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Gaceta Medica de Mexico 2017Congenital eye malformations are the second most common cause of childhood blindness and are originated by disruption of the normal process of eye development during... (Review)
Review
Congenital eye malformations are the second most common cause of childhood blindness and are originated by disruption of the normal process of eye development during embryonic stage. Their etiology is variable, although monogenic causes are of great importance as they have a high risk of familial recurrence. Included among the most severe congenital eye abnormalities are microphthalmia, defined by an abnormally small eye, and anophthalmia, characterized by congenital absence of ocular structures. The currrent knowledge of the genes involved in human microphthalmia and anophthalmia in humans is revised in this work.
Topics: Anophthalmos; Child; Eye Abnormalities; Gene Expression Regulation, Developmental; Humans; Microphthalmos
PubMed: 29414965
DOI: 10.24875/GMM.17002604 -
BMC Biology Feb 2023Microphthalmia, anophthalmia, and coloboma (MAC) spectrum disease encompasses a group of eye malformations which play a role in childhood visual impairment. Although the...
BACKGROUND
Microphthalmia, anophthalmia, and coloboma (MAC) spectrum disease encompasses a group of eye malformations which play a role in childhood visual impairment. Although the predominant cause of eye malformations is known to be heritable in nature, with 80% of cases displaying loss-of-function mutations in the ocular developmental genes OTX2 or SOX2, the genetic abnormalities underlying the remaining cases of MAC are incompletely understood. This study intended to identify the novel genes and pathways required for early eye development. Additionally, pathways involved in eye formation during embryogenesis are also incompletely understood. This study aims to identify the novel genes and pathways required for early eye development through systematic forward screening of the mammalian genome.
RESULTS
Query of the International Mouse Phenotyping Consortium (IMPC) database (data release 17.0, August 01, 2022) identified 74 unique knockout lines (genes) with genetically associated eye defects in mouse embryos. The vast majority of eye abnormalities were small or absent eyes, findings most relevant to MAC spectrum disease in humans. A literature search showed that 27 of the 74 lines had previously published knockout mouse models, of which only 15 had ocular defects identified in the original publications. These 12 previously published gene knockouts with no reported ocular abnormalities and the 47 unpublished knockouts with ocular abnormalities identified by the IMPC represent 59 genes not previously associated with early eye development in mice. Of these 59, we identified 19 genes with a reported human eye phenotype. Overall, mining of the IMPC data yielded 40 previously unimplicated genes linked to mammalian eye development. Bioinformatic analysis showed that several of the IMPC genes colocalized to several protein anabolic and pluripotency pathways in early eye development. Of note, our analysis suggests that the serine-glycine pathway producing glycine, a mitochondrial one-carbon donator to folate one-carbon metabolism (FOCM), is essential for eye formation.
CONCLUSIONS
Using genome-wide phenotype screening of single-gene knockout mouse lines, STRING analysis, and bioinformatic methods, this study identified genes heretofore unassociated with MAC phenotypes providing models to research novel molecular and cellular mechanisms involved in eye development. These findings have the potential to hasten the diagnosis and treatment of this congenital blinding disease.
Topics: Humans; Mice; Animals; Eye Abnormalities; Anophthalmos; Microphthalmos; Coloboma; Mice, Knockout; Embryonic Development; Phenotype; Eye; Mammals
PubMed: 36737727
DOI: 10.1186/s12915-022-01475-0 -
Ophthalmic Plastic and Reconstructive... 2014To review and summarize current management of anophthalmic syndrome-enophthalmos, superior sulcus syndrome, lower eyelid laxity, and upper eyelid ptosis. (Review)
Review
PURPOSE
To review and summarize current management of anophthalmic syndrome-enophthalmos, superior sulcus syndrome, lower eyelid laxity, and upper eyelid ptosis.
METHODS
The authors performed a PubMed search of all articles published in English on the management of anophthalmic socket syndrome.
RESULTS
A review of 37 articles demonstrated that anophthalmic syndrome occurs in a significant proportion of this patient population. Primary prevention through careful selection of primary orbital implant is ideal. Residual mild deficits can then be corrected through prosthesis modification. When modification of the prosthesis is no longer sufficient, specifically targeted procedures become necessary.
