference in anophthalmic flora. However, the 3D-printed acrylic resin, as an artificial eye material, displayed potential advantages in reducing the colonization of opportunistic pathogens. All subjective clinical evaluation parameters exhibited enhanced outcomes after three months of prosthesis use, emphasizing the need for an adaptation period during which patients complains are alleviated. In comparison with PMMA, 3D-printed acrylic resin showcased a certain degree of anti-colonization ability against pathogenic bacteria, along with a significant level of patient comfort, suggesting its potential as a promising material for ocular prostheses.
TRIAL REGISTRATION
This parallel double-blinded RCT has been registered at ClinicalTrials.gov with identification number: NCT05584865, 18/10/2022.
Topics: Humans; Eye, Artificial; Polymethyl Methacrylate; Agar; Anophthalmos; Acrylic Resins; Printing, Three-Dimensional
PubMed: 38110937
DOI: 10.1186/s12903-023-03746-w -
Clinical Genetics Nov 2015Anophthalmia/microphthalmia (A/M) is a genetically heterogeneous birth defect for which the etiology is unknown in more than 50% of patients. We used exome sequencing...
Anophthalmia/microphthalmia (A/M) is a genetically heterogeneous birth defect for which the etiology is unknown in more than 50% of patients. We used exome sequencing with the ACE Exome(TM) (Personalis, Inc; 18 cases) and UCSF Genomics Core (21 cases) to sequence 28 patients with A/M and four patients with varied developmental eye defects. In the 28 patients with A/M, we identified de novo mutations in three patients (OTX2, p.(Gln91His), RARB, p.Arg387Cys and GDF6, p.Ala249Glu) and inherited mutations in STRA6 in two patients. In patients with developmental eye defects, a female with cataracts and cardiomyopathy had a de novo COL4A1 mutation, p.(Gly773Arg), expanding the phenotype associated with COL4A1 to include cardiomyopathy. A male with a chorioretinal defect, microcephaly, seizures and sensorineural deafness had two PNPT1 mutations, p.(Ala507Ser) and c.401-1G>A, and we describe eye defects associated with this gene for the first time. Exome sequencing was efficient for identifying mutations in pathogenic genes for which there is no clinical testing available and for identifying cases that expand phenotypic spectra, such as the PNPT1 and COL4A1-associated disorders described here.
Topics: Anophthalmos; Collagen Type IV; DNA Mutational Analysis; Exome; Exoribonucleases; Eye Abnormalities; Female; Humans; Infant; Male; Membrane Proteins; Microphthalmos; Mutation; Otx Transcription Factors; Receptors, Retinoic Acid
PubMed: 25457163
DOI: 10.1111/cge.12543 -
Frontiers in Cellular and Infection... 2023To explore the changes of bacterial flora in anophthalmic patients wearing ocular prosthesis (OP) and the microbiome diversity in conditions of different OP materials.
PURPOSE
To explore the changes of bacterial flora in anophthalmic patients wearing ocular prosthesis (OP) and the microbiome diversity in conditions of different OP materials.
METHODS
A cross-sectional clinical study was conducted, involving 19 OP patients and 23 healthy subjects. Samples were collected from the upper, lower palpebral, caruncle, and fornix conjunctiva. 16S rRNA sequencing was applied to identify the bacterial flora in the samples. The eye comfort of each OP patient was determined by a questionnaire. In addition, demographics information of each participant was also collected.
RESULTS
The diversity and richness of ocular flora in OP patients were significantly higher than that in healthy subjects. The results of flora species analysis also indicated that in OP patients, pathogenic microorganisms such as and increased significantly, while the resident flora of and decreased significantly. Within the self-comparison of OP patients, compared with Polymethyl Methacrylate (PMMA), prosthetic material of glass will lead to the increased colonization of opportunistic pathogens such as and , while gender and age have no significant impact on ocular flora.
CONCLUSIONS
The ocular flora of OP patients was significantly different from that of healthy people. Abundant colonization of pathogenic microorganisms may have an important potential relationship with eye discomfort and eye diseases of OP patients. PMMA, as an artificial eye material, demonstrated potential advantages in reducing the colonization of opportunistic pathogens.
Topics: Humans; Eye, Artificial; Lacrimal Apparatus; Polymethyl Methacrylate; Cross-Sectional Studies; RNA, Ribosomal, 16S; Anophthalmos; Bacteria; Microbiota
PubMed: 36960044
DOI: 10.3389/fcimb.2023.1117673 -
European Journal of Human Genetics :... Apr 2016Anophthalmia and microphthalmia (A/M) are developmental ocular malformations defined as the complete absence or reduction in size of the eye. A/M is a highly...