CONCLUSIONS
Ocularists and oculoplastic surgeons should work together closely to treat anophthalmic syndrome. Future studies should establish uniform measurement criteria as the next step in validating the benefit and limitation of each technique.
Topics: Anophthalmos; Blepharoptosis; Enophthalmos; Humans; Muscle Weakness; Oculomotor Muscles; Orbital Implants
PubMed: 24988502
DOI: 10.1097/IOP.0000000000000217 -
Journal of AAPOS : the Official... Apr 2019To study the effects of an individualized treatment approach to children with congenital microphthalmos and anophthalmos.
PURPOSE
To study the effects of an individualized treatment approach to children with congenital microphthalmos and anophthalmos.
METHODS
Patients with congenital microphthalmos or anopthalmos with orbital cysts who were referred to Beijing Tongren Hospital between July 2009 and July 2017 were included in this retrospective case series study. For patients ≤6 years of age, the cyst was retained to promote orbital development unless a prosthesis could not be fitted at all or disproportionate orbital growth was detected. Hydrogel orbit expanders were implanted initially if orbital volume was poor. For patients >6 years of age, the cyst was removed if it caused cosmetic problems or unsatisfactory prosthesis fitting. Eyelid procedures were performed after puberty to improve appearance.
RESULTS
The study included 26 orbits of 24 patients. Of the 14 patients ≤6 years, 3 underwent cyst excision, 8 were treated with conformers only, and 3 had hydrogel orbit expander implantation initially. Of the 10 patients >6 years, 1 had the cyst removed, 5 had eyelid surgeries without removing the cyst, 3 wore an artificial eye without any surgery, and 1 used no prosthesis. During the follow-up period (range, 6 months to 8 years), 23 patients had a good cosmetic outcome and were eventually able to retain an ocular prosthesis; 1 patient could not wear prostheses but refused further treatment. No procedure-related complications were noted.
CONCLUSIONS
The individualized treatment of congenital microphthalmos and anophthalmos with orbital cysts depends on the patient's age at presentation, the growth pattern of the cyst, and the volume of the affected orbit.
Topics: Adolescent; Adult; Anophthalmos; Child; Child, Preschool; Cysts; Eye, Artificial; Female; Humans; Infant; Male; Microphthalmos; Orbital Diseases; Prosthesis Fitting; Retrospective Studies; Tissue Expansion; Tissue Expansion Devices; Treatment Outcome; Young Adult
PubMed: 30928365
DOI: 10.1016/j.jaapos.2018.10.015 -
Ophthalmic Genetics Apr 2022To report ocular outcome, somatic co-morbidities, genetics, and quality of life in children born with anophthalmia (A) or microphthalmia (M). (Review)
Review
PURPOSE
To report ocular outcome, somatic co-morbidities, genetics, and quality of life in children born with anophthalmia (A) or microphthalmia (M).
METHODS
Thirty-five children (19 boys) with A/M underwent ophthalmological examinations and a review of medical records. Parents of 12/22 cases completed the Pediatric Quality of Life Inventory (PedsQL).
RESULTS
Age at examination ranged from 7 months to 18 years (median 2.3 years). Ten cases were totally blind or had light perception. Isolated A/M occurred in 16/35 cases, while somatic, psychomotor, neuroradiological and/or genetic pathology occurred in 19/35 cases both in the bilateral (7/9) and in the unilateral group (12/26). Among 26 unilateral cases, 4/16 with one normal eye had associated problems compared to 9/10 if the contralateral eye was pathological ( < .01). There was an increased risk for heart defects in children with psychomotor delay ( = .04). Pathogenic genetic abnormalities were identified in 10/24 cases. Neuroimaging demonstrated pathology in 14/20 cases with corpus callosum dysgenesis (6/20) being the most common. The median total PedsQL score of parent reports for ages 2-12 was 52.4 (range 22.6-100).
CONCLUSIONS
Somatic, psychomotor and/or neuroradiological pathologies were more common in bila-teral than unilateral cases, but the difference was not significant. There was decreased risk in unilateral cases with one normal eye. Genetic defects occurred in both unilateral and bilateral cases. Health-related quality of life was reduced.