Anophthalmia and microphthalmia (A/M) are developmental ocular malformations defined as the complete absence or reduction in size of the eye. A/M is a highly heterogeneous disorder with SOX2 and FOXE3 playing major roles in dominant and recessive pedigrees, respectively; however, the majority of cases lack a genetic etiology. We analyzed 28 probands affected with A/M spectrum (without mutations in SOX2/FOXE3) by whole-exome sequencing. Analysis of 83 known A/M factors identified pathogenic/likely pathogenic variants in PAX6, OTX2 and NDP in three patients. A novel heterozygous likely pathogenic variant in PAX6, c.767T>C, p.(Val256Ala), was identified in two brothers with bilateral microphthalmia, coloboma, primary aphakia, iris hypoplasia, sclerocornea and congenital glaucoma; the unaffected mother appears to be a mosaic carrier. While A/M has been reported as a rare feature, this is the first report of congenital primary aphakia in association with PAX6 and the identified allele represents the first variant in the PAX6 homeodomain to be associated with A/M. A novel pathogenic variant in OTX2, c.651delC, p.(Thr218Hisfs*76), in a patient with syndromic bilateral anophthalmia and a hemizygous pathogenic variant in NDP, c.293 C>T, p.(Pro98Leu), in two brothers with isolated bilateral microphthalmia and sclerocornea were also identified. Pathogenic/likely pathogenic variants were not discovered in the 25 remaining A/M cases. This study underscores the utility of whole-exome sequencing for identification of causative mutations in highly variable ocular phenotypes as well as the extreme genetic heterogeneity of A/M conditions.
Topics: Adolescent; Adult; Anophthalmos; Child; Coloboma; Exome; Eye Proteins; Female; Heterozygote; Humans; Male; Microphthalmos; Mutation; Nerve Tissue Proteins; Otx Transcription Factors; PAX6 Transcription Factor
PubMed: 26130484
DOI: 10.1038/ejhg.2015.155 -
The Journal of Clinical Endocrinology... Jul 2019The transcription factor RAX is a paired-type homeoprotein that plays a critical role in eye and forebrain development of vertebrate species. RAX knockout mice have...
CONTEXT
The transcription factor RAX is a paired-type homeoprotein that plays a critical role in eye and forebrain development of vertebrate species. RAX knockout mice have anophthalmia, cleft palate, and an abnormal hypothalamus and display perinatal lethality. In humans, homozygous or compound heterozygous RAX mutations have been reported to cause bilateral microphthalmia or anophthalmia without consistent associated features. Congenital hypopituitarism can be associated with various eye or craniofacial anomalies; however, the co-occurrence of congenital hypopituitarism, anophthalmia, cleft palate, and diabetes insipidus has been very rare.
RESULTS
We report the case of a child with anophthalmia, congenital hypopituitarism, diabetes insipidus, and bilateral cleft lip and palate who had a homozygous frameshift truncating mutation c.266delC (p.Pro89Argfs*114) in exon 1 of the RAX gene. Rax knockout mice show loss of ventral forebrain structures, pituitary, and basosphenoid bone and palate and a misplaced anterior pituitary gland along the roof of the oral cavity.
CONCLUSIONS
Our patient's phenotype was more severe than that reported in other patients. Although most of the previously reported patients with RAX mutations showed either a missense or some less severe mutation in at least one of their RAX alleles, our patient was homozygous for truncating mutations that would yield a severe, null protein phenotype. The severity of the genetic defect, the precise match between the knockout mouse and the patient's endocrine phenotypes, and the prominent roles of RAX in eye and pituitary development and diencephalic patterning suggest that the RAX null mutations could fully account for the observed phenotype.
Topics: Animals; Anophthalmos; Antidiuretic Agents; Cleft Lip; Cleft Palate; Deamino Arginine Vasopressin; Diabetes Insipidus; Eye Proteins; Frameshift Mutation; Homeodomain Proteins; Hormone Replacement Therapy; Human Growth Hormone; Humans; Hydrocortisone; Hypopituitarism; Infant, Newborn; Magnetic Resonance Imaging; Male; Melatonin; Mice, Knockout; Pituitary Gland; Thyroxine; Transcription Factors
PubMed: 30811539
DOI: 10.1210/jc.2018-02316