Topics: Anophthalmos; Child; Child, Preschool; Female; Humans; Infant; Male; Microphthalmos; Morbidity; Quality of Life
PubMed: 35105264
DOI: 10.1080/13816810.2021.1989600 -
Human Genetics Sep 2019Eye formation is the result of coordinated induction and differentiation processes during embryogenesis. Disruption of any one of these events has the potential to cause... (Review)
Review
Eye formation is the result of coordinated induction and differentiation processes during embryogenesis. Disruption of any one of these events has the potential to cause ocular growth and structural defects, such as anophthalmia and microphthalmia (A/M). A/M can be isolated or occur with systemic anomalies, when they may form part of a recognizable syndrome. Their etiology includes genetic and environmental factors; several hundred genes involved in ocular development have been identified in humans or animal models. In humans, around 30 genes have been repeatedly implicated in A/M families, although many other genes have been described in single cases or families, and some genetic syndromes include eye anomalies occasionally as part of a wider phenotype. As a result of this broad genetic heterogeneity, with one or two notable exceptions, each gene explains only a small percentage of cases. Given the overlapping phenotypes, these genes can be most efficiently tested on panels or by whole exome/genome sequencing for the purposes of molecular diagnosis. However, despite whole exome/genome testing more than half of patients currently remain without a molecular diagnosis. The proportion of undiagnosed cases is even higher in those individuals with unilateral or milder phenotypes. Furthermore, even when a strong gene candidate is available for a patient, issues of incomplete penetrance and germinal mosaicism make diagnosis and genetic counseling challenging. In this review, we present the main genes implicated in non-syndromic human A/M phenotypes and, for practical purposes, classify them according to the most frequent or predominant phenotype each is associated with. Our intention is that this will allow clinicians to rank and prioritize their molecular analyses and interpretations according to the phenotypes of their patients.
Topics: Animals; Anophthalmos; Exome; Eye; Eye Abnormalities; Humans; Microphthalmos; Phenotype; Syndrome
PubMed: 30762128
DOI: 10.1007/s00439-019-01977-y -
The British Journal of Ophthalmology Sep 2023To evaluate treatment with custom, three-dimensional (3D) printed conformers for socket expansion in congenital microphthalmia and anophthalmia (MICA).
BACKGROUND/AIMS
To evaluate treatment with custom, three-dimensional (3D) printed conformers for socket expansion in congenital microphthalmia and anophthalmia (MICA).
METHODS
Retrospective analysis of prospective cohort from 2016 to 2020. All children received custom-made 3D-printed conformers increasing in size. We measured height, width, thickness, surface and volume of first and consecutive conformers, as well as horizontal palpebral fissure length (HPF) at start and follow-up visits. We analysed these parameters for severely (<45%) and moderately (>45%-75%) affected children, based on affected axial length on ultrasonography.
RESULTS
We included 18 cases (9 severe, 9 moderate) with a total of 174 conformers (88 severe, 86 moderate) and a mean follow-up of 2.8 years (range 1.3-4.8). The mean relative HPF increased from 77% to 93% with 16/17 cases reaching >80%, and 12/17 cases >90% symmetry. Horizontal and vertical conformer dimensions increased up to 10 months of treatment, with a steeper slope for the severe group (10.5% vs 5.5% for height and 9.0% vs 6.1% for width gain per treatment month, for severe and moderate MICA, respectively). After 10 months of treatment conformer height and width increased only slightly. No serious complications were observed.
CONCLUSION
3D-design and printing of solid conformers results in highly acceptable horizontal eyelid symmetry in the treatment of congenital MICA. The mean increase in conformer height and width in the first 10 months should be about 170% for moderate and about 200% for severe MICA. The presented conformer size formulas can aid ophthalmologists and ocularists to plan conformer treatment.
Topics: Child; Humans; Anophthalmos; Retrospective Studies; Microphthalmos; Workflow; Prospective Studies; Computer-Aided Design; Printing, Three-Dimensional
PubMed: 35477668
DOI: 10.1136/bjophthalmol-2021-320882 -
Seminars in Ophthalmology 2018Reconstruction of the anophthalmic socket allows the use of an ocular prosthesis and rehabilitation of facial appearance. Dermis-fat grafting is one option in volume... (Review)
Review
Reconstruction of the anophthalmic socket allows the use of an ocular prosthesis and rehabilitation of facial appearance. Dermis-fat grafting is one option in volume augmentation of the anophthalmic socket and presents unique benefits, including increased surface area within the socket and the ability to grow with pediatric patients. Postoperative complications of this procedure are relatively common. Minor complications, such as graft hirsutism, keratinization, and conjunctival cysts or granulomas, are managed easily by observation or simple intervention. Major complications, such as graft atrophy, infection, or ulceration, may prevent good prosthesis fit and may require return to the operating room.
Topics: Adipose Tissue; Anophthalmos; Autografts; Dermis; Eye, Artificial; Humans; Orbit; Orbital Implants; Postoperative Complications
PubMed: 29144832
DOI: 10.1080/08820538.2017.1353830 -
Seminars in Ophthalmology May 2023Blindness with no light perception is clinically irreversible. This cross-sectional hospital-based study analyzed patients presenting with no light perception in at...
Blindness with no light perception is clinically irreversible. This cross-sectional hospital-based study analyzed patients presenting with no light perception in at least one eye. Between 2010 and 2022, 60,668 (1.85%) such patients were identified, of which 3,476 (5.73%) had bilateral and 57,192 (94.27%) had unilateral blindness. The major causes were glaucoma (21.8%), trauma (17.7%), phthisis bulbi (13.1%), retinal diseases (10.6%), anophthalmos (7.8%), and optic atrophy (4.9%). The majority of the affected individuals were adults (89.9%) and male (64%), and affected individuals were more likely to be from the lower socio-economic strata (3.14%) and from a rural location (1.99%). Despite recent therapeutic advances in ophthalmology, many patients with blindness cannot be restored to sight. Although preventive measures can mitigate sight loss to some extent, regenerative therapies, retinal and ciliary body transplantation, and whole eyeball transplantation need to be developed as sight restorative procedures to help those who currently have no hope of regaining vision.
Topics: Adult; Humans; Male; Cross-Sectional Studies; Blindness; Glaucoma; Retinal Diseases; Retina; Vision, Low; Prevalence
PubMed: 36967577
DOI: 10.1080/08820538.2023.2194980 -
Human Genetics Sep 2019As new genes for A/M are identified in the genomic era, the number of syndromes associated with A/M has greatly expanded. In this review, we provide a brief synopsis of... (Review)
Review
As new genes for A/M are identified in the genomic era, the number of syndromes associated with A/M has greatly expanded. In this review, we provide a brief synopsis of the clinical presentation and molecular genetic etiology of previously characterized pathways involved in A/M, including the Sex-determining region Y-box 2 (SOX2), Orthodenticle Homeobox 2 (OTX2) and Paired box protein-6 (PAX6) genes, and the Stimulated by retinoic acid gene 6 homolog (STRA6), Aldehyde Dehydrogenase 1 Family Member A3 (ALDH1A3), and RA Receptor Beta (RARβ) genes that are involved in retinoic acid synthesis. Less common genetic causes of A/M, including genes involved in BMP signaling [Bone Morphogenetic Protein 4 (BMP4), Bone Morphogenetic Protein 7 (BMP7) and SPARC-related modular calcium-binding protein 1 (SMOC1)], genes involved in the mitochondrial respiratory chain complex [Holocytochrome c-type synthase (HCCS), Cytochrome C Oxidase Subunit 7B (COX7B), and NADH:Ubiquinone Oxidoreductase subunit B11 (NDUFB11)], the BCL-6 corepressor gene (BCOR), Yes-Associated Protein 1 (YAP1) and Transcription Factor AP-2 Alpha (TFAP2α), are more briefly discussed. We also review several recently described genes and pathways associated with A/M, including Smoothened (SMO) that is involved in Sonic hedgehog (SHH) signaling, Structural maintenance of chromosomes flexible hinge domain containing 1 (SMCHD1) and Solute carrier family 25 member 24 (SLC25A24), emphasizing phenotype-genotype correlations and shared pathways where relevant.
Topics: Animals; Anophthalmos; Genetic Association Studies; Genotype; Humans; Microphthalmos; Phenotype; Syndrome
PubMed: 30374660
DOI: 10.1007/s00439-018-1949-1